Gallbladder Cancer Research Articles

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

ASO Author Reflections: Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer

Solitary fibrous tumor of the gallbladder: a case report

Abstract Background Primary solitary fibrous tumors (SFTs) of the gallbladder are rare. Here, we report the case of a patient who underwent surgical treatment for a primary SFT originating in the gallbladder. Case presentation A 48-mm gallbladder tumor was detected in a 70-year-old man using abdominal ultrasonography at a primary hospital, and he was subsequently referred to our department. A 50-mm enhanced tumor in the gallbladder was identified using computed tomography. Magnetic resonance imaging revealed a smooth-marginated tumor with hyperintensity on T2-weighted imaging. 18F-Fluorodeoxyglucose positron emission tomography confirmed high-level fluorodeoxyglucose uptake in the gallbladder tumor in the early phase without increasing uptake in the later phase. Surgical resection was planned to evaluate the tumor diagnosis. Initially, we performed open cholecystectomy with wedge resection of the gallbladder bed. Intraoperative pathological examination suggested gallbladder cancer; therefore, we performed radical surgery, including resection of the common bile duct, extended radical lymphadenectomy, and choledochojejunostomy. Ultimately, the final pathological examination revealed an SFT originating from the gallbladder with a negative surgical margin. Postoperatively, the patient developed bile leakage that was treated with tube drainage. The patient recovered satisfactorily and was discharged on postoperative day 20. At 24 months postoperatively, the patient was in good general condition without recurrence. Conclusions We report a rare case of a primary SFT originating in the gallbladder. Clinicians should be aware that SFT can be found in the gallbladder, and when it is difficult to make a preoperative diagnosis, surgical treatment should be considered.

Challenges in Diagnosing and Managing Sarcomatoid Carcinoma of the Gallbladder and Synchronous Colon Cancer

Challenges in Diagnosing and Managing Sarcomatoid Carcinoma of the Gallbladder and Synchronous Colon Cancer

Expression of Concern: Up-regulated microRNA-33b inhibits epithelial-mesenchymal transition in gallbladder cancer through downregulating CROCC.

Expression of Concern: Up-regulated microRNA-33b inhibits epithelial-mesenchymal transition in gallbladder cancer through downregulating CROCC.

Endoscopic diagnosis and management of gallbladder carcinoma in minimally invasive era: New needs, new models

Endoscopic diagnosis and management of gallbladder carcinoma in minimally invasive era: New needs, new models

Advantage of Log Odds of Metastatic Lymph Nodes After Curative-Intent Resection of Gallbladder Cancer.

Lymph node metastasis (LNM) is among the most important predictors of poor prognosis after surgery for gallbladder cancer (GBC). Traditionally, staging has been based on the raw count of LNM, with a high risk of understaging patients who undergo inadequate lymph node dissection (LND). The log odds of metastatic lymph nodes (LODDS) may represent an alternative staging approach to stratify patients more accurately after resection of GBC. In this cross-sectional study, patients who underwent curative-intent surgery with LND for GBC were identified from an international database. Two predictive models were built and compared, each integrating a different lymph nodes status indicator [i.e., American Joint Committee on Cancer (AJCC) and LODDS]. Among 199 patients, the median number of lymph nodes examined was 5 [interquartile range (IQR): 3.0, 8.0]; most patients had T1 (n = 26, 13.1%) or T2 (n = 97, 48.7%) disease, and a subset had LNM (n = 87, 44.0%). Multivariable Cox analysis demonstrated LODDS was an independent predictor of overall survival [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.5-2.3; p < 0.001]. The LODDS model demonstrated better performance compared with a traditional model that utilized the AJCC N category [concordance (C) index: 0.814 versus 0.763; p < 0.001]. Patients classified as high- versus low-risk based on LODDS had much worse overall survival (OS) (4.9% versus 83.7%, respectively; p < 0.001). The LODDS model performance remained high even among patients with inadequateLND (< 6 LN) (C index: 0.87). An online calculator was developed ( https://catalano-giovanni.shinyapps.io/LoddsGBC/ ). A novel prognostic model based on LODDS may overcome the inherent limitations of the current AJCC staging system, reducing understaging among patients with fewer than six total lymph nodes evaluated.

