The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

Downregulated Acetyl-CoA Acyltransferase 2 Promoted the Progression of Hepatocellular Carcinoma and Participated in the Formation of Immunosuppressive Microenvironment.

Background: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC). Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism. Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks. Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.

Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.

BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.

Comprehensive Analysis of RAPGEF2 for Predicting Prognosis and Immunotherapy Response in Patients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the sixth most common tumor worldwide. Additionally, deletion of RAPGEF2 plays a critical role in CNV and related to tumor immune microenvironment, whereas the prognostic potential of RAPGEF2 in HCC patient needs to be explored. Methods: We looked for prognostic potential genes in HCC using a variety of R programs. Then, using the LASSO Cox regression, we thoroughly evaluated and integrated the RAPGEF2-related genes from TCGA database. Meanwhile, utilizing TCGA and ICGA databases, the link between RAPGEF2 and immunotherapy response in HCC was studied. In vivo, the effect of RAPGEF2 on tumor development and the capacity of natural killer (NK) cells to recruit were confirmed. To ascertain the connection between RAPGEF2-related genes and the prognosis of HCC, a prognostic model was created and validated. Result: We demonstrated RAPGEF2 has a differential expression, and patients with deletion of RAPGEF2 gene get shorter survival in HCC. Additionally, the tissues without RAPGEF2 have a weaker ability to recruit the NK cells and response to immunotherapy. After that, we scoured the database for eight RAPGEF2-related genes linked with a better prognosis in HCC patients. Additionally, silencing RAPGEF2 accelerated tumor development in the HCC mouse model and decreased CD56+ NK cell recruitment in HCC tissues. TCGA database was used to classify patients into low- and high-risk categories based on the expression of related genes. Patients in the low-risk group had a significantly greater overall survival than those in the high-risk group (P < 0.001). Meanwhile, the low-risk group demonstrated connections with the NK cell and immunotherapy response. Finally, the prognostic nomogram showed a high sensitivity and specificity for predicting the survival of HCC patients at 1, 2, and 3 years. Conclusion: The prognostic model based on RAPGEF2 and RAPGEF2-related genes showed an excellent predictive performance in terms of prognosis and immunotherapy response in HCC, therefore establishing a unique prognostic model for clinical assessment of HCC patients.

Automatic Lung Nodule Segmentation and Intra-Nodular Heterogeneity Image Generation.

Automatic segmentation of lung nodules on computed tomography (CT) images is challenging owing to the variability of morphology, location, and intensity. In addition, few segmentation methods can capture intra-nodular heterogeneity to assist lung nodule diagnosis. In this study, we propose an end-to-end architecture to perform fully automated segmentation of multiple types of lung nodules and generate intra-nodular heterogeneity images for clinical use. To this end, a hybrid loss is considered by introducing a Faster R-CNN model based on generalized intersection over union loss in generative adversarial network. The Lung Image Database Consortium image collection dataset, comprising 2,635 lung nodules, was combined with 3,200 lung nodules from five hospitals for this study. Compared with manual segmentation by radiologists, the proposed model obtained an average dice coefficient (DC) of 82.05% on the test dataset. Compared with U-net, NoduleNet, nnU-net, and other three models, the proposed method achieved comparable performance on lung nodule segmentation and generated more vivid and valid intra-nodular heterogeneity images, which are beneficial in radiological diagnosis. In an external test of 91 patients from another hospital, the proposed model achieved an average DC of 81.61%. The proposed method effectively addresses the challenges of inevitable human interaction and additional pre-processing procedures in the existing solutions for lung nodule segmentation. In addition, the results show that the intra-nodular heterogeneity images generated by the proposed model are suitable to facilitate lung nodule diagnosis in radiology.

Circ-LAMP1 contributes to the growth and metastasis of cholangiocarcinoma via miR-556-5p and miR-567 mediated YY1 activation.

