Clinical significance of determining the level of biliary calprotectin in patients with cholangiocarcinoma or choledocholithiasis / 临床肝胆病杂志

ObjectiveTo investigate the difference in the level of biliary calprotectin between patients with cholangiocarcinoma and those with choledocholithiasis. MethodsClinical data and bile samples were collected from 34 patients with cholangiocarcinoma and 78 patients with choledocholithiasis who were diagnosed and treated with endoscopic retrograde cholangiopancreatography in The First Affiliated Hospital of Anhui Medical University from May 2021 to September 2022. Fluorescence lateral flow immunoassay was used to measure the levels of calprotectin， hemoglobin， and lactoferrin in bile. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Spearman correlation test was used for correlation analysis； the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsCompared with the choledocholithiasis group， the cholangiocarcinoma group had significant increases in the levels of calprotectin ［4 795.50 （2 286.79‍ ‍—‍ ‍20 179.73） ng/mL vs 411.16 （67.03‍ ‍—‍ ‍1 991.88） ng/mL， Z=5.572， P<0.001］ and fluoride ［115.70 （109.10‍ — ‍125.50） mmol/L vs 106.60 （98.60‍ ‍—‍ ‍114.40） mmol/L， Z=2.702， P=0.007］. The patients with cholangiocarcinoma were further divided into high cholangiocarcinoma group and low cholangiocarcinoma group， and there was no significant difference between the two groups in the level of calprotectin ［3 867.71 （2 235.66‍ — ‍26 407.40） ng/mL vs 4 795.50 （2 361.15‍ — ‍13 070.53） ng/mL， Z=0.129， P>0.05］. Biliary calprotectin level was correlated with white blood cell count， hemoglobin concentration， and lactoferrin concentration in bile （r=0.316， 0.353， and 0.464， all P<0.05）. The ROC curve analysis showed that biliary calprotectin （with a sensitivity of 79.4% and a specificity of 75.6%）， blood CA19-9 （with a sensitivity of 82.4% and a specificity of 78.2%）， and their combination （with a sensitivity of 88.2% and a specificity of 73.1%） had good sensitivity and specificity in the diagnosis of cholangiocarcinoma. ConclusionThere is an increase in the level of biliary calprotectin in patients with cholangiocarcinoma， and therefore， it might become a biomarker for the diagnosis of cholangiocarcinoma.

Role of tumor-associated macrophages in cholangiocarcinoma / 临床肝胆病杂志

Cholangiocarcinoma (CCA) is a highly malignant biliary tumor with strong invasion and poor prognosis and is insensitive to radiotherapy and chemotherapy. Tumor-associated macrophage (TAM) is an important component of the tumor microenvironment. CCA cells recruit TAM into tumor tissue by releasing cytokines and polarize them into M2 TAM, which promotes the progression of CCA through various mechanisms such as assisting immune escape, promoting tumor cell proliferation, regulating angiogenesis, promoting tumor metastasis, and mediating immune resistance. As an emerging target of tumor immunotherapy, TAM provides new ideas for targeted therapy for CCA. This article reviews the mechanisms of TAM in promoting the progression of CCA and immunotherapy targeting TAM in recent years.

Neoadjuvant and adjuvant therapy of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Intrahepatic cholangiocarcinoma (ICC) refers to adenocarcinoma originating from the secondary bile ducts and their branches within the liver, with high malignancy and poor prognosis. Radical surgical resection is currently the only possible way to cure ICC, but only some patients meet the surgical standards, and even with surgical resection, about 60% of patients will relapse within 1~2 years. Neoadjuvant therapy and adjuvant therapy are important perioperative treatment methods for ICC, with the aim of reducing postoperative recurrence and improving postoperative survival. This article aims to elaborate on the current status and research progress of neoadjuvant therapy and adjuvant therapy for ICC.

