Carcinoma gall bladder

kathmandu medical college, department of surgery

1. Carcinoma Gall bladder

2. Objectives: Epidemiology Etiology Pathology and pathogenesis Clinical presentation diagnosis Treatment Prognosis

3. Epidemiology 6500 cases annually (USA) 5 th most common cause of GI malignancy (USA) Incidence increases with age 2-6 times more common in female

4. Ca GB - distribution

5. Risk factors Cholelithiasis 75-98% of all patient with Ca GB Cholesterols type stones Old age Female Anomalous pancreaticobiliary duct junction Typhoid carriers- chronic inflammation Others- IBD

6. The risk of developing gallbladder carcinoma increases directly with increasing gallstone size  Relative Risk =2.4 with stone size 2- 2.9cm diameter Relative risk 10.1 with >3cm diameter stones

7. Lahmar A, Abid SB, Arfa MN, Bayar R, Khalfallah MT, Mzabi-Regaya S. Metachronous cancer of gallbladder and pancreas with pancreatobiliary maljunction .  World Journal of Gastrointestinal Surgery . 2010;2(4):143-146. doi:10.4240/wjgs.v2.i4.143. Anomalous pancreaticobiliary duct junction with an incidence of 3.2% in patients undergoing ERCP or operative Cholangiopancreatography

8. Refluxed proteolytic pancreatic enzymes are activated in the biliary tract and may induce biliary tract carcinoma The reflux of bile may activate pancreatic enzymes which may cause chronic inflammation and metaplastic epithelial change in the pancreatic duct and pancreatic cancer may eventually develop

9. Etiology Gall stones and chronic inflammation 3.3 to 3% among patients with GSD Porcelain GB (10-25%) Helicobacter bilis and Helicobacter pylori (about six fold higher risk) Chemicals  methyldopa,oral contraceptives, isoniazid , and occupational exposure in the rubber

10. Anatomic consideration The location of the primary tumor within the gallbladder and the proximity of the portal vein, hepatic artery, and bile duct are all important factors in the surgical management of this tumor

11. The gallbladder is attached to segments IVb and V of the liver and these segments are involved early in tumors of the fundus and body of the gallbladder-  limited segmental resection often possible

12. Tumors of the infundibulum or cystic duct readily obstruct the common bile duct and may involve the portal vein. As with cholangiocarcinoma the tumor may be unresectable early in its course-- tumor of this region require extended liver resections due to proximity to portal pedicles

13. Pathology GB epithelium progresses from dysplasia to carcinoma in situ to invasive carcinoma Area of dysplasia and carcinoma in situ is often missed in routine cholecystectomy specimens as there are no associated gross characteristics that would target an area for histological sections Carcinoma in situ may appear within the Rokitansky aschoff sinuses and often mistaken for invasive carcinoma

14. Rate of progression of precursor lesions to invasive carcinoma has estimated around 15 years

15. Gross

16. Gross morphology Difficult to diffrentiate grossly from chronic cholecystitis at early stages and are often found incidentally on pathologic sections 60% - fundus 30% body 10% neck

17. Tumor arising from neck and hartmanns pouch may infiltrate the cystic duct and common bile duct make it clinically indistinguishable form hilar bile ducts tumor

18. Infiltrative- m/c Nodular Combined nodular- infiltrative- m/c Papillary Combined papillary- infiltrative

19. Infiltrative tumors cause thickening and indurations of GB wall and extending to entire GB Spreads in the subserosal plane w hich is the same as the surgical plane used for routine cholecystectomy  if tumor unrecognized during surgery leads to regional dissemination Becomes more advanced if infiltrates liver

20. Nodular type Early invasion through GB wall into liver or neighboring structures Easier to control surgically than infiltrative whose margins are less defined

21. Papillary ca exhibit a polypoid or cauliflower like appearance Better prognosis May be larger filling the lumen but with minimal invasion

22. Histopathological grading G1- well differentiated G3- undifferentiated Majority of patient present with G3 poorly differentiated tumors

23. Tumor bilogy Multiple genetic changes P53 and k- ras gene mutation

24. Pattern of spread Along peritoneal cavity Along needle biopsy sites Laparoscopic port sites

25. direct extension to liver and other adjacent organs Gall bladder has thin wall, narrow lamina propia , and single muscle layer Once penetrates to thin muscle layer has access to major lymphatic and vascular channels

26. tumor penetration into or through the muscularis has prognostic implications because the lymphatic drainage of the gallbladder lies in the layer between the muscle and the serosa . Also, most simple cholecystectomies for gallstone leave the serosa on the liver side because the subserosal plane is the easiest for dissection. Thus, simple cholecystectomies performed for unsuspected gallbladder cancer is likely to leave a positive margin for any tumor that penetrates the muscle layer

27. Autospy 94.4 % lymphatic mets 64 .% hematogenous dissemination Hematogenous form small veins extensding directly from gall bladder to portal venous system of GB fossa leading to segment IV and V of liver or via larger veins to portal venous branch of segment V and VIII

