Advanced Gallbladder Cancer Research Articles

A Single-Center Analysis of Patient Characteristics and Overall Survival in Patients with Resectable Gallbladder Cancer.

Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. A total of 94 patients with GBC were included in the study. Median age was 71 (62-77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9-5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery.

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT).

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT. Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250mg/m2 to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20. Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9months (95% CI 7.6-10.3months) vs 10months (95% CI 8-9.8months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7months vs 8months, while in those who received CT followed by CTRT, the median OS was 14months vs 13months (p = 0.65) in non-RPLN group vs RPLN group, respectively. Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

Different biliary tract cancers, same operation: Importance of cancer origin in patients with hilar-invading tumors.

For patients with biliary tract cancer involving the hepatic hilum, major hepatic resection with extrahepatic bile duct resection may be required. In addition to perihilar cholangiocarcinoma (PHCC), the same extent of surgery is used in advanced gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHCC) with hilar involvement. Few studies compare prognostic factors and long-term outcomes across tumor types. This study compared risk characteristics and outcomes after surgery in all subtypes of biliary tract cancer with hilar involvement. Patients with biliary tract cancer with hilar involvement undergoing major liver resection and extrahepatic bile duct resection between 2011 and 2021 at a single center were retrospectively analyzed. The primary postoperative outcome was overall survival. Secondary outcomes were recurrence-free survival and postoperative complications. Survival analysis was performed with Cox regression analysis and Kaplan-Meier method. One-hundred and eight patients were included. Seventy-three (67%) had PHCC, 24 (22%) had GBC, and 11 (10%) had IHCC. Hilar-invading IHCC and GBC had more adverse histopathological factors like lymph node positivity (p = 0.021), higher number of positive nodes (p = 0.043), and larger tumor size (p < 0.001) compared with PHCC. Peritoneal invasion and lymph node positivity were significant independent predictors for survival (p = 0.011 and p = 0.004, respectively). Median overall survival was 29 months for PHCC, 22 months for GBC and 21 months for IHCC (p = 0.53). IHCC tended to recur earlier (p = 0.046) than GBC and PHCC (6, 15, and 18 months, respectively). Patients with biliary tract cancer with hilar involvement undergoing major liver resection and resection of extrahepatic bile ducts had similar overall survival regardless of subtype, while IHCC recurred earlier. Peritoneal cancer invasion was common in all subtypes, including PHCC, and was an independent prognostic factor. This finding may support routine reporting of peritoneal invasion-status in resected biliary tract cancer.

Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer

BackgroundLenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC).MethodsPatients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety.ResultsA total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2–20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2–26.9) and 6.1 (95% CI: 4.9–7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil–lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported.ConclusionAnti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.

Evaluation of malignancy in gallbladder tumors using the apparent diffusion coefficient obtained by diffusion‑weighted MRI.

The utility of the apparent diffusion coefficient (ADC) of diffusion-weighted image (DWI) magnetic resonance imaging was examined for evaluating malignancy and prognosis in gallbladder tumors. A total of 63 patients (benign tumors, n=33; cancer, n=30) were included after surgical resection for gallbladder tumors, and their mean ADC values by DWI were obtained. Cases of advanced gallbladder cancer (n=25) were divided into ADCHigh and ADCLow groups, and clinicopathological factors were compared. In 63 cases, ADC values in advanced gallbladder cancer were significantly lower compared with benign tumors and non-advanced gallbladder cancer (P<0.05), and ADC values in early gallbladder cancer were also significantly lower compared with benign tumors (P<0.05). In 25 advanced gallbladder cancer cases, the ADCLow group tended to have a higher rate of advanced stage disease (P=0.09). Disease-free survival and overall survival (OS) of the ADCLow group were worse compared with the ADCHigh group (P<0.01). In the multivariate analysis of OS, poor differentiation and low ADC value were independent prognostic factors. ADC values may be useful for evaluating tumor malignancies in gallbladder tumors.

