Gallbladder Carcinoma (GBC) is the most common malignancy of the biliary tract and the sixth most common malignancy of the gastrointestinal tract worldwide [8
]. It is an aggressive and a late symptomatic disease and most of the patients are treated at advanced stages. The prognosis is usually dismal and the 5 year survival rates have been reported to be less than 5% for the more advanced stages [9
]. The countries with a high incidence of gallbladder cancer include Chile, Poland, India and Japan. A very high incidence of this cancer has been reported among women in northern India (21.5/100,000) and among female Native American Indians (14.5/1000,000) [10
The early-stage carcinoma is typically diagnosed incidentally because of the inflammatory symptoms which are related to the coexistent cholelithiasis or cholecystitis. Incidental Gallbladder Carcinoma (IGBC) is the carcinoma of the gallbladder which is suspected for the first time during cholecystectomy or which is found on the histological examination of the gallbladder. With the increasingly widespread acceptance of LC and the difficulties in diagnosing GBC preoperatively, the number of cases of IGBC during and after LCs has increased. The female gender and advanced age are the demographic risk factors for GBC. All the six cases of the incidentally detected gallbladder carcinoma in this series were females and their average age was 53 years. A review of the literature showed that 0.19% to 3.3% of the patients who underwent cholecystectomies for presumed benign diseases were found to have carcinomas of the gallbladder [1-5] Tantia et al., in a study of LC cases from the Indian metropolis of Kolkata, reported an incidence of 0.59% of IGBC [2
]. The present study which was based in New Delhi, India showed an incidence of 0.96% of IGBC among LC cases over a five and a half year period.
GBC either remains asymptomatic for a long time or it presents with very non-specific symptoms like pain in the abdomen, vomiting, anorexia, jaundice, a gallbladder mass and fever. In this study, two patients presented with the features of acute cholecystitis and four patients with chronic calculous cholecystitis. The association of GBC with cholelithiasis and chronic gallbladder inflammation is well known. The causes of the gallbladder mucosal inflammation include infection, drugs (such as isoniazid and methyldopa), congenital anomalies (such as choledochal cysts and the anomalous junction of the pancreaticobiliary ducts) and primary sclerosing cholangitis. It has been presumed that a longstanding chronic inflammation which is caused by cholelithiasis plays a role in the tumour progression and that carcinogenesis and gallstones are seen in 54-97% of the patients of GBC [11
]. However, while most of the patients of GBC will have a history of cholelithiasis, only 0.3-3% of the patients with gallstones develop GBC. In this series, all the 6 patients who were detected to have IGBC had symptomatic gallstone disease for which LCs were undertaken. The other risk factors include a porcelain(calcified) gallbladder, a typhoid carrier state and gallbladder polyps [12
]. Nakajima et al., reported a 45% risk of cancer for the polyps which measured greater than 15mm [13
]. A more recent study in which gallbladder adenomas were analyzed in 91 patients, suggested a classification which was based upon the immunophenotype which was expressed, i.e. pyloric, intestinal, foveolar, and biliary and it indicated that these lesions played a minor role in the pathway of the gallbladder carcinogenesis [14
The ultrasonographic findings in early stage GBCs are subtle, with considerable overlaps with the findings of acute and chronic cholecystitis. The features such as a thickened gallbladder wall, gallbladder or CBD stones, a gallbladder mass and a pericholecystic collection are not characteristic of GBC and they can be associated with cholecystitis. A pseudotumoural inflammatory condition of the gallbladder, xanthogranulomatous cholecystitis, is also known to radiologically simulate GBC [15
]. Multiple gallstones were seen in all the 6 cases of IGBC in this series, along with thickened walls (> 3mm) in 4 cases. A pericholecystic collection was noted in one case of acute cholecystitis.
A difficult gallbladder at surgery usually raises the suspicion of cancer. Unusual findings at surgery such as a gallbladder mass, dense adhesions of the organs which are adjacent to the gallbladder and a difficult dissection of the gallbladder from the liverbed are all pointers to the presence of a possible malignancy, as was seen in case no [6
]. A severe, destructive inflammation with adhesions is also an important feature of xanthogranulomatous cholecystitis and some series have also reported a simultaneous xanthogranulomatous cholecystitis and a GBC in a small proportion of the cases [16
Gallbladder carcinomas are epithelial in origin and they account for 98% of all the gallbladder malignancies. Among these, adenocarcinomas account for 90% of all the carcinomas of the gallbladder. A majority (68%) are diffusely infiltrating, while the remainder exhibit intraluminal polypoid growth [17
]. The submucosal spread of the infiltrating carcinomas appears grossly as focal or diffuse areas of wall thickening, nodularity or induration in the gallbladder wall. Similar gross features were seen in all the 6 cases of IGBC in this series and none of them showed any intraluminal growth or mass lesion. Because the flat infiltrating GBCs and the GBCs with cholecystitis and numerous stones are difficult to diagnose preoperatively, Yokomuro et al recommended taking frozen sections in that subset of patients who were of advanced ages (older than 70 years), who had a long history of stones, or those who had a thickened gallbladder wall [18
]. However, Zhang et al., in their study, showed that frozen section was not a definitive diagnostic procedure and that it does not reliably measure the depth of invasion of the GBCs. One Histologically, all the 6 cases in this series were adenocarcinomas, with 3 cases in pT1a /IMC, and 1 case each in pT1b, pT2 and pT3. The pathologic staging was recognized as an important prognostic factor and a clinicopathological study of 13 cases of IMC suggested that a simple cholecystectomy was curative at this early stage, though a larger series with a long term follow up is necessary to validate this [19
]. The authors recommended that the entire gallbladder be submitted for a microscopic examination and that at least 3 levels be obtained from each paraffin block which demonstrated a carcinoma, so as to be certain that the muscularis propria was not invaded. On the other hand, a re-exploration with a liver resection and a porta-hepatis lymph node dissection is a radical procedure which is carried out after further imaging, to rule out disseminated disease, which has proven to be beneficial in T2 and T3 gallbladder carcinomas which were first noted after laparoscopic cholecystectomies [20,21].