Radical Cholecystectomy.pptx

gall bladder cancer management

1. Radical Cholecystectomy Pushpa Lal Bhadel FCPS Resident KMH Department of General Surgery

2. Introduction Rare malignancy Aggressive tumor with poor prognosis Predominantly occurring in elderly

3. Epidemiology Manifested in 6 th -7 th decades of life 2-3 times common in women Ethnicity plays important role According to SEER incidence of GBC in US is 1-2/100,000 population 1 In Nepal 2 : 3.3% primary malignancy 1.4% incidental primary GBC 1 Rahman, R., Simoes , E. J., Schmaltz, C., Jackson, C. S., & Ibdah , J. A. (2017). Trend analysis and survival of primary gallbladder cancer in the United States: A 1973-2009 population-based study.  Cancer Medicine ,  6 (4), 874–880 . 2 Shrestha, R., Tiwari, M., Ranabhat , S. K., Aryal , G., Rauniyar , S. K., & Shrestha, H. G. (2010). Incidental gallbladder carcinoma: Value of routine histological examination of cholecystectomy specimens.  Nepal Medical College Journal: NMCJ ,  12 (2), 90–94

4. Fig: Incidence of gallbladder cancer worldwide

5. Etiology Prevailing theory: chronic inflammation with subsequent cellular proliferation Risk factors: Gallstones Choledochal cyst Primary sclerosing cholangitis (PSC) Anomalous Pancreaticobiliary Junction (APBJ) Old age Typhoid carrier/H. pylori infection Females Gall bladder polyp (>10mm) GB wall calcification/ Porcelain GB Exposure to carcinogens Drugs

6. Pathology Adenocarcinoma: 80-90% Papillary Nodular Tubular Squamous cell carcinoma Adenosquamous cell carcinoma Oat cell carcinoma Anaplastic carcinoma

7. Pattern of spread Via lymphatics Via venous drainage Direct invasion into liver parenchyma At the time of diagnosis: 25% localized to GB 35% regional node involvement/ extension into adjacent liver 40% distant metastasis

8. Clinical Presentation 90% originate from fundus or body: produce symptoms in advanced stage Early invasive GBC: asymptomatic or non-specific symptoms that mimics cholelithiasis or cholecystitis Symptomatic: RUQ pain, abdominal discomfort, nausea, vomiting, anorexia Advanced GBC: malaise, weight loss, jaundice, abdominal mass, ascites Palpable GB on physical examination: Courvoisier’s Sign

9. Diagnostic evaluation Ultrasound: Suspicious findings: Solitary or displaced stone, mural thickening or calcification, mass protruding into the lumen, fixed mass in GB, loss of interface between GB and liver, direct liver infiltration Overall accuracy limited Sensitivity 70-100% 1 1 Brunicardi , F., et al. (2014) Schwartz’s Principles of Surgery. 10th Edition, McGraw-Hill Education, New York

10. Computed Tomography (CT) scan: For pt. with US-detected GB lesion/ incidentally diagnosed GBC following simple cholecystectomy Sensitivity: 71%, specificity: 92% 1 CT findings: Polypoid mass protruding into the lumen/completely filling it, focal/diffuse thickening of GB wall, mass in GB fossa with GB being indiscernible, liver invasion, suspected nodal involvement, distant mets GBC complicated with simple cholecystitis: higher frequency of LN enlargement, more-extensive wall thickness, focal irregularity in wall thickness, less distention of GB 1 Bo, X., Chen, E., Wang, J., Nan, L., Xin, Y., Wang, C., Lu, Q., Rao, S., Pang, L., Li, M., Lu, P., Zhang, D., Liu, H., & Wang, Y. (2019). Diagnostic accuracy of imaging modalities in differentiating xanthogranulomatous cholecystitis from gallbladder cancer.  Annals of Translational Medicine ,  7 (22), 627. https://doi.org/10.21037/atm.2019.11.35

11. Features of advanced disease include: Intrahepatic biliary dilatation  Invasion of adjacent structures Lymphadenopathy Peritoneal carcinomatosis hepatic and other distant metastases

