Treatment Of Hilar Cholangiocarcinoma Research Articles

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Short-term and long-term clinical outcomes of combined major vessel resection for hilar cholangiocarcinoma: a propensity score analysis.

In the treatment of hilar cholangiocarcinoma (HCCA), combined resection of important hepatic vessels remains controversial. The purpose of this study was to compare the postoperative complications and prognosis of combined and non-combined major vessel resections in patients undergoing radical resection for HCCA. In this study, patients with HCCA who underwent curative resection between January 2007 and December 2018 were retrospectively enrolled. Postoperative complications and prognosis between the groups were compared using propensity score-matching (PSM) analysis. There were 310 patients included in this study. The portal vein resection (PVR) and hepatic artery resection (HAR) groups had a higher incidence of postoperative complications than the control group. Patients in the HAR group had an increased risk of abdominal and pleural effusion after surgery. Patients who underwent combined PVR had better overall survival (OS; P = 0.020) and disease-free survival (DFS; P = 0.020). After curative-intent resection, patients in the HAR group had improved OS (P = 0.027) and DFS (P = 0.023). The postoperative complications of combined vascular resection (VR) did not worsen long-term survival for patients. In patients with HCCA, combined VR improved prognosis. The postoperative complications of combined VR do not worsen patient survival. Therefore, radical surgical resection is recommended.

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats

The study objective was to observe the treatment effect of the farnesoid X receptor (FXR) agonist GW4064 in a rat model of hilar cholangiocarcinoma to explore a new therapeutic target for gene therapy for hilar cholangiocarcinoma. Eighty male Wistar rats were randomly divided into four groups (treatment group, model group, control group and sham operation group, 20 rats in each group). The four groups were fed a standard diet. The treatment group and the model group were injected with a suspension of cholangiocarcinoma QBC939 cells into the hilar bile duct with a microsyringe, the control group was injected with normal saline, and the sham operation group was not injected with anything. A modified tail suspension test (TST) was used to evaluate the vitality of the rats. At 4 weeks, one rat in the treatment group and model group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma occurred in the treatment group and model group. Then, the treatment group was injected with GW4064 intraperitoneally at a dose of 50 mg/kg/day. One week after injection, the rats in the four groups were euthanized. Pathological examination confirmed that tumours had formed, and hilar bile duct tissues were taken from the four groups. FXR, Bsep, Ntcp and NF-κB expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After three weeks, the rats in the treatment group and model group ate less, and their weight was significantly reduced. Six weeks later, hilar cholangiocarcinoma was detected in the treatment group and model group. After treatment with GW4064, the ratios of FXR/GAPDH mRNA, Bsep/GAPDH mRNA, Ntcp/GAPDH mRNA and NF-κBp65/GAPDH mRNA were significantly different among the four groups. Under a light microscope, FXR protein reacted with anti-FXR antibody, Bsep protein reacted with anti-Bsep antibody, Ntcp protein reacted with anti-Ntcp antibody and NF-κBp65 protein reacted with anti-NF-κBp65 antibody, and they showed granular expression. Every pathological section included 4,800 cells, and there were different numbers of positive cells in each group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues. GW4064 increased the expression of FXR in tumour tissues. These findings suggest that FXR may be a new therapeutic target and that GW4064 may be helpful in the treatment of hilar cholangiocarcinoma.

