The role of autophagy in cholangiocarcinogenesis and its development is intricate. Autophagy has a dual role in cholangiocarcinoma, and understanding the function and mechanism of autophagy in cholangiocarcinoma is pivotal in guiding therapeutic approaches to its treatment in clinical settings. Recent studies have revealed that autophagy is involved in the complex biological behavior of cholangiocarcinoma. In this review, we have summarized the genes and drugs that would promote or inhibit autophagy, leading to change in cellular behaviors of cholangiocarcinoma, including apoptosis, proliferation, invasion and migration, and influence its cellular drug resistance. In addition, we concluded the signaling pathways modulating autophagy in cholangiocarcinoma cells, including PI3K/AKT/mTOR,p38MAPK,AMPK/mTOR,LKB1-AMPK, and AKT/WNK1, and ERK signaling pathways, which subsequently impacting apoptosis, death, migration, invasion, and proliferation. In conclusion, we would like that we can provide ideas for future cholangiocarcinoma treatment by comprehensively summarizing the latest studies on the relationship between autophagy and cholangiocarcinoma, including the factors affecting autophagy and related signaling pathways.

The bile duct transports bile fluid from the liver to the gallbladder and small intestine. It contains bioactive peptides, including galanin (GAL) and its receptors (GAL1-3-R). Spexin (SPX), a member of the GAL peptide family, activates GAL2-R and GAL3-R. Its expression in perihilar bile ducts or in perihilar cholangiocarcinoma (pCCA), the most common biliary cancer, is largely unknown. This study investigated SPX expression in healthy, cholestatic, and malignant bile duct tissues. Immunohistochemistry was used to evaluate SPX in healthy (n = 4), peritumoral (PIT) (n = 23) and pCCA (n = 34) tissues. Score values of SPX expression were calculated and statistically analyzed. In healthy and PIT tissues with or without cholestasis, SPX expression was predominantly observed in cholangiocytes and nerve fibers. In pCCA, tumor cells also expressed SPX. SPX levels were similar across healthy, peritumoral, and cholangiocytes/tumor cells. In a small pCCA patient cohort (n = 19), SPX expression did not correlate with tumor grade or patient survival (p = 0.0838). The substantial expression of SPX in cholangiocytes and nerve fibers in the bile duct indicates that SPX contributes via galaninergic signaling to gall bladder function. The presence of SPX in submucosal nerve fibers suggests a neuromodulatory role, possibly involving bile duct motility. SPX expression did not correlate with survival in pCCA, whereas previous findings on GAL suggest a prognostic value. This highlights the need for joint studies of SPX and GAL in larger cohorts.

BackgroundIntrahepatic cholangiocarcinoma (ICC) presents a significant clinical challenge due to its high fatality rate and limited surgical candidacy. With only 30-40% of patients eligible for surgery upon diagnosis, alternative therapies are imperative. This study assesses the efficacy of Yttrium-90 (Y-90) radioembolization for unresectable ICC patients in a non-university tertiary care center (NUTCC).MethodsA retrospective analysis of 15 unresectable ICC patients treated with Y-90 radioembolization was conducted. Tumor response, survival, and adverse events were evaluated using RECIST criteria.Results60% of patients exhibited partial response, and 20% showed stable disease, with notable tumor size reduction and a median survival of 14 months. Minimal adverse effects were observed, indicating Y-90's favorable safety profile.ConclusionY-90 radioembolization shows potential in reducing tumor burden and enhancing survival rates with minimal adverse effects for unresectable ICC. Larger prospective studies are needed to confirm its efficacy and define its role in ICC treatment protocols.

Intrahepatic cholangiocarcinoma (ICC) is a malignancy with rising incidence and mortality in the United States. This study aimed to investigate temporal trends in the place of death among patients with ICC and assess demographic disparities.

We used the CDC WONDER database (2003-2020) for a retrospective study of patients who died from intrahepatic cholangiocarcinoma identified through death certificates. Place of death was categorized as hospice, home, inpatient, nursing home, or other. Age-adjusted mortality rates were calculated per 100 000. Temporal trends were assessed using the Mann-Kendall trend test, and associations between demographic characteristics and place of death were examined using the χ 2 test.

Of 101 631 ICC-related deaths (AAMR: 1.61; 95% CI 1.60-1.62), the AAMR rose from 1.19 (95% CI 1.15-1.23) in 2003 to 2.04 (95% CI 2.00-2.08) in 2020. Over the study period, home was the most frequent place of death (44.6%), followed by inpatient facilities (28.4%), hospice (11.1%), and nursing homes (9.5%). Deaths at home and in hospice increased significantly (p < 0.01), while inpatient and nursing home deaths declined (p < 0.01). Disparities were observed across race, sex, age groups, and urbanization. Younger patients more often died in inpatient facilities, and minority racial groups were less likely to die at home or utilize hospice.