12. Magnetic Resonance Imaging (MRI): Reliable in staging of advanced GBC MRI + MRCP: sensitive in detection of obstructive jaundice, liver invasion and hepatic/LN metastasis Difficult to delineate invasion into duodenum or omental mets Sensitivity for hepatic invasion 100%, LN invasion 92% 1 1 Schwartz, L. H., Black, J., Fong, Y., Jarnagin , W., Blumgart , L., Gruen, D., Winston, C., & Panicek , D. M. (2002). Gallbladder carcinoma: Findings at MR imaging with MR cholangiopancreatography.  Journal of Computer Assisted Tomography ,  26 (3), 405–410

13. Endoscopic ultrasound (EUS): To access the depth of tumor invasion into the wall of GB To define LN involvement in porta hepatis and peripancreatic regions Means to obtain bile for cytologic analysis: 73% sensitivity for diagnosis of GBC 1 EUS guided FNA for FB mass Specificity: 92%, specificity 88% 2 2 Azuma, T., Yoshikawa, T., Araida , T., & Takasaki, K. (2001). Differential diagnosis of polypoid lesions of the gallbladder by endoscopic ultrasonography.  American Journal of Surgery ,  181 (1), 65–70 1 Mohandas, K. M., Swaroop, V. S., Gullar , S. U., Dave, U. R., Jagannath, P., & DeSouza , L. J. (1994). Diagnosis of malignant obstructive jaundice by bile cytology: Results improved by dilating the bile duct strictures.  Gastrointestinal Endoscopy ,  40 (2 Pt 1), 150–154

14. Laboratory studies: Non diagnostic Elevated liver enzymes: serum bilirubin, ALP Tumor markers: carcinoembryonic antigen (CEA) or carbohydrate antigen(CA) 19-9 For staging evaluation: Chest X-ray/CT PET-CT

15. Staging systems Modified Nevin System (Donohue et.al. 1990, Nevin et.al. 1976) Japanese Biliary Surgical Society System ( Onoyama et.al. 1995) AJCC/UICC TNM staging system ( Beahrs and Myers 1983)

16. Tumor, Node, Metastasis (TNM) staging 1 1 Zhu AX, Pawalik TM, Kooby DA, et al. Gallbladder. In: AJCC Cancer Staging Manual, 8th ed, Amin MB (Ed), AJCC, Chicago 2017. p.303

17. Management Resection remains the only potential for cure Simple cholecystectomy Radical (Extended) cholecystectomy Bile duct resection Hepatic resection Lymph node dissection Laparoscopic port site resection

18. Radical Cholecystectomy En bloc removal of gall bladder with a rim of at least 2 cm adjacent gall bladder bed Formal central liver resection (segments IVb and V) may be appropriate depending upon the location of tumor (fundus, body, neck) Laparoscopic vs open surgery? Wullstein , C., Woeste , G., Barkhausen , S., Gross, E., & Hopt , U. T. (2002). Do complications related to laparoscopic cholecystectomy influence the prognosis of gallbladder cancer?  Surgical Endoscopy ,  16 (5), 828–832 Matthews, J. B. (2010). Planned laparoscopic approach for early-stage gallbladder cancer : The glass is one-third full.  Archives of Surgery (Chicago, Ill.: 1960) ,  145 (2), 133

19. Extent of liver resection: wedge vs segment IVb/V

20. In some cased it involves resection of Entire liver lobe (hepatic lobectomy) Suprapancreatic segment of extrahepatic bile duct (bile duct resection) Regional LN dissection in an En bloc fashion. Main difference between this procedure and original radical cholecystectomy described by Glenn et.al compromise the extent of regional lymphadenectomy and presence or absence of bile duct resection. Fig. Extended" radical cholecystectomy for gallbladder cancer. The dashed line indicates the scope of wedge resection. The double-headed arrows indicate lines of division of the extrahepatic bile duct. The pale blue area indicates the extent of regional lymph node dissection

21. Bile duct resection Tumor extending into CBD or negative cystic duct margin (via frozen section) can’t be achieved: extrahepatic bile duct resection should be performed Reconstruction with Roux-en-Y hepaticojejunostomy Some recommends routine excision of extrahepatic bile duct as a mean of achieving more complete lymphadenectomy When ducts compromised during skeletonization of porta hepatis: resection and reconstruction is warranted

