Biliary Malignancy Research Articles

Biliary Reconstruction with Hepaticoduodenostomy Versus Hepaticojejunostomy After Choledochal Cyst Resection: A Narrative Review.

Choledochal cysts (CCs), a congenital anomaly resulting in the abnormal dilation of the biliary ductal system, are most often identified in patients younger than 10 years of age. Regardless of clinical presentation, the cornerstone of therapy for CCs is complete surgical excision with reconstruction with either hepaticoduodenostomy or hepaticojejunostomy. Although both procedures are used by surgeons for the correction of CCs, evidence on clinical outcomes following both approaches is inconclusive as to which may offer superior reconstruction. This narrative review aims to compare the current literature regarding both approaches by evaluating their anatomic and operative considerations, as well as their perioperative, postoperative, and long-term outcomes. Future studies should closely focus on long-term, comparative outcomes, including the risk of biliary malignancy, and refine techniques to minimize complications, such as biliary reflux and bowel obstruction, in order to improve care for pediatric patients undergoing treatment for CCs.

The genetically predicted causal associations between circulating 3-hydroxybutyrate levels and malignant neoplasms: A pan-cancer Mendelian randomization study

The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI]=0.28[0.14-0.57] p=3.92e-04), biliary malignancies (OR[95%CI]=0.30[0.15-0.60], p=7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI]=0.25[0.09-0.71], p=9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI]=0.76[0.58-0.99], p=0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI]=-0.073[-0.122∼-0.024], p=0.0034) and enhanced susceptibility to HCC (OR[95%CI]=13.9[9.76-19.79], p=3.14e-48), biliary malignancies (OR[95%CI]=4.04[3.22-5.07], p=1.64e-33), nasopharyngeal cancer (OR[95%CI]=3.26[1.10-9.67], p=0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI]=1.27[1.13-1.44], p=1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI]=1.076[1.01-1.15], p=0.034). Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

Clinical and Genomic Characterization of ERBB2-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort.

Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations. Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets. A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024). The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

Management of a Todani Type 1b Choledochal Cyst: Case report

This case report describes the management of a Todani Type 1b choledochal cyst in a 26-year-old woman who presented with chronic epigastric dyspepsia and acute epigastric pain. MRI revealed a cystic dilatation of the distal common bile duct. The patient underwent successful surgical excision of the cyst, cystic duct, and gallbladder, followed by reconstruction with a Roux-en-Y hepaticojejunostomy. The postoperative course was uneventful, with discharge on the sixth day. This case highlights the importance of timely diagnosis and surgical intervention to prevent complications such as biliary cirrhosis and malignancy.

Survival after targeted chemotherapy and unresectable biliary malignancies (systematic review and meta-analysis)

Aim. To evaluate the survival rate of patients with unresectable biliary malignancies under targeted chemotherapy in order to identify the most promising adjuvant regimens.Materials and methods. The study involves publications in PubMed Central, RSCI, and Cochrane databases. Heterogeneity was assessed graphically (blobograms) and statistically (τ 2 and I2 ).Results. Meta-analysis of five-year survival revealed a greater pooled estimate of the period in the main groups treated with targeted chemotherapy – 295 ± 71 days (95% CI 144–408; p <0.001) against comparison groups – 205 ± 81 days (95% CI 81–426; p <0.001). Study heterogeneity was considered moderate (I2 = 0%, p = 0.06). No significant publication errors and biases were revealed in both meta-analyses.Conclusion. Targeted chemotherapy increases the overall survival of patients with unresectable malignancies of the bile ducts. Systemic chemotherapy based on gemcitabine and cisplatin with addition of ivosidenib, a selective inhibitor of mutant IDH1, showed the best efficacy.

Efficacy and safety of camrelizumab combined with chemotherapy in the treatment of advanced biliary malignancy and associations between peripheral blood lymphocyte subsets and clinical outcomes.

Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

Effect of pancreatobiliary reflux on macrophage-secreted IL-8, PI3K/NFκB pathway, and promotion of cholangiocarcinoma progression.

73 Background: Persistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression. Methods: Overall, 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated. Results: The bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway. Conclusions: PBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression.

Development and in vitro evaluation of ursolic acid-loaded poly(lactic-co-glycolic acid) nanoparticles in cholangiocarcinoma.