51P A phase II trial of camrelizumab in combination with hepatic arterial infusion chemotherapy (HAIC) for initially unresectable advanced extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer (GBC): An interim report

51P A phase II trial of camrelizumab in combination with hepatic arterial infusion chemotherapy (HAIC) for initially unresectable advanced extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer (GBC): An interim report

Combined pancreaticoduodenectomy for advanced gallbladder cancer: Indications, surgical outcomes, and limitations

BackgroundThis study aimed to elucidate the clinical value of combined pancreaticoduodenectomy (PD) for advanced gallbladder cancer according to the mode of cancer spread in the pancreaticoduodenal region. MethodsPatients who underwent combined PD for advanced gallbladder cancer were retrospectively reviewed. The mode of cancer spread in the pancreaticoduodenal region was defined as involvement of peripancreatic organs/structures alone, peripancreatic nodal metastasis alone, or both. Surgical outcomes were compared among these modes of spread. ResultsFifty-seven patients were included. Rates of severe morbidity and mortality were 52.6% and 3.5%, respectively. The mode of cancer spread was involvement of peripancreatic organs/structures alone in 16 patients, peripancreatic nodal metastasis alone in 17, and both in 24; R0 resection rates differed significantly among the groups (87.5% vs. 94.1% vs. 37.5%; p < 0.001). Overall survival (OS) was significantly worse in patients with both modes of spread (5-year OS, 8.3%) than in those with involvement of peripancreatic organs/structures alone (5-year OS, 37.9%; p < 0.001) and those with peripancreatic nodal metastasis alone (5-year OS, 29.4%; p = 0.011). OS was similar between pM0 patients with both modes of spread and pM1 patients (5-year OS, 16.7% vs. 8.7%; p = 0.605). Multivariate analysis identified mode of cancer spread as an independent prognostic factor (p = 0.006). ConclusionsCombined PD could be oncologically justified for advanced gallbladder cancer with involvement of peripancreatic organs/structures alone or peripancreatic nodal metastasis alone in the pancreaticoduodenal region. This procedure would not be indicated in patients with both modes of spread.

Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management.

Introduction Cholecystectomy, the surgical removal of the gallbladder, is a common procedure worldwide. Despite no visible anomalies, routine histopathological examination (HPE) of gallbladder specimens post-surgery is standard practice to exclude pathologies, notably gallbladder cancer (GBC). Incidence rates of GBC vary geographically and ethnically. Surgical intervention is recommended for advanced GBC stages, while early stages may require cholecystectomy alone. Although rare, GBC and bile duct cancers pose increased risks in certain demographics, such as women and individuals over 65. Routine HPE practices vary globally based on resource availability and GBC incidence. This study assesses the necessity of routine HPE by evaluating the selective processing of gallbladder specimens suspected of GBC, prioritizing patient safety. Materials and methods This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine HPEfor excised gallbladder specimens. Adhering to routine HPE policy, the study encompassed all elective and emergency cholecystectomies performed from January 2023 to December 2023, excluding pediatric cases, concurrent surgical procedures, and those with suspected malignancy. Demographic data, surgery indications, intraoperative findings, histopathological results, and incidental gallbladder cancer (IGC)outcomes were analyzed. Pathology reports and case documentation were reviewed for cancerous pathology indicators. Results Over the one-year study period from January 2023 to December 2023, a total of 266 gallbladder specimens were subjected to HPEpost-cholecystectomy. Of these, 201 were female and 65 were male, yielding a male-to-female ratio of 3:1. Elective cholecystectomy was performed on 56.4% (150) of patients, while 43.6% (116) underwent emergency procedures. Laparoscopic cholecystectomy (LC) was the primary surgical approach, except for one case requiring conversion to an open procedure. None of the patients exhibited GBC; however, 3.3% (9) displayed premalignant histopathological features in their specimens. Conclusion In conclusion, adopting a selective approach, where only gallbladder specimens with macroscopic abnormalities undergo HPE, seems prudent, especially in regions with low GBCincidence. Our study, which revealed no cases of GBC, supports this approach. It not only reduces the risk of missing incidental carcinoma in clinically unsuspected cases but also proves cost-effective and reduces the histopathology department workload without compromising patient outcomes. Therefore, we advocate for routine macroscopic examination of gallbladder specimens for abnormalities before HPE submission, particularly in cholecystectomy patients with gallstone disease.

