Gall bladder cancer is the fifth most common malignancy ofthe gastrointestinal tract.  It is incidentally detected in 0.34 –2% of all cholecystectomies in different series.[1,2]

Carcinoma gall bladder (CaGB) is a rapidly growingaggressive neoplasm with early metastatic spread and dismalprognosis. The 5-year survival is less than 5%.[3] IncidentalCaGB is defined in this study as carcinoma of the gall bladderunrecognised before surgery and detected intra-operativelyor after examination of the resected gallbladder specimenduring the histopathological examination. The initialpresentation of the most incidental CaGB is indistinguishablefrom benign biliary or gastric diseases. This along with theanatomical location of the gallbladder results in a delayeddiagnosis of CaGB. The rapid growth of the tumour and theproximity of the gall bladder to vital vascular structures makethis a rapidly fatal disease if surgical resection is unsuccessful.[4,5,6] However, incidental CaGB is more likely tobe an early stage disease amenable to attempts at curativeresection.  The management depends on the time of diagnosis(intra-operative or after histopathological examination). Radicalsurgery either in the same sitting or at reoperation has beenassociated with a significantly improved survival compared tonon-curative resection or simple cholecystectomy.[7,8,9,10,11,12,13,14] Wepresent 7 cases of incidentally detected CaGB which weremanaged by radical resection with curative intent.

Methods

From December 1999 through June 2005, a total of 72 casesof gallbladder cancer were treated by the authors. Seven casesof incidental CaGB were included in this study andretrospectively reviewed. All seven patients had undergone laparoscopic cholecystectomy (LC) for presumed benigngallstone disease. Six patients were referred to us after primarysurgery elsewhere and one was initially operated on at ourinstitute.

In all cases, the history, clinical presentation, pre-operativeinvestigations and findings at surgery and surgical procedureswere recorded. In all cases conversion to open surgery,accidental opening of the gall bladder, and the method to extractthe gallbladder specimen (use of bag) and the site (port) wererecorded. An extent of disease evaluation to assessresectability was carried out in all patients, which includedchest X-rays, contrast enhanced computed tomogram (CECT)of the abdomen and pelvis and liver function tests. Thehistopathology of the resected gallbladder was independentlyreviewed.

Results

The patients included 6 female and 1 male. The median agewas 56 years. All had initially presented with episodes of biliarycolic for periods ranging from 6 to 30 months before primarysurgery. None had constitutional symptoms like anorexia,weight loss or jaundice. One patient had a previous history ofacute pancreatitis which was thought to have a biliary cause.Preoperative liver function tests were normal in all cases andthe preoperative ultrasonogram showed chronic cholecystitiswith cholelithiasis in 6 patients. The remaining patient had anisoechoic mass lesion in the gall bladder in the ultrasonogrambut a subsequent CECT of the abdomen showed a normalgall bladder with sludge. In only 2 patients a diagnosis ofCaGB was suspected intraoperatively. One was referred to usafter a partial cholecystectomy. In the second, which wasoperated on in our institute, intraoperative suspicion wasconfirmed by frozen section. Six out of the 7 patients wereasymptomatic after the initial surgery. One patient had recurring episodes of abdominal pain and later (after 10 months)presented with epigastric port site metastasis.

All seven patients underwent reoperation with radicalsurgery with curative intent of achieving R0 resection. Surgeryincluded liver resection, lymphadenectomy, excision of the common bile duct and port site and scar excision. Liverresection including the segments IVB and V was done in 5patients and in 2 patients resection of a wedge of hepaticparenchyma of more than 2 cm thickness which included thegall bladder bed was performed. Lymphadenectomy includedclearance of the hepatoduodenal pedicle, thepancreatoduodenal block, the hepatic artery and the celiacplexus. In 5 patients the common bile duct was excised withperformance of a hepaticojejunostomy.

The initial histopathologies of the resected gallbladderswere reviewed.  All 7 patients had adenocarcinoma; 1 hadwell differentiated, 3 had moderately differentiated and theremaining 3 had poorly differentiated tumours. In 5 cases thetumour had infiltrated through the serosa (pT3). In 2 cases theperimuscular connective tissue was involved (pT2). Cysticlymph nodes were involved in 5 patients and thepericholedochal nodes were positive in 2 cases.  Hepaticinfiltration was present in 5 cases.  The stage was II andbeyond in all patients. Gallstones coexisted with cancer in all7 patients. All patients received adjuvant chemotherapy with 6cycles of gemcitabine and cisplatin.

There was no perioperative mortality. Postoperatively 2patients developed fever and 1 patient had minimal alteredblood in the nasogastric tube aspirate. These weresuccessfully managed conservatively.

After a follow up of between 6 months and 50 months 5patients are still alive.  One patient died after 2 months withcholangitis and sepsis. One patient succumbed to metastaticdisease after 12 months. The detailed results of the patientsare given in Table I.