Cholangiocarcinoma (CCA), an epithelial biliary tract malignancy, is a significant health concern in the Greater Mekong Subregion, particularly in northeastern Thailand. Prior to the development of advanced stages, CCA is typically asymptomatic, thereby limiting treatment options and chemotherapeutic effectiveness. Ursolic acid (UA), a triterpenoid derived from plants, was previously discovered to inhibit CCA cell growth through induction of apoptosis. Nevertheless, the therapeutic effectiveness of UA is limited by its poor solubility in water and low bioavailability; therefore, dimethyl sulfoxide (DMSO) is utilized as a solvent to treat UA with CCA cells. Enhancing cellular uptake and reducing toxicity, the utilization of polymeric nanoparticles (NPs) proves beneficial. In this study, UA-loaded PLGA nanoparticles (UA-PLGA NPs) were synthesized using nanoprecipitation and characterized through in silico formation analysis, average particle size, surface functional groups and ζ-potential measurements, electron microscopic imaging, drug loading efficiency and drug release studies, stability, hemo- and biocompatibility, cytotoxicity and cellular uptake assays. Molecular dynamics simulations validated the loading of UA into PLGA via hydrogen bonding. The synthesized UA-PLGA NPs had a spherical shape with an average size of 240 nm, a negative ζ-potential, good stability, great hemo- and bio-compatibility and an encapsulation efficiency of 98%. The NPs exhibited a characteristic of a simple diffusion-controlled Fickian process, as predicted by the Peppas-Sahlin drug release kinetic model. UA-PLGA NPs exhibited cytotoxic effects on KKU-213A and KKU-055 CCA cells even when dispersed in media without organic solvent, i.e., DMSO, highlighting the ability of PLGA NPs to overcome the poor water solubility of UA. Rhodamine 6G (R6G) was loaded into PLGA NPs using the same approach as UA-PLGA NPs, demonstrating effective delivery of the dye into CCA cells. These findings suggest that UA-PLGA NPs showed promise as a potential phytochemical delivery system for CCA treatment.

Imaging of Biliary Tree Abnormalities.

Pathologic conditions of the biliary system, although common, can be difficult to diagnose clinically. Challenges in biliary imaging include anatomic variants and the dynamic nature of the biliary tract, which can change with age and intervention, blurring the boundaries of normal and abnormal. Choledochal cysts can have numerous appearances and are important to diagnose given the risk of cholangiocarcinoma potentially requiring surgical resection. Choledocholithiasis, the most common cause of biliary dilatation, can be difficult to detect at US and CT, with MRI having the highest sensitivity. However, knowledge of the imaging pitfalls of MRI and MR cholangiopancreatography is crucial to avoid misinterpretation. Newer concepts in biliary tract malignancy include intraductal papillary biliary neoplasms that may develop into cholangiocarcinoma. New paradigms in the classification of cholangiocarcinoma correspond to the wide range of imaging appearances of the disease and have implications for prognosis. Accurately staging cholangiocarcinoma is imperative, given expanding curative options including transplant and more aggressive surgical options. Infections of the biliary tree include acute cholangitis or recurrent pyogenic cholangitis, characterized by obstruction, strictures, and central biliary dilatation. Inflammatory conditions include primary sclerosing cholangitis, which features strictures and fibrosis but can be difficult to differentiate from secondary causes of sclerosing cholangitis, including more recently described entities such as immunoglobulin G4-related sclerosing cholangitis and COVID-19 secondary sclerosing cholangitis. The authors describe a wide variety of benign and malignant biliary tract abnormalities, highlight differentiating features of the cholangitides, provide an approach to interpretation based on the pattern of imaging findings, and discuss pearls and pitfalls of imaging to facilitate accurate diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

Molecular Imaging in Gallbladder and Biliary Tract Malignancies

Molecular Imaging in Gallbladder and Biliary Tract Malignancies

Risk factors for recurrent biliary obstruction following suprapapillary placement of a plastic stent as preoperative biliary drainage for perihilar biliary malignancy.