Analysis of 17 cases of Vaterian system adenomyomatous hyperplasia / 中华肝胆外科杂志

Objective:To study the features of adenomyomatous hyperplasia (AH) of the Vaterian system (common bile duct and ampulla of Vater) to help in the diagnosis and management of this disease.Methods:A retrospective analysis on the data of 17 patients who had a postoperative pathological diagnosis of AH of the Vaterian system treated from January 2005 to December 2021 at the First Medical Center of the PLA General Hospital was carried out with 12 males and 5 females, aged (58.4±11.3) years. The clinical presentations, treatment and postoperative pathology of these patients were analyzed. Patients with dysplasia of the tubular mucosal epithelium in the non-cancerous area around the AH under microscopy were included in the AH with dysplasia group ( n=8), and those without dysplasia were included in the control group ( n=9). The clinical characteristics of the two groups were compared. Results:The main clinical symptoms were abdominal pain in 8 patients, jaundice in 7 patients and fever in 2 patients. Preoperative imaging showed 10 cases of occupying lesions and 6 cases of abnormally dilated intrahepatic and extrahepatic bile ducts without obvious lesions or stones or biliary tract injury stenosis. Sixteen patients underwent radical pancreaticoduodenectomy, and 1 patient underwent extrahepatic biliary resection combined with choledochojejunostomy for bile duct obstruction due to biliary stones, 3 patients had combined malignant tumors, 1 patient had a carcinoma of AH origin at the ampulla of Vater, and the other 2 patients had neoplastic lesions in the mucosal epithelium adjacent to the AH (cholangiocarcinoma and ampullary carcinoma, respectively). There were no significant differences in age, gender, bile duct stones, cholangitis, combined carcinoma and liver function indexes between the two groups of patients with AH of the Vaterian system (all P>0.05). Conclusion:Adenomyomatous hyperplasia of the Vaterian system was difficult to distinguish preoperatively from malignant tumors basing on its clinical presentations or imaging findings. Such patients are recommended to be treated surgically.

The effectiveness and safety of laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: a meta-analysis / 中华肝胆外科杂志

Objective:To compare the effectiveness and safety of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) for intrahepatic cholangiocarcinoma(ICC).Methods:PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine Disc, China National Knowledge Infrastructure, Wanfang Database and VIP Database were searched from inception of these databases to May 2022 to compare LH versus OH for ICC. The duration of operation, intraoperative bleeding, proportion of patients with intraoperative blood transfusion, number of resected lymph nodes, proportion of patients with R 0 resection margin, duration of hepatic occlusion, hospital stay, incidence of postoperative complication and postoperative mortality were compared between the two groups. Meta-analysis was carried out using the Review Manager 5.1 software, and the mean difference ( MD) or odds ratio ( OR) was used as the effect index. Results:This meta-analysis included twelve articles, all of which were retrospective cohort studies, with 3 189 patients. There were 667 patients in the LH group and 2 512 in the OH group. Meta-analysis showed that when compared to the OH group, the LH group had significantly less intraoperative bleeding ( MD=-116.06, 95% CI: -173.07--59.06, P<0.001), less proportion of patients receiving intraoperative blood transfusion ( OR=0.25, 95% CI: 0.10-0.62, P=0.003), less number of lymph nodes removed ( MD=-101.91, 95% CI: -124.78--79.03, P<0.001), less patients underwent portal occlusion ( OR=0.37, 95% CI: 0.14 - 0.99, P=0.050), shorter hospital stay ( MD=-2.43, 95% CI: -4.59--0.28, P=0.030) and less postoperative complications ( OR=0.41, 95% CI: 0.28-0.61, P<0.001). However, the proportion of patients with R 0 margin ( OR=1.49, 95% CI: 1.14-1.95, P=0.003) in the LH group was significantly higher than the OH group. There were no significant differences in operative time and postoperative mortality between the 2 groups. Conclusion:LH was more effective and safe than OH in the treatment of ICC. However, its long-term effect still needs to be verified by large randomized controlled trials.

