Abstract:Intrahepatic cholangiocarcinoma (ICC) is a highly malignant primary liver tumor with a poor prognosis. In recent years, research on ICC has surged, with the number of related publications in the PubMed database increasing annually. However, research progress has mainly focused on molecular mechanisms and systemic therapy, while advancements in surgical treatments for ICC have been relatively slow. Traditionally, ICC has been commonly regarded as a uniform disease entity in clinical practice. There are considerable controversies regarding ICC, including its epidemiological characteristics, clinicopathologic features, and molecular biology traits. Appropriate classification is the cornerstone of ICC research. This paper reviews the relevant literature at home and abroad to address its heterogeneity from different perspectives on the controversies surrounding ICC.

Abstract:Background and Aims Hilar cholangiocarcinoma (HCCA) is a prevalent malignant biliary tumor encountered in clinical practice with a unique anatomical location, high invasiveness, and great surgical difficulty. In recent years, with the development of laparoscopic technology and minimally invasive surgical techniques, laparoscopic radical resection of HCCA has been performed in some large hepatobiliary medical centers. This approach has advantages over traditional open radical resection of HCCA, but there is still some controversy regarding the choice between these surgical methods. This study was conducted to compare the efficacy and safety of laparoscopic versus open radical resection of HCCA through a Meta-analysis, providing evidence-based medical references for clinical practice.Methods The clinical studies comparing laparoscopic and open radical resection of HCCA were collected by searching multiple domestic and international databases. The search period spanned from the inception of each database to August 31, 2023. After screening the literature based on inclusion and exclusion criteria, data extraction, and quality assessment of the included studies, a meta-analysis was performed using RevMan 5.3 software.Results A total of 20 studies were included, involving 1 036 patients, of which 457 underwent laparoscopic radical resection of HCCA (laparoscopic group), and 579 underwent open radical resection of HCCA (open group). The meta-analysis results indicated that, in terms of primary outcomes, the laparoscopic group had a higher number of lymph nodes dissected (MD=0.61, 95% CI = 0.11-1.12, P<0.05) and a higher R₀ resection rate (OR=2.47, 95% CI=1.47-4.14, P<0.05), but had no statistically significant differences in the overall postoperative complication rate or the 1-, 2-, and 3-year survival rates compared with the open group (all P>0.05). For secondary outcomes, the laparoscopic group had a longer operative time (MD=51.39, 95% CI=44.78-57.99, P<0.05), less intraoperative blood loss (MD=-75.29, 95% CI=-92.46--58.12, P<0.05), and shorter incision length (MD=-10.25, 95% CI=-19.12--1.38, P<0.05), as well as shorter length of postoperative hospital stay, time to postoperative food intake, and time to postoperative ambulation compared with the open group (all P<0.05).Conclusion The current evidence suggests that laparoscopic radical resection of HCCA is safe and effective, with an increased number of lymph nodes dissected, a higher R₀ resection rate, and less trauma. However, due to the limitations of the studies, more high-quality research is needed to validate these conclusions further.

