Establishment and validation of a nomogram containing cytokeratin fragment antigen 21-1 for the differential diagnosis of intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Background: Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Results: Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. Conclusions: This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study.

Background: Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients. Methods: We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort. Results: Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS). Conclusions: Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

Successful intrahepatic cholangiocarcinoma conversion surgery after administration of fibroblast growth factor receptor inhibitor.

We describe a case of a 47-year-old male patient with initially unresectable intrahepatic cholangiocarcinoma of the right liver lobe with tumor thrombi extending from the right bile duct to the common and left bile ducts. Conventional chemotherapy with gemcitabine and cisplatin for 19 months resulted in progressive disease. Subsequently, a comprehensive genome profile revealed fibroblast growth factor receptor 2 rearrangement, and hence, pemigatinib administration was initiated. After 6 months of pemigatinib therapy, significant shrinking of the tumor and disappearance of the tumor thrombi in the common and left bile duct were observed. Subsequently, the patient underwent conversion surgery, resulting in successful radical resection of the tumor. The patient has been disease-free for 7 months.

Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol.

Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Methods: Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Discussion: Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. Trial Registration: ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.

Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.

USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT.

Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development. Herein, we identified Ubiquitin-specific peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT. USP8 was overexpressed in human tumor tissues and correlated with worse survival. Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT. USP8 worked as a bona fide deubiquitylase of OGT. It stabilized OGT in a deubiquitylation activity-dependent manner. Meanwhile, DUB-IN3, the USP8 inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma. In addition, USP8 depletion promoted the response of iCCA to pemigatinib. In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT. The USP8-OGT axis could be a potential target for iCCA therapy.

Tumour burden score combined with albumin-to-alkaline phosphatase ratio predicts prognosis in patients with intrahepatic cholangiocarcinoma.

Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.

Preventing futile surgery in Intrahepatic and Perihilar cholangiocarcinomas: Can we identify preoperative factors to improve patient selection and optimize outcomes?

BACKGROUND: Intraoperative unresectability, postoperative deaths and early recurrences remain devastating futile events in the surgical management of Intrahepatic cholangiocarcinomas (iCCA) and Perihilar cholangiocarcinomas (pCCA). The present study aims to determine the preoperative predictors of futile surgery in cholangiocarcinomas. METHODS: Consecutive hepatectomies for iCCA and pCCA, between September 2010 and June 2022 were included. Futility of surgery was defined as either intraoperative unresectability, postoperative 30-day mortality or recurrence within six months of surgery. Multivariable logistic regression was used to identify predictors of futility. RESULTS: One hundred and fifty patients of iCCA and pCCA underwent surgery during the time period. Thirty-seven (38.1 %) out of 97 patients of iCCA and 25(47.16 %) out of 53 patients of pCCA underwent futile resection. The predictive factors of futile surgery for iCCA were tumour number (≥2) (OR, 9.705; 95%CI, 2.378-39.614; p = 0.002), serum aspartate transaminase (OR, 8.31; 95%CI, 2.796-24.703; p < 0.001) and serum CA-19.9 (>37 U/ml) (OR, 2.95; 95%CI, 1.051-8.283; p = 0.04). The predictive factors of futility for pCCA were lymph node involvement (OR, 7.636; 95%CI, 1.824-31.979; p = 0.005) and serum alkaline phosphatase (>562.5 U/L) (OR, 11.211; 95%CI, 1.752-71.750; p = 0.011). CONCLUSION: Futile surgery was observed in over one third of our patients. Five strong preoperative predictors of futility were identified. Careful analysis of these factors may reduce futile surgical explorations.

Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF).

Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.

Response to trametinib, hydroxychloroquine, and bevacizumab in a young woman with NRAS-mutated metastatic intrahepatic cholangiocarcinoma: a case report.

Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with NRAS-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in RAS-mutated tumors.

Machine learning to predict the early recurrence of intrahepatic cholangiocarcinoma: A systematic review and meta­analysis.