HPB SO27 - Reconsidering Routine Histopathological Examination of Gallbladder Specimens in Cholecystectomy: Optimizing Clinical Practice and Resource Management

Abstract Background Cholecystectomy, the removal of the gallbladder, is a common surgery performed globally. Routine histopathological examination (HPE) of gallbladder specimens post-surgery aims to detect pathologies like gallbladder cancer (GBC). GBC incidence varies by region and ethnicity, with higher risks in women and those over 65. Advanced GBC stages often require surgery, while early stages may only need cholecystectomy. Global HPE practices differ based on resources and GBC rates. This study evaluates the necessity of routine HPE by examining the selective processing of specimens suspected of GBC, ensuring patient safety while potentially optimizing resource use. Method This retrospective cohort study conducted at Redland Hospital, a district general hospital in Australia, investigated the necessity of routine histopathological examination (HPE) for 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 histopathological examination (HPE) post-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 gallbladder carcinoma (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 histopathological examination (HPE), seems prudent, especially in regions with low gallbladder cancer (GBC) incidence. 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.

HPB SO22 - Clinical outcomes following radical cholecystectomies, a single centre experience in review

Abstract Background Gallbladder carcinoma (GBC) is a rare disease with dismal prognosis. The majority of cases are identified at an advanced state that preclude curative approaches which would usually necessitate removal of the gallbladder with en-block wedge hepatectomy of segment 4b/5 as well as periportal lymphadenectomy. The purpose of this study was to analyze our outcomes for patients undergoing a radical cholecystectomy for suspected GBC. Method A retrospective analysis of patients who underwent radical cholecystecomies at Queen’s Medical Centre, Nottingham, UK between 1st January 2014 and October 2023 was performed. Patients with concomitant primaries, incidental GBC or completion liver resection following index cholecystectomy were excluded. Results 41 patients were eligible for analysis, those were comprised of 13 males and 28 females with a median age of 67 (IQR 57-72) years. The incidence of malignancy on histology was 31.7% (GBC n=11, metastatic renal carcinoma n=1, metastatic melanoma n=1). Cystic margin assessment by frozen section was performed in 41% of cases. In cases with confirmed gallbladder cancer, the median tumour size was 30mm, positive periportal lymph nodes were identified in two patients while R0 resection was achieved in all cases. The median length of stay following surgery was 5 days (IQR 5-7) while Clavien Dindo complication grade ≥ III were experienced in 12% ( return to theatre for leak from repaired cholecysto-duodenal fistula n=1, IR drainage of post operative collection n=3, ITU stay for cardiac arrhythmia n=1). The pathologies encountered in benign cases (n=28) were compatible with chronic cholecystitis (53.5%, n=15), concurrent chronic cholecystitis and adenomyomatosis (21.4%, n=6), xanthogranulomatous cholecystitis (10.7%, n=3), adenomyomatosis (7.1%, n=2), follicular cholecystitis (3.5%, n=1), benign GB polyps (3.5%, n=1). Conclusion Radical cholecystectomy remains the standard of care for suspected GBC however sufficient preoperative counselling is prudent given likelihood of benign disease on histology.

BN SO44 - Is routine histological analysis of excised gallbladders necessary?