Abstract:Background and Aims Metal stents and intraluminal irradiation with ¹²⁵I seeds are the preferred non-surgical treatments for malignant biliary obstruction, with proven efficacy in improving patient survival outcomes. However, the incidence of restenosis in metal stents remains high, and the factors contributing to this are not well understood, with no reliable predictive models currently available. Therefore, this study investigated the factors influencing metal stent restenosis in malignant biliary obstruction, developed a predictive model, and validated its performance.Methods A total of 110 patients with malignant biliary obstruction who received metal stents and ¹²⁵I seed intraluminal irradiation for the first time between January 2019 and March 2022 were selected. Patients were divided into restenosis and non-restenosis groups based on whether restenosis occurred within 12 months after operation. Univariate analysis and LASSO regression were initially used to screen for characteristic variables associated with stent restenosis, followed by Logistic regression to further analyze the related influencing factors. A nomogram predictive model was constructed using R language, and its value was assessed using the concordance index (C-index), Hosmer-Lemeshow goodness-of-fit test, the area under the receiver operating characteristic curve (AUC), and clinical impact curves. An additional 50 patients with malignant biliary obstruction from the same center, who received metal stents and ¹²⁵I seed intraluminal irradiation for the first time during a different period, were selected as an external validation dataset, and the κ statistic was used to compare the concordance rate between the nomogram prediction of restenosis and clinical reality.Results Of the 110 patients, 58 cases of restenosis occurred within 12 months after operation. Univariate analysis showed that diabetes, total bilirubin (TBIL), carbohydrate antigen 19-9 (CA19-9), postoperative biliary infection, gallstones, albumin level, radiofrequency ablation, and photodynamic therapy were associated with restenosis (all P<0.05). Logistic regression analysis identified TBIL, CA19-9, postoperative biliary infection, gallstones, radiofrequency ablation, and photodynamic therapy as independent factors associated with metal stent restenosis in malignant biliary obstruction (all P<0.05). The nomogram predictive model based on Logistic regression had a C-index of 0.838, and the Hosmer-Lemeshow goodness-of-fit test indicated no significant difference between the predicted and observed values (χ²=2.796, P=0.803). The AUC of the constructed nomogram for predicting metal stent restenosis in malignant biliary obstruction was 0.838 (95% CI=0.762-0.913), and the clinical impact curve showed a high concordance between the predicted high-risk group and actual outcomes across various threshold probabilities. Using the nomogram predictive model to predict the external validation dataset showed a concordance rate of 94.00% between the predicted restenosis rate and the actual one, with a κ value of 0.880.Conclusion TBIL, CA19-9, postoperative biliary infection, gallstones, radiofrequency ablation, and photodynamic therapy are independent factors associated with metal stent restenosis in malignant biliary obstruction. The predictive model based on these factors demonstrates good predictive ability and may provide a reference for early clinical identification of high-risk patients.

Abstract:Background and Aims Once bile duct injury occurs during laparoscopic cholecystectomy (LC), it can cause both physical and psychological suffering for the patient, negating the actual benefits of minimally invasive surgery. However, it is an adverse event that biliary surgeons in clinical practice cannot altogether avoid. With the ongoing development of minimally invasive surgical techniques, cases of laparoscopic repair of bile duct injury during LC have increasingly been reported. However, some scholars have questioned the safety and efficacy of these procedures, making it a controversial topic. This study summarized the data of patients undergoing laparoscopic repair for LC-related bile duct injuries performed in recent years and explored their feasibility and safety.Methods The clinical and follow-up data of 11 cases of LC-related bile duct injuries repaired through laparoscopic surgery at the Department of Hepatobiliary Surgery, Ningxia Hui Autonomous Region People's Hospital, from March 2019 to March 2023, were retrospectively analyzed. Bile duct injury during LC was diagnosed based on suspected bile leakage and intraoperative cholangiography. Bile duct injury after LC was assessed and confirmed through clinical manifestations, enhanced abdominal CT, MRCP, and laparoscopic exploration.Results Among the 11 patients, 4 were males and 7 were females. The Strasberg-Bismuth classification was used to categorize bile duct injury of patients, which included 3 cases of type C, 1 case of type D, 1 case of type E1, 3 cases of type E2, 2 cases of type E3, and 1 case of type E4. All patients completed the repair surgery of bile duct injury, of whom 7 cases underwent immediate intraoperative repair surgery (6 cases underwent total laparoscopic bile duct end-to-end anastomosis or repair, 1 case underwent laparoscopic-assisted small incision hepaticojejunostomy), and 4 cases underwent early bile duct injury repair surgery following LC (1 underwent total laparoscopic biliary-enteric anastomosis and 3 underwent laparoscopic-assisted small incision hepaticojejunostomy). The average time for the repair surgery was (173.63±44.33) minutes, and the median intraoperative blood loss was 100 (90–140) mL. There were no perioperative deaths, and no complications such as bile leakage or bile duct bleeding at the anastomosis sites were observed. The average length of hospital stay was (14.27±2.93) d. The average follow-up time for all patients was (38.09±17.23) months except for one patient with Strasberg-Bismuth type C bile duct injury who developed right hepatic duct stricture three months after laparoscopic proper hepatic duct repair and was successfully treated with laparoscopic right hepaticojejunostomy, no other complications, such as bile duct strictures or reflux cholangitis were observed during the follow-up period.Conclusion In hepatobiliary centers with advanced laparoscopic techniques, performing laparoscopic surgery to repair LC-related bile duct injury is relatively safe and feasible. However, it is essential to accurately assess the indications for surgery based on the Strasberg-Bismuth classification of bile duct injury and to implement an appropriate repair strategy as early as possible.

