Multifocal hepatic lesions represent a distinctive subgroup within intrahepatic cholangiocarcinoma(iCCA), the management of these patients remains controversial. This study aimed to compare the survival of intrahepatic cholangiocarcinoma (iCCA) with different numbers of hepatic lesions and select patients benefiting most from surgery in multifocal iCCA.

A cohort of 354 consecutive iCCA patients were included. Based on the number of hepatic lesions, patients were classified as follows: solitary tumors (type I), 2 or 3 hepatic lesions in the same-sided hepatic lobe (type II), and more than three hepatic lesions in the same-sided hepatic lobe (type III). Stabilized inverse probability treatment weighting (IPTW) was conducted for accurate prognosis comparisons. Furthermore, the long-term prognosis was compared between different American Joint Committee on Cancer.

Among all patients, multifocal iCCA presented significantly worse overall survival (OS) and recurrence-free survival (RFS) than solitary tumor (p < 0.001 and p < 0.001), 11.9% (n = 42), and 14.4% (n = 51) patients were classified into type II, and type III, respectively. After IPTW, type II exhibited similar while type III exhibited worse RFS and OS to type I cohort (solitary tumors) (p < 0.001and p < 0.001). Multivariable Cox analysis also identified type III tumors as an independent risk factor for OS (HR 1.95, 95% CI:1.33-2.87, p < 0.001). Among AJCC stage II (T2N0M0) patients, multifocal iCCA presented significantly worse OS than solitary tumors (vascular invasion) (p = 0.018), and type II exhibited similar while type III exhibited worse OS than solitary tumors (p = 0.500 and p = 0.040). Compared with stage III patients, type II exhibited better while type III exhibited similar OS (p < 0.001 and p = 0.300).

Multifocal iCCA presented a significantly worse prognosis, the number of hepatic lesions significantly influenced the prognosis of multifocal iCCA. Patients with type II tumors may derive comparable oncological benefits from surgery compared with solitary tumors, radical surgery still be strongly recommended as the preferred treatment.

Gallbladder and biliary tract cancer (GBTC) presents a worldwide health challenge with a poor prognosis. Previous studies indicated an escalating burden and potential health inequalities, necessitating an updated investigation.

This study utilized data from the Global Burden of Disease (GBD) study, covering 204 countries from 1990 to 2021. Joinpoint regression evaluated temporal trends in age-standardized incidence rates (ASIR) and age-standardized disability-adjusted life years rates (ASDR) for GBTC. The Bayesian age-period-cohort (BAPC) model projected disease burden up to 2050. Inequality analysis assessed disparities by genders across countries, and decomposition analysis determined the contributions of demographic and epidemiological factors.

From 1990 to 2021, the incident cases of GBTC increased from 107,797 to 216,768, while Disability-Adjusted Life Years (DALYs) rose from 2,326,089 years to 3,732,121. Joinpoint regression analysis revealed a global decrease in ASIR (AAPC = -0.39, 95% CI: -0.49 to -0.28) and ASDR (AAPC = -0.97, 95% CI: -1.07 to -0.88). Gender disparities were notable, with a polar reversal observed: females exhibited consistently higher ASDR levels across three decades, although both ASDR and ASIR showed continuous decreases. In contrast, males experienced a decreased ASDR but increased ASIR, with both metrics eventually surpassing those of females. The projection model also suggested diverging ASIR trends between genders. Cross-country inequality analysis revealed persistent disparities, where higher SDI countries continue to bear a greater burden, and global improvement in health equity for males remains insufficient. Decomposition analysis indicated that population growth and ageing were primary drivers of disease burden increase, whereas epidemiological changes contributed to a reduction, particularly in higher SDI quintiles.

Despite improvements, GBTC burden is still greater in high SDI regions compared to lower SDI areas, contrary to expectations. Unexpected polar reversal of gender differences warrants further attention.

Studies on lung metastases from extrahepatic cholangiocarcinoma (ECC) are rare. This study aims to fill this gap by analyzing the influencing factors, prognosis, and chemotherapeutic efficacy of ECC lung metastases, and to provide insights for optimizing medical care for patients with ECC lung metastases.