Discussion

Incidental carcinoma gallbladder (CaGB) is detected in 0.34-2% of all cholecystectomies in large series.[1,2] Ten to twentypercent of all CaGB are first detected by the pathologistexamining the excised gall bladder specimen.[3] The medianage of patients detected with incidental CaGB is generallyhigher than the typical patients with cholelithiasis. But theclinical, radiological or laboratory profile is not different fromthat of the patients with cholelithiasis. Gallstones are presentin 60-90% of cases of incidental CaGB.[3,4]

Almost all cholecystectomies are now performedlaparoscopically. Laparoscopic cholecystectomy has howeverseveral oncological disadvantages compared to the openprocedure.[15,16] Several studies have shown thatpneumoperitoneum with carbon dioxide (CO₂) causes greaterperitoneal tumour growth.[15,16] Desquammation of malignantcells due to excessive manipulation of the gallbladder maycause diffuse peritoneal carcinomatosis. In additionlaparoscopic cholecystectomy is carried out subserosallywhich can expose neoplastic tumour cells to the peritonealcavity. A high index of suspicion should be maintained in allcholecystectomies, particularly if associated with a change inpreviously stable lithic symptomatology, asymmetricalthickening of the gall bladder, long standing cholelithiasis,polyps more than 1 cm in diameter or porcelain gall bladder.Conversion to an open procedure in all cases where CaGB issuspected is indicated.[17,18] In cases when carcinoma issuspected after extraction of the gall bladder after laparoscopiccholecystectomy, the specimen should be cut open andexamined meticulously. A frozen section should then beperformed. If the frozen section confirms the diagnosis of cancergallbladder, subsequent treatment will depend on the depthof tumour invasion. When the diagnosis of cancer gall bladderis made on postoperative histology, treatment should betailored to the stage of the disease process. Before proceedingfor radical re-resection accurate staging and assessment ofphysiological and general status of the patient must be done.Restaging is primarily done by CECT scan of the abdomen.[18]

In case of a T_1a tumour, which is limited to mucosa only,simple cholecystectomy is sufficient. If there was no spillageof bile or perforation of the gallbladder during surgery and thegallbladder was removed through a sterile nonpermeable bagthan there is no need for excision of the port sites, otherwiseexcision of the port sites should be performed.[1,3,12] The 5-yearsurvival for T_1a tumour is greater than 85% with simplecholecystectomy.[19]

In T_1b tumours, which involve the muscularis mucosa layer,the recommended treatment is extended cholecystectomy.This comprises limited liver resection (> 2 cm liver parenchymaaround the gallbladder bed) in addition to lymph nodeclearance around the pericholedochal and hepatoduodenalligaments and excision of the port sites.[1,2,3,7,8,12] T_1b tumour isassociated with 15% lymph node involvement which makes itmandatory to undertake lymph node clearance.[20]

In T₂ tumours, which involve the serosa, the recommendedtreatment is standard liver resection consisting of segmentsIVB and V along with lymph nodes, clearance of the hepaticpedicle, pancreaticoduodenal lymph nodes, along the hepaticartery up to the celiac trunk, and excision of the port sites.[7,8,9,10,11,12,13,14, 21] If cancer cells are found at the end of the cystic duct in aresected specimen, common bile duct resection withreconstruction should be performed. Five year survival of 60-85% has been reported in patients with T₂ tumors after radicalre-resection.[10,11, 21] In our series there were 2 patients with T₂tumor. Wedge resection of the liver was done with lymph nodeexcision and both the patients have done well.

It is very rare to get T₃ and T₄ disease incidentally. If thissituation is encountered only selected patients should beconsidered for radical re-resection. T₃ lesions are associated with residual liver or lymph node disease in 36.4% and 45.5%of cases, respectively.[7] The results of radical surgery in T₃ and T₄ incidentally detected gallbladder cancer is nothomogenous.[6,13] The role of radical resection in T₃ and T₄ tumours remains debatable. Many authors report no 5-yearsurvival for patients with T₃ and T₄ lesions and some report15–63% in T₃ and 7–25% in T₄ lesions.[5] In our series 5 patientshad T₃ tumour. Segmental liver resection with bile duct excisionand lymph node dissection was done. Three patients havebeen well but 2 patients died within 12 months. There is areport of 67% 5-year survival in patients with T₃ disease whounderwent complete resection.9 Even with a poor prognosismany authors advocate radical resection because of a possiblelong term survival in T₃ and T₄ stage disease.[7,9]

Conclusion

The treatment options for incidental CaGB is evolving. A highindex of suspicion is needed to identify patients at high risk forcancer gall bladder in a presumed benign gallbladder diseaseundergoing surgery. There is growing evidence to suggestthat in resectable tumours, re-exploration and aggressive re-resection are beneficial. The role of chemotherapy andradiotherapy need further evaluation.

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