Abstract:Background and Aims Bile duct injuries and defects can occur during hepatobiliary surgery due to various reasons. Minor defects can be repaired by direct suturing, while more significant defects often require end-to-end bile duct anastomosis or Roux-en-Y cholangiojejunostomy. These latter procedures are more complex and end-to-end anastomosis may lead to bile leakage or bile duct stricture due to tension at the anastomotic site and issues with blood supply. Cholangiojejunostomy alters the normal physiological pathway and is associated with more complications. Therefore, seeking a safer, more effective, and simpler method for bile duct repair is necessary. This study was performed to investigate the clinical efficacy and application value of using the serosal surface of the round ligament of the liver to repair bile duct defects.Methods The clinical data of 13 patients who underwent bile duct defect repair using the serosal surface of the round ligament of the liver in 6 hospitals between May 2008 and March 2023 were retrospectively analyzed.Results Among the 13 patients, 3 were males and 10 were females, with ages ranging from 40 to 68 years (mean age 55.6 years). The underlying conditions included gallstones in 2 cases, gastric cancer in 1 case, inflammatory bile duct stricture in 4 cases, hepatocellular carcinoma in the left inner lobe of the liver in 2 cases, and other malignancies in 4 cases. Postoperative bile leakage occurred in 6 patients (46.2%), with bile leakage resolving in 5 patients within 7 to 27 d after surgery through the bile duct and abdominal drainage and in 1 patient within 56 d after the operation. There were no perioperative deaths. Cholangiography imaging was performed in 7 patients, with no signs of bile leakage, bile duct stricture, or bile duct stones observed. Two patients underwent bile duct endoscopy, showing no demarcation between the bile duct mucosa and the serosa of the round ligament of the liver. The follow-up period ranged from 3 months to 14 years. One patient exhibited mild dilatation of the left intrahepatic bile duct, possibly due to stricture at the left hepatic duct repair site, The other 12 patients showed no stricture or cystic dilatation at the repair site.Conclusion Repairing bile duct defects with the serosal surface of the round ligament of the liver has a good effect and is simple and easy to perform, which is worthy of clinical promotion and application.

Abstract:Background and Aims Cholecystoenteric fistula (CEF) is a rare complication of gallbladder disease that is difficult to diagnose and complex to treat. Therefore, this study was performed to explore its clinical diagnostic methods and treatment approaches by summarizing and analyzing cases of cholelithiasis complicated with CEF that the authors treated.Methods The clinical data of 21 patients with cholelithiasis complicated by CEF who underwent surgical treatment in the Department of General Surgery of the First Affiliated Hospital of Soochow University from January 2019 to December 2023 were retrospectively analyzed.Results Among the 21 patients, 14 had cholecystoduodenal fistula, 3 had cholecystocolonic fistula, and 4 had cholecystogastric fistula. Two cases of cholecystoduodenal fistula were diagnosed before the operation. All patients were scheduled for elective laparoscopic surgery, with 11 completing laparoscopic surgery and 10 converting to open surgery. The size of the fistulas ranged from 0.15 to 3.0 cm, with an average of (0.75±0.70) cm. The duration of surgery ranged from 89 to 270 min, averaging (169±50) min. Intraoperative blood loss ranged from 10 to 200 mL, with an average of (58±63) mL. Postoperative hospital stay ranged from 1 to 90 ds, with a median of 7 ds. The time to postoperative removal of the abdominal drainage tube ranged from 2 to 90 d, with a median of 7 d. The time to resume liquid diet after the operation ranged from 1 to 15 d, with a median of 3 d. Compared to conversion to open surgery, laparoscopic surgery had advantages in reducing intraoperative blood loss, shortening surgery duration, and reducing hospital stay. One patient experienced a postoperative wound infection, which was treated and cured with debridement and suturing. Another patient developed acute myocardial infarction postoperatively and recovered after treatment in the ICU. No patient deaths occurred. During the follow-up period of 5 to 12 months (mean 11 months), no complications such as bile leakage, intestinal leakage, biliary infection, or intestinal obstruction were observed.Conclusion For patients clinically suspected of having CEF, combining the patient's medical history with appropriate use of CT, MRCP, and other imaging techniques can help improve the preoperative diagnosis rate of this condition. In terms of treatment for CEF, the principle involves the complete removal of the diseased gallbladder and fistula, along with the repair of the fistula opening. Selective laparoscopic surgery for treating CEF is safe and feasible.