The prediction of early recurrent of intrahepatic cholangiocarcinoma (ICC) has been widely investigated; however, the predictive value is currently insufficient. To determine the effectiveness of machine learning (ML) for the diagnosis of early recurrent intrahepatic cholangiocarcinoma (ICC), particularly in comparison with clinical models, the present study aimed to determine which ML model had the best diagnostic performance for inpatients with recurrent ICC. In order to search for studies which could be included, three electronic databases were screened from inception to November 2023. A pairwise meta-analysis was performed to evaluate the diagnostic accuracy of the random effects model. A network meta-analysis was performed to identify the most effective ML-based diagnostic model based on the surface under the cumulative ranking curve score. A total of 5 studies of acceptable quality containing 1,247 patients with ICC were included in the present study. Following pairwise meta-analysis, it was found that the ML-based diagnostic accuracy was greater than that of clinical models (surface under the cumulative ranking curve score closer to 1, with significant differences), which initially proved that the ML-based diagnostic power was more optimal than that of clinical models. According to the network meta-analysis, the nomogram performed the best, indicating that this ML model achieved the best diagnostic accuracy for patients with recurrent ICC. In conclusion, the application of ML-based diagnostic models for patients with recurrent ICC was more optimal than the application of the clinical model. The nomogram model ranked first among the models and is therefore recommended for patients with recurrent ICC.

Remarkable response to capmatinib in a patient with intrahepatic cholangiocarcinoma harboring TFG-MET fusion.

Dysregulation of mesenchymal-epithelial transition factor (MET) gene due to amplification, mutation, and fusion has been reported in various types of human cancers. Recently, the efficacy of small-molecule tyrosine kinase inhibitors (TKIs) targeting MET has been demonstrated in a wide range of MET-dysregulated tumors. The majority of biliary tract cancers including intrahepatic cholangiocarcinoma (iCCA) are diagnosed at an advanced stage, and the utility of conventional chemotherapy is limited. Here, we present a case of metastatic iCCA harboring TFG-MET gene fusion, which demonstrated a remarkable response to treatment with capmatinib, a selective MET inhibitor. The patient was a 46-year-old man diagnosed with iCCA with hepatic, intraabdominal lymph nodes, and peritoneal metastases. Comprehensive genomic profiling (CGP) revealed TFG-MET gene fusion in his tumor. After becoming refractory to standard chemotherapy, he received capmatinib, which resulted in a marked shrinkage of the liver masses and lymph node metastases, as well as a drastic decrease in serum CA19-9 level. Our case reinforces the importance of CGP in exploring targeted therapy and supports the potential role of capmatinib in the treatment of tumors harboring MET fusions.

FGFR2 fusion/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma.

Increasing evidence highlights that fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement shows important therapeutic value for patients with intrahepatic cholangiocarcinoma (ICC). This study aims to explore the association of FGFR2 status with the prognosis and immune cell infiltration profiles of patients with ICC. A total of 226 ICC tissue samples from patients who received surgery at the Department of Liver Surgery at Zhongshan Hospital, Fudan University, were collected retrospectively and assigned to a primary cohort (n = 152) and validation cohort (n = 74) group. Fluorescence in situ hybridization was performed to determine FGFR2 status. Multiplex immunofluorescence (mIF) staining and immunohistochemistry were performed to identify immune cells. Thirty-two (14.2%) ICC tissues presented with FGFR2 fusion/rearrangement. FGFR2 fusion/rearrangement was associated with low levels of carcinoembryonic antigen (CEA, P = .026) and gamma glutamyl transferase (γ-GGT, P = .003), low TNM (P = .012), CNLC (P = .008) staging as well as low tumor cell differentiation (P = .016). Multivariate COX regression analyses revealed that FGFR2 fusion/rearrangement was an independent protective factor for both overall survival (OS) and relapse-free survival in patients with ICC. Furthermore, correlation analysis revealed that an FGFR2 fusion/rearrangement was associated with low levels of Tregs and N2 neutrophils and high levels of N1 neutrophils infiltrating into tumors but not with CD8+ T-cell or macrophage tumor infiltration. FGFR2 fusion/rearrangement may exert a profound impact on the prognosis of ICC patients and reprogram the tumor microenvironment to be an immune-activated state. FGFR2 status may be used for ICC prognostic stratification and as an immunotherapeutic target in patients with ICC.

