Beruflich Dokumente
Kultur Dokumente
Patient factors Tumour biology (angio-invasion, grade, type of tumor, gene-expression profile) Quality of the surgical resection Quality of the pathological examination
Adjuvant chemotherapy is reserved for stage III patients and some, high risk stage II patients
Recurrence rate and survival rates are related to the number of examined lymph nodes It is not known exactly how many lymph nodes have to be examined, numbers vary from 8, 12, 18 to an unlimited number In 75% of cases less than the recommended 12 nodes are examined
(Law et al JSO 2003, Le Voyer JCO 2003, TepperJCO 2001, Wong Dis Colon Rectum 2002, Wright AnnSurg Oncol 2003, Goldstein AM J Surg Path 2002, Kelder Dis Colon Rectum 2008)
Pitfalls: Less than 1% of the node is examined 70% of the metastases are found in nodes < 5 mm
Ultrastaging
Multiple level sectioning: 15-20% upstaging (Diest et al, Sem Surg Onc 2001) Immunohistochemistry: 10-76% upstaging (Feezor et al Ann Surg Onc 2002) PCR 46-54% upstaging (Liefers N Eng J Med 1998, Bilchik JCO 2001, Hayashi Lancet 1995)
Problems:
Micrometastases
Iddings et al Ann Surg Oncol 2006 meta-analysis Retrospective molecular detection of metastases by RT-PCR shows an adverse effect on survival in stage II patients IHC detected micrometastases do not have a significant effect on survival (there is a survival difference, no significance due to heterogeneity in studies)
With a minimal number of 12 nodes, the pathologist probably only takes a sample of the lymph node basin We need the best possible sample
Sentinel node: The first lymph node with the most direct drainage from a tumor site which has the highest potential to contain metastases when present*
SN procedure - history
1923 Braithwaite lymphatic flow from ileocecal valve with indigocarmine 1950 Weinberg - lymphatic mapping with pontine sky blue to identify the thoracic duct and lymph nodes in gastric and pulmonary cancer 1960 Gould SN in parotid carcinoma 1977 Cabaas SN procedure in penile cancer 1992 Morton - SN procedure in melanoma with patent blue 1994 Giuliano SN procedure in breast cancer
Easy access for injection of blue dye and/or radio-active colloid Prevention of an unnecessary lymphadenectomy when negative SN Positive SN lymphadenectomy in 2nd stage Nodal upstaging by the detection of micrometastases through the use of ultrastaging techniques on the SN
Colorectal cancer
Access less easy No indication for limited dissection one stage procedure is preferred Nodal upstaging through ultrastaging techniques on the SN Detection of aberrant lymphatic drainage patterns, leading to an adjustment of the initial resection
Risk factors: involved mesorectal nodes, female sex, advanced T-stage, lymphovascular invasion
Yano Br J Surg 2008
182 studies SN in colorectal cancer, 48 prospective, 33 in review 1794 patients Success rate 90%, sensitivity 70%, specificity 81% Heterogeneity of trials, one group (Saha/Bilchik) shows better results Importance of learning curve and patient selection
* (Bembenek Ann Surg 2007, Bilchik Arch Surg 2006, Saha Am J Surg 2006, Kelder/Braat Int J colorectal dis 2007, Kitagawa Dis Col Rectum 2002, Saha Ann Surg Oncol 2001)
Advanced tumour stage with overt nodal disease skip metastases Previous colorectal surgery High body mass index of patients More than one tumour Long interval between injection of dye and SN detection Too many surgeons performing few procedures Preoperative (chemo)-radiation rectal cancer
*Joosten Br J Surg 1999, Bertagnolli Ann Surg 2004, Read Dis Col Rectum 2005, Bembenek Surgery 2004, Braat Br J Surg 2005
Rectum: infraperitoneal location, bulky mesentery (submucosal injection) Pathologist: intact mesorectum to detect the circumferential margin Pre-operative (chemo) radiation alters lymphatic flow by obliteration of lymphatic channels
Possible solutions: No pre-operative (chemo) radiation no option in the Netherlands Use of radio active colloid and SN retrieval by pathologist after surgery
*Kitagawa Dis Col Rectum 2002, Saha Ann Surg Oncol 2001, Bilchik eur J Cancer 2002, Bembenek Surgery 2004, Braat Br J Surg 2005
No pre-operative radiation Use of radio active colloid 43 pts with rectal cancer, Sensitivity of SN procedure 92%, Specitivity 90% 10% of patients with lower rectal cancer showed lateral SNs
(Saha Ann Surg Oncol 2001, Bilchik eur J Cancer 2002)
USA
No pre-operative radiation in most cases Use of blue dye, in vivo and ex vivo SN detection by pathologist postoperatively 92 pts with rectal cancer , success rate 91% (failure associated with RT) No report on lateral nodes Sensitivity 92%, Specitivity 100%, Neg pred value 96% Upstaging 25%
48 pts, 37 pts pre-operative radiotherapy SN detection with radio active colloid, ex vivo 46/48 pts SN identified Sensitivity 44%, false negative 56% SN only correctly predicted nodal status in pts without radiation In 4 pts SN outside the mesorectum, 1 node positive
34 pts, all pre-operative radiotherapy SN detection with Patent blue dye, in vivo and ex vivo 26/34 pts SN identified Sensitivity 40%, false negative 60%, neg predictive value 73%
Additional effect: blue dye assists the pathologist in identifying (small) lymph nodes with or without metastases
2 yr follow up of 92 pts with stage II colon cancer and SN procedure: 30% upstaging IHC + PCR 12 recurrences (all 12 with micrometastases) No recurrences in patients with negative SN (p=0.002)
Detection of aberrant lymphatic drainage (2-10%) Blue staining of the lymph nodes which assists the pathologist in detecting more and smaller nodes and the right nodes Ultrastaging by IHC/PCR
Upstaging might lead to stadium migration: some of the patients with micrometastases in the current stage II group are actually stage III patients
Rectal cancer:
No SN procedure after pre-operative radiotherapy Without radiotherapy, the SN might be able to select patients for lateral lymphadenectomy in lower rectal cancer
Colon cancer:
Upstaging by detection of micrometastases seems important for survival Prospective randomized trial to evaluate the effect of the SN procedure on recurrence and survival in patients with stage I/II colon cancer