Abstract:Background and Aims In recent years, the incidence of intrahepatic cholangiocarcinoma (ICC) has increased. Due to its insidious onset and atypical early symptoms, most ICC patients are diagnosed at a late stage, leading to a poor prognosis. ICC cell lines are valuable in vitro models widely used in basic and clinical research on ICC. In-depth studies and drug screening of these cell lines may improve patient outcomes. Increasing evidence suggests that the morphological structure of tumor cells significantly impacts tumor development, progression, and drug sensitivity. Only a limited number of ICC cell lines derived from Chinese patients have been established, and their characteristics, particularly their ultrastructural features, are not fully characterized. Therefore, this study investigated the morphological and ultrastructural characteristics of the ICC-X1 cell line, aiming to provide a reference for future research.Methods The newly established Chinese human ICC cell line ICC-X1 was cultured and processed. The microscopic structure, surface morphology, and ultrastructure of ICC-X1 cells, including the cell membrane, cytoplasm, and organelles, were observed and analyzed using light, scanning, and transmission electron microscopy, respectively.Results Under optical microscopy, ICC-X1 cells exhibited adherent growth, predominantly polygonal and short spindle-shaped morphology, with a high prevalence of mononuclear cells, large nuclei, and scant cytoplasm, resulting in an increased nucleocytoplasmic ratio. When adequately nourished, the cells showed layered growth and lost contact inhibition. Scanning electron microscopy revealed an abundance of microvilli surrounding the ICC-X1 cells, with uniform thickness and length and long pseudopodia. Transmission electron microscopy showed that ICC-X1 cells had giant, eccentrically placed nuclei with uneven electron density of chromatin, and abundant mitochondria and ribosomes were observed.Conclusion This study provides detailed data on the morphology and ultrastructure of the ICC-X1 cell line, offering insights and perspectives for exploring the relationship between ICC cell structure and function and investigating the mechanisms of ICC drug resistance.

