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Constantin Brncui University of Trgu-Jiu

Students League of Constantin Brncui University

~ Scientific Review ~

No. 3/2014

ISSN-e: 2344 0007


ISSN-L: 2344 0007

Trgu-Jiu 2014

Supplement No. 3/2014

Cover: Batcu Alexandru


Editing: Mrcu Flavius-Cristian

Director: Mrcu Flavius-Cristian


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Responsibility for the content of the paper is entirely to the authors.

December 2014

SCIENTIFIC COMMITTEE:
Prof. univ. dr. Adrian Gorun, Secretary
General, National Commission for Prognosis.
Prof. univ. dr. ing. Ecaterina Andronescu,
University Politehnica of Bucharest.
Prof. univ. dr. Michael Shafir, Doctoral
School in International Relations and
Security Studies, Babes-Bolyai University.
Prof. univ. dr. Nastas Kovcs Lucian, The
Romanian Academy Cluj-Napoca, "George
Baritiu" History Institute.
Prof. univ. dr. Adrian Ivan, Doctoral
School in International Relations and
Security Studies, Babes-Bolyai University.
Prof. Dr. Miskolczy Ambrus, Eotovos
Lorand Univeristy (ELTE), Hungary.
Dr. Gregg Alexander, University of the Free
State, South Africa.
Professor, dr. jur. et phil. Ditlev Tamm,
Center for retskulturelle studier (CRS),
University of Copenhagen.
Prof. univ. dr. Iancu Elena Anca,
Alexandru Ioan Cuza Police Academy,
Bucharest.
Prof. univ. dr. Victor Munteanu, Christian
University "Dimitrie Cantemir".
Prof. univ. dr. Florin Mller, Unviersity
of Bucharest.
Prof. univ. dr. Ilias Nicolae, University of
Petrosani.
Prof. Univ. dr. Doinia Ariton, Danubius
University of Galati.
Prof. Univ. dr. Ioan Deac, National Defence
University "Carol I".
Prof. univ. dr. ing. Gheorghe Solomon,
University Politehnica of Bucharest.
Prof. univ. dr. Iuliana Ciochin,
"Constantin Brncoveanu" University.
Prof. univ. dr. ing. Marius Bulgaru,
Technical University of Cluj-Napoca.
Prof. univ. dr. Nicolae Todea, University "1
Decembrie 1918" of Alba Iulia.
Prof. univ, dr.ing. Mircea Neagoe,
Transilvania University of Brasov.
Prof. univ. dr. Niculescu George,
"Constantin Brncui" University of TrguJiu.
Prof. univ. dr. Moise Bojinc, "Constantin
Brncui" University of Trgu-Jiu.
Prof. univ. dr. Popescu Luminia,
"Constantin Brncui" University of TrguJiu.

Prof. univ. dr. Cruceru Mihai, "Constantin


Brncui" University of Trgu-Jiu.
Prof. univ. dr. Gmneci Gheorghe,
Universitatea "Constantin Brncui" din
Trgu-Jiu.
Prof. univ. dr. Ghimii tefan Sorinel,
"Constantin Brncui" University of TrguJiu.
Prof. univ. dr. Bc Monica Delia,
"Constantin Brncui" University of TrguJiu.
Prof. univ. dr. Babucea Ana Gabriela,
"Constantin Brncui" University of TrguJiu.
C.S II Du Paul, Romanian Diplomatic
Institute.
Conf. univ. dr. Rzvan Ctlin Dobrea,
Academy of Economic Studies.
Pr. Conf. univ. dr. Dumitru A. Vanca,
University "1 Decembrie 1918" of Alba Iulia.
Conf. univ. dr. Purec Sorin, "Constantin
Brncui" University of Trgu-Jiu.
Conf. univ. dr. Neamu Liviu, "Constantin
Brncui" University of Trgu-Jiu.
C.S. III Manolache Viorella, Institute of the
Political Science and International Relations,
Romanian Academy
Lect. univ. dr. Tomescu Ina Raluca,
"Constantin Brncui" University of TrguJiu.
Lect. univ. dr. Dan Ionescu, "Lucian Blaga"
University of Sibiu.
Lect. univ. dr. Hadrian Gorun, "Constantin
Brncui" University of Trgu-Jiu.
Lect. univ. dr. Rujan Cristinel, "Constantin
Brncui" University of Trgu-Jiu.
Lect. univ. dr. Trocan Laura Magdalena,
"Constantin Brncui" University of TrguJiu.
Lect. univ. dr. Simionescu Elena
Giorgiana, "Constantin Brncui" University
of Trgu-Jiu.
Lect. univ. dr. Gavrilescu Alin, "Constantin
Brncui" University of Trgu-Jiu.
Lect. univ. dr. Plstoi Camelia, "Constantin
Brncui" University of Trgu-Jiu.
.l. dr. Ciofu Cristian Florin, "Constantin
Brncui" University of Trgu-Jiu.

Supplement No. 3/2014

CONTENT
MEDICINE

INTEROBSERVER VARIABILITY IN PLACENTAL HISTOPATHOLOGY DIAGNOSIS OF


INFLAMMATORY LESIONS: A STATISTICAL EXPERIMENT ..........................................................6
Zamfir-Radu IONESCU
Georgiana-Cristina IONESCU
Diana-Ioana VOICU
Maria SAJIN
THE STAPHYLOCOCCUS WARNERI BIOFILM FORMATORY STRAIN ISOLATION IN THE
PERIPROSTHETIC HIP INFECTION BY THE SONICATION TECHNIQUE: CASE REPORT........ 14
Adrian CURSARU
Raluca MIHAILESCU
Victoria ARAMA
Ctlin Florin CRSTOIU
MULTIPLE OR METASTATIC OSTEOSARCOMA, IN YOUNG MALE
PATIENT: CASE REPORT ...................................................................................................................... 20
Zsombor PANTI
Catalin CIRSTOIU
MILD SYMPTOMS IN PRIMARY SPONTANEOUS PNEUMOTHORAX IN THE
EMERGENCY ROOM .............................................................................................................................. 27
Roxana CHELER
Siegfried ALBU
Adriana BIDIC
HYPOCAPNIA AS TRIGGER FOR THE DIAGNOSTIC PROTOCOL IN
PULMONARY EMBOLISM ..................................................................................................................... 32
Roxana CHELER
Adriana BIDIC
Siegfried ALBU
ARTHROSCOPIC BANKART WITH METTALIC SUTURE ANCHORS FOR UNSTABLE
DISLOCATING SHOULDERS: CASE REPORT .................................................................................... 38
Alexandru LUPU
Razvan ENE
ACUTE STROKE IN EMERGENCY ROOM TREATED WITH NEW INTERNATIONAL
PROTOCOL - THROMBOLYSIS ............................................................................................................ 44
Liviu ULMEANU
IMPLICATIONS OF UTERINE ARTERY EMBOLIZATION FOR UTERINE
FIBROMATOSIS ...................................................................................................................................... 49
Diana VOICU
Liviu POPOVICI
Dragos DAVITOIU
Ioana ROTAR
IMPACT OF MATERNAL HYPERTENSION ON THE INTRAUTERINE GROWTH RESTRICTED
NEONATE ................................................................................................................................................. 58
Luiza RADULESCU
Irina HORHOIANU
Costin BERCEANU
Adriana DAN
MANAGEMENT OF OCULAR CICATRICIAL PEMPHIGOID ........................................................... 66
Corina Ioana BUTEA-SIMIONESCU
Speranta SCHMITZER
PREGNANCY-A METABOLIC CHALLENGE ...................................................................................... 73
Oana BODEAN
Simona VLADAREANU
Elvira BRATILA
Monica CIRSTOIU
PREVALENCE OF CELIAC DISEASE IN WOMEN WITH FERTILITY DISORDERS ...................... 79
Cosmin CIORA
Alexandru LUPU
Mircea DICULESCU

December 2014

QUALITY OF LIFE FOR HEAD AND NECK CANCER PATIENTS .................................................... 87


Bogdan POPESCU
erban Vifor Gabriel BERTETEANU
Raluca GRIGORE
Oana PUN
Cristian Radu POPESCU
Rzvan SCUNAU
HYDATID CYST LOCATED IN THE MAIN BILE DUCT-A RARE DIFFERENTIAL DIAGNOSIS OF
OBSTRUCTIVE JAUNDICE IN PREGNANCY ...................................................................................... 92
Tudor NSTSESCU
Drago DAVIOIU
Constantin BUDIN
Oana BODEAN
RDW AS A NOVEL MARKER OF DISEASE ACTIVITY IN CROHNS DISEASE: TESTING A
HYPOTHESIS IN AN IBD TERTIARY CARE CENTER IN ROMANIA............................................. 100
Cristian TIERANU
Ciprian GIGEA
RECURRENT GIANT CELL TUMOR OF SUPERIOR PUBIC RAMUS: CASE REPORT................ 108
Nica MIHAI
Ene RAZVAN
Popescu DAN
THE INCIDENCE OF ARTERIAL HYPERTENSION THAT COMPLICATES PREGNANCY,
PARTURITION AND POSTPARTUM PERIOD IS INCREASING
- DEPARTMENT EXPERIENCE - ......................................................................................................... 114
Octavian MUNTEANU
Alexandra ZLATIANU
Elvira BRATILA
Monica CIRSTOIU
DEVELOPMENT OF SCORING SYSTEM FOR EVALUATING THE RISK OF CEPHALOPELVIC
DISPROPORTION .................................................................................................................................. 120
Octavian MUNTEANU
Alexandru ISPAS
Costin BERCEANU
Simona VLADAREANU
SURGICAL ONCOPLASTIC TECHNIQUE FOR GIANT FIBROADENOMA ................................... 127
R. SCUNAU
B. POPESCU
C. BLLU
I. HORHOIANU
C. COZMA
S. VOICULESCU
THE ASSESSMENT OF POSTPROCEDURE RESULTS IN THE CASE OF PATIENTS OPERATED ON
USING THE FEMTOLASIK METHOD WITH THE ALCON/WAVELIGHT FS200 FEMTO & EX500
EXCIMER REFRACTIVE SUITE.......................................................................................................... 132
Constantin MIHAI
Tiberiu Octavian IVANA
Calin Petru TATARU
UPDATE ON INFLAMMATORY BOWEL DISEASES ETHIOPATOGENICS .................................. 140
Alexandru LUPU
Cosmin CIORA
Mircea DICULESCU
INFORMATION ABOUT RESEARCH AND SCIENCE TODAY JOURNAL.....144

Supplement No. 3/2014

Medicine

INTEROBSERVER VARIABILITY IN PLACENTAL


HISTOPATHOLOGY DIAGNOSIS OF INFLAMMATORY
LESIONS: A STATISTICAL EXPERIMENT

Zamfir-Radu IONESCU1
Georgiana-Cristina IONESCU 2
Diana-Ioana VOICU3
Maria SAJIN4

ABSTRACT:
THE WORLDWIDE TREND FOR MEDICAL PRACTICE, IN GENERAL, AND FOR HISTOPATHOLOGICAL
LESIONS DIAGNOSIS, IN PARTICULAR, TURNS IN FAVOR FOR PROTOCOL USE, AS IN MANY
COUNTRIES AND SPECIALTIES, THESE ARE NOT WELL IMPLEMENTED. OUR AIM REFERS TO AN
EXPERIMENT THAT INVOLVED FIVE AVERAGE EXPERIENCED OBSERVERS THAT EXAMINED 10
PLACENTAS WITH CHORIOAMNIONITIS, 4 ACUTE CASES AND 6 CHRONIC CASES. THEY HAD TO
ISSUE THE DEGREE OF EXTENT OF BASIC LESIONS: HYALINE DEPOSITION, INFLAMMATION,
FIBROSIS, NECROSIS AND HYPEREMIA. THE INSTRUMENT USED WAS A LIKERT SCALE WITH FIVE
DEGREES OF INTENSITY. KAPPA STATISTICAL CALCULATIONS PROVED A SLIGHT DIFFERENCE
BETWEEN THE FIVE EXAMINATORS IN REGARDING THE APPRECIATION OF LESION SEVERITY. THE
INTEROBSERVER AGREMEENT WAS BETWEEN 0.04 TO 0.14 WITH HIGHER CONSISTENCY TOWARD
OBVIOUS LESIONS WITH ALPHA VALUES FROM 0.61 TO 0.81.THUS SHOWING THE NECESSITY FOR A
FAR PRECISE DIAGNOSIS PROTOCOL TO BE IMPLEMENTED, AS THE LESIONS IN
CHORIOAMNIONITIS PLACENTA MA BE VERY DIFFICULT TO APRECIATE.
KEY WORDS: INTEROBSERVER AGREEMENT, CHORIOAMNIONITIS, PLACENTA,
INFLAMMATION, HISTOPATHOLOGY, DIAGNOSIS.

INTRODUCTION
Chorioamnionitis (CHO) or amniotic infection is an inflammation of the membranes
and chorion, produced due to ascending microbial bacterial flora in the setting of membrane
1

PhD, Department of Pathology, Emergency University Hospital, Bucharest, Romania; e-mail:


dr.raduionescu@yahoo.com.
2
Department of Neonatology and Pediatrics, University Hospital, Bucharest, Romania; e-mail:
oprea_22@yahoo.com.
3
MD. Department of Obstetrics and Gynecology, Emergency University Hospital, Bucharest, Romania.
4
M.D., PhD, Department of Pathology, The University Emergency Hospital, Bucharest, Romania; Head of
Morphology and Pathology Department, The University of Medicine and Pharmacy, Carol Davila, Bucharest;
e-mail: maria_sajin@yahoo.com.

December 2014

rupture. However, CHO may appear with intact membrane features as it may be produced
bay infracellular agents like Ureaplasma species and Mycoplasma hominis, incidentally
discovered in lower genital tract at over 70% of women 5. Between clinical and histologic
CHO still exists a large gap, the latter being based on pathologic findings on microscopic
examination of the placenta that might encompass clinically unapparent chorioamnionitis as
well as clinically obvious CHO. The clinical signs are represented by the presence of fever,
uterine tenderness, maternal or fetal tachycardia and purulent amniotic fluid, in the absence
of other etiologies for these signs and symptoms 6. Pregnant women consultation may reveal
no sign or symptoms of infection or it may reveal clinical aspects that could lead to a
misdiagnosis, like ill appearing female patient, even toxic, with hypotension, diaphoresis,
cool or clammy skin7. Therefore, the accuracy of diagnosis in CHO, either acute or chronic,
is not always reliable, as some studies show that fever have 61% accuracy, with high
specificity an low sensitivity, and tachycardia with 52.4% accuracy with a very low
sensitivity, thus histologic placental abnormalities consistent with CHO being a more
frequent discovery with no prior specific symptomatology8. Blood count may reveal maternal
leukocytosis (white blood cells>12000-15000 / mm3) or the presence of a left shift or
bandemia. Some studies proved high-levels of C-reactive protein together the presence of
soluble intercellular adhesion molecule 1 (sICAM 1) and interleukin 6 in CHO, but at least
some of these markers are far from being reliable to use on a routine basis9. Some authors
suggest high increase in third day of newborns of WBC to be strongly correlated with CHO 10.
Histologic chorioamnionitis is defined by the existence of acute inflammatory changes on the
microscopic examination of amniotic membranes and chorion in placenta and funisitis. This
implies the presence of polymorphonuclear leukocytes per high power field, graded trough
detailed systems of lesion classification, location, degeneration in order to estimate intensity
and CHO evolution11. The pathologist and the gynecologist should grossly observe either a
normal placenta or with dull, opaque membranes with yellow-green color and amniotic fluid
that have opalescent aspect, even cloudy (figure 1, figure 2). Purulent exudate may be
present. Microscopically, neutrophil infiltrate of membranes, funisitis and chorionic plate
vasculitis (figure 3). Acute intervillositis and peripheral funisitis may be present, either due to
inframicrobial agents or fungi, like Listeria or Candida 12.

Alan T N Tita and William W Andrews, Diagnosis and Management of Clinical Chorioamnionitis, Clinics
in Perinatology 37, no. 2 (June 2010): 33954, doi:10.1016/j.clp.2010.02.003.
6
J. W. Riggs and J. D. Blanco, Pathophysiology, Diagnosis, and Management of Intraamniotic Infection.,
Seminars in Perinatology 22, no. 4 (August 1998): 25159.
7
O. Apantaku and V. Mulik, Maternal Intra-Partum Fever., Journal of Obstetrics and Gynaecology: The
Journal of the Institute of Obstetrics and Gynaecology 27, no. 1 (January 2007): 1215,
doi:10.1080/01443610601016644.
8
W M Curtin et al., Accuracy of Signs of Clinical Chorioamnionitis in the Term Parturient, J Perinatol 33,
no. 6 (June 2013): 42228.
9
Rafli van de Laar et al., Accuracy of C-Reactive Protein Determination in Predicting Chorioamnionitis and
Neonatal Infection in Pregnant Women with Premature Rupture of Membranes: A Systematic Review,
European Journal of Obstetrics & Gynecology and Reproductive Biology 147, no. 2 (December 2009): 12429,
doi:10.1016/j.ejogrb.2009.09.017.
10
Vincenzo Zanardo et al., Relationship between the Neonatal White Blood Cell Count and Histologic
Chorioamnionitis in Preterm Newborns, The Journal of Maternal-Fetal & Neonatal Medicine 25, no. 12
(December 1, 2012): 276972, doi:10.3109/14767058.2012.712562.
11
Claudia Holzman et al., Histologic Chorioamnionitis and Preterm Delivery., American Journal of
Epidemiology 166, no. 7 (October 1, 2007): 78694, doi:10.1093/aje/kwm168.
12
http://www.pathologyoutlines.com/topic/placentachorioamnionitis.html, 16 December, 2014
5

Supplement No. 3/2014

Figure 1. - Acute chorioamniotitis placenta from a 33 weeks gestation with parenchima necrosis,
purulent exsudate over amniotic membranes and haemorrhage (personal collection).

Figure 2. Chorioamnionitis in a placenta from a 36 weeks gestation. Membranes with a yellow


discoloration, necrosis and diffuse haemorrhage (personal collection).

SUBJECTS AND METHODS


This study purpose is to identify and to investigate the simple variability of pathologist
observers participating in evaluating the degree of lesions in 10 female patients with
inflammatory placentas, admitted in the Department of Obstetrics and Gynecology of
University Emergency Hospital Bucharest, between 1 st January 2012 and 1 st February 2013,
in 50 slides of archived paraffin tissue blocks, routine stained in haematoxylin-eosin,
sectioned in 3 m thickness. High resolution photographs were taken from the slides, in those
areas with most obvious pathologic modifications of the placenta, with all microscopic
objectives (4x10, 40x10, and 10x10) and used for data collection. The factors quantified for
interobserver statistics were: acute inflammation degree, the extent of hyaline depositions,
extent of fibrosis, necrosis and hyperemia. We used the Likert scale, frequently used in
8

December 2014

pathology kappa statistics, with a classical five factor type, depicted in Table 1, following the
experimental model used by other pathologists in different studies 13. Calculations have been
made using Excel spreadsheet with the aid of Cronbachs alpha and kappa statistics, superior
to Kuder and Richardson formula, which can be used with non-dichotomous, continuous
data.
Factor used in study
1 = inexistent / very low frequency (widespread) of
lesion
2 = low frequency / widespread of lesion
3 = moderate frequency / widespread of lesion
4 = moderate-severe frequency / widespread of
lesion
5 = severe frequency / widespread of lesion

Surface
percentage:
<10%

Reliability
(alpha statistics)
0.92

10-30%
30-50%
50-70%

0.31
0.81
0.46

70-100%

0.61

Table 1. Likert scale showing factors used in our study for


evaluation of pathologic findings.

RESULTS
The patients were diagnosed with 6 chronic CHO (mean gestational age of 26.9 weeks)
and 4 acute CHO cases (mean gestational age of 19 weeks). The placentas were sampled
from women with a mean age of 29 years, in a range from 15 to 43 years old, and a mean
gestational age of 23.7 weeks old, within a range from 6 to 36 weeks. In these cases, one
woman was admitted with CHO with an abscess formation and one case with obvious
amniotic membrane involvement in inflammatory process, with purulent exudate and
lacerations.
In the ten cases that were selected, we observed 4 abortions (mean gestational age of
13.5 weeks), 5 premature newborn babies (mean gestational age of 29.2 weeks) and 1 term,
aged 37 weeks (figure 3, figure 4).
Descriptive statistics of newborn babies in the
study
6
5

4
3

2
1
0

Abortions

Premature newborns

Term newborns

Figure 3. Newborn statistics in studied group.

Martin Simmonds et al., Intraobserver and Interobserver Variability for the Histologic Diagnosis of
Chorioamnionitis, American Journal of Obstetrics and Gynecology 190, no. 1 (January 2004): 15255,
doi:10.1016/S0002-9378(03)00870-6.
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Supplement No. 3/2014

Descriptive statistics of
inflamatory placentas

Chronic CHO

Chorioamnionitis

Acute CHO

Figure 4. Chorioamniotitis dichotomy in studied group.

The appreciation of these lesions by the observers implied in this trial proved no
agreement in between, with lowest kappa, (0.02) for acute inflammation detection, and
highest kappa for hyaline (0.20) as this lesion becomes far obvious at the gestational ages for
our cases (Table 2). The p-values, with one exception in acute inflammation (p<0.66),
indicates a strong presumption against null hypothesis, showing that obtaining the detected
kappa values by random chance is very unlikely (p<0.05). The reliability tests proved
acceptable in appreciating almost inexistent or moderate extent of lesions for all factors of
study, as depicted in Table 1, while low frequency lesions assessment was considered
unsatisfactory.
Statistics

Acute inflammation

Hyaline

Fibrosis

Necrosis

Hyperemia

kappa

0.021

0.208

0.147

0.105

0.142

p-value

0.665

0.0003

0.006

0.025

0.004

Table 2 Kappa statistics for agreement between observers in lesions quantifing.

DISCUSSIONS
The overall tendency was either to underestimate the existence of lesions, either to
overestimate them, while moderate lesions were, paradoxically easy to recognize and asses
equally for all factors (figure 5), probably due to their high incidence among amniotic
inflammation. The unreliability of agreement of implied observers is mainly affected by
many subjective, ubiquitous factors, like little experience in detecting vasodilation anomalies,
interpreted as active hyperemia (figure 6), hyaline deposition (figure 7), or stromal
hypercellularity for some tissue samples, while a slight involvement increase for these
elements, mentioned above, could become pathologically important.

10

December 2014

Figure 5. - Descriptive statistics of lesion quantification using


Likert scales for proposed factors.

Figure 6. - Villi in a term gestation placenta (37 weeks), with vasculosyncitial knots, interpreted as
hyperemia due to hypoxic mechanism (personal collection).

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Supplement No. 3/2014

Figure 7. Fibrnioid and hyaline deposition inside the intervillous space, in a second trimester (22 weeks)
normal placenta (personal collection).

Nowadays, significant discordance of diagnosis for placenta histologic abnormalities,


like hydatidiform mole, observed by different authors, tend to persist as new criteria are
required for more accurate classification of diseases 14. In some situations, the degree of acute
inflammation is difficult to evaluate as many sampling and surgical artifacts may afflict the
lesions reality in the tissue, while stromal cells may undergo different morphological
modifications that might become, at some point, physiological. As seen in figure 5, hyaline
and fibrosis are ubiquitous in all examined samples, while necrosis volume correlates with
the amplitude of inflammation.
Tissue necrosis and fibrinoid, present outside of an inflammatory process, may be
unspecific and normal, as the gestation approaches term15. The use of immunochemistry in
identifying leucocytes increases significantly diagnosis accuracy, especially of CD3+, CD4+
and CD8+ positive cells in a moderate amount, and almost no CD20+ and CD56+ positive
cells, for chronic CHO16, while Hoffbauer cells expression, positive for CD68 monocyte and
macrophage markers, decreases significantly17.
CONCLUSION
As the difficulty of placental histopathology diagnosis increases, the necessity of
implementing a reliable microscopic grading protocol arises. In conclusion, at the present
moment, although routine HE sections examination remains reliable, observer variability
Masaharu Fukunaga et al., Interobserver and Intraobserver Variability in the Diagnosis of Hydatidiform
Mole., The American Journal of Surgical Pathology 29, no. 7 (July 2005): 94247.
15
Baergen, N. Rebecca et al., Manual of Pathology of the Human Placenta, Second Ed, Springer, New York,
2011, doi: 10.1007/978-1-4419-7494-5.
16
S. M. Jacques and F. Qureshi, Chronic Chorioamnionitis: A Clinicopathologic and Immunohistochemical
Study., Human Pathology 29, no. 12 (December 1998): 145761.
17
Marie-Therese N. Vinnars et al., The Number of CD68(+) (Hofbauer) Cells Is Decreased in Placentas with
Chorioamnionitis and with Advancing Gestational Age., Pediatric and Developmental Pathology: The Official
Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 13, no. 4 (August 2010):
68, doi:10.2350/09-03-0632-OA.1.
14

12

December 2014

remains high in assessing frequent lesions and inflammation amplitude. This could be
corrected with the aid of immunohistochemical identification of polymorphonuclears in tissue
and the use of semi-automatic, computer assisted, histologic scanning and measurements, due
to artificial intelligence algorithms.
AKNOWLEDGEMENTS
Special thanks go to the funded Doctoral School from the University of Pharmacy and
Medicine Carol Davila and to the Bucharest University Emergency Hospital, Department
of Gynecology and Obstetrics and the Department of Pathology. Our special thanks go, also,
to the medical students at UMF Carol Davila , The Faculty of General Medicine, in third
year, Ioana Sonia Iordache, Ana Maria Cpn, Larisa Catrinescu, Magda Iorgulescu,
Antonia Sima, Victor George Chiper and Bogdan Gon, for volutary aid in accomplishing
data collecting and calculations for this study.

13

Supplement No. 3/2014

Medicine

THE STAPHYLOCOCCUS WARNERI BIOFILM


FORMATORY STRAIN ISOLATION IN THE
PERIPROSTHETIC HIP INFECTION BY THE SONICATION
TECHNIQUE: CASE REPORT

Adrian CURSARU1
Raluca MIHAILESCU2
Victoria ARAMA3
Ctlin Florin CRSTOIU 4

ABSTARCT
WE REPORT THE CASE OF A 71 YEARS OLD WOMAN WITH RIGHT PRIMARY OSTEOARTHRITIS OF
THE HIP SURGED WITH CEMENTED HIP ARTHROPLASTY WICH THREE YEARS LATER ACCUSES PAIN
AT THE PROSTHESIS HIP WITH NONSPECIFIC INFLAMMATORY BLOOD TESTS FOR INFECTION AND
WITH NEGATIVE CULTURES. IN THE ABSENCE OF A BACTERIA GROWTH THE PROSTHETIC
IMPLANT WAS SENT TO A SPECIALIZED LAB IN ORDER TO SONICATE IT. AFTER ONLY 3 DAYS AFTER
THIS PROCEDURE THE ISOLATION OF STAPHYLOCOCCUS WARNERI STRAIN SUCCEEDED AND 4
MOUNTHS AFTER THE REMOVAL OF THE HIP PROSTHESIS A REVISON PROSTHESIS WAS
INSTALLED. AFTER THE ARTHROPLASTY REVISION , THE PATIENT HAD A FAVOURABLE
EVOLUTION AT GENERAL AND LOCAL LEVEL AND ALSO A GOOD SOCIAL INTEGRATION AT 4
MONTHS AFTER THE SURGERY, NEVER AGAIN PRESENTING ANY SIGNS OF INFECTION.
KEY WORDS: SONICATION, PERIPROSTHETIC INFECTION, BACTERIAL CULTURE

INTRODUCTION:
Adhesion of bacteria to human tissue surfaces and implanted prosthesis surfaces is an
important step in the pathogenesis of periprosthetic infection having as a result the
impossibility of their issolation and identification through the standard cultures.

*All authors had equal contribution


1
Emergency University Hospital of Bucharest - Orthopedics and Traumatology department, Romania; UMF
Carol Davila, Bucharest, Romania, cursaru_adrian@yahoo.com
2
UMF Carol Davila, Bucharest, Romania; Institutul Naional de boli infecioase Prof. Dr. Matei Bal
Bucharest, Romania
3
UMF Carol Davila, Bucharest, Romania; Institutul Naional de boli infecioase Prof. Dr. Matei Bal
Bucharest, Romania
4
Emergency University Hospital of Bucharest - Orthopedics and Traumatology department, Romania; UMF
Carol Davila, Bucharest, Romania

14

December 2014

CASE REPORT:
We report the case of a 71 years old woman with right primary osteoarthritis of the hip
surged with cemented total hip arthroplasty 3 years ago, with a good post-surgery evolution
for the next 2 years when the patient, after suffering a trauma by falling from her own height
is presenting with a periprosthetic fracture ( Weber b ) in which fracture reduction and the
osteosynthesis with Dall Miles plate was performed. One year later the patient accuses pain at
the prosthesis hip ( in the absence of a fistula ) accompanied by the relative functional
impotence. At the local examination no changes at post surgery scar are observed. The X
Ray it reveals precocious loosening signs ( figure 1 ). The results of the inflammatory blood
tests are not suggestive as for the septic phenomenon:
The leukocytes values ( 8.80 x10/L ) and fibrinogen ( 392 mg/dl ) within normal
limits.
The protein C ( 7,87 mg/l ) and the erythrocyte sedimentation rate ( 18 mm/h ) slightly
increased.
Setting the periprosthetic hip infection diagnosis at this stage is difficult, but the debut
of the inexplicable pain and the specific images suggest a possible septical evolution. In order
to sustain this diagnosis a puncture aspiration is done from the periprosthetic fluid in order to
do the cultures and the antibiogram on conventional smears ( Gram / Giemsa for bacteria
cultures as well as for fungus ), the aspirate being collected into sterile tubes and then sent to
the lab. The result was read after a period of 5 days ( the standard time for bacteria growth ).5

Preoperative X-Ray prosthesis loosening


Figure 1

Microbiological culture
Figure 2

After this incubation period the bacteria result was negative, presenting some segments
of fibrin, some rare inflammatory cells in the absence of a growing bacteria or fungus.
Appearance of a fistula during hospitalization ( while keeping negative cultures) lead to the
decision of prosthesis removal and mounting a cement spacer ( figure 3 ). The surgery of
prosthesis removal consisted of chemical debridement ( 8 liters of saline solution were used )
5

Osmon D.R, Berbari E.F Diagnosis and management of prosthetic joint infection: clinical practice guidelines
by the infectious diseases society of America., Clin Infect Dis;56:e125, 2013

15

Supplement No. 3/2014

and mechanical debridement. It was done the complete removal of the whole prosthetic
implant and the Dall Miles plate and mounting an antibiotic loaded cement spacer. In the
moment of the surgery 6 tissue biopsies were collected from the periprosthetic with specific
inflammatory look which were inoculated in agar environment and incubated at 37 degrees
for 5 days. In the absence of a bacteria growth until this moment, the prosthetic implant was
sent to a specialized lab in order to sonicate it.

Preoperative X-Ray cement spacer


Figure 3

Revision Arthroplasty
Figure 4

The sonication process6 consisted of adding Ringer solution ( 500 ml ) under sterile
conditions in the recipient ( figure 5 ) containing the implant, then processing by vortexing
for 30 seconds, followed by sonication ( figure 6 ). for 1 minute, and the resulted liquid was
poured on the Agar motherboards for the aerobic and anaerobic cultures.
The values needed for diagnosing an infection after the sonication process were
considered as below7:
1. >50 CFU/ml ( Colony Forming Unit )
2. 10-40 CFU/ml in the presence of the clinical symptoms and the increased
inflammatory blood tests.
3. Presence under 10 CFU/ml infirm the microbiological diagnosis of infection.

sterile recipient containing the implant


.
Figure 5

sonication system
Figure 6

Trampuz A, Piper KE, Jacobson MJ. Sonication of removed hip and knee prostheses for diagnosis of infection.
N Engl J Med;357:654, 2007
7
Osmon D.R, Berbari E.F Diagnosis and management of prosthetic joint infection: clinical practice guidelines
by the infectious diseases society of America., Clin Infect Dis;56:e125, 2013

16

December 2014

After only 3 days after this procedure the isolation of staphylococcus warneri strain
succeeded ( figure 2 ). This strain has the capacity of forming a biofilm on the surface of the
implant followed by cell agglomeration in multiple layers secreting matrix formatting
substances in which infection agents can be found.8
Because of the changes in the cell metabolism settled by complex signal paths from the
biofilms, staphylococcus warneri passes to a dormant phase, a phase of minimum cell
proliferation which makes also impossible its isolation by conventional cultures. The
periprosthetic infections with this type of bacteria strain biofilm formation are very hard both
to treat and diagnose, the new formed matrix ensuring a real barrier against cells lines of
defense and to the diffusion mechanism of the antibiotics. The low level of cell proliferation
affects dramatically the bactericide action of the antibiotics as well as the cultures in vitro in
the scope of the bacteriological diagnosis. Forming the biofilms is a slow process, this being
a specific of the late infections. The bacteria able to form this biofilm has a low virulence
compared to the strains able to generate early infections, as in our case, a late infection
accompanied by a little clinical signs making it hard to differentiate from the aseptic implant
failure. After identifying the responsible germ for the infection, the antibiogram was done (
after 18 hours [Tabel 1] ) which revealed a high resistance to penicillin and gentamicin with
sensitivity to vancomycin and clindamycin.

Antibiogram result at 18 hoursTable 1

After the surgery the patient received intravenous antibiotics ( 20 days) , as per the
result of the antibiogram with cephalosporins 3 rd generation (cefort 1g at 12 hours ) and
vancomycin ( 1g at 12 hours ). The intravenous antibiotherapy was followed by oral
antibiotherapy with fluorochinolone for 30. The clinical and laboratory reevaluations ( blood
test for inflammation ) at the 6 weeks control indicate a general and local favourable
evolution with the normalization of all inflammatory samples; 4 months after the removal of
the hip prosthesis the cement spacer ablation was done and a revision prothesis was installed
( figure 4 ).
8

Scorzolini L, Lichtner M, Iannetta M, Mengoni F, Russo G, Panni AS, Vasto M, Bove M, Villani C,
Mastroianni CM, Vullo V. Sonication technique improves microbiological diagnosis in patients treated with
antibiotics before surgery for prosthetic joint infections. New Microbiol. 2014 Jul;37(3):321-8. Epub 2014 Jul 1.