FXR expression in rats of hilar cholangiocarcinoma

The study objective was to detect the expression of farnesoid X receptor (FXR) in a rat model of hilar cholangiocarcinoma to provide a new therapeutic target for gene therapy in hilar cholangiocarcinoma. Sixty male Wistar rats (weighing 190 ± 8 g) were randomly divided into three groups (experimental group, control group and sham operation group, 20 rats in each group). The three groups were fed a standard diet. The QBC939 cell suspension of cholangiocarcinoma was injected into the hilar bile duct in the experimental group with a microsyringe. The control group was injected with normal saline, and the sham operation group was not injected with any drugs. A modified tail suspension test (TST) was used to evaluate the mental state and physical activity of rats every day. At 5 weeks, one rat in the experimental group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at one and half months. After one and half months, hilar cholangiocarcinoma only occurred in the experimental group. Pathological examination confirmed the formation of tumours, and hilar bile duct tissues were taken from the three groups. FXR expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After two weeks, the rats in the experimental group ate less, and their weight was significantly reduced. One and half months later, hilar cholangiocarcinoma was detected in 16 rats in the experimental group. The levels of alanine aminotransferase and aspartate transaminase in the experimental group were higher than those in the other two groups. The ratio of FXR/GAPDH mRNA was significantly different among the hilar cholangiocarcinoma, control and sham operation groups. Under the light microscope, FXR protein reacted with anti-FXR antibody and showed granular expression. Every pathological section included 4800 cells. A total of 1856 positive cells were in the experimental group, 3279 positive cells were in the control group, and 3371 positive cells were in the sham operation group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues, suggesting that drugs targeting FXR may be a new strategy for the treatment of hilar cholangiocarcinoma.

Space-Making Particle Therapy for Unresectable Hilar Cholangiocarcinoma

Introduction: Although the primary treatment option for hilar cholangiocarcinoma (HC) has been surgical resection, most patients present with unresectable advanced tumors at the time of diagnosis. Particle therapy (PT) holds great potential for HC, even though the anatomical proximity to the gastrointestinal tract prevents delivering a radical dose to the tumor. Space-making PT (SMPT), consisting of spacer placement surgery and subsequent PT, has been developed to minimize complications and maximize the therapeutic benefit of dose escalation for HC. This study aimed to conduct a dosimetric evaluation and examine the effectiveness of SMPT for the treatment of HC. Methods: Between 2007 and 2018, 12 patients with unresectable HC treated with SMPT were enrolled. The treatment outcomes and effectiveness of spacer placement surgery were evaluated through analyses of pre- and post-surgical parameters of dose-volume histograms. Results: All patients completed the planned SMPT protocol. The median survival time was 29.6 months, and the 1- and 3-year overall survival rates were 82.5% and 45.8%, respectively. The mean V95% value (volume irradiated with 95% of the planned treatment dose) of the gross tumor volume and clinical target volume after spacer placement surgery improved to 98.5% and 96.6% from preoperative values of 85.6% and 78.1%, respectively (p = 0.0196 and p = 0.0053, respectively). Grade 3 or higher adverse events after SMPT were seen in 6 patients. Discussion/Conclusion: SMPT led to improvements in dosimetric parameters and showed good feasibility and excellent outcomes. SMPT can be a promising novel alternative for unresectable HC.

Prediction and prevention of severe complications following radical surgical treatment of hilar cholangiocarcinoma

This literature review highlights the recent advances in the prevention and prognosis of purulent-septic complications, post-resection liver failure, and other severe postoperative complications following the surgical treatment of hilar cholangiocarcinoma. The data obtained from the analysis of the recent scientific publications indicate the relevance of this problem. Research should be prioritized to formulate combined methods that can assess the risk of perioperative complications.

Left-side vs. right-side hepatectomy for hilar cholangiocarcinoma: a meta-analysis

