Intrahepatic Gallbladder Research Articles

Formation and rupture of liver hematomas caused by intrahepatic gallbladder perforation: A case report and review of literature

Formation and rupture of liver hematomas caused by intrahepatic gallbladder perforation: A case report and review of literature

A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy.

To evaluate the efficacy and safety of nanvuranlat [an L-type amino acid transporter 1 inhibitor] monotherapy as a later-line treatment in advanced, metastatic, and refractory biliary tract cancers. A multicenter, randomized, double-blind, placebo-controlled phase II study was conducted across fourteen leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of 5 consecutive days, followed by 9 days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and disease control rate. Subgroup analysis was performed in patients with high L-type amino acid transporter 1 expression and biliary tract cancer subtypes. A total of 211 patients were screened, of which 105 eligible patients were randomized. Among these, 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared with placebo (HR, 0.56; 95% confidence interval, 0.34-0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory biliary tract cancer with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.

Genetic issues in ICP.

Intrahepatic cholestasis of pregnancy (ICP) is the commonest gestational liver disorder with variable global incidence. Genetic susceptibility, combined with hormonal and environmental influences, contributes to ICP aetiology. Adverse pregnancy outcomes linked to elevated serum bile acids highlight the importance of comprehensive risk assessment. ABCB4 and ABCB11 gene variants play a significant role in about 20% of severe ICP cases. Several other genes including ATP8B1, NR1H4, ABCC2, TJP2, SERPINA1, GCKR and HNF4A have also been implicated with ICP. Additionally, ABCB4 variants elevate the risk of drug-induced intrahepatic cholestasis, gallstone disease, gallbladder and bile duct carcinoma, liver cirrhosis and abnormal liver function tests. Genetic variations, both rare and common, intricately contribute to ICP susceptibility. Leveraging genetic insights holds promise for personalised management and intervention strategies. Further research is needed to elucidate variant-specific phenotypic expressions and therapeutic implications, advancing precision medicine in ICP management.

Differing genetic variants associated with liver fat and their contrasting relationships with cardiovascular diseases and cancer

The mechanisms underlying the association of steatotic liver disease with cardiovascular and cancer outcomes are poorly understood. We aimed to use MRI-derived measures of liver fat and genetics to investigate causal mechanisms that link higher liver fat to various health outcomes. We conducted a genome-wide association study on 37,358 UK Biobank participants to identify genetic variants associated with liver fat measured from MRI scans. We used a Mendelian randomisation approach to investigate the causal effect of liver fat on health outcomes independent of BMI, alcohol consumption and lipids using data from published genome-wide association studies and FinnGen. We identified 13 genetic variants associated with liver fat that had differing effects on the risks of health outcomes. Genetic variants associated with impaired hepatic triglyceride export showed liver fat-increasing alleles to be correlated with a reduced risk of coronary artery disease and myocardial infarction but an elevated risk of type 2 diabetes, while variants associated with enhanced de novo lipogenesis showed liver fat-increasing alleles to be linked to a higher risk of myocardial infarction and coronary artery disease. Genetically higher liver fat content increased the risk of non-alcohol-related cirrhosis, hepatocellular carcinoma, and intrahepatic bile duct and gallbladder cancers, exhibiting a dose-dependent relationship, irrespective of the mechanism. This study provides fresh insight into the heterogeneous effect of liver fat on health outcomes. It challenges the notion that liver fat per se is an independent risk factor for cardiovascular disease, underscoring the dependency of this association on the specific mechanisms that drive fat accumulation in the liver. However, excess liver fat, regardless of the underlying mechanism, appears to be causally linked to cirrhosis and cancers in a dose-dependent manner. This research advances our understanding of the heterogeneity in mechanisms influencing liver fat accumulation, providing new insights into how liver fat accumulation may impact various health outcomes. The findings challenge the notion that liver fat is an independent risk factor for cardiovascular disease and highlight the mechanistic effect of some genetic variants on fat accumulation and the development of cardiovascular diseases. This study is of particular importance for healthcare professionals including physicians and researchers, as well as patients, as it allows for more targeted and personalised treatment by understanding the relationship between liver fat and various health outcomes. The findings emphasise the need for a personalised management approach and a reshaping of risk assessment criteria. It also provides room for prioritising a clinical intervention aimed at reducing liver fat content (likely via intentional weight loss) that could help protect against liver-related fibrosis and cancer.