17

Supplement No. 3/2014

During the surgery revision 6 tissular byopsies and periarticular fluid were taken and
being sent to the microbiologically lab in order to identify if any latent bacteria still exists.
After the arthroplasty revision, the patient had a favourable evolution at general and local
level and also a good social integration 4 months after the surgery, never again presenting any
signs of infection.
CONCLUSION:
We stress out the importance of the ultrasound procedure of separation and bacteria
identifying in this case report after only 3 days as against to conventional cultures, because of
a little bacteria quantity ( able to cause a late infection ) as well as bacteria collonizing at the
prosthetic implant level with forming a biofilm at its surface 9 having as a result the
impossibility of their issolation and identification through the standard cultures.
As a conclusion, staphylococcus warneri as well as other strains able to form a biofilm
on the prosthetic implant by using the sonication technique make possible their isolation and
identification10 contributing so at forming a complete bacteriological diagnosis ( including
antibiogram ), and, consequently, at a correct therapy with substantial improvement of the
treatment in periprosthetic infections.

Lass R, Giurea A, Kubista B, Hirschl AM, Graninger W, Presterl E, Windhager R, Holinka J Bacterial
adherence to different components of total hip prosthesis in patients with prosthetic joint infection.. Int Orthop.
2014 Aug;38(8):1597-602. doi: 10.1007/s00264-014-2358-2. Epub 2014 May 10
10
Li Z, Zhang C, Wang B, Wang H, Chen X, Mhwald H, Cui X Sonochemical Fabrication of Dual-Targeted
Redox-Responsive Smart Microcarriers.. ACS Appl Mater Interfaces. 2014 Dec 5

18

December 2014

REFERENCES
1.

2.

3.

4.

5.
6.
7.
8.

9.

Arun M, Subramanyam K, Mariashibu TS, Theboral J, Shivanandhan G, Manickavasagam M,


Ganapathi A., Application of Sonication in Combination with Vacuum Infiltration Enhances the
Agrobacterium-Mediated Genetic Transformation in Indian Soybean Cultivars. Appl Biochem
Biotechnol. 2014 Dec 6
Camille Piffaut, Sbastien Lustig, Frdric Laurent1, Christian Chidiac, Tristan Ferry,Small
colony variant-producing S aureus prosthesis joint infection highlighted by sonication and treated with
prolonged high doses of daptomycin BMJ Case Reports; doi:10.1136/bcr-2013-008637, 2013
Holinka J, Pilz M, Hirschl AM, Graninger W, Windhager R,, Differential bacterial load on
components of total knee prosthesis in patients with prosthetic joint infection. Presterl E. Int J Artif
Organs.;35(10):735-41. doi: 10.5301/ijao.5000152. 2012 Oct
Lass R, Giurea A, Kubista B, Hirschl AM, Graninger W, Presterl E, Windhager R, Holinka J
Bacterial adherence to different components of total hip prosthesis in patients with prosthetic joint
infection.. Int Orthop. 2014 Aug;38(8):1597-602. doi: 10.1007/s00264-014-2358-2. Epub 2014 May 10
Li Z, Zhang C, Wang B, Wang H, Chen X, Mhwald H, Cui X Sonochemical Fabrication of DualTargeted Redox-Responsive Smart Microcarriers.. ACS Appl Mater Interfaces. 2014 Dec 5.
Osmon D.R, Berbari E.F Diagnosis and management of prosthetic joint infection: clinical practice
guidelines by the infectious diseases society of America., Clin Infect Dis;56:e125, 2013
Saeed K. J Diagnostics in prosthetic joint infections. Antimicrob Chemother. 69 Suppl 1:i11-9. doi:
10.1093/jac/dku248. 2014 Sep;
Scorzolini L, Lichtner M, Iannetta M, Mengoni F, Russo G, Panni AS, Vasto M, Bove M, Villani
C, Mastroianni CM, Vullo V. Sonication technique improves microbiological diagnosis in patients
treated with antibiotics before surgery for prosthetic joint infections. New Microbiol. 2014
Jul;37(3):321-8. Epub 2014 Jul 1.
Trampuz A, Piper KE, Jacobson MJ. Sonication of removed hip and knee prostheses for diagnosis
of infection. N Engl J Med;357:654, 2007

19

Supplement No. 3/2014

Medicine

MULTIPLE OR METASTATIC OSTEOSARCOMA, IN


YOUNG MALE PATIENT: CASE REPORT

Zsombor PANTI1
Catalin CIRSTOIU2

ABSTARCT
OSTEOSARCOMA AS A MLIGNANT TUMOR HAS A PRESERVED PROGNOSIS, WHICH DEPENDS ON
THE EARLY, CORRECT DIAGNOSIS. SURGICAL AND ADJUVANT CHEMITHERAPY ALLOWS A GOOD
PROGNOSIS.
A 17 YEAR OLD MALE PATIENT PRESENTED TO OUR INSTITUTION, WITH A RECENT APPEARED
PALPABLE MASS OF PROXIMAL THIRD OF THE LEFT LEG. CLINICAL AND PARA CLINICAL
INVESTIGATION PUT ON EVIDENCE AN OSTEOSARCOMA. THE PATEINT UNDERGOES TO
CHEMOTHERAPY AND SURGICAL LIMP SPARING SURGERY WITH MODULAR PROSTHESIS
RECONSTRUCTION. 6 MONTHS AFTER SURGERYA SLIGHT PAIN APPEARS ON THE RIGHT DISTAL
THIGH AND CHEST, BIOPSY CT AND BONE SCINTIGRAPHY REVEALS OSTEOSARCOMA. THIS CASE
UNDERLINES THE IMPORTANCE OF EARLY AND CORRECT DIAGNOSIS. FURTHER RESEARCHES ARE
NEEDED IN ORDER TO KNOW THE EXACT MECHANISM OF THE APPEARNCE OF MULTIPLE
METACHRONOUS OSTEOSARCOMA. OUR CASE REPORT PRESENTS A RARE APPEARNCE OF
OSTEOSARCOMA, WITH A REDUCED NUMBER OF SIMILAR REPORTS IN THE REVIEWED
LITERATURE.
KEY WORDS: OSTEOSARCOMA, LIMB-SPARING SURGERY, MODULAR PROSTHESIS

INTRODUCTION
Osteosarcoma is the second most common primary malignant bone tumor. It is
characterized by malignant proliferation of bone cells, it can occur at any age. The incidence
of primary high grade osteosarcoma is 1-3/1000000, per year; it occurs most frequently on
the second decades of life. It can affect the entire skeleton; however most frequently affects
the distal femur, proximal tibia and proximal humerus3.
The etiology of osteosarcoma is still unclear; several theories have been described,
which may lead to malignant proliferation of bone cells. Fuchs B. et al underline the presence
of chemical agents like beryllium, viruses, irradiation as potential factors in the etiology of
osteosarcoma. Recent studies show that hereditary diseases, like retinoblastoma, Rothmund-

*All authors have equal contribution.


1
Orthopaedics and Traumatology Department of University Emergency Hospital Bucharest, Romania,
panti.zsombor@gmail.com
2
Orthopaedics and Traumatology Department of University Emergency Hospital Bucharest, Romania;
University of Medicine and Pharmacy Carol Davila Bucharest. Romania
3
Beaty James H. Malignant tumors of bine. Campbells Oerative Orthopaedics 11TH edition, Mosby 2007,
901-907

20

December 2014

Thomson syndrome, Bloom syndrome, Li-Fraumeni syndrome increase the risk of


developing osteosarcoma4 5.
The symptoms of primary osteosarcoma are not specific, it consist of progressive
localized pain, which can be sever in late stages. The presence of night pain can be an
important sign for the true diagnosis. The radiological aspects consist of osteolytic lesions,
with bone production and destruction zone, with ill defined border. Codmans triangle as
periostal reaction suggests the malignant character of the lesions 6 7.
The surgical treatment of primary localized osteosarcoma consisted of the complete
removal or amputation of the affected limb. Nowadays due to the advent of chemotherapy
and the use of special modular prosthesis the aim in the treatment of osteosarcomas is limbsparing surgery for a better life quality of patients8.
In this paper we present a case of a patient with primary localized osteosarcoma, who
underwent to limb-sparing surgery with special prosthesis implantation.
CASE REPORT
A 17 year old male patient presented to orthopedics institution in the University
Emergency Hospital of Bucharest, with a palpable mass in the proximal third of the left leg,
with any remarkable medical personal history in the past. The symptoms appeared
approximately 8 months before presentation. The symptoms first consisted of slight pain with
a progressive character. According the patient mentions pain often occurred at night in the
last few weeks.
The clinical exam reveals a palpable mass of the proximal third of the antero-lateral
region of the left leg, with an approximate 10/7 cm size. The tumor was fixed to the deeper
tissues, the covering skin modification suggests the infiltrating and fast growing character of
the tumor. (Figure 1.)

Figure 1. Aspect of the tumor at the


clinical examination.

Figure 2. X-ray of the left leg showing ill


determined osteolytic lesions with periostal
reaction

Fuchs B, Pritchard DJ. Etiology of osteosarcoma. Clin Orthop Relat Res. 2002; 397:40-52.
Ottaviani G, Jaffe N. The etiology of osteosarcoma. Cancer Treat Res. 2009; 152:15-32.
6
Jacobs P, Radiological diagnosis of osteosarcoma. Proc R Soc Med. 1976; 69(8): 543546.
7
Hopper KD, Moser RP, Haseman DB, et al. Osteosarcomatosis. Radiology 1990; 175:22339.
8
Amstutz HC. Multiple osteogenic sarcomata: metastatic or multicentric: report of two cases and review of
literature. Cancer1969; 24: 923931.
5

21

Supplement No. 3/2014

After clincal exam standard X-ray examination was performed (Figure 2.), in order to
achieve better anatomical details of the tumor CT and MRI was performed, which confirms
the malignant character of the tumor, without any pathological modification of the chest,
abdomen, skull and pelvis (Figure 3.)

Figure 3. CT showing an expansive process of the proximal third of the left tibia with an
approximately 70mm, with periostal reaction and muscular invasion.

During laboratory examination the following parameters were changed: PT: 78,4%
(N:80-130); Alkaline phosphates 447 U/L (N:40-136 U/L); ESR: 39mm/h (N: 5-10mm/h).
Other laboratory results were within normal ranges.
After incision biopsy the hystological result was high grade malignancy osteosarcoma.
Due to the fast growing, highly malignant character of the tumor and in order to prevent
secondary metastasizes the patient undergoest to limb-sparing surgery with modular
prosthesis reconstruction.
The surgical procedure consisted of the resection of the proximal 1/3 of the tibia and of
the proximal extremity of the fibula with an anterior approach of the knee and proximal leg.
In order to reconstruct the extensor apparatus of the limb, the patellar tendon was des-inserted
from the tibial tuberosity. (Figure 4)

Figure 4. Tumoral piece after surgical removal of the tumor .

The preparation of the distal femur was performed with centromedullar guided distal
cut. For reconstruction of the knee joint and the proximal third of tibia special modular
prosthesis was used (Zimmer) The patellar tendon was reinserted in anatomical position on
the tibial part of the prosthesis, with gastrocnemius covering flap. (Figure 5)

22

December 2014

Figure 5. Modular prosthesis (A); distal femur cut (B); reconstruction


process with covering flap(C)

The removed bony and soft tissue components of the tumor were sent for further
histological examination. The results of the histological analysis confirm that the resection
was performed in between oncological limits, without any malignant cells in the resection
zone. Rehabilitation was begun on the second day after surgery with passive motions which
was followed by active motion exercises. Postoperative evolution of the patient was good,
partial weight bearing was achieved after 7 days of surgery. After 44 days of hospitalization
the patient leaves our institution. (Figure 6)

Figure 6. Postoperative X-ray of the reconstruction

23

Supplement No. 3/2014

6 Months after surgery the patient accuses slight dorsal chest pain and right distal thigh
pain, symptoms, which appeared a few weeks ago without disturbing the daily life. Standard
X-ray of the right lover limb reveals an osteolytical lesion of the distal third of the femur. Full
body CT scan evidences a space occupying process in the right costo-vertebral space at T3T4 level and also describes an osteolytic and osteoproductive process in the distal third of the
femur, whith periostal reaction. Bone scintigraphy with Tc 99m shows hypercaptation in
metabolic phase in the aforementioned thoracic and right femur region (Figure 7, 8)
Dispite of the adjuvant chemotherapy after surgical intervention, histological analysis
of the newly appeared lesion confirms the osteosarcom of the right distal femur, and of the
thorax.

Figure 7. CT scan of the thorax, space


occupying process in the right costo-vertebral
space.

Figure 8. Bone scintigraphy showing hypercaptation,


visible in thorax and in the right distal third of the
femur.

DISCUSSION
Metachronous osteosarcoma is rare type of bone malignancy with poor prognosis. The
pathology of metachronous osteosarcoma, is still unclear 9 10. initially, multiple primary
malignancies were favored, due to the absence of metastatic routes and the presence of
genetic mutations and hereditary diseases. Recent studies have proved that metastases can
appear, with similar mechanism to prostatic cancer metastases, via Batson venous plexus 11.
Hatori et al in a recent study demonstrated lymphatic spread to the lungs as possible routes
for metastases, which in the case of our patient could be the explanation of the appearance of
the space occupying process on the right costovertebral space 12.
Surgical treatment with modular prosthesis reconstruction of ostesarcoma, allows limb
salvage and do not affect the quality of life. The Surgical and chemotherapeutical
combination in therapy has proven its efficacy. Despite of the good short term results after
surgical and adjuvant chemotherapy, the appearance of the tumor in the thorax and the right
femur worsens the prognosis13 14.

Silverman G. Multiple osteogenic sarcoma. Arch Pathol 1936; 21 :8895.


Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric
Oncology Group study. J Clin Oncol 1998;16 :36413648.
11
Currall VA and Dixon JH, Synchronous Multifocal Osteosarcoma: Case Report and Literature Review
Volume 2006, 13
12
Hatori M, Ohtani H, Yamada N, Uzuki M, Kokubun S. Synchronous multifocal osteosarcoma with lymphatic
spread in the lung: an autopsy case report. Japanese Journal of Clinical Oncology.2001; 31(11):562566.
13
Thompson RC Jr, Cheng EY, Clohisy DR, et al. Results of treatment for metastatic osteosarcoma with
neoadjuvant chemotherapy and surgery. Clin Orthop 2002;397: 240247.
10

24

December 2014

This case underlines the importance of early and correct diagnosis. The mechanism of
the newly appeared tumors during chemotherapy is unclear, possible explanation is the
different chemosensitivty of the tumoral cells.
CONCLUSIONS
Early diagnosed, high grade localized osteosarcoma with surgical, so called limbsparing, treatment
with modular prosthetic reconstruction allows a better life quality.
Surgical treatment and adjuvant chemotherapy makes this pathology to have a good
prognostic index. Unfortunately with a still unclear mechanism, the appearance of metastases
and metachronous osteosarcoma worsens the prognosis
Our case report presents a rare appearance of osteosarcoma, with a reduced number of
similar reports in the reviewed literature.

14

Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric
Oncology Group study. J Clin Oncol 1998;16:36418.

25

Supplement No. 3/2014

REFERENCES
1.

Amstutz HC. Multiple osteogenic sarcomata: metastatic or multicentric: report of two cases and review
of literature. Cancer1969; 24: 92331.
2. Beaty James H. Malignant tumors of bine. Campbells Oerative Orthopaedics 11TH edition, Mosby
2007, 901-907
3. Currall VA and Dixon JH, Synchronous Multifocal Osteosarcoma: Case Report and Literature Review
Volume 2006, 13
4. Fuchs B, Pritchard DJ. Etiology of osteosarcoma. Clin Orthop Relat Res. 2002; 397:40-52.
5. Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric
Oncology Group study. J Clin Oncol 1998;16 :36413648.
6. Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric
Oncology Group study. J Clin Oncol 1998;16:36418.
7. Hatori M, Ohtani H, Yamada N, Uzuki M, Kokubun S. Synchronous multifocal osteosarcoma with
lymphatic spread in the lung: an autopsy case report. Japanese Journal of Clinical Oncology.2001;
31(11):562566.
8. Hopper KD, Moser RP, Haseman DB, et al. Osteosarcomatosis. Radiology 1990; 175:22339.
9. Jacobs P, Radiological diagnosis of osteosarcoma. Proc R Soc Med. 1976; 69(8): 543546.
10. Ottaviani G, Jaffe N. The etiology of osteosarcoma. Cancer Treat Res. 2009; 152:15-32.
11. Silverman G. Multiple osteogenic sarcoma. Arch Pathol 1936; 21 :8895.
12. Thompson RC Jr, Cheng EY, Clohisy DR, et al. Results of treatment for metastatic osteosarcoma with
neoadjuvant chemotherapy and surgery. Clin Orthop 2002;397: 240247.

26

December 2014

Medicine

MILD SYMPTOMS IN PRIMARY SPONTANEOUS


PNEUMOTHORAX IN THE EMERGENCY ROOM

Roxana CHELER1
Siegfried ALBU2
Adriana BIDIC 3

ABSTRACT:
THIS ARTICLE ANALYZES THE CASES OF PRIMARY SPONTANEOUS PNEUMOTHORAX PRESENTED IN
THE EMERGENCY UNIT OF THE EMERGENCY UNIVERSITARY CLINICAL HOSPITAL BUCHAREST IN
THE PERIOD JANUARY DECEMBER 2014. IT EMPHASIZES THE HIGH FREQUENCY OF CASES
SHOWING ONLY MILD SYMPTOMS, IN YOUNG PATIENTS, AND THE RISK OF UNDERDIAGNOSIS OF
THE CONDITION.
KEY WORDS: PNEUMOTHORAX, SPONTANEOUS, MILD SYMPTOMS, SMOKERS, YOUNG
PATIENTS

INTRODUCTION
Pneumothorax is defined as a collection of gas in the pleural space that results in
complete or partial collapse of the lung. A pneumothorax may occur spontaneously, or may
be secondary to underlying lung disease, chest trauma, mechanical ventilation, or perforated
esophagus.
Spontaneous pneumothorax most commonly occurs in previously healthy adults,
mainly smokers, between 20 and 40 years of age. In such patients there is a strong tendency
toward recurrence of the pneumothorax. Air leaks into the pleural space due to rupture of
small blebs on the surface of the visceral pleura. These blebs tend to be situated at the apex of
the lung, perhaps due to the more negative pleural pressure around the lung apex.
Symptoms include sudden onset unilateral pleuritic chest pain, dyspnea, and sometimes
a cough. Classical physical signs may or may not be present (depending upon the size of the
pneumothorax): tachypnea, tachycardia, hyper-resonant percussion and diminished breath
sounds over the affected side. The chest radiography reveals a visible visceral pleural edge
with no lung markings between this edge and the chest wall.

MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest


MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest, siegfried.albu@gmail.com
3
MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest
2

27

Supplement No. 3/2014

Approximately 50 percent of patients with spontaneous pnneumothorax have a


recurrence, and the incidence of further recurrence is even higher following the second
episode.
Management of spontaneous pneumothorax includes watchful waiting, with or without
supplemental oxygen, simple aspiration, or tube drainage, with or without medical
pleurodesis
MATERIALS AND METHOD
This article brings up the experience of the Emergency Unit Emergency Universitary
Clinical Hospital Bucharest in the period January December 2014. There were 18 cases of
spontaneous pneumothorax presented at the ER in this time period, out of which 14 were
male, and only 4 female, with an average age of 29 for the male patients and 28 for the
female.
Number of Patients and Average Age

29

30

28

25
20
15

14

Male
Female

10
5

0
No of Patients

Average Age

Out of the 18 cases, 12 were smokers (66%). The commonest complain was pleuritic
chest pain, of moderate intensity . On the Numeric Rating Scale for pain, only one patient
accused severe pain, with an intensity of 9.

28

December 2014

Pain Intensity

1, 5%
3, 17%

1 to 3
4 to 6

14, 78%

6 to 10

Dyspnea was a less common complaint, only 4 patients presented with shortness of
breath, out of which only 2 presented with O2 saturation under 90%.
Physical examination didnt reveal in more than half of the cases the classical physical
signs of tachypnea, hyper-resonant percussion and diminished breath sounds. All patients
were further investigated, arterial blood gas samples and chest radiographs were taken in all
cases.

Clinical Findings

Dyspnea

Hyperresonance

13

5
No Breath Sounds

No Clinical Signs

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Supplement No. 3/2014

Figure 1 Right spontaneous pneumothorax in a 25 year old male

All presented cases were admitted in the Thoracic Surgery clinic of the Emergency
Universitary Clinical Hospital Bucharest, the usual treatment consisting in chest tube
drainage.
CONCLUSIONS
Spontaneous pneumothorax affects mainly young people, usually males and smokers,
which may present with mild symptoms in the ER, thereby the risk of easily underdiagnosing
the condition, especially taking into account the overcrowding of ER units in Romania. The
diagnosis of spontaneous pneumothorax must be considered in all cases of chest pain, with or
without other signs or symptoms, especially in the presence of risk factors like young age and
smoking.
30

December 2014

REFERENCES
1.

2.

Saunders, Nicholas A., Ingram, Roland H. Jr., Diseases of the Pleura, Mediastinum, and
Diaphragm, in Harrisons Principles of Internal Medicine, Ninth Edition, edited by Kurt J.
Isselbacher, Raymond D. Adams, Eugene Braunwald, Robert G. Petersdorf, Jean D. Wilson
(McGraw-Hill, 1980), 1268
Wyatt, J.P., Illingworth, R.N., Graham, C.A., Clancy, M.J., Robertson, C.A., Oxford Handbook of
Emergency Medicine, 114-115

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Supplement No. 3/2014

Medicine

HYPOCAPNIA AS TRIGGER FOR THE DIAGNOSTIC


PROTOCOL IN PULMONARY EMBOLISM

Roxana CHELER1
Adriana BIDIC 2
Siegfried ALBU3

ABSTRACT:
THE ARTICLE ANALYZES THE CASES OF PULMONARY EMBOLISM PRESENTED IN THE EMERGENCY
UNIT OF THE EMERGENCY UNIVERSITARY CLINICAL HOSPITAL IN THE PERIOD JANUARY
DECEMBER 2014 AND EMPHASIZES THE IMPORTANCE OF HYPOCAPNIA AS A TRIGGER FOR THE
INITIATION OF THE DIAGNOSTIC PROTOCOL FOR PULMONARY EMBOLISM. IT CORRELATES
CLINICAL, LABORATORY, AND IMAGISTIC DATA FROM 79 PATIENTS DIAGNOSED WITH PULMONARY
EMBOLISM IN THIS TIME PERIOD. THE PRESENCE OF HYPOCAPNIA IN THE MAJORITY OF THE
PATIENTS IS ASCERTAINED, WITH THE RECOMMANDATION FOR EVALUATING ITS UTILITY IN THE
DIAGNOSIS OF PULMONARY EMBOLISM.
KEY WORDS: PULMONARY EMBOLISM, HYPOCAPNIA, DYSPNEA, ARTERIAL BLOOD GAS

INTRODUCTION
Pulmonary embolism (PE) is a dramatic and life-threatening complication of
underlying deep venous thrombosis. Most clinically relevant pulmonary emboli originate as
proximal venous thrombi in the leg or pelvic veins. Pulmonary embolism occurs when
thrombi detach and are carried through the great veins to the pulmonary circulation.
Pulmonary vascular occlusion has important physiologic consequences which lead to the
manifestations of illness as well as to clues to diagnosis. Pulmonary embolism has an impact
most notably on gas exchange and the circulation. Physical obstruction to pulmonary artery
flow creates dead space in the segments served by the affected arteries. The creation of dead
space has several effects on the partial pressure of carbon dioxide (P CO2) and end-tidal CO2
(ETCO2), which can provide clues to the diagnosis. If minute ventilation does not change, P CO2
will rise. However, most patients augment minute ventilation more than necessary to
maintain elimination of CO2, so that PCO2 typically falls with pulmonary embolism. 4

MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest


MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest
3
MD, Emergency Unit, Emergency Universitary Clinical Hospital, Bucharest, siegfried.albu@gmail.com
4
Nuala J. Meyer, Gregory A. Schmidt, Pulmonary Embolic Disorders: Thrombus, Air, and Fat, in Principles
of Critical Care, Third Edition, ed. Jesse B. Hall et al. (McGraw-Hill, 2005), 347-348
2

32

December 2014

This articles aim is to evaluate the presence of hypocapnia in patients with pulmonary
embolism and its eventual use as a marker in the diagnosis of the condition.
MATERIALS AND METHOD
The article presents the experience of the Emergency Unit Emergency Universitary
Clinical Hospital Bucharest in the period January December 2014. There were 79 patients
diagnosed with pulmonary embolism. Out of these, 42 (53.1%) were female, and 37 (46.9%)
were male. The most affected age group was over 60 years (see following charts), with 62
patients (78.4%). Symptoms included dyspnea in 54 patients (68%), syncope in 4 patients
(5.06%), chest pain in 11 cases (13.92%). 15 patients (18.98%) were asymptomatic or with
atypical complaints.

Figure 1. Age Distribution in


Pulmonary Embolism
1
1

90 - 100 Years

80 - 90 Years

11
10

70 - 80 Years
60 - 70 Years

15

11

Male
Female

34
4
4

50 - 60 Years

40 - 50 Years
30 - 40 Years

01

20 - 30 Years

01
0

10

20

Figure 2. Clinical Symptoms in PE

Dyspnea

15

Syncope

11
54
4

Chest Pain
Other

Out of the 79 examined patients, 69 (87.3%) had a PCO2 < 35 mmHg. Out of 29 patients
diagnosed with high-risk PE, 27 had hypocapnia (93.1%). Out of 39 patients diagnosed with
intermediate risk PE, 33 presented with hypocapnia (84.61%). In contrast, hypoxemia was
present at only 49 patients (62.02%).
33

Intermediate-risk PE

Supplement No. 3/2014

Figure 3. Hypocapnia in PE

39

6
33
29

PE - All Patients

2
No of Patients

27

Pco2 > 35 mmHg

79

Pco2 < 35 mmHg

10

69
0

50

100

D-dimer testing showed elevated D-dimer levels in most of the patients.


Electrocardiographic changes (right bundle-branch block, inversion of T-waves in leads V1V4, S1Q3T3 pattern) were present in 31 cases (39.2%). Haemodynamic instability was
present in 23 patients (29.11%).
Figure 4. D-Dimer Levels in PE

12,
15%
22,
28%

> 3.5 mcg/l

45, 57%

2 - 3.5 mcg/l
< 2 mcg/l

The diagnosis of pulmonary embolism was confirmed in all cases by thoracic computer
tomography with intravenous contrast. The patients were admitted in the cardiology clinic of
the Emergency Universitary Clinical Hospital.

34

December 2014

Figure 5. Massive bilateral PE in a 67 year old female patient5

Figure 6. Massive bilateral PE in a 67 year old female patient6

5
6

Department of Radiology and Medical Imagistics, SUUB


Department of Radiology and Medical Imagistics, SUUB

35

Supplement No. 3/2014

CONCLUSION
Hypocapnia is associated in a significant percentage with the diagnosis of pulmonary
embolism, confirmed by CT imaging. As this article shows, hypocapnia may be used as a
trigger in initiating the protocol for diagnosis of pulmonary embolism in the emergency
department. Monitoring and careful investigation of all patients presenting with hypocapnia
in the emergency room is also recommended.

36

December 2014

REFERENCES
1.

Meyer, Nuala J., Schmidt, Gregory A., Pulmonary Embolic Disorders: Thrombus, Air, and Fat,in
Principles of Critical Care, Third Edition,edited by Jesse B. Hall, Gregory A. Schmidt, Laurence D.
H. Wood, McGraw-Hill, 2005, 347-348

37

Supplement No. 3/2014

Medicine

ARTHROSCOPIC BANKART WITH METTALIC SUTURE


ANCHORS FOR UNSTABLE DISLOCATING SHOULDERS:
CASE REPORT

Alexandru LUPU1
Razvan ENE2

ABSTARCT
WE PRESENT A CASE OF ARTHROSCOPIC FIXATION FOR BANKART LESION WITH METTALIC
SUTURE ANCHORS AT A 18-YEAR-OLD TEENAGER WHO SUSTAINED RECURRENT DISLOCATIONS ON
HIS LEFT SHOULDER, THE FIRST EPISODE HAVING OCCURRED TWO MONTHS BEFORE THE
SURGERY. DISLOCATION OF THE HUMERAL HEAD IS A COMMON TRAUMATIC DISORDER AND
MOST FREQUENTTHE DISLOCATION IS ANTEROINFERIOR ACCORDINGLY THIS CAUSES A
DETACHMENT OF THE ANTEROINFERIOR CAPSULOLABRAL COMPLEX. THE CLINICAL
EXAMINATION, RADIOGRAPHS AND MRI DESCRIBED THE BANKART LESION THUS THE
ARTHROSCOPIC TREATMENT WAS CHOSEN AND THE FIXATION OF THE LABRUM WAS PERFORMED
WITH SUTURE ANCHORS IN THE POSITION OF 1, 3 AND 5 O'CLOCK. AFTER THE SURGERY THE
SHOULDER REHABILITATION WAS INTRODUCED ON THE INSTANT.
KEY WORDS: BANKART LESION, SUTURE ANCHORS, SHOULDER ARTHROSCOPY, RECURRENT
DISLOCATIONS, ARTHROSCOPIC FIXATION.

INTRODUCTION
The Bankart lesion, also called the avulsion fractures of the anterior glenoid rim,
represents the injury of the anterior glenoid labrum due to anterior shoulder dislocation and is
associated with anteroinferiorglenohumeral instability. There are described two types of
labral tears: SLAP tears and Bankart lesions. Concerning the Bankart lesions, these are
located in the 3-6 o'clock position where the humeral head dislocates and due to the labral
tears the shoulder is often unstable and suffers multiple dislocations. It is known that the
incidence ranges from 4% to 70% in the literature the male patients having an increased
prelevance. 3
*All authors had equal contribution
1
Orthopaedics-Traumatology Department of Bucharest Emergency University Hospital; Carol Davila
University of Medicine and Pharmacy, Bucharest.
2
Orthopaedics-Traumatology Department of Bucharest Emergency University Hospital; Carol Davila
University of Medicine and Pharmacy, Bucharest, razvan77ene@yahoo.com
3
Davidson PA, Tibone JE. Anterior-inferior (5 o'clock) portal for shoulder arthroscopy.Arthroscopy. 1995; Lo
IK, Parten PM, Burkhart SS. The invented pear glenoid: an indicator of significant glenoid bone loss.
Arthroscopy. 2002; Burkhart SS, DeBeer JF, Tehrany AM, et al. Quantifying glenoid bone loss arthroscopically
in shoulder instability. Arthroscopy, 2002

38

December 2014

CASE REPORT:
A 18-year-old left handed teenager presents in our clinic with pain and partial
functional impotence on his left shoulder. These simptoms occurred after recurrent anterior
dislocations, two months before the first episode. After clinical, X Ray and MRI
investigations( Fig. 1) the diagnosis of Bankart lesion is established. The recurent
dislocations always occurred while the pacient's practice exercises with weights. The
symptoms of severe pain and deformity decreased after a spontaneous reduction while lifting
his left arm. During the clinical examination we also perceived shoulder instability and the
patient noticed that his left shoulder was feeling unsteady and nevertheless the humeral head
could actually slip out of the joint in distinct positions for instance when the arm was across
the body. The physical exam highlighted differences between active and passive motion
which indicates capsular contracture and therewith were performed tests for anterior
instability such as the apprehension sign and sulcus sign. Manual examination of the left
shoulder emphasized anteroinferior instability while the contralateral right shoulder showed
no instability which indicates that the left shoulder instability was due to a traumatic injury.
As well, the patient claimed that the pain in the past two months often interfered with sleep
and sustained limitations in activity and the prior treatment he tried was rest and antiinflammatory medication. After all the examinations it was decided to be performed the
arthroscopic Bankart repair with 2 mettalic suture anchors. (Fig. 2).

Bony Bankart: glenoid rim fracture ( IRM- view )


Fig. 1

Mettalic suture anchor (Arthroscopic view)


Fig. 2

Therefore, the patient was placed in the so called beach-chair position under general
anesthesia and a posterior and two anterior approaches were used. The Bankart lesion, the
capsular tears and the rotator cuff were acknowledged and after the ligament has been
completely disengaged just than the glenoid neck was prepared with a burr. Still than, we
used an arthroscopic elevator to mobilize the capsulo-labral sleeve from the glenoid and we
could also see the subscapularis muscle just underneath the mobilized labral tissue. ( Fig. 3).
Forwards, we used the burr for creating a bleeding bone surface on the glenoid rim and also

39

Supplement No. 3/2014

removed the cartilage from the glenoid face allowing the surgeon to place the suture anchors
on the glenoid face. It was used the switching stick technique for placing one set of sutures
outside of the working posterior cannula while the remaining suture pair was separated with
one strand exiting the posterior cannula. Using a suture hook we saw into the inferior
glenohumeral ligament in the immediate vicinity of the anchor using it as a suture shuttling
device.( Fig. 4).

Anterior glenohumeral injury- Arthroscopic view


Fig. 3

Types of suture anchors


Fig.4

Moreover, we made the stability test but only after having inserted three double-louded
anchors and six high-strength sutures retrograded through the detached labrum. We could
observe from the antero-inferior portal the humeral head which was well centered into the
glenoid cavity. After surgery an X-ray inspection has been made, ( Fig.5 ), the patient's upper
limb was settled in a sling in neutral rotation for a minimum of 30 days, passive exercise was
permitted at postoperative 3 weeks and active exercise scarcely at 5 weeks after the Bankart
surgery.

