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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.
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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.
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Objective To investigate the value of different immune and inflammatory indices in predicting the survival outcome of patients with intrahepatic cholangiocarcinoma (ICC) after curative-intent resection. Methods A retrospective analysis was performed for the case data of 122 patients with ICC who underwent curative-intent resection in Affiliated Hospital of Weifang Medical University and Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2017 to analyze the correlation of neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), systemic immune-inflammation index (SII), prognostic inflammation index (PII), inflammation score (IS), and systemic inflammation score (SIS) with the disease-free survival (DFS) and overall survival of ICC patients after surgery, and the value of the above indices in predicting prognosis was evaluated. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups; the Cox regression model was used for univariate and multivariate analyses, and hazard ratio ( HR ) and 95% confidence interval [ CI ] were calculated. Results The univariate survival analysis showed that NLR ( HR =2.212, P =0.004), LMR ( HR =0.403, P =0.012), PII ( HR =3.013, P < 0.001), prognostic nutritional index (PNI) ( HR =0.530, P =0.019), IS ( HR =1.809, P =0.001), SII ( HR =2.107, P =0.002), and SIS ( HR =2.225, P < 0.001) were predictive factors for postoperative DFS of patients with ICC, and NLR ( HR =2.416, P =0.009), LMR ( HR =0.297, P =0.008), PII ( HR =3.288, P < 0.001), PNI ( HR =0.292, P =0.003), IS ( HR =2.048, P =0.002), SII ( HR =1.839, P =0.049), and SIS ( HR =2.335, P < 0.001) were predictive factors for postoperative OS of patients with ICC. The multivariate survival analysis showed that high levels of PII ( HR =2.146, P =0.035) and SIS ( HR =2.511, P < 0.001) were independent influencing factors for postoperative DFS of ICC patients, and high levels of PII ( HR =2.981, P =0.009), PNI ( HR =0.261, P =0.002), and SIS ( HR =2.294, P =0.010) were independent influencing factors for postoperative OS. The patients with a high level of PII tended to have advanced tumor T stage ( χ 2 =8.777, P =0.003) and M stage ( P =0.029), and the patients with high-grade SIS tended to have advanced N stage ( χ 2 =9.985, P =0.030) and M stage ( χ 2 =8.574, P =0.012). Conclusion Among the various inflammation indices, PII and SIS are recommended for preoperative stratification and prediction of the outcome of ICC patients after curative-intent resection.
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Biliary tract carcinomas (BTC) is characterized by high hetergenity. Despite being classified as rare cancers worldwide, the incidence of biliary tract carcinomas is increasing in China due to significant geographic variation. The current global needs for the treatment of BTC are far from being met, with advanced chemotherapy providing only limited survival benefits. Molecular targeted therapy, immunotherapy, and drug combination therapy have begun to flourish in recent years as its genetic characteristics are gradually revealed. This review summarized the therapeutically important targets of BTC, such as fibroblast growth factor receptor, isocitrate dehydrogenase and neurotrophic tyrosine receptor kinase as well as the advances in the research and development of their inhibitors, and prospects for precision targeted therapy for BTC.
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Cholangiocarcinoma is a malignant tumor of the biliary tract with high heterogeneity and poor prognosis. Surgery is the only cure for early cholangiocarcinoma, but about two thirds of the patients are already advanced at the time of initial diagnosis. First-line chemotherapy in patients with advanced cholangiocarcinoma does not lead to viable survival. In recent years, with the development of second-generation sequencing technology, potential targets in cholangiocarcinoma have been continuously discovered, and a series of clinical trials have been carried out accordingly. Among them, clinical trials of drugs targeting fibroblast growth factor receptors (FGFRs) have yielded promising results. This article reviews the current status and research progress of drugs targeting FGFRs in the treatment of advanced cholangiocarcinoma.
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Objective:To study the differences in preoperative examination indexes between pancreatic head cancer and distal bile duct cancer, and to establish a preliminary prediction model to provide reference for clinical decision-making.Methods:Retrospective analysis was conducted on 243 consecutive patients who underwent open radical pancreaticoduodenectomy from January 1, 2015 to December 31, 2019 at the Chinese PLA General Hospital. There were 177 males and 66 females, aged (58.9±8.9) years old. Based on postoperative pathological results, these 243 patients were divided into the pancreatic head cancer group ( n=113) and the distal bile duct cancer group ( n=130). The clinical data of the two groups were collected. Minimum absolute value convergence and selection operator regression were used to screen the best predictors of pancreatic head cancer. The rms package was used to construct the nomogram model, and k-fold cross was used for internal validation. Results:Seven best predictive indexes are selected: age, rate of weight loss, main pancreatic duct diameter, neutrophil/lymphocyte, DTR (DBil/TBil), carcinoembryonic antigen and CA125. Based on these indexes, a nomogram prediction model was constructed with the C-index of 0.868 after k-fold cross-validation, indicating that discrimination of the model to be acceptable. Validation using calibration curve exhibited good concordance between the predicted probability with the ideal probability ( P=0.728). Conclusion:The nomogram prediction model established in this study effectively predicted patients with pancreatic head cancer, and helped preoperatively to differentiate pancreatic head cancer from distal cholangiocarcinoma.