282P Nivolumab and ipilimumab combination treatment in advanced intrahepatic cholangiocarcinoma and gallbladder cancer

282P Nivolumab and ipilimumab combination treatment in advanced intrahepatic cholangiocarcinoma and gallbladder cancer

Can laparoscopic surgery be the preferred strategy for gallbladder cancer?

Gallbladder cancer, notoriously known for its high malignancy, predominantly requires radical surgery as the treatment of choice. Although laparoscopic techniques have become increasingly prevalent in abdominal surgeries in recent years, the progress of laparoscopic techniques in gallbladder cancer is relatively slow. Due to the anatomical complexity, technical difficulty, and biological features of gallbladder cancer that is prone to metastasis and dissemination, traditional open surgery is still the main surgical approach. This study aims to reappraisal the current state of laparoscopic surgery for gallbladder cancer by appraising clinical practice and research evidence. Laparoscopic surgery for various stages of gallbladder cancer, including early, advanced, incidental, and unresectable gallbladder cancer were discussed. The promise and limitations of laparoscopic techniques are systematically explored.

Progress and controversy in minimally invasive approach to radical cholecystectomy for gallbladder cancer

Surgical treatment is one of the most important forms of treatment in patients with gallbladder cancer. With the development of minimally invasive technology, the feasibility, safety and efficacy of minimally invasive approaches such as laparoscopic or robotic-assisted radical cholecystectomy for gallbladder cancer have received continuous attention.For patients with an early T-stage (Tis or T1a), laparoscopic simple cholecystectomy is safe and economical, with a good prognosis for postoperative patients, and it has been widely accepted and performed. Radical resection of advanced gallbladder cancer requires resection of the gallbladder, its liver bed, and other neighboring invaded organs, as well as clearance of regional lymph nodes, which requires experienced gallbladder cancer treatment teams to strictly grasp the indications, select appropriate patients, and formulate a good surgical strategy to ensure the therapeutic effect. Meanwhile, robot-assisted radical resection for gallbladder cancer has been performed in a few centers and shows good clinical potential, but more high-quality studies are needed to further evaluate its value in gallbladder cancer treatment.

Applications of artificial intelligence in biliary tract cancers.

Biliary tract cancers are malignant neoplasms arising from bile duct epithelial cells. They include cholangiocarcinomas and gallbladder cancer. Gallbladder cancer has a marked geographical preference and is one of the most common cancers in women in northernIndia. Biliary tract cancers are usually diagnosed at an advanced, unresectable stage. Hence, the prognosis is extremely dismal. The five-year survival rate in advanced gallbladder cancer is < 5%. Hence, early detection and radical surgery are critical to improving biliary tract cancer prognoses. Radiological imaging plays an essential role in diagnosing and managing biliary tract cancers. However, the diagnosis is challenging because the biliary tract is affected by many diseases that may have radiological appearances similar to cancer. Artificial intelligence (AI) can improve radiologists' performance in various tasks. Deep learning (DL)-based approaches are increasingly incorporated into medical imaging to improve diagnostic performance. This paper reviews the AI-based strategies in biliary tract cancers to improve the diagnosis and prognosis.

SWOG 1609 cohort 48: anti-CTLA-4 and anti-PD-1 for advanced gallbladder cancer.

