Application of a New Approach for Laparoscopic Resection of Bismuth IIIa Hilar Cholangiocarcinoma.

Background: Hilar cholangiocarcinoma (HCCA) has a high degree of malignancy and poor prognosis, and the best long-term prognosis can only be achieved by radical resection. However, the surgical steps are complicated, and the operating space is limited, making it hard to complete laparoscopically. So our team proposes a new surgical approach for laparoscopic left-liver-first anterior radical modular orthotopic right hemihepatectomy (Lap-Larmorh). In this way, we can simplify the operation steps and reduce the difficulty. Materials and Methods: We recorded and analyzed the clinical data of 26 patients with type IIIa HCCA, who underwent laparoscopic radical resection in our department from December 2018 to January 2023. According to the laparoscopic surgical approach, we divided the patients into the new approach (NA) group (n = 14) using the Lap-Lamorh and the traditional approach (TA) group (n = 12) not using the Lap-Lamorh. Results: All surgeries in this study were completed laparoscopically with no conversion to open surgery. The operation time in the NA group and TA group had statistically significant differences, which was 372.5 (332.8, 420.0) minutes versus 423.5 (385.8, 498.8) minutes (P = .019). The two groups showed no significant difference in other characteristics (P > .05). Only 1 patient suffered from transient liver failure due to portal vein thrombosis. Patients with pleural effusion or ascites were cured by catheter drainage and enhanced nutrition. Conclusion: Lap-Larmorh reduces the difficulty of serving the vessels at the second and third hepatic hilum by splitting the right and left livers early intraoperatively. The new approach is more suitable for the narrow space of laparoscopic surgery and reflects the no-touch principle of oncology.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study.

Background: The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. Methods: A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. Results: The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. Conclusions: The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.

Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma.

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

New lignanamides and alkaloids from Chelidonium majus and their anti-inflammation activity.

Two new lignanamides, majusamides A and B (1 and 2), and two new alkaloids, chelidoniumine (3) and tetrahydrocoptisine N-oxide (4), together with six known hydroxycinnamic acid amides (HCCA) were isolated from the 75% ethanol extract of Chelidonium majus through the silica gel, Sephadex LH-20, MCI, ODS column chromatography, and semi-HPLC. Their structures were determined on the basis of spectroscopic data and physico-chemical methods. The absolute configurations of 1-3 were determined by electronic circular dichroism (ECD) calculations. The anti-inflammatory activities of all the isolates on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. Compounds 7 and 9 exhibited moderate inhibitory activity with IC50 values of 25.3 ±â€¯0.5 and 23.5 ±â€¯1.7 µM, respectively.

Clinical practice of basin-shaped hepaticojejunostomy following hilar resection of stage III/IV hilar cholangiocarcinoma.

BACKGROUND: Radical surgery for Bismuth type III/IV hilar cholangiocellular carcinoma, which was usually considered unresectable, seems to improve prognosis by increasing the surgical curability rate. However, the dilemma of multiple billiary stumps and high postoperative complication rate caused by hepato-enteric anastomosis has been the main impediment. Thus, we practiced and introduce a new technique called "basin-shaped" hepaticojejunostomy to improve the treatment. METHODS: Thirty-two cases with Bismuth type III/IV hilar cholangiocarcinoma admitted to our department from Aug. 2013 to Dec. 2015 and who underwent hilar resection and resection segment 4(or plus resection segment 1) were reconstructed by "basin-shaped" hepaticojejunostomy. The clinical data were collected and analyzed. RESULTS: All patients underwent successful R0 high hilar resection following basin-shaped hepaticojejunostomy and were discharged from the hospital without severe postoperative complications. The average operation time for hepato-enteric anastomosis was 42.1 ± 8.5 min. The postoperative bile leakage rate was 3.1% (1/32), and the biliary infection rate was 6.2% (2/32). Within a median follow-up of 25.6 months, none of the patients developed local recurrence around the hepato-enteric anastomosis. CONCLUSIONS: For patients with Bismuth type III/IV hilar cholangiocellular carcinoma who underwent resection segment 4(or plus resection segment 1), basin-shaped hepaticojejunostomy was a safe, simple and valid method for bile duct reconstruction, with a relatively low incidence of postoperative complications.

Long Non-Coding RNA MALAT1 Interacts With miR-204 to Modulate Human Hilar Cholangiocarcinoma Proliferation, Migration, and Invasion by Targeting CXCR4.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in many kinds of cancers. However, the exact effects and molecular mechanisms of MALAT1 in human hilar cholangiocarcinoma (HCCA) progression are still unknown. Here, we investigated the role of MALAT1 in human HCCA cell lines and clinical tumor samples in order to determine the function of this lncRNA. In our research, lncRNA-MALAT1 was specifically upregulated in HCCA tissues and cell lines, and was associated with pathological T stage, a larger tumor size, and perineural invasion. Knockdown of MALAT1 inhibited the proliferation, migration, and invasion of human HCCA cell. In addition, chemokine receptor-4 (CXCR4) was involved in MALAT1 induced human HCCA growth, migration, and invasion. By using online tools and a series of mechanistic analysis, we also demonstrated that miR-204-dependent CXCR4 regulation was required in MALAT1 modulating HCCA cell growth, migration and invasion. Taken together, our data indicated that MALAT1 might play an oncogenic role in HCCA through miR-204-dependent CXCR4 regulation, and could be regarded as a therapeutic target in HCCA. J. Cell. Biochem. 118: 3643-3653, 2017. © 2017 Wiley Periodicals, Inc.