22. Fig. Roux-en-Y hepaticojejunostomy with b iliary stent placement to reduce stricture at the anastomosis

23. Inter aortocaval LN sampling Interaortocaval (16b1) LN involvement in GBC : sign of advanced disease with a dismal prognosis equivalent to that of distant metastasis CT indicator (size >10 mm and heterogeneous internal architecture) of 16b1 LN But positive predictive value is less That’s why detection of 16b1 LNs, intraoperative biopsy and frozen section analysis of these nodes have been proposed 1 1 Noji , T., Kondo, S., Hirano, S.  et al.  CT evaluation of paraaortic lymph node metastasis in patients with biliary cancer.  J Gastroenterol   40,  739–743 (2005)

24. Lymph node dissection Indicated whether or not bile duct resection is performed if GBC >T1a LN mets found in 35-80% with tumors invading perimuscular connective tissues(≥T2) 1 More reliable predictors of poor outcome after surgery 5-yr survival: 57% without vs 12% with LN metastases 2 Involves removal of all LN in porta hepatis and along hepaticoduodenal ligaments including those of cystic duct, CBD, hepatic artery and portal vein 1 Pilgrim, C. H. C., Usatoff , V., & Evans, P. (2009). Consideration of anatomical structures relevant to the surgical strategy for managing gallbladder carcinoma.  European Journal of Surgical Oncology: The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology ,  35 (11), 1131–1136. 2 Birnbaum, D. J., Viganò , L., Russolillo , N., Langella , S., Ferrero, A., & Capussotti , L. (2015). Lymph node metastases in patients undergoing surgery for a gallbladder cancer. Extension of the lymph node dissection and prognostic value of the lymph node ratio.  Annals of Surgical Oncology ,  22 (3), 811–818

25. Standard lymphadenectomy

26. Lymph node dissection cont. At least 6 LNs should be removed for proper staging 1 Number of metastatic LN and LN ratio are more prognostic than location of metastatic LN 1 Zhu AX, Pawlik TM, Kooby DA. et al. Gallbladder. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), Springer 2017. p.303

27. Hepatic resection Either margin-negative resection with at least 2cm non-anatomic wedge resection of GB fossa OR anatomic wedge resection of segment IVb and V 1 Tumors of fundus and body of GB: far from the inflow structures of liver Various resection margins proposed: ranging from 1-5 cm 2 No data to showing benefit for anatomic resection of segments IVb and V with localized diseases 3 Anatomic resection: reduces risk of bleeding and bile leakage 4 1 Blumgart LH. Surgery of the Liver, Biliary Tract and Pancreas, 4th edition, Saunders, Philadelphia 2007 2 Endo, I., Shimada, H., Takimoto , A., Fujii , Y., Miura, Y., Sugita, M., Morioka, D., Masunari, H., Tanaka, K., Sekido , H., & Togo, S. (2004). Microscopic liver metastasis: Prognostic factor for patients with pT2 gallbladder carcinoma.  World Journal of Surgery ,  28 (7), 692–696 3 Sicklick , J. K., & Choti , M. A. (2005). Controversies in the surgical management of cholangiocarcinoma and gallbladder cancer.  Seminars in Oncology ,  32 (6 Suppl 9), S112-117 4 Scheingraber , S., Justinger , C., Stremovskaia , T., Weinrich, M., Igna , D., & Schilling, M. K. (2007). The standardized surgical approach improves outcome of gallbladder cancer.  World Journal of Surgical Oncology ,  5 , 55

28. Hepatic resection cont. Veins from GB drain into middle hepatic vein via cholecysto -hepatic veins 1 Direct lymphatic drainage into liver has also been demonstrated 1 More aggressive surgery like extended right hepatectomy for tumor infiltration into segments IV, V and VII 1 Misra , M. C., & Guleria , S. (2006). Management of cancer gallbladder found as a surprise on a resected gallbladder specimen.  Journal of Surgical Oncology ,  93 (8), 690–698

29. Conclusion : Tumor biology and stage, rather than extent of resection, predict outcome after resection for gallbladder cancer. Major hepatic resections, including major hepatectomy and CBD excision, are appropriate when necessary to clear disease but are not mandatory in all cases.