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Objective:To investigate the application value of digital single-operator peroral cholangioscopy on the preoperative evaluation of extrahepatic cholangiocarcinoma.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 172 patients with extrahepatic cholangiocarcinoma who were admitted to the First Affiliated Hospital of Army Medical University from December 1, 2017 to April 1, 2022 were collected. There were 91 males and 81 females, aged 65(range, 45?68)years. Of 172 patients, 36 cases undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the experimental group, and 136 cases not undergoing preoperative digital single-operator peroral cholangioscopy examination were allocated into the control group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) surgical conditions. Propensity score matching was done by the 1:1 nearest neighbor matching method and caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1,Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 172 patients, 60 cases were successfully matched, including 30 cases in the experiment group and 30 cases in the control group, respectively. Before propensity score matching, cases with or without preoperative bile drainage were 27, 9 in the experiment group, versus 62, 74 in the control group, showing a significant difference between the two groups ( χ2=9.86, P<0.05). The above indicators were 23, 7 in the experiment group, and 23, 7 in the control group after propensity score matching, showing no significant difference between the two groups ( χ2=0.00, P>0.05). The elimination of preoperative bile drainage confounding bias ensured comparability between the two groups. (2) Surgical conditions. After propensity score matching, there were 10 cases and 0 case without surgery in the two groups. Cases undergoing radical operation including R 0, R 1, R 2 resection were 16, 0, 4 in the experiment group, versus 18, 6, 6 in the control group, showing a significant difference between the two groups ( χ2=6.85, P<0.05). Conclusions:Preoperative digital single-operator peroral cholangioscopy exami-nation can improve the R 0 resection rate of extrahepatic cholangiocarcinoma.
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Objective:To analyse the correlation between the lymph nodes, the number of positive lymph nodes, the positive rate of lymph nodes and the long-term prognosis of patients with distal cholangiocarcinoma.Methods:The clinical data and follow-up results of 104 patients with distal cholangiocarcinoma admitted to Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2015 to December 2021 were retrospectively analyzed using a retrospective cohort study. All patients underwent pancreaticoduodenectomy. According to the nature of the patients′ lymph nodes, the number of positive lymph nodes, and the positive rate of lymph nodes, the X-tile software was used to analyze data respectively, and the critical value of SUVmax were determined, and the patients were divided into low-risk group and high-risk group by critical values. Based on this critical value, the patients were divided into low-risk groups and high-risk groups. There were 37 patients in the lymph node positive group and 67 patients in the negative group. In the lymph node positive group, according to the number of positive lymph nodes (the cut-off value=2), they were divided into the low-risk group( n=14), the high-risk group( n=23); grouped according to the lymph node positive rate (the cut off=0.13), and divided into the low-risk group( n=15), and the high-risk group( n=22). After grouping according to different lymph node parameters, the preoperative general data such as age, gender, laboratory examination, etc., the correlation between perioperative complications and long-term prognosis were analyzed. The measurement data conforming to the normal distribution was expressed as mean ± standard deviation( ± s), and the t test was used for comparison between groups; the measurement data that was not normally distributed was expressed as M ( Q1, Q3), and the comparison between groups was performed by the rank sum test. The enumeration data were expressed by the number of cases, and the comparison between groups was performed using the chi-square test. If the total number of cases was less than 50, and Fisher′s exact test was used. The optimal cut-off values for different lymph node parameters were determined using the x-tile 3.6.1 software. Survival curves were calculated and drawn using the Kaplan-Meier method, and the survival rates were compared using the Log-rank test. Results:All patients successfully underwent the operation, 5 patients(4.8%) died during the perioperative period. The median postoperative survival time of lymph node-positive patients and lymph node-negative patients was 17 months and 36 months, respectively, and the overall survival rates at 1, 3, and 5 years were 64.9%, 23.9%, 23.9%, and 81.5%, 49.8%, 41.7%( P=0.003). Among the patients grouped according to the number of positive lymph nodes, the median postoperative survival time of patients in the low-risk group and the high-risk group was 21 months and 17 months, and the 1-, 3-, and 5-year overall survival rates of the two groups were were 77.1%, 42.9%, 42.9% and 58.2%, 13.8%, 13.8%( P=0.284), respectively. Among the patients grouped according to the positive rate of lymph nodes, the median postoperative survival time of the patients in the low-risk group and the high-risk group was 30 months and 15 months, and the 1-, 3-, and 5-year overall survival rates of the two groups were 85.6%, 42.7%, 42.7% and 51.3%, 10.3%, 0.3%( P=0.020), respectively. Conclusions:Radical pancreaticoduodenectomy is the standard procedure for patients with distal cholangiocarcinoma. The prognosis of patients with positive lymph nodes is worse. For patients with positive lymph nodes, the positive rate of lymph nodes is a better predictor of the long-term prognosis compared with the number of positive lymph nodes.
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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.
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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.