ICC-related deaths in the USA nearly doubled over the study period, with a marked shift from inpatient and nursing home deaths to hospice and home. Demographic disparities in end-of-life care underscore the need for targeted interventions to improve equitable access to palliative services.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and is characterized by huge heterogeneity, difficult diagnosis, and poor prognosis. Fibrosis-associated heterogeneity in CCA serves as an indicator of the malignant progression of cancer; however, a precise approach to deciphering fibrosis heterogeneity is still lacking. Typically, the tissue proteome is profiled by analyzing bulk tissues, which gives average results of different cell types, especially for CCA tissues in which cancer cells occupy a very small proportion. Laser microdissection (LMD) can precisely dissect CCA cell clusters, but the required manual, time-consuming annotation limits its efficiency. Herein, we develop π-CellSeg-CCA, a pathological image analysis algorithm based on Mask R-CNN and ResNet-18, to enable automated annotation of CCA and normal bile duct regions for LMD and achieve an enhanced recognition accuracy of ∼90%. Driven by π-CellSeg-CCA, we develop a new strategy by integrating a machine learning algorithm, LMD, simple and integrated spintip-based proteomics technology (SISPROT), and high-sensitivity mass spectrometry to decipher CCA fibrosis-associated pathological heterogeneity. We identify over 8000 proteins, including marker proteins specifically expressed in CCA from only 1 mm2 samples. A protein specifically upregulated in fibrosis CCA, MUC16, is further investigated to reveal its association with worse prognosis and its contribution to the progression of CCA. We expect that the algorithm-assisted cell-type proteomics strategy is promising for studying the tumor microenvironment with limited clinical materials.

Lactylation, a novel form of lactate-mediated protein post-translational modification (PTM), has been identified as a crucial regulator of gene expression and protein function through the modification of both histone and non-histone proteins. Liver disease is frequently characterized by a reprogramming of glucose metabolism and subsequent lactate accumulation. Recent research has implicated lactylation in a diverse array of hepatic pathologies, including liver injury, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Consequently, lactylation has emerged as a pivotal regulatory mechanism in liver disease pathogenesis. This review aims to elucidate the intricate regulatory and functional mechanisms underlying lactylation, synthesize recent advancements in its role in various liver diseases, and highlight its potential as a therapeutic target for future interventions in hepatic disorders.

This study aims to discover the role of lncRNA MIR17HG, referred to as MIR17HG, in cisplatin resistance for cholangiocarcinoma (CCA).

QRT-PCR was conducted to measure the expression of MIR17HG in cisplatin-resistant/sensitive CCA cells and clinical CCA specimens. Log-rank test was used to analyze the survival curve. Cck8-assay and flow cytometry were employed to detect the sensitivity of CCA cells to cisplatin and the apoptosis rate following different treatments, respectively. The next-generation sequencing was carried out to get gene transcripts after silencing MIR17HG in HCCC-9810 cells. The LncBase database was used to predict the target miRNA of MIR17HG, and MS2 RIP assay and dual luciferase assay were conducted to confirm their binding. MiRwalk database and the RNA sequencing data were utilized to screen the key genes regulated by MIR17HG/miR-138-5p axis and a dual luciferase assay was performed to confirm the binding site of miR-138-5p with AKAP9. Immunoblotting was further employed to give assistant evidence. Rescue experiments were performed to observe the function of miR-138-5p and AKAP9 in MIR17HG-induced cisplatin resistance.

MIR17HG overexpression predicts cisplatin resistance and poor prognosis in CCA. MIR17HG could bind with miR-138-5p to release AKAP9, thereby inhibiting cisplatin-induced apoptosis and promoting cisplatin resistance in CCA. MIR17HG silencing in CCA cells leads to expression alteration of genes, which are enriched in platinum resistance-related pathways.

LncRNA MIR17HG regulates platinum resistance-associated genes and promotes cisplatin resistance partially via the miR-138-5p/AKAP9 axis by inhibiting cisplatin-induced apoptosis in CCA.

Perihilar cholangiocarcinoma presents unique challenges in perioperative management, requiring a comprehensive approach to optimize patient outcomes.

This case study focuses on the multidisciplinary management and innovative interventions performed in the perioperative care of a patient with hilar cholangiocarcinoma.

A comprehensive assessment and treatment strategy involving neoadjuvant therapy and interventional radiology techniques were implemented. Neoadjuvant chemotherapy was administered to reduce tumor size and improve resectability. The crucial role of interventional radiology in managing postoperative complications is highlighted, particularly in the case of massive pulmonary embolism.

