Discussion
In this study, females outnumbered males with male to female ratio of 1:7. Female predominance is also reported by similar studies. The mean age 32.25±5.3 years ranging from 19 to 80 years, slightly higher than that reported in other studies.
Over ninety one per cent patients presented with pain upper abdomen, a number significantly lower than that reported by Laghari et al. where all patients had upper abdominal pain. None of the patients in our study had any evidence of malignancy either clinically or on ultrasound examination.
The most common histopathological finding in our study was chronic cholecystitis; 203 (92.3%) specimens were reported as chronic inflammation with mucosal ulceration, denudation, metaplasia to dysplasia and wall infiltration by chronic inflammatory cells like neutrophils, macrophages, plasma cells and varying degrees of fibrosis. A similar study by Memon also reports chronic cholecystitis as major histopathological finding, identified in 64.8% cases.
Empyema of the gallbladder is often difficult to distinguish from uncomplicated acute cholecystitis. In this study, 3 (1.3%) cases were reported as acute cholecystitis with empyema of gallbladder. This is in stark contrast to 31.5% cases of empyema associated with cholecystitis as reported by Memon. Mucocele of the gallbladder has an incidence of 3 percent. In this study, 3.2 cases presented as cholecystitis with mucocele; reported incidence of mucocele is, however, several times higher.
Gallbladder polyps have an incidence ranging from 4.6 to 6.9 per cent. In our study, one case of gallbladder polyp was identified. This low incidence can be attributed to small number of cases in our series. The only polyp discovered in our study was in a female. However, the prevalence of this pathology is much higher amongst males.
In our series, incidental carcinoma of gallbladder was found in 6 cases (2.7%). These gallbladders showed no gross abnormality per-operatively. The incidence of gallbladder malignancy in this series was considerably low compared to other studies, which show an incidence varying from 6.9 to 12 per cent. The low incidence of malignancy in our series can be attributed to high sensitivity to exclusion criteria, where all patients with any preoperative evidence of malignancy, no matter how trivial, were excluded from the study. Low incidence of malignancy in our patients can also be attributed to increased acceptance and early reporting for laparoscopic cholecystectomy due to resort to day-care surgery at our institution. Samad reports an incidence of 1.1% of malignancy in patients who underwent cholecystectomy for presumed chronic cholecystitis with cholelithiasis.
All patients in our series presented with longstanding history of chronic cholecystitis. There were no symptoms or signs suggestive of underlying malignancy in any patient; gallbladder malignancy usually does not have any characteristic clinical features with over 90 per cent of patients presenting with symptoms of acute or chronic cholecystitis. Although ultrasound has a high diagnostic accuracy for both advanced and early gallbladder cancer, none of the six carcinomas in this series were picked on preoperative ultrasound. In addition, all six gallbladder specimens showed no macroscopic evidence of malignancy when they were opened during surgery. This is in contrast to the study by De Zoyasa et al. in whom all four cancers were suspected either on preoperative ultrasound or grossly during surgery; they suggest a more selective approach to gallbladder histology which may have saved both time and cost without having any unfavorable effects on patients well-being. Similar observations and recommendations are made by other studies. The issue of routine histopathology of all gallbladder specimen therefore remains unresolved; the need to send every specimen for histopathology or otherwise therefore depends on the expertise of the ultrasonologist as it depends on the skill of the operating surgeon. We, however, advocate routine histopathology of all gallbladders removed at surgery since the subsequent report would provide evidence of malignancy on solid grounds.
Although there are myriad of premalignant conditions, carcinoma gallbladder has a strong association with gallstones. The strong association between the two warrants attention paid to histopathology of specimen in all cases undergoing cholecystectomy for cholelithiasis, irrespective of presence or otherwise of any gross abnormalities. It is widely reported that long standing mucosal irritation by the stones cause atypical cellular changes and increased cellular proliferation. It has been hypothesized that in long standing cases, these areas of hyperplasia progress to metaplasia and carcinoma-in- situ. Studies confirm presence of such changes in the vicinity of gallbladder carcinoma. The incidence of malignancy in our study was 2.7%, which is similar to that reported by Khan AH.
Histopathology revealed adenocarcinoma of gallbladder in six patients. One tumor was in stage T1b, two in T2 while one was in stage T3. While Cholecystectomy is an adequate treatment for pT1 tumors, pT2 and pT3 tumors require revision surgery to achieve a tumor-free surgical margin, along with lymph node dissection. Three patients with the unexpected gallbladder cancer in stages T2 and T3 underwent a second standard revision procedure including transection of liver segments 4b and 5 (T2) and right hepatectomy (T3) with lymphadenectomy. These patients were followed up the oncological department for a period varying from 6 months to one year before being lost to follow up.
All six cases of incidentally diagnosed malignancies had associated gallstones, thereby strongly supporting the role of chronic irritation by long standing gallstones as etiological factor for carcinoma gall bladder.
Grading of cancer was found well differentiated to poorly differentiated adenocarcinoma, no case of squamous cell carcinoma, or other variant of cancerous histopathology seen.