Sameer Smadi MD.

Cholangiocarcinoma
Definition of Cholangiocarcinoma

Bile duct cancers arising from ductal
epithelial cells

Refers to cancers arising in the intrahepatic
(~5-15%), perihilar (~60-70%), or distal
(extrahepatic ~25%) biliary tree

Represents approx. 3% of all gastro-
intestinal malignancies
Definition of Cholangiocarcinoma

Bismuth-Corlette Classification subdivides
perihilar cholangiocarcinomas based on pattern
of involvement of hepatic ducts
Type I: tumors occurring below the confluence of the
left and right hepatic ducts
Type II : tumors reaching the confluence
Types IIIA/IIIb: tumors occluding the common
hepatic duct and either the right or left hepatic duct
Type IV: tumors that are multicentric, or that involve
the confluence and both the right or left hepatic duct

Klatskin tumors occur at the bifurcation of the
proper hepatic duct
(A) The anatomic location of cholangiocarcinoma can be described as intrahepatic, distal extrahepatic or hilar.
Cholangiocarcinomas can be further described based on their macroscopic or cholangiographic appearance. (B) Nonhilar
lesions can be described as mass-forming, periductal or intraductal, or as mixed mass-forming and periductal. For
extrahepatic lesions the terms periductal, mass-like and intraductal correspond to the alternative designations of
sclerosing, nodular and papillary. (C) Hilar lesions can be described using the Bismuth classification.70 Type I tumors are
found below the confluence of the left and right hepatic ducts. Type II tumors reach the confluence of the left and right
hepatic ducts. Type IIIa and IIIb tumors occlude the common hepatic duct and either the right or the left hepatic duct,
respectively. Type IV tumors are multicentric or they involve the confluence and both the right and left hepatic ducts. A
combined anatomicmorphologic classification is useful for patient management and can provide consistency in clinical or
epidemiologic studies. Tumors are shown in (B) and (C) in yellow

Incidence:
1.0 per 100,000 per year
Male to female ration of 1.3:1
Average age of presentation is 50-70
Etiology:
Common features of risk factors include biliary stasis, bile
duct stones, and infection.
PSC, Choledocal cysts, hepatolithiasis, chlonorchis or
typhoid infections.
Other risk factors include liver flukes, nitrosoamines,
dioxin exposure.
Presentation:
Typically painless jaundice, may include pruritus, RUQ
pain, anorexia, fatigue, and weight loss.

Work-up
Typically Alk phos will be elevated to 1.5 to 5 times normal, and transaminase levels will
be 1-2 times normal. CEA or CA 19-9 may also be elevated but these test are not
diagnostic.
Pathology

Adenocarcinoma (90%)
Slow growing, locally invasive, mucin-producing
Perineural spread, metastases uncommon
Three subtypes of adenocarcinoma
Sclerosing
Majority of cholangiocarcinomas
Characterized by an intense desmoplastic reaction
Early ductal invasion leads to low resectability rates
Nodular
Constricting annular lesion of the bile duct
Papillary
Present as bulky masses occurring in the bile duct lumen
Present early with biliary obstruction
Highest resectability rates
Clinical

Triad
Cholestasis
Abdominal pain (30-50 %)
Weight loss (30-50 %)
Pruritus (66 %)
Clay-colored stools, dark urine.
Jaundice (~90 %)
Hepatomegaly
RUQ mass
Courvoisier's sign
Intrahepatic cholangioCA typically presents without
biliary obstruction
Laboratory

Elevations in:
Total bilirubin (>10 mg/dL)
Direct bilirubin
Alkaline phosphatase (usually increased 2- to 10-fold)
5'-nucleotidase
Gamma glutamyltransferase
Transaminase levels initially normal
With chronic biliary obstruction, liver dysfunction may
ensue with elevation in ALT/AST and PT
Differential Diagnosis

Choledocholithiasis
Benign bile duct strictures (usually postoperative),
Sclerosing cholangitis
Compression of the CBD (secondary to chronic
pancreatitis or pancreatic cancer)

Diagnosis

Tumor markers
Serum CEA >5.2 ng/mL(sensitivity 68%, specificity 82%)
CA 19-9
Radiographic studies
Transabdominal ultrasound- may reveal ductal dilatation
(intrahepatic >6mm)
CT/helical CT- can also detect vascular invasion
Helical CT (esp. portal venous phase)- can delinieate nodal
basins
May be superior to MRI with respect to predicting
resectability
MRCP- may be coming the imaging modality of choice