Dysregulation of circular RNAs (circRNAs) executes important regulatory roles in carcinogenesis. Nonetheless, few studies focused on the mechanisms of circRNAs in cholangiocarcinoma (CCA). qRT-PCR was applied to verify the dysregulated circRNAs in CCA. Fisher's exact test, Kaplan-Meier analysis and Cox regression model were utilized to investigate the clinical implications of circ-LAMP1 in the patients with CCA. The viability, apoptosis, migration and invasion of CCA cells were detected after silencing/overexpression of circ-LAMP1. Xenograft and lung metastasis assays were performed to verify the in vitro results. The regulatory networks of circ-LAMP1 were unveiled by bioinformatic analysis, RNA immunoprecipitation (RIP), RNA pulldown and luciferase reporter assays. Up-regulation of circ-LAMP1 was found in CCA tissue samples and cell lines. Enhanced level of circ-LAMP1 was linked to clinical severity, high post-operative recurrence and poor prognosis for the patients with CCA. Gain/loss-of-function assays confirmed the oncogenic role of circ-LAMP1 in mediating cell growth, apoptosis, migration and invasion. Nevertheless, the level of circ-LAMP1 had no effect on normal biliary epithelium proliferation and apoptosis. Animal study further verified the in vitro data. Mechanistically, circ-LAMP1 directly sponged miR-556-5p and miR-567, thereby releasing their suppression on YY1 at post-transcriptional level. Rescue assay indicated that the oncogenic role of circ-LAMP1 is partially dependent on its modulation of YY1 in CCA. In summary, this study suggested that circ-LAMP1 might be used as a promising biomarker/therapeutic target for CCA.

A Circular RNA, Cholangiocarcinoma-Associated Circular RNA 1, Contributes to Cholangiocarcinoma Progression, Induces Angiogenesis, and Disrupts Vascular Endothelial Barriers.

BACKGROUND AND AIMS: Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). APPROACH AND RESULTS: CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile-derived EVs (BEVs). CCA-associated circRNA 1 (circ-CCAC1) expression was measured by quantitative real-time PCR. The clinical importance of circ-CCAC1 was analyzed by receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The functions of circ-CCAC1 and exosomal circ-CCAC1 were explored in CCA cells and human umbilical vein endothelial cells (HUVECs), respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ-CCAC1 in CCA cells and HUVECs. Circ-CCAC1 levels were increased in cancerous bile-resident EVs and tissues. The diagnostic and prognostic values of circ-CCAC1 were identified in patients with CCA. For CCA cells, circ-CCAC1 increased cell progression by sponging miR-514a-5p to up-regulate Yin Yang 1 (YY1). Meanwhile, YY1 directly bound to the promoter of calcium modulating ligand to activate its transcription. Moreover, circ-CCAC1 from CCA-derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ-CCAC1 increased cell leakiness by sequestering enhancer of zeste homolog 2 in the cytoplasm, thus elevating SH3 domain-containing GRB2-like protein 2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ-CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. CONCLUSIONS: Circ-CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.

MORC2 promotes cell growth and metastasis in human cholangiocarcinoma and is negatively regulated by miR-186-5p.

Microrchidia family CW-type zinc finger 2 (MORC2) is a ubiquitously expressed protein that contributes to chromatin remodeling, DNA repair, and lipogenesis. However, its role in cholangiocarcinoma (CCA) remains largely unknown. The aim of this study was to investigate the expression profile of MORC2 and its potential functions in CCA progression. The results showed that MORC2 was upregulated in human CCA specimens and cell lines. MORC2 expression was significantly associated with serum CA19-9 levels (P = 0.009), TNM stage (P = 0.003) and lymph node invasion (P = 0.004). Furthermore, high MORC2 expression was associated with poor 5-year survival (P = 0.016). Functional experiments revealed that MORC2 knockdown could suppress CCA cell proliferation, migration, and invasion both in vivo and in vitro. Mechanically, we found that MORC2 promoted CCA cell metastasis through the EMT process and enhanced proliferation via the Akt signaling pathway. Moreover, MORC2 was negatively regulated by miR-186-5p. MiR-186-5p could influence CCA cell proliferation, migration and metastasis by regulating MORC2. Taken together, the findings of this study demonstrated the oncogenic role of MORC2 in CCA tumorigenesis and metastasis, and clarified an underlying regulatory mechanism mediating MORC2 upregulation, which may provide a novel therapeutic target in CCA treatment.