The usefulness of endoscopic biliary stenting by deploying a plastic stent suprapapillary, called inside-stent (IS) placement, as preoperative biliary drainage (PBD) for perihilar biliary malignancy (PHBM) has been demonstrated. This study investigated risk factors for recurrent biliary obstruction (RBO) after IS placement. Consecutive patients with potentially resectable PHBM treated with IS placement as PBD between 2017 and 2023 at Nagoya University Hospital were retrospectively reviewed. A total of 157 patients were included, with RBO occurring in 34 (22%) patients. The non-RBO rates were 83% at 30 days, 77% at 60 days, and 57% at 90 days. The most common cause of RBO was stent occlusion (n = 14), followed by segmental cholangitis (n = 12) and stent migration (n = 8). Stent migration and occlusion occurred more frequently within and after 1 week post-stenting, respectively. In multivariate analysis, biliary infection before IS was the sole risk factor for RBO, with a hazard ratio of 2.404 (95% confidence interval 1.163-4.972; p = .018). This risk was reduced by temporary endoscopic nasobiliary drainage prior to definitive IS placement. Biliary infection before IS was identified as an independent risk factor for RBO in patients with PHBM with IS as PBD. Clinical trial registration number: UMIN000025631.

356 The Role of Cancer Cachexia in Influencing Outcomes in Pancreatic & Biliary Malignancy

Abstract Aim To investigate the influence of cancer cachexia on outcomes and clinicopathological variables in pancreatico-biliary malignancies. Method Patients who underwent pancreaticoduodenectomy for malignancy from 2007-2020 at the Glasgow Royal Infirmary were included in this study. Pre-operative single-slice CT scan images were collected for cross sectional analysis of body composition using the semi-automated segmentation programme, SliceOmatic. Body composition measurements were represented as z-scores to account for age and sex. Results Subcutaneous fat radiodensity (SFD) was significantly lower in ampullary adenocarcinoma (-0.17+/-0.95), duodenal adenocarcinoma (-0.03+/-1.08), and cholangiocarcinoma (-0.18+/-1.00) groups compared to the pancreatic cancer group (0.12+/-1.00) (P=0.09). Skeletal muscle index (SMI) was significantly higher in those diagnosed with cholangiocarcinoma compared to all other indications (0.20+/-0.91 vs -0.04+/-1.02, P=0.05). Disease-specific and recurrence-free median survival was lower in those with low SMI compared to those with high SMI for all indications (35 months vs 41 months, 13 months vs 18 months).When comparing those who underwent up-front resection to those who received neoadjuvant therapy, visceral fat index (VFI) was found to be higher (0.06+/-1.00 vs -0.21+/-0.99, P=0.03) and skeletal muscle density was found to be lower (-0.05+/-1.01 vs 0.18+/-0.96, P=0.04). SFD was also found to be significantly lower in those with AJCC stage 1 compared to all other stages (-0.21+/-0.86 vs 0.07+/-1.01, P=0.03). Conclusions Adverse body composition may influence outcomes in pancreatic and biliary malignancy; however, this influence appears to be modest at best. Clinical applications of body composition analysis may be limited to serial monitoring of patients within the context of their treatment pathway.

Minimally Invasive Management of Postoperative Complications in Patients with Cholangiocarcinoma

AbstractCholangiocarcinoma is a rare, aggressive biliary tract malignancy representing only 3% of digestive cancers worldwide. Late diagnosis is common, which results in less than one-third of patients being eligible for surgical resection or liver transplantation. Surgery, however, is not without associated morbidity and mortality. This article seeks to review minimally invasive techniques for the management of complications following liver transplantation and hepatic resection for patients with cholangiocarcinoma.

Role of Multi-Detector Computed Tomography (MDCT) in Assessment of Biliary Neoplasms