We retrieved data from the Surveillance, Epidemiology and End Results (SEER) database for patients with metastatic ECC (stage M1) from 2018 to 2021. The study analyzed these characteristics using descriptive statistics. To calculate Hazard Ratios (HR), multivariate COX regression analyses were performed. Overall survival (OS) was estimated using the Kaplan-Meier method, and the survival of patients between groups was compared using the log-rank test.

A total of 762 people participated in the study, 50.4% of whom were men. At the time of diagnosis, 17.8% of patients had pulmonary metastases. 52.5% received chemotherapy. Multivariate COX analysis identified lung metastases as a significant risk factor for death from metastatic ECC (HR 1.64, CI 1.32-2.03, p < 0.001). Treatment with chemotherapy (HR 0.20, CI 0.17-0.25, p < 0.001) and female sex (HR 0.80, CI 0.67-0.94, p = 0.008) were associated with a better prognosis. Therefore, we further compared the prognosis and chemotherapy outcomes of male and female patients with ECC lung metastases. The median survival of male patients with and without lung metastases was 2 and 5 months, respectively (p = 0.016), whereas there was no significant difference in female patients (p = 0.19). Regardless of gender, patients with lung metastases had significantly worse OS even after receiving chemotherapy (p = 0.0065 in the male group and p = 0.0075 in the female group). Regardless of gender, patients with lung metastases who did not receive chemotherapy had significantly shorter overall survival than those who received chemotherapy. Not receiving chemotherapy vs. receiving chemotherapy (male: 1 month vs. 5 months, p < 0.0001; female: 2 months vs. 9 months, p < 0.0001).

Pulmonary metastasis is an important prognostic factor in ECC and is associated with poorer survival, especially in male patients. Therefore, preventive measures and effective control of lung metastases (e.g., chemotherapy), especially in male patients, may improve survival in patients with ECC.

Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy affecting the liver and biliary system. Enhanced understanding of the pathogenic mechanisms underlying iCCA tumorigenesis and the discovery of appropriate therapeutic targets are imperative to improve patient outcomes. In this study, we investigated the functions and regulations of solute carrier family 16 member 3 (SLC16A3), which has been reported to be a biomarker of poor prognosis in iCCA. High SLC16A3 expression was enriched in KRAS viral oncogene homolog-mutated iCCA tumors, and mutant KRAS elevated SLC16A3 expression via the PI3K-AKT-mTORC1-HIF1α pathway. SLC16A3 not only enhanced glycolysis but also induced epigenetic reprogramming to regulate iCCA progression. Phosphorylation of SLC16A3 at S436 was vital for its oncogenic function and was linked to iCCA progression. Casein kinase 2 (CK2) directly phosphorylated SLC16A3 at S436, and CK2 inhibition with CX-4945 (silmitasertib) reduced the growth of KRAS-mutated iCCA tumor xenografts and patient-derived organoids. Together, this study provides valuable insights into the diverse functions of SLC16A3 in iCCA and comprehensively elucidates the upstream regulatory mechanisms, providing potential therapeutic strategies for patients with iCCA with KRAS mutations. Significance: Characterization of the oncogenic function and regulators of SLC16A3 in intrahepatic cholangiocarcinogenesis revealed the potential of CK2 inhibitors as a promising treatment for KRAS-mutated tumors.

Abdominal aortic calcification (AAC), an indicator of systemic arteriosclerosis, is associated with short- and long-term outcomes in malignancies. We investigated the prognostic impact of AAC in patients who underwent hepatectomy for intrahepatic cholangiocarcinoma (IHCC).

The study cohort comprised 46 patients who underwent hepatectomy for IHCC between January 2008 and September 2020. The AAC volume measured by preoperative computed tomography was used to construct a model of the calcified segment from the renal artery to the common iliac artery bifurcation. We investigated the relationship between AAC and the long-term outcomes. The AAC volume cutoff value was calculated from a receiver-operating characteristic curve based on the three-year survival.

According to our cutoff AAC volume of 3,700 mm3, 11 patients (24%) had high AAC volumes. The high-AAC group was significantly older than the low-AAC group (73 vs. 62 years old, p < 0.01). A multivariate analysis of the cancer-specific survival showed that a high serum carbohydrate antigen 19-9 concentration (hazard ratio [HR] 5.57, p = 0.01), high AAC volume (HR 3.03, p = 0.04), and [high?] T3 or T4 levels (HR 9.05, p < 0.01) were independently associated with a poor prognosis.

