Re-resection is indicated in patients with pathologically confirmed T1b, T2 or T3 disease without evidence of metastatic disease. R0 resection is the goal and to achieve it, often repeated operations are done as R1 or R2 margin status is accompanied with significantly worse immediate, medium and long-term outcome. But extensive resections to achieve R0 resection margin status in gallbladder carcinomas is also associated with increased morbidity, but not survival (11). Re-resection is generally accepted for T2 and T3 disease, while the role of resection in patients with T1b disease is more controversial. However, there is significant improvement in overall survival in well-selected patients with T1b disease who undergo re-resection compared to those who do not (12, 13). Thus, current standard of care is to recommend re-resection for incidental T1b, T2 and T3 gallbladder carcinoma.
Staging laparoscopy is performed prior to performing a laparotomy to rule out the possibility of distant metastasis in the abdomen. Disseminated disease is relatively uncommon among IGBC and staging laparoscopy provides a very low yield. However, patients with poorly/ undifferentiated i.e. high grade carcinomas, T3 or positive-margin gallbladder carcinomas are at high risk for disseminated disease and selecting these patients for staging laparoscopy may increase its yield (14). In any suspicious patient for distant metastasis, PET/CT restages the patient and staging laparoscopy can be avoided in such type of patients as seen in one of our patient (patient no. 3) of stage pT3NxMx (Figs. 1 and 2) and in this patient treatment plan was changed to chemotherapy.
PET/CT is the most advanced technology for structural, functional, and molecular phenotyping of carcinoma at the whole-body level. PET/CT scan provides the information about local as well as distant disease involvement and is routinely used. It’s applications in oncology includes diagnosis, staging, therapy monitoring and treatment stratification (15). The sensitivity and specificity of PET/CT for detection of distant metastases is higher than conventional imaging.
FDG PET-CT has high diagnostic performance in detecting residual / recurrent disease as well as metastases in IGBC. Thus FDG PET/CT plays a major impact on clinical decision-making in re-resection (16) and staging laparoscopy. PET/CT helps in reducing the number of patients undergoing non therapeutic re-exploration in patients with T1b or greater disease (17). In one of our patient (patient no. 8) having pT1bNx, treatment plan was changed from radical cholecystectomy to no treatment (Fig. 3). Our study supports the same as PET/CT reduces re-resection and also staging laparoscopy, so it increases overall survival.
In our study, two patients (patient no. 13 and 16) had pT2 stage, local liver infiltration and distant metastases on PET/CT. These patients received chemotherapy and Fig. 4 shows a representative image for the same. Overtreatment can also be avoided, as one of our patient who was negative on PET/CT (patient no. 10) having pT2 stage, G2 grade and R0 margin underwent radical cholecystectomy and chemotherapy (Fig. 5).
There is paucity of literature on utility of PET/CT in gall bladder carcinoma specially in IGBC restaging (16, 17). Jean M. Butte et al described the role of PET/CT in incidental gallbladder cancer patients and concluded that in stage T1b or greater IGBC, 18F FDG PET/CT helps to reduce the number of patients undergoing non-therapeutic re-exploration, determines prognosis and selection of patients for potentially curative treatment (17). Our study supports the same and reduces the number of patients undergoing radical cholecystectomy in pT1b and pT2 stages. In these patients, no treatment was given as they were negative on 18F FDG PET/CT.
Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. In T2 tumor, location i.e. peritoneal side versus hepatic side, predicts the pattern of recurrence and survival (18). Our study supports this study and does not support the study of Lafaro K et al which failed to demonstrate the independent prognostic value of primary tumor location in patients with T2 gallbladder carcinoma (19). In our study, PET/CT was positive in those patients having T2b stage (3/5 i.e. 60%), in the form of infiltration into liver.
Patients with incidental T2 gallbladder carcinoma, often have residual liver disease, which reduces survival. Consideration should be given to reclassify such patients to reflect the adverse survival (20). PET/CT helps to detect the residual tumour in resected liver. We have classified these patients on PET/CT in our study, as FDG PET/CT has high diagnostic performance in detecting residual tumour (16). Histopathological reports must mention about T2 stage, either it is T2a or T2b stage. In our study sample, this was missing in 4 out of total 11 patients having T2 disease (36.3%). The patients having T2b stage have more chances of having liver infiltration as seen in our study (60%). One out of two patients was positive on PET/CT having T2a stage.
Histopathological grade is an independent prognostic factor for overall survival and disease free survival in gallbladder carcinoma. Histopathological reports must contain detailed grade of the tumour, which was missing in few of our patients (5/17 patients, 29.4%).
In our study, one patient (patient no. 6) was of high-grade neuroendocrine carcinoma. This histopathological type of cancer is staged according to the gallbladder carcinoma staging system (according to AJCC 8th edition). Neuroendocrine gallbladder carcinoma is relatively rare and in terms of treatment available. Surgical treatment is the best choice and active multi-mode comprehensive treatment significantly prolongs survival times in these patients (21). This patient had pT2a stage and had residual disease in liver detected on PET/CT (Fig. 6). Among all the neuroendocrine tumors, prevalence in gallbladder is 0.5%, which accounts for approximately 2.1% of all gallbladder carcinoma (21). As most of these patients do not have any manifestations of carcinoid syndrome (22), our patient also did not have any such manifestations. Neuroendocrine gallbladder carcinoma patients have lower survival rate compared with other types of gallbladder cancer (23). Due to the low incidence and limited availability of studies, there is no uniform standard treatment for neuroendocrine gallbladder carcinoma (21, 24). In these patients we can perform somatostatin receptor (SSTR) PET/CT like Ga68 DOTANOC/DOTATATE PET/CT and can provide Lu177 DOTATATE peptide receptor radionuclide therapy (PRRT) if SSTR uptake is present. Lu177 DOTATATE PRRT leads to both clinical and biochemical improvement and provides superior progression-free survival and overall survival rates substantially in most of the neuroendocrine tumors patients (25, 26).