Gallbladder cancer (GBC) is a highly aggressive malignancy with dismal prognosis. GBC is characterized by marked geographic predilection. GBC has distinct morphological types that pose unique challenges in diagnosis and differentiation from benign lesions. There are no specific clinical or serological markers of GBC. Imaging plays a key role not only in diagnosis and staging but also in prognostication. Ultrasound (US) is the initial test of choice that allows risk stratification in wall thickening and polypoidal type of gallbladder lesions. US findings guide further investigations and management. Computed tomography (CT) is the test of choice for staging GBC as it allows comprehensive evaluation of the gallbladder lesion, liver involvement, lymph nodes, peritoneum, and other distant sites for potential metastases. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography allow better delineation of the biliary system involvement. Contrast-enhanced US and advanced MRI techniques including diffusion-weighted imaging and dynamic contrast-enhanced MRI are used as problem-solving tools in cases where distinction from benign lesion is challenging at US and CT. Positron emission tomography is also used in selected cases for accurate staging of the disease. In this review, we provide an up-to-date insight into the role of imaging in diagnosis, staging, and prognostication of GBC.

The role of neoadjuvant therapy (NAT) in gallbladder cancer (GBC) is not well established. We sought to evaluate the effect of NAT on postoperative outcomes following surgical resection of GBC. We hypothesized that patients receiving NAT would have similar rates of 30-day mortality, readmission, and postoperative complications (e.g. bile leakage and liver failure) compared to those who did not receive NAT.

The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Hepatectomy database was queried for patients that underwent surgery for GBC. Propensity scores were calculated to match patients in a 1:2 ratio based on age, comorbidities, functional status, and tumor staging.

A total of 37 patients undergoing NAT were matched to 74 patients without NAT. There was no difference in any matched characteristics. Compared to the NAT group, the no NAT cohort had similar rates of postoperative bile leakage (NAT 13.5 % vs. no NAT 10.8 %, p = 0.31), postoperative liver failure (5.4 %, vs. 8.1 %, p = 0.60), 30-day readmission (10.8 % vs. 10.8 %, p = 1.00), and 30-day mortality (10.8 % vs. 2.7 %, p = 0.075). All 30-day complications were similar except for a higher rate of postoperative blood transfusion (NAT 32.4 % vs. no NAT 10.8 %, p = 0.005).

In patients undergoing surgical resection for GBC, those with and without NAT had similar rates of readmission and 30-day mortality, however NAT was associated with an increased risk for transfusion. Despite use of a large national database, this study may be underpowered to adequately assess the effect of NAT on perioperative GBC outcomes and thus warrants further investigation.

Gallbladder cancer (GBC) is one of the commonest biliary malignancies seen in India, Argentina, and Japan. The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs. Early detection is the only way to improve the outcome. There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC. Therefore, it is important and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis, early diagnosis, treatment, and prognostication. As India being one of the largest hubs for GBC in the world, it is important to know how the country has progressed on GBC. In this review, we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.

Up to 60% of incidentally detected gallbladder cancers (GBCs) have a primary stage of pathologic T2 stage (pT2), defined by invasion of the peri-adventitial tissue by the tumour, a plane breached during a simple cholecystectomy. This study assesses the impact of incidental detection of pT2 GBCs on survival outcomes.

Retrospective analysis of pT2 GBCs undergoing a curative resection was performed. Patients who received neoadjuvant chemotherapy before an upfront radical resection were excluded. Outcomes of patients undergoing upfront surgery (uGBC) and incidentally detected tumours (iGBC) were compared.

From a total of 1356 patients, 425 patients with pT2 GBCs were included. Of these, 118 (27.7%) and 307 (72.23%) patients were in the uGBC and iGBC groups, respectively. Patients with iGBC had significantly higher locoregional, (62 [19.8%] vs. 11 [9.3%]; p = 0.009), liver, (36 [11.5%] vs. 4 [3.4%]; p = 0.01), and abdominal wall recurrences (23 [7.4%] vs. 1 [0.8%]; p = 0.009). Five-year disease free survival rates were 68.7% and 49.2% in the uGBC and iGBC groups, respectively (p = 0.013). Five-year overall survival rates were 71.7% and 64.6% in the uGBC and iGBC groups, respectively (p = 0.317).

Incidentally detected pT2 GBCs have significantly poorer outcomes compared to similarly staged patients undergoing an upfront radical cholecystectomy.

