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Gall bladder carcinoma
- 1. Gall Bladder Carcinoma Presenter- Dr.Pooja Pandey PGJR-2 Moderator-Dr. S.P.Sharma Ass.Professor Department of General Surgery
- 2. Gall Bladder Carcinoma Learning Objective • Introduction • Epidemiology • Cause • Clinical picture • Investigation • TNM Classification • Treatment • Survival • References
- 3. Gall Bladder Carcinoma Introduction • Aggressive malignant disease. • Extremely poor prognosis. • No specific presenting symptoms. • High proportion of patients - advanced disease. • Earlier stage disease- a more aggressive surgical approach.
- 4. Gall Bladder Carcinoma Epidemiology Incidence • 6th and 7th decades of life • 2-3 F>M • Ethnicity –highest incidence in India and Pakistan. • Worldwide, the highest incidence rates (up to 8.0 / 100,000 in men and 22 / 100,000 in women) occur among populations in the Indian subcontinent. • Among North American populations , Native Americans and immigrants from Latin America have the highest rates.
- 5. Gall Bladder Carcinoma Cause • Chronic inflammation with subsequent cellular proliferation. • Risk factor – cholelithiasis (7times,90%) • 3% of gall stone with cholecystitis • Relative risk- less –size <2cm,2-3cm • It is 10 or more with >3cm • Xanthogranulomatous cholecystitis.
- 6. Gall Bladder Carcinoma Cause • Porcelain gall bladder (25%) and 90% of them are inoperable tumours. • Gallbladder polyp > 10 mm(1cm), >3in no, adenomatous polyp. • Other risk factors – choledochal cysts • Cholesteroses of gallbladder • Primary Sclerosing Cholangitis .
- 7. Gall Bladder Carcinoma Cause • Anomalous pancreaticobiliary duct junction (APBDJ )(20%) • Chronic typhoid carriers, Inflammatory bowel disease, Hepatitis B and Hepatitis C virus infection. • Nitrosamines • Carcinogen (radon)
- 8. Gall Bladder Carcinoma Types • Gross Types of Carcinoma Gallbladder • Polypoid /papillary—better prognosis. • Scirrhous /nodular. • Proliferative/infiltrative.
- 9. Gall Bladder Carcinoma Pathology and staging • Microscopy • Commonly - adenocarcinoma (90%); occasionally squamous cell carcinoma, small cell carcinoma ,lymphoma , sarcoma , adenosquamous or carcinoid tumor . • 25% show only localized disease; 35% have lymph node spread; 40% have distant spread at the time of first diagnosis.
- 10. Gall Bladder Carcinoma Pathology and staging contd.. • Dysplasia to carcinoma in situ to invasive carcinoma. • Altered genes include p53, k-ras, p16ink4a, and erbb2/her2. • Papillary subtype-indolent course , limited to gall bladder wall , better prognosis . • Most gallbladder carcinomas- systemic disease at the time of presentation, with 35% nodal disease and 40% distant metastases.
- 11. Gall Bladder Carcinoma Pathology and staging contd… • Adenomas -high prevalence β-catenin mutations. • Dysplastic lesions and cancers associated with APBD - high prevalence of K- ras mutations and a low prevalence of β-catenin mutations. • p53 and P16INK4A mutations are not seen in adenomas or dysplastic lesions, and thus appear to be later events in gallbladder carcinogenesis
- 12. Gall Bladder Carcinoma Pathology and staging contd.. • Draining nodal basin -hepatoduodenal ligament periaortic nodes near the celiac axis or pancreaticoduodenal nodes around the superior mesenteric artery. • Direct spread to liver (segment IV and V), bile duct, duodenum, colon and kidney. • Blood spread—to liver, lungs and bones. • Perineural spread • Transperitoneal spread.