Abstract:Background and Aims Research has shown that microRNA-9 (miR-9) is downregulated in various malignant tumors, but its expression and function in gastric cancer remain unclear. In a previous study, we predicted using bioinformatics methods that Bcl-2-associated athanogene 4 (BAG4) might be a target gene of miR-9, and we also found that BAG4 is highly expressed in gastric cancer tissues. Therefore, this study investigated the expression and function of miR-9 in gastric cancer and its relationship with BAG4.Methods The expression levels of miR-9 in gastric cancer tissues and adjacent non-cancerous tissues, as well as in gastric cancer cell lines and normal gastric mucosal cells, were detected using qRT-PCR. After overexpressing and knocking down miR-9 in gastric cancer cells using miR-9 mimics and inhibitors, cell proliferation was assessed using the CCK-8 assay and colony formation assay, and cell invasion was evaluated using a Transwell invasion assay. The targeting relationship between miR-9 and BAG4 was analyzed using a luciferase reporter assay. Then, the expression of BAG4 in gastric cancer cells transfected with miR-9 mimics or si-BAG4 was detected by qRT-PCR and Western blot, and related functional experiments were performed for validation.Results The expression of miR-9 was significantly lower in gastric cancer tissues (vs. adjacent non-cancerous tissues) and gastric cancer cell lines (vs. normal gastric mucosal cells) (all P<0.05). The expression of miR-9 was significantly associated with tumor size, depth of tumor invasion, lymph node metastasis, distant metastasis, and TNM stage in gastric cancer patients (all P<0.05). Patients with high miR-9 expression had a significantly higher overall survival rate than those with low miR-9 expression (P=0.028). Overexpression of miR-9 in gastric cancer cells significantly reduced proliferation and invasion abilities, while miR-9 knockdown significantly enhanced these abilities (both P<0.05). The luciferase reporter assay indicated that BAG4 was a downstream target gene of miR-9. In gastric cancer cells, both mRNA and protein expression levels of BAG4 were significantly reduced after transfection with miR-9 mimics or si-BAG4, while both mRNA and protein expression levels of BAG4 were significantly increased after transfection with miR-9 inhibitors (all P<0.05). Proliferation and invasion abilities of gastric cancer cells transfected with si-BAG4 were significantly reduced, and the co-transfection of miR-9 inhibitors reversed the effects of si-BAG4 on cell proliferation and invasion (all P<0.05).Conclusion miR-9 is downregulated in gastric cancer, and its expression is closely related to adverse biological characteristics of gastric cancer. The mechanism of action of miR-9 may involve negatively regulating BAG4 expression, thereby affecting the proliferation and invasion of gastric cancer cells.

Abstract:Background and Aims There is ongoing debate about whether oral antibiotics should be added to mechanical bowel preparation (MBP) and prophylactic intravenous antibiotics, which are routinely administered before elective colorectal surgery. This study conducted to evaluate the effectiveness and clinical value of combining oral antibiotics with MBP in reducing postoperative anastomotic leakage (AL) and surgical site infections (SSI) in elective laparoscopic colorectal cancer (CRC) surgery using a prospective randomized controlled design.Methods From January to October 2023 the Third Xiangya Hospital, Central South University, eligible patients scheduled for elective laparoscopic CRC surgery were prospectively enrolled and randomly assigned to either a study group (oral antibiotics combined with MBP) or a control group (MBP alone). All patients received routine preoperative intravenous antibiotics. Standard laparoscopic CRC radical surgery was performed by the same surgical team. Using the incidence rates of AL and SSI within postoperative 30 d as the primary outcomes, the efficacy of the two bowel preparation methods was compared, and subgroup analyses were conducted for patients undergoing right-sided colon surgery and those undergoing left-sided colon or rectal surgery.Results A total of 192 patients were enrolled, with 96 patients in each group, showing comparable baseline characteristics. The study group had significantly shorter abdominal drain retention time, total hospital stay, and postoperative hospital stay compared to the control group (all P<0.05). No significant differences were observed between the two groups in terms of operative time, intraoperative blood loss, time to first gas passage, time to first bowel movement, time to start drinking and eating, and duration of postoperative intravenous antibiotic use (all P>0.05). The study group had a lower incidence of postoperative AL compared to the control group, but the difference was not statistically significant (3.13% vs. 5.21%, P=0.718). The overall SSI rate was significantly lower in the study group than that in the control group (6.25% vs. 27.08%, P<0.001), mainly due to differences in superficial incisional SSI (2.08% vs. 11.46%, P=0.010) and deep incisional SSI (1.04% vs. 10.42%, P=0.005). No significant differences were observed in the rates of other complications, and 30-d readmission, reoperation, or mortality between the two groups (all P>0.05). Some nutritional and inflammatory markers on postoperative day 1 and 3 were better in the study group (all P<0.05). Subgroup analysis showed no significant differences in AL and overall SSI rates between the study and control groups for patients undergoing right-sided colon surgery (both P>0.05). However, for left-sided colon or rectal surgery, the study group had significantly lower overall SSI rate (6.67% vs. 35.00%, P<0.001), mainly due to differences in superficial incisional SSI (1.67% vs. 15.00%, P=0.008) and deep incisional SSI (1.67% vs. 13.33%, P=0.038).Conclusion Preoperative administration of oral antibiotics combined with MBP significantly reduces the overall incidence of SSI and promotes postoperative recovery in elective laparoscopic CRC surgery, especially in left-sided colon or rectal surgery. This bowel preparation regimen is recommended for elective laparoscopic left-sided colon or rectal surgery.