Mettalic suture anchor (X-Ray)


Fig. 5

40

December 2014

DISCUSSION
Bankart lesions, over time, have been generally treated by open reduction, however,
arthroscopic reduction and internal fixation using cancellous screws or suture anchors,
newly, had successful effects concerning the recurrence rate and also functions in shoulders4.
Arthur Sydney Blundell described the Bankart lesion as being a traumatic detachment of the
glenoid labrum and this type of lesion is described in over 85% of all cases after traumatic
anterior dislocation. The mechanism consists in the fact that the humeral head is forced
against the joint capsule and inferior glenohumeral ligament which it stretches afterwords, by
way of traction, the fibrous labrum is pulled off from the inferior half of the anterior rim of
the glenoid5.
Therewith, Bankart described the respectively lesion in no more than 27 cases in 19231938 and he insistently denied the presence of a glenoid rim fracture in any of his cases. The
shoulder almost all the time dislocates antero-inferior because of the acromion, coracoid
process and the rotator cuff that confines the motion to superior. In the case of the anteroinferior dislocation, damages are made to the antero-inferior rim of the glenoid in the 3-6
o'clock position mostly young patients having Bankart fractures or Bankart lesions. By these
circumstances patients obtain instabillity and recurrent dislocations6. It is also very important
to distinguish the shoulder instability from other causes of shoulder dysfunction for instance
arthritis rotator cuff tear or snapping scapula. Always the efficiency of a surgical procedure
depends, on one hand, on the health and motivation of the patient and on the other hand, on
the condition of the shoulder and besides that, the surgery is considered for patients with
recurrent instability, feelings of unsteadiness after a traumatic shoulder dislocation or with an
atraumatic instability but that has not responded to the rehabilitation program. It is known
that shoulder function and stability are restored after 2 years from the surgery in most cases,
the range of motion is minimally reduced and only a few charge a 20 degrees loss of external
rotation7. Sleeping, performing activities of daily living and engaging in recreational activities
are just a few improvments. In another train of thoughts, it has been established that the
majority of the arthroscopic Bankart repair failures were due to the presence of glenohumeral
bone defects thus it is high-class recommended to assess the amount of glenohumeral bone
loss at each patient 8. All in all, the outcomes of arthroscopic repair of Bankart lesions are
favorable, this case being confirmed by Netto et al who reported some encouraging results. A
study based on a number of 50 patients under the age of 40 with traumatic anterior shoulder
4

Jana M, Srivastava DN, Sharma R et al. Spectrum of magnetic resonance imaging findings in clinical
glenohumeral instability. Indian J Radiol Imaging, 2011; Porcellini G, Campi, Paladini P Arthroscopic approach
to acute bonzBankart lesion. Arthroscopy 2002
5
T. Sano, H Matsuoka, and K Nakayama, Arthroscopic treatment of an anterior glenoid fracture with a
cannulated, headless screw and suture anchors: a case report, Knee Surgery, Sports Traumatology,
Arthroscopy, 2009; Doo-Sup Kim & Chang-Ho Yi &Yeu-Seung Yoon- Arthroscopic repair for combined
Bankart and superiorlabral anterior posterior lesions: a comparative study between primary and recurrent
anterior dislocation in the shoulder; International Orthopaedics (SICOT) (2011)
6
Abrams JS, Savoie FH, Tauro JC, et al. Recent advance in the evalution and treatment of shoulderinstability:
anterior, posterior, and multidirectional. Arthroscopy. 2002
7
Burkhart SS, deBeer JF. Traumatic glenohumeral bone defects and their relationship to failure of arthroscopic
Bankart repairs: significance of the inverted-pear glenoid and the humeral engaging Hill Sachs lesion. 2000; P.
J. Millett and S. Braun, The Bony Bankart Bridge procedure: a new arthroscopic techniquie for reduction and
internal fixation of a Bony Bankart lesion, Arthroscopy, 2009; Gerard WW Ee*, Sedeek Mohamed and
Andrew HC Tan - Long term results of arthroscopic bankart repair for traumatic anterior shoulder instability;
Journal of Orthopaedic Surgery and Research 2011
8
Kandzira F, Jager A, Bischof F, et al. Arthroscopic labrum refixation for post traumatic anterior
instability:suture anchor versus transglenoid fixation technique. Arthroscopy. 2000; Elrod BF. Arthroscopic
reconstruction of traumatic anterior instability. Op Tech Sports Med, 1997

41

Supplement No. 3/2014

instability and a Bankart lesion, aimlessly assigned to receive open or arthroscopic treatment,
showed afterv a follow-up period of 37 months a significant difference favorable to the
patients treated with the arthroscopic technique but without clinical relevance. Furthermore,
there was no statistically significant difference concerning complications, failure or range of
motion between these two techniques.9
Waterman et al also analysed the outcomes of 3,854 military patients who passed
through a Bankart repair, mostly having been performed arthroscopically,between 2003 and
2010. In this lot of patients a percentage of 92% was represented by men and the mean age
was 28 years, The results showed that the rate of surgical failure for the patients who
underwent arthroscopic Bankart repair was of 4,5%, significantly lower than the other lot, the
patients operated by the open anterior stabilization technique, which recorded a percentage
of 7,7% of failure. Thus, it was determined that the risk factors for surgical failure were the
open repair, younger age and inpatient status and the retrospectively analyzed complications
were turned out to be the, for both cases, recurrent instability, stiffness and nevertheless,
neurovascular injury10. Therewith, Ateschrang A. et al preffered method was revealed to be
the arthroscopic Bankart repair, the most important reasons being the shorter time of
hospitalization after the surgery and the shorter operation time 11. Kim et al also reported on
89 patients charging posttraumatic anterior shoulder instability that were treated in 59 cases
arthroscopically and in 30 cases with open procedure. All the patients were received
operation with suture anchors and at the follow-up evaluation it was highlighted that the
percentage of good to excellent results meaning 91,5% was for the arthroscopic group,higher
than in the open repaired group (86,6 %)12.
CONCLUSIONS
The latest arthroscopic stabilization techniques are technically demanding and the most
important benefits are represented by decreased morbidity, faster recovery and rehabilitation
and, nevertheless, diminished patient pain.Suture anchors are an excellent mean of reinsertion
of the capsule-labral complex andWalch-Duplay test is an easily applicable test for the
evaluation of activity, stability, pain and mobility of the shoulder after arthroscopic Bankart
repair 13. The hospitalization time is shorter, thereby, the patient is discharged the next day
after the surgery which leads to lower costs for maintenance.

Netto, N. A., Tamaoki, M.J.S., Lenza, M., Santos, J.B.G.D, Matsumoto, M. H., Faloppa, F., &Belloti,
J.C.Treatmet of Bankart lesions in traumatic anterior arthroscopy and open techniques. Arthroscopy, The
Journal ofArthroscopic& Related Surgery. 2012
10
Waterman, B. R., Burns, T. C., McCriskin, B., kilcoyne, K., Cameron, K.L., & Owens, B. D. Outcomes after
Bankart Repair in a Military Population: Predictors for Surgical Revision and Long- Term Disalitity.
Arthroscopy: The Journal of Arthroscopic& Related Surgery. 2014
11
Ateschrang A, Fiedler S, Schrter S, Stckle U, Freude T, Kraus TM. Duration of inability for work and
return to physical work after arthroscopic and open labrum refixation. Z OrthopUnfall. 2014;
12
Kim S-H, Ha K I, KIM S-H. Suture anchor capsulorraphy in the traumatic anterior shoulder instability: Open
versus arthroscopic technique. AAOS 67th Annual Meeting 2000
13
Sugaya H Kon Y, Tsuchiya Arthroscopic repair of glenoid fractures using suture anchors. Arthroscopy 2005;
Boszotta H, Helperstorfer W. Arthroscopic transglenoid suture repair for initial anterior shoulder dislocation.
Arthroscopy. 2000

42

December 2014

REFERENCES
1.
2.
3.
4.
5.
6.

7.

8.
9.

10.
11.
12.
13.
14.

15.

16.
17.
18.
19.

Davidson PA, Tibone JE. Anterior-inferior (5 o'clock) portal for shoulder arthroscopy.Arthroscopy.
1995
Lo IK, Parten PM, Burkhart SS. The invented pear glenoid: an indicator of significant glenoid bone
loss. Arthroscopy. 2002
Burkhart SS, DeBeer JF, Tehrany AM, et al. Quantifying glenoid bone loss arthroscopically in
shoulder instability. Arthroscopy, 2002
Jana M, Srivastava DN, Sharma R et al. Spectrum of magnetic resonance imaging findings in
clinical glenohumeral instability. Indian J Radiol Imaging, 2011
Porcellini G, Campi, Paladini P Arthroscopic approach to acute bonzBankart lesion. Arthroscopy
2002
T. Sano, H Matsuoka, and K Nakayama, Arthroscopic treatment of an anterior glenoid fracture
with a cannulated, headless screw and suture anchors: a case report, Knee Surgery, Sports
Traumatology, Arthroscopy, 2009
Doo-Sup Kim & Chang-Ho Yi &Yeu-Seung Yoon- Arthroscopic repair for combined Bankart and
superiorlabral anterior posterior lesions: a comparative study between primary and recurrent anterior
dislocation in the shoulder; International Orthopaedics (SICOT) (2011)
Abrams JS, Savoie FH, Tauro JC, et al. Recent advance in the evalution and treatment of
shoulderinstability: anterior, posterior, and multidirectional. Arthroscopy. 2002
Burkhart SS, deBeer JF. Traumatic glenohumeral bone defects and their relationship to failure of
arthroscopic Bankart repairs: significance of the inverted-pear glenoid and the humeral engaging Hill
Sachs lesion. 2000
P. J. Millett and S. Braun, The Bony Bankart Bridge procedure: a new arthroscopic techniquie for
reduction and internal fixation of a Bony Bankart lesion, Arthroscopy, 2009
Gerard WW Ee*, Sedeek Mohamed and Andrew HC Tan - Long term results of arthroscopic bankart
repair for traumatic anterior shoulder instability; Journal of Orthopaedic Surgery and Research 2011
Kandzira F, Jager A, Bischof F, et al. Arthroscopic labrum refixation for post traumatic anterior
instability:suture anchor versus transglenoid fixation technique. Arthroscopy. 2000
Elrod BF. Arthroscopic reconstruction of traumatic anterior instability. Op Tech Sports Med, 1997
Netto, N. A., Tamaoki, M.J.S., Lenza, M., Santos, J.B.G.D, Matsumoto, M. H., Faloppa, F.,
&Belloti, J.C.Treatmet of Bankart lesions in traumatic anterior arthroscopy and open techniques.
Arthroscopy, The Journal ofArthroscopic& Related Surgery. 2012
Waterman, B. R., Burns, T. C., McCriskin, B., kilcoyne, K., Cameron, K.L., & Owens, B. D.
Outcomes after Bankart Repair in a Military Population: Predictors for Surgical Revision and LongTerm Disalitity. Arthroscopy: The Journal of Arthroscopic& Related Surgery. 2014
Ateschrang A, Fiedler S, Schrter S, Stckle U, Freude T, Kraus TM. Duration of inability for
work and return to physical work after arthroscopic and open labrum refixation. Z OrthopUnfall. 2014;
Kim S-H, Ha K I, KIM S-H. Suture anchor capsulorraphy in the traumatic anterior shoulder
instability: Open versus arthroscopic technique. AAOS 67th Annual Meeting 2000
Sugaya H Kon Y, Tsuchiya Arthroscopic repair of glenoid fractures using suture anchors.
Arthroscopy 2005.
Boszotta H, Helperstorfer W. Arthroscopic transglenoid suture repair for initial anterior shoulder
dislocation. Arthroscopy. 2000;

43

Supplement No. 3/2014

Medicine

ACUTE STROKE IN EMERGENCY ROOM TREATED WITH


NEW INTERNATIONAL PROTOCOL - THROMBOLYSIS

Liviu ULMEANU1

ABSTRACT:
THIS PRESENTATION REFERS TO THE CURRENT MANAGEMENT AND TREATMENT OF ADULTS WITH
ISCHEMIC STROKE EXEMPLIFYING RAPID NEUROLOGICAL RECOVERY THANKS TO NEW METHODS
OF TREATMENT USING ALTEPLASE THROMBOLYSIS ACCORDING TO NEW GUIDELINES FOR THE
TREATMENT OF ISCHEMIC STROKE.
KEY WORDS: STROKE, GUIDELINES, THROMBOLYSIS, ALTEPLASE

INTRODUCTION
This was a case study in which a male patient (NN) with acute ischemic stroke was
treated in the Emergency Room of the University Hospital of Emergency Bucharest by
applying thrombolysis with alteplase as treatment2 protocol3. After the initial treatment phase,
the patient was admitted to the Clinic of Neurology of the same hospital.
MAIN TEXT
Patient NN is 48 years old and is known with surgery about a month ago for a herniated
disc in the lumbar spine. He is hypertensive and follows home treatment with Enalapril. NN
is brought to the emergency room of the University Hospital of Emergency Bucharest, for
sudden alteration of consciousness and motor deficit in his left limbs. Symptoms started 2
hours and 30 minutes prior to hospital presentation with a violent headache, followed by
fallout episode from his own height and loss of consciousness. Subsequently, the patient has
progressive alteration of general state and left limb motor deficit (debut 09:00).
The neurological objective at emergency room: 1) At the time of presentation: drowsy
patient, vigilant at verbal stimuli, does not speak, performs inconstant simple orders,
mydriasis in his left eye, left hemiplegia and paretic motor limb deficit in the right limbs, the
plantar cutaneous reflex does not occur bilaterally. 2) After 20 minutes the Glasgow Coma
Scale score was 4 points, left eye mydriasis and photo-motor reflex absent at the same level,

MD., Emergency Department, University Hospital of Emergency Bucharest, liviu_ulm@yahoo.com


The treatment has benefits shown in Effect of treatment delay, age, and stroke severity on the effects of
intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data
from randomised trials
3
The protocol described in Diagnostics and treatment guide for cerebrovascular diseases was used
2

44

December 2014

tetraparesis with plegic leftlimb motor deficit, nociceptive stimulation is defended in


abnormal extension of the upper limbs, plantar cutaneous reflex does not occur bilaterally.

A)

B)

C)

Figure 14: Native brain CT A) Axial view, B) Sagittal view, C) Coronal view

The National Institutes of Health Stroke Scale score at 12: 30 was 25 points. An
emergency native brain CT was performed that did not show any recent endocranial vascular
modifications or focal, diffuse infra density or supratentorial abnormalities. The ASPECTS
score was 10 points.
Given that the patient did not have contraindications and was in the therapeutic
window, at 12:45, the thrombolytic therapy was initiated intravenously with Actilyse 0.9 mg/
kg. During thrombolysis, the blood pressure was maintained in the range of 170 / 70-110 / 50
mmHg. The patient showed no adverse reaction to the administration of Actilyse. Previously,
the benefits and risks of therapy with reteplase were explained to the family, which
understood, accepted and signed the informed consent.
At the end of thrombolysis, 1:45 p.m., the patient was conscious, cooperative, and
slightly drowsy, with discrete dysarthria. He could perform simple and complex orders and
4

The Computer Tomography images are given courtesy of the Imagistics Department, University Hospital of
Emergency Bucharest

45

Supplement No. 3/2014

he had equal intermediate pupils, without any signs of deficit in the sphere of the cranial
nerves. The patient could mobilize all the limbs symmetrically. The Glasgow Coma Scale
score was 15 points and the National Institutes of Health Stroke Scale score was 2 points. The
procedure took place in the Emergency Room the University Hospital of Emergency
Bucharest.

Figure 25: Cerebral angiography A) Right carotid artery, B) Left carotid artery

Figure 36: Cerebral angiography Left vertebral artery with left cerebral posterior artery imputed

The images are given courtesy of the Imagistics Department - Angiograph, University Hospital of Emergency
Bucharest
6
The images are given courtesy of the Imagistics Department - Angiograph, University Hospital of Emergency
Bucharest

46

December 2014

Subsequently, a "4 vessels" cerebral angiography was undertaken, in order to see a


distal thrombus in the left posterior cerebral artery (fig. nr. 2 and fig. nr. 3).
Several investigations were performed:
Electrocardiogram - sinus rhythm with a heart rate of 100 beats per minute without
repolarization alterations;
Transthoracic cardiac ultrasound - showed no suggestive images of thrombus, undilated cavities, predominantly septal left ventricular hypertrophy, left ventricular
wall kinetics with normal ejection fraction 70%, without valvulopathy
hemodynamically significant, free pericardia;
Laboratory tests - mixed dyslipidemia without any pathological values;
Native brain computer tomography at 24 hours after thrombolysis - small hypodense
area left occipital cortical-subcortical with ischemic appearance; area with appearance
of ischemia in the left thalamus which determines fingerprinting the lateral ventricle
of this part - lesions are superficial and deep, situated in the territory of the left
posterior cerebral artery, fluid periencefalic spaces with dimensions in the age limits,
symmetrical ventricular system on the midline.
During hospitalization, the patient's evolution was favorable. At discharge, the patient
shows paresthesia with character of numbness in the right upper limb without focal
neurological signs.
CONCLUSION
Despite a bad prognosis, with a high risk of death, the treatment with Alteplase
increased the patients odds of a good stroke outcome. With earlier treatment applied he had a
full neurological recovery and the chance of living a normal life thereon.

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Supplement No. 3/2014

REFERENCES
1.

2.
3.
4.

Ovidiu, Bjenaru; Ghid de diagnostic si tratament pentru bolile cerebrovasculare (Diagnostics and
treatment guide for cerebrovascular diseases), Ministerul Sanatatii, Last Accessed on 22.12.2014,
http://www.ms.ro/documente/ghid%201_8292_5994.pdf ;
Bret S., Stetka; Helmi L., Lutsep;, New Stroke Management Guidelines: A Quick and Easy Guide,
Article in Medscape Neurology, February 27, 2013;
Susan, Jeffrey; New AHA/ASA Guidelines for Acute Stroke Treatment, Article in Medscape
Neurology, January 31, 2013;
Jonathan, Emberson; Kennedy R., Lees; Patrick, Lyden; et. al., Effect of treatment delay, age, and
stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a
meta-analysis of individual patient data from randomised trials, The Lancet Journal, Volume 384, No.
9958, p19291935, 29 November 2014;

48

December 2014

Medicine

IMPLICATIONS OF UTERINE ARTERY EMBOLIZATION


FOR UTERINE FIBROMATOSIS

Diana VOICU1
Liviu POPOVICI2
Dragos DAVITOIU 3
Ioana ROTAR4

ABSTRACT:
THE PRESENT STUDY EXAMINES THE FAVORABLE EFFECT OF UTERINE ARTERY EMBOLIZATION
IN MINIMALLY INVASIVE TREATMENT OF SYMPTOMATIC UTERINE FIBROIDS AT WOMEN AGED
BETWEEN 20 AND 70 YEARS. ARE PRESENTED PATHOLOGICAL ASPECTS, TECHNIQUE AND
COMPLICATIONS AND CONSEQUENCES OF THE UTERINE EMBOLIZATION.
CONCLUSION. UTERINE ARTERY EMBOLIZATION RESULTS IN A REDUCTION OF THE VOLUME OF
MYOMAS AND IS NEEDED ESPECIALLY AS A PRIMARY THERAPY BUT CAN ALSO BE USED AS
ADJUNCTIVE THERAPY IN THE UTERUS CONSERVATIVE INTERVENTIONS FOR REDUCING THE
NUMBER OF TOTAL HYSTERECTOMIES IN FAVOR OF CONSERVATIVE MYOMECTOMY.
IN THE STUDY GROUP WE OBSERVED NORMALIZATION OF MENSTRUAL CYCLES SINCE THE
FIRST TWO MENSTRUAL CYCLES IN A 70% OF PATIENTS AND THE EFFICACY WAS 88% ON
REDUCTION THE MENOMETRORRHAGIA.
KEY WORDS: UTERINE ARTERY EMBOLIZATION, UTERINE FIBROID, METRORRHAGIA.

INTRODUCTION
Uterine artery embolization is a minimally invasive technique becoming more popular
as a safe and effective alternative to replace hysterectomy and myomectomy.
The most frequent benign gynecological pathology is uterine fibroid, which
complication is abundant menometrorrhagia that can reach up to severe iron deficiency
anemia3.
Uterine artery embolization was inspired by techniques used in neuroradiology which
consists in inducing necrosis of myoma which involves cutting off blood flow to the fibroid,
causing it to shrink, using inframilimetric embolic agents.
1

MD, Department of Obstetrics and Gynecology, University Emergency Hospital Bucharest, Romania
MD, PhDc, Department of Obstetrics and Gynecology, University Emergency Hospital Bucharest, Romania
3
MD, PhD, Department of Surgery, University Emergency Hospital Bucharest, Romania
4
Assistant Professor MD, PhD, Department of Obstetrics and Gynecology, University of Medicine and
Pharmacy Iuliu Hatieganu Cluj-Napoca, Romania
2

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Supplement No. 3/2014

In 1993 J. Jacques Merland and J. Ravina performed uterine artery embolization as an


alternative to surgery; the tehnique was a real success4.
Embolization procedure is a minimally invasive technique that determines ischemia of
the fibroid structures and gradual resorption of the nodules in time 5.
Uterine fibroid is a benign tumor composed of myometrial and connective tissue 6,7.
Depending on the predominance of connective/muscular tissue the tumor is called fibroid,
myoma (uterine leiomyoma) fibromyoma or fibroleiomyoma8.
Uterine fibroids (leiomyoma, fibroleiomyoma) affect a large number of women of
childbearing age (20% -40% of the patients)9.
Despite the fact that their cause is still unknown, yet there is considerable evidence that
estrogens and progestogens stimulate tumor growth proliferation, as the fibroids rarely
appear before menarche and regress after menopause10-13.
Uterine fibroids are the most common benign tumors in women and the leading
indication for hysterectomies in the USA14,15.
Uterine artery embolization principle consists of devascularisation (ischemia) target
sites (fibromyomas, arteriovenous malformation, cervical malignancies etc) with embolic
agents that obstruct the vascular lumen and determine cutting off blood flow to the fibroid,
causing it to shrink2.
Uterine fibroids benefit most from this technique and the most frequent symptom,
which requires embolization, is uterine bleeding (menometrorrhagia). The only sure method
until 20 years ago to cure uterine fibroids was hysterectomy, thus existence of uterine fibroids
were the indication in 30-70% cases of radical hysterectomy16-18.
Principle of the uterine embolization is induction of necrosis, fibrous organization and
gradual resorption of the fibroma and succeed only when the fibroma is intensely
vascularized19.
Uterine artery embolization is contraindicated during pregnancy or renal disease with
severe renal insufficiency, pelvic inflammatory disease, genital cancers (ovarian,
endometrial). A relative contraindication is the severe allergy to the contrast 20.
In our study the uterine embolization and angiography were performed in the
Angiography Laboratory of the Radiology Department of the Emergency University
Hospital Bucharest under maximum aseptic conditions. The following materials were used:
- scalpel blade
- puncture needle 21G, 18G
- introductory set 4F (french) or 5F
- depending on the vascular anatomy catheter 4F, 5F
- Syringe 5, 10 and 20 ml
- 1% lidocaine, heparin saline.
Some authors recommend the use of microcatheter 3F in case of small diameter vessels
21
. Uterine artery embolization was performed in an angiographic laboratory using
fluoroscopic guidance under local anesthesia. An access sheath and guidewire were
introduced into the artery (radial or femoral). In order to select the uterine vessels for
embolization, a guiding catheter was used and placed into the uterine artery under xray fluoroscopy guidance. At the level of the uterine artery an angiogram with contrast was
performed to confirm placement of the catheter and the embolizing agent were injected.
Blood flow to the fibroid started to fade significantly, causing the uterine fibroid to shrink.
Vascular arterial puncture involves a Seldinger; we used 4F or 5F arterial sheath.
50

December 2014

We used the following embolization agents:


1. Polyvinyl PVA particles (Contour, Ivalon)
2. TachoComb, Gelaspon, Gelfoam
3. Embosfere-sized particles in suspension.
Although it is a minimal invasive procedure, the uterine artery embolization procedure
does not exclude the possibility of complications. These complications can be divided into
three categories:
- Immediate - directly related to endovascular intervention
- Acute - occurs in the first 30 days post procedure
- Late - installed after 30 days of the embolization.

Minor

Major

Immediate

3.5 %

Acute

13 %

Late

8.5 %

Late

1.5 %

Alergy 2.5 %
Puncture site
hematoma 1 %
Endometritis
Urinary infectios
Variabile intensity
pain
Fibroid expulsion
Transient
amenorrhea
Permanent
amenorrhea
Severe sepsis
caused by uterine
necrosis 2 cases
(total
hysterectomy)
important
metrorrhagia total hysterectomy

Table 1 Complications in the studied group

We present the pathological findings - obtained by the two myomectomy performed


after 2 and 6 months after uterine artery embolization. Macroscopic appearance after 6
months: myomas appear diminished in volume, whitish, avascular (absent peripheral
circulation), cleavage easy with adjacent myometrium, which is apparently normal
vascularity. Microscopic appearance at 6 months post fibroid embolization reveals hyaline
sclerosis and normal appearance of the myometrium.

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Supplement No. 3/2014

Figure 1- Histological appearance 6 months after embolization: a fibroid hyaline sclerosis, normal
appearance of the myometrium

Figure 2- Polivinilformaldehid fragments in the lumen of the peripheral vessel of a myoma, absence of
inflammatory reaction.

MATERIALS AND METHODS


The personal research involved a retrospective epidemiological analysis - associated
with a clinical trial for a period of three years: 01.01.2010-31.12.2012. The studied group
includes 200 patients hospitalized in the Department of Obstetrics and Gynecology .We used
as working material data from observation sheets, clinic archive, surgical protocols, data from
the statistics department of the hospital. The 200 patients in the research group were selected
based on clinical diagnosis and imaging: symptomatic uterine fibroids (bleeding, pain,
compression neighboring organs), infertility, cervical cancer in terminal stage (III-IV) with
significant bleeding. Infertility caused by uterine fibroids was established by history (> 2
52

December 2014

miscarriages in the first quarter and II) clinical examination and imaging diagnosis
(ultrasound and nuclear magnetic resonance).
Year

Cervical

Fibroids

Total

Cervical and

cancer stage

tubal

III-IV

pregnancies

2010

7 (2%)

342 (97%)

4 (1%)

353

2011

13 (5.2%)

233 (94%)

2 (0.8%)

248

2012

6 (5.3%)

277 (92.4%)

7 (2.3%)

300

Total

36 (4%)

852 (94.6%)

13(1.9%)

901

Table 2 - Total cases of uterine embolization during 2010-2012 in Radiology Department of the
Emergency University Hospital Bucharest

Of the total 200 uterine artery embolizations, 38.2% were performed as adjuvant
therapy, and 61.8% as primary therapy.

Uterine artery embolization


type
124
Primary therapy
76
Adjuvant therapy
Total
200

No of cases

Percentage
61.8 %
38.2 %
100 %

Table 3 - Types of uterine embolization of the study group

A total of 76 cases were operated (46 cases of myomectomia, and 30 clasic


hysterectomy.
No of cases

Adjuvant therapy

Percentage

Myomectomies

46

60.5 %

Hysterectomies

30

39.5 %

Total

76

100 %

Table 4 Total cases of uterine embolization as adjuvant therapy

Patients who received adjuvant embolization had the same symptoms as those
embolized as primary intent. In all cases postoperative evolution was favorable,
intraoperative bleeding was minimal. The clinical and imaging evaluations performed at
3/6 months after myomectomy found disappearance of metrorrhagia and menstruation
returned to normal. The 36 patients in the study group with the diagnosis of "Advanced
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Supplement No. 3/2014

cervical cancer stages III-IV" were not monitored because uterine artery embolization was
an emergency method as a hemostatic therapy not therapeutic method.
In the studied group - 159 patients were aged 30-50 (79.5%); after the age of 50
years the percentage drops to 6%, while the extremely age group (20-30 years old) is
14.5%.
Age

No of cases

Percentage

20-30

29

14.5 %

30-40

121

60.5 %

40-50

38

19 %

50-60

12

6%

60-70

0%

Total

200

100 %

Table 5 - Incidence by age

Uterine artery embolization is recommended for younger patients (20-40 years) as


primary therapy (conservative). Rank parity does not seem to significantly influence the
incidence of uterine fibroids, because in our studied group 40% of patients (80 patients) were
nulliparous and 47.5% (95 patients) were primiparous and secundiparous. Latest research
promotes uterine embolization, even in young women who wish to preserve fertility, being
communicated over 100 cases of pregnancies obtained after embolization, apparently without
negative influence on pregnancy25.
Patients we includied in the study were those who had been diagnosed with
"symptomatic fibroids". In our study group, 164 patients (82%) experienced uterine bleeding
. Symptoms due to compression (urinary frequency, constipation) of pelvic organ
neighborhood (bladder, rectum) and the feeling of fullness, discomfort were found in 47
patients (23.5%). Severe dysmenorrhea was voiced by 10 patients (12%).
Number of patients
Median age
Symptoms:
menometrorrhagia
anemia
disorder caused by the compression
of neighborhood organs
infertility
previous myomectomy (followed by
relapses)
severe dysmenorrhea

200
40
164 (82 %)
120 (60%)
47 (23.5 %)
56 (28 %)
16 (8 %)
10 (12 %)

Table 6 - Frequency of clinical symptoms in the study group

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December 2014

Menorrhagia and menometrorrhagia, are the most common symptoms which require
in most cases hospitalization.
No. Crt.

Anatomoclinical

No. of cases

Percentage

150

75

classification
1

Interstitial fibroids
(intramural)

Submucosal fibroids

26

13

Subserosal fibroids

13

6.5

0.5

10

200

100

sessile
4

Subserosal fibroids
pedunculated

Interstitial fibroid
developed in the
supporting
structures (round
ligament, broad
ligament,
or uterosacral
ligament)

Total

Table 7- Anatomoclinical types of uterine fibroids in the study group

The size of the myomas did not exceed 150 mm, ranging between 20-140 mm in diameter.
Diameter (mm)

No of patients

Percentage

20-40

30

15 %

40-60

90

45 %

60-80

40

20 %

80-140

40

20 %

Table 8 - Dimensions of myomas in the studied group

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Supplement No. 3/2014

Patients whose fibroid diameter was between 20 and 60 mm received embolization as


primary therapy. Embolization was performed as adjuvant therapy in larger tumors.
RESULTS AND DISCUSSION
In the last two decades (since 1995) endovascular techniques extended to the
therapeutic possibility in the genital benign pathology (uterine fibroids, endometriosis,
vascular malformations) but also in the malignant pathology (cervical cancer).
In our study conducted over a period of three years: from 2010 to 2012 we studied a
group of 200 patients - aged between 20 to 60 years - with the diagnosis of uterine
fibromyoma. The higher incidence of the disease was noted in the age group 30-50 - 159
cases (79.5%) from the study group. Embolization as primary therapy was performed in 124
(61.8%) cases and 76 (38.2%) patients received embolization as adjuvant therapy.
Embolization as adjuvant therapy allowed the successful of 76 surgical operations of
which 46 myomectomies and 30 hysterectomies.
Also we observed normalization of menstrual cycles since the first two menstrual
cycles in a 70% of patients and the efficacy was 88% on reduction the menometrorrhagia.
CONCLUSIONS
Uterine artery embolization is a technique that avoids surgery only when the cases are
properly selected.
This procedure avoids myomectomy or hysterectomy morbidity in 78% of cases.
If our study group, we demonstrated that uterine artery embolization is a safe and
effective method which produces permanent infarction of the fibroid tissue without
subsequent relapse. In case of malignant pathology, bleeding complications that may arise in
advanced stages of cervical cancer, embolization has proved the most effective method in
correcting and removing uterine bleeding as adjuvant therapy.
In conclusion, endovascular therapy is the optimal solution for solving bleeding
complications that can occur in gynecologic or obstetric pathology - according to reasons
given above.

56

December 2014

REFERENCES
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2.
3.
4.
5.
6.
7.

8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.

23.
24.
25.