The neoadjuvant therapy successfully reduced tumor size, enabling an R0 surgical resection. Additionally, interventional radiology interventions, such as percutaneous pharmaco-mechanical thrombectomy, effectively addressed the life-threatening complication of massive pulmonary embolism.

This article highlights the importance of a collaborative, multidisciplinary approach in managing complex oncological surgeries, especially regarding the hospital's rescue capacity for severe postoperative complications. Emergent management with interventional radiology had a central role in resolving life-threatening complications.

The term cholangiocarcinoma (CCA) includes a group of malignant tumors that develop in the efferent bile ducts and are characterized by a high degree of heterogeneity. These differences between intrahepatic, perihilar and distal CCAs run through all aspects of the disease including the etiology, pathogenesis, symptoms, diagnostics and treatment. This review article presents the current developments in this field of diseases. We highlight surgical innovations in the clinical routine and the application of new systemic forms of treatment to augment the oncological radicality of surgery.

Alopecia areata (AA) is an autoimmune skin disease. Observational studies have reported an association between AA and cancer. However, the causal relationship between AA and cancer has not been reported. We employed a two-sample Mendelian randomization (MR) study to assess the causality between AA and 17 subtypes of cancers.

We employed a two-sample Mendelian randomization (MR) study to assess the causality between AA and 17 subtypes of cancers. AA and cancers' association genome-wide association study (GWAS) data were collected. The inverse variance weighted (IVW) method was utilized as the principal method in our Mendelian randomization (MR) study, with additional use of the MR-Egger, weighted median, simple mode, and weighted mode methods. After that, we explored the underlying biological mechanisms by Bioinformatic Analysis.

According to our MR analysis, AA has a causal relationship with hepatic bile duct cancer (HBDC, (odds ratio [OR] = 0.944, 95% confidence interval [CI] = 0.896-0.994, P-value = 0.030) and colorectal cancer (CRC, OR = 0.981, 95% CI = 0.963-0.999, P-value = 0.046). AA could decrease the risk of HBDC and CRC. No causal link between AA and other subtypes of cancers was observed. No heterogeneity or pleiotropy was observed. Furthermore, disease-related genes were obtained, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that the set of genes associated with immunity-inflammatory signaling pathway.

This study provided new evidence of the relationship between AA with HBDC and CRC. AA may play a protective role in both HBDC and CRC progression. This could provide newer avenues for research in search of treatment for HBDC and CRC.

Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches.

In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials.

At this moment, dozens of clinical trials in phases I to III are evaluating the role of cancer immunotherapy in this setting, with the hope of adding more therapeutic options for BTC patients. Future research must focus on the development of novel agents and combinations, but the validation of biomarkers remains an urgent need. As more research results emerge, novel combinatorial strategies are destined to further transform the treatment paradigm for this heterogeneous and aggressive tumor type.

Photodynamic therapy (PDT) induced lipid peroxidation reaction can lead to necrosis and apoptosis of extrahepatic cholangiocarcinoma (ECC) cells, reducing the tumor load. However, the depth of action of PDT is shallow, and its therapy efficacy is weak, making it difficult to achieve eradication even with multiple treatments.

This study aims to investigate the mechanism and main pathways of ferroptosis in cholangiocarcinoma under Hematoporphyrin-mediated photodynamic therapy, and to compare the effects of different ferroptosis inducers on photodynamic therapy-induced ferroptosis in cholangiocarcinoma. To provide an experimental basis for selecting appropriate ferroptosis-inducing agents and synergizing with photodynamic therapy during the clinical perioperative period.

The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of cholangiocarcinoma cells following PDT. Flow cytometry was used to detect apoptotic cell percentage and cell cycle changes to assess the enhanced photodynamic production of reactive oxygen species (ROS) by different ferroptosis inducers, confocal imaging was used to de-assay ROS content. Western blot analysis was employed to detect the expression of GPX4 、FSP1、ASCL4 and SLC7A11. Furthermore, a fluorescence spectrophotometric assay was used to quantify the alterations in lipid peroxides (MDA, LPO, GSH, and Fe2+).

The combination of PDT with Lenvatinib or Erastin resulted in increased ROS levels, and decreased GSH content, tumor cells were inhibited in the G2 phase, and the proportion of apoptotic cells increased. Additionally, GPX4, FSP1, and SLC7A11 protein expression decreased, whereas ASCL4 increased This was accompanied by heightened levels of Fe2+, LPO, and MDA. Induction of the ferroptosis pathway was observed to enhance the therapeutic efficacy of PDT.