Research progress of exocrine non-coding RNA in cholangiocarcinoma / 中华肝胆外科杂志

Cholangiocarcinoma is the second most common malignant tumor in primary liver tumors, which has high malignant degree and poor prognosis. At present, there is no satisfactory and effective treatment method. Exosomes from various cells carry a variety of substances and act on the receptor cells, transmitting biological messages between different cells to regulate a variety of physiological and pathological changes. Exosomes can affect the tumor microenvironment and further mediate the tumorigenesis and progression of tumors via multiple approaches. Increasing studies have demonstrated that the non-coding RNA (ncRNAs) carried by tumor-derived exosomes is involved in regulating the occurrence, development and metastasis of cholangiocarcinoma. Combined with the current research progress, this article summarizes the role, diagnosis and treatment value of exosome ncRNAs in cholangiocarcinoma, so as to provide references for follow-up research.

Current status of targeted therapy for cholangiocarcinoma / 国际外科学杂志

Cholangiocarcinoma is a group of highly invasive and heterogeneous biliary malignancies originating from any part of the biliary tree. At present, the most ideal treatment is still radical surgery.Gemcitabine combined with cisplatin (gem-cis) has been recognized as the standard first-line chemotherapy regimen for patients with unresectable, advanced or metastatic disease.In recent years, with the proposal of precision medicine and the development of next-generation sequencing technologies, A large number of important cholangiocarcinoma targets have been discovered, such as FGFR, IDH, VEGFR, BRAF, MET, etc., and the research on corresponding target drugs is booming.By referring to relevant literature and data, combined with domestic and foreign clinical trials, this paper reviews the important targets of cholangiocarcinoma and the latest progress of targeted drug therapy.

Clinical effect of liver transplantation on hilar cholangiocarcinoma / 国际外科学杂志

Hilar cholangiocarcinoma(HCCA) is a relatively rare disease with great invasiveness. Traditionally, radical resection has been considered the cornerstone of its treatment. However, only less than 40% of cases can be resected. Surgical resection is complex, risky and difficult to achieve R0 resection and may lead to various postoperative complications. In recent years, the combination of neoadjuvant chemoradiotherapy with liver transplantation(LT) has provided an option for patients with unresectable diseases, and strict patient screening criteria has allowed LT protocol to achieve promising therapeutic effects in PCCA. In order to provide an intellectual background for the choice of LT protocol in the clinical treatment of HCCA patients, this article will review the application standards of LT in HCCA, summarize the application status of LT in patients with different resectability, compare the prognostic effect of resection and LT, and introduce the advantages of LT in the treatment of HCCA associated with primary sclerosing cholangitis(PSC).

Research progress and prospect of surgical treatment of intrahepatic cholangiocarcinoma in the era of liver transplantation / 国际外科学杂志

The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.

Application of 3D printing in surgical treatment of hepatobiliary malignancies / 国际外科学杂志

At present, surgical treatment is the most effective method for the treatment of hepatobiliary malignant tumor. However, due to the complex anatomical structure of hepatobiliary region, accompanied by vascular variation, and with the continuous update of medical concepts, the requirements for surgery are more strict. Traditional imaging examination has reached a bottleneck in the support of surgical treatment, while 3D printing technology is compared with the former. It showed strong advantages in preoperative program planning and improving the effect of intraoperative precise resection. At the same time, it also shows great potential for medical assistance and disease treatment in the production of bioactive models, and 3D printing technology has obviously enhanced the understanding of surgery for young doctors, and medical staff can create a variety of highly practical 3D printing models under the existing conditions. In the future, it is expected to overcome the limitations of materials and technology and bring higher therapeutic benefits for the majority of patients.

Perfil clínico-patológico de pacientes con cáncer hepatobiliar en dos hospitales de referencia en Lima, Perú / Clinicopathological profile of patients with hepatobiliary cancers at two main referral hospitals in Lima, Peru

RESUMEN Objetivo: El objetivo del estudio fue describir las características clínico-patológicas de individuos diagnosticados de cáncer de hígado, vías biliares o vesícula. Materiales y métodos: Entre el 2006 y 2017, se diagnosticaron 89 pacientes (57% mujeres; media: 62 años) con estos canceres en dos hospitales nacionales de Lima, Perú. Resultados: Los resultados mostraron que, independientemente del tipo de cáncer, 64% de los participantes habían sido diagnosticados en estadios avanzados. La anemia fue más frecuente en los pacientes con cáncer de vías biliares e hígado y en estadios avanzados. Se observó mayor frecuencia (32%) de hipertensión arterial (HTA) en el grupo con cáncer de hígado. El análisis por edad mostró que en los pacientes mayores de 50 años la HTA fue más frecuente. Asimismo, sujetos menores de 50 años reportaron antecedentes de infecciones previas en mayor frecuencia (50%), siendo Hepatitis B (HBV) la más común. Conclusiones: Este estudio describe las características clínico-patológicas de base de una neoplasia poco estudiada en el ámbito nacional.