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

Cadonilimab in combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial.

e16158 Background: PD-1 or PD-L1 inhibitors plus chemotherapy as the first-line treatment has been proven to be effective in improving the prognosis of advanced biliary tract cancer (BTC) patients. However, there is still considerable demand for further improvement of BTC patients’ prognosis. This trial aims to evaluate the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) plus gemcitabine and cisplatin for patients with advanced BTC in first -line treatment. Methods: In this phase II, single-arm trial, we will enroll 65 patients with previously untreated, unresectable, locally advanced or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, days 1, every three weeks) plus gemcitabine (1000 mg/m2, days 1, 8, Q3W), and cisplatin (25 mg/m2, days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, days 1, Q3W) until disease progression or unacceptable toxicity. Treatment response was evaluated with image-based assessment according to response evaluation criteria insolid tumors (RECIST) version 1.1. by two experienced experts and further explored multiple methods, such as 3D visualisation and Spectral computed tomography Scan. The primary endpoint was the objective response rate (ORR); the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included associations between response, molecular characteristics, and the immune microenvironment. Results: Between June 30, and January 31, 2024, a total of 30 patients have undergone at least one imaging evaluation. 66.7% of these patients were diagnosed with ICC, 23.3% with GBC, and 10% with ECC. The mean age was 58.4 years, and 60% of the patients were male. 24 (80%) patients had metastasis. Among them, 1 (3.3%) patient acheived complete response (CR), 15 (50%) patients had partial response (PR) and 8 (26.7%) patients presented with stable disease (SD). The ORR was 53.3% and the DCR was 80%. The most common treatment-related adverse events (TRAEs) of any grade were rash (80%) and anaemia (76.7%). Grade 3 TRAEs were observed in 66.7% of the patients. The most frequent grade 3 TRAEs were anaemia (33.3%), and leukocytopenia (33.3%). No grade 4 or 5 events were observed. All patients were microsatellite stable (MSS), and the median TMB was 2.88 (0-109.44) Muts/Mb. Conclusions: Cadonilimab plus gemcitabine and cisplatin shown a promising efficacy and acceptable safety profile as first-line treatment for advanced BTC patients. Clinical trial information: NCT05978609 .

Management of biliary tract cancers in early-onset patients: A nested multicenter retrospective study of the ACABI GERCOR PRONOBIL cohort.

Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders. We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method. Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029). Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.

Characterizing the burden of biliary tract cancers across 28 hospitals in Ontario, Canada.

The incidence of biliary tract cancers (BTC) appears to be increasing worldwide. We analyzed the characteristics of BTC-related hospitalizations under medical services across 28 hospitals in Ontario, Canada. This study uses data collected by GEMINI, a hospital research data network. BTC-related hospitalizations from 2015 to 2021 under the Department of Medicine or intensive care unit were captured using the International Classification of Diseases, 10th revision, codes for intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, and gallbladder cancers. A total of 4596 BTC-related hospitalizations (2720 iCCA, 1269 extrahepatic cholangiocarcinoma, 607 gallbladder cancers) were analyzed. The number of unique patients with BTC-related hospitalizations increased over time. For iCCA-related hospitalizations, the total number of hospitalizations increased (from 385 in 2016 to 420 in 2021, p=.005), the hospital length of stay decreased over the study period (mean 10days [SD, 12] in 2016 to 9days [SD, 8] in 2021, p=.04), and the number of in-hospital deaths was stable (from 68 [18%] in 2016 to 55 [13%] in 2021, p=.62). Other outcomes such as 30-day readmissions, medical imaging tests, intensive care unit-specific hospitalizations, and length of stay were stable over time for all cohorts. The cost of hospitalization for the BTC cohort increased from median $8203 CAD (interquartile range, 5063-15,543) in 2017 to $8507 CAD (interquartile range, 5345-14,755) in 2021. This real-world data analysis showed a rising number of patients with BTC-related hospitalizations and rising number of iCCA-related hospitalizations across 28 hospitals in Ontario between 2015 and 2021.