Greenberg MD, Kazamel TI Medical and socioeconomic impact of uterine fibroids. Obstet Gynecol
Clin North Am, 1995; 22:625-36
J.H. Ravina, A. Aymard - Embolisation artrielle particulaire: un nouveau traitement des
hmorragies des liomyomes utrins, La Presse Medicale, Tome 27, No 7, pp. 299-304, 1998.
Goodwin S. Uterine artery embolization for the treatment of uterine leiomyomata embolization,
Cardiovasc Int Rad, 2003, 26(6):522-7.
Kempson RL, Hendrickson MR: Smooth muscle, endometrial stromal, and mixed Mllerian tumors
of the uterus. Mod Pathol 2000, 13(3):328342.
Parker WH: Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril 2007,
87(4):72536. Review
Florin Stamatian - Obstetrica i Ginecologie, Ginecologie vol II, ed Echinox, cap XLVI, 488-495
Kjerulff KH, Erickson AB, Langerberg PW Chronic gynecologic conditions reported by US
women: Findings from the National Health Interview Survey, 1984 to 1992. Am J Public Health, 1996;
86:195-6.
Rein MS, Barbieri RL, Friedman AJ: Progesterone: a critical role in the pathogenesis of uterine
myomas. Am J Obstet Gynecol 1995, 172(1 Pt 1):1418.
Andersen J: Growth factors and cytokines in uterine leiomyomas. Semin Reprod Endocrinol 1996,
14(3):269282.
Fields KR, Neinstein LS: Uterine myomas in adolescents: case reports and a review of the literature. J
Pediatr Adolesc Gynecol 1996, 9(4):195198.
Cramer SF, Patel A: The frequency of uterine leiomyomas. Am J Clin Pathol 1990, 94(4):435438.
Farquhar CM, Steiner CA: Hysterectomy rates in the United States 19901997. Obstet
Gynecol 2002, 99(2):229234.
Merrill RM: Hysterectomy surveillance in the United States, 1997 through 2005. Med Sci Monit 2008,
14(1):CR24-CR31.
Pelage JP, Le Dref O, Soyer P si colab. - Fibroid-related menorrhagia: Treatment with superselective
embolization of the uterine arteries and midterm follow-up. Radiology,2000; 215:428-431.
Wilcox LS, Koonin LM, Pokras R, Strauss LT, Xia Z, Peterson HB Hysterectomy in the United
States, 1988-1990. Obstet Gynecol, 1994; 83:549-55.
Broder MS, Kanouse DE, Mittman BS, Bernstein SJ The appropriateness of recommendations for
hysterectomy in Southern California. Obstet Gynecol, 2000; 95:199-205.
Vessey MP, Villard-Mackintosh L, Macpherson K, Coulter A, Yeates D The epidemiology of
hysterectomy: findings in a large cohort study. Br J Obstet Gynaecol, 1992; 99:402-7.
Worthington-Kirsch RL, Hutchins FL, Popky GL - Uterine artery embolization for the management
of leiomyomas: quality of life assessment and clinical response. Radiology,1998; 208:625-629.
Ravina JH, Aymard A, Ciraru-Vigneron N si colab. - Arterial embolization of uterine myoma:
results apropos of 286 cases. J Gynecol Obstet Biol Reprod, 2000; 29:272-275.
Klein A, Schwartz ML - Uterine artery embolization for the treatment of uterine fibroids: an
outpatient procedure. Am J Obstetr Gynecol, 2001; 184:1556-60.
Du J, Zuo Y, Chen X, Hu X, Lin H, Luo P, Hong D Clinical observation of transcatheter uterine
artery embolization for uterine myoma. Zhonghua Fu Chan Ke Za Zhi, 2002; 37(1):12-5.
Spies JB, Benenati JF, Worthington-Kirsch RL, Pelage JP Initial Experience with Use of Trisacryl Gelatin Microspheres for Uterine Artery Embolization for Leiomyomata. J Vasc Interv
Radiol, 2001; 12(9):1059-1063.
D Iacob Lembolisation des artres utrines dans le traitement de myomes utrins: tat des lieuse,
Gync Obstt Fertilit, 2004, vol 52, No 11, pag 927-935.
Yuri Kitamura M.D., Susan M. Ascher - Imaging manifestations of complications associated with
uterine artery embolization, Radio Graphics, 2005, 25:S119-S132.
Spies JB - New Trends in the Management of Uterine Fibroids. Presented at the 3rd World Congress
on Controversies in Obstetrics, Gynecology & Infertility meeting in Washington, DC,

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Medicine

IMPACT OF MATERNAL HYPERTENSION ON THE


INTRAUTERINE GROWTH RESTRICTED NEONATE

Luiza RADULESCU 1
Irina HORHOIANU 2
Costin BERCEANU 3
Adriana DAN4

ABSTRACT
OBJECTIVE
INTRAUTERINE GROWTH RESTRICTION AND MATERNAL HYPERTENSION COMPLICATE A
SIGNIFICANT PROPORTION OF PREGNANCIES AND TOGHETHER THEY SIGNIFICANTLY
CONTRIBUTE TO THE INCREASE OF MATERNAL AND NEONATAL MORBIDITY AND MORTALITY. OUR
STUDY AIMED TO ASSESS MATERNAL AND NEONATAL COMPLICATIONS ASSOCIATED WITH
MATERNAL HYPERTENSION AND INTRAUTERINE GROWTH RESTRICTION.
MATERIAL AND METHOD
WE ANALYZED IN A RETROSPECTIVE STUDY ALL PATIENTS THAT GAVE BIRTH IN THE BUCHAREST
UNIVERSITY EMERGENCY HOSPITAL, THAT WERE DIAGNOSED WITH INTRAUTERINE GROWTH
RESTRICTION AND MATERNAL HYPERTENSION BETWEEN 2010-2012. THE DATA WE COLLECTED
CONTAINED INFORMATION ON MATERNAL HEALTH (DEGREE OF HYPERTENSION ASSOCIATED
WITH BIRTH COMPLICATIONS, OTHER MORBIDITIES AND TYPE OF BIRTH) AND NEONATAL STATUS
(BIRTH WEIGHT, GESTATIONAL AGE, APGAR SCORE AND ASSOCIATED DISEASES).
RESULTS
A HIGHER INCIDENCE OF INTRAUTERINE GROWTH RESTRICTION A HIGHER RATE OF CESAREAN
SURGERY, PREMATURE BIRTHS AND A HIGHER FREQUENCY OF THROMBOEMBOLIC
COMPLICATIONS WAS OBSERVED IN PATIENTS WITH ASSOCIATED HYPERTENSION, AS WELL AS AN
INCREASED FREQUENCY THROMBOCYTOPENIA, NEUTROPENIA, AN INCREASED NEED FOR
INTENSIVE POSTNATAL CARE AND RESPIRATORY DISTRESS WAS ASSOCIATED IN THEIR CHILDREN.
CONCLUSIONS
COMPLICATIONS INCREASE AS WELL IN SEVERITY AND NUMBER WITH THE INCREASING RATE OF
MATERNAL HYPERTENSION. CORRECT DIAGNOSTIC OF INTRAUTERINE GROWTH RESTRICTED
NEONATES IS IMPORTANT IN ORDER TO MONITOR AND MANAGE THE COMPLICATIONS
ASSOCIATED WITH MATERNAL HYPERTENSION AND IT INVOLVES A CLOSE COLLABORATION
BETWEEN NEONATOLOGIST, OBSTETRICIAN AND FAMILY DOCTOR.
KEY WORDS:
PREECLAMPSIA

MATERNAL

HYPERTENSION,

INTRAUTERINE

GROWTH

RESTRICTION,

Department of Neonatology, Bucharest Emergency University Hospital, Romania


Department of Obstetrics and Gynecology, Bucharest Emergency University Hospital, Romania
3
Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Craiova, Romania
4
Department of Neonatology, Bucharest Emergency University Hospital, Romania
2

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INTRODUCTION
Intrauterine growth restriction (RCIU) is an important public health problem in both
industrialized and developing countries, leading to the association of a high degree of
perinatal morbidity on short and long term and increased mortality. The incidence of fetal
growth restriction varies depending on the population under examination (including
geographic location and standard curves used as reference) and is estimated by the World
Health Organization to be between 8-26% in the general obstetric population. 5
Maternal hypertension complicates a high number of pregnancies and significantly
contributes to maternal, fetal and neonatal morbidity and mortality, with a prevalence of 622%.6
World Health Organization evaluated in systematic reviews maternal mortality
worldwide and found that in developed countries, 16 percent of maternal deaths were caused
by hypertensive disorders, exceeding the other main causes: hemorrhage -13%, abortion - 8%
and sepsis - 2 percent, estimating that world wide 60,000 women die each year due to
preeclampsia.7
The definition of hypertension in pregnancy comprises several distinct entities in terms
of etiopathogenesis and clinical approach, resulting in different outcome and prognosis.
According to updated ESC guidelines the following forms of hypertension are defined:
1.Pre-pregnancy hypertension or chronic hypertension, diagnosed before 20 weeks or
even earlier, known and/or treated and that persists 42 days postpartum;
2. Gestational hypertension, diagnosed de novo after 20 weeks of pregnancy. When it is
associated with proteinuria, then it is considered to be preeclampsia. And the most severe
form of preeclampsia, associating seizure is eclampsia.
3. Pre-existing hypertension with preeclampsia overlap
4. Unclassified antenatal hypertension (with reclassification after 42 days postpartum). 8
In addition to hypertension being a risk factor in the development of intrauterine growth
restriction, intrauterine growth restriction is an independent risk factor in the development
arterial hypertension in adulthood9 so that the two entities make a really vicious circle. Given
that one of the criteria for the diagnosis of intrauterine growth restriction is low birth weight
according to gestational age, several studies have reported an inverse relation between body
mass and high blood pressure both in children10 and in adults11.

1. World Health Organization 2005 World Health Statistics 2005. Geneva: World Health Organization
6
Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in
Pregnancy American Journal of Obstetrics and Gynecolology. 2000;183:S1S22
7
Khan KS et al: WHO analysis of causes of maternal death: A systematic review. Lancet 367:1066, 2006.
8
ESC Guidelines on the management of cardiovascular diseases during pregnancy. European Heart Journal
(2011) 32, 31473197
9
Mzayek F. et al. The association of birth weight with developmental trends in blood pressure from childhood
through mid-adulthood. In: American Journal of Epidemiology. 2007, 166(4), p. 413-420.
10
Gamborg M. et al Birth weight and systolic blood pressure in adolescence and adulthood: meta-regression
analysis of sex- and age-specific results from 20 Nordic studies. In: American Journal of Epidemiology. 2007,
166(6), p. 634-645.
11
Gamborg M. et al. Life course path analysis of birth weight, childhood growth and adult systolic blood
pressure. In: Epidemiol. 2009, 169(10), p. 1167- 1178.

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Supplement No. 3/2014

Due to the abundant and controversial data in the medical literature we decided to
evaluate the maternal and neonatal consequences of maternal hypertension associated with
intrauterine growth restriction.
MATERIAL AND METHOD
The medical data of all patients who gave birth between 1 January 2010 - 31 December
2012 in the Obstetrics and Gynecology Clinic in the Bucharest Emergency University
Hospital were evaluated. Inclusion criteria were the diagnosis of neonatal intrauterine growth
restriction and maternal hypertension. Twins or triplets were excluded. Intrauterine growth
restriction was defined as fetal weight below the tenth percentile. Data collected included
information on maternal health (degree of hypertension , associated complications of birth
and type of birth) and status of newborns (GN, VG, associated diseases and Apgar score).
Patients who had other comorbidities associated and twin pregnancy were excluded. The data
were obtained from observation charts of patients and newborns.
Statistical analysis was performed using SPSS version 19 and Microsoft Excel.
We used descriptive analysis (mean, median, maximum, minimum, standard deviation,
variance) and Crosstabulation for checking Apgar score frequency among patients with low
weight for gestational age.
RESULTS
Out of 12948 patients that gave birth between 1st January 2010 31st December 2012,
2847 were included in the study. Out of the 2847 patients diagnosed with intrauterine growth
restriction, 34% (968/2847) were diagnosed with maternal hypertension. The analyzed
sample showed that 71,7% (694/968) of the cases had gestational hypertension, 25,6%
(248/968) preeclampsia, 1,8% (18/968) eclampsia and 0,9% (9/968) developed HELLP.
(Figure 1)
Statistical analysis showed that the mean gestational age was 34.511.187 in the
sample that was diagnosed with hypertension and intrauterine growth restriction (Table 1). In
the comparison group the mean gestational age was 37,511,125 (Table 2)
Distribution of births by gestational age showed that the highest frequency was 36.6%
(355/968) among those with intrauterine growth restriction and maternal hypertension for a
gestational age of 36 weeks as opposed to the comparison group where the highest frequency
was 39,7% (746/1879) for a gestational age of 37 weeks.
Mean Apgar score at 1 minute was 7.63 0.892 and 8.16 0.523 for 5 minutes in the
growth restricted group as opposed to the comparison group where the mean Apgar score at 1
minute was 8.73 0.461 and 9.31 0.674 for 5 minutes.
We found an increase in values from 1minute Apgar scores to 5 minutes for each
group.
The complications associated were more frequent and more severe, both for the mother
and the newborn, in the group that had been diagnosed with both intrauterine growth and
hypertension as opposed to the group that had only intrauterine growth restriction. (Figure 2),
(Figure 3). Also the cesarean rates were higher in the group with both pathologies, 66,6%
(645/968) as opposed to 58,9% (1107/1879) in the comparison group.
DISCUSSIONS AND CONCLUSIONS
The incidence for intrauterine growth restriction varies according to the cut-off limit for
weight and according to the World Health Organization it varies between 8-26% [1]. The
intrauterine growth restriction incidence was higher underlining the negative effect of
maternal hypertension on neonatal outcome.
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December 2014

In the case of these neonatal patients with RCIU, caesarean section was imposed in 645
cases out of which 376 in maternal interest (iterative caesarean operations, cases of
preeclampsia, maternal hypertension exacerbated by pregnancy previa etc.), and 269 in
interest of the fetus and the benefic effects of this attitude were translated by the fact that out
of 2847 pregnancies monitored with ultrasound, none resulted in utero fetal death.
The postpartum neonatal adaptation was better in the comparison group, with no
maternal hypertension, with a higher mean for 1 minute Apgar score as well as for the 5
minute Apgar score.
The neonatal evolution of newborns was generally good, with an increase in value of
Apgar Scor from 1 minute to 5 minutes, in both groups, indicating a close collaboration
between the obstetricians, the neonatologists and the anesthesiologist.
The complications associated to the first group had a higher frequency that the
complications associated to the second group confirming the data from literature, that
maternal hypertension12 in association with intrauterine growth restriction increases both
maternal and fetal morbidities. 13

Srinivas, S K et al. Rethinking IUGR in Preeclampsia: Dependent or Independent of Maternal


Hypertension? Journal of Perinatology 29.10 (2009): 680684. PMC. Web. 14 Dec. 2014.
13
Muhammad T. et al. Maternal factors associated with intrauterine growth restriction. J Ayub Med Coll
Abbottabad. 2010 Oct-Dec;22(4):64-9.
12

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REFERENCES
1.

ESC Guidelines on the management of cardiovascular diseases during pregnancy. European Heart
Journal (2011) 32, 31473197
2. Gamborg M. et al Birth weight and systolic blood pressure in adolescence and adulthood: metaregression analysis of sex- and age-specific results from 20 Nordic studies. In: American Journal of
Epidemiology. 2007, 166(6), p. 634-645.
3. Gamborg M. et al. Life course path analysis of birth weight, childhood growth and adult systolic blood
pressure. In: Epidemiol. 2009, 169(10), p. 1167- 1178.
4. Khan KS et al: WHO analysis of causes of maternal death: A systematic review. Lancet 367:1066,
2006.
5. Mzayek F. et al. The association of birth weight with developmental trends in blood pressure from
childhood through mid-adulthood. In: American Journal of Epidemiology. 2007, 166(4), p. 413-420.
6. Muhammad T. et al. Maternal factors associated with intrauterine growth restriction.
7. J Ayub Med Coll Abbottabad. 2010 Oct-Dec;22(4):64-9.
8. Srinivas, S K et al. Rethinking IUGR in Preeclampsia: Dependent or Independent of Maternal
Hypertension? Journal of Perinatology 29.10 (2009): 680684. PMC. Web. 14 Dec. 2014.
9. Report of the National High Blood Pressure Education Program Working Group on High Blood
Pressure in Pregnancy American Journal of Obstetrics and Gynecolology. 2000;183:S1S22
10. World Health Organization 2005 World Health Statistics 2005. Geneva: World Health Organization
Figure 1 Distribution of hypertension in the analyzed sample

Hypertension type
Eclampsia
1.8%

HELLP
0.9%

Preeclampsia
25.6%

Gestational
hypertension
71.7%

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December 2014

Table 1: Frequency of gestational age in the HTA IUGR group

Valid

968

Missing

Mean

34,51

Std. Deviation

1,187

Minimum

29,00

Maximum

40,00

Table 2: Frequency of gestational age in the IUGR group

Valid

1879

Missing

Mean

37,51

Std. Deviation

1,125

Minimum

31,00

Maximum

40,00

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Supplement No. 3/2014

Figure 2. Frequency of associated maternal complications

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December 2014

Figure 3. Frequency of associated neonatal complications

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Medicine

MANAGEMENT OF OCULAR CICATRICIAL PEMPHIGOID

Corina Ioana BUTEA-SIMIONESCU1


Speranta SCHMITZER 2

ABSTRACT
THE OCULAR CICATRICIAL PEMPHIGOID BELONGS TO A FAMILY OF CHRONICALLY PROGRESSIVE
AUTOIMMUNE DISORDERS, PREDOMINANTLY AFFECTING MUCOUS MEMBRANES. THE KEY
FEATURE IS THE CHRONICALLY ACTIVE CONJUNCTIVAL INFLAMMATION WITH CONSECUTIVE
FIBROSIS, LEADING TO LOSS OF VISION. UNFORTUNATELY, THE EARLY LESIONS ARE SUBTLE AND
HARD TO IDENTIFY, MANY PATIENTS BEING TREATED FOR CHRONIC CONJUNCTIVITIS FOR YEARS.
THE TREATMENT IS GENERAL AND LOCAL, MEDICAL AND SURGICAL, CONDUCTED BY BOTH THE
OPHTHALMOLOGIST AND THE DERMATOLOGIST. MULTIDISCIPLINARY APPROACH AND EARLY
DIAGNOSIS ARE THE KEYS TO PREVENTING SERIOUS COMPLICATIONS.
KEYWORDS: PEMPHIGOID, OCULAR, MANAGEMENT

INTRODUCTION
Cicatricial pemphigoid is a rare inherited disorder characterized by erosive mucosal
lesions that in time lead to fibrosis. The most common areas involved are the oral mucosa and
the conjunctiva. Cicatricial pemphigoid is a chronic and progressive disease with severe longterm complications. 3 The first mention of pemphigoid lesions of the conjunctiva is in 1793
by Wichman. In 1878 Von Graefe first described the progressive nature of the disease to its
final stage. The term ocular cicatricial pemphigoid refers to ocular lesions in cicatricial
pemphigoid but the ophthalmologist must take into account that this is a systemic disease. 4
The purpose of this article is first of all to draw attention to this rare but debilitating disease
and also to underline that the key to an early diagnosis is clinical suspicion.
EPIDEMIOLOGY
In literature the incidence varies between 1/20000 and 1/46000 with a women: men
ratio of 2:1.5 However, although the incidence is apparently low, it is considered that a much
larger number of cases remain undiagnosed in the early stages and are being treated for
1

MD, PhD student, OFTALMESTET Clinic Bucharest, corina_popa@ymail.com


MD, PhD, OFTALMESTET Clinic Bucharest
3
Harrisonss Principles of Internal Medicine 17th ed, 2008, McGraw-Hill, page 340
4
Douglas S. Holsclaw Ocular Cicatricial Pemphigoid International Ophthalmology Clinics, 1998, vol 38,
Issue 4, 89-106
5
Chang JH, McCluskey PJ. Ocular cicatricial pemphigoid: manifestations and management.Curr Allergy
Asthma Rep 2005;5:3338
2

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"chronic conjunctivitis" for several years until the condition progresses to the final stages.
The average age at diagnosis is between 60-70 years but because of the nonspecific changes
in the early stages, the lesions may occur as early as 40 years6, although in our practice we
have had a patient who started showing symptoms and subtle conjunctival lesions in her early
30s. In cicatricial pemphigoid, the most frequently involved is the conjunctiva (60-80%) and
pharyngeal and oral mucosa (30-84%), and less the nasal, laryngeal, esophageal, anogenital
mucosa.7 Approximately 50% of patients with ocular cicatricial pemphigoid present
extraocular lesions. 8
PATHOGENESIS
Ocular cicatricial pemphigoid is an autoimmune disorder that is triggered in susceptible
individuals by a precipitating factor. It is believed that patients presenting HLA-DQw7 gene
have a 9.6% higher risk of developing ocular cicatricial pemphigoid scar.9 The trigger can be
conjunctival surgery in a predisposed individual or a drug. In 1970 a new antihypertensive
agent called practolol triggered a series of ocular cicatricial pemphigoid cases.10 It is also
considered that topical glaucoma medications can induce subconjunctival fibrosis after long
time usage (pilocarpine, timolol). 11 Immunohistochemically this disease is characterized by
the formation of deposits of immunoglobulin A, G, M and complement (C3) at the basal
membrane of the conjunctival epithelium, forming autoantibodies against various structures
of the basal membrane. Autoantigens have been identified that are involved in the
pathogenesis of ocular cicatricial pemphigoid, such as BP180, BP230, 64 integrin, laminin
5 and collagen type VII. Also, in the active phases of the disease elevated levels of
interleukins 4, 5, 6, tumor necrosis factor alpha (TNF-) have been found in the patients
serum suggesting a poor regulation of the immune system.
CLINICAL ASPECTS
Ocular cicatricial pemphigoid begins with nonspecific symptoms, patients complain of
foreign body sensation, local irritation, burning and epiphora and there may be a recurrent
papillary conjunctivitis. Some patients do not describe symptoms until advanced stages.
Damage is initially unilateral but progresses within 2 years to the fellow eye.12
The progression of the disease is characterized by four stages. Stage 1 mimics a chronic
conjunctivitis with discrete subepithelial fibrosis of the conjunctiva or erosions of the tarsal
conjunctiva. Fibrosis is easily overlooked and can be best seen in the tarsal conjunctiva as
fine, whitish striations (Fig1a, 1b).

Albert&Jakobiecs Principles and Practice of Ophthalmology 3rd ed, Saunders-Elsevier 2008, vol 1, chapter 46
Myron Yanoff&Jay S.Duker Ophthalmology 4th ed, Saunders-Elsevier 2013, section 4, chapter 4.10
8
Elder MJ, Lightman S, Dart JK: Role of cyclophosphamide and high dose steroid in ocular cicatricial
pemphigoid. Br J Ophthalmol 1995; 79:246-264.
9
Ahmed AR, Foster CS, Zaltas M, et al: Association of DQw7 (DQb10301) with ocular cicatricial
pemphigoid. Proc Natl Acad Sci USA 1991; 88:1157911582.
10
Wright P: Cicatrizing conjunctivitis. Trans Ophthalmol Soc UK 1986; 105:1.
11
Hirst LW, Werblin T, Novak M, et al: Druginduced cicatrizing conjunctivitis simulating ocular pemphigoid.
Cornea 1982; 1:121.
12
Laforest C, Huilgol SC, Casson R, et al. Autoimmune bullous diseases: ocular manifestations and
management. Drugs 2005;65:176779.
6
7

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Fig 1a

Fig 1b

In stage 2 the fibrosis process continues and leads to fornixes shortening, more obvious
in the lower conjunctival fornix. (Fig 2).

Fig 2

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Stage 3 is characterized by the occurrence of symblepharon and stenosis of the lacrimal


puncta and the lacrimal ducts. The disease is most commonly diagnosed in this stage. (Fig3)

Fig 3

The last stage is considered the biggest therapeutical challenge with severe dry eye,
ankiloblepharon and corneal keratinization. (Fig 4)

Fig 4

A noteworthy aspect is that this condition leads in time to severe dry eye syndrome.
Due to the ongoing process of fibrosis, conjunctival tear glands are destroyed resulting in
aqueous and mucin component deficiency in the tear film. Dry eye with simblepharon and
trichiasis lead to corneal neovascularization and corneal injury with visual impairment.13
Systemic lesions occur, as mentioned, in the oral, laryngeal, esophageal, nasal,
anogenital mucosa. Any patient with suspected ocular cicatricial pemphigoid requires a
detailed history to find out if they present dysphagia or difficulty breathing.

13

Albert&Jakobiecs Principles and Practice of Ophthalmology 3rd ed, Saunders-Elsevier 2008, vol 1, chapter 46

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DIAGNOSIS
There are a wide variety of diseases that can cause lesions similar to ocular cicatricial
pemphigoid, such as atopic keratoconjunctivitis, ocular rosacea, sequelae after chemical
burns, Stevens-Johnson syndrome, trachoma, conjunctivitis with adenovirus or trauma but
most of them can be excluded based only on the medical history of the patient. Positive
diagnosis requires a conjunctival biopsy. Taking the biopsy requires experience as any
surgical procedure can accelerate the fibrosis. Where possible the biopsy should include a
damaged area and normal tissue. Direct immunofluorescence is used to highlight linear
deposits of immunoglobulin and complement in basement membrane of the conjunctival
epithelium. If the result is negative but clinical suspicion is high immunoperoxidase assay or
electron microscope can be used. 14
TREATMENT
Treatment of ocular cicatricial pemphigoid patients is difficult and requires an
interdisciplinary approach with both ophthalmologist and dermatologist. The goal of the
treatment is to control inflammation and to stop the process of fibrosis, which once installed,
is not reversible. The ophthalmologist monitors and assesses inflammatory activity of the
conjunctiva, performs surgery when necessary and the dermatologist initiates and monitors
the systemic treatment.
Systemically, the first-line treatment is prednisone followed by dapsone, methotrexate
or azathioprine. When the therapeutic response is incomplete or evolution is very fast
cyclophosphamide is administered and for refractory cases or who have severe adverse
reactions immunoglobulin (within 1 year) or biological therapy (rituximab) is recommended.
This regimen is initiated and supervised by a dermatologist and it is not the purpose of this
article.
Local treatment of ocular cicatricial pemphigoid lesions is primarily a supportive one.
For dry eye syndrome artificial tears and ointments are prescribed and to relieve
inflammation in the acute phase topical non-steroidal or steroidal anti-inflammatory drugs
may be used, depending on the appearance of the cornea.
Any surgery is performed only when the systemic status of the patient is stable and the
disease is kept under control with appropriate therapy for at least 6 weeks prior to surgery15.
For trichiasis epilation can be performed but is doesnt offer good long-term results.
Electrolysis or crioablation of lash follicles give better results. Dry eye can be managed by
occlusion of the lacrimal puncta and for meibomian glands disfunction, eyelid massage and
tetracycline orally. For fornixes retraction, if the inflammation is controlled and the disease is
in an inactive phase, you can use an oral mucosal graft from an area without lesions or
amniotic membrane to reconstruct the fornices and to provide better ocular motility. (Fig5a,
5b)

Albert&Jakobiecs Principles and Practice of Ophthalmology 3 rd ed, Saunders-Elsevier 2008, vol 1, chapter
46
15
Heiligenhans A, Shore JW, Rubin PA, Foster CS. Long-term results of mucous membrane grafting in ocular
cicatricial pemphigoid. Ophthalmology. 1993;100:1283.
14

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Fig 5a Stage 4 ocular


cicatricial pemphigoid

Fig 5b Same patient, after


oral mucosa graft in the
inferior fornix

Corneal surgery is contraindicated in patients with severe ocular cicatricial pemphigoid.


Penetrating keratoplasty can be practiced only in certain patients with good eyelid function
and without the tear film disorders. Unfortunately, most patients have corneal hypoesthesia,
severe dry eye and altered eyelid dynamics. For these patients keratoprosthesis is the only
surgical alternative that offers real opportunities for visual rehabilitation.16
CONCLUSIONS
Ocular cicatricial pemphigoid prognosis depends on how early it is diagnosed and
treated. At the time of diagnosis up to 60% of patients are already in stage 3.17 This condition
remains very difficult to treat due to its progressive autoimmune character and the absence of
early diagnostic methods. The best option for early diagnosis remains the clinical suspicion
based on the physicians experience. Also, being a systemic disease, the patient should be
investigated for evidence of other mucosal lesions, oral, esophageal, etc. Although there are
multiple treatment options, the results are still unsatisfactory. Due to the autoimmune
character, the ophthalmological treatment, both medical and surgical, is palliative, not
curative.
Albert&Jakobiecs Principles and Practice of Ophthalmology 3rd ed, Saunders-Elsevier 2008, vol 1, chapter
46
17
Myron Yanoff&Jay S.Duker Ophthalmology 4th ed, Saunders-Elsevier 2013, section 4, chapter 4.10
16

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REFERENCES
1.

Ahmed AR, Foster CS, Zaltas M, et al: Association of DQw7 (DQb10301) with ocular
cicatricial pemphigoid. Proc Natl Acad Sci USA 1991; 88:1157911582
2. Albert&Jakobiecs Principles and Practice of Ophthalmology 3rd ed, Saunders-Elsevier 2008, vol
1, chapter 46
3. Chang JH, McCluskey PJ. Ocular cicatricial pemphigoid: manifestations and management.Curr
Allergy Asthma Rep 2005;5:3338
4. Douglas S. Holsclaw Ocular Cicatricial Pemphigoid International Ophthalmology Clinics, 1998,
vol 38, Issue 4, 89-106
5. Elder MJ, Lightman S, Dart JK: Role of cyclophosphamide and high dose steroid in ocular
cicatricial pemphigoid. Br J Ophthalmol 1995; 79:246-264
6. Harrisonss Principles of Internal Medicine 17th ed, 2008, McGraw-Hill, page 340
7. Heiligenhans A, Shore JW, Rubin PA, Foster CS. Long-term results of mucous membrane
grafting in ocular cicatricial pemphigoid. Ophthalmology. 1993;100:1283
8. Hirst LW, Werblin T, Novak M, et al: Druginduced cicatrizing conjunctivitis simulating ocular
pemphigoid. Cornea 1982; 1:121.
9. Laforest C, Huilgol SC, Casson R, et al. Autoimmune bullous diseases: ocular manifestations
and management. Drugs 2005;65:176779.
10. Myron Yanoff&Jay S.Duker Ophthalmology 4th ed, Saunders-Elsevier 2013, section 4, chapter
4.10
11. Wright P: Cicatrizing conjunctivitis. Trans Ophthalmol Soc UK 1986; 105:1.

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December 2014

Medicine

PREGNANCY-A METABOLIC CHALLENGE

Oana BODEAN 1
Simona VLADAREANU 2
Elvira BRATILA3
Monica CIRSTOIU4

ABSTRACT:
PREGNANCY INVOLVES METABOLIC CHANGES WHICH OCCUR IN ORDER TO SUSTAIN A PROPER
GROWTH AND DEVELOPMENT OF THE FETUS. A SERIES OF PREEXISTING OR COINCIDENT
METABOLIC ALTERATIONS PREDISPOSE TO FURTHER COMPLICATIONS DURING THIS PARTICULAR
STAGE IN A WOMAN`S LIFE. OBESITY AND METABOLIC SYNDROME PREDISPOSE TO
CARDIOVASCULAR DISEASE, GESTATIONAL DIABETES, IMPAIRED RENAL FUNCTION AND OTHER
EVENTS THAT LEAD TO SEVERE OUTCOMES SUCH AS PREECLAMPSIA. IN THIS ARTICLE WE
DISCUSS A FEW METABOLIC ASPECTS INVOLVED IN THE PATHOPHYSIOLOGY OF PREECLAMPSIA,
ACCORDING TO OUR EXPERIENCE AT THE BUCHAREST EMERGENCY UNIVERSITY HOSPITAL.
KEYWORDS: PREECLAMPSIA, METABOLISM, HYPERTENSION

INTRODUCTION
An increasing number of pregnancies develop complications related to different
metabolic changes. Obesity, gestational diabetes5, 6, pregnancy-induced hypertension, blood
clot disorders are such complications transforming a physiological pregnancy into a high risk
condition.
High blood pressure during pregnancy is quite frequent among women who have
certain risk factors to develop such disease. The most dangerous form of hypertension during
pregnancy is called preeclampsia and is defined as the onset of blood pressure values higher
than 140/90mmHg, edema and proteinuria (>0.3g/24h) after 20 weeks of gestation7-10.
Women who are overweight or obese (Body Mass Index>30) have an increased risk of
developing preeclampsia which can evolve into its severe form, that of eclampsia, causing
eclamptic seizures, even death of both mother and foetus.

PHD, Department of Obstetrics and Gynecology, Bucharest Emergency University Hospital,


oanamb8@gmail.com
2
Department of Neonatology, ELIAS Emergency University Hospital Bucharest, Carol Davila University
of Medicine and Pharmacy
3
Department of Obstetrics and Gynecology, St. Pantelimon Hospital Bucharest
4
Department of Obstetrics and Gynecology, Emergency University Hospital Bucharest, Carol Davila
University of Medicine and Pharmacy

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The metabolic changes taking place during pregnancy are complex. The pregnancy
itself can be considered a metabolic stress test11, 12.
In this article we discuss a few metabolic aspects involved in the pathophysiology of
preeclampsia, according to our experience at the Bucharest Emergency University Hospital.
MATERIALS AND METHODS
The study included 406 singleton pregnancies admitted in the Bucharest Emergency
University Hospital between January 2012 and December 2013 and diagnosed with
pregnancy-induced hypertension during the current gestation. Data was collected from
patients` files and analyzed by the Department of Statistics. Patients with known preexisting
hypertension prior to pregnancy were excluded.
RESULTS AND DISCUSSIONS
From a total number of 3665 pregnancies registered during one year in our hospital, a
number of 406 were diagnosed with different types of pregnancy-induced hypertension.
A total of 111 cases developed preeclampsia during their pregnancy. These patients
also associated a series of conditions, as illustrated in Chart 1. Obesity was diagnosed in 45
pregnant patients. Gestational diabetes mellitus was found in 30 cases. Renal insufficiency
complicated 10 cases. The rest of our patients had other or no relevant pathology. The weight
of the newborns varied, from those with intrauterine growth restriction due to placental
insufficiency to large for gestational age and macrosoms delivered by women with
gestational diabetes mellitus.
Placental insufficiency was investigated by ultrasound, the patients showing impaired
placental development (Figure 1), altered placental perfusion, abnormal placental vascularity,
abnormal placental insertion (Figure 2), calcium deposits, and early placental maturation. The
abnormal placentas were sent to the pathology department after delivery. Intraoperatory
images of abnormal placentas are shown in Figure 3 and Figure 4.

Figure 1. Placental insufficiency. Circumvalate placenta with calcium deposits.

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December 2014

Figure 2. Low insertion of the placenta

Conditions associated with preeclampsia


50
45

No. of Patients

40
35
30
25
20
15
10
5
0
Obesity

Gestational Diabetes
Melitus

Renal Insufficiency

Other/None

Chart 1 . Conditions associated with preeclampsia

The etiology of preeclampsia is still unclear, although there is much research being
done in this field, from epidemiology studies to the newest metabolomics 1-4, trying to
investigate the wide range of possible mechanisms involved.