28. 1 2 3

29. 1-pericholedochal, nodes along the common bile duct 2- cystic duct, node(s) along the cystic duct 3-retroportal, nodes posterior to the portal vein and cephalad to the uncinate process 4-posterior superior pancreaticoduodenal , nodes on the posterosuperior aspect of the head of the pancreas

30. 5-hepatic artery, nodes along the common or proper hepatic artery 6-right celiac, nodes located right of the celiac axis and posterior to the common hepatic artery 7-hilar, nodes within the porta hepatis

31. Radiologic investigation Discontinious GB mucosa Echogenic mucosa Submucosal echolucency Inhomogenous mass replacing all or part of GB Diffuse thickening of GB wall Lypmh nodes- a soft tissue mass with AP diameter of atleast 10mm showing ring like heterogenous enhancement ( 89% accuracy) Positive LN may alter surgeons decisions to operate or change operative approach

32. MRCP More detail information than CT sccan and Usg Angiography Portal vein and hepatic artery encasement avoids unneccesay laparotomy EUS Peripancreatic and periportal adenotpathy Needle bipdy can be performed

33. Endoscopic and percutaneous cholangiographs GB cancer with obstructive jaundice- direct invasion or compression of CHD or by pericholedochal LN Intraheptic bile ducts obstruction. High ALP Planning of palliative managemt of Gall bladder carcinoma Also indicated in atypical cases with vague sypmtoms and abnormal lft where other imaging modalities have not yeilded diagnosis Stricturing , distortion or nonfiling of bile ducts draining segment IV and V with no effects on other segmental ducts

34. Biliary colic or chronic cholecystitis , elderly patients with atypical symptoms, suspicious lab findings ( anemia, hypoalbunemnia or abnormal LFT) USG- mnass , abnormal mucosal finnding , or segmental duct dilatation CT scan Lab or radiologic investigation shows evidence for ductal obstruction MRCP , ERCP or PTC Advanced mass encroaching on the porta hepatis  duplex USG or arteriography

35. Preop pathologic diagnosis Suscpicious mass- pre op biopsy contoversial Cholec ( ystectomy as diagnositic biopsy unaccesptale ERCP and bile cytology (73% sensitivity) Percutaneous FNAC- mass not considered for surgical resection ( 88% accuracy) Percutaneous core needle biospy if FNAC fails as high chance of needle tract seeding

36. staging Modified Nevin system ( Donohue et.a l 1990, Nevin et. al 1976) Japanese Biliary Surgical Society system ( Onoyama et al 1995) AJCC/UICC TNM staging system ( Beahrs and Myers 1983)

37. management Stage O and Stage I ( Tis, T1a – Ca invades lamina propia but don’t extend to muscularis ) frequently detected on pathological examination Imaging based staging Watch cholecystectomy specimen to ensure negative margin

38. Margin postive No evidence of residual or metastatic GB ca But cystic duct margin positive Rexploration with CBD excision , regional lymphadenectomy and HJ Margin negative,negative imaging No further surgery

39. Stage T1b ( cancer that invases the muscularis but don’t extend to perimusccular connective tissue T1 b cancer treat same as T2 Ca GB

40. Stage II ( T2NOMO) T2- cancer invasion into perimuscular connectivetissue of GB regional LN mets - 28-63% Rexploration with liver resection and regional lymphadenectomy of hepatoduodenal ligament

41. Preoperative T2 suscpicious staging In no contraindication Proceed for exploration with en bloc resection of GB and adjacent liver to depth of at least 2 cm with regional lymphadenectomy of hepatoduodenal ligament Non anatomic Anatomic segment 4b, 5 resection – less bleeding

42. Stage III T3 lesions ( locally advanced cancers that perforate the GB serosa or directly invade the liver and/ or one adjacent organ and T1-T3 lesions associated with regional LN mets

43. Stage III Careful planning,individualized Liver invasion- hepatic resection seg 4b and 5 Trisegmentectomy if GB foss bridges both right and left hepatic lobes Enbloc resection of hepatic flexure of colon Long term survival- 15-63%

44. Stage IV IV A-Invasion to main portal vein, common hepatic artery, multiple extrahepatic organs Stage IVB N2 and or distance mets Uresectable Main portal vein, CHA if reseccted – confers morbidity and mortality ares

45. Adjuvant therapies Adjuvant chemoradiotherapy after resection External beam or intraoperative radiation therapy alone or in combination with 5FU- decreasse local recurrence Data inadequate

46. palliation Goal- relief pain, manifestation of biliary obstruction ( pruritis and cholangitis) and bowel obstruction Endscopic stenting than surgical bypass in weeks to month survival Palliative radiotherapy Regional intra- arterial chemotherapy andchemoradiotherapy Gemcitabine plus cisplantin

47. outcome Five year survival % T1N0 39 T2N0 15 T3N0 12

48. T1- 85-100% with radical resection- T2 80-90% T3 15-63% T4 2-25%

49. Radical resection of node positive- 60% 5 year survival

50. Morbidity and mortality Morbidity--5-54% Mortality- 0-21% More the extensive dissection more morbidity and mortalitiy rates

51. CT GB cancer protocol Dual phase contrast – arterial and venous