30. Laparoscopic port site resection Laparoscopic manipulation doesn’t diminish the survival of patients with incidentally found GBC 1 Some recommend port site excision at the time of reexploration after lap cholecystectomy 2 Radical resection doesn’t require resection of previous port sites 3 Tumor found in previous port site is a marker for disseminated peritoneal disease Thus removal of port site will not be curative 4 1 Maker, A. V., Butte, J. M., Oxenberg , J., Kuk, D., Gonen , M., Fong, Y., Dematteo , R. P., D’Angelica , M. I., Allen, P. J., & Jarnagin , W. R. (2012). Is port site resection necessary in the surgical management of gallbladder cancer?  Annals of Surgical Oncology ,  19 (2), 409–417 2 Giuliante , F., Ardito , F., Vellone , M., Clemente, G., & Nuzzo, G. (2006). Port-sites excision for gallbladder cancer incidentally found after laparoscopic cholecystectomy.  American Journal of Surgery ,  191 (1), 114–116 3 Maker, A. V., Butte, J. M., Oxenberg , J., Kuk, D., Gonen , M., Fong, Y., Dematteo , R. P., D’Angelica , M. I., Allen, P. J., & Jarnagin , W. R. (2012). Is port site resection necessary in the surgical management of gallbladder cancer?  Annals of Surgical Oncology ,  19 (2), 409–417 4 Berger-Richardson, D., Chesney, T. R., Englesakis , M., Govindarajan, A., Cleary, S. P., & Swallow, C. J. (2017). Trends in port-site metastasis after laparoscopic resection of incidental gallbladder cancer: A systematic review.  Surgery ,  161 (3), 618–62

31. Surgery for Gall bladder cancer Accurate staging of the disease Proper patient selection & surgical planning Identifying patient who would or would not benefit from surgery Detect metastatic disease (US, CT, MRI, PET) Locoregionally advanced disease (resectability?/need for downstaging) Avoiding non-therapeutic laparotomy Staging laparoscopy Advanced extended laparoscopic staging

32. Unresectable disease Absolute contraindication to resection: Liver mets Peritoneal mets Malignant ascites Tumor involvement of paraaortic, paracaval, SMA and/or Celiac artery LN Extensive involvement of hepaticoduodenal ligament by tumor either directly or through LN involvement Encasement or occlusion of major vessels (common hepatic artery or main portal vein) by tumor

33. Unresectable disease cont. Relative contraindication to resection: Pre-operative jaundice in fundus based GBC Perihilar-type GBC arising from infundibulum or cystic duct

34. Identifies metastatic disease or other findings that contraindicate tumor resection 1 Recommended prior to laparotomy for all suspected or proven GBC >pT1b 2 Use of two ports avoid missing detectable lesions Staging laparoscopy 1 Shih, S. P., Schulick , R. D., Cameron, J. L., Lillemoe , K. D., Pitt, H. A., Choti , M. A., Campbell, K. A., Yeo, C. J., & Talamini , M. A. (2007). Gallbladder cancer: The role of laparoscopy and radical resection.  Annals of Surgery ,  245 (6), 893–901 2 Agarwal, A. K., Kalayarasan , R., Javed , A., Gupta, N., & Nag, H. H. (2013). The role of staging laparoscopy in primary gall bladder cancer--an analysis of 409 patients: A prospective study to evaluate the role of staging laparoscopy in the management of gallbladder cancer.  Annals of Surgery ,  258 (2), 318–323

35. Staging laparoscopy cont. A prospective study of primary GBC patients between May 2006 and December 2011 : Of the 409 primary GBC patients who underwent SL, 95 had disseminated disease [(surface liver metastasis (n = 29) and peritoneal deposits (n = 66)].  The overall yield of SL was 23.2% (95/409)

36. Staging laparoscopy cont. Discussion:  Disseminated disease is relatively uncommon in patients with IGBC and SL provides a very low yield. However, patients with poorly differentiated, T3 or positive-margin gallbladder tumors are at high risk for Disseminated Disease and targeting these patients may increase the yield of SL