Our findings suggest that Erastin or Lenvatinib can enhance the induction of ferroptosis in cholangiocarcinoma cells by photodynamic therapy by increasing intracellular ROS and inhibiting intracellular antioxidant pathways.

Lim Domain and Actin Binding protein1 (lima1) influence cancer cell function. Thus far, functional role of lima1 in cholangiocarcinoma remains unknown. We used public databases, in vitro experiments, and multi-omics analysis to investigate the Lima1 in cholangiocarcinoma. Our results showed that lima1 expression is significantly upregulated and high levels of lima1 are significantly associated with vascular invasion in cholangiocarcinoma. Furthermore, lima1 knocking out inhibits the RBE cell invasion. Multi-omics data suggest that lima1 affect a broad spectrum of cancer related pathways, promoting tumor progression and metastatic ability in cholangiocarcinoma. This study provides insights into molecular associations of lima1 with tumorigenesist and establishes a preliminary picture of the correlation network in cholangiocarcinoma.

Shoulder pain is a common type of musculoskeletal pain. While musculoskeletal issues are primary causes of shoulder pain, it is important to note that referred pain in the shoulder area can also originate from non-musculoskeletal problems.

A 60-year-old male presented with a month-long stabbing pain in the right shoulder that was worsened by deep breathing. He had no trauma history or neurological symptoms. He also experienced a 5 kg weight loss over 3 months. Physical examination was normal. Shoulder X-ray suggested degenerative arthritis. Despite medication including opioids, his pain persisted and worsened to a 10/10 severity, spreading to the right flank and anterior chest.

An abdominal CT scan revealed multiple hepatic nodules, ascites, and right pleural effusion, suggesting a systemic condition.

This prompted immediate referral to oncology, where subsequent investigations confirmed the diagnosis of intrahepatic cholangiocarcinoma.

The patient deteriorated and passed away during the buildup phase for cancer treatment.

This case underscores the importance of considering systemic conditions in patients presenting with seemingly localized symptoms such as shoulder pain. It highlights the significance of thorough evaluation and prompt referral for further investigations when necessary.

Hilar 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.

HCCA 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.

miR-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.

miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.

Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).

Cholangiocarcinoma (CCA) is a heterogeneous and aggressive malignancy with limited therapeutic options and poor prognosis. The identification of reliable prognostic biomarkers and a deeper understanding of the molecular subtypes are critical for the development of targeted therapies and improvement of patient outcomes. This study aims to uncover oxidative stress-related genes (ORGs) in CCA and develop a prognostic risk model using comprehensive transcriptomic analysis from The Cancer Genome Atlas (TCGA). Through LASSO regression analysis, we identified prognosis-related ORGs and constructed a prognostic signature consisting of six ORGs. This signature demonstrated strong predictive performance in survival analysis and ROC curve assessment. Functional enrichment and GSEA analyses revealed significant enrichment of immune-related pathways among different risk groups. GSVA analysis indicated reduced activity in inflammation and oxidative stress pathways in the high-risk subgroup, and xCell results showed lower immune cell infiltration levels in this group. Additionally, immune checkpoint genes and immune-related pathways were downregulated in the high-risk subgroup. Our research has developed a unique prognostic model focusing on oxidative stress, enabling accurate forecasting of patient outcomes and providing crucial insights and recommendations for the prognosis of individuals with CCA. Future studies should aim to validate these findings in clinical settings and further explore therapeutic targets within oxidative stress pathways.

Intrahepatic cholangiocarcinoma (iCC) is an aggressive tumor, usually detected at an advanced stage. Our aim was to investigate the potential of body composition analysis (BCA) derived from presurgical staging computed tomography (CT) in predicting perisurgical complications.

In this retrospective cohort study, we enrolled 86 patients who underwent CT imaging prior to liver surgery. Cox and logistic regression were performed to assess risk factors for prolonged hospital and intensive care unit (ICU) stays, as well as the occurrence of various complications. BCA parameters served as covariates besides conventional risk factors.

Postoperative complications after resection of iCC significantly prolonged the overall length of hospitalization (p < .001). Presence of sarcopenia was associated with longer ICU stays. Complications were common, with 62.5% classified as Clavien-Dindo grade IIIa or lower and 37.5% as more severe. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were identified as risk factors for complications, including bile leakage (in 24 cases, p = .025), pleural effusions (in 26 cases, p = .025), and intra-abdominal abscess formation (in 24 cases, p = .043). SAT was associated with severe complications requiring interventional therapy, whereas VAT was correlated with abscess formation. Despite normal prevalence of obesity (22%), body mass index (BMI) did not have an impact on the development of perioperative complications.