Abstract Background Biliary neoplasms are commonly encountered in the day-to-day radiological practice and can be benign or malignant. Multidetector CT (MDCT) is a noninvasive imaging modality for evaluation of patients with biliary obstruction, to localize the cause of obstruction, detect the presence of mass lesion, and define its extension and identify remote metastasis. Objective To find out the role of MDCT scan in the evaluation of biliary neoplasms with respect to nature, cause and level of obstruction. Methods During the period from January 2022 to August 2022, the present study included 30 patients with clinically suspected biliary obstruction and previously radiological or laboratory diagnosed cases of biliary malignancy after fulfilling the inclusion and exclusion criteria and taking written /verbal informed consent. 16 patients were males and 14 were females, their ages ranged between 36– 85 years with mean age of 64years old. Results The mean age of participants was 63.73±11.11 years old; and slight male predominance (53.3%). in correlation to histopathological findings, MDCT was 95.2% sensitive in detection of cholangiocarcinoma (20/21*100). It was 100% sensitive in detection of combined cholangiocarcinoma & HCC (1/1*100). Also it was 85.75 sensitive in detection of gall bladder carcinoma (6/7*100). While it was false positive in detection a case of HCC. The sensitivity of MDCT to detect biliary neoplasm is 96.4% (27/28*100) with specificity of 0% (0/2*100), the positive predictive value is 93.1% (27/29*100) while the negative predictive value is 0% (0/1%). We found significant association between MDCT Final outcome with resectability (P-value 0.002) and between resectability and TNM Staging (P-value <0.0001) Conclusion Multidetector computed tomography MDCT can be considered a noninvasive fast with high sensitivity imaging tool in the assessment of patients with biliary neoplasms. The MDCT is satisfactory for staging of biliary neoplasms and for accurate preoperative assessment of the tumor extent.

Endoscopic Ablation of Perihilar Biliary Malignancies

AbstractCholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells and is subdivided based on the location within the biliary tree. The treatment of CCA differs based on the anatomical involvement within the biliary tree. Perihilar CCA (pCCA) arises between the cystic duct and the secondary branches of the right and left hepatic ducts. Surgical resection and liver transplantation offer the only hope for cure in pCCA, but, unfortunately, more than 80% of patients are considered surgically unresectable at the time of diagnosis resulting in a limited overall life expectancy of less than 1 year. For patients with surgically unresectable pCCA, treatment options are limited and include chemotherapy/chemoradiotherapy and biliary drainage via endoscopic stenting or percutaneous drainage with minimal overall survival benefits. However, endobiliary ablation options like photodynamic therapy (PDT), radiofrequency ablation (RFA), and, to a lesser degree, intraluminal brachytherapy have shown improvements in overall survival and improvements in stent patency and now should be considered for all cases of surgically unresectable pCCA. In fact, the 2023 American College of Gastroenterology (ACG) Clinical Guidelines on the diagnosis and management of biliary strictures recommend endobiliary ablation (PDT or RFA) for patients with surgically unresectable pCCA rather than stenting alone.

Gallbladder cancer: Progress in the Indian subcontinent.

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

CT-based muscle and adipose measurements predict prognosis in patients with digestive system malignancy

The role of skeletal muscle and adipose tissue in the progression of cancer has been gradually discussed, but it needs further exploration. The objective of this study was to provide an in-depth analysis of skeletal muscle and fat in digestive malignancies and to construct novel predictors for clinical management. This is a retrospective study that includes data from Cancer Center, the First Hospital of Jilin University. Basic characteristic information was analyzed by T tests. Correlation matrices were drawn to explore the relationship between CT-related indicators and other indicators. Cox risk regression analyses were performed to analyze the association between the overall survivals (OS) and various types of indicators. A new indicator body composition score (BCS) was then created and a time-dependent receiver operating characteristic curve was plotted to analyze the efficacy of the BCS. Finally, a nomogram was produced to develop a scored-CT system based on BCS and other indicators. C-index and calibration curve analyses were performed to validate the predictive accuracy of the scored-CT system. A total of 575 participants were enrolled in the study. Cox risk regression model revealed that VFD, L3 SMI and VFA/SFA were associated with prognosis of cancer patients. After adjustment, BCS index based on CT was significantly associated with prognosis, both in all study population and in subgroup analysis according to tumor types (all study population: HR 2.036, P < 0.001; colorectal cancer: HR 2.693, P < 0.001; hepatocellular carcinoma: HR 4.863, P < 0.001; esophageal cancer: HR 4.431, P = 0.008; pancreatic cancer: HR 1.905, P = 0.016; biliary system malignancies: HR 23.829, P = 0.035). The scored-CT system was constructed according to tumor type, stage, KPS, PG-SGA and BCS index, and it was of great predictive validity. This study identified VFD, L3 SMI and VFA/SFA associated with digestive malignancies outcomes. BCS was created and the scored-CT system was established to predict the OS of cancer patients.