37. Resectable disease Early T stage disease: tumors confined to the wall of GB ( ie , stage 0, I or II; Tis, T1 or T2) Tumors extending beyond the mucosa ( ie , T1a): better outcomes with more radical surgery 1 1 Sternby Eilard , M., Lundgren, L., Cahlin , C., Strandell , A., Svanberg , T., & Sandström , P. (2017). Surgical treatment for gallbladder cancer—A systematic literature review.  Scandinavian Journal of Gastroenterology ,  52 (5), 505–514

38. T1a: Tumors limited to lamina propria Cystic duct margin negative Simple cholecystectomy alone is adequate 1 Cure rate: 73-100% 1 Re-resection for T1a tumors doesn’t appear to provide an overall survival benefit 2 1 Wakai , T., Shirai, Y., Yokoyama, N., Nagakura , S., Watanabe, H., & Hatakeyama , K. (2001). Early gallbladder carcinoma does not warrant radical resection.  The British Journal of Surgery ,  88 (5), 675–678 2 You, D. D., Lee, H. G., Paik, K. Y., Heo , J. S., Choi, S. H., & Choi, D. W. (2008). What is an adequate extent of resection for T1 gallbladder cancers?  Annals of Surgery ,  247 (5), 835–838

39. T1b: Tumor invades muscular layer Optimal approach is controversial, Pt benefit from more radical approach Higher incidence of LN metastases compared to T1a (15% vs 2.5%) 1 High loco-regional recurrence 50-60% High rates of liver involvement 0-13% Median survival advantage >3 yrs : extended vs simple cholecystectomy 2 9.85 vs 6.42 years 1 de Aretxabala , X. A., Roa , I. S., Burgos, L. A., Araya, J. C., Villaseca, M. A., & Silva, J. A. (1997). Curative resection in potentially resectable tumours of the gallbladder.  The European Journal of Surgery = Acta Chirurgica ,  163 (6), 419–426 2 Abramson, M. A., Pandharipande , P., Ruan , D., Gold, J. S., & Whang, E. E. (2009). Radical resection for T1b gallbladder cancer: A decision analysis.  HPB: The Official Journal of the International Hepato Pancreato Biliary Association ,  11 (8), 656–663

40. Method : R etrospective cohort study from the National Cancer Data Base (2004-2012) with non-metastatic T1b GBC Conclusion:  <50% of the patients with a T1b GBC primary tumor undergo the recommended surgical treatment. Given that 15% of these patients have nodal metastasis and in light of the previously described benefits of adjuvant therapy for node positive GBC, failure to perform RC-RL risks incomplete staging and thus undertreatment for patients with T1b GBC.

41. T2: Invades the peri muscular connective tissue on the peritoneal side, without involvement of serosa Extended cholecystectomy is indicated 1 High chance of residual disease 40-76% High chance of liver 2 (10%) and LN 3 (30-60%) involvement High rates of local recurrence after simple cholecystectomy 1 Wright, B. E., Lee, C. C., Iddings, D. M., Kavanagh, M., & Bilchik , A. J. (2007). Management of T2 gallbladder cancer: Are practice patterns consistent with national recommendations?  American Journal of Surgery ,  194 (6), 820–825; discussion 825-826 3 Shimada, H., Endo, I., Togo, S., Nakano, A., Izumi, T., & Nakagawara , G. (1997). The role of lymph node dissection in the treatment of gallbladder carcinoma.  Cancer ,  79 (5), 892–899. https://doi.org/10.1002/(sici)1097-0142(19970301)79:5<892::aid-cncr4>3.0.co;2-e 2 Pawlik , T. M., Gleisner , A. L., Vigano, L., Kooby , D. A., Bauer, T. W., Frilling, A., Adams, R. B., Staley, C. A., Trindade, E. N., Schulick , R. D., Choti , M. A., & Capussotti , L. (2007). Incidence of finding residual disease for incidental gallbladder carcinoma: Implications for re-resection.  Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract ,  11 (11), 1478–1486; discussion 1486-1487