GoalsWe aim to draw a conclusion which type of hepatectomy could be the priority for hilar cholangiocarcinoma patients.BackgroundSurgery is established as only potentially curative treatment for hilar cholangiocarcinoma. However, whether hepatectomy should be preferred to the left-side hepatectomy, which includes left hemihepatectomy, extended left hemihepatectomy, and left trisectionectomy, or right-side hepatectomy, which represents right hemihepatectomy, extended right hemihepatectomy, and right trisectionectomy, is debated. In this meta-analysis, we evaluated and compared the efficacy and safety of left-side hepatectomy and right-side hepatectomy in patients with hilar cholangiocarcinoma.StudyWe systematically retrieved the MEDLINE, PubMed, and Cochrane library and related bibliography up to February 2020. The primary outcome is overall survival, and the secondary outcome includes 1-, 3-, and 5-year survival rates, morbidity, mortality, R0 resection rate, and operation time. Based on heterogeneity, fixed-effects model or random-effects models were established through meta-analysis.ResultsEleven studies (11 cohort studies, totally 1031 patients) were involved in this study. The overall survival of patients who underwent left-side hepatectomy was comparable to that of patients who underwent right-side hepatectomy (hazard ratio, 1.27 [95% confidence interval, 0.98–1.63]). And there was no significant difference observed in 1-year (relative risk, 1.01 [95% CI, 0.89–1.15]), 3-year (relative risk, 0.94 [95% confidence interval, 0.80–1.11]), and 5-year survival (relative risk, 0.82 [95% confidence interval, 0.67–1.01]) rates between the left-side hepatectomy group and the right-side hepatectomy group. Comparing with the right-side hepatectomy cluster, the hilar cholangiocarcinoma patients in the left-side hepatectomy cluster presented better overall postoperative morbidity (relative risk, 0.82 [95% confidence interval, 0.71–0.96]) and major postoperative morbidity (relative risk, 0.73 [95% confidence interval, 0.56–0.95]). The post-hepatectomy liver failure rate (relative risk, 0.22 [95% confidence interval, 0.09–0.56]) and procedure-related mortality (relative risk, 0.41 [95% confidence interval, 0.23–0.70]) in the left-side hepatectomy group were better than those of the right-side hepatectomy group. Besides, the R0 resection rate was similar between the left-side hepatectomy group and the right-side hepatectomy group (relative risk, 0.95 [95% confidence interval, 0.87–1.03]). And the operation time for the left-side hepatectomy was significantly longer than that for the right-side hepatectomy (mean difference, 38.68 [95% confidence interval, 7.41–69.95]).ConclusionThrough meta-analysis, we explored the comparable long-term outcomes and better short-term outcomes in the left-side hepatectomy group as is compared to the right-side hepatectomy group of hilar cholangiocarcinoma patients. In this study, the evidence obtained might indicate that the choice of left-side hepatectomy or right-side hepatectomy depends on the site of hilar cholangiocarcinoma in every patient.

Application of endoscopic nasobiliary cutting in the treatment of hilar cholangiocarcinoma

Abstract Objective The aim of the study was to study the clinical efficacy and prognosis of endoscopically cutting the nasobiliary duct and leaving its residual segment as a biliary stent in the treatment of hilar cholangiocarcinoma (HC). Methods The clinical data of 55 patients with HC treated by endoscopic biliary drainage at the Gastrointestinal Endoscopy Center of our hospital (Renmin Hospital of Wuhan University, China) from August 2017 to August 2019 were retrospectively analyzed. According to different drainage schemes, patients were divided into the endoscopic nasobiliary cutting group (n = 26) and the endoscopic retrograde biliary drainage (ERBD) group (n = 29). The postoperative liver function indexes, incidence of postoperative complications, median patency period of stents, and median survival time of patients were compared between the two groups. Results Liver function indexes (total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase) were significantly decreased in 55 patients a week postoperaticely (P < 0.05), and decreases in liver function indexes in the endoscopic nasobiliary cutting group were more significant than those in the ERBD group (P < 0.05). The incidence of biliary tract infection in the endoscopic nasobiliary cutting group was significantly lower than that in the ERBD group (15.40% vs. 41.4%, P < 0.05). In the endoscopic nasobiliary cutting subgroups, there were 1 and 3 cases of biliary tract infection in the gastric antrum cutting group (n = 21) and duodenal papilla cutting group (n = 5), respectively, and 0 cases and 2 cases of displacement, respectively; there was a statistically significant difference in terms of complications between the two subgroups (P < 0.05). The median patency period (190 days) and median survival time (230 days) in the nasobiliary duct cutting group were higher than those (169 days and 202 days) in the ERBD group, but there was no significant difference (P > 0.05). Conclusion The nasobiliary duct was cut by using endoscopic scissors in Stage II after the bile was fully drained through the nasobiliary duct. The residual segment could still support the bile duct and drain bile. The reduction of jaundice and the recovery of liver enzymes were significant, and the incidence of biliary tract infection was low. Cutting off the nasobiliary duct at the duodenal papilla results in a higher incidence of biliary tract infection, and the residual segment of the nasobiliary duct is more likely to be displaced. Endoscopic nasobiliary-cutting drainage is an effective, simple, and safe method to reduce jaundice in the palliative treatment of HC.