BCA is a useful tool for preoperative risk stratification in patients with iCC and is superior to BMI assessment. Increased SAT and VAT were associated with the risk of perisurgical complications, prolonging hospitalization. Therefore, BCA derived from routine staging CT should be considered in the preoperative assessment of patients with iCC.

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer, carries a grim prognosis with a 5-year survival rate of 5%-15%. Standard chemotherapy regimens for CCA, gemcitabine plus cisplatin (GemCis) or its recently approved combination with durvalumab demonstrate dismal clinical activity, yielding a median survival of 12-14 months. Increased serotonin accumulation and secretion have been implicated in the oncogenic activity of CCA. This study investigated the therapeutic efficacy of telotristat ethyl (TE), a tryptophan hydroxylase inhibitor blocking serotonin biosynthesis, in combination with standard chemotherapies in preclinical CCA models. Nab-paclitaxel (NPT) significantly enhanced animal survival (60%), surpassing the marginal effects of TE (11%) or GemCis (9%) in peritoneal dissemination xenografts. Combining TE with GemCis (26%) or NPT (68%) further increased survival rates. In intrahepatic (iCCA), distal (dCCA) and perihilar (pCCA) subcutaneous xenografts, TE exhibited substantial tumour growth inhibition (41%-53%) compared to NPT (56%-69%) or GemCis (37%-58%). The combination of TE with chemotherapy demonstrated enhanced tumour growth inhibition in all three cell-derived xenografts (67%-90%). PDX studies revealed TE's marked inhibition of tumour growth (40%-73%) compared to GemCis (80%-86%) or NPT (57%-76%). Again, combining TE with chemotherapy exhibited an additive effect. Tumour cell proliferation reduction aligned with tumour growth inhibition in all CDX and PDX tumours. Furthermore, TE treatment consistently decreased serotonin levels in all tumours under all therapeutic conditions. This investigation decisively demonstrated the antitumor efficacy of TE across a spectrum of CCA preclinical models, suggesting that combination therapies involving TE, particularly for patients exhibiting serotonin overexpression, hold the promise of improving clinical CCA therapy.

Circular RNA (circRNA) is a unique type of noncoding RNA molecule characterized by its closed-loop structure. Functionally versatile, circRNAs play pivotal roles in gene expression regulation, protein activity modulation, and participation in cell signaling processes. In the context of cancers of the digestive system, the Wnt signaling pathway holds particular significance. Anomalous activation of the Wnt pathway serves as a primary catalyst for the development of colorectal cancer. Extensive research underscores the notable participation of circRNAs associated with the Wnt pathway in the progression of digestive system tumors. These circRNAs exhibit pronounced dysregulation across esophageal cancer, gastric cancer, liver cancer, colorectal cancer, pancreatic cancer, and cholangiocarcinoma. Furthermore, the altered expression of circRNAs linked to the Wnt pathway correlates with prognostic factors in digestive system tumors. Additionally, circRNAs related to the Wnt pathway showcase potential as diagnostic, therapeutic, and prognostic markers within the realm of digestive system tumors. This comprehensive review outlines the interplay between circRNAs and the Wnt signaling pathway in cancers of the digestive system. It seeks to provide a comprehensive perspective on their association while delving into ongoing research that explores the clinical applications of circRNAs associated with the Wnt pathway.

Naja atra bites often result in immediate and severe illness. The venom of N. atra contains a complex mixture of toxins that can cause significant damage to the patient's skin tissue. If left untreated, this condition can progress to localized necrosis, potentially resulting in impairment or even amputation in severe cases. Despite the known effects of the venom, the exact mechanisms underlying this tissue necrosis are not fully understood. This study aimed to investigate the protein components responsible for tissue necrosis induced by N. atra venom at both the organism-wide and molecular levels. To achieve this, venom was injected into Bama miniature pigs to cause ulcers, and exudate samples were collected at various time points after injection. Label-free proteomics analysis identified 1119, 1016, 938, 864, and 855 proteins in the exudate at 6, 12, 24, 36, and 48 h post-injection, respectively. Further analysis revealed 431 differentially expressed proteins, with S100A8, MMP-2, MIF, and IDH2 identified as proteins associated with local tissue necrosis. In this study, we established a Bama miniature pig model for N. atra venom injection and performed proteomic analysis of the wound exudate, which provides important insights into the molecular pathology of snakebite-induced tissue necrosis and potential theoretical bases for clinical treatment. Proteomic data from this study can be accessed through ProteomeXchange using the identifier PXD052498.

Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics.

Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016-2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people.

In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs.

The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas.