- 13. Gall Bladder Carcinoma Staging Nevin’s staging: Stage I – Intramural Stage II – Spread to muscularis propria Stage III – Spread to serosa Stage IV – Spread to cystic lymph node of Lund Stage V – Direct spread to adjacent organs/metastases
- 14. Gall Bladder Carcinoma Staging • AJCC 8th Edition
- 17. Gall Bladder Carcinoma Clinical presentation • Location - Fundus and body of gall bladder • Acute cholecystitis to chronic cholecystitis features • Weight loss • Jaundice • Abdominal mass • Chronic epigastric pain • Early satiety • Fullness • Hepatomegaly • Ascites
- 18. Gall Bladder Carcinoma Three clinical presentations – • 1. Clinically obvious type - pain, obstructive jaundice, mass. • 2. Early GB cancer mimics GB stone disease. • 3. Atypical as unusual features
- 19. Gall Bladder Carcinoma Investigations • Ultrasound abdomen. • CT abdomen to see operability. • US-guided FNAC. • Liver function tests. • MRCP. • Laparoscopy. • CA 19-9 is elevated in 80% of cases
- 20. Gall Bladder Carcinoma Investigation contd… • Ultrasound of abdomen-irregularly shaped lesion in the subhepatic space, heterogeneous mass in the gallbladder lumen, and asymmetrically thickened gallbladder wall . • Polyp larger than 10 mm should raise the suspicion of gallbladder cancer.
- 21. Gall Bladder Carcinoma Investigation contd.. • CT abdomen- staging and treatment • Peritoneal metastases, • Hepatic parenchymal metastases, • Lymphadenopathy, • And adjacent vascular involvement . • Triphasic CT can be used to identify Hepatic arterial or portal venous involvement. • Percutaneous tissue diagnosis.
- 22. Gall Bladder Carcinoma Treatment • Resection - remains the only potential for cure. • Patients with gallbladder cancer can be divided into four • Specific subgroups of presentation:- Patients with an incidental polyp on imaging, Patients with an incidental finding of gallbladder cancer at the time of or after cholecystectomy, Patients suspected of having gallbladder cancer preoperatively, and Patients with advanced disease at presentation.
- 23. Gall Bladder Carcinoma Treatment • Gallbladder polyp- > 10 mm-Open cholecystectomy laparoscopic - may convert a potentially curable disease into an incurable one. • Gallbladder cancer after cholecystectomy- • Depends on depth of penetration of the gallbladder wall and surgical margins. • T1a (lamina propria)- cholecystectomy (nodal disease<3%) • T1b-(muscularis,no CT )- cholecystectomy as long as margins are –ve • T1b (with perineural ,lymphatic and vascular invasion )-Extended cholecystectomy (Ro resection ) • Port site recurrence- excision of all port site
- 25. Gall Bladder Carcinoma Treatment • Gallbladder cancer after cholecystectomy- • T2 lesions-muscularis &<= serosa -radical cholecystectomy. • Standard cholecystectomy alone is not done - 40% of these patients have lymph node metastases and up to 25% have positive margins. • Gallbladder cancer is generally unresponsive to other therapies, the presence of any residual disease after operative intervention predicts poor outcome.
- 26. Gall Bladder Carcinoma Treatment • Patients suspected of having gallbladder cancer preoperatively. • Resectable cases without metastasis- open cholecystectomy • Unresectable - diagnostic laparoscopy -to identify small volume peritoneal or hepatic metastases that would preclude a resection, thereby avoiding an unnecessary operation.
- 27. Gall Bladder Carcinoma Treatment • Patients suspected of having gallbladder cancer preoperatively. • Palliative • T3and T4- Radical resection -segments IVB and V but more often requires a central hepatectomy, including all of segments IV, V, and VIII. • For Ro-Direct extension of tumor into adjacent structures such as the hepatic flexure is not a contraindication to resection as long as negative margins can be obtained. • Debulking without possibility of complete resection has no role in the management of gallbladder cancer.
- 28. Gall Bladder Carcinoma Radical resection
- 30. Gall Bladder Carcinoma Treatment • Patients with advanced disease at presentation(unresctable and metastatic) • Advanced Biliary Cancer (ABC)-02 trial, 2010 - locally advanced or metastatic biliary tract cancer (of whom ~36% had gallbladder cancer) demonstrated that the combination of gemcitabine + cisplatin (11.7months) is associated with improved overall and progression-free survival compared to gemcitabine alone(8.1months) • Pembrolizumab is now approved for the treatment of patients with all metastatic and unresectable solid tumors having defective mismatch repair who have progressed through prior therapy and for whom there are no satisfactory treatment alternatives.