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A list of etiologic factors is presented in Table 1:


Etiologic factors of preeclampsia
1. Abnormal implantation of the placenta
2. Angiogenic factors
3. Immune factors and inflammation
4. Genetic factors
5. Endothelial and vascular disorders
Table 1. Etiologic factors of preeclampsia

Figure 3. Abnormal placenta with calcium deposits

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Figure 4. Abnormal placental vascularization

At a metabolic level, preeclampsia is characterized by increased insulin resistance,


high levels of serum lipids, decreased filtration in the glomeruli, alteration of uric acid
clearance and changes in the rennin-angiotensin-aldosterone system 13.
The same risk factors involved in the onset of preeclampsia are also involved in the
occurrence of cardiovascular conditions. Recent studies state that women who develop
metabolic syndrome during pregnancy have an increased risk of developing cardiovascular
disease later in life 14, 15.
Metabolic syndrome is defined as a cluster of metabolic abnormalities that appear to
directly promote the development of atherosclerotic cardiovascular disease and are
characterized by chronic low-grade systemic inflammation. A faulty lifestyle, obesity and
genetic predisposition also represent risk factors to developing metabolic syndrome in the
general population, regardless of gender. 1,2
Obese women are predisposed to have severe pregnancy outcomes. The American
College of Obstetricians and Gynecologists sustain that the total weight gain during
pregnancy for a woman with a normal pre-pregnancy BMI should be 11.5-16 kg. The adipose
tissue acts like a real endocrine organ, producing hormones, cytokines and other substances
which affect metabolism of both mother and fetus. Such cytokines (e.g. leptin, visfatin,
resistin, vaspin) seem to correlate with different changes in the glucose metabolism of the
mother and with fetal growth. Research in this field is new and quite promising.
CONCLUSIONS
Obesity, chronic hypertension, increased insulin resistance, impaired renal function,
systemic inflammation involve metabolic changes common to both preeclampsia and
cardiovascular disease.
Fetal growth and development are related to maternal metabolic changes and to
maternal preexisting metabolic conditions, such as obesity, diabetes or chronic hypertension.

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REFFERENCES
1. Balkau, B. Valensi, P.: A review of`the metabolic syndrome, Diabetes and Metabolism, vol. 33, no.6,
pp. 405413, 2007

2. Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E: Metabolic profiling, metabolomic and
3.
4.
5.
6.
7.
8.
9.
10.
11.

12.
13.
14.
15.

metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat
Protoc 2007: 26922703.
Beaglehole R, Bonita R: Tackling NCDs: a different approach is needed. Lancet 2012 379: 1873.
Blank V, Hirsch E, Challis JR, Romero R, Lye SJ: Cytokine signaling, inflammation,
innateimmunity and preterm labour - a workshop report. Placenta. 2008; 29
Catalano PM, Kirwan J et al.: Gestational diabetes and insulin resistance: role in short- and longterm implications for mother and fetus. Journal of Nutrition 2003; 133: 1674-83.
Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS: Effect of treatment of gestational
diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005 352: 24772486.
Duley L: The global impact of pre-eclampsia and eclampsia. Semin Perinatololy 2009 33: 130137.
Diaz SO, Pinto J, Graca G, Duarte IF, Barros AS et al.: Metabolic biomarkers of prenatal disorders:
an exploratory NMR metabonomics study of second trimester maternal urine and blood plasma.
Journal Proteome 2011 37323742.
Ghulmiyyah L, Sibai B: Maternal mortality from preeclampsia/eclampsia. Semin Perinatology 2011
36: 5659.
Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth.
Lancet. 2008; 371:7584.
Lauenborg, E, Mathiesen, T. Hansen et al.: The prevalence of the metabolic syndrome in a Danish
population of women with previous gestational diabetes mellitus is three-fold higher than in the general
population,
The
Journal
of
Clinical
Endocrinology
and Metabolism, vol. 90, no. 7, pp. 40044010, 2005.
Luoto, T., Kinnunen, M. Aittasalo et al.: Primary prevention of gestational diabetes mellitus and
large-for-gestational age newborns by lifestyle counseling: a cluster-randomized controlled trial, PLoS
Medicine, vol. 8, no. 5, 2011.
Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, Chaiworapongsa T, Mazor
M.: The preterm parturition syndrome. British Journal of Obstetrics and Gynecology. 2006; 113
Solomon CG, Seely EW: Brief review: hypertension in pregnancy: a manifestation of the insulin
resistance syndrome? Hypertension 2001; 37: 232-9.
Warrington J., George E., Palei A: Recent Advances in the Understanding of the Pathophysiology of
Preeclampsia in Hypertension 2013;62:666-673.

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Medicine

PREVALENCE OF CELIAC DISEASE IN WOMEN WITH


FERTILITY DISORDERS
Cosmin CIORA1
Alexandru LUPU2
Mircea DICULESCU3

ABSTRACT:
BECAUSE SUBCLINICAL CELIAC DISEASE MAY DECREASE FERTILITY OR COMPLICATE
PREGNANCY, WE SCREENED WOMEN WITH FERTILITY DISORDERS AND WOMEN WITH
FUNCTIONAL DYSPEPSIA, FOR ANTI-TISSUE TRANSGLUTAMINASE ANTIBODIES IN SERUM TO FIND
UNDIAGNOSED CELIAC DISEASE
METHOD: WE SCREENED WOMEN WITH RECURRENT MISCARRIAGE OF UNKNOWN AETIOLOGY (N
= 36), UNEXPLAINED INFERTILITY (N = 46) AND WOMEN WITH FUNCTIONAL DYSPEPSIA (N = 112),
FOR ANTI-TISSUE TRANSGLUTAMINASE ANTIBODIES IN SERUM TO FIND UNDIAGNOSED CELIAC
DISEASE. ONE WOMAN (2.7%) WITH RECURRENT MISCARRIAGE, TWO WOMEN (4.35%) WITH
UNEXPLAINED INFERTILITY AND ONE WOMAN IN THE CONTROL GROUP (0.9%), WERE
CONSIDERED TO HAVE CELIAC DISEASE. ALL WOMEN WITH POSITIVE SEROLOGIC FINDINGS (4
CASES) UNDERWENT JEJUNAL BIOPSY AND OF THEM HAD HISTOLOGICAL EVIDENCE OF CELIAC
DISEASE.
RESULTS: THE PREVALENCE OF CELIAC DISEASE IN INFERTILE WOMEN SEEMS HIGHER (3 OUT
OF 82, 3.65%) IN THE STUDY GROUP THAN IN THE GENERAL POPULATION (1 OUT OF 112, 0.9%),
AND PARTICULARLY IN THE SUBGROUP WITH UNEXPLAINED INFERTILITY (2 OUT OF 46, 4.35%)
CONCLUSIONS: UNDIAGNOSED CELIAC DISEASE IS A RISK FACTOR FOR INFERTILITY AND
RECURRENT MISCARRIAGE OF UNKNOWN AETIOLOGY. WOMEN SEEKING MEDICAL ADVICE FOR
THIS PARTICULAR CONDITION SHOULD BE SCREENED FOR CELIAC DISEASE. ADOPTION OF A
GLUTEN-FREE DIET COULD HAVE A POSITIVE IMPACT ON FERTILITY IN THIS GROUP OF
PATIENTS. IT SEEMS RATIONAL THAT SEROLOGICAL TESTS SHOULD BE PERFORMED AS ROUTINE
INVESTIGATION IN THESE CASES. THE RECOMMENDED STRATEGY IS INDIVIDUALLY CASEORIENTED.
KEY WORDS: CELIAC DISEASE, INFERTILITY,
ANTIBODIES, JEJUNAL BIOPSY, RECURRENT ABORTION

ANTI-TISSUE

TRANSGLUTAMINASE

Gastroenterology and Hepatology Clinic, Fundeni Clinical Institute; UMF Carol Davila, Gastroenterology and
Hepatology Fundeni, cioracsz@yahoo.com
2
Gastroenterology and Hepatology Clinic, Fundeni Clinical Institute; UMF Carol Davila, Gastroenterology and
Hepatology Fundeni
3
Gastroenterology and Hepatology Clinic, Fundeni Clinical Institute; UMF Carol Davila, Gastroenterology and
Hepatology Fundeni

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INTRODUCTION: Celiac disease is a unique autoimmune disorder, unique because


the environmental precipitant is known. The disorder was previously called celiac sprue,
based on the Dutch word sprue, which was used to describe a disease similar to tropical sprue
that is characterized by diarrhea, emaciation, aphthous stomatitis, and malabsorptin (1).
Celiac disease is precipitated, in genetically predisposed persons, by the ingestion of gluten,
the major storage protein of wheat and similar grains.
The prevalence of dyspepsia is up to 40% in population-based study. Functional
dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related
functional disorder, characterized by the presence of persistent or recurrent pain or discomfort
centered in the upper abdomen, neither relief by defecation, nor association with the onset of
a change in stool frequency or form (2). Celiac disease (CD) is a common autoimmune
enteropathy, with a prevalence around 1% in the general population. The prevalence of CD is
higher in patients with dyspepsia, but not in a statistically significant way (5).
CELIAC DISEASE AND INFERTILITY
The highest prevalence of the disease is met in females during their reproductive life
(6). Celiac disease is seldom considered in the evaluation of infertility, and the link between
the two has been referred to many times in the literature as a neglected clinical association.
It is estimated that approximately 7.414% of women are infertile in North America, with
15% of this infertility attributed to unexplained factors after hormonal and anatomical causes
have been ruled out (3). Higher prevalence of CD in unexplained infertility was again
demonstrated in an Italian study investigating the prevalence of CD in women undergoing
assisted reproductive techniques (ARTs) (3). Undiagnosed CD may be particularly
devastating in women who experience recurrent abortions and perinatal complications (4).
The increased proportion of nondiarrheal celiac disease has been attributed to the
introduction of serologic testing and increased awareness among practicing clinicians.
Women having unexplained infertility, recurrent abortions, stillbirths, or IUGR could have
subclinical celiac disease, which can be detected by serologic screening tests. Therefore,
consideration should be given to serologic screening for celiac disease in patients with poor
reproductive performance.
Undiagnosed CD is in fact a risk factor for infertility. This may have a significant
impact on the management of infertility, since women seeking medical advice for this
particular condition should be screened for CD. Ultimately, adoption of a GFD could have a
positive impact on fertility in this group of patients.
CELIAC DISEASE AND FUNCTIONAL DYSPEPSIA
Celiac disease is still under diagnosed in all age groups; the form with obvious
symptoms is found in only a limited number of cases; in most patients, particularly adults, the
disease has an atypical symptomatology or is completely silent. As regards mass screening, at
the moment there is no evidence that supports this approach, since in the apparently healthy
population the prevalence of CD varies in relationship with geographical areas [9].
Furthermore, a cost-effectiveness analysis in support of a mass screening program has not
been performed. Case-finding is believed to be the most appropriate diagnostic approach to
adopt for asymptomatic patients or for patients with subtle clinical features. This approach is
particularly effective and becomes more so if in the selection of subjects to be investigated
their family doctors are involved. The activation of a celiac awareness program in the
primary-care setting focusing on selective serological screening of high risk groups has
doubled the number of cases diagnosed from among the adult asymptomatic population.

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It was recently observed that CD had a greater prevalence, with respect to the general
population, in dyspeptic patients and that 30%-40% of CD patients have dyspeptic symptoms.
Recent investigations have shown that most patients affected by CD, in particular adults, do
not have the typical symptoms of the disease, thus they remain misdiagnosed, delaying the
diagnosis until an older age. In a study conducted on paucisymptomatic patients over 65
years old that had seen both family doctors and specialists, it was documented that the correct
diagnosis was made with an average delay of 28 years. Several studies performed celiac
disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsyproved prevalence that ranged from 0.5% to 2% (5).
In a recent meta-analysis by Ford et al (14), the authors provided a pooled prevalence
of biopsy-proven CD of 1.0%, similar to that in the general population, when duodenum
biopsy was performed as first-line investigation.
METHODS: We screened women with recurrent miscarriage of unknown aetiology (n
= 36), unexplained inferti lity (n = 46) and women with functional dyspepsia (n = 112), for
anti-tissue transglutaminase antibodies in serum to find undiagnosed coeliac disease. One
woman (2.7%) with recurrent miscarriage, two women (4.35%) with unexplained infertility
and one woman in the control group (0.9%), were considered to have coeliac disease. All
women with positive serologic findings (4 cases) underwent jejunal biopsy and all of them
had histological evidence of coeliac disease. Infertility was attributed to unexplained factors
after hormonal and anatomical causes have been ruled out (3,8).
Spontaneous pregnancy loss is a surprisingly common occurrence, with
approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure.
Recurrent pregnancy loss (RPL) has been inconsistently defined. When defined as 2
consecutive pregnancy losses prior to 20 weeks from the last menstrual period, it affects
approximately 1% to 2% of women.
Clinical evaluation for recognized causes of reccurent abortion was performed at the
discretion of the physician and included testing for uterine abnormalities, parental karyotype
defects, endocrinological abnormalities, antiphospholipid syndrome, luteal phase defects, and
heritable thrombophilias. Women were excluded from the final analysis if testing indicated a
potential etiology for their RPL. None had clinical features of celiac disease.
Functional dyspepsia (FD) is a condition commonly seen in gastroenterological
practice. With the introduction of Rome III criteria in 2006, a new approach for categorizing
patients has been recommended (9),
Table 1. Rome III Diagnostic Criteria for Functional Dyspepsia

Functional Dyspepsia
At least 3 months, with onset at least 6 months previously, of 1 or more of the following:
1. Bothersome postprandial fullness
2. Early satiation
3. Epigastric pain
4. Epigastric burning
5. No evidence of structural disease (including at upper endoscopy) that is likely to explain
the symptoms

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The diagnosis was supported by tTGA positiviy in all cases. Anti-tTG have a high
specificity and sensitivity in the screening of celiac disease, while requiring a second method
of confirmation (13). Gastroscopy was performed in 4 women out of 4, and the histological
diagnosis was positive for coeliac disease in all 4 cases. HLA testing was not performed. All
patients were following a normal diet when included in the study.
Statistical and graphical evaluations were performed with OriginPro8 programme. P Test (
TTEST function- returns probability t`Student) is statistically significant when values are less
or equal to 0.05.
RESULTS:
A number of 194 patients were investigated, out of which 112 healthy controls (without
celiac disease) and 82 patients with infertility disorders- 36 with recurrent miscarriage of
unknown aetiology (n = 36), unexplained infertility (n = 46). On the following presentation
we will refer to 3 independent groups.
We also mention the following:
Healthy controls group, n=112
Recurrent miscarriage of unknown aetiology, n = 36
Unexplained infertility, n = 46
The graphical design was performed using OriginPro8 programme.
65
60

57.73

55

Percent (%)

50
45
40
35
30

23.71

25

18.56

20
15
10
Control

Infertility

R. miscarriage

Figure 1. Procentual representation of the 3 groups components

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Mean values (years)

30

29.83

29.85

Control

Infertility

28.42

25

20

15

10

R. miscarriage

Figure2. The mean age of women with a history of recurrent spontaneous abortion were 28.42 years, of
women with infertility 29.85 years, and of control women 29.83 years respectively.
N total

Mean

Standard

SE of

Lower

Upper

Deviation

mean

95% CI

95% CI

of Mean

of Mean

Minimum

Median

Maximu
m

112

29.83036

4.72274

0.44626

28.94607

30.71465

21

29

41

46

29.84783

4.16316

0.61382

28.61152

31.08413

22

29

37

36

28.41667

4.12224

0.68704

27.0219

29.81143

21

28

37

4.35%

Procentaj (%)

2.78%

0.89%

0
Control

Infertility

R. miscarriage

Figure3. One (2.78%) of 36 subjects in the group with recurrent spontaneous abortion 2 (4.35%) of 46 women
in the group with infertility, and 1 (0.89%) of 112 in the control group were tested positive for IgA tTG

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4.0

3.66%

3.5

Procentaj (%)

3.0
2.5
2.0
1.5
1.0

0.89 %

0.5
0.0

Control

Fertility disorders

Figure 4. Three (3.66%) of 82 subjects in the group fertility disorders (recurrent spontaneous abortion
and idiopathic infertility, and 1 (0.89%) of 112 in the control group were tested positive for IgA tTG

The prevalence of anemia in IgA tTGseropositive women in the group with recurrent
spontaneous abortion was 100%, in the group with infertility 50%, and in the control group
0%
None of the 4 IgA tTGseropositive women had overt signs of malnutrition, showed
stunting of growth, or were underweight. Therefore, nutritional factors were probably not of
major importance in unfavorable pregnancy outcomes.
Agreater prevalence of positive serology for celiac disease was seen in patients with
hemoglobin<12 gm/dL (15). Iron and folate deficiency anemia are seen more often in patients
with celiac disease because these nutrients are absorbed in the upper two parts of the intestine
where damage can occur in earlier stages. Anemia without other clinical clues of intestinal
malabsorption is one of the most common extraintestinal manifestations of celiac disease (15,
16). The number of seropositive subjects with anemia is too small to draw any significant
conclusion.
DISCUSSION
Celiac disease is rarely considered as a diagnosis when evaluating infertility (6), and
the literature term for this connection is neglicted clinical association (7). In North
America 7-14 % of the women are infertile. Among these ,aprox 15 % have idiopathic
infertility, once the anatomic and endocrine causes are excluded(10). This leads to the
conclusion that aprox 1 % of women suffer from idiopathic infertility. Female patients with
celiac disease may present with amenorrhea, repeated spontaneous misscarriages, iron
deficiency anemia, premature births, low weight babies on birth, but sometimes they may be
completely asymptomatic (11,18). If we consider the mean age on diagnosis as 40-50 years
and the delay in diagnosing, we can say that most of the women suffering from Coeliac
disease un diagnosed when they are close to menopause. This means that most of their
reproductive life can be affected by a undiagnosed coeliac disease (12).
There are presently no guidelines for CD testing in patients with infertility or in women
with a history of adverse pregnancy outcomes, although CD prevalence has been shown to be
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higher in these groups than in the general population (8). Owing to the higher risk of CD in
these populations, and the likelihood that the GFD improves pregnancy and fertility
outcomes, we argue that given the low cost of serological screening compared with the great
medical expense associated with infertility and complications of pregnancy, CD testing
should be strongly considered.
Undiagnosed CD is in fact a risk factor for infertility. This may have a significant
impact on the management of infertility, since women seeking medical advice for this
particular condition should be screened for CD. Ultimately, adoption of a GFD could have a
positive impact on fertility in this group of patients.
ACKNOWLEDGEMENT: This paper is supported by the Sectoral Operational
Programme Human Resources Development (SOP HRD), financed from the European Social
Fund and by the Romanian Government under the contract number
POSDRU/159/1.5/S/132395

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REFERENCES
1.
2.

3.
4.
5.

6.
7.
8.
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13.
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Celiac Disease.Peter H.R. Green, M.D., and Christophe Cellier, M.D., Ph.D.N Engl J Med 2007;
357:1731-1743 October 25, 2007DOI: 10.1056/NEJMra071600
Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy. Petrarca L, Nenna R,
Mastrogiorgio G, Florio M, Brighi M, Pontone S. World J Methodol. 2014 Sep 26;4(3):189-96. doi:
10.5662/wjm.v4.i3.189. ECollection 2014.
Tiboni GM, Grazia de Vita M, Faricelli R, et al. Serological testing for celiac disease in women
undergoing assisted reproduction techniques. Hum Reprod. 2006;21(2):376379
Gasbarrini A, Torre ES, Trivellini C, et al. Recurrent spontaneous abortion and intrauterine fetal
growth retardation as symptoms of celiac disease. Lancet. 2000;356(9227):399400.
Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy. Petrarca L, Nenna R,
Mastrogiorgio G, Florio M, Brighi M, Pontone S. World J Methodol. 2014 Sep 26;4(3):189-96. doi:
10.5662/wjm.v4.i3.189. eCollection 2014.
Meloni GF, Dessole S, Vargiu N, et al. The prevalence of celiac disease in infertility. Hum Reprod.
1999;14(11):27592761
Reproductive life disorders in Italian celiac women. A case-control study. Domenico Martinelli,
Francesca Fortunato, Silvio Tafuri, Cinzia A Germinario, BMC Gastroenterol 2010; 10:89.
Review [Reproductive aspects of celiac disease]. Stazi AV, Trinti B. Ann Ital Med Int. 2005 Jul-Sep;
20(3):143-57.
All Roads Lead to Rome: Update on Rome III Criteria and New Treatment Options. Shih DQ1, Kwan
LY. Gastroenterol Rep. 2007 Winter;1(2):56-65.
Stephen EH, Chandra A. Declining estimates of infertility in the United States: 19822002.
Fertil.Steril 2006;86(3):516523. [PubMed: 16952500
Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Patients.An Evidence-Based
Analysis.Ont Health Technol Assess Ser. 2011; 11(3): 163.
Reproductive changes associated with celiac disease. Hugh James Freeman. World J Gastroenterol.
Dec 14, 2010; 16(46): 58105814.
Clinical Utility of Serologic Testing for Celiac Disease in Asymptomatic Patients.An Evidence-Based
Analysis.Ont Health Technol Assess Ser. 2011; 11(3): 163.
Ford AC, Ching E, Moayyedi P. Meta-analysis: yield of diagnostic tests for coeliac disease in
dyspepsia. Aliment Pharmacol Ther 2009; 30: 28-36 [PMID: 19416130 DOI: 10.1111/j.13652036.2009.04008.x]
Celiac disease,anemia and pregnancy.Haslam N, Lock RJ, Unsworth DJ. Clin Lab 2001;47:4679.
Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood
2007; 109:41221.
Bottaro G, Cataldo F, Rotolo N, Spina M, Corazza GR. The clinical pattern of subclinical/silent
celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 1999;94:6916.
Cosmin CIORA , Mircea DICULESCU. Fertility disorders associated to coeliac diseaseretrospective study. Research and Science Today 2(8)/2014 , 231-238.

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December 2014

Medicine

QUALITY OF LIFE FOR HEAD AND NECK CANCER


PATIENTS

Bogdan POPESCU 1
erban Vifor Gabriel BERTETEANU 2
Raluca GRIGORE3
Oana PUN4
Cristian Radu POPESCU 5
Rzvan SCUNAU6

ABSTRACT
HEAD AND NECK CANCER PATIENTS ARE A GROUP OF PATIENTS THAT REQUIRE A CERTAIN
AMOUNT OF ATTENTION DUE TO THE IMPLICATIONS OF THE ILLNESS ON THE QUALITY OF LIFE
AND THEIR RELATIONSHIP WITH FAMILY AND SOCIETY. THE MOST FREQUENT SITES AFFECTED BY
MALIGNANCY ARE THE ORAL CAVITY AND THE OROPHARYNX, FOLLOWED BY THE HYPOPHARYNX
AND THE LARYNX. HEAD AND NECK CANCER AFFECTS THE UPPER AERO-DIGESTIVE TRACT
LEADING TO IMPAIRED BREATHING, FEEDING AND SPEAKING. TAILORED ONCOLOGY THERAPY
ALONG WITH PSYCHOLOGICAL COUNSELING, NUTRITIONAL MANAGEMENT THERAPY NEED TO BE
DECISIVE MEDICAL OPTIONS THAT A CANCER PATIENT SHOULD HAVE ACCESS TO.
KEY-WORDS: CANCER, SELF-DETERMINATION, TRACHEOSTOMA, DEPRESSION, ONCOLOGY
THERAPY

INTRODUCTION
Head and neck cancer patients are a group of patients that require a certain amount of
attention due to the implications of the illness on the quality of life and their relationship with
family and society. Most of the head and neck cancers have the histology of squamous cell
carcinoma, other histology being possible and took into consideration when necessary. This
particular type of cancer is usually present in the 50 to 60 years of age group of patients.
However, recent studies showed that dramatic changes took place in the age distribution over
University of Medicine Carol Davila,Colea Clinical Hospital, Bucharest, E.N.T. Department
University of Medicine Carol Davila,Colea Clinical Hospital, Bucharest, E.N.T. Department
3
University of Medicine Carol Davila,Colea Clinical Hospital, Bucharest, E.N.T. Department
4
University of Medicine Carol Davila,Colea Clinical Hospital, Bucharest, E.N.T. Department
5
University of Medicine Carol Davila,Colea Clinical Hospital, Bucharest, E.N.T. Department
6
Department of General Surgery, University of Medicine Carol Davila, Colea Clinical Hospital, Bucharest,
razvan.scaunasu@gmail.com
1
2

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the past 3 decades. This meaning that young patients, with ages between 25 and 40 years, are
more likely to have the disease. For young, vibrant and active adults such a diagnosis is life
altering in the most profound ways possible. Changes are present in the life of any other
patient in this situation, but the psychological implications in young adults are more
devastating than in older patients. Recent studies indicate that incidence of the head and neck
malignant pathology is increasing [1,2]. This may be due to increased narcotics abuse and the
presence of human papilloma virus at the level of the mucosa of the upper aero-digestive tract
[3,4,5].
Head and neck cancer affects the upper aero-digestive tract this meaning that breathing,
feeding and speaking are impaired. Fundamental physiological functions are altered by the
presence of malignant neoplasia in the head and neck region. The most frequent sites affected
by malignancy are the oral cavity and the oropharynx, followed by the hypopharynx and the
larynx. Of course, other sites are also affected by the occurrence of the solid malignant
disease such as, nasal cavity, paranasal sinuses, salivary glands, soft tissue, lymphatic system,
ear.
The quality of life of each individual is defined by the personal well-being and the
interaction with society members. Breathing and feeding are essential for an individual and
speaking is the tool for social bonding. When these are impaired several events take place.
Malignant tumors located in the hypopharynx and the supraglottic larynx manifest a
tendency to induce odinophagia and dysphagia which result in partial feeding or, at the
extreme, in the impossibility of feeding. The result of this is the appearance of malnutrition
directed towards malignant cachexia. The stage of malnutrition is in direct correlation to the
site of the primary tumor, the stage of the disease, histology type, tumor grading,
comorbidities, risk factors and immune status. Malignant disease is consumptive therefor
energy deposits are diminished. At first fatty tissue is reduced and in the late stages of the
disease proteins are being metabolized. The reparatory processes are impaired and immune
function is altered making the organism more susceptible to endogenous and external
environment aggressions. In terms of patients perception this is translated into a more
passive attitude, lack of will and interest in the normal situations of life, all the way to
depression. The lack of energy makes normal activities harder to be performed, decreased
efficacy and on a global scale reduces the well-being of the patient.
Treatment of the malignant disease of the upper digestive tract in all stages of the
disease should be considered in an oncology committee in which several specialist need to be
part of. Regarding the oncology treatment the surgeon, the radiotherapist, the oncologist play
a decisive role in determining the optimal course of action. However, patients need to be
addressed in a complete manner. Psychological counseling, nutritional management therapy
are two decisive medical options that a cancer patient should have access to.
Feeding head and neck cancer patients
It is well known that nutritional therapy plays an important role in the outcome of the
oncology therapy. When nutrition is to be considered in an oncological patient there are a few
principles that need to be taken into consideration. The informative principle requires that a
cancer patient is informed by the physician about the need for enteral, parenteral or mixed
nutrition, the advantages and disadvantages of each method. In addition to this principle the
patient has the right of self-determination. The patient has the right to chose a certain
nutritional therapy after being presented with all the options and, of course, the nutrition
therapy should be tailored according to the patients preferences. The self-determination
principle is more likely to be followed by the physician in late-stage patients when only

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palliative care is possible. In these cases the will of the patient should govern the entire
medical care, assuring (a minimum of) the best quality of life possible.
Patients in which the surgical procedure altered the status of the upper digestive tube
need to be fed through a naso-gastric feeding tube or via PEG (percutaneous endoscopic
gastrostomy). Both have advantages and disadvantages that must be discussed with the
patient. The decision making should involve the patient due to the social implications of
placing a naso-gastric tube. Most of the patients that come to the E.N.T. Department of
Colea Clinical Hospital are from a rural environment where evident signs of disease lead to
banishment. This is due to the incomplete understanding of the disease by the people and,
ultimately by their lack of medical culture. Still, this is a particular situation that most
patients want to avoid. The question Am I really going to have a tube inserted inside my
nose? is still being asked before the patients agree to the surgical treatment as an imposition
to their social lives. Therefor counseling should be considered for these patients.
Ensuring the air pahway and speaking
No doubt that for the head and neck cancer patients the most important thing is to make
sure that the patient has a clear upper airway path. Tumors located in the glottic and
subglottic regions of the larynx make the passage of air into the lungs difficult or impossible
in some cases. These are the situations in which tracheostomy is imperative. Total
laryngectomy is one of the surgical interventions that leads to a definitive tracheostomy.
Other situations include partial laryngectomies with endolaringeal complications. The
perspective of a tracheostomy tube is very unpleasant for the patient. Most of the patients that
undergo a total laryngectomy ask the E.N.T. surgeon about voice rehabilitation options. This
is because despite the life-threatening disease patients have difficulties in accepting the
impossibility of communication with fellow individuals. The presence of the tracheostoma
leads to altered properties of the air that goes into the lungs because of the lack of purifying,
humidifying and heating processes that take place inside the upper airways. This might lead
to the formation of crusts, tracheal and bronchal deposits, infections of the inferior airways.
In terms of quality of life for the patientsthis situation leads to coughing, exteriorizing
secretions through the tracheostoma and ocasinally bleeding. The bleeding occurs because of
the fact that the plastic tracheostomy tube is a foreign body inside the trachea.
The management of the tracheostomy includes aspiration of the secretions, cleaning
and constant attention to lessions induced by the tracheostomy tube.
The ability of speaking and the voice rehabilitation options are considered by the
patients as an improvement in the quality of life. This is why each preoperative discussion
with a patient that undergoes a total laryngectomy needs to address the problem of voice
rehabilitation. It is easier for the patient to accept the removal of the voice organ knowing
that eventually speech will be possible.
There are 3 methods for rehabilitating a laryngectomised patient speaking-wise. None
of the 3 methods have 100% chances of success, therefor the patient needs to be aware of all
the possibilities. One of the methods is the use of a laryngophone which is a digital device
that converts vibrations of the neck in sound processed by a sound processor and expressed
through a speaker. In our experience some 50% of the patients manage to use this device in
an optimum manner. Those who cannot adapt to the device can benefit from one of the other
2 types of voice rehabilitation.
Erigmophonia, or esophageal voice, is another type of voice rehabilitation in which the
patients are taught to use a volume of air traveling from the stomach to the oral cavity to set
the pharynx walls into vibration and by this produce sounds. This is a non-invasive technique

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of voice rehabilitation. Still, the main disadvantage is that only some 30% of patients manage
to master the technique.
The last of the voice rehabilitation procedures that may be attempted for a
laryngectomised patient is the insertion of a voice prosthesis. There are different types of
voice prosthesis but the functioning principle is the same. The surgeon creates a
communication between the trachea and the cervical esophagus at the top of the tracheostoma
through which he inserts the voice prosthesis. This device allows the unidirectional passing of
air from the trachea towards the cervical esophagus due to unidirectional valve when the
tracheostoma is shut by the patients fingers. This setting makes sure that food and secretions
do not enter the trachea. The volume of air that is pushed up towards the tracheostoma is
pointed to the walls of the cervical esophagus and the remaining pharynx in the attempt to set
the mucosa into vibration. The esophagus and pharynx mucosa acts like pseudo vocal cords
generating the primary sound. The advantage of the method is that as much as 80% of the
patients manage to speak when using a voice prosthesis. There are several disadvantages that
have to be taken into consideration such as, remaining eso-tracheal fistula, tracheal ang lung
infections, aspiration of food and liquids into the lungs, complex management of the voice
prosthesis. A voice prosthesis needs to be replaced every other 3 months, this being a time
management problem for the patient and, nonetheless a money consuming activity.
The use of fingers to close up the tracheostomy in order for the patient to speak has
been replaced by the introduction of the hands-free systems for the voice prosthesis. It is a
simple valve placed at the surface of the skin that allows air to go only into the lungs and
only a small amount of air through the tracheostomy. Most of the air goes through the voice
prosthesis allowing the patient to speak freely. The use of such devices improves the quality
of life for larynx cancer patients.
CONCLUSIONS
The quality of life for head and neck cancer patients is a concept which modern
medicine has to operate with due to moral, ethical and legal reasons. E.N.T. surgeons need to
explain to their patients the entire therapy plan with all the consequences, advantages and
disadvantages. The self-determination of the patient is of outmost importance and the patient
needs to be involved into the decision making process. The probability of a tracheostomy and
the lack of speech abilities are pitfalls for the patients and the physician needs to be prepared
to offer solutions. This is a field of neverending questions for the head and neck cancer
patients that need to be reinserted into the family and social life without considering this to be
un unsurpassable condition.

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December 2014

REFERENCES
1.

2.

3.

4.
5.

Majchrzak E, Szybiak B, Wegner A, Pienkowski P, Pazdrowski J, Luczewski L, et al. Oral cavity


and oropharyngeal squamous cell carcinoma in young adults: a review of the literature. Radiology
Oncology. Mar 2014;48(1):1-10.
Gayar OH, Ruterbusch JJ, Elshaikh M, Cote M, Ghanem T, Hall F, et al. Oropharyngeal
Carcinoma in Young Adults: An Alarming National Trend. Otolaryngology Head Neck Surgery. Jan 22
2014;
Verschuur HP, Irish JC, O'Sullivan B, Goh C, Gullane PJ, Pintilie M. A matched control study of
treatment outcome in young patients with squamous cell carcinoma of the head and neck.
Laryngoscope. Feb 1999;109(2 Pt 1):249-58.
Shiboski CH, Schmidt BL, Jordan RC. Tongue and tonsil carcinoma: increasing trends in the U.S.
population ages 20-44 years. Cancer. May 1 2005;103(9):1843-9.
Schantz SP, Byers RM, Goepfert H, Shallenberger RC, Beddingfield N. The implication of tobacco
use in the young adult with head and neck cancer. Cancer. Oct 1 1988;62(7):1374-80.