Biliary tract cancers (BTCs) are a heterogeneous group of tumors with high malignancy, poor prognosis, and limited treatment options.

To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.

This open-label, non-randomized, double-center, phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University. Eligible patients were administered nab-paclitaxel (150 mg/m2, day 1) and capecitabine (2000 mg/m2, twice daily, days 1-7) in 14-day cycles until experiencing intolerable toxicity or disease progression. The primary outcome was the objective response rate (ORR). The secondary outcomes included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and safety.

A total of 44 patients successfully completed the trial, with a median age of 64.00 years (interquartile range, 35.00-76.00), and 26 (59.09%) were females. Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage. Among the remaining 43 patients undergoing at least one imaging assessment, the ORR was 23.26% [95% confidence interval (CI): 11.80%-38.60%], and the DCR was 69.77% (95%CI: 53.90%-82.80%). The median OS was 14.1 months (95%CI: 8.3-19.9), and the median PFS was 4.4 months (95%CI: 2.5-6.3). A total of 41 patients (93.18%) experienced at least one adverse event (AE), with 10 patients (22.73%) encountering grade ≥ 3 AEs, and the most frequent AEs of any grade were alopecia (79.50%), leukopenia (54.55%), neutropenia (52.27%), and liver dysfunction (40.91%), and no treatment-related deaths were documented.

Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis. Adenocarcinoma is the most common pathological type of cholangiocarcinomas, but rare squamous, adenosquamous, and mucinous variants have been reported without adequate clinical data.

This report describes a rare case of primary squamous cell carcinoma (SCC) of the intrahepatic bile duct. The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms. Examination revealed hepatitis B surface antigen positivity, a slight increase in alfa-fetoprotein to 16.34 ng/mL, and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe, which was initially thought to be hepatocellular carcinoma. Laparoscopic resection was performed, and the final pathology suggested a rare primary SCC of the intrahepatic bile duct. Immunohistochemistry indicated positivity for villin, partial positivity for p63, and negativity for hepatocyte, CK7, CK8, CK19, and CK20. The Ki-67 index was approximately 60%. The patient received six cycles of Tegio chemotherapy. A new lesion was detected in the liver after 15 months. The surgery was performed, and the patient was followed-up at a local hospital. To date, no new lesions have been observed.

Surgery is the first choice for resectable lesions, and combined chemotherapy based on pathology is essential for increasing overall survival.

Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways.

The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe2+), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo.

PDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the mitochondria in affected cells. Furthermore, ROS levels rose, accompanied by an increase in the proportion of apoptotic-positive cells. The expressions of Bax and Caspase-3 were upregulated, while the Bcl-2 was downregulated. Meanwhile, PDT triggered ferroptosis, marked by decreased expressions of GPX4 and SLC7A11, and reduced GSH levels. This was accompanied by upregulation of P53 expression and heightened levels of Fe2+, LPO, MDA, and LDH. After inducing the ferroptosis pathway, the therapeutic effect of PDT was enhanced, the tumor tissue was further reduced, and the degree of malignancy was reduced.

PDT promotes apoptosis and ferroptosis of cholangiocarcinoma cells by activating the P53/SLC7A11/GPX4 signaling pathway and inhibits the growth of cholangiocarcinoma. Inducing ferroptosis can enhance the effectiveness of photodynamic therapy.

Cholangiocarcinoma (CCA), a highly aggressive primary liver cancer arising from the bile duct epithelium, represents a substantial proportion of hepatobiliary malignancies, posing formidable challenges in diagnosis and treatment. Notably, the global incidence of intrahepatic CCA has seen a rise, necessitating a critical examination of diagnostic and management strategies, especially due to presence of close imaging mimics such as hepatocellular carcinoma (HCC) and combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). Hence, it is imperative to understand the role of various imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), elucidating their strengths, and limitations in diagnostic precision and staging accuracy. Beyond conventional approaches, there is emerging significance of functional imaging tools including positron emission tomography (PET)-CT and diffusion-weighted (DW)-MRI, providing pivotal insights into diagnosis, therapeutic assessment, and prognostic evaluation. This comprehensive review explores the risk factors, classification, clinical features, and role of imaging in the holistic spectrum of diagnosis, staging, management, and restaging for CCA, hence serving as a valuable resource for radiologists evaluating CCA.

Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis.

CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells.

Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup.

Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.

Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.