The safety and efficacy of combined hepatic artery resection in treatment of hilar cholangiocarcinoma: a meta-analysis

Objective: To evaluate the safety and effectiveness of combined hepatic artery resection for the treatment of hilar cholangiocarcinoma. Methods: We searched Pubmed, The Cochrane Library, Embase, Web of Science, China Knowledge Network, Wanfang Data Resource System, Vip-Chinese Sci-tech Journal System Database, and China Biomedical Literature Database, and collected the randomized controlled studies or retrospective studies on the safety and efficacy of combined hepatic artery resection and non-hepatic artery resection in the treatment of hilar cholangiocarcinoma. The search period is from January 1, 2006 to December 31, 2019. Review Manager 5.3 software was used to analyze the extracted data indicators. Results: A total of 14 articles were collected, and a total of 2 374 patients with hilar cholangiocarcinoma were included in the study. Meta-analysis results showed that the perioperative mortality in the hepatic artery resection (HAR) group was higher than that of the control group (OR=1.70, 95%CI=0.02-2.90, P=0.05), and the total postoperative morbidity rate was higher than that of the control group (OR=1.28, 95%CI= 0.93-1.76, P=0.13), both of which were not statistically significant compared with the control group. Subgroup analysis showed that the incidence of liver failure (OR=1.15, 95%CI= 0.73-1.82, P=0.54), biliary fistula (OR=1.20, 95%CI= 0.78-1.84, P=0.40), and abdominal infection in the two groups (OR=0.98, 95%CI= 0.53-1.83, P=0.95) was without significant difference. The R0 resection rate of the HAR group was higher than that of the control group, and the difference was not statistically significant (OR=1.08, 95%CI=0.66-1.75, P=0.77). The rates of lymph node metastasis in the HAR group were higher than that in the control group (OR= 2.48, 95%CI= 1.05-5.84, P=0.04). One-year(OR=0.48, 95%CI= 0.32-0.72, P=0.000 5), 3-year (OR= 0.51, 95%CI=0.36-0.72, P=0.000 1), and 5-year (OR=0.50, 95%CI=0.35-0.70, P<0.000 1) survival rates of HAR group were lower than those of the control group. The survival rates of patients in HAR group treated with combined chemotherapy drugs after operation were significantly improved (OR= 7.33, P=0.02). Conclusions: The safety of combined HAR treatment for hilar cholangiocarcinoma is acceptable, but poor postoperative survival may be related to the high lymph node metastasis rate. Therefore, it is still necessary to be cautious in carrying out this operation. Combined with adjuvant chemotherapy after surgery may improve survival.

The Value of Modified Mesohepatectomy in the Treatment of Hilar Cholangiocarcinoma

The Value of Modified Mesohepatectomy in the Treatment of Hilar Cholangiocarcinoma

Cholangiocarcinoma, 10-Year Survival After Liver Transplantation: A Case Report

Cholangiocarcinoma is the second most common neoplasm in the liver, with a very poor, short-term prognosis. Today, surgery associated with or without an adjuvant is the only curative treatment. Liver transplantation (LT) is the best treatment for hepatocellular carcinoma tumor. In recent years, treatment of hilar cholangiocarcinoma by LT associated with neoadjuvant therapy has been studied under a criterion. But could it be possible to apply LT like the curative treatment of intrahepatic cholangiocarcinoma (iCC)? Initially the answer is no, but there are different studies about incidental LT in patients with iCC that demonstrate survival over 40% to 50%. In our center, we conducted a review of 468 transplants completed between 2002 and 2018, and we identified 1 case of incidental LT in a patient with iCC with an overall survival of 10 years. Because there is currently an increase in donors owing to the expansion of the criteria, a study to consider extending the criteria of LT to include iCC would be beneficial.