42. Subdivided depending on the invasion site into: T2a (peritoneal) T2b (hepatic) T2b has worse prognosis Extended cholecystectomy should be mandated in pt with T2b (hepatic) but not T2a (peritoneal) disease 1 This approach, however is not universally accepted Standard of care: extended cholecystectomy for all resectable T2 disease 2 1 Lee, W., Jeong , C.-Y., Jang, J. Y., Kim, Y. H., Roh , Y. H., Kim, K. W., Kang, S. H., Yoon, M. H., Seo , H. I., Yun, S. P., Park, J.-I., Jung, B.-H., Shin, D. H., Choi, Y. I., Moon, H. H., Chu, C. W., Ryu, J. H., Yang, K., Park, Y. M., & Hong, S.-C. (2017). Do hepatic-sided tumors require more extensive resection than peritoneal-sided tumors in patients with T2 gallbladder cancer? Results of a retrospective multicenter study.  Surgery ,  162 (3) 2 Kwon, W., Kim, H., Han, Y., Hwang, Y. J., Kim, S. G., Kwon, H. J., Vinuela , E., Járufe , N., Roa , J. C., Han, I. W., Heo , J. S., Choi, S.-H., Choi, D. W., Ahn , K. S., Kang, K. J., Lee, W., Jeong , C.-Y., Hong, S.-C., Troncoso , A. T., … Jang, J.-Y. (2020). Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: An international multicentre study.  The British Journal of Surgery ,  107 (10), 1334–1343

43. Survival in patient with T2 lesion is related to the number of LN removed 1 5 yr survival is 24-40% without resection and may approach to 80-100 after re-resection 2 1 Downing, S. R., Cadogan, K.-A., Ortega, G., Oyetunji , T. A., Siram , S. M., Chang, D. C., Ahuja, N., Leffall , L. D., & Frederick, W. A. I. (2011). Early-stage gallbladder cancer in the Surveillance, Epidemiology, and End Results database: Effect of extended surgical resection.  Archives of Surgery (Chicago, Ill.: 1960) ,  146 (6), 734–738 2 Toyonaga , T., Chijiiwa , K., Nakano, K., Noshiro , H., Yamaguchi, K., Sada , M., Terasaka , R., Konomi, K., Nishikata , F., & Tanaka, M. (2003). Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma.  World Journal of Surgery ,  27 (3), 266–271

44. Locally advanced and node positive disease In past because of overall poor prognosis: surgeons were reluctant to perform surgery 1 Support for radical surgery with reports indicating long term survival in pt with T3 and T4 tumors, 15 to 63% and 7 to 25% of pt respectively 2 1 Cubertafond , P., Mathonnet , M., Gainant , A., & Launois , B. (1999). Radical surgery for gallbladder cancer. Results of the french surgical association survey.  Hepato-Gastroenterology ,  46 (27), 1567–1571 2 Kayahara , M., & Nagakawa , T. (2007). Recent trends of gallbladder cancer in Japan: An analysis of 4,770 patients.  Cancer ,  110 (3), 572–580

45. Some groups advocate even more extensive resection: Hepatectomy, pancreaticoduodenectomy, colectomy and nephrectomy Medial survival of 17mths, 2% mortality rate 1 But morbidity and mortality rates are high (48 to 54% and 15 to 18% respectively) Study of 79 major hepatectomies had longer survival 32 mths as compared to 10 mths for major hepatectomies + pancreaticoduodenectomy 2 1 Dixon, E., Vollmer, C. M., Sahajpal , A., Cattral , M., Grant, D., Doig, C., Hemming, A., Taylor, B., Langer, B., Greig, P., & Gallinger , S. (2005). An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: A 12-year study at a North American Center.  Annals of Surgery ,  241 (3), 385–394 2 Mizuno, T., Ebata, T., Yokoyama, Y., Igami , T., Yamaguchi, J., Onoe , S., Watanabe, N., Ando, M., & Nagino , M. (2019). Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer.  The British Journal of Surgery ,  106 (5), 626–635