Humoral hypercalcemia of malignancy (HHM) comprises the majority of cases with malignancy-related hypercalcemia and is mediated by elevated parathyroid hormone-related peptide (PTHrP). HHM is rare in cholangiocarcinoma and has been reported only in a few case reports and series. We report a case of a 63-year-old male with a history of locally advanced fibroblast growth factor receptor (FGFR) fusion-positive intrahepatic cholangiocarcinoma who presented with recurrent HHM. The first episode of his hypercalcemia occurred 15 months after the initial diagnosis of cholangiocarcinoma and coincided with disease progression. The hypercalcemia was treated with zoledronic acid, and an FGFR inhibitor was started for the treatment of his malignancy. The second hypercalcemia episode occurred nine months later, with evidence of further disease progression. HHM is associated with poor clinical outcomes; a high index of suspicion should be present to identify and treat this complication in cases of cholangiocarcinoma promptly. With an increased understanding of the molecular alterations underlying cholangiocarcinoma, it will also be necessary to further evaluate its co-occurrence with HHM as the specific molecular alterations in this setting could lay the groundwork for targeted therapies and improve risk stratification for these patients.

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.

Alpha-2-Glycoprotein 1, Zinc-binding (AZGP1, ZAG) is a secreted protein that is synthesized by adipocytes and epithelial cells; it is downregulated in several malignancies such as breast, prostate, liver and lung cancers. However, its function remains unclear in cholangiocarcinoma (CCA). Here, we evaluated the impact AZGP1 in CCA using Gene Expression Omnibus (GEO) and GEPIA. In addition, we analysed AZGP1 expression using quantitative reverse transcription PCR and western blotting. Expression of AZGP1 was nearly deficient in CCA patients and cell lines and was associated with poor prognosis. AZGP1 overexpression upregulated apoptosis markers. Co-immunoprecipitation experiments showed that AZGP1 interacts with tripartite motif-containing protein 25 (TRIM25), and tissue microarray and bioinformatic analysis showed that AZGP1 is negatively correlated with TRIM25 expression in CCA. Thereafter, TRIM25 knockdown led to AZGP1 upregulation and induced cancer cell apoptosis. TRIM25 targets AZGP1 for degradation by catalysing its ubiquitination. AZGP1 overexpression significantly suppressed tumour growth in a xenograft mouse model. This study findings suggest that AZGP1 is a potential therapeutic target or a diagnostic biomarker for treating patients with CCA.

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.

Definition of textbook outcome (TO), defined as a single indicator combining the most advantageous short-term outcomes, is still lacking for perihilar cholangiocarcinoma (PHC). The primary endpoint of the present study is to analyze the rate of achievement of a disease-specific TO for PHC within a high volume tertiary referral centre. Secondary endpoints are to identify predictive factors of TO-achievement and to analyze the impact of achieving TO on long-term results.

Between 2010 and 2022, a total of 237 patients undergoing combined liver and biliary resection for PHC at tertiary referral centre were included. Disease-specific TO were defined as: no 90-day mortality, no postoperative complications, no readmission, no intraoperative transfusions and resection margins. A logistic regression model was developed to identify predictors associated with TO-achievement. Kaplan-Meier curves were designed to determine TO's impact on survival.

TO was achieved in 60 (25.3%) patients. At multivariate logistic regression, preoperative biliary drainage [odds ratio (OR) 2.90 (1.13-3.40), P =0.026], high prognostic nutritional index [OR 7.11 (6.71-9.43), P =0.007[ and minimally invasive approach [OR 3.57 (2.31-3.62), P =0.013] were identified as independent predictors of TO. High ASA score [OR 0.38 (0.17-0.82), P =0.013] decreased the odds of TO. A significant improvement in both overall survival and disease-free survival was associated to TO fulfilment.

Since the achievement of TO correlates with better disease-free and overall survival, every effort should be made to ameliorate modifiable aspects prior to surery: management within referral centres with dedicated experience in biliary tract cancer and preoperative optimization protocol may positively contribute to improve postoperative outcomes, increasing the chance to obtain TO. Moreover, the implementation of advanced minimally invasive programs plays as well.

Tumorigenesis exemplifies the complex process of neoplasm origination, which is characterised by somatic genetic alterations and abnormal cellular growth. This multidimensional phenomenon transforms previously dormant cells into malignant equivalents, resulting in uncontrollable proliferation and clonal expansion. Various elements, including random mutations, harmful environmental substances, and genetic predispositions, influence tumorigenesis's aetiology. MicroRNAs (miRNAs) are now recognised as crucial determinants of gene expression and key players in several biological methods, including oncogenesis. A well-known hypoxia-inducible miRNA is MiR-210, which is of particular interest because of its complicated role in the aetiology of cancer and a variation of physiological and pathological situations. MiR-210 significantly impacts cancer by controlling the hypoxia-inducible factor (HIF) signalling pathway. By supporting angiogenesis, metabolic reprogramming, and cellular survival in hypoxic microenvironments, HIF signalling orchestrates adaptive responses, accelerating the unstoppable development of tumorous growth. Targeting several components of this cascade, including HIF-1, HIF-3, and FIH-1, MiR-210 plays a vital role in modifying HIF signalling and carefully controlling the HIF-mediated response and cellular fates in hypoxic environments. To understand the complexities of this relationship, careful investigation is required at the intersection of MiR-210 and HIF signalling. Understanding this relationship is crucial for uncovering the mechanisms underlying cancer aetiology and developing cutting-edge therapeutic approaches. The current review emphasises MiR-210's significance as a vital regulator of the HIF signalling cascade, with substantial implications spanning a range of tumor pathogenesis.