Diagnosis

Cholangiography
ERCP or PTC
Useful if suspected level of obstruction is distal
Preoperative drainage of the biliary tree
Obtain diagnostic bile samples or brush cytology (low
sensitivity)
Endoscopic ultrasound
Useful for visualizing distal tumors and regional nodes
Can be used for EUS-guided biopsy of tumors and
enlarged nodes
PET
High glucose uptake of biliary duct epithelium
Angiography (rarely used)
Staging laparoscopy

Diagnosis

Role of Staging laparoscopy
Tissue diagnosis important in the
setting of:
Strictures of unknown origin (e.g.
bile duct stones, PSC)
Family/patient request for a
definitive diagnosis
Prior to chemotherapy or radiation
therapy

Management

Poor prognosis- avg. 5-year survival ~5-10%
Resectability rate superior for distal tumors
resectability rates for intrahepatic 60%, perihilar 56%, and
distal lesions 91% (Nakeeb A; Pitt HA, JHU 1996)
Negative margins achieved in 20-40% of proximal tumors
cases, 50% of distal tumor cases

Management

Accepted guidelines for resectability (accurately
determined at operative exploration)
Absence of N2 nodal metastases or distant liver metastases
Absence of vascular (portal vein, hepatic artery) invasion
Absence of extrahepatic adjacent organ invasion
Absence of disseminated disease
Management

Pre-operative biliary decompression
Liver dysfunction increases postoperative
morbidity and mortality
Arch Surg 2000 (Cherqui et. al.)
Study demonstrated increased post-op morbidity in
jaundiced patients not undergoing pre-operative
drainage (vs. nonjaundiced patients)
Pre-operative portal vein embolization
Induce liver hypertrophy to increase limits of safe
resection
No demonstrated improvement in clincial outcome
Management

Surgical Procedures
Distal lesions: pancreaticoduodenectomy (5-yr survival
rates 15-25%)
Intrahepatic cholangiocarcinoma: hepatic resection (3-yr
survival rates 22- 66%)
Perihilar cholangiocarcinoma (5-yr survival rates 10-45%;
outcomes in PSC patients dismal)
Type I and II lesions: en bloc resection of extrahepatic
bile ducts and gallbladder with 5 to 10 mm bile duct
margins, regional lymphadenectomy with Roux-en-Y
hepaticojejunostomy.
Type III and Type IV lesions: hepatectomy and portal
vein resection
Role of liver transplantation
Bismuth-collette Type IV
Recently, an extended bile duct
resection combined with total
hepatectomy,
pancreatoduodenectomy, and
orthotopic liver transplantation
(HPLTx) was proposed to eradicate the
entire biliary tract without cutting off
the hepatoduodenal ligament.
Liver transplantation may be a
therapeutic option for the patients
with 1) unresectability confirmed at
laparotomy; 2) advanced tumor with
infiltration of the adjacent tissues that
an R0 resection is hardly to be
achieved; 3) local intrahepatic
recurrence of the tumor; and 4)
advanced hepatic cirrhosis and
primary sclerosing cholangitis without
enough residual functional liver
tissues after resection.
Hepatic Tumors
Benign Solid liver tumors
Hepatic Adenoma
Reproductive women
75% with abdominal pain on
presentation.
Chance of rupture is
significant (25% with
hepatocellular adenoma)
Increased fat signal on MRI
Cold on Tc-MAA scan.
Resection remains the
standard of therapy for lesions
larger than 4 cm.
Benign Solid liver tumors
Focal Nodular Hyperplasia
Not associated with
symptoms.
No risk of rupture or
malignant degeneration
Characteristic central scar,
hot on Tc-MAA scan.
Early embryologic vascular
injury.
If symptomatic, lesion may be
resected.
Lesions are often peripheral
and thus lap. Resection should
be advocated.
Benign Solid liver tumors
Hemangiomas
Chronic RUQ pain
CT or MRI diagnostic
Resection if symptoms
are ascribed to the
hemangioma
Malignant Liver Tumors
HCC is one of the most common solid human
cancers, with an annual incidence estimated to be
approximately 1 million new patients.
In addition the liver is second only to lymph nodes
as a common site of mets from other solid tumors.
It is not uncommon, particularly with colorectal
cancer for the liver to be the only site of metastasis.
Resection of both primary disease and isolated
metastatic disease may result is significant long
term survival benefits in 20-45% of patients.
Presentation:
Mostly diagnosed through imaging performed for some
other indication, as part of a screening protocol, or during
follow-up for a known primary malignancy of another
organ site.
Symptoms may include dull right upper quadrant pain,
fullness or bloating, and in some instances nausea or
vomiting, or systemic complaints.
History: high-risk behaviors or known hepatitis virus
infection, travel to areas where hepatitis B or C is endemic,
alcohol use, exposure to hepatotoxins, use of oral
contraceptives or hormone replacement therapy, or a
history of hereditary liver diseases