The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis.

Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT.

Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups.

NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.

The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India.

Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed.

There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50-65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100-100); 61% (95% CI: 45-83); 30% (95% CI: 21-43); and 9% (95% CI: 6-13) for stages I-IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39-64), compared to 29% (95% CI: 22-38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6-14) in patients who were palliated (N = 107) (p = <0.0001).

The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III-IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required.

Evidence for adjuvant chemotherapy in gallbladder cancer (GBC) is conflicting, with a postulated beneficial effect reported in T2 stage or higher, and node-positive tumours. This study aims to assess the survival benefit of peri-operative chemotherapy in stage II (pT2N0) GBCs.

A retrospective analysis of stage II GBCs who underwent curative surgical resection was done. Patients receiving neo-adjuvant therapy (NACT) prior to resection of the gallbladder primary were excluded. Primary endpoint was disease-free survival, and outcomes of patients who received chemotherapy were compared to those who did not. Survival curves were plotted using a Kaplan-Meier analysis and difference between the survival curves was analysed using a log-rank test.

Two hundred seventy-six patients of stage II GBC were included, of whom 188 (68.1%) received chemotherapy and 88 (31.8%) did not. Forty-one (21.8%) patients received chemotherapy in the neo-adjuvant setting. There was no significant difference in the survival of patients who did and did not receive chemotherapy (5-year DFS 67.8% vs 66%, p = 0.795). There was no significant difference in the survival of patients who received chemotherapy in the adjuvant or neo-adjuvant setting (5-year DFS 66.4% vs 71.8%, p = 0.541). There was no statistically significant difference in the survival of patients with high-risk histologic features and who did and did not receive chemotherapy (3-year DFS 72.4% vs 56%; p = 0.379).

Routine use of chemotherapy, either in the adjuvant or neo-adjuvant setting, offers no survival advantage in stage II (pT2N0) gallbladder cancers.

Gallbladder cancer is uncommon but highly fatal. Surgery remains the only potentially curative treatment for localized or locoregionally advanced gallbladder cancer. The rate of use of neoadjuvant and adjuvant chemotherapy in resectable gallbladder cancer is unknown.

To assess factors associated with the use of neoadjuvant and adjuvant chemotherapy in patients with resectable gallbladder cancer and survival outcomes.

The National Cancer Database was used to identify 6391 adults who underwent definitive surgical resection for gallbladder cancers between January 1, 2004, and January 1, 2016. Data analysis was performed from January 15 to February 15, 2020. Patients with localized or locoregionally advanced gallbladder cancers (ie, categories cTx-cT4, cN0-2, and cM0) were categorized as receiving neoadjuvant chemotherapy, adjuvant chemotherapy, or surgery alone. Categorical variables were compared using the χ2 test, with 1:3 nearest-neighbor propensity score matching based on neoadjuvant chemotherapy. Survival outcomes between groups were compared using Kaplan-Meier and Cox proportional hazards regression analyses.

The use and survival outcomes of adjuvant and neoadjuvant chemotherapy.

Of 6391 patients who underwent definitive surgery for gallbladder cancer, 4559 were women (71.3%); median age was 68 (IQR, 59-77) years. A total of 3145 patients (49.2%) received adjuvant chemotherapy, 3145 patients (49.2%) underwent surgery without chemotherapy, and 101 patients (1.6%) received neoadjuvant chemotherapy. Neoadjuvant chemotherapy use was associated with treatment at an academic facility (61 patients [60%] vs 38 patients [38%] treated in a nonacademic facility; P < .001) and in those with private insurance (65 patients [65%] vs 11 patients [11%] with Medicaid insurance; P < .001). Surgery alone was frequently used in older patients (median age, 72 [IQR, 63-81] years vs 59 [IQR, 52-66] years in patients with neoadjuvant chemotherapy; P < .001), those with Medicare insurance (1925 patients [57%] vs 1438 patients [43%] with adjuvant chemotherapy; P < .001), and patients with a higher comorbidity index score (326 patients [62%] vs 197 patients [38%] with adjuvant chemotherapy; P < .001). Adjuvant or neoadjuvant chemotherapy was used more frequently than surgery in patients with node-positive cancer (1482 [67.2%] vs 53 [65.4%] vs 912 [49.7%]). On propensity score matching analysis, adjuvant chemotherapy was associated with longer survival than surgery alone (22 vs 18 months, hazard ratio [HR], 0.78; 95% CI, 0.63-0.96); survival with neoadjuvant chemotherapy was not statistically significant compared with surgery alone and adjuvant chemotherapy groups (27 months, HR, 0.78; 95% CI, 0.58-1.04). However, in patients with node-positive gallbladder cancer, neoadjuvant therapy was associated with longer median overall survival (30 months [95% CI, 24-36 months] vs 14 months [95% CI, 11-17] in patients with surgery alone; P = .002).