Neoadjuvant and adjuvant therapy for biliary tract cancer: Advances and limitations.

Biliary tract cancers (BTC), a rare and aggressive consortium of malignancies, consisting of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma. While most patients present with metastatic disease, a minority of patients with BTC are eligible for curative surgical resection at the time of presentation. However, these patients have poor 5-year overall survival rates and high rates of recurrence, necessitating the improvement of the neoadjuvant and adjuvant treatment of BTC. In this review, we assess the neoadjuvant and adjuvant clinical trials for the treatment of BTC and discuss the challenges and limitations of clinical trials, as well as future directions for the treatment of BTC.

Characterizing outcomes of ERBB2-amplified biliary tract cancer.

492 Background: A subset of biliary tract cancers (BTC) feature amplification (amp) of the human epidermal growth factor receptor 2 ( ERBB2) gene. The prognostic role and treatment in these patients (pts) are poorly understood. This study aims to characterize the clinical outcomes and molecular profiles of ERBB2-amp BTC. Methods: We conducted a retrospective analysis of clinical outcomes data and next-generation sequencing (NGS) at MD Anderson (MDA) and Foundation Medicine (FMI) from 2009-2023 in pts with ERBB2-amp BTC including all classes of genomic alterations (GA) in other genes. Progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test. Results: 80 pts (MDA) were identified with ERBB2-amp BTC with documented treatment and NGS data. Pts (Table) who received ERBB2-directed therapy (22.4 vs. 12.0 m, p=0.004), surgery (21.0 vs. 12.0 m, p=0.002), local therapy with RT/ablation/Y90 (excluding surgical pts, 20.6 vs. 11.6 m, p = 0.0001) had significantly longer OS. Median PFS (mPFS) without ERBB2-directed therapy for 1st, 2nd, and 3rd line systemic therapy was 4.1, 3, and 2.2 m. mPFS with all ERBB2-directed therapy was 4.1 m, but that of gemcitabine (gem)-based plus trastuzumab (tt) and 5FU-based plus tt was 7.8 and 3.8 m (p=0.018). The most common concurrent-GA at MDA, any co-amps (72.7%; 19.2 vs. 20.3 m, p=0.69) and TP53 inactivating mutation (70.4%; 16.6 vs. 14.9 m, p=0.89), had no OS association; 3rd most common co-GA found, CDK12 amp (46.4%), had a trend toward a better OS (19.2 vs. 14.3 m, p=0.089). FMI database showed ERBB2 amp in 3.2%, 5.4%, and 8.9% in intrahepatic cholangiocarcinoma (iCCA), extrahepatic CCA, and gallbladder cancer. The most common co-GA included TP53, CDKN2A/B, and CCNE1. FGFR2 fusions (iCCA) were mutually exclusive with ERBB2 amp (0%, MDA/FMI); IDH1 (iCCA) with ERBB2 amp, 5.7 and 4.3% (MDA and FMI). Conclusions: ERBB2-amp BTC has shorter mPFS or mOS without ERBB2-directed therapy, surgery, or local therapy, suggesting clinical benefit from multi-disciplinary care and targeted therapy. Co-GA with ERBB2-amp did not demonstrate a significant association with survival outcomes. [Table: see text]

Immunotherapy for the treatment of biliary tract cancer: an evolving landscape.

Biliary tract cancers (BTCs), consisting of intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, are an aggressive, heterogeneous malignancy. They are most often diagnosed in the locally advanced or metastatic setting, at which point treatment consists of systemic therapy or best supportive care. Our understanding of the tumor microenvironment and the molecular classification has led to the identification of targetable mutations, such as isocitrate dehydrogenase 1 and fibroblast growth factor receptor 2. Despite the identification of these genomic alterations, until recently, little advancement had been made in the first-line setting for advanced BTC. While immunotherapy (IO) has revolutionized the treatment of many malignancies, the use of IO in BTC had yielded limited results prior to TOPAZ-1. In this review, we discuss the systemic therapeutic advances for BTC over the past decade, the rationale for immunotherapy in BTC, prior trials utilizing IO in BTC, and current and emerging immune-based therapeutic options. We further analyze the culmination of these advances, which resulted in the approval of durvalumab with gemcitabine and cisplatin for the first-line treatment of BTC per TOPAZ-1. We also discuss the results of KEYNOTE-966, which similarly reported improved clinical outcomes with the use of pembrolizumab in combination with gemcitabine and cisplatin.