Abstract Background Gallbladder cancer is rare representing &amp;lt;1% of annual cancer diagnoses in the UK. It is more common in females (2.4/100,000 vs 1/100,000) with a peak age incidence of 85–89-years. Our trust routinely histologically analyses all resected gallbladders, over 1000 per year, regardless of indication. Our pathologists estimate that each specimen costs £75 to analyse, reflecting an annual cost of over £80,000. A 2021 systematic review suggested selective histological analysis is safe, reduces laboratory burden and costs. We aimed to assess our centre’s cholecystectomy specimens to ascertain the incidental gallbladder cancer diagnoses and explore the possibility of selective analysis. Method A retrospective search of our pathology database was carried out for the terms “cancer” and “gallbladder” from 2015 to 2018 inclusive. After exclusion of non-gallbladder primary cancers, all selected cases electronic notes were retrospectively reviewed. The primary outcome was the incidental findings of gallbladder cancer. Secondary outcomes were the indications for surgery, intraoperative findings, histological macroscopic description, final diagnosis and further management where applicable. Results We identified 4421 gallbladder specimens of which 12 (0.27%) identified cancer. The ratio of female to male diagnoses was 5:1 and the median age was 73.5 years. Of the 12 cancers, 7 (0.16%) of these were incidental findings, with 5 having surgery for symptomatic gallstones and 2 for gallbladder polyps. The 5 symptomatic gallstones patients all had grossly abnormal macroscopic appearances of the serosa, dense adhesions or exudate; all were confirmed as gallbladder adenocarcinoma. Three patients were fit enough for limited liver resection. Conclusion Our results demonstrate that across four years the rate of incidental gallbladder adenocarcinoma diagnosed by cholecystectomy was 0.16%. In all non-polypoidal cases (0.11%), the gallbladder was macroscopically abnormal. This suggests that with careful criteria, selective gallbladder histological analysis may reduce laboratory burden and therefore costs associated with elective gallbladder surgery. With increasing emphasis to improve efficiency and rationalise healthcare spending, our results suggest that selective histological analysis may be safe and effective. However, given the consequences of missing a cancer diagnosis it would require a larger scale multi centre study to support a move in this direction.

Comparison of treatment models for single primary advanced gallbladder cancer

PurposeTreatment for advanced gallbladder cancer (GBC) remains controversial, with various recommendations regarding the choice and combination of surgery and adjuvant therapy. The present article is targeting for the exploration of optimal treatment models for advanced GBC.MethodsAJCC (American Joint Committee on Cancer, 8th edition) stage III and stage IV GBC, were defined as advanced GBC. Patients with advanced GBC were identified using the Surveillance, Epidemiology, and End Results (SEER) database and departmental cohort. Because of the most representative, only gallbladder adenocarcinoma (GBAC) patients were selected. Based on their surgical status (No, Non-radical and Radical surgery), chemotherapy status (Chemotherapy, No chemotherapy), and radiotherapy status (Radiotherapy, No radiotherapy), treatment models were categorized. For the purposes of evaluating the treatment outcomes of various treatment models and determining the risk element for cancer-specific survival (CSS), Cox regression analysis was applied. Kaplan-Meier curves were used before and after adjusting for covariates, with log-rank tests used to analyze discrepancies between curves. Immunotherapy was analyzed using clinical data from departmental cohort. Finally, to compensate for the limitations of the database, a review examines the progress in treatment models for advanced GBC.Results5,154 patients aged over 18 years with solitary primary advanced GBC were identified from the SEER database. In advanced GBC patients, the treatment model has emerged as a significant prognostic factor. “Radical surgery + Chemotherapy + Radiotherapy” models maximally improved the CSS of advanced GBC before and after adjusting for covariates, while “No surgery + No chemotherapy + No radiotherapy” model had the lowest CSS. The present conclusions were supported even after subgroup analysis by AJCC stage. The efficacy of immunotherapy was demonstrated in the departmental cohort analysis. Additionally, this article provides a comprehensive overview of recent advancements in various emerging treatment strategies.ConclusionEven when optimal treatment model cannot be pursued, providing comprehensive combinations of treatments to advanced GBC patients whenever possible is always beneficial for their survival.

BN SO24 - Predicting incidental gallbladder cancer: A protocol for identifying predictive factors of incidentally detected gallbladder cancer and prospective validation of a scoring system to allow selective histological analysis of the gallbladder