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Medicine

HYDATID CYST LOCATED IN THE MAIN BILE DUCT-A


RARE DIFFERENTIAL DIAGNOSIS OF OBSTRUCTIVE
JAUNDICE IN PREGNANCY

Tudor NSTSESCU1
Drago DAVIOIU2
Constantin BUDIN3
Oana BODEAN 4

ABSTRACT:
HEPATIC DISORDERS IN PREGNANCY MAY BE UNIQUE TO PREGNANCY, PREEXISTING,
COINCIDENT WITH PREGNANCY AND POSSIBLY EXACERBATED BY THIS CONDITION. MOST
COMMON NONOBSTETRIC CAUSES INCLUDE OBSTRUCTION BY GALLSTONES AND VIRAL
HEPATITIS. TUMORS OR PARASITES ARE LESS FREQUENT. A DIFFERENTIAL DIAGNOSE MUST
ALWAYS INCLUDE HYDATID DISEASE ESPECIALLY IN ENDEMIC COUNTRIES. PRIMARY
EXTRAHEPATIC HYDATID CYSTS ARE RARE. WE PRESENT THE CASE OF A 33 WEEKS PREGNANT
PATIENT WITH OBSTRUCTIVE JAUNDICE DUE TO A HYDATID CYST LOCATED IN THE MAIN BILE
DUCT, WHICH IS A VERY UNUSUAL SITUATION.
KEYWORDS: OBSTRUCTIVE JAUNDICE, PREGNANCY, HYDATID CYST

INTRODUCTION:
Jaundice during pregnancy is caused by a broad spectrum of pathologic conditions,
some of them with no direct relation to gestation itself. The yellowish discoloration of the
skin and mucous membranes caused by high bilirubin levels is visible when bilirubin exceeds
3 mg/dl.
In the general population, jaundice is classified as follows, according to the mechanism
and level of production: pre-hepatic (hemolytic), hepatocellular and post-hepatic
(cholestatic).
The main medical conditions representing possible causes of jaundice during pregnancy
are (Houston et al. 2000): acute fatty liver of pregnancy, viral hepatitis, choledocholithiasis,
HELLP syndrome, idiopathic cholestasis of pregnancy, severe preeclampsia.

Department of General Surgery, Bucharest Emergency University Hospital


Department of General Surgery, Bucharest Emergency University Hospital
3
Department of General Surgery, Bucharest Emergency University Hospital
4
PHD, Carol Davila University of Medicine and Pharmacy Bucharest, Department of Obstetrics and
Gynecology, Bucharest Emergency University Hospital, oanamb8@gmail.com
2

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In the general population, post-hepatic jaundice is caused by a mechanic obstruction of


the biliary system. The most common causes are gallstones, tumors of the pancreas and
parasites.
Hydatid disease is an endemic zoonotic infection produced by larvae belonging to the
genus Echinococcus. Hydatid cysts develop mostly inside the liver, but they can occur
anywhere in the body. The parasite can travel through portal circulation, lymphatic system,
biliary tract and also, by dissemination of daughter cysts in the peritoneal cavity or other
cavities.
The occurrence of primary hydatid cysts in the gallbladder is extremely rare - only 6
cases reported in the English medical literature in 2010 (Krasniqi et al., 2010). The
occurrence of primary hydatid cysts in the main biliary duct is extremely rare, and also,
finding such pathologic condition during pregnancy makes the differential diagnosis for
obstructive jaundice more challenging.
CASE REPORT
We present the case of a 29 year-old woman, gravida 2, para 2, who at 33 weeks of
gestation was admitted, in September 2014, to local district hospital for jaundice of the skin
and mucous membranes lasting for 3 days. The abdominal ultrasound examination performed
at the local district hospital suggested a large tumor or large gallstone located in the biliary
tract and the patient was transferred to the Bucharest Emergency University Hospital.
At the admission, the patient had jaundice of the skin and mucous membranes, pain in
the epigastrium, constipation for 3 days, dark urine, normal blood pressure and no other
clinical symptoms. There was nothing significant to extract from her medical history and the
possibility of viral hepatitis was excluded by rapid serologic testing. The patient was not
taking any medication and had not ingested any toxins before the symptoms appeared.
The patient did not accuse any uterine contractions or any alarming symptoms related
directly to pregnancy. Therefore, she was evaluated by the General Surgery Department, the
Gastroenterology Department and another abdominal ultrasound was performed.
The General Surgery Department reported: yellow discolouration of the skin and sclera.
Abdominal moderate distension and tenderness in the right upper quadrant. A mass was
palpated in the right upper quadrant. Darkened urine and pale stools.
The abdominal ultrasound examination described: Distended Wirsung duct (up to 3
mm), distended intrahepatic bile ducts (up to 13 mm) and main bile duct (up to 16 mm),
without images of stones or masses.
Laboratory investigations show leucocytosis with neutrophylia (Leu# = 13.130/mm3,
Neu% = 90.5%), elevated levels of alanine aminotransferase (ALT = 75 U/L), aspartate
aminostrasferase (AST = 79 U/L)and gamma-glutamyl transferase (GGT = 141 U/L), total
bilirubin and it's fractions (total bilirubin = 8.01 mg/dL, direct bilirubin = 6.36 mg/dL),
hypercholesterolemia (total cholesterol = 295 mg/dL) and hypertriglyceridemia (triglycerides
= 476 mg/dL), without coagulopathies.
The patient was transferred to the Gastroenterology Department of Colentina Hospital
for further investigations. The ultrasound examinations suggested a large dilated gallbladder,
9/3.4cm, double splitted, dilated intrahepatic biliary duct, main biliary duct of 2.3cm, dilated
in its extrahepatic region. At the level of the hilum there was a clearly contoured but split
mass of 4/8.8cm, surrounded by its own wall, having a mixed structure and no peristaltic
movements. It was suspected to be a part of the duodenum.
Because no other investigations could reveal the cause of obstruction and both mother
and foetus were at risk, an abdominal computer tomography was performed, with permission
of the Gynecology Department and the patients` informed consent. CT examination
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concluded that there was the possibility of a voluminous (55 mm x 110 mm), heterogeneous
mass, externally obstructing the biliary duct, extended from visceral surface of liver and
hepatic pedicle to cephalic portion of the pancreas (figure 1, figure 2).

Figure 1. CT-scan of the upper abdomen: dilated intrahepatic and extrahepatic bile ducts, heterogenous tissue
mass between visceral liver surface, hepatic pedicle and cephalic portion of the pancreas.

Figure 2. CT-scan of the upper abdomen: liver (F), aorta (AO), gallblader (VB), tumoral mass (probably biliary
main duct - CBP).

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Imagistic investigations were completed with cholangio-MRI. That non-invasive


investigation confirmed biliary ducts and Wirsung duct dilatation (figure 3) but could not
confirm the presence of a tumor described at CT-scan.

Figure 3. Cholangio-MRI sequence: dilated intrahepatic and extrahepatic bile ducts, dilated Wirsung duct.

The patient was transferred back to the Bucharest Emergency University Hospital
where she received corticoid treatment for the prevention of prematurity related
complications.
In the following days, the bilirubin levels continued to increase and an ERCP is
performed. At cholangiography the main biliary duct appears horizontalized, 17 18 mm
diameter, cystic duct is long and tortuous, but the gallblader was not opacified. It drained bile
and biliary sludge. A biliary 8.5 Fr stent was placed transpapillary.
Bilirubin levels dropped for two days, but continued to increase 3 days after the ERCP
(TB=10.08 mg/dl, DB=8.2 mg/dl).
Facing the controversial results of investigations and clinic presentation, the medical
team of general surgeons and obstetricians decide to perform a C-section to deliver the
newborn safely and also to explore the abdominal cavity.
The obstetricians extracted a live 2350 g male newborn. The skin of the newborn, the
placenta and the membranes appeared to be yellowish and impregnated with meconium. The
baby was immediately transferred to the Neonatology Department and received Apgar Score
8.
The general surgeons continued to explore the abdominal cavity after the C-section
delivery was completed, and found a very long (about 200 mm), tense gallbladder, main
biliary duct about 18 mm diameter, without any palpable tumoral mass (figure 4). An
anterograde cholecystectomy and supraduodenal longitudinal choledocotomy were performed
(figure 5).

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Figure 4. Intra-operatory view: the gallbladder is


pulled down. The dilated coledoc can be seen.

Figure 5. Intra-operator view: choledocotomy

Exploring the coledoc, the surgeons extract a few gelatinous membranes and biliary
sludge (figure 6). Inside the coledoc, a Kehr tube is placed for external drainage of the bile.
The peritoneal cavity is washed with saline solution. Multiple drainage of the peritoneal
cavity is placed prior to closing the patient.
The hystopathological examination confirms the extracted membranes as hydatid cyst
membranes.

Figure 6. Gelatinous membranes and biliary


sludge extracted from coledoc.

Figure 7. Control-cholangiografy performed 12


days after surgery

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The patient is transferred to the Intensive Care Unit where she recovered well.
The Kehr tube was removed 12 days after surgery, after control-cholangiography was
performed (figure7).
The bilirubin levels decreased to normal and the patient was released from the hospital
13 days after the surgery.
The premature newborn had a total bilirubin level of 3.56 mg/dL in day 1 and
developed neonatal jaundice with total bilirubin levels of 9.03 mg/dL in day 6 and needed
specific therapy. He was released from hospital at 13 days after birth in good clinical
condition, with no jaundice symptoms or other complications.
At discharge the patient received Albendazole p.o. therapy (800 mg/day).
DICUSSION
Hydatid disease (HD), also known as cystic echinococcosis, is a zoonotic parasitic
disease of human and mammalians caused by the larval stage of tapeworm Echinococcus
granulosus. E. granulosus normally exist among dogs and sheep and in its life cycle, humans
sometimes become accidental intermediate host. Humans can orally ingest the E. granulosus
eggs from infected excretions by handling the animal or egg-containing feces, plants, eating
vegetables, uncooked fruits, or drinking contaminated water. Hydatid disease is widely
spread in many endemic regions: North Africa, Turkey, South France and The Balkan
Peninsula. It is a disease of rural areas where farming is practiced traditionally. The hydatid
cyst can occur also in non-endemic countries because of the upsurge of emigration and trade.
The liver, followed by the lung are the most common sites of infection, but that disease
can affect in 10% of cases other atypical sites, such as muscle, bone, brain, spleen. Rare
locations, such as pancreatic, mammary, scrotal, adrenal, cardiac interventricular septum,
ovarian were reported.
Hydatid disease is seen in subjects of any age and sex, although it is more common in
those of 20 40 years old.
The clinical features of cystic echinococcosis are highly variable. The spectrum of
symptoms depends on the involved organs, size of cysts and their sites within the affected
organ or organs, interaction between the expanding and adjacent organ structures, particularly
bile ducts and the vascular system of the liver, complications caused by rupture of cyst,
bacterial infection of cysts and spread of protoscolices and larval material into bile ducts or
blood vessels, immunologic reactions such as asthma, anaphylaxis, or membranous
nephropathy secondary to release of antigenic material.
The rate of growth of cysts is variable depending on the strain differences and the organ
involved. Typicaly measurements state that the average cyst growth is 1 to 1.5 cm per year.
Patients come to the clinicians attention for variable reasons, such as when a large cyst
has some mechanical effect on organ function or rupture of a cyst. The cyst may also be
accidentally discovered, during imagistic examination.
The combination of imaging and serology usually enables diagnosis. The standard
diagnostic approach for cystic echinococcosis involves imaging techniques, predominantly
ultrasonography, computer tomography (CT), X-ray examinations, and confirmation by
detection of specific serum antibodies by immunodiagnostic tests.
Serological tests are commonly employed to supplement the imaging data in the
diagnosis of hydatid cyst. The current gold standard serology test for echinococcosis detects
IgG antibodies to hydatid cyst fluid-derive native or recombinant antigen B subunits.
Sometimes cystic echinococcosis is difficult to treat. This disease can be medical or
surgical managed. Clinical management includes albendazol or mebendazole therapy,

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especially in small cysts. Larger cyst (>10 cm diameter) preferably undergo surgical
resection.
We didnt found any report of intrabilliary main duct localization of the hydatid cyst,
without other sites. The mechanism of cyst development at this level can only be supposed.
A possible scenario can be the intraluminal migration of the small hydatid cyst
developed near the biliary intrahepatic system in the common biliary duct and then in the
main biliary duct.
Another possible scenario is that the cyst was translocated in the main biliary duct by
the pathological conditions that associate the presence of the bilirhagia.
The third option can be the evacuation of the hepatic, juxtaductal, hydatic cyst in the
biliary tract. If one of them is blocked, the cyst will grow in the main biliary tract.
CONCLUSION
Hydatid disease is a zoonotic parasitic disease of human and mammalians caused by the
larval stage of tapeworm Echinococcus granulosus.
The most common sites of localization are the liver and the lung.
The standard diagnostic approach for cystic echinococcosis involves imaging
techniques, predominantly ultrasonography, computed tomography (CT), X-ray
examinations, and confirmation by detection of specific serum antibodies by
immunodiagnostic tests.
The diagnosis of unique hydatid cyst located at this level implies strong difficulties,
especially when appropriate imagistic methods cannot be used.
The difficulty of the shown case was raised by the pregnancy, limiting other possible
investigations (contrast administration, irradiation), the absence of other cyst in typical sites
and a low grade of epidemiological suspicions.

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Atin H, Shyamapada P, Saswati H: An unusual case of hydatid cyst of the ovary and pouch of Douglas
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Craig PS, McManus DP, Lightowlers MW: Prevention and control of cystic echinococcosis. Lancet
Infectious Diseases 2007, 7:385-94.
Brown RA, Millar AIW, Steiner Z, Krige JEJ, Burkimsher D, Cywes S: Hydarid cyst of the pancreas: a
case report in a child. European Journal Of Pediatric Surgery 1995, 5:121-4
Budke CM: Global socioeconomic impact of cystic echinococcosis. Emergency Infectious Diseases 2006,
12:56-64
Bolognese A, Barbarosos A, Muttillo IA: Echinococcus cyst of the pancreas: description of a case and
review of the literature. Chirurgia Oct 2000; 21 (10):389e93
Creasy RK, Resnik R.: Maternal fetal medicine: principles and practice. Maternal Fetal Medicine,
Philadelphia: WB Saunders, 1994.
De Rosa F, Teggi A: Treatment of Echinococcus granulosus hydatid disease with albendazole. Ann Trop
Medical Parasitology 1990;84(5):46772
Eckert J, Gottstein B, Heath D, Liu FJ: Prevention of echinococcosis in humans and safety precautions.
In: Eckert J, Gemmell MA, Meslin F-X, Pawlowski ZS, eds. WHO/OIE Manual on Echinococcosis in
Humans and Animals: a Public Health Problem of Global Concern. Paris: World Organization for Animal
Health 2001;23847.
Escudero MD, Sabater L, Calvete J, Camps B, Labios M, Lledo S: Arterial hypertension due to primary
adrenal hydatid cyst. Surgery 2002;132:894-895.
Gharbi HA, Hassine W, Brauner MW, Dupuch K. Ultrasound examination of the hydatic liver.
Radiology 1989, 139:45963
Gupta S, Verma D, Kumar R: A rare presentation of hydatid disease: Breast lump. Journal of Case
Reports 2014; 4(2): 331-333.
Houston J et al.: Jaundice and Disseminated Intravascular Coagulopathy in Pregnancy. Journal of the
American Board of Family Medicine. 2000;13(1)
Knox T, Olans L:.Liver disease in pregnancy. New England Journal of Medicine 1996;335:569-76.
Krasniqi et al.: Primary hydatid cyst of the gallbladder: a case report. Journal of Medical Case Reports
2010, 4:29
Ipek G, Omeroglu SN, Goksedef D, Balkanay OO, Kanbur E, Engin E, et al. Large cardiac hydatid cyst
in the interventricular septum. Texas Heart Institute Journal 2011;38:719-22.
Irdem A, Deniz H, Kervancoglu M, Kervancoglu S: A cardiac cyst hydatid in the interventricular
septum. Turk Gogus Kalp Dama 2014;22:174-6
Nagpal V, Kohli K, Chowdhary A, Kumar A, Andley M, Ravi B: Breast lump as a presentation of a
hydatid disease. Trop Doct 2006;36(1):57-8.
Sheng Y, Gerber DA: Complications and management of an echinococcal cyst of the liver. Journal of
American College of Surgeons 2008;206(6):12223.
Zaidi S.: Case report: Some rare presentations of hydatid cyst: two case reports. Cases Journal 2009;2:62
Zapatero J, Madrigal L, Lago J, Baschwitz B, Perez E, Candelas J:. Surgical treatment of thoracic
hydatidosis. A review of 100 cases. European Journal of Cardiothoracic Surgery 1989;3:43640

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Medicine

RDW AS A NOVEL MARKER OF DISEASE ACTIVITY IN


CROHNS DISEASE: TESTING A HYPOTHESIS IN AN IBD
TERTIARY CARE CENTER IN ROMANIA
Cristian TIERANU1
Ciprian GIGEA2

ABSTRACT
BACKGROUND: ONE OF THE MOST COMMON COMPLICATIONS IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASE (IBD), EITHER CROHNS DISEASE (CD) OR ULCERATIVE COLITIS (UC), IS ANEMIA.
RED BLOOD CELL DISTRIBUTION WIDTH (RDW) QUANTITATIVELY MEASURES THE SIZE
VARIABILITY OF THE RED BLOOD CELL POPULATION AND MIGHT INCREASE EVEN BEFORE
ANEMIA MANIFESTS ITSELF. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE USEFULNESS OF
RDW IN THE EVALUATION OF DISEASE ACTIVITY IN CD BY COMPARISON WITH ALREADY
ACCEPTED MARKERS OF ACTIVITY SCH AS ERYTHROCYTE SEDIMENTATION RATE (ESR), CREACTIVE PROTEIN (CRP) AND FIBRINOGEN LEVELS. WE ENROLLED 148 PATIENTS WITH CROHNS
DISEASE, AND 51 PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS) AS THE CONTROL GROUP.
RESULTS: RDW WAS SIGNIFICANTLY HIGHER ONLY FOR PATIENTS WITH SEVERE DISEASE
ACTIVITY (P=0.02). RDW HAD SIGNIFICANTLY HIGHER VALUES FOR THE PATIENTS WITH CD
(P=0.004). RDW WAS THE MOST SENSITIVE AND SPECIFIC MARKER FOR CD WITH INFLAMMATORY
PATTERN (P<0.001). ADDITIONALLY, RDW SHOWED A CORRELATION WITH THE EXTRAINTESTINAL
MANIFESTATIONS OF CD (P<0.05).
CONCLUSIONS: RDW IS NOT SUFFICIENTLY SENSITIVE OR SPECIFIC TO DIAGNOSE
INDEPENDENTLY THE FLARES OF ACTIVITY IN IBD. RDW CAN BE AN ADDITIONAL MARKER IN
DIFFERENTIATING CD ACTIVITY FLARES FROM OVERIMPOSED FUNCTIONAL DISORDERS (IBS).
RDW CORRELATES SIGNIFICANTLY WITH EXTRAINTESTINAL MANIFESTATIONS AND
INFLAMMATORY PATTERN OF CD.
KEYWORDS:
RDW,
INFLAMMATORY
EXTRAINTESTINAL MANIFESTATIONS

BOWEL

DISEASE,

ACTIVITY,

CRP,

ESR,

INTRODUCTION
Inflammatory bowel diseases(IBD) are chronic inflammatory diseases of unknown
origin and affect different segments of the gut. There are two mainly defined diseases
included in the group, Crohns Disease(CD) and Ulcerative colitis(UC). They are
characterized by recurring remission and exacerbation periods. CD is a lifelong disease
resulting from a complex interaction between genetic and environmental factors, however
1

Department of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest; Resident in


Gastroenterology, MD, PhD student, e-mail adress: tieranucristian@gmail.com
2
University of Medicine and Pharmacy Carol Davila, Bucharest

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observed predominantly in developed countries of the world 1. There is a distinct North-South


gradient within Europe, with a recent increase of incidence in Southern countries.
To diagnose and determine disease activity of CD there are noninvasive laboratory
markers, endoscopic procedures (such as ileocolonoscopy) and imaging techniques: MR or
CT enterography/enteroclysis has the highest diagnostic accuracy for the detection of
intestinal involvement of CD including extramural complications, whereas small bowel
capsule endoscopy is reserved for patients with a high clinical suspicion of CD despite
negative investigation by the previously mentioned techniques1. However, because of the
invasiveness and cost of endoscopic procedures and the cost of advanced imaging techniques
there are several laboratory markers used to determine inflammation and disease activity such
as: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hgb),
platelet counts( PLT), as well as new investigations such as: fecal calprotectin3, VEGF4,
TREM5, micro-RNA6, factor XIII7, Feritin and transferin saturation8, ANCA and ASCA9,
interleukins 6 and 1, soluble interleukin-2 receptor and soluble intercellular adhesion
molecule-1(ICAM-1) 10. None of these tests, however, have a high specificity or sensibility
for monitoring disease activity in CD, nor a high usability as diagnostic markers. Recent
studies have revealed that many of the mentioned markers, especially those with higher
specificity and sensibility than the rest, are expensive and not widely available. This entails
the need for a new way to test IBD disease activity inexpensively and non-invasive as well as
not potentially harmful to the patients. Several studies have evaluated and demonstrated the
potential of red cell distribution width(RDW) as a valuable marker for the diagnostic and
monitoring of disease activity in IBD11-14.
MATERIALS AND METHODS
1. Selection of study participants
This is a cross sectional observational cohort study performed in the Department of
Gastroenterology, Fundeni National Institute for Gastroenterology and Hepatology. A total of
148 IBD patients with ages ranging from 20 to 73 years participated in the study. The patients
were diagnosed with CD in various stages of activity that was clinically, imagistically,
endoscopically and histopathologically confirmed. Additionally, the clinical and laboratory
parameters of the patients were reviewed to confirm the diagnosis. A group of 51 patients
diagnosed with irritable bowel syndrome with diarrhea(IBS-d), with no laboratory, imagistic
or endoscopic abnormalities was employed as a control group due to the frequent need for
differential diagnosis with IBD in this group of patients. These control patients had normal
laboratory tests, without any inflammation.
Pacients without a clear diagnosis of CD or without insufficient clinical and laboratory
and endoscopic data to support the diagnosis were excluded from the study.
The study group was divided into 2 subgroups, based on the status of disease activity
(either active or in remission) and the active disease subgroup was further divided into
activity severity groups based on the CDAI score and clinical criteria (mild, moderate and
severe activity respectively).
The CD subgroup was also split into 3 groups groups based on disease pattern,
inflammatory, structuring or fistulising, respectively. The clinical evaluation criteria used
were CD location, perianal lesions, presence of endoscopic lesions, extraintestinal
manifestations.
The laboratory parameters used were Hgb levels (ranging from 12 to 14 g/dl),
ESR(with a threshold of 15 mm/hr), CRP(with a threshold of 2 mg/l), fibrinogen(threshold of
400 mg/dl) and RDW-SD (range from 39 to 46 FL).

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The age, gender, disease location, pattern and disease activity for each patient were
recorded. All enrolled patients were required to have biological tests such as complete blood
count(CBC), ESR, CRP. All CBC parameters, ESR and CRP values were assessed. Initial
comparisons were made for RDW values between the IBS control group and CD group.
Then, the patients were grouped based on their disease activity score in groups of actively/in
remission CD and different severity CD, and RDW levels were compared between the active
and remission period subgroups, as well as between each activity state. Finally, ESR and
CRP levels were compared among the groups and crosswise with the control group.
2. Statistical evaluation
SPSS for Windows version 20.0 was used for the statistical analyses. For the evaluation
of the data from the study, descriptive statistical methods (meanstandard deviation),
Students t-test and the Mann-Whitney U Test were used to establish potential differences
between the averages of 2 independent groups for parameters with and without normal
distributions, respectively. The Kruskal-Wallis test was used for variance analysis of
intergroup values. The one-way ANOVA test was used for normal distribution, one-way
variance analysis. In order to determine a potential significant correlation of RDW with CRP,
ESR, clinical symptoms or disease pattern between multiple groups, Spearmans rank
correlation coefficient was used. Receiver operating characteristic(ROC) curve analysis was
used to calculate sensitivity and specificity levels. For comparisons of qualitative data, the
chi-squared test was used. The results in the 95% confidence interval and p-values of less
than 0.05 were considered to be significant.
Table 1. Demographic and clinical characteristics of the controls and the patients with IBD
Characteristic

Control group (n=51)

CD(n=148)

P-value

Age, yr

54.4315.29

38.86.458

<0.001

Sex(F/M)

38/13

79/69

<0.001
-

Localization of disease,
n(%)
Ileitis

30(20%)

Colitis

88(60%)

Ileocolitis

30(20%)

Clinical activity, n(%)

Active disease

100(68%)

In remission

48(32%)

RESULTS
There were significant differences in age between the CD group and its subgroups and
the control group with IBS. The median age among the patients with CD was 38.86.46,
underlining the prevalence of CD occurrence at a young age, whereas the patients in the
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control group were significantly older, with a median age of 54.4315.29 years. There was
also a significant gender distribution difference between the IBD group and control, with the
distribution being similar (52% women, 48% men respectively) among the patients with CD,
and in the favor of women for the IBS-d group (75% women). Table 1 presents the
demographic and clinical characteristics of the two groups.
The laboratory parameters from the patients with CD compared to those of the control
group are presented in table 2. When the CD patients were compared based on their disease
state, active disease versus remission, we observed the following: 1) regardless of disease
state, the RDW level was statistically different between control, active and in remission
disease; 2) the RDW values between active and in remission subgroups were not statistically
different( p= 0.13); 3) with regards to activity state, RDW was significantly different only for
the severe activity stage of CD (ANOVA test p-value=0.01; Mann-Whitney U test p-value
<0.001); 4) there was no statistically significant difference in RDW levels between disease
patterns (p-value = 0.46);
CRP and ESR levels in patients with active disease were significantly higher than those
with CD in remission or control. The Pearson correlation (table 3) indicated that increased
inflammatory parameters such as ESR, CRP and Fibrinogen were significantly correlated
with an increased RDW level in patients with active disease. The inflammatory markers
themselves were also significantly correlated. All these correlations indicate that RDW levels
increase in the presence of inflammation similarly to other inflammatory markers, thus giving
the possibility of RDW to be considered an indicator of active inflammation.
Table 4 and Fig. 1 show comparisons with the other inflammatory parameters (ESR,
CRP, Fibrinogen and Hgb, in patients with inflammatory CD. Only for that particular disease
pattern did the ROC curve for RDW-SD show an increased AOC (area under curve of 0.493)
compared to the other markers(except CRP) and the largest confidence interval of all the
markers used( for a 95% confidence level, the lower bound was 0.35 and the upper bound
0.637). RDW-SD was the second most specific indicator with 63% (after Fibrinogen at 85%)
and had the lowest sensitivity with 48%. The most sensitive indicator for the CD patients was
CRP with 87.5% but its specificity was 37%. Overall, in CD patients, RDW was not a
signifficant indicator for disease activity, in terms of specificity and sensibility, whereas
CRP, VSH and Fibrinogen were statistically signifficant (table 5).
Table 2.Comparison of Laboratory Parameters of CD group and Controls (One-way ANOVA test)
Parameter

Control group

CD group

P Value

(n=51)

Active disease
(n=100)

In remission (n=48)

RDW-SD(FL)

42.513.1

466.5

44.444.9

0.001

Hbg(g/dl)

13.631.3

12.32.3

13.71.5

<0.001

ESR(mm/hr)

28.415.7

36.619.6

22.613

0.003

CRP(mg/dl)

5.83.7

31.750

513

0.001

Fibrinogen(mg/dl)

340.399

456140.4

328.690.7

<0.001

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Table 3.Correlation of RDW with other inflammatory parameters ( Pearson Correlation)


Parameter

Pearson Correlation

P value

CRP(mg/dl)

0.15

0.059

ESR(mm/hr)

0.28

0.005

Fibrinogen(mg/dl)

0.23

0.002

Hbg(g/dl)

-0.4

<0.001

Table 4. Statistical data for RDW, CRP, ESR, Hbg and Fibrinogen in the active CD group

Crohns disease
inflammatory pattern

Area Under the Curve


Area
Asymptotic 95% Confidence Interval
Lower Bound

Upper Bound

RDW(FL)

0,493

,350

,637

CRP(mg/l)

0,495

,346

,645

ESR(mm/h)

0,482

,334

,630

Fibrinogen(mg/dl)

0,423

,271

,575

Fs
Fig. 1. ROC curves for CRP, ESR, Fibrinogen and RDW compared to the activity level of inflammatory pattern
CD(the area under curve for RDW is 0.493

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Table 5. Sensibility and specificity for RDW-SD, CRP, VSH and Fibrinogen as disease activity markers
Parameters

AUC(95% CI)

Highest value

Sensitivity(%)

Specificity(%)

P value

RDW-SD(FL)

0.584(0.4480.720)

46

48

63

0.229

46.5

37

66

47

35.4

66

0.85

87.5

33

1.05

87.5

41

1.5

83

52

15

85

22

16.5

83

30

19

81

33

400

58

85

410

56

85

425

54

89

CRP(mg/dl)

VSH(mm/h)

Fibrinogen(mg/dl)

0.794(0.6870.901)

0.694(0.5760.813)

0.815(0.7170.913)

<0.001

0.005

<0.001

DISCUSSION
Nowadays, many tests in the field of CD are pointed towards the identification of a
marker or test for the detection and assessment of the active disease that are easy to perform,
affordable, noninvasive, and doable with the equipment available in the majority of the
clinics worldwide. In our study, we investigated the correlation of RDW with ESR, CRP and
Fibrinogen. Furthermore, a control group was included in the study to assess alterations in
RDW between these controls and the CD patients. There were significant increases observed
in RDW-SD, ESR and CRP in all groups compared to the control group. There was also a
signifficant increase of all the markers in the active disease periods of CD compared to the
control group. This demonstrated the correlation between ESR, CRP, Fibrinogen and RDWSD in CD.
The evaluation of RDW values in CD patients would be an affordable and easy test to
do in most clinics, without any excess expenses.
Our study is concordant with the previous ones11-14 in terms of correlation between
inflammatory markers and RDW-SD for activity flares of CD, and also for differentiating
between IBD and IBS-d. We consider that the results obtained for the inflammatory pattern
of CD could be explained by the greatest inflammatory burden of these patients compared to
other patterns of activity. In these patients, multiple pathophysiological mechanisms of
anemia concur thus giving rise to microcytosis and elevation in RDW-SD. The same
explanation is acceptable for the association IBD-extraintestinal manifestations. Another
explanation for this correlation would be the fact that these patients usually present with
altered nutritional status which leads to heterogeneous cell population and increased RDW
values18. It has been already demonstrated that elevated RDW is more frequently seen in iron
deficiency states than in thalassemia or anemia of chronic disease this way explaining
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probably the higher RDW in purely inflammatory pattern of CD rather that structuring or
fistulising CD. 19
Finally, is to be mentioned that in the past several years, there have been many studies
which have investigated the relation between RDW levels and cardiac and non-cardiac
death15-17, which could be an interesting aspect in the study of cardiac diseases associated to
IBD.
CONCLUSIONS
RDW values did not correlate with symptoms or location of CD probably because it is a
marker of the general inflammatory burden. It was neither more sensitive nor more specific
as compared to the other markers of activity for evaluation of CD. However, the differences
in median values between CD in remission and severe activity, and also between active CD
and control group, were statistically significant making RDW an useful tool for defining
active disease. There was also seen an association between RDW and the other makers of
inflammation used in the study, confirming the fact that RDW is in fact correlated with
systemic inflammatory burden.
Taking into consideration the other studies already published on this theme 11-14, we can
conclude that RDW could be an useful parameter for evaluating activity in CD, being a cheap
investigation as it is found on every CBC. In correlation with the other markers already used,
it could be useful in patients where endoscopic investigations are forbidden or noncontributive , and also in cases with difficult diagnosis.

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disease: Beyond the established markers. J Cro Col (2011) 5; 381-391
Iskandar HN, Ciorba MA. Biomarkers in inflammatory bowel disease: current practices and recent
advances. Tran Res (2012) 159; 313-325
Yeil A, enante E, Bayolu IV, et al. Red Cell Distribution Width: A Novel Marker of Activity in
Inflammatory Bowel Disease. Gut 2011; 4 ; 460-467
Arhan M, nal IK, Ta A, Kurt M, et al. The role of red cell distribution width as a marker in
inflammatory bowel disease. Turk J Med Sci (2011) 41(2); 227-234
Sond CS et al. Association between red cell distribution width and disease activity in patients with
inflamatory bowel disease. Digestive diseases and sciences, (2012) 577; 1033-1038
Cakal B et al. Red Cell distribution width for assessment of activity of inflammatory bowel disease,
Dig dis sci (2009); p 842-847
Farkas K, Papp M, Nyari T, et al. Red Blood Cell Distribution Width in Combination with
Serological Markers can Help in the Differentiation between Crohns Disease and Ulcerative Colitis.
The Open Gastroenterology J (2010) 4; 1-4
Pascual- Figal DA, Bonaque JC, Redondo B, et al. Red Blood Cell Distribution width predicts longterm outcome regardless of anaemia status in acute heart failure patients. Eu J of Heart Failure (2009)
11; 840-846
Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms, greater
impairment in functional capacity and a significant increase in mortality in pacients with advanced
heart failure. J Am Coll Cardiol (2002) 39; 1780 1786
Groenveld HF, Januzzi JL, Damman K, et al. Anemia and mortality in heart failure patients a
systematic review and meta-analysis. J Am Coll Cardiol (2008) 52; 818-827
Mitchell RM, Robinson TJ. Monitoring dietary compliance in coeliac disease using red cell
distribution width. Int J Clin Pract.2002;56:249250.
Johnson MA. Iron: nutrition monitoring and nutrition status assessment. J Nutr. 1990;120(Suppl
11):14861491.