Most patients with advanced gallbladder cancer are treated with multiagent chemotherapy. Immune checkpoint inhibitors offer the possibility of a durable response with less toxicity. This prospective, multicenter, open-label study was designed to evaluate the anticancer activity of nivolumab plus ipilimumab in patients with advanced gallbladder cancer. Nineteen patients with advanced gallbladder cancer refractory to ≥1 previous therapy received nivolumab 240mg intravenously every 2weeks and ipilimumab 1mg/kg intravenously every 6weeks until disease progression or unacceptable toxicity. The primary end point was confirmed radiographic overall response rate (ORR) (complete response [CR]+partial response [PR] confirmed on subsequent scan); secondary end points included unconfirmed overall response, clinical benefit rate (confirmed and unconfirmed responses+stable disease >6months), progression-free survival, overall survival, and toxicity. The confirmed ORR was 16% (CR, n=1 [5%]; PR, n=2 [11%]); all were microsatellite stable, and the confirmed CR had undetectable programmed death-ligand 1 by immunohistochemistry. The unconfirmed ORR and clinical benefit rates were both 32%. The median duration of response was 14.8months (range, 4-35.1+ months). The 6-month progression-free survival was 26% (95% CI, 12-55). The median overall survival was 7.0months (95% CI, 3.9-19.1). The most common toxicities were fatigue (32%), anemia (26%), and anorexia (26%). Aspartate aminotransferase elevation was the most common grade 3/4 toxicity (11%). There was 1 possibly related death (sepsis with attendant hepatic failure). Ipilimumab plus nivolumab was well tolerated and showed modest efficacy with durable responses in previously treated patients with advanced gallbladder cancer. NCT02834013 (ClincialTrials.gov). This prospective study assessed the efficacy and safety of nivolumab plus ipilimumab in 19 patients with advanced gallbladder cancer refractory to previous therapy. The combination demonstrated modest efficacy with a 16% confirmed overall response rate, durable responses, and manageable toxicities, suggesting potential benefits for this challenging patient population.

Predictors of Toxicity in a Randomized Study of Consolidation Chemoradiation Versus Observation After First Line Chemotherapy in Advanced Gall Bladder Cancers

PURPOSEGBC usually presents in advanced stage. First-line CT is the standard of care and there is no other option for responders than to wait for disease progression. We conducted a randomised study of consolidation CTRT versus observation in responders to first line CT (NCT05493956) which showed an improvement in overall survival by 6 months and therefore is practice changing. We are reporting the toxicity and factors predicting toxicity due to CTRT so that it informs appropriate patient selection. MATERIALS & METHODSResponders to first line CT (partial response, stable disease) were randomised to CTRT versus observation after 4 cycles. CTRT was delivered by 3DCRT (along-with concurrent capecitabine at 1250 mg/m2) to a dose of 45Gy in 25 fractions to GBC and lymphatics followed by a boost of 9 Gy in 5 fractions to the GBC. Toxicities documented during CTRT were recorded using the RTOG criteria. Dose volume data were correlated with the radiation induced side effects. RESULTSAmong 135 patients enrolled both arms are well balanced demographically and 58% patients had T4 tumours, 42% had N2 and 15% had paraaortic LN (PALN), 27% underwent upfront stenting. Grade 3 adverse events like anaemia, dyspepsia, hepatotoxicity (Child Pugh B), GI bleed due to CTRT was observed in 9%,1.5%,13% and 5.8% respectively. Age >58 years(p=0.02), PTV1volume (>919cc, p=0.02), PTV2 volume (>380cc, p=0.01), mean liver dose (>28 Gy, p=0.07), Liver V40 (>50%, p=0.02) predicted radiation induced liver disease (RILD). An ROC analysis revealed a cut-off value of PTV1volume of 800 cc (sensitivity and specificity of 75% and 54%) and PTV2volume of 300 cc (sensitivity and specificity of 81% and 65%) for prediction of hepatotoxicity. Duodenum V45 >45% (p=0.02) predicted grade 3 anaemia. Numerically high V15 duodenum (98%, p=0.11), large PTV2 volume >484cc (p=0.06) and prior stenting had predilection for GI bleed. CONCLUSIONConsolidation CTRT is tolerable in those with PTV1 volume less than 800 cc, PTV 2 volume less than 300 cc, Liver V40 <50%, Duodenum V45<45%.

Prognostic Significance of HER2 Expression in Advanced Gallbladder Cancer

Prognostic Significance of HER2 Expression in Advanced Gallbladder Cancer

Hepatic arterial infusion chemotherapy combined with bevacizumab plus a PD-1 inhibitor for gallbladder cancer with hepatic oligometastasis: a real-world study.