ABSTRACT Objective: The aim of the study was to describe the clinicopathological profile of patients diagnosed with liver, bile ducts or gallbladder cancer. Materials and methods: Between 2006 and 2017, 89 patients (57% female; mean age: 62 years-old) with these cancers were diagnosed at two national hospitals in Lima, Peru. Results: Most patients (64%) had advanced stages of disease. Anemia was more frequent in patients with bile duct and liver cancer and in advanced stages. Hypertension (HTN) was frequent among liver cancer patients (32%). The analysis by age showed that HTN was more frequent in patients over 50 years. Likewise, people under 50 years had more frequent history of previous infections (50%), Hepatitis B (HBV) being the most common. Conclusions: This study describes the baseline clinicopathological characteristics of a malignancy poorly studied in Peru.

Application value of Da Vinci robotic surgical system in radical resection of perihilar cholan-giocarcinoma / 中华消化外科杂志

Objective:To investigate the application value of Da Vinci robotic surgical system in radical resection of perihilar cholangiocarcinoma (pCCA).Methods:The retrospective and descrip-tive study was conducted. The clinicopathological data of 10 patients undergoing Da Vinci robotic radical resetion of pCCA in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2018 to March 2021 were collected. There were 6 males and 4 females, aged (58±7)years. Observtaion indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. The patients were followed up by telephone interview and outpatient service to detect survival of patients and tumor recurrence up to June 2021. Measurement data with normal distribution were expressed as Mean± SD, and measurement data with skewed distribu-tion were represented as M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 10 patients underwent Da Vinci robotic radical resection of pCCA succe-ssfully, without conversion to laparotomy or intraoperative blood transfusion. The operation time of 10 patients was (465±87)minutes, and the volume of intraoperative blood loss was (167±81)mL. Of the 10 patients, 1 case of Bismuth type Ⅲb had a positive surgical margin and the remaining 9 cases had R 0 resection. (2) Postoperative situations: the time to gastric tube extraction was (2.3±1.9)days, and the duration of postoperative hospital stay of the 10 patients was (19.9±9.0)days. Among the 10 patients, there was no second operation or perioperative death. Of the 10 patients, 6 cases had perioperative complications, including 5 cases wth pleural effusion, 3 cases with peritoneal effusion, and 1 case with intestinal obstruction, some patients had multiple complications. After symptomatic conservative treatment, pleural effusion and peritoneal effusion disappeared and intestinal obstruction was improved. None of the 10 patients had serious complica-tions such as bleeding, biliary fistula or intestinal fistula. (3) Follow-up: 10 patients were followed up for 3-20 months, with a median follow-up time of 11 months. During the follow-up, 3 of 10 patients had tumor recurrence which occurred in intrahepatic bile duct of residual liver, and no implantation metastasis was found in the rest of abdominal cavity. Of the 7 unrecurrent patients, 1 case died of gastrointestinal bleeding and multiple organ failure. Nine of 10 patients survived well. Conclusion:The Da Vinci robotic surgical system used for radical operation of pCCA is feasible.

Mechanism of action of ferroptosis in cholangiocarcinoma / 临床肝胆病杂志

The incidence and mortality rates of cholangiocarcinoma (CCA) are increasing constantly, and it is of great importance to explore new therapeutic targets. Ferroptosis, a unique pattern of cell death caused by iron-dependent cellular oxidative injury, is closely associated with iron metabolism and oxidative stress imbalance in cancer and has become a research hotspot in the field of tumor. This article introduces the mechanism of ferroptosis and the research advances in ferroptosis involved in the development and progression of CCA, and it is pointed out that the regulatory mechanism of ferroptosis has an important clinical value in the malignant progression of CCA.