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Medicine

RECURRENT GIANT CELL TUMOR OF SUPERIOR PUBIC


RAMUS: CASE REPORT

Nica MIHAI1
Ene RAZVAN2
Popescu DAN3

ABSTRACT:
GIANT CELL TUMOR (GCT) OF BONE IS A BENING, LOCALLY AGGRESSIVE TUMOR THAT TYPICALLY
AFFECTS THE EPIHYSEAL OR METAPHYSEAL REGION OF LONG BONES. GCT OF THE PUBIC RAMUS
IS A VERY RARE ENTITY. WE PRESENT THE CASE OF A 19 YEAR OLD FEMALE DIAGNOSED AND
TREATED FOR GCT OF THE SUPERIOR PUBIC RAMUS AT AGE 16 WHO PRESENTED WITH PAIN OF
THE RIGHT INGUINAL REGION. THE IMAGING STUDIES REVEALED A LYTIC EXPANSIVE LESION OF
THE SUPERIOR PUBIC RAMUS AND HISTOPATHOLOGY CONFIRMED THE DIAGNOSIS OF
RECURRENT GCT. SURGICAL EXCISION OF THE TUMOR BY ANTERIOR APPROACH AND GRAFTING
WITH CANCELLOUS BONE ALLOGRAFT WAS PERFORMED. GIANT CELL TUMOR OF THE PELVIC
BONE IS A RARE ENTITY BUT IT SHOULD BE CONSIDERED ALONG OTHER DIFFERENTIALS, EVEN
FOR UNCOMMON AGE GROUPS. RECURRENCE IS POSSIBLE EVEN YEARS AFTER THE SURGICAL
TREAMENT WHICH INVOLVES EXCISION WITH OR WITHOUT GRAFTING.
KEY WORDS: GIANT CELL TUMOR, PELVIC, CURETTAGE, RECURRENCE.

INTRODUCTION
Giant cell tumor (GCT) was first described by Sir Astley Cooper in 1818, and accounts
for up to 9.5% of primary bone tumors. 4 GCT of the bone is a benign, locally aggressive
tumour that typically affects the epiphyseal or metaphyseal region of long bones, most
commonly involving the distal femur, proximal tibia, distal radius and proximal humerus in
order of frequency. 5 It typically presents in adults between age of 20 to 50 with localized
swelling and pain. 6 Females are slightly more affected than males. 7 Giant cell tumor of pelvis
is uncommon, accounting for only 1.5 to 6% of cases of GCT. 8 In the pelvis ilium is the most
* All authors contributed equally to this work.
1
Orthopaedics and Traumatology Department of University Emergency Hospital Bucharest, Romania,
2
Orthopaedics and Traumatology Department of University Emergency Hospital Bucharest, Romania;
University of Medicine and Pharmacy Carol Davila Bucharest, Romania, razvan77ene@yahoo.com
3
Orthopaedics and Traumatology Department of University Emergency Hospital Bucharest, Romania,
4
Murphey MD et al., From the Archives of AFIP, 1283-1309.
5
Reid et al., World Health Organization classification of tumours, 309-312.
6
Blake et al., Large pelvic giant cell tumor: A case report, 1050-4.
7
Sanjay et al., Treatment of giant-cell tumor of the pelvis, 75:1466-75.
8
Cheng et al., Periacetabular giant cell tumor, 67:537-41.

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common site of involvement; ischium and pubis are less frequently involved. 9 The most
commonly recommended treatment for giant cell tumors of bone consists of intralesional
procedures such as curettage, and filing of the defect either with bone grafts or bone cement.
The local recurrence rate depends on the surgical treatment and can be up to 40%. 10,11,12,13
CASE REPORT
A 19 year old female presented to our clinic with dull pain localised to the right
inguinal region, right hip joint and pubic region for the last 4 months. The female patient
also complained of difficulty walking for last several weeks caused by the hip joint pain. Her
medical history was significant for a primary giant cell tumour of the right superiour pubic
ramus diagnosed at age 16 and treated with curettage.
Physical examination revealed a hardly palpable immobile, bony, hard mass on the
right aspect of the pubic region. The right femoral and other peripheral pulses were normal
and no inguinal lymphadenopathy was noted. There was no local warmth and erythema of the
overlying skin. The right hip joint range of motion was within normal limits and the
neurological examination of lower extremity was without any deficit. Systemic examination
of the patient was unremarkable.
The routine laboratory results were within the normal limits. The serum calcium level
was 9.6 mg/dl, serum phosphorus level 3.8 mg/dL and alkaline phosphatase level was 161
IU/L (Normal: 40-136 IU/L).
Plain x-rays of the pelvis showed a well-defined, medullary in origin, lytic lesion involving
the right superior pubic ramus.(Fig.1) Chest x-ray did not reveal any abnormality.(Fig.2).

Fig.1 Lytic bone lesion involving the


right superior pubic ramus.

Fig.2 Chest x-ray showing no


pulmonary lesions

Patne et al., Giant-cell tumor of the pubic bone: A case report, 15:1148.
Campanacci M., Bone and soft tissue tumors, 117-51.
11
Campanacci M. et al., Giant-cell tumor of bone, 69 (1): 106-14.
12
Blackley et al., Treatment of giant-cell tumors of long bones with curettage and bone-grafting, 81 (6): 811-20.
13
Balke et al., Treatment options for recurrent giant cell tumors of bone, 135 (1): 149-58.
10

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A computed tomography of the pelvis was performed (Fig.3), confirming the expansive
lytic lesion of 64mm x 22mm arising from the right superior pubic ramus which does not
break through the cortex, with an internal pattern uniform in appearance, excepting the
presence of a few widely scattered fine lines of increased density. A whole body bone scan
performed using Technetium 99m-MDP, which revealed increased fixation of the
radioisotope in the tumoral region. (Fig.4)

Fig.3 Pelvis CT-scan showing a lytic bone lesion of the right superior pubic ramus

Fig.4 Technetium 99m-MDP bone scintigraphy showing increased fixation


of the radioisotope in the superior right pubic ramus area

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An incisional biopsy of the mass and the subsequent histopathological examination of


the samples confirmed the diagnosis of recurrent giant cell tumour of bone. The histological
appearance was one of uniformly scattered multinucleated giant cells within a background of
mononuclear stromal cells with frequent mitoses, but with no cellular atypia. Therefore a
second surgical intervention was performed which comprised an anterior approach of the
tumoral site, thorough curettage (Fig.5) and grafting (Fig.7) with secured and freeze-dried
cancellous bone allograft.(Fig.8) The surgery was not followed by adjuvant radiotherapy or
chemotherapy. The postoperative evolution of the patient was uneventful.

Fig.5 Intraoperative view of the


lesion after curettage

Fig.7 Freeze-dried cancellous


bone allograft used

Fig.6 Intraoperative view of the


lesion after grafting

Fig.8 Postoperative x-ray

DISCUSSION
Treatment of giant cell tumours of the pelvis is particularly challenging, owing to the
difficult anatomical location and the locally aggressive nature of the lesion, added to the
relatively long time usually required to achieve the diagnosis. 1 Giant cell tumors of bone
rarely affect the pelvis. Leggon et al. 2 indicated that the local recurrence rate for GCT of the
pelvis and sacrum seems higher than for any other location. There are different modalities of
1
2

Enneking WF., The anatomic considerations in tumor surgery, 483-529.


Leggon R E et al., Giant cell tumor of the pelvis and sacrum, (423): 196-207.

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treatment of pelvic GCT. Radiotherapy has high rate of recurrence (44%) and poses a high
risk of subsequent soft tissue sarcomas (12%). The risk increases with time, so that the rate
might be even higher with a longer follow-up.3 Thus treatment should be essentially surgical
which involves surgical excision. The choice of treatment should be individualized to allow
for the least possible morbidity without compromising the oncological outcome. Excision can
be extralesional which achieves 90% local tumor control but poor functional outcome 4 or it
can be intralesional which has a higher local recurrence rate but with good functional
outcome. 5
Moreover giant cell tumors of bone have their peak incidence in the second and third
decades of life. 6 There are very few series that document giant cell tumor of bone (GCT) in
the immature skeleton, and the reported incidence in literature varies from 1.8% to
10.6%. The biological behavior of the disease is similar to that seen in adults, except a
marked female preponderance. 7
The reported case demonstrates all the characteristics of a typical bone giant cell tumor
case (clinical presentation, radiological appearence, recurrence histological appearance) but
its relatively rare location and even more uncommon age of occurance and recurrence makes
it a unique entity.
CONCLUSION
Curettage with or without resection is the treatment of choice of GCT involving the
pelvic bones, which provides a good local control but a possible recurrence should be
considered even at years after the curative treatment. A diagnostic of GCT must be
considered along other differentials (aneurysmal cyst, osteolytic osteogenic sarcoma, solitary
myeloma, reticulosarcoma, eosinophilic granuloma, chondroblastoma) of an expansive, lytic
lesion even for age groups very uncharacteristic for this type of tumor.

Tucker M A et al., Bone sarcomas linked to radiotherapy and chemotherapy in children, 317 (10): 588-93.
Gitelis S et al., Intralesional excision compared with en bloc resection of giant cell tumors of bone, 17:164855.
5
Bloodgood JC., The conservative treatment of giant cell sarcoma, 56:210-39.
6
Balke M et al., Giant cell tumor of bone: treatment and outcome of 214 cases, 134 (9): 969-78.
7
Puri et al., Giant Cell Tumor of Bone in Children and Adolescents Journal of Pediatric Orthopaedics, 635-639.
4

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December 2014

REFERENCES
1.

2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

13.
14.

15.

16.
17.

Balke M, Ahrens H, Streitbuerger A, Koehler G, Winkelmann W, Gosheger G, Hardes J.


Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 2008a; 135 (1):
149-58
Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G, Hardes J, Gosheger
G.; Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol, 2008b;
134 (9): 969-78
Blackley H R, Wunder J S, Davis A M, White L M, Kandel R, Bell R S.; Treatment of giant-cell
tumors of long bones with curettage and bone-grafting. J Bone Joint Surg Am, 1999; 81 (6): 811-20
Blake SM, Gie GA.; Large pelvic giant cell tumor: A case report and a review of current treatment
modalities. J Arthroplasty 2004; 19:1050-4
Bloodgood JC.; The conservative treatment of giant cell sarcoma, with the study of bone
transplantation. Ann Surg, 1912; 56:210-39
Campanacci M.; Bone and soft tissue tumors. New York: Springer. 1990; 117-51
Campanacci M, Baldini N, Boriani S, Sudanese A.; Giant-cell tumor of bone. J Bone Joint Surg Am,
1987; 69 (1): 106-14
Cheng MT, Chen TH, Chen WM.; Periacetabular giant cell tumor treated with intralesional excision
and allograft reconstruction. J Chin Med Assoc 2004; 67:537-41
Enneking WF.; The anatomic considerations in tumor surgery : pelvis. In : Enneking WF (ed).
Musculoskeletal Tumor Surgery. Churchill Livingstone, New York, 1983, vol 2; 483-529
Gitelis S, Mallin BA, Piasecki P.; Intralesional excision compared with en bloc resection of giant cell
tumors of bone. J Bone Joint Surg, 1993; 17:1648-55
Leggon R E, Zlotecki R, Reith J, Scarborough M T.; Giant cell tumor of the pelvis and sacrum: 17
cases and analysis of the literature. Clin Orthop, 2004; (423): 196-207
Murphey MD et al.; From the Archives of AFIP. Imaging of Giant Cell Tumor and Giant Cell
Reparative Granuloma of Bone: Radiologic-Pathologic Correlation. Radiographics 2001; 5: 12831309
Patne SC, Kumar M, Sadaf L.; Giant-cell tumor of the pubic bone: A case report. Int J Orthop Surg,
2009;15:1148
Puri, Ajay MS, Agarwal, Manish G. MS, DNB; Shah, Mandip MS, Jambhekar, Nirmala A. MD,
Anchan, Chetan MS, Behle, Sanica MD; Giant Cell Tumor of Bone in Children and Adolescents
Journal of Pediatric Orthopaedics, September 2007, Volume 27, Issue 6; 635-639
Reid RR, Banerjee SS, Sciot R.; Giant cell tumour. In: Fletcher CDH, Unni KK, Mertens F, editors.
World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue
and bone. Lyon: IARC Press 2002; 309-12
Sanjay BK, Frassica FJ, Frassica DA.; Treatment of giant-cell tumor of the pelvis. J Bone Joint Surg
Am, 1993; 75:1466-75
Tucker M A, DAngio G J, Boice J D, Jr., Strong L C, Li F P, Stovall M, Stone B J, Green D M,
Lombardi F, Newton W, Hoover R N, Fraumeni J F, Jr. Bone sarcomas linked to radiotherapy and
chemotherapy in children. N Engl J Med 1987; 317 (10): 588-93.

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Medicine

THE INCIDENCE OF ARTERIAL HYPERTENSION THAT


COMPLICATES PREGNANCY, PARTURITION AND
POSTPARTUM PERIOD IS INCREASING
- DEPARTMENT EXPERIENCE -

Octavian MUNTEANU 1
Alexandra ZLATIANU 2
Elvira BRATILA3
Monica CIRSTOIU4

ABSTRACT:
ARTERIAL HYPERTENSION THAT COMPLICATES PREGNANCY, PARTURITION AND POSTPARTUM
PERIOD IS A MAJOR PUBLIC HEALTH ISSUE, DUE TO ITS INCREASED, BOTH FETAL AND
MATERNAL, MORBIDITY AND MORTALITY. THIS STUDY WAS UNDERTAKEN IN ORDER TO
DETERMINE THE INCIDENCE OF DIFFERENT CATEGORIES OF ARTERIAL HYPERTENSION WHICH
COMPLICATE PREGNANCY, PARTURITION AND POSTPARTUM PERIOD, IN OUR DEPARTMENT. WE
RETROSPECTIVELY ANALYZED THE CHARTS OF PATIENTS WHO DELIVERED IN THE DEPARTMENT
OF OBSTETRICS AND GYNECOLOGY OF THE UNIVERSITY EMERGENCY HOSPITAL BUCHAREST
BETWEEN 01.01.2007 - 31.12.2013 DIAGNOSED WITH A FORM OF ARTERIAL HYPERTENSION THAT
COMPLICATED PREGNANCY, PARTURITION AND POSTPARTUM PERIOD. WE HAVE OBSERVED AN
INCREASED INCIDENCE OF ALL FORMS OF ARTERIAL HYPERTENSION THAT COMPLICATES
PREGNANCY, PARTURITION AND POSTPARTUM PERIOD, ESPECIALLY THE MODERATE AND SEVERE
TYPES OF PREECLAMPSIA.
KEY WORDS: GESTATIONAL HYPERTENSION, PREECLAMPSIA, ECLAMPSIA, INCIDENCE

INTRODUCTION
Arterial hypertension complicates approximately 4 % of all pregnancies1,6,8.
Hypertensive disorders are among the most common medical conditions of pregnancy2,7-10.
Arterial hypertension that complicates pregnancy, parturition and postpartum period, is a

Assistant Professor MD, PhDc, Department of Anatomy, University of Medicine and Pharmacy Carol
Davila Bucharest, Romania, email: octav_munteanu@yahoo.com
2
MD, Resident Physician in Pediatric Surgery, Sfantul Pantelimon Emergency Hospital, Bucharest, Romania
3
Lecturer MD, PhD, Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Carol
Davila Bucharest, Romania
4
Associate Professor MD, PhD, Department of Obstetrics and Gynecology, University of Medicine and
Pharmacy Carol Davila Bucharest, Romania
1

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December 2014

major public health issue, due to its increased, both fetal and maternal, morbidity and
mortality1,3,5.
The pathogenesis of pregnancy induced hypertension is not completely know, however
it has been demonstrated that the placenta plays a key role 9.
According to The National High Blood Pressure Education Program Working Group on
High Blood Pressure in Pregnancy, hypertensive conditions during pregnancy are classified
into 4 categories4:
Chronic hypertension - blood pressure > 140/90 mmHg before pregnancy or
before 20 weeks of gestation.
Preeclampsia/eclampsia
o Mild preeclampsia blood pressure > 140/90 mmHg during two
determinations, in a woman who was normotensive before 20 weeks of
gestation.
o Severe preeclampsia blood pressure > 160/110mmHg or elevated blood
pressure (> 140/90 mmHg) that associates: proteinuria/ pulmonary
edema/oliguria/epigastric pain/thrombocytopenia
o Eclampsia seizures in a patient with preeclampsia
Preeclampsia superimposed on chronic hypertension
Gestational hypertension
Arterial hypertension that complicates pregnancy, parturition and postpartum period
has severe consequences, both maternal and fetal, and for that matter, a precocious diagnoses
and an accurate evaluation of the severity of the disease are highly important in order to
appoint an adequate treatment, thus decreasing the risk of complications 11.
This study was undertaken in order to determine the incidence of different forms of
arterial hypertension which complicate pregnancy, parturition and postpartum period, in our
department.
MATERIALS AND METHODS
We retrospectively analyzed the charts of patients who delivered in the Department of
Obstetrics and Gynecology of the University Emergency Hospital Bucharest between
01.01.2007 - 31.12.2013 diagnosed with a form of arterial hypertension that complicated
pregnancy, parturition and postpartum period. The information was obtained from the
inpatient charts and computerized database of the Statistical Unit at Bucharest Emergency
University Hospital. All statistical analyses were conducted using the SPSS version 19.
RESULTS
Between 01.01.2007 and 31.12.2013, 31399 patients delivered in the Department of
Obstetrics and Gynecology of the University Emergency Hospital Bucharest. 7,93% cases
(n=2491) a form of arterial hypertension complicated pregnancy, parturition and postpartum

period.
Figure 2. presents the distribution of pregnancies complicated by a form of arterial
hypertension between 01.01.2007 and 31.12.2013.

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432

450

406

403

400
340

350

333

351

300
250

226

200
150
100
50
0
2007

2008

2009

2010

2011

2012

2013

Figure 1. The distribution of pregnancies complicated by a form of arterial


hypertension between 2007-2013

Following the diagnostic codes, 5 categories were assorted: chronic hypertension,


gestational hypertension, mild preeclampsia, severe preeclampsia and eclampsia. We
analyzed the distribution of these categories in each year (see Figure 2., Figure 3., Figure 4.,
Figure 5., Figure 6., Figure 7., Figure 8.).

Figure 2. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2007

Figure 4. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2009

Figure 3. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2008

Figure 5. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2010

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December 2014

Figure 6. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2011

Figure 7. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2012

Figure 9. The distribution of categories of


hypertension that complicated pregnancy,
parturition and postpartum period in 2013

We evaluated and compared the incidence of the 5 assorted categories of arterial


hypertension between the 7 years studied (see Figure 10).
Chronic hypertension

Gestational hypertension

Severe preeclampsia

Eclampsia

Mil d preeclampsia

250

200

150

100

50

0
2007

2008

2009

2010

2011

2012

2013

Figure 10. The distribution of categories of hypertension that complicated pregnancy,


parturition and postpartum period between 2007 and 2013

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During the 7 years studied the most frequent category of hypertension that complicated
pregnancy, parturition and postpartum period was gestational hypertension 1254 cases. The
rarest type was eclampsia 35 cases (see Figure 10).
CONCLUSION
Even if from 2009, the number of deliveries in our department is decreasing,
proportionally, we have observed an increased incidence of all forms of arterial hypertension
that complicates pregnancy, parturition and postpartum period, especially the moderate and
severe types of preeclampsia.

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December 2014

REFERENCES
1.

Berg, Cynthia J., William M. Callaghan, Carla Syverson, and Zsakeba Henderson. "Pregnancyrelated mortality in the United States, 1998 to 2005." Obstetrics & Gynecology 116, no. 6 (2010):
1302-1309.
2. Brown, Mark A., Marshall D. Lindheimer, Michael de Swiet, Andre Van Assche, and Jean-Marie
Moutquin. "The classification and diagnosis of the hypertensive disorders of pregnancy: statement
from the International Society for the Study of Hypertension in Pregnancy (ISSHP)." Hypertension in
pregnancy 20, no. 1 (2001): ix-xiv.
3. Callaghan, William M., Andreea A. Creanga, and Elena V. Kuklina. "Severe maternal morbidity
among delivery and postpartum hospitalizations in the United States." Obstetrics & Gynecology 120,
no. 5 (2012): 1029-1036.
4. Hopkins, Michael P. "Report of the national high blood pressure education program working group on
high blood pressure in pregnancy." American journal of obstetrics and gynecology 183, no. 1 (2000):
1-258
5. MacKay, Andrea P., Cynthia J. Berg, Xiang Liu, Catherine Duran, and Donna L. Hoyert.
"Changes in pregnancy mortality ascertainment: United States, 19992005." Obstetrics & Gynecology
118, no. 1 (2011): 104-110.
6. Magee, Laura A., Michael Helewa, Jean-Marie Moutquin, Peter von Dadelszen, Hypertension
Guideline Committee, and Strategic Training Initiative in Research in the Reproductive Health
Sciences (STIRRHS) Scholars. "Diagnosis, evaluation, and management of the hypertensive disorders
of pregnancy." Journal of obstetrics and gynaecology Canada 30, no. 3 Suppl (2008): S1-48.
7. Moser, Marvin, Catherine M. Brown, Carl H. Rose, and Vesna D. Garovic. "Hypertension in
pregnancy: is it time for a new approach to treatment?." Journal of hypertension 30, no. 6 (2012): 1092.
8. Podymow, Tiina, and Phyllis August. "Hypertension in pregnancy." Advances in chronic kidney
disease 14, no. 2 (2007): 178-190.
9. Redman, Christopher WG, SigLinda Jacobson, and Robin Russell. "Hypertension in pregnancy."
de Swiet's Medical Disorders in Obstetric Practice, Fifth Edition (2010): 153-181.
10. Scantlebury, Dawn C., Gary L. Schwartz, Letitia A. Acquah, Wendy M. White, Marvin Moser,
and Vesna D. Garovic. "The treatment of hypertension during pregnancy: when should blood pressure
medications be started?." Current cardiology reports 15, no. 11 (2013): 1-10.
11. Verlohren, Stefan, Holger Stepan, and Ralf Dechend. "Angiogenic growth factors in the diagnosis
and prediction of pre-eclampsia." Clinical Science 122, no. 2 (2012): 43-52.

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Medicine

DEVELOPMENT OF SCORING SYSTEM FOR EVALUATING


THE RISK OF CEPHALOPELVIC DISPROPORTION

Octavian MUNTEANU1
Alexandru ISPAS2
Costin BERCEANU3
Simona VLADAREANU4

ABSTRACT:
CEPHALOPELVIC DISPROPORTION IS AN IMBALANCE BETWEEN THE DIMENSIONS OF THE FETAL
CRANIUM AND MATERNAL PELVIS THAT PREVENTS OPTIMAL DESCENT OF THE FETUS THROUGH
THE PELVI-GENITAL CANAL. EVALUATING THE RISK OF CEPHALOPELVIC DISPROPORTION IS
ESSENTIAL IN ORDER TO DECREASE BOTH MATERNAL AND FETAL MORBIDITY.
WE EVALUATED 80 PATIENTS WHO DELIVERED IN THE DEPARTMENT OF OBSTETRICS AND
GYNECOLOGY OF UNIVERSITY EMERGENCY HOSPITAL BUCHAREST. THE PATIENTS WERE DIVIDED
INTO TWO GROUPS. IN GROUP A WE ENROLLED 40 PATIENTS THAT WERE DIAGNOSED WITH
CEPHALOPELVIC DISPROPORTION AND THE FETUS WAS EXTRACTED BY CESAREAN SECTION. IN
GROUP B WE INCLUDED 50 PATIENTS WITH RISK FACTORS FOR CEPHALOPELVIC DISPROPORTION
WHO DELIVERED VAGINALLY. THE MATERNAL RISK FACTORS FOR CEPHALOPELVIC
DISPROPORTION (AGE, HEIGHT, WEIGHT AND WEIGHT GAIN DURING PREGNANCY) WERE
ANALYZED AND COMPARED BETWEEN THE TWO GROUPS
WE DEVELOPED A SCORING SYSTEM THAT ALLOWS AN EARLY RISK ASSESSMENT OF
CEPHALOPELVIC DISPROPORTION, FACILITATING DIAGNOSIS AND PROPER MANAGEMENT OF
THESE PATIENTS.
KEY WORDS: CEPHALOPELVIC DISPROPORTION, SCORING SYSTEM, AGE, WEIGHT, HEIGHT,
WEIGHT GAIN DURING PREGNANCY

Assistant Professor MD, PhDc, Department of Anatomy, University of Medicine and Pharmacy Carol
Davila Bucharest, Romania, email: octav_munteanu@yahoo.com
2
Professor MD, PhD, Department of Anatomy, University of Medicine and Pharmacy Carol Davila
Bucharest, Romania
3
Assistant Professor MD, PhD, Department of Obstetrics and Gynecology, University of Medicine and
Pharmacy Craiova, Romania
4
Lecturer MD, PhD, Department of Neonatology, University of Medicine and Pharmacy Carol Davila
Bucharest, Romania
1

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December 2014

INTRODUCTION
Dystocia is defined as difficult labor that requires in most cases the extraction of the
fetus by Cesarean section1,6,7. The cause of dystocic labor is either anatomic cepahalopelvic
disproportion or functional anomalies of uterine contraction1,6,7,14.
Cephalopelvic disproportion is an imbalance between the dimensions of the fetal
cranium and maternal pelvis that prevents optimal descent of the fetus through the pelvigenital canal5,6,10,12,14,16,17.
Due to lifestyle changes the incidence of voluminous and macrosome fetuses is
increasing, and especially in the group of primiparous patients cephalopelvic disproportion is
one of the most frequent indications for extracting the fetus by Cesarean section 2-4,8,11,12,14.
Cepaholopelvic disproportion is a major public health condition with potentially
critical consequences for both mother and fetus 3,8,12 . Numerous studies have detected risk
factors for cephalopelvic disproportion that can be easily evaluated during the admission of
the patient in the delivery room : maternal - height, weight, age, weight gain during
pregnancy and parity and fetal - estimated birth weight and pubis-fundal height)9,10-13,15,17.
However, in Romania, a protocol for early risk assessment of cephalopelvic
disproportion has not yet been elaborated.
This study was undertaken in order to develop a scoring system for early risk
assessment of cephalopelvic disproportion.
MATERIALS AND METHODS
We prospectively evaluated 80 patients with risk factors for cephalopelvic
disproportion, who delivered in the Department of Obstetrics and Gynecology of University
Emergency Hospital Bucharest, following the subsequent inclusion/exclusion criteria:
inclusion criteria:
o The age of the patient > 15 years-old, < 40 years-old
o Singleton pregnancy
o Gestational age > 37 weeks of gestation
o Spontaneous onset of labor
o Cervical dilatation at admission in the delivery room </= 4 cm
o The patient monitored in the hospital at least 4 hours
exclusion criteria:
o Patients with pregnancy induced hypertension
o Patients with fever or suspected chorioamiotitis
o Patients who received antibiotics in the last 3 days
o Dead fetus
o Spontaneously ruptured amniotic membranes > 4 hours before the admission
in the delivery room
The patients were divided into two groups. In group A we enrolled 40 patients that
were diagnosed with cephalopelvic disproportion and the fetus was extracted by Cesarean
section. In group B we included 50 patients with risk factors for cepaholopelvic disproportion
who delivered vaginally.
The maternal risk factors for cephalopelvic disproportion (age, height, weight, weight
gain during pregnancy) were analyzed and compared between the two groups. All analyses
were conducted using the SPSS version 19. p-value <0.05 was considered statistically
significant.

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RESULTS
We evaluated and compared for all the patients enrolled in the study and between the
two formed groups the maternal age, height, weight and weight gain during pregnancy (see
Table 1.).
Group A

Group B

Total

Age (Years)
Mean standard deviation
Minim/Maxim

27.35 7.87
16/39

26.65 5.22
16/39

27 6.64
16/39

Height (centimeters)
Mean standard deviation
Minim/Maxim

162.63 5.77
145/172

166.55 4.64
155/175

164.59 5.57
145/175

Weight (kilograms)
Mean standard deviation
Minim/Maxim

80.55 10.50
59/109

75.28 8.05
61/91

77.91 9.67
59/109

Weight gain during


pregnancy (kilograms)
Mean standard deviation
Minim/Maxim

19.25 4.97
9/30

14.23 4.42
7/24

16.74 5.31
7/30

Table 1. Descriptive analysis of the risk factors for cephalopelvic disproportion between groups A
and B

Following the descriptive analysis of the patients enrolled in the study, we decided to
assort each risk factor for cephalopelvic disproportion into 3 arbitrary categories.
Patients from both groups were distributed into 3 categories according to maternal age
(see Figure 1. and Figure 2.):
- I category: age between 16 and 20 years-old
- II category: age between 21 and 30 years-old
- III category: age between 31 and 39 years-old

Figure 1. The distribution of patients in group


A according to maternal age

Figure 2. The distribution of patients in group


B according to maternal age

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Patients from both groups were distributed into 3 categories according to maternal
weight (see Figure 3. and Figure 4.):
- I category: weight < 70 kilograms
- II category: weight between 71 and 85 kilograms
- III category: weight > 86 kilograms

Figure 3. The distribution of patients in group


A according to maternal weight

Figure 4. The distribution of patients in group


B according to maternal weight

Patients from both groups were distributed into 3 categories according to maternal
height (see Figure 5. and Figure 6.):
- I category: height < 159 centimeters
- II category: height between 160 and 169 centimeters
- III category: height > 170 centimeters

Figure 5. The distribution of patients in group


A according to maternal height

Figure 6. The distribution of patients in group


B according to maternal height

Patients from both groups were distributed into 3 categories according to maternal
weight gain during preganancy (see Figure 7. and Figure 8.):
- I category: weight gain during pregnancy < 15 kilograms
- II category: weight gain during pregnancy between 16 and 20 kilograms
- III category: weight gain during pregnancy > 21 kilograms

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Figure 7. The distribution of patients in group


A according to maternal weight gain during
pregnancy

Figure 8. The distribution of patients in group


B according to maternal weight gain during
pregnancy

DISCUSSIONS
Analyzing the results of our study it is obvious that maternal age and weight gain
during pregnancy are the risk factors with the highest impact of correlation with
cephalopelvic disproportion. However, the previously demonstrated risk factors of
cephalopelvic disproportion, maternal height and weight are not statistically significant in this
study 9,10-13,15,17.
According to the results of this study we elaborated a scoring system for early risk
assessment of cephalopelvic disproportion using maternal age, weight, height and weight
gain during pregnancy (see Table 2).

16 - 20
21 - 30

2
1

< 159
160 - 169

1
2

< 70
71 - 85

1
2

Weight gain
during
pregnancy
(kilograms)
< 15
16 - 20

31- 39

> 170

> 86

> 21

Age
(years)

Risk
Height
Risk
score (centimeters) score

Weight
(kilograms)

Risk
score

Risk
score
1
2
3

The risk of cephalopelvic disproportion


Low
Medium
High

4-6
7-9
10 12

Table 2. Scoring system for early risk assessment of cephalopelvic disproportion

We decided to develop a scoring system using only maternal age, height, weight and
weight during pregnancy due to the fact that these parameters can be easily determined
during the emergency admission of the patient in the delivery room. The scoring system
assorts each patient in one of the three categories: low/medium/high risk of cephalopelvic
disproportion.

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CONCLUSION
Evaluating the risk of cephalopelvic disproportion is essential in order to decrease both
maternal and fetal morbidity. The developed scoring system allows an early risk assessment
of cephalopelvic disproportion, facilitating diagnosis and proper management of these
patients.
ACKNOWLEDGEMENT
This paper is supported by the Sectoral Operational Programme Human Resources
Development (SOP HRD), financed from the European Social Fund and by the Romanian
Government under the contract number POSDRU/159/1.5/S/137390/.

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2.

3.

4.
5.

6.
7.
8.

9.

10.

11.

12.

13.

14.
15.
16.

17.

American College of Obstetricians and Gynecologists. "Dystocia and the augmentation of labor." Practice
bulletin 49 (2003);102:1445-54.
Barber, Emma L., Lisbet S. Lundsberg, Kathleen Belanger, Christian M. Pettker, Edmund F. Funai,
and Jessica L. Illuzzi. "Indications contributing to the increasing cesarean delivery rate." Obstetrics and
gynecology 118, no. 1 (2011): 29-38.
Betrn, Ana P., A. Metin Gulmezoglu, Michael Robson, Mario Merialdi, Joo P. Souza, Daniel
Wojdyla, Mariana Widmer et al. "WHO global survey on maternal and perinatal health in Latin America:
classifying caesarean sections." Reproductive Health 6, no. 18 (2009).
Branch, David Ware, and Robert M. Silver. "Managing the primary cesarean delivery rate." Clinical
obstetrics and gynecology 55, no. 4 (2012): 946-960.
Chittiphavorn, Suwicha, Sutham Pinjaroen, Chitkasaem Suwanrath, and Karanrat Soonthornpun.
"Clinical practice guideline for cesarean section due to cephalopelvic disproportion." Journal-Medical
Association of Thailand 89, no. 6 (2006): 735.
Cunningham, F., Kenneth Leveno, Steven Bloom, Catherine Y. Spong, and Jodi Dashe. Williams
Obstetrics 23/E. McGraw Hill Professional, 2010: 544-64.
Danforth, David Newton. Danforth's obstetrics and gynecology. Edited by Ronald S. Gibbs. Lippincott
Williams & Wilkins, 2013:27-34,84-92.
Lumbiganon, Pisake, Malinee Laopaiboon, A. Metin Glmezoglu, Joo Paulo Souza, Surasak
Taneepanichskul, Pang Ruyan, Deepika Eranjanie Attygalle et al. "Method of delivery and pregnancy
outcomes in Asia: the WHO global survey on maternal and perinatal health 200708." The Lancet 375, no.
9713 (2010): 490-499.
Khunpradit, Suthit, Jayanton Patumanond, and Chamaiporn Tawichasri. "Risk indicators for cesarean
section due to cephalopelvic disproportion in Lamphun hospital." Journal-Medical Association of Thailand
88 (2005): S63.
Kovavisarach, Ekachai, and Paweena Buddeewong. "Diagnosis of Cephalopelvic Disproportion or
Failure to Progress of Labor in Rajavithi Hospital Compare with The Criteria of Royal Thai College of
Obstetricians and Gynaecologists." Thai Journal of Obstetrics and Gynaecology 18, no. 2 (2012): 77-81.
Munteanu, O., A. L. T. Ispas, F. Filipoiu, L. A. I. Bulescu, Laura Stroica, E. Tarta-Arsene, Diana
Secara, and Monica Cirstoiu. "Do the classical anatomical criteria for establishing the diagnosis of
cephalopelvic disproportion need to be reevaluated?." Romanian Journal of Functional & Clinical, Macro& Microscopical Anatomy & of Anthropology/Revista Romna de Anatomie Functionala si Clinica, Macro
si Microscopica si de Antropologie 12, no. 2 (2013).
Munteanu, Octavian, Luiza Radulescu, Alexandru T. Ispas, Florin C. Cirstoiu, Monica M. Cirstoiu.
Can fetal cranial circumference determine the cause and predict cephalo-pelvic disproportion?. Gineco.eu
9, no. 3 (2013): 118-121.
Navolan, Dan, Andrei Cristian, Badiu Diana, Tigla Alexandru, Constantinescu Simona, and Vladareanu
Radu. The implications of pre-pregnancy overweight in the pregnancy outcomes and further
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Shields, Sara G., Stephen D. Ratcliffe, Patricia Fontaine, and Larry Leeman. "Dystocia in nulliparous
women." American Family Physician 75, no. 11 (2007): 1671-78.
Surapanthapisit, Papungkorn, and Wiboolphan Thitadilok. "Risk factors of caesarean section due to
cephalopelvic disproportion." Journal-Medical Association of Thailand 89, no. 4 (2006): S105-11.
Suwanrath-Kengpol, Chitkasaem, Sutham Pinjaroen, Oermporn Krisanapan, and Porntip Petmanee.
"Effect of a clinical practice guideline on physician compliance." International Journal for Quality in
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Wianwiset, W. "Risk Factors of Caesarean Delivery due to Cephalopelvic Disproportion in Nulliparous
Women at Sisaket Hospital." Thai Journal of Obstetrics and Gynaecology 19 (2011): 158-164.