Laparoscopic cholecystectomy in situs inversus with partially intrahepatic gallbladder: a case report

Situs inversus totalis (SIT) is a rare condition with mirrored visceral organs. Biliary colic has delayed diagnosis in this cohort of patients. Laparoscopic cholecystectomy (LC) in such condition is a technically challenging procedure and requires preoperative imaging. We report a case of a 37 years old lady with pain in left upper abdomen for last 1 year. Upon evaluation, she was diagnosed with cholelithiasis with SIT. MRCP was done to delineate the anatomy. The patient underwent LC in a split-leg position with mirrored port position by a right-handed surgeon. The duration of surgery was 90 minutes and the patient was discharged uneventfully in 48 hours and was well on one-week follow-up. LC is considered a safe surgery in patients with SIT. It requires an experienced surgeon, re-training of visual-motor coordination and modification of surgical steps.

Comparative Genomic Analysis and Clinical Outcomes of BRAF-mutated Advanced Biliary Tract Cancers.

BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC. We analyzed two nonoverlapping cohorts. We examined the genomic landscape of BRAF-mutated iCCA in a "genomic cohort" [187 class I, 82 class II, 113 class III BRAF mutants and 8,026 wildtype (WT)]. We also analyzed median progression-free survival (PFS) and overall survival (OS) on first-line chemotherapy in a separate multi-institutional "clinical cohort" of patients with BTC (including iCCA and extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer; 41 class I, 32 class II+III BRAF mutants and 1,042 WT). In the entire BTC clinical cohort, the median PFS was shorter for class I [HR, 2.11 (P < 0.001)] and class II+III [HR, 1.72 (P = 0.007)] as compared with BRAF WT. OS was also shorter in class I [HR, 2.04 (P = 0.011)] and class II+III [HR, 1.86 (P = 0.002)] as compared with BRAF WT. In the iCCA subgroup, class I alterations were mutually exclusive with FGFR2, IDH1/2, ERBB2, and KRAS mutations. Class II+III mutations appear to be mutually exclusive with FGFR2 and KRAS. In BTC, all classes of BRAF mutations are associated with a worse prognosis. BRAF mutations occur in 5% of iCCA subgroup and may be mutually exclusive with other targetable mutations.

Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis.

Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC. Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible. A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs-15 studies), perihilar-distal CCAs (p/dCCAs-7 studies), and gallbladder cancer (GBC-5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively. From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.

Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study

BackgroundThe aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. MethodsThis study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. ResultsOf the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien–Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). ConclusionPostoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

Sintilimab plus nab-paclitaxel as second-line treatment for advanced biliary tract cancer: study protocol for an investigator-initiated phase 2 trial (NapaSinti trial)

BackgroundBiliary tract cancer (BTC) is a relatively rare but highly aggressive malignancy. However, there is currently no satisfactory second-line regimen for patients without specific genetic mutations. Nanoparticle albumin–bound paclitaxel, also known as nab-paclitaxel (Abraxane, Bristol Myers Squibb), has shown activity in patients with BTC. Studies investigating the immunogenic features of BTC suggested that checkpoint inhibition may lead to antitumor immune responses. In recent years, improved survival has been observed in patients treated with chemotherapy combined with immunotherapy across multiple cancer types, including BTC. This clinical trial aims to evaluate the efficacy and safety of second-line sintilimab in combination with nab-paclitaxel in advanced BTC patients.MethodsThe NapaSinti trial is a prospective, nonrandomized, open-label, phase 2 study conducted at a tertiary hospital in Chengdu, China. Eligible patients are those with histologically or cytologically confirmed locally advanced non-resectable or metastatic adenocarcinoma in the biliary tract (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), aged between 18 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who have experienced disease progression after prior gemcitabine- or fluorouracil-based chemotherapy and have not received taxane or immune checkpoint inhibitor treatment. Enrolled patients will receive intravenous administration of sintilimab 200 mg on day 1 and nab-paclitaxel 125 mg/m2 on days 1 and 8, every three weeks. The primary endpoint is the objective response rate (ORR), while the secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety. Exploratory objectives aim to identify biomarkers and molecular signatures for predicting response or prognosis. Using Simon’s two-stage design, a total of 63 participants will be enrolled in the study. This trial was initiated in March 2022 in China.DiscussionThe NapaSinti trial evaluates the efficacy and safety of second-line sintilimab plus nab-paclitaxel for advanced biliary tract cancer. Additionally, the trial provides an opportunity for translational research.Trial registrationChinese Clinical Trial Registry ChiCTR2100052118. Registered October 19, 2021.