46. T3: Tumor invades through serosa Extended cholecystectomy en bloc with involved adjacent organ Conclusion : Tumor biology and stage, rather than extent of resection, predict outcome after resection for gallbladder cancer. Major hepatic resections, including major hepatectomy and CBD excision, are appropriate when necessary to clear disease but are not mandatory in all cases

47. T4: Invades main portal vein, hepatic artery and adjacent extrahepatic organs Generally locally unresectable Curative resection in selected patient with stage IVa disease (T4, N0-1,M0)

48. Node positive: Tumor involvement of locoregional LN: 5-yr survival rate - 28-60% with radical resection 1 Radical lymphadenectomy results are less favorable of nodal disease beyond hepatoduodenal ligament, posterosuperior pancreaticoduodenal area and along common hepatic artery 1 FNA + ve tumors: surgery done for palliation of specific problems 1 Chijiiwa , K., Noshiro , H., Nakano, K., Okido , M., Sugitani , A., Yamaguchi, K., & Tanaka, M. (2000). Role of surgery for gallbladder carcinoma with special reference to lymph node metastasis and stage using western and Japanese classification systems.  World Journal of Surgery ,  24 (10), 1271–1276; discussion 1277

49. Managing incidental GBC found on pathology Incidental GC: 0.25-1.5% of pt undergoing lap chole 1 Should undergo staging evaluation with imaging modalities Management depends upon the disease extent (T stage) If the T stage of resected, incidental GBC is T1b, T2 or T3: surgical reeploration and re-resection 1 Duffy, A., Capanu , M., Abou-Alfa, G. K., Huitzil , D., Jarnagin , W., Fong, Y., D’Angelica , M., Dematteo , R. P., Blumgart , L. H., & O’Reilly, E. M. (2008). Gallbladder cancer ( Gbc ): 10-year experience at memorial sloan-kettering cancer centre ( Mskcc ).  Journal of Surgical Oncology ,  98 (7), 485–489

50. Optimal timing of re-resection: Reoperations between 4 th -8 th week from original cholecystectomy had better overall survival 1 4 weeks: 23.7 mths , 8 weeks: 26.6 mths Due to reduced inflammation and full appreciation of subclinical disease (compared with reoperating <4 week) but does not allow too much time for disease dissemination 1 Ethun , C. G., Postlewait , L. M., Le, N., Pawlik , T. M., Buettner, S., Poultsides , G., Tran, T., Idrees, K., Isom, C. A., Fields, R. C., Jin , L. X., Weber, S. M., Salem, A., Martin, R. C. G., Scoggins, C., Shen, P., Mogal , H. D., Schmidt, C., Beal, E., … Maithel , S. K. (2017). Association of optimal time interval to re-resection for incidental gallbladder cancer with overall survival: A multi-institution analysis from the us extrahepatic biliary malignancy consortium.  JAMA Surgery ,  152 (2), 143–149

51. Managing incidental GBC intraoperatively Surgeon should maintain high index of suspicion in pt with risk factors If obvious malignant lesion encountered: best not to sample the lesion laparoscopically to reduce the hazard of seeding Procedure should be converted to open resection, of resection will be undertaken Completing the cholecystectomy and obtain frozen section, if positive: extended cholecystectomy

52. To compare patients with gallbladder cancer presenting for therapy with and without prior operation elsewhere to determine if an initial noncurative procedure alters outcome Mortality, complication, and long-term survival were the same

53. The scoring model to predict IGBC includes age, female gender, previous cholecystitis, and either jaundice or acute cholecystitis The scoring system was applied to three risk-groups, based on the risk of having IGBC, eg. the high-risk group (>8 points) included 7878 patients, with 154 observed and 148 expected IGBC cases.