Safety and Efficacy of Laparoscopic Radiofrequency Ablation for Hepatic Hemangiomas: A Multicenter Retrospective Study.

INTRODUCTION: Radiofrequency ablation (RFA) is an effective and minimally invasive technique for the management of hepatic hemangiomas (HHs). This study aims to assess the safety and efficacy of laparoscopic RFA for HHs. MATERIAL AND METHODS: Forty-four patients with 50 hepatic hemangiomas (5-10 cm in diameter) undergoing laparoscopic RFA from January 2012 to May 2015 at three tertiary hospitals in China were retrospectively analyzed. RESULTS: Thirty-three patients with subcapsular hemangiomas were treated with a laparoscopic approach, and 11 patients with lesions in the liver parenchyma were treated with a combined laparoscopy and an ultrasound-guided percutaneous approach. No conversion to open surgery or two-step surgery occurred during the study period. Patients with small hemangiomas (< 7 cm) required a significantly shorter operating time (71.1 ± 20.18 min vs. 106 ± 23.55 min, p = 0.000) and fewer punctures compared with patients with large hemangiomas (> 7 cm) (4.61 ± 1.09 vs. 6.73 ±1.01, P < 0.05). According to the Dindo-Clavien classification, 15 patients experienced 34 Grade 1 complications, and two had complications of Grade 3a. All complications were resolved by conservative treatment. Forty-three (86.0%) HHs in 38 patients were completely ablated after RFA, and 7 (14.0%) HHs in 6 patients were incompletely ablated. All patients were followed up for 6-24 months (mean 15 ± 6 months). CONCLUSION: The data showed that laparoscopic RFA is an effective treatment for small (< 10 cm) HHs. While the incidence of postoperative complications remains high, the majority of complications are minor. Patients undergoing laparoscopic RFA for HHs, even for the small ones, should be carefully selected.

Laparoscopic management of gastric gastrointestinal stromal tumors: A retrospective 10-year single-center experience.

AIM: To determine the feasibility, safety, and oncological outcome of laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) based on favorable or unfavorable location. METHODS: Our hospital database included 207 patients who underwent laparoscopic removal of gastric GISTs from January 2004 to September 2015. Patient demographics, clinical presentation, surgery, histopathology, postoperative course, and oncological outcomes were reviewed and analyzed. RESULTS: Gastric GIST in favorable locations was present in 81/207 (39.1%) cases, and in unfavorable locations in 126/207 (60.9%) cases. Overall mean tumor size was 3.28 ± 1.82 cm. No conversions occurred, and complete R0 resection was achieved in 207 (100%) cases. There were three incidences of iatrogenic tumor rupture. The feasibility and safety of laparoscopic surgery were comparable in both groups with no statistical difference between unfavorable and favorable location groups, respectively: for operative time: 83.86 ± 44.41 vs 80.77 ± 36.46 min, P = 0.627; conversion rate: 0% vs 0%; estimated blood loss: 27.74 ± 45.2 vs 29.59 ± 41.18 mL, P = 0.780; tumor rupture during surgery: 0.90% vs 2.82%, P = 0.322; or postoperative complications: 3.74% vs 7.04%, P = 0.325. The follow-up period recurrence rate was 1.89% with no significant differences between the two groups (3.03% vs 0%, P = 0.447). Overall 5-year survival rate was 98.76% and survival rates were similar between the two groups: 98.99% vs 98.39%, P = 0.623 (unfavorable vs favorable, respectively). CONCLUSION: The laparoscopic approach for gastric GISTs is safe and feasible with well-accepted oncological surgical outcomes. Strategies for laparoscopic resection should be selected according to the location and size of the tumor. Laparoscopic treatment of gastric GISTs in unfavorable locations should not be restricted in gastrointestinal centers.

Results of adjuvant radiation therapy for locoregional perihilar cholangiocarcinoma after curative intent resection.