In this cohort study, use of adjuvant and neoadjuvant chemotherapy was low in patients with surgically resected gallbladder cancers. Chemotherapy was used more frequently than surgery in lymph node-positive disease compared with lymph node-negative disease. Adjuvant chemotherapy was associated with a survival advantage in resectable gallbladder cancer, and neoadjuvant chemotherapy was associated with increased survival in node-positive gallbladder cancers. These findings suggest that adjuvant chemotherapy and neoadjuvant chemotherapy should be considered in treatment of gallbladder cancer.

Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways.

Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS).

Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%.

Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

Gallbladder carcinoma (GBC) is among one of the gastrointestinal malignancies with extremely dismal prognosis. This is due to the advanced stage at presentation. Majority of the patients with GBC are not considered candidates for surgery because of the locally advanced disease or metastases. However, with the accumulating evidence regarding the role of neoadjuvant chemotherapy, there is a need to correctly identify a subset of patients with locally advanced GBC who will benefit maximally from neoadjuvant chemotherapy and will be successfully downstaged to receive curative (R0) surgery. In this context, there is a lack of consensus and different groups have resorted to criteria for locally advanced disease eligible for neoadjuvant chemotherapy based on personal or institutional experiences. Imaging plays a critical role in the evaluation of patients with GBC as it helps stratify patients into resectable and unresectable. Imaging also has the potential to identify patients with locally advanced GBC and hence facilitate neoadjuvant chemotherapy and improve outcomes. In this review, we evaluate the various criteria for locally advanced GBC and the role of imaging in this scenario.

The neutrophil-lymphocyte ratio (NLR) is an immune response-related indicator and it is associated with poor prognosis of various cancers. The carbohydrate antigen19-9 (CA19-9) is a tumor-associated antigen and it has prognostic relevance in gallbladder carcinoma (GBC). We aimed to analyze whether preoperative NLR and serum CA19-9 were associated with outcomes of GBC patients after surgery with curative intent.Between January 2010 and May 2015, 90 resectable GBC patients who underwent curative surgery in our institution were included. All final diagnoses were confirmed by pathologic examination. The demographics, clinical, and histopathology data were analyzed. The Cox regression proportional hazard model and Kaplan-Meier method were used to assess prognostic factors.The cutoff values of 4.33 and 250.90 U/mL were defined as high NLR and high CA19-9, respectively. The univariate analyses showed that TNM stage, lymph node metastasis, the degree of tumor differentiation, margin status, combined hepatectomy, CA19-9, NLR, and PNI were all associated with overall survival (P < .05). According to the multivariable analysis, NLR (hazard ratio (HR) 3.840, 95% confidence interval (95% CI): 2.122-6.947, P < .001), CA19-9 (HR 2.230, 95% CI: 1.297-3.835, P = .004), TNM stage (HR 3.864, 95% CI: 1.819-8.207, P < .001), lymph node metastasis (HR 1.679, 95% CI: 1.005-2.805, P = .048), and margin status (HR 1.873, 95% CI: 1.063-3.300, P = .030) were independent prognostic factors. The median survival time in low NLR and CA19-9 group was better than high NLR and CA19-9 group (P < .05).The preoperative NLR and serum CA19-9 are associated with prognosis of patients with GBC. High NLR and high CA19-9 were predictors of poor long-term outcome among patients with GBC undergoing curative surgery.

The treatment approach to node-positive gallbladder cancer has unresolved issues with regard to the management of patients with a positive superior retro-pancreatic (level 13a) node, which is the highest level of spread. The American Joint Committee on Cancer remains unclear on the status of the 13a node.

This retrospective study consisted of 165 patients with node-positive gallbladder cancer without distant metastasis. Patients were reclassified according to the American Joint Committee on Cancer eighth edition classification. The survival of patients with positive level 13a node was compared with that of patients with N1 disease (T stage-wise) and those with para-aortic nodal disease. A multivariate analysis was performed for factors affecting survival.