Gallbladder cancer (GBC) is different from other biliary tract cancers in terms of molecular phenotype and microenvironment. Specific treatments for GBC need to be urgently explored. This study preliminarily investigated the clinical value of hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab plus a programmed death receptor-1 (PD-1) inhibitor for treatment of GBC with hepatic oligometastasis. We retrospectively collected data on GBC patients with hepatic oligometastasis, who received this combination therapy. The clinical data, conversion rate, treatment response, adverse events (AEs), and short-term survival were summarized. The responses of primary gallbladder lesions and hepatic metastasis, and their effect on prognosis, were investigated. A total of 27 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 55.6% and the disease control rate (DCR) was 85.2%. Median overall survival (OS) time was 15.0 months and the 1-year survival rate was 64.0%. Median progression-free survival (PFS) time was 7.0 months and the 1-year PFS rate was 16.2%. Six patients (22.2%) were successfully converted to resection. Compared with primary gallbladder lesions, it appeared more difficult for patients with hepatic metastasis to achieve remission (ORR: 40.7% vs. 77.8%; P=0.012), but its response appeared to be closely related to the prognosis [median OS: 16.0 months in the complete response (CR) or partial response (PR) group vs. 11.0 months in the stable disease (SD) or progressive disease (PD) group, P=0.070; median PFS: 12.0 months in the CR or PR group vs. 6.5 months in the SD or PD group, P<0.001]. Preoperative CA19-9 of >1,900 U/mL and >5 cm metastatic lesions were associated with an unsatisfactory response, whereas a significant decrease of 18F-fluorodeoxyglucose (18F-FDG) uptake may be a marker of tumor remission. The combination of HAIC, a PD-1 inhibitor, and bevacizumab shows potential for advanced GBC with hepatic oligometastasis. The therapeutic response of hepatic metastasis had a greater influence on prognosis than that of primary gallbladder lesions.

Prognostic significance of HER2 expression in advanced gallbladder cancer

Prognostic significance of HER2 expression in advanced gallbladder cancer

Fatty Acid Binding Protein 1 is an Independent Prognostic Biomarker for Gallbladder Cancer with Direct Hepatic Invasion.

Background: Direct liver invasion (DI) is a predominant pathway of gallbladder cancer (GBC) metastasis, but the molecular alterations associated with DI remain addressed. This study identified specific genes correlated with DI, which may offer a potential biomarker for the diagnosis and prognosis of advanced GBC. Methods: RNA samples from 3 patients with DI of GBC were used for RNA-seq analysis. Differentially expressed genes and metabolic pathways between primary tumor (T) and DI tissue was used to analyze aberrant gene expressions. Immunohistochemistry (IHC) of fatty acid binding protein 1 (FABP1) in 62 patients with DI was engaged to evaluate its association with clinicopathological characteristics and prognosis. IHC of CD3+ and CD8+ T cells was analyzed for their correlation with FABP1 expression, clinicopathological features and prognosis. Univariate and multivariate Cox hazards regression analyses were performed to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: FABP1 mRNA levels were significantly upregulated in DI region compared to T tissue. IHC results showed identical results with elevated FABP1 (p < 0.0001). Expression of FABP1 in DI region was significantly associated with lymph node metastasis (P = 0.028), reduced DFS (P = 0.013) and OS (P = 0.022); in contrast, its expression in T region was not associated with clinicopathological characteristics and prognosis (P > 0.05). The density of CD8+ T cells in DI region with higher FABP1 expression was significantly lower than that with lower FABP1 expression (p = 0.0084). Multivariate analysis unveiled those hepatic metastatic nodules (HR = 3.35, 95%CI: 1.37-8.15, P = 0.008) and FABP1 expression in DI region (HR = 2.01, 95%CI: 1.05-3.88, P = 0.036) were high risk factors for OS, and FABP1(HR = 2.05, 95%CI: 1.04-4.06, P = 0.039) was also a high risk factor for DFS. Conclusions: Elevated expression of FABP1 in DI region serves as a potential prognostic biomarker for advanced GBC with DI.

Management of advanced Gall bladder cancer patients with obstructive jaundice: An Institutional Experience

Management of advanced Gall bladder cancer patients with obstructive jaundice: An Institutional Experience

Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis.

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.