PURPOSE: This study sought to define the role of adjuvant radiation therapy (RT) for patients with curative intent resection of perihilar cholangiocarcinoma (pCCA). PATIENTS AND METHODS: By using the Surveillance, Epidemiology and End Results (SEER) registry, 1,917 patients with non-metastatic pCCA who underwent surgical resection from 1988 to 2009 were included in this study. Propensity score methods were used to compare the survival outcomes of patients treated with and without adjuvant RT after controlling for selection bias. RESULTS: Of the 1,917 patients, 762 (39.7%) received adjuvant RT. In the unmatched population, median overall survival (OS) for patients receiving adjuvant RT compared with those undergoing surgery alone was 23 versus 22 months (P=0.651). Patients who received adjuvant RT were younger (65 vs 68 years, P<0.001), had more regional diseases (86.0% vs 76.7%, P<0.001), and had more positive lymph nodes (43.8% vs 32.2%, P<0.001). In the matched population, adjuvant RT did not show better OS (22 vs 23 months, P=0.978) or cancer-specific survival (CSS) (17 vs 18 months, P=0.554). CONCLUSION: Adjuvant RT is not associated with improved survival of patients with resected pCCA. These data suggest that adjuvant RT should not be routinely used to treat patients with pCCA outside research trials. Ideally, prospective randomized trials should be performed to verify the conclusion of this study.

Appropriate Patient Selection Is Essential for the Success of Primary Closure After Laparoscopic Common Bile Duct Exploration.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is being increasingly used for management of common bile duct (CBD) stones. Primary CBD closure has been reported to have better short-term outcomes compared to T-tube placement. However, primary CBD closure cannot be performed in all patients. AIM: This study aims to evaluate the short- and long-term outcomes of LCBDE with primary CBD closure in appropriately selected patients and compare them with T-tube drainage. METHODS: Retrospective analysis of patients undergoing LCBDE in our department from June 2011 to October 2014 was performed. Primary closure was performed in 52 patients (group A), and a T-tube was placed in 33 patients (group B). Patient demographics, intraoperative findings, postoperative stay, complications, and long-term follow-up data were recorded and compared. RESULTS: The mean operating time was much longer in group A compared to group B (113.92 vs. 95.92 min, p = 0.032). The overall complication rate (9.6 vs. 6.3%, p = 0.701) and hospital stay (4 vs. 5.11 days, p = 0.088) were similar in both groups. No patient required conversion to the open procedure. Bile leakage was more frequent in group A (5.78 vs. 0%, p = 0.279), but this was not statistically significant. All three patients with bile leakage were treated successfully by conservative measures and gradual drain withdrawal. On long-term follow-up, recurrent stones were detected in two patients in group A. No patient was found to develop CBD stricture. CONCLUSION: LCBDE and primary CBD closure has excellent short- and long-term outcomes when performed in appropriately selected patients.

Harmonic Scalpel versus Monopolar Electrocauterization in Cholecystectomy.

BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy (LC) using surgical electrocautery is considered to be the gold standard procedure for the treatment of uncomplicated cholecystitis and cholelithiasis. The objective of the current study was to evaluate the effectiveness and safety of the Harmonic scalpel, an advanced laparoscopic technique associated with less thermal damage in LC, when compared to electrocautery. METHODS: From October 2010 through June 2013, a total of 198 patients were randomly allocated to LC with a Harmonic scalpel (experimental group, 117 patients) or conventional monopolar electrocautery (control group, 81 patients). The main outcome measures were operative time, blood loss, conversion to laparotomy, postoperative hospital stay, post-LC pain, and cost effectiveness. RESULTS: The 2 groups were comparable with respect to baseline patient characteristics. When compared to conventional monopolar electrocautery, there were no significant reductions in the operative time, bleeding, frequency of conversion to laparotomy, and duration of postoperative recovery with the Harmonic scalpel (P > .05 for all). CONCLUSIONS: Laparoscopic cholecystectomy using conventional monopolar electrocautery is as effective and safe as that with the Harmonic scalpel, for treating uncomplicated cholecystitis and cholelithiasis.