The 5-year survival of patients with positive level 13a with 1-3 nodes was similar to those with N1 disease (40.2% and 32.9%, respectively) and was better than those with more distant nodal spread (P < .05). In univariate and multivariate analyses, intraoperative blood loss (hazard ratio [HR] 1.58), R1 resection (HR 1.87), and T4 disease (versus T2, HR 3.44) were poor prognosticators. Pancreaticoduodenectomy may be beneficial in T2 patients.

A positive superior retro-pancreatic node does not worsen the prognosis in an otherwise N1 disease in T1/T2 gallbladder cancer. It behaves like a regional lymph node and should be treated as such.

Studies evaluating neo-adjuvant chemotherapy (NACT) exclusively in gallbladder cancer (GBC) are few and there are no randomized trials on the subject. Locally advanced GBC and indications for NACT in GBC are not yet clearly defined.

We analysed 160 consecutive GBC patients who received NACT based on clinico-radiologic criteria suggesting high-risk disease (TMH Criteria) from January 2010 to February 2016.

On initial assessment, 140 (87.5%) patients had T3/T4 disease and 105 (65%) patients were node positive. Response rate and clinical benefit rate was 52.5% and 70% respectively. Sixty six (41.2%) patients could undergo curative intent resection. With a median follow-up of 33 months, the median OS and EFS of the entire cohort were 13 and 8 months respectively. Patient undergoing curative surgery had a statistically superior OS (49 vs. 7 months; p = 0.0001) and EFS (25 months vs. 5 months; p = 0.0001) compared to those who did not.

Locally advanced GBC remains a disease with poor prognosis. Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed good response rates. This resulted in curative surgical resection or disease stabilisation in significant proportion of patients. Patients who undergo definitive surgery after favourable response to NACT experience good survival.

The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection.

A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers. Combinations of preoperative CEA and CA19-9 were tested as potential prognostic factors.

The evaluation of preoperative CEA and CA19-9 showed that patients with both tumour markers within the normal range had the best prognosis with a median survival of 27 months and R0 rate of 86%. Patients with both tumour markers elevated had the poorest prognosis and lower R0 rate (p < 0.001). The combination of CEA and CA19-9 was an independent risk factor for overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was 0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p = 0.147).

A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection.

In this review, the authors present an updated description of gallbladder cancer in 2 sections based on presentation: disease that presents incidentally following laparoscopic cholecystectomy and malignancy that is suspected preoperatively. Elements pertaining to technical aspects of surgical resection provide the critical focus of this review and are discussed in the context of evidence-based literature on gallbladder cancer today.

GI cancer is not one cancer but is a term for the group of cancers that affect the digestive system including gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), esophageal cancer (EC), and pancreatic cancer (PC). Overall, the GI cancers are responsible for more cancers and more deaths from cancer than any other organ. 5 year survival of these cancers remains low compared to western world. Unlike the rest of the world where organ based specialities hepatobiliary, pancreatic, colorectal and esophagogastric exist, these cancers are managed in India by either a gastrointestinal surgeons, surgical oncologist, or a general surgeon with varying outcomes. The aim of this review was to collate data on GI cancers in indian continent. In colorectal cancers, data from tertiary care centres identifies the unique problem of mucinous and signet colorectal cancer. Results of rectal cancer resection in terms of technique (intersphincteric resection, extralevator aper, minimal invasive approach) to be comparable with world literature. However long term outcome and data regarding colon cancers and nationally is needed. Gastric cancer at presentation are advanced and in surgically resected patients, there is need for a trial to compare chemoradiation vs chemotherapy alone to prevent loco regional recurrence. Data on minimal invasive gastric cancer surgery may be sparse for the same reason. Theree is a lot of data on surgical techniques and perioperatve outcomes in pancreatic cancer. There is a high volume of locally advanced gallbladder cancers with efforts on to decide whether neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy is better for down staging. Considering GI cancers, a heterogeneous disease with site specific treatment options and variable outcomes, the overall data and outcomes are extremely variable. Young patients with pathology unique to the Indian subcontinent (for example, signet ring rectal cancer, GBCs) need focussed attention. Solution for such pathology needs to come from the Indian continent itself. Joint efforts to improve outcomes for GI cancer can be integrated under the national cancer grid program.