Imaging for suspected liver neoplasm
CT scan: highly sensitive at spatial discrimination and
quantification of lesions in the liver, good for pre-op
planning.
MRI: better for detecting early HCC, and distinguishing
between HCC and macroregenerative nodules.
U/S: Useful for guiding biopsy, determining tumor
vascularity, and intraoperatively to guide resections.
Other studies: PET, Angiography, Dx laporoscopy.
Treatment
HCC Treatment Options
Curative

Transplantation
Surgical Resection

Ablative Therapy
RadioFrequency Ablation (RFA)
Cryoablation
Percutaneous ETOH ablation
Non-Curative

Trans-Arterial Chemo-Embolization (TACE)
Sorafenib

Treatment
Surgery
Ultimately complete resection of the liver mass remains
the optimal choice for treatment.
Newer techniques continue to decrease the morbidity
associated with hepatic resection including stapling
techniques and laparoscopic approaches.
For patients with a single lesion and preserved liver
function, resection is curative, with 5-year survival rates of
50% to 70%
Recurrent HCC occurs in 50% to 80% of patients at 5 years
after resection, with the majority occurring within 2 years
Treatment
Radiofrequency ablation
thermal necrosis to tumors by
delivering electromagnetic energy
through needle electrodes.
RFA versus resection for patients with
single small lesions show comparable
1- and 3-year overall survival results
(100% and 72.7% versus 97.9% and
83.9%, respectively.
higher 1- and 3-year local recurrence
rates (16.3% and 18.2% versus 1.1% and
2.2%, respectively).
May also be considered as a bridge to
transplantation.
Treatment
Transplantation
Choosing the patient who can maximize each organ is of
paramount importance and is dictated by the Milan
criteria.
The consensus is that liver transplantation is indicated in
patients with HCC with at least a 50% chance of survival at
5 years
Most series demonstrate a survival advantage for HCC
patients from transplantation over all other modalities.
In an ideal world without an organ shortage, timely liver
transplantation would offer better survival rates than
resection by offering both decreased tumor recurrence and
a treatment of the underlying liver disease.
Milan criteria for HCC in liver
cirrhosis
Cha, et al: Ann Surg, Volume 238(3).September 2003.315-323
Colorectal neuroendocrine


Non Colorectal neuroendocrine


Surgical resection is currently accepted
as a safe, and also the only potentially
curative treatment available for patients
with colorectal liver metastases.
Chance of long-term survival with
rates ranging from 25% to 50% at 5
years
During the last decade, significant
technical advances have been
accomplished in liver surgery.
They allow bilobar resections with very
low mortality (around 1%) and low
morbidity
HV Analysis labeled
Colon cancer with liver metastasis

Unless there is an absolute prohibitive
medical risk, all patients with
potentially liver mets.
should have careful evaluation to
determine whether they have
potentially resectable disease .
SYNCHRONOUS COLORECTAL LIVER
METASTASES
Liver mets is detected in 15-25% of
colorectal cancer cases
Have been presumed to represent
more aggressive tumour
No evidence that these patients do
worse after liver resection
Should these patients have
concurrent or staged liver
resection?

