Data on optimal extent of resection for various stages of gallbladder cancer are lacking. This study aims to evaluate disease-free (DFS) and overall survival (OS) after simple (SC) versus radical cholecystectomy (RC) for gallbladder cancer in the Australian context, and assesses factors associated with post-operative morbidity.

Multi-centre, retrospective cohort analysis including all gallbladder cancer patients who underwent resection across six Australian institutions between January 2010 and January 2020.

Of 63 patients included, 31 underwent SC and 32 had RC. Liver and other organ resection correlated with prolonged median DFS (41.9 vs. 13.1 months, HR 0.492 [95% CI 0.245-0.987], P = 0.042) and OS on univariate analysis of all patients (55.8% survived five years follow-up at study conclusion vs. median 18.4 months, HR 0.66 [95% CI 0.446-0.972], P = 0.036) but failed to demonstrate effect on multivariable analysis (OS HR 0.31 [95% CI 0.09-1.04], P = 0.057). RC was associated with a higher 30-day complication rate (n = 21 [65.6%] vs. n = 15 [48.4%], P = 0.310) compared to SC, although not statistically significant. There was no significant difference in the major morbidity rate (Clavien-Dindo ≥ Grade III) observed after SC (n = 7 [22.6%]) compared with RC (n = 6 [18.7%], P = 0.754). Neoadjuvant therapy was not utilized and adjuvant treatment used infrequently.

Extended gallbladder cancer resection was associated with prolonged OS and DFS but also considerable post-operative morbidity. Further studies are warranted to determine the optimal extent of surgical resection by stage of gallbladder cancer.

Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.

The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC).

Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC.

Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared.

In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)].

The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.