Comparison study for surgical outcomes of right versus left side hemihepatectomy to treat hilar cholangiocellular carcinoma.

PurposeMajor liver resection and radical lymph node dissection has been accepted as a definite treatment of choice for hilar cholangiocarcinoma (HC). However, the perioperative and survival outcomes of right hemihepatectomy (RH) and left hemihepatectomy (LH) still remain controversial. Thus, this study aimed to compare the surgical and oncological outcomes of RH and LH in HC patients.MethodsFrom January 2000 to January 2018, a total of 326 patients underwent surgical resection for HC at Yonsei University College of Medicine in Seoul, Korea. Among the 326 patients, we excluded 130 patients and selected 196 patients, who underwent hemihepatectomy with caudate lobectomy. Among these 196 patients, 114 patients underwent RH, and 82 patients underwent LH. We compared the clinicopathological features as well as the surgical and oncologic outcomes of the RH and LH groups.ResultsThere were no significant differences in disease-free survival (P = 0.473) or overall survival (P = 0.946) in the RH and LH groups. The LH group had fewer complications compared with the RH group, including postoperative ascites (RH: 15 [13.2%] vs. LH: 3 [3.7%], P = 0.023); however, the LH group had more bile leakage complications (RH: 5 [4.4%] vs. LH: 12 [14.6%], P = 0.012). The average time lag from portal vein embolization to operation was 25.80 ± 12.06 days (n = 45). There was no difference in postoperative liver failure (P = 0.402), although there were significantly more frequent ascites after RH (P = 0.023).ConclusionLH might be a good alternative option for the surgical treatment of HC given appropriate tumor location and biliary anatomy indications.

Analysis of the curative effect and prognosis factors of surgical treatment for hilar cholangiocarcinoma