Abstract:Background and Aims Pancreatic cancer is a malignant tumor with a very poor prognosis, and obesity, as a widespread health issue, is thought to be associated with various cancers. This study uses Mendelian randomization (MR) to analyze the causal relationship between obesity and pancreatic cancer to provide scientific evidence for preventing and intervening in pancreatic cancer.Methods Single nucleotide polymorphism (SNP) data for eight obesity-related anthropometric measures were downloaded from the IEU database as instrumental variables. Genome-wide association study (GWAS) data for pancreatic cancer were also obtained from the Finnish R10 database. The study employed inverse variance weighting (IVW), Mendelian randomization-Egger (MR-Egger), and Cochran's Q test to assess data heterogeneity. Potential causal relationships were further evaluated using IVW, MR-Egger, weighted median, weighted mode, Bayesian weighted Mendelian randomization, and constrained maximum likelihood Meta-analysis. MR-PRESSO and leave-one-out analyses were also used to identify and exclude outlier SNPs, ensuring result accuracy.Results Using 6 MR analysis methods to assess potential causal relationships, the study found that pancreatic cancer has a possible causal relationship with body mass index (BMI), basal metabolic rate, hip circumference, trunk fat mass, trunk fat-free mass, trunk predicted mass, and whole body fat-free mass (all P<0.05). No evidence of horizontal pleiotropy or heterogeneity was found. The consistent direction of β values across the 6 different MR analysis methods further confirmed that BMI, hip circumference, and trunk fat mass were positively correlated with an increased risk of pancreatic cancer, providing robustness to the results.Conclusion There is a causal relationship between obesity and pancreatic cancer, suggesting that improving obesity status may reduce the risk of pancreatic cancer.

Abstract:Background and Aims Colorectal cancer (CRC) is a highly prevalent tumor worldwide, and chemotherapy resistance poses a significant challenge in its clinical treatment. Regulating autophagy in CRC can counteract tumor cell resistance to chemotherapy, making autophagy a prominent research focus in CRC studies. This study was conducted to investigate the global research trends and hotspots in the field of CRC autophagy from 2011 to 2023 through a bibliometric analysis, to provide a reference for identifying key research areas and future directions in this field.Methods Relevant literature on CRC autophagy was retrieved from the Web of Science database and exported in RefWorks format, including full records and citation references. The data was then imported into CiteSpace and VOSviewer software for visualization analysis of annual publications, countries, institutions, authors, journals, citation status, and keywords from 2011 to 2023 to identify research hotspots and trends in this field.Results A total of 1 758 papers were published between 2011 and 2023, showing an upward trend in publication volume. The top five countries in terms of publication volume were China, the United States, South Korea, Japan, and Italy. The top five institutions with the highest number of publications were Sun Yat-sen University, Shanghai Jiao Tong University, Fudan University, Southern Medical University, and China Medical University. The top five authors with the most publications were Zhou Shufeng, He Zhixu, Yang Yinxue, Zhou Zhiwei, and Zhang Xueji. The top five co-cited journals were Autophagy, Cancer Research, Cell, Journal of Biological Chemistry, and Nature. The most frequently cited study in CRC autophagy research is the 2008 work by Beth Levine and colleagues titled "Autophagy in the Pathogenesis of Disease". Research hotspots in the field included the relationship between CRC autophagy and treatment and prognosis, molecular mechanisms of CRC autophagy, and identifying targets for chemotherapy drugs by regulating CRC autophagy. Emerging trends in CRC autophagy research included the interactions between non-coding RNAs, intestinal microecology, the tumor microenvironment, and CRC autophagy.Conclusion The main research hotspots in CRC autophagy are the roles of related signaling pathways on the biological functions of CRC and the search for new drug targets to regulate CRC autophagy to improve treatment outcomes. Exploring the interactions between non-coding RNA, gut microbiota, the tumor microenvironment, and CRC autophagy is likely to become a future research trend.