Study on the changes of cellular immune function after endoscopic radiofrequency ablation in extrahepatic cholangiocarcinoma / 肿瘤研究与临床

Objective:To investigate the effect of radiofrequency ablation treatment of extrahepatic cholangiocarcinoma under endoscopic retrograde cholangiopancreatography on the cellular immune function of patients with extrahepatic cholangiocarcinoma.Methods:A prospective cohort study was conducted on 78 patients with inoperable extrahepatic cholangiocarcinoma who visited Shanxi Provincial People's Hospital from October 2019 to January 2022. All of 78 patients underwent endoscopic radiofrequency ablation. Peripheral venous blood was collected from all patients at 1 day before treatment, 1 week after treatment and 1 month after treatment. Lymphocyte subsets were detected by flow cytometry, and levels of cytokines were detected by enzyme-linked immunosorbent assay. Seventy-eight healthy subjects with the same age and gender as the patients were selected as healthy controls, and the same indicators were tested.Results:The patient's peripheral blood total bilirubin was (193±83) μmol/L at 1 day before treatment, and decreased to (55±49) μmol/L at 1 week after treatment ( t = 16.70, P < 0.001); γ-glutamyltransferase was (242±108) U/L at 1 day before treatment, and decreased to (92±70) U/L at 1 week after treatment ( t = 19.12, P < 0.001). The proportion of natural killer (NK) cells, CD3 + T cells, CD4 + T cells, ratio of CD4 + T cells to CD8 + T cells (CD4/CD8) and level of interferon γ (IFN-γ) of patients at 1 day before treatment were lower than those of healthy control group (all P < 0.05), the proportion of CD8 + T cells and regulatory T cells was higher than those of healthy control group (both P < 0.001), and there was no significant difference in the levels of interleukin 4 (IL-4) between the patients at 1 day before treatment and the healthy control group ( P = 0.545). At 1 week and 1 month after treatment, the proportion of NK cells, CD3 + T cells, CD4 + T cells, CD4/CD8 and IFN-γ level in patients increased compared with 1 day before treatment (all P < 0.001), and decreased at 1 month after treatment compared with 1 week after treatment (all P < 0.001). At 1 week and 1 month after treatment, the proportion of CD8 + T cells and IL-4 level in patients decreased compared with 1 day before treatment (both P < 0.001), and increased at 1 month after treatment compared with 1 week after treatment (both P < 0.001). At 1 week and 1 month after treatment, the proportion of regulatory T cells decreased compared with 1 day before treatment (both P < 0.001), and decreased at 1 month after treatment compared with 1 week after treatment ( P < 0.001). Conclusions:Patients with extrahepatic cholangiocarcinoma are at a low level of immunity. Endoscopic radiofrequency ablation treatment can alleviate the patient's immunosuppression, enhance the patient's cellular immunity.

Comprehensive analysis of differential methylation genes in cholangiocarcinoma and identification of prognosis-related genes glucosaminyl (N-acetyl) transferase 1 and neurotrophic receptor tyrosine kinase 3 / 肿瘤研究与临床

Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.

Open surgery in the treatment of patients with hilar cholangiocarcinoma: a study on curative efficacy and prognostic factors / 中华肝胆外科杂志