Abstract Background Incidental Gallbladder Cancer (iGBC) is a rare complication of cholecystectomy, with a UK incidence of 0.14-0.3%. Despite its rarity, most gallbladder specimens are analysed histologically. Some comparable countries undertake Selective Histological Analysis (SHA), selecting high-risk specimens for histology based on clinical judgement or postoperative inspection. However, evidence suggests a third of diagnoses can be missed with these approaches. Swedish and Dutch diagnostic scores incorporate few risk factors and are not generalisable to the UK. We present a protocol for a UK study aiming to develop a detailed diagnostic score for iGBC to reliably stratify patients by their risk of iGBC. Method This UK multicentre, cross-sectional, trainee-led study includes adult patients undergoing cholecystectomy for benign indications. It incorporates a feasibility study and an adaptive design, and has been submitted for ethical review. A parallel qualitative study will explore attitudes towards the risk of iGBC and the acceptability of SHA among patients and healthcare professionals. The feasibility phase will include 500 patients over six months, collecting data on patient risk factors for iGBC, preoperative investigations, operative findings, and histology results. Exclusion criteria include cholecystectomy as a secondary procedure, polyps over 5mm, and conditions known to increase the risk of biliary tract cancers. Results Following the feasibility phase, the recruitment rate and data completeness will be evaluated. Outcomes will be assessed against anticipated values, and collaborators will be surveyed to identify challenges with data collection. Necessary adjustments to the electronic case record form or overall protocol will be made, and the recruitment target will be recalculated based on an updated sample size calculation. When the study meets specified progression criteria, additional sites will be recruited, and data collection will continue to meet the required sample size. A detailed statistical analysis plan will be provided at a later date. Conclusion This protocol describes a UK diagnostic modelling study aimed at developing a risk-stratification score for iGBC in patients undergoing routine cholecystectomy, identifying high-risk patients and facilitating SHA.

HPB SO07 - Update to the role of staging laparoscopies in stratifying patients by operability in perihilar cholangiocarcinoma

Abstract Background Radical resection of perihilar cholangiocarcinoma (pCCA) is only an option for the minority presenting at an early stage. Sensitivity of radiological imaging to detect liver and peritoneal metastases is insufficient. Our published 2017 cohort study demonstrated over a quarter of patients with no radiologically detectable metastatic disease were subsequently found to have unresectable disease by staging laparoscopy. However, less than 3% of these patients had preoperative PET-CT, which is now strongly recommended in new national guidance.Advances in CT and MRI sensitivity and increased PET-CT use demanded a reassessment of the need for staging laparoscopy in diagnostic assessment of resectability. Method All patients referred to a tertiary UK hepatobiliary centre with a new diagnosis of radiologically suspected or biopsy-proven pCCA from January 2020 to January 2024 were included (n=305). Patients were identified through a prospectively maintained cancer database. Electronic health records were interrogated for demographic data, preoperative radiological imaging, and details related to operative procedures. Those referred with, or subsequently found to have, any of the following conditions were excluded: recurrent pCCA, intrahepatic or distal cholangiocarcinoma, gallbladder cancer or benign hepatobiliary disease. Results All patients underwent CT chest, abdomen and pelvis. 194 (64%) received contrast MRI liver or MRCP. Based on these, 242 (79%) had locally advanced or metastatic cancer, comorbidities precluding resection or otherwise declined surgery. PET-CT was employed to investigate all remaining 63 patients, which discovered metastatic disease in 16 patients (25%). 47 patients proceeded to staging laparoscopy. This yielded metastatic or locally advanced disease in five patients (11%); a near-statistically significant drop compared to our previously published yield of 27.2% (p=0.060). Two (5%) had open-and-close laparotomies for irresectable disease, compared to 16 of 114 (14%) in our 2017 publication (p=0.14). Conclusion Technological advances of CT and MRI and use of PET-CT have vastly improved detection of irresectable pCCA. This study reinforces the merits of PET-CT in identifying occult disease, and we would encourage units that undertake these resections to utilise this imaging modality prior to undertaking staging laparoscopy. Nevertheless, peritoneal spread remains challenging to exclude radiologically, and diagnostic laparoscopy endures as a vital tool in the prevention of open-and-close laparotomies.