- 31. Gall Bladder Carcinoma Treatment • Patients with advanced disease at presentation. • Goal of therapy - palliation of symptoms. • Jaundice – Endoscopic biliary stent and self expanding endobiliary metal stent. •
- 32. Gall Bladder Carcinoma Treatment • Patients with advanced disease at presentation. • Pain- oral narcotics ,parenteral opioids and Percutaneous neurolysis of the celiac ganglion. • Intestinal obstruction-usually gastric outlet obstruction from local extension of tumor - an endoscopic duodenal wall stent.
- 33. Gall Bladder Carcinoma Adjuvant therapy • Neither chemotherapy nor radiation therapy - survival benefit. • External beam or intraoperative radiation therapy alone or in combination with 5- flourouracil (5-fu) has been associated with diminished rates of local recurrence. • Recently results, of the phase iii multicenter BILCAP trial from the United Kingdom, were reported. • Subgroup analysis from an older phase iii trial adjuvant treatment with fluorouracil and mitomycin c or observation showed improved survival with adjuvant treatment for patients with gallbladder cancer but not cholangiocarcinoma.
- 34. Gall Bladder Carcinoma Survival • Dependent on the stage of disease at presentation and whether surgical resection is performed. • T1a &T1b- excellent prognosis. • T2 lesions depends on nodal status, and radical resection improves 5-year survival from approximately 20% to >60%.
- 35. Gall Bladder Carcinoma Survival contd … • 5-year survival rates for patients with T1N0, T2N0, and T3N0 (or no depositive) disease are 39%, 15%, and 5%, respectively. • The 5-year survival of patients with T3 tumors is < 20%, and T4 lesions –months • Metastatic disease at presentation - median survival of 13 months.
- 36. Gall Bladder Carcinoma References • Sabiston text book of surgery 20th edition pg no-1512-1514. • SRB manual of surgery 5th edition pg no 659-660 • Maingot’s abdominal operation 13th edition pg no 2989-3009. • Bailey & Love’s short practice of surgery ,27th edition ,volume 2, pg no 1209-1211 • Pandey M, Shukla VK. Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. Eur J Cancer Prevent. Aug 2003; 12(4):269-272. • Elnemr A, Ohta T, Kayahara M, et al. Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer. Hepatogastroenterology. Mar-Apr 2001;48(38):382-386.
- 37. Gall Bladder Carcinoma References • Primrose JN, Fox R, Palmer DH et al. Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. Journal of Clinical Oncology 35, no. 15_suppl (May 20 2017) 4006-4006. • Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer. Oct 15 2002;95(8):1685-95. • Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. Apr 8 2010;362(14): 1273- 1281. • Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. Jul 28 2017; 357(6349):409-413.
- 38. Gall Bladder Carcinoma Thank You!
Editor's Notes
- entities that may also cause inflammation in the gallbladder wall, such as APBJ, choledochal cysts, and PSC. Extensive calcification of the wall of the gallbladder can cause a brittle gallbladder wall, leading to what is termed porcelain gallbladder, less than 10% of patients with porcelain gallbladder.
- APBDJ-a long common channel, formed by an abnormally proximal junction between the pancreatic and common bile ducts (CBDs), and elevated sphincter of Oddi pressures create a predisposition to reflux pancreatic exocrine secretions into the bile ducts.
- APBDJ-a long common channel, formed by an abnormally proximal junction between the pancreatic and common bile ducts (CBDs), and elevated sphincter of Oddi pressures create a predisposition to reflux pancreatic exocrine secretions into the bile ducts.
- Papillary cancers tend to grow within the gallbladder lumen and are less likely to invade the liver or to metastasize to lymph nodes; they are associated with the best prognosis. Infiltrative or nodular cancers have a more diffuse pattern of growth that is difficult to recognize on imaging studies. These lesions are more likely to have invaded the liver and to have metastasized to lymph nodes by the time of diagnosis.