Objective:To study the efficacy of different surgical methods in treatment of hilar cholangiocarcinoma (HCCA), and to analyze the factors affecting long-term prognosis of HCCA patients after surgical treatment.Methods:The clinical data of 105 patients who underwent surgical treatment for HCCA at the First Affiliated Hospital of Soochow University from April 2010 to October 2021 were retrospectively analysed. There were 58 males and 47 females, with age (64.2±10.6) years old. Data analysed included surgical treatments, postoperative pathological data, perioperative complications and survival on follow-up. The Kaplan Meier survival curve was plotted, and the log-rank test and Cox proportional hazard model were performed to analyze the key factors affecting long-term prognosis.Results:Of 105 patients, 4 (3.8%) patients died during the perioperative period, and 58 patients (55.2%) developed complications with included 32 (30.5%) patients with pleural effusion and 12 (11.4%) patients with biliary leakage. The follow-up data was available in 85 patients with the overall median survival time of 19 months, and the 1-, 3-, 5-year cumulative survival rates of 58.1%, 27.0% and 24.8% respectively. The 1-, 3-, and 5-year cumulative survival rates for the R 0 resection patients ( n=59) were 69.4%, 36.2%, 27.4%, respectively, which were significantly better than 49.4%, 12.3%, 0% for the R 1/2 resection patients ( n=20), and 0% for the palliative drainage patients ( n=6) (all P<0.05). Univariate analysis and Cox multivariate analysis showed that age ≥70 years ( HR=2.158, 95% CI: 1.175-3.965), preoperative CA19-9 level ≥1 015 U/ml ( HR=1.981, 95% CI: 1.009-3.894), resection margin ( HR=2.587, 95% CI: 1.371-4.881), and lymph node metastasis ( HR=2.308, 95% CI: 1.167-4.567) were independent risk factors for long-term prognosis of HCCA patients (all P<0.05). Conclusions:R 0 resection was an effective way to prolong survival of patients with HCCA. Age, preoperative CA19-9 level, resection margin and lymph node metastasis were related to long-term survival of HCCA patients.

Construction of a prognostic nomogram based on pathology for long-term survival after radical resection of intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To establish and evaluate a nomogram for long-term survival of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.Methods:The data of ICC patients who underwent radical resection for the first time at Zhongshan Hospital, Fudan University from January 2014 to December 2017 were retrospectively analyzed. Of 167 patients who were enrolled, there were 104 males and 63 females, with the age of (60.3±10.9) years. Tumor tissues were collected for immunohistochemical staining and interpretation. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to analyze influencing factors of postoperative long-term survival after ICC. R software was used to construct a nomogram in predicting ICC prognosis.Results:Cox regression analysis showed that TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression to be independent risk factors associated with poor long-term survival after radical resection. The prognostic nomogram model of ICC was constructed based on these factors. The C-index was 0.821. The nomogram model consistency index had a high degree of prognostic differentiation. The 45° diagonal of the 3-year postoperative calibration curve which represented the actual survival fitted well with the segmented line which represented the predicted survival of the nomogram. The area under the receiver operating characteristic curve of the nomogram model was higher than that of AJCC TNM staging (0.894 vs. 0.803, z=4.10, P<0.001). The nomogram model was more effective in predicting postoperative survival of ICC patients than the TNM staging. Conclusion:TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression were independent risk factors for postoperative survival of ICC. The nomogram model could better evaluate long-term prognosis of ICC patients after radical resection than the traditional TNM staging system.

Risk factors for textbook outcomes of intrahepatic cholangiocarcinoma after hepatectomy / 中华消化外科杂志