Objective To exlore and analyze the curative effect and pognostic factors of surgical treatment for hilar cholangiocarcinoma. Methods The clinical data and prognosis of 92 patients with hilar cholangiocarcinoma admitted to Anhui Provincial Hospital Affiliated to Anhui Medical University from January 2010 to January 2018 were retrospectively analyzed. There were 58 males and 34 females, with an age range of 35-81 years and average age of 61.3 years. Among them, 50 patients underwent radical resection of tumors (radical operation group), and 42 patients were discussed to undergo radical operation before operation, but only palliative resection of tumors or simple biliary drainage (palliative operation group) were performed because of the high location of tumors or distant metastasis during operation. Of the 50 patients who received radical surgery, 27 underwent simple perihepatic portectomy (perihepatic hilar resection group), and 23 underwent combined hepatic lobectomy (extended hepatectomy group). The incidence of perioperative complications, perioperative mortality and long-term survival rate of all patients were collected. The data of clinical cases included in the study were analyzed by univariate and multivariate analysis, and the relationship between perioperative mortality and prognosis survival time was discussed. The measurement data that accord with normal distribution were expressed by (Mean±SD). The comparison between the two groups was performed by t-test, the comparison between multiple groups was performed by one-way ANOVA; Measurement data with non-normal distribution were described as M(P25, P75), and comparison between groups was done using Mann-Whitney U test. The comparison between counting data groups was performed by chi-square test. Results Ninety-two patients included in this study successfully completed the operation. One patient died during the perioperative period, with a mortality rate of 1.09%. The incidence of complications was 35.87%. Biliary tract infection and bile leakage were the most common complications. The incidence of complications was 14.13%(13/92) and 9.78%(9/92) respectively. The survival time of patients in the radical operation group 34.23(13.00, 52.25) months was significantly different from that in the palliative operation group 4.75(2.88, 7.25) months (Z=-6.708, P=0.000). There was no significant difference in the survival time between the extended hepatectomy group 33.87(13.00, 56.00) months and the simple perihepatectomy group 34.54(13.00, 51.00) months (Z=-0.156, P=0.876). Univariate analysis showed that the factors related to the prognosis of hilar cholangiocarcinoma were preoperative history of calculi, tumor size, preoperative highest serum total bilirubin level, preoperative CA19-9 level, surgical modality and tumor differentiation(HR=0.200, 2.692, 2.942, 4.350, 3.740, 0.198; 95%CI: 0.043-0.938, 0.995-7.283, 1.022-8.469, 1.174-16.114, 1.229-11.382, 0.049~0.806, P<0.05). Multivariate analysis showed that tumor size, tumor differentiation and surgical modality were related to hilar cholangiocarcinoma. Surgical prognosis of patients with cholangiocarcinoma was significantly correlated(OR=1.034, 6.444, 12.527; 95%CI: 1.007-1.062, 1.012-41.037, 3.187-49.243, P<0.05). Conclusions Radical resection is an effective way to improve the survival of patients with hilar cholangiocarcinoma. The effective grasp of surgical indications can improve the overall treatment prognosis. Key words: Bile duct neoplasms; Surgical procedures, operative; Prognosis; Treatment outcome; Complications

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma: Review of the literature.

Cholangiocarcinoma (CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA (iCCA), hilar CCA (hCCA) and distal CCA (dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor’s extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy (RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant (OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.

Progress in surgical treatment of hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a dread disease for humankind due to its high level of malignant, quick metastatic, and high mortality rate. Some patients get treated at the stage of obstructive jaundice, when the intestines are mostly or even completely obstructed, whom can not be radically treated since it can only lead to many complications and a low level of life quality. Despite the various ways of curing this disease, we will talk about the latest progress of surgical excision, palliative treatment, as well as liver transplantation in the eyes of surgical skills. This essay aims to summarize the latest treatment for hilar cholangiocarcinoma in the area of surgery, updating our knowledges, as a way of upgrading our skills and transforming our minds, so as to raise the life quality of our patients by avoiding complications. At the same time, it can provide some ideas for further research in this area. Besides, the paper sheds light on the current treatment of the disease by pointing out some questions on clinical works, which also focuses on lowering the death rate and raising the life quality of our patients. Key words: Bile duct neoplasms; Surgical procedures, operative; Treatment outcome

Analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma

Objective To analyze the prognostic factors in the surgical treatment of hilar cholangiocarcinoma. Methods The retrospective case-control study was conducted. The clinicopathological data of 93 patients [61 males and 32 females, age (64±8)years with the range of 43-84 years] with hilar cholangiocarcinoma who underwent surgical treatments in the General Hospital of the Northern Theater from January 2010 to December 2017 were collected. According to preoperative different staging and intraoperative exploration of hilar cholangiocarcinoma, corresponding operations were performed. Observation indicators: (1) surgical treatment situations; (2) tumor typing, staging and degree of differentiation: ① tumor typing and staging, ② degree of tumor differentiation; (3) follow-up situations; (4) analysis of prognostic factors: ①univariate analysis, ②multivariate analysis; (5) subgroup analysis. Follow-up using outpatient examination and telephone interview was performed to detect survival time and survival rate of patients up to December 31, 2017. Kaplan-Meier method was used to calculate survival time and survival rate and to draw survival curves. Survival situations were analyzed by Log-rank test. The univariate analysis and multivariate analysis were performed using the Log-rank test and COX proportional hazard model respectively. Results (1) Surgical treatment situations: 93 patients underwent surgical treatments, including 51 undergoing radical resection, 23 undergoing palliative resection, 16 undergoing internal biliary drainage or external drainage, 3 undergoing abdominal laparotomy and intraoperative biopsy. (2) Tumor typing, staging and degree of differentiation. ① Tumor typing and staging: of the 93 patients with hilar cholangiocarcinoma, Bismuth-Corlette type Ⅰ, Ⅱ, Ⅲa, Ⅲb and Ⅳ were detected in 26, 22 , 9, 18 and 18 patients. TNM stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were detected in 7, 34, 22 and 30 patients, Mayo Clinic stage 1, 2, 3, 4 were detected in 20, 19, 51 and 3 patients. ② Degree of tumor differentiation: results of pathological examination showed 16 of 93 patients with highly differentiated adenocarcinoma, 35 with moderately differentiated adenocarcinoma, 37 with poorly differentiated adenocarcinoma, 4 with mucinous adenocarcinoma and 1 with papillary adenocarcinoma. (3) Follow-up situations: 93 patients were followed up for 6-36 months, with a median time of 24 months. The survival time of 93 patients was (21.4±2.1)months and the 1-, 2-, 3-year overall survival rates were 62.2%, 34.9% and 17.1%, respectively. (4) Analysis of prognostic factors: ① results of univariate analysis showed that preoperative level of TBil, preoperative level of CA19-9, preoperative level of CA24-2, surgical methods, lymph node metastasis, vascular invasion, TNM staging, Mayo Clinic staging, degree of tumor differentiation were related factors affecting prognosis of patients with hilar cholangiocarcinoma (χ2=6.321, 7.357, 6.590, 22.088, 11.173, 22.914, 23.326, 25.966, 39.512, P 0.05). Of the 35 patients with vascular invasion, the overall survival time was (7.0±2.0)months and 1-, 2-, 3-year survival rates were 14.5%, 7.3%, 0 respectively in 18 with portal vein invasion only, (10.0±2.1)months and 37.5%, 18.8%, and 18.8% respectively in 8 with hepatic artery invasion, showing no statistically significant difference between the two groups (χ2=0.905, P>0.05). Conclusions Preoperative level of TBil, preoperative level of CA19-9, surgical procedures, vascular invasion and degree of tumor differentiation are independent prognostic factors for patients with hilar cholangiocarcinoma. Radical resection can prolong the survival time of patients compared with other surgical treatments. Key words: Hilar cholangiocarcinoma; Surgical procedures, operative; Tumor typing; Tumor staging; Degree of tumor differentiation; Prognosis analysis

Efficacy of liver transplantation for hilar cholangiocarcinoma: A protocol for a systematic review and meta-analysis.

Background:Either liver transplantation or surgical resection is available for selected patients with hilar cholangiocarcinoma. However, the comparative effectiveness between liver transplantation and liver resection remains unknown. The aim of our study is to evaluate the relative effectiveness between liver transplantation and surgical resection in patients with hilar cholangiocarcinoma.Methods:We will systematically search for eligible studies in PubMed, Embase, and the Cochrane library. The primary outcomes are overall survival rates including 1-, 3-, or 5-year survival rates. The second outcomes are postoperative complications. The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies.Results:The results will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide a comprehensive evidence summary of the comparison between liver transplantation or surgical resection in the treatment of hilar cholangiocarcinoma.