AAC is a useful predictor of the oncological prognosis in patients undergoing hepatectomy for IHCC.

Malignant biliary obstruction can, in rare cases, arise from metastases to the biliary tree from distant primary tumors. This phenomenon often poses a diagnostic challenge, as bile duct metastases may clinically and radiologically mimic primary biliary tumors, such as cholangiocarcinoma. We present a unique case of solitary, synchronous intraductal biliary metastasis in a patient with colorectal adenocarcinoma that led to biliary obstruction. The patient initially presented with a new diagnosis of colon cancer at the hepatic flexure and was found, on cross-sectional imaging, to have biliary obstruction due to an intraductal mass. Initially, the nature of the intraductal lesion was uncertain; however, it was ultimately confirmed through histopathological examination to be metastatic colorectal adenocarcinoma. This case underscores the difficulty of distinguishing metastatic biliary obstruction from primary biliary tumors and highlights the importance of considering metastatic disease in atypical presentations of biliary masses. We discuss several key radiologic and histopathological features that may help differentiate intraductal colorectal adenocarcinoma metastases from primary biliary tumors.

Biliary tract carcinomas (BTC) are malignant epithelial neoplasms subdivided anatomically into: gallbladder carcinomas and carcinomas of the bile duct or cholangiocarcinomas (CCA); including intrahepatic, hilar/perihilar, and distal CCA. Adenocarcinoma accounts for the most common BTC (over 90% of all carcinomas), while other histological subtypes represent rarer forms including: poorly cohesive/signet ring cell carcinoma, which has a greater malignant potential than conventional BTC and a poorer prognosis. Only few cases have been reported in the literature to date. The positive diagnosis remains on histology. Herein, we describe a new case of poorly cohesive carcinoma of bile duct extending to the gallbladder in a 60 years old women with a fatal outcome, to raise awareness of this rare entity and to provide data for larger series.

Cancer disparities are well-established across measures of cancer incidence and mortality. Cholangiocarcinoma, a common hepatic malignancy, is no exception to these inequities. Globally and within the United States, Asian, Hispanic, and Indigenous peoples of the Americas, Alaskan Natives, and Pacific Islander populations experience higher incidence rates of cholangiocarcinoma. These same groups and non-Hispanic Black individuals simultaneously experience lower disease-specific survival, highlighting the role of social factors in cholangiocarcinoma outcome inequities. Higher age-standardized death rates from cholangiocarcinoma are associated with a lower social determinant index (SDI) in Andean Latin America, Southern Latin America, and Central sub-Saharan Africa. SDI, which evaluates education, fertility, and income, can be used to model the social determinants of health (SDOH). The SDOH also affect cholangiocarcinoma survival in the United States as factors such as migratory status, insurance status, and geographic location can cause treatment delays and worsened outcomes. Despite these inequities, limited research exists on the topic of disparities in cholangiocarcinoma when compared with other malignancies, and clinical trial under-representation remains a significant concern. Representing diverse populations in cholangiocarcinoma clinical trials is exceedingly important as populations with the highest incidence are simultaneously under-represented in clinical trials. Diversity in clinical trial enrollment and research regarding cholangiocarcinoma is needed to create robust databases and biobanks that can be used to develop targeted treatments and guidelines. In addition, risk factors, including parasitic infections, infectious diseases, and environmental exposures, are associated with cholangiocarcinoma but vary by global region, highlighting the need to study unique risk factors for cholangiocarcinoma across diverse populations. Without research that represents the populations that suffer most from this cancer, incidence and mortality inequities will continue to have a disproportionate burden.

Identifying past, present, and future temporal trends in gallbladder and biliary tract cancer (GBTC) can increase public awareness and promote changes in prevention and treatment strategies.

The incidence and death rates of GBTC between 1990 and 2021 were extracted from the Global Burden of Disease study 2021 and assessed according to country, region, year, age, and sex. Time trends were measured using the average annual percentage change (AAPC) and projections of the burden of disease for 2022 to 2045 were made using the Bayesian age-period-cohort model.

In 2021, there were 216,768.3 new cases (95% uncertainty interval [UI], 181,888.0-245,237.6) and 171,961.2 deaths (95% UI, 142,351.8-194,238.4) in GBTC globally. The increases in incidence and deaths were 101.09% and 74.26%, respectively, compared with 1990. The GBTC burden was higher in females and older adults. However, age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) trended downward from 1990 to 2021, with AAPC at -0.39 (95% CI, -0.52 to -0.26) and -0.88 (95% CI, -0.96 to -0.79), respectively. Although the ASIR and ASDR for both sexes are projected to decline gradually from 2022 to 2045, the incidence and deaths are expected to increase steadily. In addition, the global proportion of GBTC deaths owing to high body mass index in 2021 was 12.66% for females and 10.48% for males, which did not change significantly from 1990.

GBTC is becoming a major global health burden, especially among females and older adults. Given the increasing burden of an aging population, there is a need to reduce the incidence of this disease by adopting effective strategies and measures targeting risk factors.

Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3-4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases.

Intrahepatic cholangiocarcinoma (ICC)originates from the epithelial cells of the intrahepatic bile ducts, with insidious onset and strong invasiveness, and most of the cases are found in the advanced stage, with extremely poor prognosis. In advanced stages, distant metastases to the lungs, bones, and brain are common, but distant soft tissue (subcutaneous and skeletal muscle) and breast metastases are rare, and simultaneous metastases to all three rare sites had not been reported. We report a 69-year-old woman with right upper abdominal pain who underwent a plain and enhanced CT scan of the upper abdomen, which revealed an intrahepatic space-occupying lesion, as well as subcutaneous and peritoneal nodules in the abdomen. To further evaluate the presence of other metastases, an 18F-FDG PET/CT scan was performed, which showed abnormal FDG uptake in the liver, peritoneum, left upper femur, right breast, subcutaneous tissues of the thoracic and abdominal regions, and skeletal muscle, while the corresponding CT densities of part of the skeletal muscle and the left upper femur did not show any significant abnormality. Pathologic confirmation of ICC with multiple metastases was obtained by puncture biopsy of the liver and subcutaneous nodes. This case demonstrates the advantages of 18F-FDG PET/CT in comprehensively evaluating systemic metastasis of ICC and detecting occult metastases, which is of great significance in its clinical diagnosis and staging.

Cholangiocarcinoma (CCA) is a malignant biliary system tumor and the second most common primary hepatic neoplasm, following hepatocellular carcinoma. CCA still has an extremely high unfavorable prognosis, regardless of type and location, and complete surgical resection remains the only curative therapeutic option; however, due to the underhanded onset and rapid progression of CCA, most patients present with advanced stages at first diagnosis, with only 30 to 60% of CCA patients eligible for surgery. Recent innovations in medical imaging combined with the use of radiomics and artificial intelligence (AI) can lead to improvements in the early detection, characterization, and pre-treatment staging of these tumors, guiding clinicians to make personalized therapeutic strategies. The aim of this review is to provide an overview of how radiological features of CCA can be analyzed through radiomics and with the help of AI for many different purposes, such as differential diagnosis, the prediction of lymph node metastasis, the defining of prognostic groups, and the prediction of early recurrence. The combination of radiomics with AI has immense potential. Still, its effectiveness in practice is yet to be validated by prospective multicentric studies that would allow for the development of standardized radiomics models.

CCA has a poor prognosis. Different anatomical subtypes are characterized by distinct clinical features, surgical options, and prognoses, which can potentially impact survival outcomes following radical resection. In addition to the malignancy of CCA itself, clinical staging and treatment methods are the main factors that can affect survival. This study aims to update a more reliable prediction model for the prognosis of CCA based on different anatomical locations.

A total of 1172 CCA patients (305 iCCA, 467 pCCA, and 400 dCCA) who underwent surgical resection between 2015 and 2022 were included in the analysis. The covariates included in the analysis were age, sex, tumor diameter, differentiation grade, T stage, N stage, M stage, neural invasion, cancer thrombus, history of hepatitis B or biliary calculi, and receipt of adjuvant chemotherapy. The data were randomly divided into training (80 %) and validation cohort (20 %).

We developed a nomogram of the sensitive model and calculated concordance indices of different constructed prognostic survival models. Meanwhile, we validated the effectiveness of the nomogram model and compared it with the TNM system through decision curve analysis (DCA) and internal cohort validation. The nomogram model had a better net benefit than the TNM system at any given threshold for iCCA, pCCA, and dCCA, regardless of their location.

We have updated the prognostic model for OS in CCA patients who underwent radical resection according to the different tumor locations. This model can effectively predict OS and has the potential to facilitate individual clinical decision-making.

Cholangiocarcinoma (CHOL) is a rare cancer with low survival rates. Despite advances in precision medicine targeting molecular subtypes, the immune subtypes of CHOL remain poorly understood. This study aimed to identify immune subtypes of CHOL and investigate their implications in the metabolic regulation of macrophage functions in inflammation.

We conducted a comprehensive analysis of transcriptome and single-cell sequencing data from multiple databases to classify the immune subtypes of CHOL. Immune cell infiltration within the tumor microenvironment (TME) and the metabolic pathways involved in macrophage activation and polarization were also analyzed.

Two distinct immune subtypes, immune-infiltrated CS1 and immune-depleted CS2, were identified in CHOL. CS1 exhibited a highly active TME with substantial immune cell infiltration, including macrophages, and activation of immune-related signaling pathways, such as inflammatory and interferon pathways. In contrast, CS2 was characterized by a deficiency in immune components and poorer prognosis. Metabolic regulation of macrophages, particularly the downregulation of oxidative phosphorylation in CS1, suggested a shift towards glycolysis as an energy source for activated macrophages, contributing to the immune-responsive phenotype observed in CS1. Additionally, the oncogenic role of DLX5 in CHOL was revealed, with potential impacts on macrophage functions in inflammation.

This study provides insights into immune subtype classification, novel biomarker identification, and the metabolic regulation of macrophage functions in CHOL. Understanding macrophage metabolic reprogramming within immune subtypes may contribute to the development of targeted immunotherapies for CHOL.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival.

Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+).

Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection.

Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with a poor prognosis, predominantly CA19-9 positive. High CA19-9 levels correlate with increased aggressiveness and worse outcomes. This study employs multi-omics analysis to reveal molecular features and identify therapeutic targets of CA19-9 positive ICC, aiming to support individualized treatment.

Data from seven clinical cohorts, two whole-exome sequencing cohorts, six RNA sequencing/microarray cohorts, one proteomic cohort, 20 single-cell RNA sequencing samples, and one spatial transcriptome sample were analyzed. Key findings were validated on tissue microarrays from 52 ICC samples.

CA19-9 positive ICC exhibited poorer OS (median 24.1 v.s. 51.5 months) and RFS (median 11.7 v.s. 28.2 months) compared to negative group (all P < 0.05). Genomic analysis revealed a higher KRAS mutation frequency in the positive group and a greater prevalence of IDH1/2 mutations in the negative group (all P < 0.05). Transcriptomic analysis indicated upregulated glycolysis pathways in CA19-9 positive ICC. Single-cell analysis identified specific glycolysis-related cell subclusters associated with poor prognosis, including Epi_SLC2A1, CAF_VEGFA, and Mph_SPP1. Higher hypoxia in the CA19-9 positive group led to metabolic reprogramming and promoted these cells' formation. These cells formed interactive communities promoting epithelial-mesenchymal transition (EMT) and angiogenesis. Drug sensitivity analysis identified six potential therapeutic drugs.

This study systematically elucidated the clinical, genomic, transcriptomic, and immune features of CA19-9 positive ICC. It reveals glycolysis-associated cellular communities and their cancer-promoting mechanisms, enhancing our understanding of ICC and laying the groundwork for individualized therapeutic strategies.

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.

Background: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene ITIH5, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis. Methods: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA). Results: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI). Conclusions: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.

Extrahepatic biliary neuroendocrine tumors (EBNETs) are rare. We aimed to characterize EBNETs including factors associated with survival.

The National Cancer Database was queried for patients with EBNETs from 2004 to 2016. Patients who underwent resection were examined using Cox proportional hazards regression and the Kaplan-Meier method. We compared overall survival (OS) among patients with EBNETs to those with NETs from other primary sites.

Overall, 223 patients with EBNETs were identified. Patients were predominantly male (n = 113, 50.7 %), white (n = 177, 79.4 %) and presented without distant metastasis (n = 182, 81.6 %). The majority underwent operation (n = 127, 57.9 %) with resection of the primary tumor (n = 89, 70 %). Among patients who underwent resection (n = 71), multivariable regression demonstrated older age (HR 1.11, 95 % C.I. 1.04-1.17), lymph node metastases (HR 1.19, 95 % C.I. 1.02-1.38) and poorly/undifferentiated tumors [HR 22.3, 95 % C.I. 3.78-131]) were associated with worse overall survival. Patients with EBNETs experienced abbreviated OS compared to patients with small bowel or pancreas NETs (p < 0.001), but improved OS when compared to patients with gallbladder NETs (p = 0.001).

Tumor differentiation and lymph node status significantly impact overall survival.

To examine the diagnostic performance for the longitudinal extent of extrahepatic bile duct (EHD) cancer on computed tomography (CT) after biliary drainage (BD) and investigate the appropriate timing of magnetic resonance imaging (MRI) acquisition.

This retrospective study included patients who underwent curative-intent surgery for EHD cancer and CT pre- and post-BD between November 2005 and June 2021. The biliary segment-wise longitudinal tumor extent was evaluated according to the 2019 Korean Society of Abdominal Radiology consensus recommendations, with pre-BD CT, post-BD CT, and both pre- and post-BD CT. The performance for tumor detectability was compared using generalized estimating equation (GEE) method. When preoperative MRI was performed, patients were divided into two subgroups according to the timing of MRI with respect to BD, and the performance of MRI obtained pre- and post-BD was compared.

In 105 patients (mean age: 67 ± 8 years; 74 men and 31 women), the performance for tumor detectability was superior using both CT scans compared with using post-BD CT alone (reader 1: sensitivity, 72.6% vs. 64.6%, P < 0.001; specificity, 96.9% vs. 94.8%, P = 0.063; reader 2: sensitivity, 77.2% vs. 72.9%, P = 0.126; specificity, 97.5% vs. 94.2%, P = 0.003), and it was comparable with using pre-BD CT alone. In biliary segments with a catheter, higher sensitivity and specificity were observed using both CT scans than using post-BD CT (reader 1: sensitivity, 74.4% vs. 67.5%, P = 0.006; specificity, 92.4% vs. 88.0%, P = 0.068; reader 2: sensitivity, 80.5% vs. 74.4%, P = 0.013; specificity, 94.3% vs. 88.0%, P = 0.016). Post-BD MRI (n = 30) exhibited a comparable performance to pre-BD MRI (n = 55) (reader 1: sensitivity, 77.9% vs. 75.0%, P = 0.605; specificity, 97.2% vs. 94.9%, P = 0.256; reader 2: sensitivity, 73.2% vs. 72.6%, P = 0.926; specificity, 98.4% vs. 94.9%, P = 0.068).

Pre-BD CT provided better diagnostic performance in the preoperative evaluation of EHD cancer. The longitudinal tumor extent could be accurately assessed with post-BD MRI, which was similar to pre-BD MRI.

The acquisition of pre-BD CT could be beneficial for the preoperative evaluation of EHD cancer when BD is planned. Post-BD MRI would not be significantly affected by BD in terms of the diagnostic performance of the longitudinal tumor extent.

We aimed to describe our outcomes of robotic resection for perihilar cholangiocarcinoma, the largest single institutional series in the Western hemisphere to date.

Between 2016 and 2022, we prospectively followed all patients who underwent robotic resection for perihilar cholangiocarcinoma.

In total, 23 patients underwent robotic resection for perihilar cholangiocarcinoma, 18 receiving concomitant hepatectomy. The median age was 73 years. Operative time was 470 min with an estimated blood loss of 150 mL. No intraoperative conversions to open or other intraoperative complications occurred. Median length of stay was 5 days. Four postoperative complications occurred. Three readmissions occurred within 30 days with one 90-day mortality. R0 resection was achieved in 87% of patients and R1 in 13% of patients. At a median follow-up of 27 months, 15 patients were alive without evidence of disease, two patients with local recurrence at 1 year, and six were deceased.

Utilization of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with excellent perioperative outcomes. Further studies are needed to determine the long-term oncological outcomes.

Although post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain.

Retrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria.

A total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival.

To achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.

Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments.

The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn.

Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS.

In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a heterogeneous cancer of the bile duct, and its diagnosis is often challenging.

To provide insights into state-of-the-art approaches for the diagnosis of CCA.

Literature review via PubMed search and authors' experiences.

CCA can be categorized as intrahepatic or extrahepatic. Intrahepatic CCA is further classified into small-duct-type and large-duct-type, whereas extrahepatic CCA is classified into distal and perihilar according to site of origin within the extrahepatic biliary tree. Tumor growth patterns include mass forming, periductal infiltrating, and intraductal tumors. The clinical diagnosis of CCA is challenging and usually occurs at an advanced tumor stage. Pathologic diagnosis is made difficult by tumor inaccessibility and challenges in distinguishing CCA from metastatic adenocarcinoma to the liver. Immunohistochemical stains can assist in differentiating CCA from other malignancies, such as hepatocellular carcinoma, but no distinctive CCA-specific immunohistochemical profile has been identified. Recent advances in next-generation sequencing-based high-throughput assays have identified distinct genomic profiles of CCA subtypes, including genomic alterations that are susceptible to targeted therapies or immune checkpoint inhibitors. Detailed histopathologic and molecular evaluations of CCA by pathologists are critical for correct diagnosis, subclassification, therapeutic decision-making, and prognostication. The first step toward achieving these goals is to acquire a detailed understanding of the histologic and genetic subtypes of this heterogeneous tumor group. Here, we review state-of-the-art approaches that should be applied to establish a diagnosis of CCA, including clinical presentation, histopathology, staging, and the practical use of genetic testing methodologies.

The risk factors of patients with intrahepatic cholangiocarcinoma (ICC) requiring conversion to open surgery have not been adequately studied. This study aimed to determine the risk factors and postoperative outcomes of conversion in patients with ICC.

From May 2014 to September 2022, Unplanned conversions were compared with successful LLRs.

153 patients with ICC initially underwent LLR, of which 41 (26.8%) required conversion to open surgery. Multivariate analysis for those factors that were statistically significant or confirmed by clinical studies, tumor proximity to the major vessels (OR 6.643, P < 0.001), and previous upper abdominal surgery (OR 3.140, P = 0.040) were independent predictors of unplanned conversions. Compared to successful LLRs, unplanned conversions showed longer operative times (300.0 vs. 225.0 min, P < 0.001), more blood loss (500.0 vs. 200.0 mL, P < 0.001), higher transfusion rates (46.3% vs. 11.6%, P < 0.001), longer length of stays (13.0 vs. 8.0 days, P < 0.001), and higher rates of major morbidity (39.0% vs. 11.6%, P < 0.001). However, there was no statistically significant difference in 30-day or 90-day mortality between the conversion group and the laparoscopic group.

Conversion during LLR should be anticipated in ICC patients with prior upper abdominal surgery or tumor proximity to major vessels as features.

A 37-year-old female patient was diagnosed with intrahepatic cholangiocarcinoma (ICC), with the lesion located in the right lobe of the liver. Despite radical resection, postoperative adjuvant chemotherapy and a combination of adjuvant chemotherapy and immunotherapy, the patient continued to experience multiple instances of intrahepatic tumor metastases. Furthermore, the patient exhibited significant adverse reactions to systemic chemotherapy and had poor treatment tolerance. Guidance from paraffin section fluorescence in situ hybridization gene sequencing was used to select a combination of immunotherapy and targeted therapy treatments with programmed cell death 1 (PD-1)/PD-1 ligand 1 antibody durvalumab and the targeted drug pemigatinib. The patient tolerated the treatment and has continued to survive for 28 months. According to imaging evaluations, the lesions continued to decrease, with some disappearing completely. The tumor marker carbohydrate antigen 19-9 remained normal for >9 weeks during the treatment. This report described the patient's treatment process in detail and briefly reviewed relevant literature on the treatment progress of postoperative patients with ICC.

Cholangiocarcinoma (CCA) is a highly malignant and easily metastatic bile duct tumor with poor prognosis. We aimed at studying the associated risk factors affecting distal metastasis of CCA and using nomogram to guide clinicians in predicting distal metastasis of CCA.

Based on inclusion and exclusion criteria, 345 patients with CCA were selected from the Fifth Medical Center of Chinese PLA General Hospital and were divided into distal metastases (N = 21) and non-distal metastases (N = 324). LASSO regression models were used to screen for relevant parameters and to compare basic clinical information between the two groups of patients. Risk factors for distal metastasis were identified based on the results of univariate and multivariate logistic regression analyses. The nomogram was established based on the results of multivariate logistic regression, and we drawn the corresponding correlation heat map. The predictive accuracy of the nomogram was evaluated by receiver operating characteristic (ROC) curves and calibration plots. The utility of the model in clinical applications was illustrated by applying decision curve analysis (DCA), and overall survival(OS) analysis was performed using the method of Kaplan-meier.

This study identified 4 independent risk factors for distal metastasis of CCA, including CA199, cholesterol, hypertension and margin invasion, and developed the nomogram based on this. The result of validation showed that the model had significant accuracy for diagnosis with the area under ROC (AUC) of 0.882 (95% CI: 0.843-0.914). Calibration plots and DCA showed that the model had high clinical utility.

This study established and validated a model of nomogram for predicting distal metastasis in patients with CCA. Based on this, it could guide clinicians to make better decisions and provide more accurate prognosis and treatment for patients with CCA.

The study aimed to establish radiomics models based on magnetic resonance imaging (MRI) multiparameter images to predict the survival and prognosis of patients with extrahepatic cholangiocarcinoma (ECC).

Seventy-eight patients with ECC confirmed by pathology were collected retrospectively. The radiomics model_a/b/c were constructed based on the 1/2/3-year survival of patients with ECC. The best texture features were selected according to postoperative survival time and ECC patient status to calculate the radiomics score (Rad-score). A cutoff value was selected, and patients were divided into high-risk and low-risk groups.

Model_a, model_b, and model_c were used to predict 1-, 2-, and 3-year postoperative survival rates, respectively. The area under the curve values in the training and test groups were 1.000 and 0.933 for model_a, 0.909 and 0.907 for model_b, 1.000 and 0.975 for model_c, respectively. The survival prediction model based on the Rad-score showed that the postoperative mortality risk differed significantly between risk groups (p < 0.0001).

The MRI radiomics model could be used to predict the survival and prognosis of patients with ECC.

Self-expandable metal stent (SEMS) insertion is the standard palliative treatment for unresectable malignant extrahepatic biliary obstruction (MBO). Drawbacks of conventional fully covered SEMS (FCSEMS) and uncovered SEMS (USEMS) include stent migration and tumor ingrowth, respectively. This study aimed to compare stent patency in MBO with the newly design multi-hole SEMS (MHSEMS), which has multiple small side holes in the stent membrane, with conventional FCSEMS and UCSEMS.

This retrospective study using a propensity score matching design and stent patency times of 40 patients with MHSEMS was compared to 40 and 34 patients with FCSEMS and UCSEMS during the same period, respectively. Secondary outcomes were procedure-related adverse events, clinical success rate, time to recurrent biliary obstruction (RBO), and etiology of RBO. RBO was compared using Kaplan-Meier analysis.

Baseline characteristics after matching were comparable among the 3 groups. RBO rates were 21%, 37%, and 55% for MHSEMS, FCSEMS, and UCSEMS, respectively (p = 0.014), at a mean time of 479, 353, and 306 days, respectively (MHSEMS vs UCSEMS, p = 0.002). Rate of tumor ingrowth was highest in the UCSEMS group (42.4% vs 13.2% in MHSEMS; p = 0.005 and vs 0% in FCSEMS; p < 0.001). Stent migration rate was highest in the FCSEMS group at 15.8% vs 2.6% in MHSEMS (p = 0.047) and 0% in UCSEMS (p = 0.005).

MHSEMS provided the longest stent patency time with lowest RBO rate compared to conventional SEMS by showing a lower stent migration rate than FCSEMS and a lower tumor ingrowth rate than UCSEMS.

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Using a systematic literature search of original articles published during 2022 in Gastrointestinal Endoscopy and other high-impact medical and gastroenterology journals, the 10-member Editorial Board of the American Society for Gastrointestinal Endoscopy composed a list of the 10 most significant topic areas in GI endoscopy during the study year. Each Editorial Board member was directed to consider 3 criteria in generating candidate lists-significance, novelty, and global impact on clinical practice-and subject matter consensus was facilitated by the Chair through electronic voting. The 10 identified areas collectively represent advances in the following endoscopic spheres: artificial intelligence, endoscopic submucosal dissection, Barrett's esophagus, interventional EUS, endoscopic resection techniques, pancreaticobiliary endoscopy, management of acute pancreatitis, endoscopic environmental sustainability, the NordICC trial, and spiral enteroscopy. Each board member was assigned a consensus topic area around which to summarize relevant important articles, thereby generating this précis of the "top 10" endoscopic advances of 2022.