Objective:To investigate the risk factors for textbook outcomes (TO) of intra-hepatic cholangiocarcinoma (ICC) after hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 155 ICC patients who underwent hepatectomy in the First Affiliated Hospital of Sun Yat-sen University from September 2014 to August 2019 were collected. There were 90 males and 65 females, aged 60(range, 26?82)years. Observation indicators: (1) treatment situations; (2) TO situations; (3) analysis of risk factors for postoperative TO. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative sur-vival of patients up to October 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent samples t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test, Yates' calibration chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of indicators (the optimal cut-off value). Results:(1) Treatment situations. Of the 155 patients, 46 cases underwent minor hepatectomy and 109 cases underwent major hepatectomy. Twenty-one of the 155 patients underwent combined bile duct reconstruction. Ninety-five of the 155 patients underwent lymph node dissection, including 41 cases with positive lymph node by postoperative histopathological examinations. The operation time and volume of intraoperative blood loss of the 155 patients were 250.0(range, 95.0?720.0)minutes and 300.0(range, 50.0?15 000.0)mL, respectively. The optimal cut-off values of the operation time and volume of intraoperative blood loss for TO calculated by ROC curve were 247.5 minutes and 325.0 mL, respectively. Of the 155 patients, 44 cases received intraoperative blood transfusion and 10 cases received postoperative blood transfusion (5 cases with intraoperative and postoperative blood transfusion). Seventy-four of the 155 patients had postoperative complications, including 39 cases with mild complications and 35 cases with serious complications. The total duration of hospital stay of the 155 patients was 19 (range, 8?77)days. (2) TO situations. Of the 155 patients, 150 cases achieved R 0 resection, 120 cases had no major postoperative complications, 106 cases had no perioperative blood transfusion, 79 cases had no prolonged duration of hospital stay, 152 cases had no death within postoperative 30 days and 150 cases had no readmission within 30 days after discharge. Of the 155 patients, 56 cases achieved postoperative TO, while 99 patients did not achieve TO. (3) Analysis of risk factors for postoperative TO. Results of univariate analysis showed that preoperative biliary drainage, preoperative Child-Pugh grading of liver function, preoperative asymp-tomatic leukocytosis, preoperative total bilirubin, preoperative alkaline phosphatase, preoperative CA19-9, preoperative CA125, operation time, volume of intraoperative blood loss, tumor diameter, pathological T staging and pathological N staging were related factors for preoperative TO of ICC patients undergoing hepatectomy ( χ2=4.31, 4.31, 4.38, 4.80, Z=?4.15, χ2=10.74, 15.44, 16.59, 27.53, 6.53, 6.77, 9.26, P<0.05). Bile duct reconstruction was also a related factor for postoperative TO of ICC patients ( P<0.05). Results of multivariate analysis showed that preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL were independent risk factors for postoperative TO of ICC patients undergoing hepatectomy ( odds ratio=74.77, 11.73, 2.40,4.86, 6.42, 95% confidence intervals as 1.80?113.39, 1.19?115.54, 1.04?5.53, 1.78?13.26, 2.41?17.11, P<0.05). Conclusions:Preoperative biliary drainage, preoperative asymptomatic leukocytosis, preoperative CA19-9 >35 U/mL, preoperative CA125 >35 U/mL and volume of intraoperative blood loss >325.0 mL are independent risk factors for postoperative TO of ICC patients undergoing hepatectomy.

Immunotherapy research progress of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma is a primary hepatic malignant tumor with high malignancy and poor prognosis. In addition to surgical resection, there are no clear studies showing that there are other effective treatments. In recent years, with the deepening of the research on the immune mechanism of various malignant tumors, immunotherapy has been gradually attached importance to various anti-solid tumor treatments, and has also become an important direction in the treatment of intrahepatic cholangiocarcinoma. The important role of tumor microenvironment in the immunotherapy of malignant tumors is gradually recognized. In this paper, the characteristics of immune microenvironment in intrahepatic cholangiocarcinoma has been summarized, and the application of immunotherapy in intrahepatic cholangiocarcinoma has been reviewed, with emphasis on the development of immune checkpoint inhibitors, cancer vaccines and adoptive cellular immunotherapy.

Discussion on enhanced recovery after surgery of hilar cholangiocarcinoma after operation / 国际外科学杂志

The concept of enhanced recovery after surgery has been widely accepted and applied by clinical medical staff, and has made good progress in the field of hepatobiliary pancreatic surgery in recent years. Hilar cholangiocarcinoma is one of the more complicated operations in hepatobiliary pancreatic surgery. The traditional perioperative management mode is not conducive to the early rehabilitation of patients, and the relative operation risk and the probability of postoperative complications are high. In order to promote the application of enhanced recovery after surgery in patients with hilar cholangiocarcinoma after operation, this paper systematically introduces the measures and experience of accelerated rehabilitation after operation of hilar cholangiocarcinoma from the aspects of postoperative multimodal analgesia, early activity, diet, drainage tube management, discharge and follow-up, based on the relevant literature and combined with own work experience. These measures can reduce the postoperative complications of patients with hilar cholangiocarcinoma and promote their early rehabilitation.