Biological effect of ETV4 and the underlying mechanism of its regulatory effect on epithelial­mesenchymal transition in intrahepatic cholangiocarcinoma cells.

Intrahepatic cholangiocarcinoma (ICC) is a highly invasive malignant tumor. The prognosis of patients with ICC after radical surgical resection remains poor, due to local infiltration, distant metastasis, a high recurrence rate and lack of effective treatment strategies. E26 transformation-specific sequence variant 4 (ETV4) is a pro-carcinogenic factor that is upregulated in several tumors; however, the role of ETV4 in ICC is relatively unknown. The present study aimed to determine the role of ETV4 in the Hccc9810 ICC cell line and to assess how it contributes to epithelial-mesenchymal transition (EMT) in ICC. Hccc9810 cells were infected with lentiviruses to construct stable ETV4-overexpressing cells, stable ETV4 knockdown cells and corresponding control groups. The Cell Counting Kit-8 and Transwell assays were used to quantify cell proliferation, invasion and migration, and the effects on cell cycle progression and apoptosis were detected by flow cytometry. ETV4 was identified as a driver of cell growth, invasion, migration and cell cycle progression, while restraining apoptosis in Hccc9810 cells. Reverse transcription-quantitative PCR and western blotting revealed that increased ETV4 levels may drive EMT by triggering the TGF-ß1/Smad signaling pathway. This cascade, in turn, may foster tumor cell proliferation, migration, invasion and cell cycle advancement, and hinder apoptosis.

Percutaneous liver-directed therapies of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma.

The benefits of an offline to online cognitive behavioral stress management regarding anxiety, depression, spiritual well-being, and quality of life in postoperative intrahepatic cholangiocarcinoma patients.

AIM: Cognitive behavioral stress management (CBSM) has been introduced for the postoperative cancer management, but its application in intrahepatic cholangiocarcinoma (ICC) is rare. This current study constructed an offline to online CBSM (OO-CBSM) program and applying multiple assessing scales, aiming at exploring the benefits of OO-CBSM regarding anxiety, depression, spiritual well-being, and quality of life (QoL) in postoperative ICC patients. METHODS: The study randomly assigned 68 postoperative ICC patients into OO-CBSM (N = 34) and normal care (NC) (N = 34) groups to undergo 10-week interventions. Hospital anxiety-and-depression scale (HADS), Zung's self-reporting anxiety scale (SAS), and depression scale (SDS), functional-assessment of chronic-illness therapy-spiritual well-being scale (FACIT-Sp), European quality-of-life-5 dimensions (EQ-5D), and quality-of-life questionnaire-core30 (QLQ-C30) were assessed within 6 months (M). RESULTS: HADS-anxiety scores at M3 (P = 0.049) and M6 (P = 0.009), SAS score at M6 (P = 0.028), HADS-depression score at M3 (P = 0.043), and SDS scores at M3 (P = 0.044) and M6 (P = 0.028), were lower in the OO-CBSM group versus the NC group. Meanwhile, FACIT-Sp scores at M1 (P = 0.042) and M6 (P = 0.003) were higher in the OO-CBSM group over the NC group. Besides, EQ-5D scores at M3 (P = 0.067) and M6 (P = 0.087) disclosed trends to be lower in the OO-CBSM group versus the NC group, but not statistically significant. QLQ-C30-global-health scores at M3 (P = 0.049) and M6 (P = 0.033), and QLQ-C30-function score at M6 (P = 0.046), were higher in OO-CBSM group over NC group; but QLQ-C30-symptom score was not significantly different at any timepoints between them. CONCLUSION: OO-CBSM attenuates anxiety and depression, and advances spiritual well-being and QoL in postoperative ICC patients, indicating its potency for the ICC postoperative management.

Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

Long-term survivors after curative-intent resection for intrahepatic cholangiocarcinoma.

OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.