YOKOHAMA EXPERIENCE
39 consecutive patients
39 concurrent multivariate analysis for safety and
success rate
Poor overall survival with poorly differentiated and
mucinous adenocarcinomas (p<0.05)

Conclusion: 1 stage resection desirable except in
patients over 70 years of age and those with
poorly differentiated and mucinous
adenocarcinomas
Tanaka K et al. Surgery 2004; 136: 650-9.
TOKYO EXPERIENCE
187 consecutive patients, 1980-2002
142 concurrent, 27 staged resections
Prognosis affected by
multiple liver metastases
4 or more lymph node metastases around the primary
tumour

Conclusion: Simultaneous resection in
patients with 3 or less colorectal lymph node
metastases only

Minigawa M et al (Makuuchi). Arch Surg 2006; 141: 1006-12.
STRASBOURG EXPERIENCE
97 consecutive patients (1987-2000)
35 concurrent vs 62 staged
Concurrent resection if <4 unilobar metastases
Morbidity 23% vs 32%
Location of primary did not influence morbidity
Overall survival 1yr 94% vs 92%
3 yr 45% vs 45%
5 yr 21% vs 22%

Conclusion: Synchronous resection does not
increase morbidity or mortality rates
Weber JC et al. (Jaeck) Br J Surg 2003; 90: 956-62.
BERLIN EXPERIENCE
219 consecutive patients (1988-2005)
40 concurrent vs 179 staged
Morbidity similar
Mortality higher in concurrent group (p=0.012)
Mortality in concurrent group (n=4) after major
hepatectomy and age >70 yrs
No significant difference in long-term survival

Conclusion: decision should be based on
age and extent of liver resection
Thelen A et al. (Neuhaus) Int J Colorectal Dis 2007; Feb 21 (Epub ahead of print).
MSKCC EXPERIENCE
240 consecutive patients (1984-2001)
134 concurrent vs 106 staged
Concurrent resection: more right colon primaries (p<0.001), smaller
(p<0.001) and fewer (p<0.001) liver metastases, and less extensive
liver resection (p<0.001)
Complications: 49% vs 67% (p<0.003)
Median 10 vs 18 days in hospital (p<0.001)
Mortality n=3 vs n=3

Conclusion: Simultaneous resection safe and
efficient, with reduced morbidity and shorter
treatment time
Martin R et al. (Blumgart) J Am Coll Surg 2003; 197: 233-42.
Clinical score for predicting recurrence after hepatic resection for
metastatic colorectal cancer - analysis of 1001 consecutive cases
Fong et al, Annals of Surgery 1999; 230: 309

Nodal status of primary
Disease-free interval from primary to discovery of the liver
metastases of < 12 months
Number of tumours > 1
Preoperative CEA level > 200 ng/ml
Size of largest tumour > 5 cm

Overall actuarial survival 37% at 5 years, 22% at 10 years
Clinical Risk Score (CRS) predictive of long term outcome
(p<0.0001)
Actuarial survival 60% if CRS =1, 14% if CRS = 5

Case No. 1
55 years old female
medically free
Left hemicolectomy 2.5 years ago
-ve nodal status of primary colonic tumour
No chemotherapy
Lost follow up for two years then came with
CEA 150

CT scan







Ist Right portal vein ligation
Extended Rt. hepatectomy
Extended Rt. hepatectomy

60 years old female, diabetic
Left hemicolectomy one year ago for recto-sigmoid
tumour
3 Lymph nodes +ve
Received chemotherapy
CEA = 25

CT Scan
2
nd
case
Extended Lt. Hepatectomy
LEFT TRISECTIONECTOMY

One of the most difficult of the major hepatectomies

Technically hazardous because:
Absence of landmarks for the right fissure
Anatomic variations of the right portal structures

Remains a useful technique for:
Centrally located tumours
Hilar cholangiocarcinomas with predominant left duct
involvement

Experience with this technique is rarely reported
Extended Lt. Hepatectomy
62 years old male , diabetic , hypertensive
Rt. Hemicolectomy 6 months ago
He received chemotherapy
CEA 14
CT scan

3
rd
Case Resection of
Posterior Sector (Seg VI + VII)
3
rd
case
Posterior Sector (Seg VI and VII)
Resection
Segmental Resection
Posterior sector (Seg. VI+VII)
58 years old female , diabetic
Left hemicolectomy 8 months ago in
Palastine
Developed reco-vaginal fistula
Treated by diversion ileostomy
Referred from west bank for
chemotherapy
CEA 25
Segmental
Resection
(Seg. V
and Seg VI
Segmental resection
Parodia spaniosa
The best is yet to
come.