Incidence and Patterns of Digestive Organ Cancer in Georgia: Insights from a Population-Based Registry Study in 2021.

Digestive organ cancer, also known as gastrointestinal (GI) cancer, refers to cancer that occurs in the digestive tract. In this population-based registry study, we aimed to investigate the incidence of GI in Georgia and to identify any patterns in the occurrence of different types of this disease. The study included all cases of GI cancer that were diagnosed in Georgia in 2021. We analyzed 1635 patients' data to determine the overall and age-standardized incidence of GI cancer in the country. The analyses were performed for esophagus, stomach, colon, rectum, anus, liver and intrahepatic bile ducts, gallbladder, and pancreas separately. The descriptive statistics used in the study-specifically counts, means, proportions, and rates-were calculated using the statistical software STATA version 17.0. (StataCorp, College Station, TX, USA). The results of the study showed that the incidence of digestive organ cancer in Georgia was similar to the global average. However, there were some notable differences in the specific types of GI cancer that were most common in the country. Overall, this study provides important insights into the incidence of digestive organ cancer in Georgia and highlights the need for further research to better understand the factors that contribute to this disease.

Economic evaluation for the US of durvalumab plus gemcitabine and cisplatin (DGC) in advanced biliary tract cancer (BTC).

4081 Background: BTCs are a group of relatively rare malignancies comprised of intrahepatic cholangiocarcinoma (CCA), extrahepatic CCA, and gallbladder cancer. The first-line standard of care of gemcitabine and cisplatin (GC) has remained unchanged for the past decade, highlighting the need for novel therapies. The TOPAZ-1 trial demonstrated improved progression-free (PFS) and overall survival (OS) with durvalumab added to GC. This trial-based economic evaluation estimated the cost-effectiveness/utility of DGC versus GC from a US payer perspective. Methods: A three state partitioned survival model (Progression-free, Progressed, Death) was developed to compare costs and overall survival outcomes associated with both treatments. PFS and OS curves were digitized, and parametric functions fitted. A 5-year time horizon with a 3% discount rate/year was considered. Costs of treatment (average sales price), administration, and monitoring parameters were sourced from Centers for Medicare &amp; Medicaid Services databases; costs of adverse event management (grade 3/4 with rate ≥ 5%) were sourced from prior BTC economic evaluations. Life years (LY), quality adjusted life years (QALY), incremental cost-effectiveness and utility ratios (ICER/ICUR) were estimated in a base case (BCA) and probabilistic sensitivity analyses (PSA). A cost-effectiveness acceptability curve (CEAC) was plotted to determine the probability of either treatment being cost-effective over the other at different willingness to pay (WTP) thresholds. Results: Exponential regression was used to extrapolate DGC and GC survival curves. As shown in the table, the BCA (PSA) shows an incremental cost of DGC over GC of 131,350 (131,212), incremental LY of 0.38 (0.38), and incremental QALY of 0.26 (0.28). The BCA and (PSA) ICERs reveal an additional 345,658 (345,295) per LY gained (g) and an additional 505,192 (468,614) per QALYg. The CEAC curve shows that DGC treatment has a 50% probability of being cost-effective at a WTP threshold value of 525,000 and 100% probability at a threshold of 1,375,000 or above. Conclusions: This economic evaluation demonstrates that, in the setting of advanced BTC, DGC is associated with a slight improvement in LY and QALY, yet at a marked incremental cost, requiring a very high WTP threshold. [Table: see text]