Abstract:Cholangiocarcinoma is an epithelial-origin malignancy for which radical surgical resection is the preferred treatment option. However, most patients are diagnosed at an advanced stage, have already lost the opportunity for surgical removal and are limited to other non-surgical treatments. The standard first-line chemotherapy for advanced cholangiocarcinoma is gemcitabine combined with cisplatin, but this regimen offers a median overall survival of only 11.7 months and is associated with adverse reactions such as neutropenia, thrombocytopenia, fatigue, and anemia. A phase Ⅱ clinical study has demonstrated the potential of paclitaxel (PTX) in improving outcomes for advanced unresectable cholangiocarcinoma, thereby opening up new a application for PTX in the treatment of advanced cholangiocarcinoma. PTX primarily induces tumor cell apoptosis by regulating microtubule depolymerization, showing significant efficacy. However, its poor solubility and high toxicity have limited its clinical application. With the emergence of various novel nanocarriers, the toxicity and solubility of PTX have been greatly improved, and some products have been translated into clinical practice. Studies have confirmed that PTX nanoformulations combined with chemotherapy, targeted therapy, or immune checkpoint inhibitors offer superior efficacy in treating biliary malignancies compared to standard chemotherapy regimens, demonstrating significant clinical value. This paper summarizes the pharmacological properties and application barriers of PTX, the current status of research and development of its nanoformulations, and the progress in its application in biliary malignancies. It also proposes future research directions and potential applications for PTX nanoformulations.

Abstract:Biliary stricture, particularly fibrotic stricture caused by laparoscopic cholecystectomy and liver transplantation, is one of the clinical challenges. Excessive deposition of extracellular matrix and epithelial-mesenchymal transition resulting from various causes (such as injury, ischemia, inflammation, and immune diseases) can lead to biliary fibrosis. This fibrosis subsequently causes biliary epithelial cell proliferation, thickening of the duct wall, and gradual fibrotic narrowing of the bile duct lumen. Biliary stricture leads to poor bile flow and stasis, which can result in conditions such as suppurative cholangitis, biliary sclerosis, and even liver failure, affecting patients' quality of life and overall survival rate. The TGF-β, Wnt, and Notch signaling pathways are important mechanisms leading to biliary fibrosis, with the Wnt/PCP signaling pathway of the non-canonical Wnt pathway playing a significant role in biliary epithelial cell proliferation and the fibrosis process. Fibroblast growth factors (FGF) can regulate the fibrosis process by promoting or inhibiting these signaling pathways, and different amounts of FGF have opposing effects on fibrosis; however, the specific mechanisms of their action are not well studied. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography with stent placement are the first-line treatments for biliary stricture. Surgical treatment is reserved for patients with refractory biliary strictures or those where endoscopic stent placement is limited. Other treatment options include magnetic compression anastomosis, intraductal radiofrequency ablation, and photodynamic therapy. Tissue-engineered stents based on 3D printing, which have a biomimetic structure and good mechanical properties, show promise in partially restoring or replacing damaged tissue, enabling the regeneration and repair of the bile ducts, and thus have significant potential for clinical application. Additionally, bile duct organoids offer new avenues for biliary fibrosis repair in disease modeling, drug screening, and mechanism studies. However, these studies are still experimental despite the promising therapeutic outcomes of "artificial bile ducts" made from different active materials in animal models. Moreover, the impact of synthetic materials and bioactive factor-coated stents on the molecular mechanisms of biliary fibrosis has not been fully explored. This review focuses on the potential mechanisms of fibrotic biliary stricture and its treatment options to provide insights for clinical research and treatment of biliary stricture.