BN SO29 - Overinvestigation and unnecessary surgery for Gallbladder Polyps: An audit of compliance with ESGAR guidelines

Abstract Background Incidental gallbladder polyps are increasingly reported on abdominal ultrasound and have a theoretical association with increased risk of gallbladder cancer. Most gallbladder polyps are actually gallstones and there is little evidence for any survival benefit or reduced rates of gallbladder cancer in patients under ultrasound surveillance. ESGAR guidelines attempt to standardize and rationalize surveillance protocols, balancing the risks of missed early cancers versus the costs of surveillance investigations. This audit aims to assess the investigation and management of gallbladder polyps as per ESGAR guidelines at a single NHS trust. Method An audit was conducted at a single NHS Trust in England. Searches were conducted on the electronic patient record for patients coded for K82.8 (Gallbladder pathology: other) from 01/01/2022 to 31/12/2023. Patient records were examined for radiological imaging confirming diagnosis of gallbladder polyp. Data was analysed using Microsoft excel and compared with the 2021 ESGAR guidance on management of gallbladder polyps. Results 97 patients were included. All polyps were diagnosed with abdominal ultrasound. Patients had, on average, two ultrasounds. 51% were seen in outpatients clinic. 35 patients (36%) underwent laparoscopic cholecystectomy (including all patients with a polyp &amp;gt;10mm). Histology confirmed diagnosis of cholecystitis (69%), pseudopolyp (9%), gallbladder polyp (6%) and IPMN (3%). 74% (26/35) of patients that underwent cholecystectomy had biliary symptoms and 77% (20/26) had cholecystitis confirmed by histology. Despite having biliary symptoms at first assessment, 47% of polyp patients went on to have two ultrasounds and two clinic appointments. Conclusion The study confirms that the majority of ultrasound detected polyps are not neoplastic, and patients undergo multiple hospital visits, incurring significant non-therapeutic costs. Adherence to ESGAR guidelines is inconsistent. In the symptomatic cohort, however, a low threshold for laparoscopic cholecystectomy should be considered given the high likelihood of underlying stones.

BN SO04 - The value of routine histopathology analysis of gallbladder specimens after elective and emergency laparoscopic cholecystectomy

Abstract Background Gallbladder cancer is not among the 20 most common cancers in the UK, accounting for less than 1% of all new cancer cases with a peak rate at 85-89 years of age. There is a dominant routine conception among surgeons to send the gallbladder specimen for histopathology even if there is no gross features that raise suspicion for neoplasm. In this study, we are trying to get evidence of the value of routine histopathology analysis of gallbladder specimens after elective and emergency laparoscopic cholecystectomy surgeries in Warwick hospital. Method The record of all the patients who underwent laparoscopic cholecystectomy ( elective, expiated and emergency ) in Warwick hospital in the period between 01/07/2023 – 30/01/2024 ( 7 months) were collected, reviewed and underwent data analysis Results A total of 171 specimens were sent for histo-pathology analysis. Only one patient had low grade dysplasia with no malignant features. No routine follow-up decided for him/her after upper GIT MDT discussion. The incidence rate was 0% of neoplasm and 0.6% of low-grade dysplasia. Conclusion No specimen in the study had suspicious gross features of malignancy. Using a selective system is more logical and economic than the routine sending for histopathology after elective and emergency laparoscopic cholecystectomy if there are no suspicious features in the specimen.

Gallbladder cancer incidence and mortality rate trends in China: analysis of data from the population-based cancer registry.

Gallbladder cancer is a major health concern in China, and awareness of the associated incidence and mortality rates is particularly important given the aging population. To determine trends in gallbladder cancer incidence and mortality rates over 12years and quantitatively analyze the influence of demographic factors on these rates in China. We performed a retrospective study of 98,860 Chinese citizens using the Chinese Cancer Registry, a national database. Gallbladder cancer incidence and mortality data pertaining to patients treated between 2005 and 2017 were collected. Joinpoint regression models were used to estimate the annual percentage change (APC) and average APC (AAPC). We used age-period-cohort analyses and decomposition methods to investigate differing trends in incidence and mortality. The age-standardized gallbladder cancer incidence and mortality rates in China trended downward between 2005 and 2017, with AAPCs of -2.023% and -1.603%, respectively. Coefficients of age effect for incidence rate increased with age up to 70years and peaked at 70-79years, while coefficients of age effect for the mortality rate showed a consistent increase with age. Both coefficients of period for incidence and mortality rates increased in more recent periods; in terms of the cohort effect, coefficients of cohort for rates generally decreased in later birth years but showed a partial rise between 1982 and 1996. The crude incidence rates of gallbladder cancer according to demographic and non-demographic factors were 626.09% and -526.09% respectively (366.23% and -266.23% among men, and 6068.93% and -5968.93% among women, respectively). The rates were 543.01% and -443.01%, respectively, in urban areas and were 68.22% and 31.78%, respectively, in rural areas. The mortality rates according to demographic and non-demographic factors were -495.93% and 595.93%, respectively (-1763.10% and -1863.10% for men and -270.56% and -370.56% for women, respectively). These rates were -930.33% and 1030.33%, respectively, in urban areas and were 101.48% and -1.48%, respectively, in rural areas. The overall standardized gallbladder cancer incidence and mortality rates in China are trending downward, but not sufficiently so. Proper living and eating habits should be encouraged while exploring the establishment of long-term, standardized gallbladder cancer screening programs.