Therapeutic effects of different treatments of hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective To analyze the clinical data of patients with hilar cholangiocarcinoma (HCCA),and to compare the therapeutic effects of different methods on treating these patients.Methods The clinical data of 101 patients with HCCA in China-Japan Union Hospital of Jilin University were analyzed.Results The overall 1-year and 2-year survival rates in the radical operation group were 95.5％ and 40.9％,respectively.There was a significant difference between the radical operation group and the palliative resection group (P ＜ 0.05).The overall 1-year and 2-year survival rates in the palliative resection group were 75.0％ and 16.7％,respectively,which were much better than those in patients treated with PTCD,biliary stent on open abdominal biliary drainage (P ＜ 0.05).There were no significant differences among the PTCD,biliary stent and open abdominal biliary drainage groups (P ＞ 0.05).Conclusions Radical HCCA resection is still the best and the first choice treatment for patients with HCCA.The therapeutic effects of radical operation were much better than those of palliative resection,biliary stent,PTCD and open abdominal biliary drainage.

Dickkopf-1 expression is associated with tumorigenity and lymphatic metastasis in human hilar cholangiocarcinoma.

Dickkopf-1 (DKK1) is involved in tumorigenesis and the invasion of several tumors. However, its biological function in human hilar cholangiocarcinoma (HCCA) has not yet been documented. This study was designed to investigate the clinical significance and biological function of DKK1 in HCCA. The expression of DKK1 was investigated in thirty-seven human HCCA biopsy samples by immunohistochemistry. To further explore the biological effects of DKK1 in HCCA, transient and stable knockdown of DKK1 in two human HCCA cells (QBC939 and FRH0201) were established using small interfering or short hairpin RNA expression vector. In the present study, immunohistochemistry revealed that DKK1 was up-regulated in human HCCA tissues (24/37, 64.9%). High levels of DKK1 in human HCCA correlated with metastasis to the hilar lymph nodes (P=0.038). Genetic depletion of DKK1 in HCCA cells resulted in significantly inhibited proliferation, colony formation and migration compared with controls. Most importantly, DKK1 down-regulation impaired tumor formation capacity of HCCA cells in vivo. Subsequent investigations revealed that ß-catenin is an important target of DKK1 and DKK1 exerts its pro-invasion function at least in part through the ß-catenin/ matrix metalloproteinase-7 (MMP-7) signaling pathway. Consistently, in human HCCA tissues, DKK1 level was positively correlated with ß-catenin and MMP-7 expression, as well as tumor hilar lymphatic metastasis. Taken together, our findings indicate that DKK1 may be a crucial regulator in the tumorigenicity and invasion of human HCCA, DKK1 exerts its pro-invasion function at least in part through the ß-catenin/ MMP-7 signaling pathway, suggesting DKK1 as a potential therapeutic target for HCCA.

Analysis of the raw serum peptidomic pattern in glioma patients.

BACKGROUND: Glioma is a common and lethal type of brain tumor. Serum peptides reflected the pathological changes of the body. Here we studied the serum peptide profiles to distinguish glioma disease and measure glioma staging. METHODS: Serum peptides were captured by WCX magnetic beads and were analyzed by MALDI-TOF mass spectrometer. Sera from 53 glioma patients and 69 age-matched healthy controls were analyzed. Clinpro Tools software was used to obtain a common peak m/z list from all measured samples. An optimal subset of peptides was selected to establish a predictive classification model with the newly developed competitive adaptive reweighted sampling (CARS) variable selection method. Serum peptide profiles were classified through a partial least-squares-linear discriminate analysis (PLS-LDA). We also searched for progressively different peptide peaks that correlated with an increasing malignancy of glioma. RESULTS: The following pattern recognition equation was established with selected peptide signals: Y=-0.1113-0.113X1-0.2916X2+0.1128X3-0.2057X4-0.2047X5-0.3048X6+0.2835X7+0.3121X8-0.1458X9+0.0354X10-0.2022X11. Using this pattern, classification sensitivity and specificity achieved were 0.9057 and 0.9855, respectively. Additionally, we detected 3 peptide signals that correlated with glioma grade. Among these, the intensity of peak 2082.32 Da correlated positively with the glioma progressing, and peaks with sizes of 3316.08 Da and 6631.45 Da show a decreasing intensity with increasing glioma grade. CONCLUSIONS: 11 peptide recognition patterns and specific peak intensities might be useful for the early detection and tumor staging of glioma, but they need to be further validated and evaluated independently in clinical settings.

Clinical analysis of the operational treatment of 24 cases with hilar cholangiocarcinoma / 中国基层医药

Objective To investigate the effects of different operative models of hilar cholangiocarcinoma (HCCA) and its clinical significance. Methods The clinical data on 24 patients with HCCA were analyzed retro-spectively. Results 11 cases experienced surgical resection with 9 to 32 months of survival time. 13 cases were per-formed biloenteral draining with 1.5 to 17 months of survival time. There was no operative mortality. Conclusions The operative effects of HCCA is closely related to the operative models. A complete preoperative evaluation, appropri-ate operative model and high excision rate are very important for improving therapeutic effects.