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Medicine

SURGICAL ONCOPLASTIC TECHNIQUE FOR GIANT


FIBROADENOMA

R. SCUNAU1
B. POPESCU2
C. BLLU3
I. HORHOIANU4
C. COZMA5
S. VOICULESCU 6

ABSTRACT:
FIBROADENOMAS ARE THE MOST COMMON TUMORS AFFECTING WOMEN DURING THEIR
REPRODUCTIVE YEARS. FIBROADENOMAS WITH A DIAMETER LARGER THAN 5 CM OR A
ESTIMATED WEIGHT GREATER THAN 500 GRAMS ARE CONSIDERED GIANT FIBROADENOMAS.
THESE RAPIDLY GROWING LESIONS ARE RARE, WITH A REPORTED INCIDENCE OF ABOUT 4% OF
ALL FIBROADENOMAS. DESPITE THEIR BENIGNITY, THEIR SYMPTOMS ARE MUCH MORE SEVERE,
CAUSING PRONOUNCED ASYMMETRY OF THE BREASTS, DISTORTION OF THE OVERLYING SKIN
AND STRETCHING OF THE NIPPLE, WHICH LEAD TO EMOTIONAL DISTRESS AND DISCOMFORT IN
AFFECTED INDIVIDUALS.
ONCOPLASTIC SURGERY COMBINES BREAST NEOPLASIA MANAGEMENT PRINCIPLES WITH PLASTIC
SURGERY TECHNIQUES IN ORDER TO OBTAIN BOTH AN ONCOLOGIC AND COSMETIC SUCCES.
EVEN THOUGH USUALLY IT REFERS TO BREAST CANCER, ONCOPLASTIC SURGERY SKILLS CAN BE
APPLIED FOR THE EXCISION OF LARGE BENIGN TUMORS, SUCH AS GIANT FIBROADENOMAS.
IN THIS ARTICLE, WE PRESENT A CASE OF A 18 YEARS OLD PATIENT ADMITTED IN GENERAL
SURGERY DEPARTMENT OF COLEA HOSPITAL, DIAGNOSED WITH GIANT FIBROADENOMA AND
MANAGED BY MAKING USE OF ONCOPLASTIC TECHNIQUES.
KEY WORDS: BREAST NEOPLASIA, CHRONIC PAIN, LYMPHADENECTOMY, MASTECTOMY.

Department of General Surgery, University of Medicine Carol Davila, Colea Clinical Hospital, Bucharest
University of Medicine and Pharmacy Carol Davila, Bucharest, dr.bpopescu@gmail.com
3
University of Medicine and Pharmacy Carol Davila, Bucharest.
4
University of Medicine and Pharmacy Carol Davila, Bucharest.
5
Department of General Surgery, University of Medicine Carol Davila, Colea Clinical Hospital, Bucharest
6
Department of General Surgery, University of Medicine Carol Davila, Colea Clinical Hospital, Bucharest
1
2

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INTRODUCTION
Fibroadenomas are the most common tumors affecting women during their
reproductive years. They are benign biphasic tumors, with epithelial and stromal components,
that are stimulated by hormonal activity and undergo atrophic changes in menopause. 1,2
Most are discovered during clinical breast examinations or by patient self-breast
examination and, typically, present as a non-painful, firm, smooth, with a well-defined
contour mass or, sometimes, multiple masses. When diagnosed in a young woman, the term
juvenile fibroadenoma is more appropriate.
Fibroadenomas with a diameter larger than 5 cm or a estimated weight greater than 500
grams are considered giant fibroadenomas. 3,4 These rapidly growing lesions are rare, with a
reported incidence of about 4% of all fibroadenomas, but their symptoms are much more
severe, causing pronounced asymmetry of the breast, distortion of the overlying skin and
stretching of the nipple.2 Despite their benignity, these giant lesions cause significant
emotional distress and discomfort in affected individuals.
The traditional management options available to women diagnosed with a common
fibroadenoma include either periodic reassessment or tumor ablation using surgery or various
minimal invasive techniques. Giant fiabroadenomas, on the other hand, pose a significant
challenge and currently there is no consistent surgical approach for this pathology. 5
Oncoplastic surgery combines breast neoplasia management principles with plastic
surgery techniques in order to obtain both an oncologic and cosmetic succes. Even though
usually it refers to breast cancer, oncoplastic surgery skills can be applied for the excision of
large benign tumors, such as giant fibroadenomas. 6,7
In this article, we present a case with a juvenile giant fibroadenoma managed by
making use of oncoplastic techniques.
MAIN TEXT
MATHERIALS AND METHODS
We describe the case of a 18 years old patient, admitted in General Surgery Department
of Colea Hospital. She presented for a large mass on the right breast, which was noticed six
month before and had a history of rapid development in the last 3 months. The patient didnt
have a history of breast pathology or hormone therapy medication.
The tumor was painless, with no nipple discharge and no history of trauma. The patient
did not complain of recent fever onset or significant weight loss.
Clinical examination revealed pronounced enlargement and asymmetry of the right
breast caused by a tumor with benign features, approximately 7 cm in diameter, with regular
shape, well circumscribed, firm consistency, nonadherent to the underlying structures,
distorting the overlying skin, without accompanying axillary lymphadenopathy. (Fig. 1)

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Figure 1

Figure 2

Blood tests and chest X-ray exam were within normal limits. Mammography was not
performed because of its limited accuracy for young women with dense breast. Right breast
ultrasound detected a solid mass with 66.8 mm length and 51 mm width, ovoid, wellcircumscribed, smooth contour, without axillary node enlargement, classified as BIRADS 3.
A differential diagnosis of giant juvenile fibroadenoma, phyllodes tumor and stromal
hyperplasia was considered for a patient of this age group. The definitive diagnosis was
confirmed by resorting to core needle biopsy under ultrasound guidance and histopathlogical
examination.
Surgical treatment was decided and performed under general anaesthesia. Considering
the tumor location and the need to elevate the areola, the oncoplastic round block technique
was decided. A ring of skin 25 mm in width was de-epithelialized in circular shape along the
areolar margin. Subcutaneous tissue was then incised and the fibroadenoma was removed
using sharp and blunt dissection.

Figure 3

Figure 4

Dissection was facilitated by good exposure and the use of supportive sutures through
the fibroadenoma, intended for better manoeuvrability.
A firm encapsulated mass was excised with maximal preservation of the normal breast
parenchyma. (Fig. 3) After removal, the resulting cavity was obliterated using resorbable
sutures and a drainage tube was placed. The skin defect was mended using inverting and
circular intradermal resorbable sutures. (Fig. 4)
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RESULTS
Post operatively the patient had a fast recovery with no complications. The drainage
tube was removed the following morning. A compressive dressing was used until discharge
on day thre postoperatively. The procedure achieved complete tumoral resection, along with
breast tissue reshaping and mastopexy, by resorting to oncoplastic surgical techniques.
DISCUSSIONS
The causes that determine the emergence and rapid development of giant fibroadenoma
are still unknown, and the disease is considered idiopathic. Analyses of the cellular
components of fibroadenomas by means of polymerase chain reaction demonstrated that both
the stromal and the epithelial cells are polyclonal, supporting the theory that fibroadenomas
are hyperplastic lesions associated with aberration of the normal maturation of the breast.2,8
The pattern of growth in a fibroadenoma is believed to be determined by the epithelial
component, as stromal mitotic activity was found to be higher for those elements. 9
Since the diagnosis of fibroadenomas based on physical examination is only 50% to
67% accurate, for solid lesions such as a fibroadenoma, a core needle biopsy is more
appropriate, can yield more tissue to be examined, and is a way to avoid surgical biopsy.
Surgical treatment may lead to undesirable scarring or extensive ductal damage and
many common cases of breast fibroadenomas do not have surgical indication, and for those
who do have it, there are multiple ultra-minimal-invasive alternatives to surgery
(radiofrequency, focused ultrasound, crioablation). Also, successful endoscopic breast tumor
excision has been reported by some authors. 10 Despite this fibroadenomas can be bothersome
for the patient, causing discomfort or emotional distress, and most surgeons will respect an
informed patients preference for surgical excision.
CONCLUSION
Benign breast tumors, especially when giant or multiple, pose a challenge in obtaining
complete wide excision with minimal breast deformity and minimal residual scars, in
addition to the high risk of recurrence.
Surgical treatment may lead to undesirable scarring or extensive ductal damage, with
with severe consequences, especially for the young patient.
The use of an oncoplastic surgical technique, such as round block, as treatment for
giant benign tumors can considerably reduce these unwanted effects.
AKNOWLEDGEMENT
This paper was co-financed from the European Social Fund, through the Sectorial
Operational Programme Human Resources Development 2007-2013, project number
POSDRU/159/1.5/S/138907 "Excellence in scientific interdisciplinary research, doctoral and
postdoctoral, in the economic, social and medical fields - EXCELIS", coordinator The
Bucharest University of Economic Studies.

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REFERENCES
Rosen PP: Rosens breast pathology. 3rd edition. Lippincott Williams&Wilkins; 2009.
Ron Greenberg, MD, Yehuda Skornick, MD, Ofer Kaplan, MD, Management of Breast
Fibroadenomas, J GEN INTERN MED 1998;13:640-645.
3. Wilkinson S, Anderson TJ, Rifkind E, Chetty U, Forrest AP: Fibroadenoma of the breast: A followup of conservative management. Br J Surg 1989; 76:390-391.
4. Iglehart JD, Kalein CM: Diseases of the Breast. In: Townsend CM, ed. Sabiston Textbook of
Surgery, 16th ed., Philadelphia, Pa: WB Saunders Co, 2001, pp 555-590.
5. Naraynsingh V, Maharaj D, Rampaul R. Swiss-Roll operation for giant fibroadenomas. Breast
Journal 2002;8:46-6.
6. Hung-Wen Lai, Yao-Lung Kuo, Chin-Chen Su, Chih-Jung Chen, Sou-Jen Kuo, Shou-Tung
Chen, Dar-Ren Chen, Round block technique is a useful oncoplastic procedure for multicentric
fibroadenomas. Surgeon, Surgeon 2014 Apr 21. Epub 2014 Apr 21.
7. Nour, F. Gharieb, M. Tashkandi, T. Helmy, Oncoplastic breast surgery for the management of giant
and multiple benign breast lesions, European Surgery, Volume 43, Issue 5, pp 295-301, October 2011.
8. Noquchi S, Motomura K, Inaji H, Imorka S. Clonal analysis of fibroadenoma and phylloides tumor
of the breast. Cancer Res. 1993; 53(17) :4071-4.
9. Sawhney N, Garrahan N, Douglas Jones AG, Williams ED. Epithelial stromal interaction in tumors:
a morphologic study of fibroepithelial tumors of the breast. Cancer. 1992;70(8):2115-20.
10. Agarwal B, Agarwal S, Gupta M, Mahajan K. Transaxillary endoscopic excision of benign breast
lumps: a new technique. Surg Endosc 2008;22:407-10.
11. Dixon JM, Dobie V, Lamb J, et al. Assessment of the acceptability of conservative management
fibroadenoma of the breast. Br J Surg. 1996;83:264-5.
1.
2.

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Medicine

THE ASSESSMENT OF POSTPROCEDURE RESULTS


IN THE CASE OF PATIENTS OPERATED ON USING
THE FEMTOLASIK METHOD WITH THE
ALCON/WAVELIGHT FS200 FEMTO & EX500
EXCIMER REFRACTIVE SUITE

Constantin MIHAI1
Tiberiu Octavian IVANA 2
Calin Petru TATARU 3

ABSTRACT:
THE ASSESSMENT OF THE RESULTS OBTAINED THROUGH THE FEMTO LASIK TECHNIQUE AS
CONSEQUENCE OF THE REFRACTIVE SURGERY FOR THE CORRECTION OF REFRACTIVE ERRORS IN
CASE OF 34 PATIENTS OPERATED USING THE WAVELIGHT (FS200 FEMTO LASER & EX500 LASER
EXCIMER) REFRACTIVE SUITE, TRYING TO DEMONSTRATE THE EFFICIENCY, STABILITY AND
SAFETY OF THE METHOD.
KEY WORDS: FEMTO LASIK, LASER EXCIMER, ABLATION, REFRACTION, REFRACTIVE SURGERY

INTRODUCTION
Myopia represents the most frequent refractive error, having as etiological factors both
genetic and environmental factors, so that the ethiology cannot be accurate in all cases. (9).
The refractive errors at global level are thought to have affected around 2 billion people
around the world.
The treatment of the refractive errors consists in optical correction contract lens,
glasses or surgical correction (the use of excimer laser or phakic implant).
One of the most promising and interesting discoveries in the refractive surgery of the
last decades is, without a doubt, the apparition of the LASIK procedure (laser in situ
keratomileusis).
LASIK is a fusion of old and new technologies, with roots in keratomileusis (from the
Greek keras=cornea and smileusis= sculpture) and the automated lamellar keratoplasty
(ALK).
The femtosecond laser has become in a short period of time the technology embraced
by the majority of surgeons that use the LASIK technique (4), especially due to the decrease
1

MD, PhD Student, ALCOR Clinic Bucharest, Romania, constantinmihai3@yahoo.com


MD, PhD Student, County Hospital Pitesti, Ophthalmology Department
3
MD, PHD, Emergency Eye Hospital, Bucharest, Lecturer UMF Carol Davila, Bucharest
2

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in the postprocedure inflammation, and due to the easiness with which the flap is elevated,
using the last variants of these lasers (12).
Winkler von Mohrenfels et al (17) have reported in a pilot study performed in 20
eyes, the first clinical results by using the Femto LASIK technique, with sure, stable and
efficient results.
MAIN TEXT
A descriptive-prospective study was performed on a number of 61 eyes subjected to a
surgery intervention for the correction of different refractive errors ( myopia and mixed
astigmatism), by means of the Femto-LASIK method, using the refractive suite Alcon
Wavelight composed of the femtosecond laser FS200 and the excimer laser EX500,
operated and evaluated between May 2013 - July 2014. The study enrolled a lot of 34
patients, eligible for the Femto LASIK technique.
The purpose of the refractive surgery by using the FEMTO LASIK technique is to
eliminate or reduce the dependence of contact lenses or glasses for the daily activities.
Depending on the thickness of the cornea the myopia can be corrected up to -12 dioptres,
provided that the thickness of the residual corneal stroma remains within the safety limits
(minimum 300 m.). If the myopia is associated with astigmatism, it is indicated to correct a
value as higher as possible of the astigmatism, but no more than 3-4 dioptres. For each
dioptre, the cornea is thinned with approx. 14 m.
The patients refractive errors need to be stable for at least one year. The refractive
stability is usually reached around 20-21 years old.
Preoperative evaluations of patients included uncorrected visual acuity (UCVA), bestcorrected visual acuity (BCVA), manifest and cycloplegic refractions, topography (Allegro
Topolyzer and Allegro Oculyzer, WaveLight GmbH), pachymetry (Allegro Oculyzer,
WaveLight GmbH), Schirmer test, measurement of the intraocular pressure. A complete
anterior segment examination and a dilated fundus examination were performed.
After the surgical intervention, the ophthalmological reassessment of the patient
( UCVA, BCVA, and manifest refraction) was made after one day, after one week, a month
and after three months.
RESULTS AND DISCUSSIONS
A number of 61 interventions were performed on 34 patients (18 women and 16
men).
With most of the patients (80%), we chose to correct the refraction error in both eyes, in
the same session, while 7 patients needed a unilateral intervention.
The patients average age was 32.7 years old (with variations between 22 - 51 years
old). Image no. 1 shows the distribution per age groups of patients subject to a FEMTO
LASIK technique:

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The distribution of patients by age


11

Nr of patients
6

20-24 years

25-29 years

30-34 years

35-39 years

40-44 years

45-49 years

2
50-54 years

0
55-59 years

Image no. 1. Distribution of patients by age groups

Mean preoperative spherical refraction was -3.87 (with a standard variation of 2.24),
the smallest spherical dioptre treated being -0.75 and the biggest dioptre of -12.5.
The astigmatism can be associated with myopia and is asymptomatic especially with
values higher of 1D.
80% of the operated myopic eyes have associated a certain degree of astigmatism,
nevertheless 70% presented a physiological astigmatism (<1D), which does not need an
optical correction. (Image no. 2)

Image no.2. The distribution of the eyes depending on cylinder dioptres

The mean of the preoperational cylindrical lens was of -0.98 (standard deviations of
0.96) with values comprised between 0 and -3.75.
The mean of the preoperational spherical equivalences was of - 4.25 (standard
deviation of 2.63) with values between -0.75 and -13.75.

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The visual acuity optimally corrected with the help of lens was, in proportion of 77%,
maximum. Therefore, a number of 47 eyes had a visual acuity of 1CC (with
correction)(results in Table no. 1).

Table no.1 The distribution of patients depending on the preoperational BCVA


BCVA

Number of patients

1 with correction

47

0.9 with correction

0.7 with correction

0.6 with correction

0.5 with correction

0.3 with correction

A percentage of 70% from the interventions obtained at one day after the surgery, an
optimal visual acuity, of 1 without correction. The rest of 10% each obtained a visual
acuity of 0.9 without correction, 0.7 without correction and respectively 0.6 without
correction. (Image no. 4)

VA one day postop - without correction

10%

10%

9%

0.9

71%

0.7
0.6

Image no. 4. Percentage distribution VA one day after the surgery

A week after the operation, the percentage of the interventions with optimal result (AV
de 1 without correction ) increases with 2%, reaching at 72%; at the same time, the
percentage of the eyes with AV of 0.9without correction increases from 10% to 12%; 8%
from the eyes reach an acuity of 0.8without correction , and another 8% have the acuity of
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Supplement No. 3/2014

0.7without correction . No intervention has, at this point, a visual acuity of less than
0.7without correction . (Image no. 5)

Image no. 5. Percentage distribution of AV one week after the operation

One month after the operation, the percentage of the eye balls operated with AV increases
from 1 without correction to 77% and the percentage of the ones with AV decreases from 0.9
without correction to 7%.
Three months after the operation, the visual acuities stabilized at 1 without correction
for 75% of the interventions, 0.9 without correction for 13% of the operated eye balls, 0.8
without correction for 8% and 0.7 without correction for 4%. Although the percentage of
interventions with maximum result decreases with 2%, the percentage of the ones with
weaker results decreases considerably as well (Av of 0.7 without correction decreases with
4%), and the percentage of eyes with AV of 0.9 without correction grows with 6%. (Image no.
6).

Image no. 6. Percentage distribution of AV after 3 months post operation

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The spherical average refraction after 3 months post operation is of 0.25D (with a
standard variation of 2), while the average cylindrical refraction is of 0.25D (with a standard
variation of 0.4).
In order to prove the degree of efficiency, it was intended to highlight the interventions
with maximum results in comparison with the ones which had satisfactory results. Thus, in 3
months, an increase of the eyes that see perfectly (from 71% to 75%) was noticed, among
the number of the eyes with satisfactory results (from 80% to 96%) (Image no. 7).

Image no. 7. The percentage of the eyes operated with AV0.8 and AV>1
(at 1 day, 1week, 1 months and 3 months post operation)

The efficiency may also be assessed through the value of the spherical equivalent (SE)
obtained post operation. This refers to the number of spherical dioptres corresponding to a
number of cylindrical dioptres and represents the sum between the spherical dioptres and
from the cylindrical dioptres.
In what concerns the stability, there may appear significant refractive alterations in the
first 3 months post operation (11), although regression may develop up to 2 years after
LASIK (8). Usually, the regression is correlated with the hyperplasia of the corneal
epithelium post operation (7) with the profoundness of the ablation, with the flattening of the
corneal curvature and the humidity (16).
CONCLUSION
Our study shows that the uncorrected AV is rapidly improving, reaching values of 1
since the first days post operation and being maintained after three months. After 3 months
postLASIK an uncorrected visual acuity of >0.8 in 96% of the cases was obtained, while
75% of the operated eyes showed uncorrected AV =1. Thus we observe that post operation,
the uncorrected AV was similar with the postoperative AV, corrected with lens.
After one month, 77% from the cases in our study reached the uncorrected AV of
1without correction as compared to other authors such as Durrie1 who reaches a percentage
of 96% or Lim (82.1%). After the visit at one month it reached 77%, in contrast with Durrie
(96%) or Lim (82.1%) (6).

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The average value of the spherical dioptres at 3 months post operation was of 0.25D
(with a standard variation of 2), and the cylindrical average dioptres were still 0.25D (with a
standard variation of 0.4). The small values, almost insignificant of the postoperative
refraction are an indicator of the stability of the results.
Our study shows that the FemtoLASIK technique for the creation of the corneal flap in
case of the 61 eyes operated was efficient and safe and the results obtained were stable for
more than 3 months; the femtosecond laser implies a rapid recovery of sight.
Tanna and collab. have performed a study o n 2000 eyes, through which they showed
that the femtosecond laser improves equally the postoperative recovery time, as well as the
uncorrected visual acuity at 3 months, as compared to the microkeratome (14). The study
explained that the improvement took place in spite of the similar predictability of the two
pieces of equipment in performing the flap. More exactly, no matter when the postoperative
assessments were made, the percentage of eyes that performed a visual acuity of 1 without
correction was significantly higher than the group treated with femtolaser than in the group
treated with the mechanical microkeratome.
Moreover, Durrie et al. (2) demonstrated that the femtosecond laser produces
statistically better results both visual, as well as in terms of contrast sensitivity.
As far as the apparition of complications is concerned, in our study, no re-intervention
was necessary, in neither of the operated cases.
While performing the flap, the loss of suction did not appear in any of the 61 operated
eyes. At the same time, no epithelial growths were noticed, to invade the edge of the flap or
other complications mentioned in other studies, such as the diffuse lamellar keratitis (15),
the presence of bubbles in the anterior chamber (5), severe disorders of the sensitivity to light
(13).
Our study, to which numerous international studies are added, shows a higher precision
and a safety of the Femto LASIK.
ACKNOWLEDGEMENT: This paper is supported by the Sectorial Operational
Programme Human Resources Development (SOP HRD), financed from the European
Social Fund and by the Romanian Government under the contract
number POSDRU/159/1.5/S/132395

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laser in situ keratomileusis: prospective contralateral eye study. J Cataract Refract Surg 2005; 31: 120126.
Gell, J. L., and A. Muller. Laser in situ keratomileusis (LASIK) for myopia from-7 to-18
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Lohmann, Chris P., and Jose L. Guell. Regression after LASIK for the treatment of myopia: the role
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creation: clinical findings and management. J Cataract Refract Surg. 2006;32(1):91-4
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retrospective comparison of visual outcomes at 3 months. J Refract Surg. 2009;25 (7Suppl): S668-71.
Tran DB, Sarayba MA, Bor Z, Garufis C, Duh YJ, Soltes CR, et al. Randomized prospective
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31: 97-105
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enhancement rates. Journal of Cataract & Refractive Surgery30.4 (2004): 798-803.
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Lohmann CP. First clinical results with a new 200 kHz femtosecond laser system. Br J Ophthalmol.
2011 Dec 16

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Medicine

UPDATE ON INFLAMMATORY BOWEL DISEASES


ETHIOPATOGENICS

Alexandru LUPU1
Cosmin CIORA2
Mircea DICULESCU3

ABSTRACT
THE INFLAMMATORY BOWEL DISEASES (IBD) CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS
(UC) ARE CHRONIC IMMUNOLOGIC DISEASES THAT CAN LEAD TO DECREASED QUALITY OF LIFE
AND INVALIDITY; IBD ARE CHARACTERIZED BY ABERRANT IMMUNE RESPONSES TO INTESTINAL
MICROBIOTA IN GENETICALLY SUSCEPTIBLE HOSTS THAT LEAD TO CHRONIC EXCESSIVE
INFLAMMATION AND IN TIME TO PROGRESSIVE GUT WALL DESTRUCTION. IBD HAVE AN
EUROPEAN INCIDENCE OF 12 TO 25 PER 100,000 PERSON-YEARS, HIGHER FOR UC THAN CD, WITH
A PREVALENCE OF 0.5-1%.
ENVIRONMENTAL FACTORS LIKE CIGARETTE SMOKING, POLLUTION, CHANGES IN DIET AND
EXCESSIVE USE OF ANTIBIOTICS ARE INCRIMINATED IN IBD PATOGENESIS.
THERE IS THOUGHT TO EXIST AN IMBALANCE IN THE INNATE AND ACQUIRED IMMUNE
RESPONSES TO NORMAL INTESTINAL MICROBIOTA THAT ACTIVATES PRO-INFLAMMATORY
CYTOKINES AND LEADS TO A CHRONIC INFLAMMATORY PROCESS AROUND THE GUT BARRIER.
THIS IN TIME LEADS TO INTESTINAL BARRIER DESTRUCTION AND EXPOSURE TO EVEN MORE
BACTERIAL PARTICLES THAT FURTHER AGGRAVATE THE INFLAMMATORY PROCESS.
GENETIC STUDIES HAVE PROVIDED MANY SUSCEPTIBLE LOCI FOR IBD. IT IS KNOWN FROM THE
LITERATURE THAT GENETIC FACTORS ACCOUNT FOR 13.6% OF CD AND 7.5% FOR UC VARIANCE.
IN THIS LITERATURE REVIEW WE HIGHLIGHT SOME ETHIOPATHOGENIC LEADS THAT ARE RECENT
TARGETS OF CLINICAL AND FUNDAMENTAL IBD RESEARCH.
KEY WORDS: IBD GENETICS, IMMUNOLOGY, THERAPEUTIC TARGETS

INTRODUCTION
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory immune
mediated diseases that affect genetic predisposed individuals and can interfere with quality of
life and working ability. Inflammatory bowel disease's (IBD) incidence in Europe is 12.7
(CD) and 24.3 (UC) per 100,000 person-years while prevalence is around 0.5-1% [1].
In genetically susceptible individuals the relationship between aberrant immune
responses and intestinal microbiota, that can be changed by diet habits [2], leads to gut barrier
1

MD. PhD Student, Departament of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest,
alexandru.c.lupu@gmail.com
2
MD. PhD Student, Departament of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest
3
Prof. PhD, Departament of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest

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December 2014

destruction and higher permeability for pathogenic bacteria. This attracts in time chronic
inflammation, edema, erosion and ulcerations that can manifest with fatigue, abdominal pain,
weight loss and chronic bloody diarrhea. Due to a high variability and multiple pathogenic
mechanisms there is still no clear etiopatogenic mechanism of IBD.
MAIN TEXT
1. Environmental factors have an important role in IBD patogenesis, for example
cigarette smoking is a known risk factor for CD because it interferes with the function of
NOD2 gene [3]. There is also a north-south, west-east prevalence gradient in IBD that is
probably due to environmental factors and diet. Current theories support the fact that an
active hygiene, secondary to the high standard of life in western society, leads to a lower
exposure to bacterial antigens in childhood and a higher incidence of IBD [4]. Changing
nutrition habits in infants with decreasing breast feeding (known to be a protective factor),
excess of antibiotic regimes, proton pump inhibitors and western diet rich in processed food,
fat, animal proteins and polyunsaturated fatty acids and low in vegetables, fiber and fruits
play an important role in changing intestinal microbiota [5] and increasing IBD prevalence.
2. Unlike general population, IBD patients have an aberrant immunologic response to
external antigenic stimuli that is increased in duration and severity [6]. Alterations in gut wall
start by loss of tight junctions between epithelial cells and destruction of mucosal layer witch
increases intestinal permeability to luminal bacterial antigens [7].
This alterations are further amplified by loss of inhibitory immune mechanisms,
macrophages and numerous pro-inflammatory cytokines activation. Until recently we
considered that immune reaction to antigens was different in CD as opposed to UC. In CD
there was a lymphocyte T helper 1 (Th1) mediated reaction that differed to the Th2 activation
seen in UC patients. A new pathogenic theory common for both CD and UC shows that the
hyperactivity of cellular immune response is mediated by the presence of Th17 lymphocytes
that are implicated in the secretion of numerous cytokines: interleukin (IL) 17, IL 22, IL 23,
IL 26 [8][9][10].
There is another theory that the chronic inflammation in IBD is secondary to an energy
imbalance. This imbalance is due to alterations in the oxidative metabolism from the
intestinal epithelial cells [11][12] and to cell-specific endoplasmic reticulum (ER) stress
which induces dysfunctions in Paneth cells, goblet cells that produce mucus and that alters
the enterocyte barrier [13][14]. The ER stress contributes to pathogenic mechanisms of
insulin-resistance in type 2 diabetes and this proves that there is o common pathogenic way in
both IBD and metabolic diseases [15].
Mitochondria are essential cellular organelles for maintaining energetic equilibrium by
adenosine triphosphate (ATP) mediated energy intake, apoptosis regulation and oxygen free
radicals production. The paper published by Bertran and his collegues prooves that excessive
levels of oxidized molecules, inhibited mitochondria and hypersensitivity to oxidative stress
are implicated in IBD pathogenesis [16].
3. Genetic susceptibility in IBD patients was demonstrated in numerous genome-wide
association studies. Nevertheless, it has been proven that there is no simple model, Mendelian
type, that could explain IBD transmission. Mono-zygotic twins have up to 67% concordance
for developing CD [17] and 15-20% for UC. By genotyping, in the last years there have been
found numerous susceptibility loci associated with IBD. There are more than 40 confirmed
loci and over 160 susceptibility loci [18]. Most of the confirmed loci are common for CD and
UC like the genes for lymphocyte Th 17 mediated immune response (IL23R, IL12B, JAK 2,
STAT 3) [19][20]. The genes that differ between the two IBD's are a good premise for future
research and new therapeutic molecules, specific for each inflammatory bowel disease in
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part. Crohn's disease is associated with autophagocytosis genes: ATG16L1, IRGM and
NOD2 while UC genetic specificity is in relation to the genes that codify the gastro-intestinal
epithelial barrier: HNF4a, E-caderin, LAMB 1 and IL 10 [21]. It's interesting that some genes
like NOD 2 and PTPN22 predispose to CD but are a protective genetic element against UC.
By genotyping rises the posibility to discover new molecules that are specific for each IBD
patogenesis in part and also the posibility to identify genetic markers that are able to predict
disease outcome and therapeutic response. A recent study identified mutations that are part of
NFkB inflammatory path; this particular mutations can predict the rate of response to anti
tumor necrosis factor alfa (anti-TNF ) molecules - a very potent immunosupressant class of
drugs [22]. Bank S. et al paper also identified new possible therapeutic targets (IL 1, IL-6,
IFN-) that can become very useful in the future.
4. IBD patients have a particular intestinal microbiota: a decrease in non-patogenic
species like Bifidobacteria, Lactobacili and Firmicutes and an increase in patogenic species
like Bacteroides and Escherichia coli [23]. In healthy subjects autophagy mechanisms are
efficient enough to eliminate intracellular pathogens from digestive tract but Hang Thi Thu
Nguyen and his colleagues have recently demonstrated that in CD patients Adherent Invasive
Escherichia coli (AIEC) suppresses autophagy gene expression (ATG 5, ATG16L1) and that
leads to the inability of clearing this bacteria from the intracellular space [24]. AIEC
persistance maintains a chronic inflammatory intestinal process with excesive proinflammatory cytokines. This is just one of the papers that highlights the importance of gut
microbiota in IBD ethiopathogenic mechanisms and the utility of prebiotics and probiotics to
obtain and maintain disease remission. Also, microbiota pathological diversity in CD and UC
is reason to justify increasingly more often fecal transplant as a new way to treat selected IBD
patients.
CONCLUSIONS
Even though all this etiopathogenic leads are valuable therapeutic targets for
fundamental and clinical gastroenterology, immunology and genetics research we are still far
away from the moment when finding "a cause and one etiologic treatment" for all IBD forms
and patients.
General diversity of etiopathogenic mechanisms as well as global heterogeneity of IBD
makes mandatory permanent literature update for every IBD specialist and also underlines the
need to better understand local geographical particularities and trends in Crohn's disease and
ulcerative colitis.
ACKNOWLEDGEMENTS
- this study was supported by the Sectorial Operational Programme Human Resources
Development (SOP HRD) financed from the European Social Fund and by the Romanian
Government under the contract POSDRU/107/1.5/S/82839

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December 2014

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