Cholangiocarcinoma (CCA) stands as an aggressive malignancy of the biliary tract. The interplay between the tumor and immune system plays a pivotal role in disease progression and treatment outcomes. Hence, the present study aimed to extensively explore the immunogenomic landscape of CCA, with the objective of unveiling unique molecular and immunological signatures that could guide personalized therapeutic approaches.

The study collected data from The Cancer Genome Atlas databases, performed gene set variation analysis for the chemokine ligand 5 (CCL5) high/low expression group, conducted principal component analysis, gene set enrichment analysis enrichment and mutation pattern analysis, generated a heatmap, and performed cox regression analysis.

The two discrete subpopulations were found to exhibit contrasting mutational and immunogenomic characteristics, emphasizing the heterogeneity of CCA. These subsets also showed pronounced discrepancies in the infiltration of immune cells, indicating diverse interactions with the tumor immune microenvironment. Furthermore, the dissimilarities in mutational patterns were observed within the two CCA subgroups, with PBRM1 and BAP1 emerging as the most frequently mutated genes. In addition, a prognostic framework was formulated and validated utilizing the expression profiles of COX16 and RSAD2 genes, effectively segregating patients into high-risk and low-risk cohorts. Furthermore, the connections between immune-related parameters and these risk groups were identified, underscoring the potential significance of the immune microenvironment in patient prognosis. In vitro experiments have shown that COX16 promotes the proliferation and metastasis of CCA cells, whereas RSAD2 inhibits it.

The present study provides an intricate depiction of the immunogenomic landscape of CCA based on CCL5 expression, thereby paving the way for novel immunotherapy strategies and prognostic assessment.

Cholangiocarcinoma (CCA) refers to malignancies of the bile ducts that arise in the intrahepatic, perihilar, or distal (extrahepatic) biliary tree, excluding the gallbladder and ampulla of Vater. Although rare, the majority of these cancers are locally advanced at presentation, making them extremely fatal. We present a case of a 65-year-old man who came in for abdominal pain and ascites and was found to have portal vein thrombosis. Initial imaging showed a hepatic lesion, raising suspicion of a hepatic malignancy. Despite the multiple imaging modalities used, the diagnosis remained uncertain. Eventually, a biopsy of the lesion showed it to be a variant of intrahepatic CCA, which has mixed features of hepatocellular carcinoma and CCA. This variant is highly malignant and poorly responsive to treatment, leading to a poor prognosis. Our patient on diagnosis was categorized as stage 4 cancer, and although treatment was initiated, she succumbed to the disease in six months. Based on our experience with this patient, we would like to highlight the significance of a multimodal imaging approach and the necessity of tissue diagnosis when the initial work-up is inconclusive since these factors will also impact the course of management.

In Bismuth type III and IV Hilar Cholangiocarcinoma (III-IV HC), surgical resection is the only chance for long-term survival. As the surgical procedure is complex and Robotic-Assisted Surgery (RAS) may be particularly suitable in this setting, the aim of this study is to evaluate the potential benefits of RAS in III-IV HC in terms of post-operative outcomes.

We conducted a systematic review using the PRISMA checklist for article selection. We searched the PubMed database and included only studies with clinical data about the treatment of III-IV HC using RAS.

A total of 12 papers involving 50 patients were included. All cases were Bismuth IIIa (n = 18), IIIb (n = 27) or IV type (n = 5) and underwent hepatectomy with biliary confluence resection and reconstruction. The mean operative time was 500 minutes with a conversion rate of 4%. The mean hospital stay was 12.2 days, and the morbidity and 30-day mortality rate were 61.9% and 2%, respectively. Over a mean follow up period of 10.1 months, 9/18 cases experienced recurrence (50%).

RAS for III-IV HC is safe and feasible, at least if performed by experienced surgeons on selected cases. The oncological outcomes appear acceptable, given the aggressiveness of this pathology, but further studies are needed to fully elucidate the exact role of robotics in this setting.