The impact of anti-EGFR therapy when added to first-line standard platinum-gemcitabine chemotherapy in advanced biliary tract cancers: A meta-analysis of randomized studies.

e16109 Background: Biliary tract cancers (BTCs) represent the second-most common primary liver cancers. They are a heterogeneous group of tumors that include Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, and ampullary carcinoma. BTCs are usually diagnosed in an advanced stage and carry a poor prognosis. A better understanding of cancer biology has led to advances in targeted treatments in other cancers but remains an unmet need in BTCs. We conducted this meta-analysis to evaluate the efficacy of anti-EGFR therapy when added to the standard platinum-gemcitabine chemotherapy as first-line in patients with advanced BTCs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of biliary tract tumors, randomized studies of first-line platinum-gemcitabine with and without anti-EGFR therapies, and studies that reported overall (OS) and progression free survival (PFS). A meta-analysis using the fixed effects and random effects models was conducted. Results: Four randomized studies with a total of 569 patients were included. Three studies were randomized phase 2 and one was randomized phase 3. Three studies used oxaliplatin and one used cisplatin in addition to gemcitabine as the standard combination. Panitumumab was used in two studies while cetuximab and erlotinib were used in one study each. The addition of anti-EGFR agent to first-line platinum-gemcitabine in advanced BTC resulted in a superior OS (HR = 0.72, 95%CI 0.61-0.85) and PFS (HR = 0.76, 95%CI 0.63-0.92). When the analysis was restricted to anti-EGFR monoclonal antibodies, their PFS benefit persisted (HR = 0.72, 95%CI 0.55-0.95), but their OS benefit failed to reach statistical significance (HR = 0.83, 95%CI 0.65-1.07). Conclusions: This is the first meta-analysis to show the addition of anti-EGFR agents to the standard first-line platinum-gemcitabine chemotherapy improves OS and PFS in advanced BTC.

The Surgical outcomes of fundus-first technique in lowering the rate of bile duct injuries and bleeding during open cholecystectomy that facing intraoperative difficulties: A single-center prospective study

Background: The problem of difficult gallbladder is not clearly defined and associated with real missing of therapeutic approaches that decreased morbidity. Moreover, the difficult gallbladder was reported as a contributing risk factor for biliary injury due to raised difficulty in surgical dissection within Calot’s triangle. The aim of this study is to determine the surgical outcomes of the open fundus-first cholecystectomy in lowering the rate of lethal intraoperative risks.&#x0D; Subjects and Methods: Our prospective study conducted during the period of January 2019 to December 2022 at Ibn Sina specialized hospital, Khartoum, Sudan, for two hundred and fifty-three patients underwent elective open fundus-first cholecystectomy for intraoperative difficulties.&#x0D; Results: the majority of cases had long-standing cholelithiasis with intraoperative difficulties revealed by pre-operative TUS and MRCP which required open fundus-first cholecystectomy in 173 (68.4%) of patients, (P-value &lt;0.05). The operative surgical time was 120 minutes in 103 patients (40.7%), (P-value &lt;0.05). During open cholecystectomy, variable intraoperative difficulties were found in all patients, (P-value &lt;0.05) and were divided into: (A) Contracted intra-hepatic gallbladder seen in 157 (62.1%) of cases; (B) Distorted anatomy within Calot's triangle seen in 135 (53.4%) of patients; and (C) Intraoperative bleeding from the liver bed was observed as bloody oozing form in 150 (59.3%) of cases. Our patients had minimal postoperative complications like mild wound infection in 8 (3.2%) of cases and mortality rate was zero. &#x0D; Conclusions: There is a need for appropriate therapeutic and preventive strategies in healthcare systems for safe dealing with difficult cholecystectomy. Unclear anatomy due to severe inflammatory dense adhesions at Calot’s triangle and CBD stones needing difficult surgeries are the most important limiting factors for fundus-first laparoscopic cholecystectomy. Hence, we humbly recommend an open approach of fundus-first cholecystectomy as safe surgical option to reduce the incidence of bile duct injuries and intra-operative bleeding.