Impact of high body mass index on gallbladder and biliary tract cancer burden in China: a comprehensive analysis of trends from 1990 to 2021.

Gallbladder and biliary tract cancer (GBTC) is a significant health burden in China, exacerbated by the rising prevalence of high body mass index (BMI). Understanding the trends and factors contributing to mortality and disability associated with GBTC is crucial for targeted public health interventions. We utilized data from the Global Burden of Disease (GBD) Study to assess the burden of GBTC attributable to high BMI in China from 1990 to 2021. Age-standardized rates of deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were analyzed. Joinpoint regression and decomposition analyses were conducted to evaluate trends and identify contributing factors, including aging, population growth, and epidemiological changes. Gender-specific differences were also assessed. In 2021, GBTC deaths attributable to high BMI in China reached 4,053, with males experiencing a higher overall burden than females, particularly in older age groups. While females showed a higher mortality and overall burden in the 60 to 79 age range, this trend reversed in older age brackets, with males experiencing steeper increases in mortality and disability-related indicators beyond age 80. The age-standardized DALYs rate mirrored this pattern, with higher rates in males in advanced age groups. From 1990 to 2021, China saw a steady increase in GBTC burden attributable to high BMI, contrasting with a global decline. Joinpoint analysis indicated marked rises in mortality and DALYs rates after 2005, especially in males. Decomposition analysis identified population growth and aging as major drivers of increased deaths, while epidemiological changes primarily contributed to rising DALYs, with a stronger impact observed in males. The burden of GBTC attributable to high BMI in China has increased substantially over the last three decades, driven by population growth, aging, and epidemiological shifts. The trends highlight a growing gender disparity, with males experiencing a greater rise in mortality and disability. Public health strategies targeting obesity and metabolic risk factors are critical to mitigating the increasing GBTC burden.

Evolution from laparoscopic to robotic radical resection for gallbladder cancer: a propensity score-matched comparative study.

The use of robotic or laparoscopic surgery for gallbladder cancer (GBC) is increasing, with reported advantages over conventional open surgery. The purpose of this study was to compare the perioperative outcomes and postoperative overall survival (OS) associated with robotic radical resection (RRR) and laparoscopic radical resection (LRR) for GBC. A total of 109 patients with GBC who underwent radical resection with the same surgical team between January 2015 and December 2023 were enrolled, with 21 patients in the RRR group and 88 cases in the LRR group. A 1:1 propensity score matching (PSM) algorithm was used to compare the surgical outcomes and postoperative prognosis between the RRR and LRR groups. Logistic regression analysis was used to identify the risk factors of postoperative overall survival (OS) and complications of Clavien-Dindo (C-D) Grades III-IV. The median follow-up time was 46 (inter-quartile range, IQR 29-70) months for the LRR group and 16 (IQR 12-34) months for the RRR group. After PSM, the baseline characteristics of the RRR and LRR groups were generally well balanced, with 21 patients in each group. RRR was associated with significantly decreased intraoperative bleeding [100.00 (50.00, 200.00) mL vs 200.00 (100.00, 300.00) mL] and higher number of lymph nodes (LNs) yield [12.00 (9.00, 15.50) vs 8.00 (6.00, 12.00)]. The two groups showed comparable outcomes in terms of the incidence of biliary reconstruction, the range of liver resection, the length of operation, the incidence of postoperative morbidity, the incidence of C-D Grades III-IV complications, number of the days of drainage tubes indwelling and postoperative hospital stay, and mortality by postoperative days 30 and 90. After PSM, the 1-, 2-, and 3-year overall survival rates were 78, 70, and 37%, respectively, in the RRR group, and 71, 59, and 48%, respectively, in the LRR group (P = 0.593). Multivariate analysis showed that the preoperative TB level ≥ 72µmol/L and biliary reconstruction were found to be the independent risk factors of C-D Grades III-IV complications. T3 stage was identified to be the risk factor for postoperative OS. Compared with LRR, RRR showed comparable perioperative outcomes in terms of length of operation, and postoperative complications, recovery, and OS. In our case series, RRR of GBC can be accomplished safely and tends to show less intraoperative bleeding and higher LNs yield.

