Gallbladder carcinoma (GBC) is a common malignancy in our part. Unfortunately, majority (70%) of our patients present with advanced stage disease and are unresectable as compared to other similar studies from Indian subcontinent [6, 7]. Only 30% of patients are subjected to curative intent surgery with a median survival of approximately 28 months. The further findings observed in the present study was high number of IGBC (7%vs. 1%) and young-onset GBC- 10%, compared to similar study in the world .
In the study by Subedi et al from Nepal, the incidence of GBC was higher in the Kathmandu Valley than the cities of India and China. Cancer of gallbladder was among the top five commonest and lethal cancers in both sex [8]. In addition to high incidence of GBC in Nepal, the presentation of patients is usually late with advanced stage of disease. Some studies have shown association of history of gallstone, smoking, and early menarche with GBC in Nepal [9, 10]. Thus, locally tailored research is important to understand the reason behind the higher incidence of GBC and identify as to whether any preventive measures could be adopted.
According to the American Cancer Society, only about 1 in 5 GBC cases will be discovered when the disease is still localized to the gallbladder [11]. The remaining cases are diagnosed when the malignancy has spread outside of the gallbladder, which drastically limits the available options for curative treatment and lowers overall survival. In line with the aforementioned study, 90% of those who underwent curative intent surgery presented to us with advanced stage of tumor (T3,N1). Unfortunately, around 10% of our patients in the study were young (< 40 years) onset GBC. They were predominantly metastatic, advanced staged with less than a year survival even after extended resections. Seventy percent (70%) of the patients had associated gallstones. This recommends for proper GBC cancer surveillance, especially considering all benign cases of cholecystectomies with a histopathological examination and addressing the associated risk factors like gall stones in context to Nepal.
The majority of GBC patients who present with jaundice will have disseminated disease even if it is not detectable on preoperative work-up or operative exploration. The en-bloc resection of the CHD/CBD, which is frequently required in these patients, is difficult and associated with positive (R1) margin status in 40% of patients [12, 13]. Despite anecdotal reports of longer postoperative survival in GBC patients presenting with the rare combination of jaundice without nodal involvement, [14] even in patients with a negative (R0) margin, the median length of disease-free survival in preoperatively jaundiced patients is only 6 months [15]. Based on these data, preoperative jaundice is considered a relative contraindication to radical resection of GBC. In contrast to the aforementioned, 56% of our patients presented with jaundice. Out of 30% of patients who underwent curative intent surgery, median overall survival of 28 months after median follow-up of 42 months (12–64 months) was reported. Our published study has shown, curative resection was possible in 9% (5/56) patients in GBC with obstructive jaundice [16]. Thus, with reference to our study, GBC with jaundice can no longer be considered as a contraindication to resection, albeit with a low rate.
Likewise, long-term survival after radical resections that included major hepatectomy, CHD/CBD and/or vascular resection or reconstruction has been anecdotally reported, [17] but these radical resections have not been associated with longer disease-free or overall survival on a population basis. Instead, they are associated with increased morbidity and mortality. Radical resections of locally advanced primary tumours should, therefore, be performed only in medically fit patients after multidisciplinary discussion. Although R0 resection for GBC is associated with longer survival, tumour biology and stage, rather than the extent of resection, are the most important predictors of survival after surgery [18].
In our study, perioperative morbidity and mortality were (23%) and (3%) respectively. The overall survival of the entire group was 9 months. Out of 30 patients who underwent curative intent surgery, 20 (66.67%) had R0 resection. Median overall survival of 28 months after median follow-up of 42 months (12–64 months) was reported. This adequately supports that radical resection for GBC renders good prognosis and prolonged overall survival. According to our study, only 30% of those presenting to us, undergo curative intent surgery. Further, only 12 (40%) of them have completed adjuvant chemotherapy. This low adjuvant therapy completion is because of lack of health insurance coverage, financial burden, geographical status and poverty.
In our study, 7% (n = 7) had incidental GBC, quite a high incidence. Out of them, 57.1% (n = 4) underwent curative intent surgery with a good prognosis. The remaining had metastatic disease due to port site metastases and delayed presentation. GBC is suspected preoperatively in only 30% of all patients.1 The remaining 70% of cases are diagnosed using postoperative incidental findings by a pathologist. Incidental GBC is high by 2–3 times compared to total GBC.In a study by Poudel et al, incidence of IGBC in cholecystectomies specimens for benign disease is 1.67% [19]. They recommended that routine histopathology of cholecystectomy specimen should be sent for early diagnosis and improve survival of patient with gall bladder cancer. Hence, gallbladder should be evaluated histo-pathologically in all patients after laparoscopic cholecystectomy, as these are the group of patients with early stage disease with better survival.
Few published studies have focused on the patterns and timing of recurrence after resection of GBC. Despite curative intent resection, up to 66% of resected patients develop recurrence, mostly within 2 years of surgery, often at the distant site [20]. In line to the aforementioned, out of 30 patients who underwent curative intent surgery, 46.6% (n = 14) had recurrence in the present study. Three patients had a local recurrence only, 3 patients had metastatic disease and local recurrence, and 8 patients had metastatic disease only. This high recurrence was because of low R0 resection, lack of completion of adjuvant chemotherapy and advanced stage disease.
Our study has some limitations. The study is limited by the small sample size of patients with GBC undergoing surgery with a curative intent. Also, this is a single centred study. Otherwise, more robust evidence could have been delivered with a multi-centre study. However, the best part of the study is that, it is one of the preliminary and prospective studies with 3 years follow-up from our part. A larger sample size, government health insurance coverage for overall treatment and multi-institutional involvement, henceforth, may provide a better insight to the incidence and prognosis of GBC.