Clinical management, pathogen spectrum and outcomes in patients with pyogenic liver abscess in a German tertiary-care hospital

Pyogenic liver abscesses (PLA) are life-threatening disorders and require immediate treatment, but structured evidence is sparse and treatment guidelines are not established. In a retrospective observational study of 221 adult PLA patients (mean age 63 years, 63% men) treated between 2013 and 2019 at the Leipzig University Medical Center, we characterized pathogen spectrum, clinical management and outcomes. Biliary malignancies (33%), cholelithiasis (23%) and ischemic biliary tract disease (16%) were most common causes of PLA. Comorbidities included malignancies (40%) and diabetes mellitus (35%). Abdominal ultrasound was the preferred initial imaging modality (58%). Enterobacterales (58%), enterococci (42%) and streptococci (18%) were identified as most frequent pathogens. 97% of patients were treated with antibiotics and 75% of patients underwent an invasive treatment procedure. The 30-day mortality was almost identical in patients with and without underlying malignancy (14.6% vs. 14.4%, p = 0.96), while the one-year outcome differed significantly (58.4% vs. 29.6%, p < 0.001). Positive blood cultures (OR 4.78, 95% CI 1.39 to 22.5, p = 0.023) and detection of Enterobacterales (OR 3.55, 95% CI 1.40 to 9.97, p = 0.010) were associated with increased 30-day-mortality. We conclude that ultrasound, extensive microbiologic diagnosis, adequate anti-infective therapy and early intervention are crucial for the management of PLA.

Incidence and demographics of bile duct cystadenocarcinoma from the National Cancer Database.

e16231 Background: Bile duct cystadenocarcinoma, a rare tumor of the biliary tree, manifests itself within both multilocular and unilocular cysts composed of mucous-secreting, cytologically malignant epithelial cell populations. While similar in presentation to other biliary tree malignancies, bile duct cystadenocarcinoma has unique morphological variations between sexes. This contrast in disease manifestation based on sex could potentially impact diagnostic imaging, testing approaches, and treatment strategies for both female and male patients. The potential impact of demographics on the prognosis of bile duct cystadenocarcinoma, along with limited literature on the subject, make it a compelling subject for hypothesis generating epidemiological inquiry. The National Cancer Database will be used to illuminate the demographic intricacies. In this pursuit, we aim to provide a demographic and incidence background to prompt future research dedicated to the understanding of bile duct cystadenocarcinoma. Methods: The National Cancer Database (NCDB) was used to complete a retrospective cohort analysis of all patients diagnosed with histologically confirmed bile duct cystadenocarcinoma from the years 2004 to 2020. Demographic factors were subjected to descriptive statistical techniques, while a comprehensive regression analysis was employed to analyze the patterns in disease incidence. Results: Between 2004 and 2020, 64 patients were diagnosed with bile duct cystadenocarcinoma in the NCDB. There was a decline of incidence per year (R2 = 0.0392). The majority of those diagnosed with this disease were female (70%). Most of the patients were from Caucasian ethnicity (73%). The average age of diagnosis was 65 years old ( SD = 12.5, range = 33-88). The highest percentage of patients were on Medicare (55%). The primary site of the cancer was in the intrahepatic bile duct (63%). 70% of patients had a Charlson-Deyo Score of 0. Stage 1 was the most detected stage (42%). The average size of the tumor when detected was 65 mm (SD = 35.5, range = 9-144 mm). Most patients (72%) received surgical treatment and the remainder received radiation or chemotherapy alone. Regarding margins post-surgery, most of the patients (56%) had no residual tumor. Almost all patients (92%) received treatment designed for cure/remission. Mean survival after diagnosis was 8 years. Conclusions: Consistent with a vast majority of case reports, our results demonstrated that the majority of cases of bile duct cystadenocarcinoma were found in women (70%). Moreover, given that a significant proportion of patients affected by this disease are covered by Medicare (55%), we contend that investigating the precise influence of demographic factors and social determinants of health in this context presents a compelling avenue for future research.

Pancreatobiliary reflux increases macrophage-secreted IL-8 and activates the PI3K/NFκB pathway to promote cholangiocarcinoma progression

BackgroundPersistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression. MethodsOverall 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated. ResultsThe bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway. ConclusionsPBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression.