Cholangiocarcinoma Research Articles

Autopsy diagnosis of diffuse intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC), a severe liver cancer, makes up to 20% of all hepatic malignancies and is difficult to diagnose early due to its often asymptomatic nature. This case report documents a rare presentation of ICC with multiple diffuse nodules not previously recorded in medical literature. A 65-year-old man with no significant medical history presented with back pain, anorexia, and significant weight loss. Elevated tumor markers and enlarged lymph nodes were observed, though imaging did not reveal a primary liver mass. Diagnostic efforts, including computed tomography and positron emission tomography scans and biopsies of lymph nodes and bone marrow, suggested adenocarcinoma of unknown primary origin. A definitive diagnosis was only made post-mortem, revealing multiple diffuse nodules in the liver identified as ICC, marking a rare presentation without a primary mass. This case highlights the diagnostic challenges posed by atypical ICC manifestations, where typical imaging does not indicate a primary mass, delaying diagnosis and treatment. The findings emphasize the importance of considering ICC in differential diagnoses in cases of unknown primary adenocarcinoma with liver involvement. The discovery of ICC with diffusely infiltrative nodules underscores the necessity for comprehensive diagnostic evaluations in patients presenting with nonspecific systemic symptoms and abnormal liver findings.

The role of exosomes in liver cancer: comprehensive insights from biological function to therapeutic applications

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.

Advanced ultrasound diagnosis of extrahepatic bile duct lesions.

Ultrasound (US) has high specificity and sensitivity, and it should be performed first for patients with suspicion of biliary tract cancer. However, the complicated anatomy in addition to the gas images makes it difficult to delineate the entire extrahepatic bile duct (EHBD). The keys to depiction of EHBD are the "J" shape manipulation in the left lateral decubitus position and the use of magnified images with high-frequency transducers. Furthermore, indirect findings such as gallbladder (GB) distension, BD dilatation, and debris echo in the GB and BD are also important for detecting occult lesions, particularly in the ampullary region of Vater. For the differential diagnosis of BD wall thickening, the spreading pattern in the long and short axial directions should be assessed first. Then, the characteristics of the innermost hyperechoic layer (IHL) and outermost hyperechoic layer (OHL) should be evaluated. Asymmetrical wall thickening, absence of IHL, and presence of irregularity or discontinuity in OHL are characteristic patterns of cholangiocarcinoma (CCA). Because CCA is the most common BD polypoid lesion, it is important to diagnose tumor extension and depth invasion in addition to differential diagnosis. Nodular-type CCA is usually hypoechoic and more likely to invade vertically. In contrast, papillary-type CCA is often hyperechoic and extends laterally. Contrast‑enhanced US may be useful for evaluating these findings. However, if the possibility of CCA cannot be ruled out or a definitive diagnosis is needed, a transpapillary biopsy or endoscopic US-guided tissue acquisition should be considered.

Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Regulatory Mechanisms, Functions, and Therapeutic Implications.

Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically "cold" tumors to "hot" tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients.

Efficacy of cisplatin-gemcitabine-durvalumab in patients with advanced biliary tract cancer experiencing early vs late disease relapse after surgery: a large real-life worldwide population.

In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial. The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS). A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]. Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC.

Integrative multi-omics analysis reveals the role of tumor-associated endothelial cells and their signature in prognosis of intrahepatic cholangiocarcinoma

This study aims to investigate the interplay between tumor-associated endothelial cells (TECs) and immune cells within the tumor microenvironment (TME) and its impact on tumor prognosis. We conducted single-cell RNA sequencing (scRNA-seq) of tumor, normal, and lymph node tissues obtained from intrahepatic cholangiocarcinoma (ICC) patients to reveal the role of TECs in tumor angiogenesis and their significant heterogeneity. Meanwhile, we identified genes highly expressed in TECs and constructed TEC signatures (TEC.Sig). Next, we calculated TEC scores of samples based on TEC.Sig. Patients with higher TEC scores exhibited a higher frequency of KRAS mutations, which was associated with increased infiltration of neutrophils and immature dendritic cells (iDCs), and decreased numbers of natural killer (NK), CD4 + T, and CD8 + T effector memory (Tem) cells, indicating an inflammation-dominated immunosuppressive phenotype. In contrast, BAP1 mutations and CXCL12 overexpression showed a contrasting trend. Spatial transcriptomics analysis and histological experiments further confirmed that TECs interacted with various tumor-killing immune cells through the CXCL12/CXCR4 axis. Multiple tumor immunotherapy datasets confirmed that the TEC.Sig could predict patient responses to immunotherapy. The TEC score is a promising and reliable biomarker for predicting genetic mutations and prognosis in ICC patients. Enhancing the regulation of the CXCL12/CXCR4 signaling pathway may represent a potential novel therapeutic target for ICC treatment.

Atezolizumab Plus Chemotherapy With or Without Bevacizumab in Advanced Biliary Tract Cancer: Clinical and Biomarker Data From the Randomized Phase II IMbrave151 Trial.

Biliary tract cancers (BTCs) harbor an immunosuppressed tumor microenvironment and respond poorly to PD-1/PD-L1 inhibitors. Bevacizumab (anti-vascular endothelial growth factor) plus chemotherapy can promote anticancer immunity, augmenting response to PD-L1 inhibition. This randomized, double-blind, proof-of-concept phase II study enrolled patients (n = 162) with previously untreated advanced BTC (IMbrave151; ClinicalTrials.gov identifier: NCT04677504). Patients were randomly assigned 1:1 to receive cycles of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) or atezolizumab plus placebo once every 3 weeks until disease progression or unacceptable toxicity. All patients received cisplatin (25 mg/m2) plus gemcitabine (1,000 mg/m2; cisplatin plus gemcitabine [CisGem]) on days 1 and 8 once every 3 weeks for up to eight cycles. Stratification of patients was by disease status, geographic region, and primary tumor location. The primary end point was progression-free survival (PFS). No formal hypothesis testing was performed. Exploratory correlative biomarker analysis was undertaken using transcriptome analysis (n = 95) and mutation profiling (n = 102) on baseline tumor samples. Between February and September 2021, 162 patients were enrolled. Median PFS was 8.3 months in the bevacizumab arm and 7.9 months in the placebo arm (stratified hazard ratio [HR], 0.67 [95% CI, 0.46 to 0.95]). Median overall survival (OS) was 14.9 and 14.6 months in the bevacizumab and placebo arms, respectively (stratified HR, 0.97 [95% CI, 0.64 to 1.47]). The incidence of grade 3 or 4 adverse events was 74% in both arms. High VEGFA gene expression was associated with improved PFS (HR, 0.44 [95% CI, 0.23 to 0.83]) in the bevacizumab arm versus placebo. In unselected patients with advanced BTC, adding bevacizumab to atezolizumab plus CisGem modestly improves PFS but not OS. High VEGFA gene expression may represent a predictive biomarker of benefit from atezolizumab/bevacizumab, warranting further investigation.

Chromosome 8q24 amplification associated with human hepatocellular carcinoma predicts MYC/ZEB1/MIZ1 transcriptional regulation.

Genomic instability is associated with late stage carcinomas and the epithelial mesenchymal transition (EMT). Of note is chromosome 8q24 amplification that has been documented in many epithelial-derived carcinomas. On this amplified region is the potent oncogene, c-myc. Not only does MYC overexpression activate targets that promote cell proliferation, it also activates transcription factors that drive EMT, including ZEB1. Further reinforcing EMT, overexpressed MYC also represses tumor suppressors involved in promoting the epithelial phenotype, including MIZ1. We predict that as carcinomas progress, chromosome 8q24 is amplified leading to high MYC levels that leads to ZEB1 expression and MIZ1 repression driving cells through EMT. To interrogate this clinically, limited cohorts of human epithelial-derived carcinomas were examined for MYC/ZEB1/MIZ1 expression patterns across increasing carcinoma grades. Interestingly, the predicted temporal patterns were only observed in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinomas. Yet MIZ1 proved to be an excellent marker to assess carcinoma progression across types. We expanded the HCC cohort and determined that c-myc amplification was restricted to grade III/IV HCC that also exhibited increased MYC and ZEB1 nuclear expression whereas cytosolic MIZ1 expression was lost and only nuclear expression retained. These same resections were obtained from only individuals who had histories of alcohol consumption that were also diagnosed with cirrhosis, metastasis and had viral hepatitis suggesting etiology-specific mechanisms of cancer progression. Finally, analysis performed in Hep3B cells determined that alterations in MYC expression promoted the predicted changes in ZEB1 and MIZ1 expression and/or distributions and in markers for EMT further suggesting a relationship among these three transcription factors in HCC and their correlation to driving EMT.

Prognostic value of the advanced lung cancer inflammation index in intrahepatic cholangiocarcinoma

IntroductionThe advanced lung cancer inflammation index (ALI), which combines inflammation and nutrition data, was recently proposed as a prognostic biomarker. We assessed the impact of ALI on overall survival (OS) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). MethodsPatients who underwent surgery for ICC were identified from an international cohort. ALI was calculated as body-mass index (BMI)∗albumin/neutrophil-to-lymphocyte ratio; patients were categorized into “low-” and “high-ALI” using log-rank statistics. The impact of ALI on OS was compared against other inflammatory markers (i.e., neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic immune inflammation index [SII = platelets∗NLR]) using Harrell's Concordance index (C-index) and the Akaike Information Criterion (AIC). To minimize intergroup differences, propensity score matching was employed. ResultsAmong 1045 patients, more than one-half of individuals underwent major hepatectomy (n = 582, 55.7 %), median tumor size was 5.5 cm (IQR, 3.8–7.8), and median ALI was 38.9 (IQR 26.5–57.2). On multivariate analysis, low ALI was an independent risk factor for worse OS (HR 1.21, 95 % CI 1.01–1.46; p = 0.04). Patients with low ALI had worse 5-year OS (36.9 % vs. 49.9 %; p < 0.001), which remained significant after PSM (36.9 % vs. 41.3 %; p = 0.039). ALI had a comparable discriminatory ability compared with NLR, PLR, and SII (C-index: 0.646 vs. 0.644 vs. 0.640 vs. 0.641, respectively), yet had a lower AIC (5475.31 vs. 5546.80 vs. 5550.45 vs. 5548.62, respectively) suggesting slightly better model fit and accuracy. ConclusionsALI was an independent predictor of OS among patients undergoing surgery for ICC. Nutritional and inflammatory markers should be incorporated into predictive models to improve prognostic stratification.

No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging.

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study

BackgroundBiliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT). However, standardized practices for BTC are lacking, and there is a need to assess the impact of current MDT treatment decisions on BTC outcomes. The purpose of this study was to investigate the role of the treatment plan proposed by the first MDT conference on survival in patients with BTC, and to identify risk factors for poor survival in this population. MethodThis nationwide, multicenter, retrospective cohort study examined data from the Danish Liver Cancer Group (2013–2020) with confirmed BTC diagnoses. Multiple imputation was used to handle missing data. Survival and variable-survival rate relationships were analyzed using the Kaplan-Meier estimator, and the Cox regression model, respectively. ResultsEligible BTC-confirmed cases: n=1923. The overall median survival was 7.7 months (95 % CI: 7.1–8.5), with a 5-year survival rate of 16.3 %. Patients over 70 years of age, with ECOG-PS 3 or 4, non-operable cases, and with unresectable tumors had lower survival rates. Surgery as the first therapeutic option showed the highest median survival (33.1 months, 95 % CI: 27.2–41.6; p < 0.0001). Multivariable analysis showed that poor ECOG-PS, palliative and neoadjuvant chemotherapy, stereotactic radiotherapy, and best supportive care significantly increased mortality risk in patients with BTC (p=0.05). ConclusionAmong the therapeutic options prescribed by the MDT for patients with BTC, surgery offered the best survival rates, likely due to patient-related prognostic factors. High ECOG-PS was linked to an increased mortality risk regardless of age, highlighting the importance of this criterion in treatment decisions.

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-Analysis Based on Individual Patient-Level Data of Randomized Trials.

While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p =0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs nal-IRI plus 5-FU/LV, 95% CI 0.93-2.07, p=0.11) and 1.36 (mFOLFIRI vs nal-IRI plus 5-FU/LV, 95% CI 0.92-2.03, p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Targeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest

BackgroundCancer-associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely have a role in tumor aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor, namely Crenigacestat, may affect cancer progression.MethodsWe used different in vitro models in 2D and established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. The results were confirmed in a xenograft model, and explanted tumoral tissues underwent transcriptomic and bioinformatic analysis.ResultshCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, while Crenigacestat significantly inhibits only the cross-talk stimulated migration. Hetero-spheroids grew larger than homo-spheroids, formed by only iCCA cells. Crenigacestat significantly reduced the invasion and growth of hetero- but not of homo-spheroids. In xenograft models, hCAFs/KKU-M213 tumors grew significantly larger than KKU-M213 tumors, but were significantly reduced in volume by Crenigacestat treatment, which also significantly decreased the fibrotic reaction. Ingenuity pathway analysis revealed that genes of hCAFs/KKU-M213 but not of KKU-M213 tumors increased tumor lesions, and that Crenigacestat treatment inhibited the modulated canonical pathways. Cell cycle checkpoints were the most notably modulated pathway and Crenigacestat reduced CCNE2 gene expression, consequently inducing cell cycle arrest. In hetero-spheroids, the number of cells increased in the G2/M cell cycle phase, while Crenigacestat significantly decreased cell numbers in the G2/M phase in hetero but not in homo-spheroids.ConclusionsThe hCAFs/iCCA cross-talk is a new target for reducing cancer progression with drugs such as Crenigacestat.Graphical abstract

Circulating miR-18a and miR-532 Levels in Extrahepatic Cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is a highly aggressive cancer of the bile ducts with a poor prognosis and limited diagnostic markers. This study aims to investigate the potential of miR-18a and miR-532 as biomarkers for CCA by exploring their correlations with clinical parameters and traditional tumor markers such as CA19.9, CEA, and AFP. Methods: This study involved a cohort of patients diagnosed with CCA. Serum levels of miR-18a and miR-532 were measured and analyzed in relation to various clinical parameters, including age, tumor markers, and histological features. Results: Serum levels of miR-18a and miR-532 were upregulated in patients with extrahepatic cholangiocarcinoma (eCCA) compared to healthy controls (p < 0.05). MiR-18a and miR-532 levels were correlated with each other (p = 0.011, Spearman's rho = 0.482) but showed no significant correlation with age or traditional tumor markers (CA19.9, CEA, AFP). No significant differences in miR-18a and miR-532 levels were observed concerning tumor localization or histological grading. For predicting tumor resectability, miR-532 at a cut-off point of 2.12 showed a sensitivity of 72.73%, specificity of 81.25%, and an AUC of 71.3%, while miR-18a, at a cut-off of 1.83, had a sensitivity of 63.64%, specificity of 75%, and an AUC of 59.7%. ROC curve analysis suggested moderate diagnostic potential for miR-18a and miR-532, with AUC values of 0.64 and 0.689, respectively. Conclusions: Although miR-18a and miR-532 showed significant upregulation in eCCA patients compared to healthy controls, they did not demonstrate significant associations with key clinical parameters, limiting their effectiveness as standalone diagnostic biomarkers. Further research involving larger, multi-center cohorts and additional molecular markers is necessary to validate these findings and explore the broader diagnostic potential of miRNAs in CCA.

Associations between pre-diagnostic plasma metabolites and biliary tract cancer risk in the prospective UK Biobank cohort.

Biliary tract cancer (BTC) is potentially influenced by metabolic dysregulation yet previous metabolomic evaluations are limited. To address this gap, we prospectively investigated associations of blood metabolites and BTC risk in the UK biobank cohort study. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between 249 plasma metabolites per standard deviation and BTC risk in 232,781 participants. We implemented exploratory factor analyses and evaluated associations between factors and BTC risk. Associations at p-value<0.001 were considered statistically significant after multiple comparison adjustments. In a median follow-up of 11.8 years, we identified 268 first primary incident BTC cases. Of 49 biomarkers significantly associated with BTC risk, 12% were fatty acids, and 49%, 31%, and 8% were cholesterol, triglyceride, and phospholipid to total lipids ratios, respectively. Multiple cholesterol ratios were inversely associated with BTC with HRs (95% CIs) of 0.74 (0.65-0.84), p<6.0x10-6. Conversely, a triglyceride ratio was positively associated with BTC with an HR (95% CI) of 1.40 (1.22-1.61), p=2.5x10-6. Congruently, a factor high in cholesterol measures and low in triglyceride measures was inversely associated with BTC. Multiple metabolite biomarkers were associated with BTC risk, suggesting metabolism has a substantial role in BTC etiology.

Probability of lymph node metastases in patients undergoing adequate lymphadenectomy during surgery for intrahepatic cholangiocarcinoma: a retrospective multicenter study

Probability of lymph node metastases in patients undergoing adequate lymphadenectomy during surgery for intrahepatic cholangiocarcinoma: a retrospective multicenter study

Novel procedure for hepatic venous outflow block after liver resection: A case report

BACKGROUND Postoperative complications like remnant hepatic vein (HV) outflow block and liver torsion can occur after right hepatectomy. Hepatic falciform ligament fixation is typically used to prevent liver torsion. We report a novel procedure to manage outflow block. CASE SUMMARY An 80-year-old man developed HV outflow block after remnant right hepatectomy, despite liver fixation and intraoperative HV flow check. He had a history of cholangiocellular carcinoma and had undergone posterior segmentectomy and choledojejunostomy. The falciform ligament fixation was inadequate to maintain liver position. Emergency surgery was performed, using an omental flap and mobilized right side colon with ileocecal region to prevent liver dislocation due to intraabdominal adhesion. His postoperative course was uneventful. CONCLUSION This is the first report providing a novel surgical procedure when the falciform ligament is insufficient for remnant liver fixation.

Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study.

Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.

Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells.

Intrahepatic cholangiocarcinoma (ICC) is a malignant liver tumor that is challenging to treat and manage and current prognostic models for the disease are inefficient or ineffective. Tumor-associated immune cells are critical for tumor development and progression. The main goal of this study was to establish models based on tumor-associated immune cells for predicting the overall survival of patients undergoing surgery for ICC. To establish 1-year and 3-year prognostic models for ICC after surgical resection. Immunohistochemical staining was performed for CD4, CD8, CD20, pan-cytokeratin (CK), and CD68 in tumors and paired adjacent tissues from 141 patients with ICC who underwent curative surgery. Selection of variables was based on regression diagnostic procedures and goodness-of-fit tests (PH assumption). Clinical parameters and pathological diagnoses, combined with the distribution of immune cells in tumors and paired adjacent tissues, were utilized to establish 1- and 3-year prognostic models. This is an important application of immune cells in the tumor microenvironment. CD4, CD8, CD20, and CK were included in the establishment of our prognostic model by stepwise selection, whereas CD68 was not significantly associated with the prognosis of ICC. By integrating clinical data associated with ICC, distinct prognostic models were derived for 1- and 3-year survival outcomes using variable selection. The 1-year prediction model yielded a C-index of 0.76 95% confidence interval (95%CI): 0.65-0.87 and the 3-year prediction model produced a C-index of 0.69 (95%CI: 0.65-0.73). Internal validation yielded a C-index of 0.761 (95%CI: 0.669-0.853) for the 1-year model and 0.693 (95%CI: 0.642-0.744) for the 3-year model. We developed Cox regression models for 1-year and 3-year survival predictions of patients with ICC who underwent resection, which has positive implications for establishing a more comprehensive prognostic model for ICC based on tumor immune microenvironment and immune cell changes in the future.

MiR-182-5p promotes the proliferation and invasion of hilar cholangiocarcinoma cells by inhibiting FBXW7

BackgroundHilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment.MethodsHCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3’UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes.ResultsmiR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 ‘UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo.ConclusionmiR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.