- venous drainage of the gallbladder includes direct venous tributaries into the liver parenchyma, these tumors may spread directly into segment IV of the liver. Transperitoneal spread is also common and can progress to carcinomatosis
- Symptoms of acute cholecystitis, with obstruction of the neck of the gallbladder, may portend a better prognosis because patients with these symptoms may present with earlier stages of disease. Weight loss, jaundice, or an abdominal mass is associated with later stages of disease. Some patients describe symptoms of chronic cholecystitis in which the pain has recently changed in quality or frequency. Other common symptoms include chronic epigastric pain, early satiety, and a sense of fullness.
- Pain in right hypochondrium, mass in right upper abdomen which is hard and nontender.
- EUS, EUS guided tissue biopsy
- In the setting of unresectability (portal vein encasement or extensive hepatic involvement) or incurability (hepatic or peritoneal metastases), percutaneous methods for confirmatory tissue diagnosis should be used PET is more sensitive than CT for the detection of distant metastases, and therefore alters management in a significant fraction of cases when used.12–14 PET is less useful in differentiating benign versus malignant disease, and therefore is limited in its ability to differentiate between residual disease and post-surgical changes after cholecystectomy. While some favor the routine use of PET, others favor using PET selectively to further evaluate indeterminate findings on CT or MRI.
- Lap is not performed due to risk of GB perforation and tumor spillage T1a-carcinoma penetrates the lamina propria but does not invade the muscle layer, cholecystectomy should suffice for therapy. The extended cholecystectomy is directed at obtaining an R0 resection of the disease, including the draining lymph node basins. Therefore, removal of the pericholedochal, periportal, hepatoduodenal, right celiac, and posterior pancreaticoduodenal lymph nodes should be included. Resection of the cystic duct margin to uninvolved mucosa may require resection of the common bile duct with Roux-en-Y reconstruction. Because local extension into the hepatic parenchyma is common, 2 cm of apparently normal hepatic parenchyma from the gallbladder fossa is resected. As port site recurrences have been reported for patients with even in situ disease, all port sites should also be excised. Ro- microscopically margin negative resection R1-removal of macroscopic disease but microscopic margins are positive for tumor R2-gross residual tumor that was not resected (primary tumor, regional nodes, and macroscopic margin involvement )
- Frozen section biopsy from cystic duct stump should be done to identify for the existence of microscopic tumour. If present, CBD resection and hepaticojejunostomy hepaticojejunostomy is done. Open approach rather than laparoscopic is ideal for carcinoma gallbladder
- T2 lesions, in which the cancer extends past the muscularis but not beyond the serosa, a similar approach with radical cholecystectomy is indicated because more than 40% of these patients have lymph node metastases and up to 25% have positive margins when treated with standard cholecystectomy alone. Because gallbladder cancer is generally unresponsive to other therapies, the presence of any residual disease after operative intervention predicts poor outcome.2
- tumors harboring defective mismatch repair were examined for response to the anti–PD-1 antibody pembrolizumab
- Common symptoms requiring palliation include jaundice, pain, and intestinal obstruction Jaundice-endoscopic biliary stenting, and self-expanding endobiliary metal stents can provide a durable solution, with less need for repeated interventions than with plastic stents.
- BILCAP trial (university of Birmingham ) . includes- capecitabine 1250mg/m2 twicw daily on days 1-14 of a 21days cycle ,for 8 cycle ,or observation commencing within 16weeks of surgery ….but prevalence is 0.09 which is not significant . Phase i- is treatment safe ? Phase ii- whether treatment work? Phase iii- whether treatment is safer than other option? Phase iv- what else do we need to know Phase iv-
- 5year survival is only 5% Overall survival of gallbladder cancer < 15%. Because most patients with gallbladder cancer present with advanced disease, the overall survival of gallbladder cancer is less than 15%.
- 5year survival is only 5% Overall survival of gallbladder cancer < 15%. Because most patients with gallbladder cancer present with advanced disease, the overall survival of gallbladder cancer is less than 15%.