54. Bile spillage Association with incomplete resection and systemic recurrence When GB cancer is suspected during LC conversion to open surgery for preventing bile spillage and achieving curative resection should be considered

55. Laparoscopic radical surgery Traditionally, Laparoscopic surgery not routinely recommended in non-incidental setting Recent studies suggest equivalent outcomes between laparoscopic and open approaches Robotic-assisted procedures have also been described and are carried out

56. Adjuvant therapy Despite conflicting data, limited level I data Currently, Gemcitabine-based regimens, often combining with platinum agent: common choice for treating GBC Gemcitabine shown to improve median overall survival (9.5 months) 1 Japanese multi-institutional trial: randomized resection f/b adjuvant mitomycin and 5-FU vs resection alone 2 5-yr survival 20.3% vs 11.6% 1 Sharma, A., Dwary , A. D., Mohanti , B. K., Deo, S. V., Pal, S., Sreenivas, V., Raina, V., Shukla, N. K., Thulkar , S., Garg, P., & Chaudhary, S. P. (2010). Best supportive care compared with chemotherapy for unresectable gall bladder cancer: A randomized controlled study.  Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology ,  28 (30), 4581–4586 2 Takada, T., Amano, H., Yasuda, H., Nimura , Y., Matsushiro , T., Kato, H., Nagakawa , T., Nakayama, T., & Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract. (2002). Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma.  Cancer ,  95 (8), 1685–1695

57. Most recently, Phase II trial: combination of Gemcitabine, Capecitabine and radiation therapy in pt with extrahepatic biliary tract and GBC showed promising results 1 1 Ben-Josef, E., Guthrie, K. A., El- Khoueiry , A. B., Corless , C. L., Zalupski , M. M., Lowy, A. M., Thomas, C. R., Alberts, S. R., Dawson, L. A., Micetich , K. C., Thomas, M. B., Siegel, A. B., & Blanke , C. D. (2015). Swog s0809: A phase ii intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma.  Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology ,  33 (24), 2617–2622

58. Neoadjuvant therapy Provide opportunity to determine biologically aggressive tumors who may not benefit from extensive operation Small case series suggest: Gemcitabine-Platinum based combinations have some role 1 Recent study from MD Anderson Cancer Center: retrospective review of their GBC resected with wide 1-cm negative margin and received either neoadjuvant or adjuvant therapy: 5-yr survival 50.6% 1 Sirohi , B., Rastogi, S., Singh, A., Sheth , V., Dawood, S., Talole , S., Ramadwar , M., Kulkarni, S., & Shrikhande , S. V. (2015). Use of gemcitabine-platinum in Indian patients with advanced gall bladder cancer.  Future Oncology (London, England) ,  11 (8), 1191–1200

59. Adjuvant therapy showed not improvement in survival, and neoadjuvant treatment had only served to significantly delay time to operation

60. Palliative procedures Palliation for jaundice, upper abdominal pain and symptoms of biliary obstruction Methods: Simple cholecystectomy Endoscopic or percutaneous biliary drainage Endoscopic stenting or intestinal bypass Biliary bypass: Patient who can tolerate surgery Recurrent obstruction Segment II cholangiojejunostomy and staying away from the hepatoduodenal ligament, the most common site of disease progression, successfully palliated the majority of patients 1 1 Kapoor, V. K., Pradeep, R., Haribhakti , S. P., Singh, V., Sikora, S. S., Saxena, R., & Kaushik, S. P. (1996). Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the gallbladder.  The British Journal of Surgery ,  83 (12), 1709–1711

61. Prognosis 5 year survival of all pt with GB cancer: <5% Median survival of 6 mths T1 treated with cholecystectomy: 85%-100%, 5 year survival T2 treated with extended cholecystectomy vs cholecystectomy: >70% vs 25%-40% Advanced disease with resectable GB: 5 year survival of 20% Median survival of pt with distant mets : 1-3mths

62. Prognosis cont.. Non-specific symptoms and advanced stage of disease at presentation: poor outcomes 5-yr survival rate: 5-12% Recurrence after resection : commonly Liver or celiac/retro pancreatic nodes Prognosis for recurrent disease: poor Death commonly d/t biliary sepsis or liver failure

63. Reference Schwartz’s Principle of surgery, 10 th edition Bailey short practice of surgery, 27 th edition Sabiston textbook of surgery, 20 th edition https://www.uptodate.com/contents/gallbladder-cancer-epidemiology-risk-factors-clinical-features-and-diagnosis?search=gallbladder%20cancer&source=search_result&selectedTitle=1~71&usage_type=default&display_rank=1#H17 Internet sources

64. Thank-you