Liver transplantation for treatment of hilar cholangiocarcinoma with a report of three cases

Objective To investigate the feasibility of liver transplantation in the treatment of inoperable hilar cholangiocarcinoma. Methods The clinical data for 3 patients with unresectable hilar cholangiocarcinoma who underwent liver transplantation in the Department of Hepatobiliary Surgery of Fuzhou General Hospital of People′s Liberation Army from January 2006 to December 2012 were retrospectively analyzed. The patients were followed up by phone, outpatient service, and hospitalization. The starting point of the follow-up was the operation date. The patient's death was the end point. The clinical and pathological features, postoperative survival, tumor recurrence, and prognostic factors were observed. The follow-up deadline was December 2017. Results All 3 patients underwent classical orthotopic liver transplantation using retrograde perfusion through inferior vena cava and no perioperative deaths occurred. All 3 patients were followed up for 10 to 132 months. During the follow-up period, of 1 patient who died of tumor recurrence, the pathological TNM stage was T4aN1M0, and both had Union for International Cancer Control stage Ⅳa, and the tumor-free survival time was 3 months, and the survival time was 12 months. Of 1 patient who died of other causes, the pathological TNM stage was T3N1M0, and both had Union for International Cancer Control stage Ⅲ, and the tumor-free survival time was 12 months, and the survival time was 12 months. One case as of the end of follow-up, the patient has survived for 132 months, the pathological TNM staging was T2aN0M0, and both had Union for International Cancer Control stage Ⅱ. Conclusions Lymph node positive and high pathological TNM stage were poor prognosis factor for hilar cholangiocarcinoma who underwent liver transplantation. Patients with early hilar cholangiocarcinoma who don′t have lymph node metastasis are expected to benefit from liver transplantation. Key words: Liver transplantation; Bile duct neoplasms; Hilar cholangiocarcinoma

From digital visual human technology to digital minimally invasive surgery: translational application of three-dimensional visualization technology in the diagnosis and treatment of hilar cholangiocarcinoma

Digital medicine underwent the conversion from human to digital medical technology and has been widely used in all aspects of clinical medicine in recent 10 years, especially in hilar cholangiocarcinoma (HCCA). It is difficult to accurately evaluate the longitudinal and vertical tumor invasion by preoperative conventional imaging assessment (CT, MRI, etc.) due to the complexity of this operation. Three-dimensional (3D) visualization can see more comprehensively, more clearly and more accurately on the basis of organs and lesions indicated by CT and MRI. Three-dimensional visualization digital medical technology can accurately, intuitively and stereoscopically display the situation of tumor invasion of the adjacent important vessels as well as the variation of vessels. It plays an important role in the aspects of preoperative evaluation, surgical planning, improving the success rate of operation and reducing complications for HCCA. It also transforms the past model of crossing the river by feeling the stone to now crossing the river by watching the stone . Therefore, it is known as the paradigm of translational medicine. Key words: Bile duct neoplasms, hilar; Hilar cholangiocarcinoma; Digital medicine; Translational medicine; Three-dimensional visualization; Three-dimensional printing; Diagnosis; Therapy

Therapy of hilar cholangiocarcinoma in the precise medicine period

Because of the special anatomical position of hilar cholangiocarcinoma and its characteristics of longitudinal and vertical invasion, it is difficult to obtain satisfactory effect by surgical resection. More and more researchers have realized that the treatment of the hilar cholangiocarcinoma should take biological characteristics of the tumor. Precise medicine using of frontier technologies and omics technologies such as proteomics and genomics, can accurately diagnose diseases at molecular level and may provide a new model for the treatment of hilar cholangiocarcinoma. The gene mutation rate of the hilar cholangiocarcinoma is higher, and the most common mutation genes are KRAS and TP53, following other genes such as CDKN2A, SMAD4, ERBB2, PTEN, APIK3CA, ARID1A, MLL3, ROBO2, RNF43, and PEG3, GNAS, etc. Such frequent, important functional mutations suggest that hilar cholangiocarcinoma may have potential therapeutic targets for molecular targeted drugs. However, due to the complex pathogenesis of the bile duct cancer, the clinical trials of most targeted drugs have not been able to achieve breakthrough progress. Surgical resection should still remain the dominant treatment. The appropriate extent of hepatectomy should be determined individually, and the minor resection is enough for most hilar cholangiocarcinoma. Key words: Bile duct neoplasms, hilar; Precise medicine; Targeted therapy; Hepatectomy