Intracholecystic Papillary Neoplasm: A Rare Differential of Carcinoma Gallbladder

Intracholecystic Papillary Neoplasm: A Rare Differential of Carcinoma Gallbladder

Super-Enhancer Reprograming Driven by SOX9 and TCF7L2 Represents Transcription-Targeted Therapeutic Vulnerability for Treating Gallbladder Cancer.

Gallbladder cancer (GBC) is a highly aggressive malignancy lacking clinically available targeted therapeutic agents. Super-enhancers (SEs) are crucial epigenetic cis-regulatory elements whose extensive reprogramming drives aberrant transcription in cancers. To study SE in GBC, the genomic distribution of H3K27ac is profiled in multiple GBC tissue and cell line samples to establish the SE landscape and its associated core regulatory circuitry (CRC). The biliary lineage factor SOX9 and Wnt pathway effector TCF7L2, two master transcription factor (TF) candidates identified by CRC analysis, are verified to co-occupy each other's SE region, forming a mutually autoregulatory loop to drive oncogenic SE reprogramming in a subset of GBC. The SOX9/TCF7L2 double-high GBC cells are highly dependent on the two TFs and enriched of SE-associated gene signatures related to stemness, ErbB and Wnt pathways. Patients with more such GBC cells exhibited significantly worse prognosis. Furthermore, SOX9/TCF7L2 double-high GBC preclinical models are found to be susceptible to SE-targeted CDK7 inhibition therapy in vitro and in vivo. Together, this study provides novel insights into the epigenetic mechanisms underlying the oncogenesis of a subset of GBCs with poorer prognosis and illustrates promising prognostic stratification and therapeutic strategies for treating those GBC patients in future clinical trials.

Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of gall bladder.

Carcinoma of gall bladder (CAGB) has poor prognosis. Molecular analysis of bile could classify indicators of CAGB. Bile samples (n=87; training cohort) were screened for proteomics and metabolomics signatures of cancer detection. In bile, CAGB showed distinct proteomic (217up-, 258 downregulated) and metabolomic phenotype (111 up-, 505 downregulated, p<0.05, FC>1.5, FDR<0.01) linked to significantly increased inflammation (coagulation, arachidonic acid, bile acid) and alternate energy pathways (pentose-phosphate pathway, amino-acid, lipid metabolism) and decreased glycolysis, cholesterol metabolism, PPAR, RAS and RAP1 signaling, oxidative phosphorylation, and others compared to GS or HC (p<0.05). Bile proteins/metabolites signatures showed significant correlation (r2>0.5, p<0.05) with clinical parameters. Metabolite/protein signature-based probability of detection for CAGB (cancer) was >90% (p<0.05) with AUC>0.94. Validation of top four metabolites: Toluene, 5,6-DHET, Creatine, and Phenylacetaldehyde in separate cohorts (n=80; bile [T1] and paired plasma [T2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. Tissue validation showed bile 5,6 DHET positively correlated with tissue PCNA (proliferation), and Caspase-3 linked to cancer development (r2>0.5, p<0.05). In conclusion, the bile molecular landscape provides critical molecular understanding and outlines metabolomic indicator panels for early CAGB detection.