Laparoscopic gastrectomy for remnant gastric cancer: Risk factors associated with conversion and a systematic analysis of literature.

BACKGROUND: In traditional opinion, history of abdominal surgery was the relative contraindication for Laparoscopic gastrectomy (LG) with high rate of conversion to Open gastrectomy (OG).Use of LG for treatment of remnant gastric cancer (RGC) has been documented in some case studies and controlled clinical trials. However, whether LG is superior, equal or inferior to OG in these patients is not clear. METHODS: English language articles published between January 2005 and January 2016 were searched in MEDLINE, Embase and the Cochrane Database of Systematic Reviews. Main outcome measures were: conversion of LG to OG, operative time, intraoperative blood loss, tumor size, positive proximal resection margin, lymph node dissection, disease stage, post-operative resumption of oral intake, postoperative hospital stay, complications, mortality and follow-up findings. Published clinical data which was in the situation of conversion to OG was collected, and the factors associated with conversion to open surgery were examined. RESULTS: Five non-randomized controlled trials and seven LG case studies were included in the systematic review. Meta-analysis of the data could not be performed due to high variation and heterogeneity in study design, study population, LG technique, and outcome measures among the included studies. Systematic analysis of the included studies showed that LG was associated with significantly shorter mean operative time, early resumption of oral intake, and shorter hospital stay, as compared to that with OG. No significant difference in complications was observed between the two groups. CONCLUSION: LG in the hands of experienced surgeons is relative feasibility and safety for RGC. Previous surgical anastomosis, previous open surgery and surgical experience were associated with conversion to OG. However, these findings should be validated with robust prospective comparative studies.

Antiproliferative effects of cinobufacini on human hepatocellular carcinoma HepG2 cells detected by atomic force microscopy.

AIM: To investigate the antiproliferative activity of cinobufacini on human hepatocellular carcinoma HepG2 cells and the possible mechanism of its action. METHODS: HepG2 cells were treated with different concentrations of cinobufacini. Cell viability was measured by methylthiazolyl tetrazolium (MTT) assay. Cell cycle distribution was analyzed by flow cytometry (FCM). Cytoskeletal and nuclear alterations were observed by fluorescein isothiocyanate-phalloidin and DAPI staining under a laser scanning confocal microscope. Changes in morphology and ultrastructure of cells were detected by atomic force microscopy (AFM) at the nanoscale level. RESULTS: MTT assay indicated that cinobufacini significantly inhibited the viability of HepG2 cells in a dose-dependent manner. With the concentration of cinobufacini increasing from 0 to 0.10 mg/mL, the cell viability decreased from 74.9% ± 2.7% to 49.41% ± 2.2% and 39.24% ± 2.1% (P < 0.05). FCM analysis demonstrated cell cycle arrest at S phase induced by cinobufacini. The immunofluorescence studies of cytoskeletal and nuclear morphology showed that after cinobufacini treatment, the regular reorganization of actin filaments in HepG2 cells become chaotic, while the nuclei were not damaged seriously. Additionally, high-resolution AFM imaging revealed that cell morphology and ultrastructure changed a lot after treatment with cinobufacini. It appeared as significant shrinkage and deep pores in the cell membrane, with larger particles and a rougher cell surface. CONCLUSION: Cinobufacini inhibits the viability of HepG2 cells via cytoskeletal destruction and cell membrane toxicity.

Laparoscopy-assisted total gastrectomy with trans-orally inserted anvil (OrVil™): a single institution experience.

AIM: To investigate the feasibility of laparoscopy-assisted total gastrectomy (LATG) using trans-orally inserted anvil (OrVil™) in terms of operative characteristics and short term outcomes. RESULTS: Characteristics of 27 patients with gastric cancer who underwent LATG from October 2009 to October 2012 in the Foshan Affiliated Hospital of South Medical University were retrospectively reviewed. Among these patients, six were reconstructed by mini-laparotomy and 21 by OrVil™. The clinicopathological characteristics, total operation time, total blood loss, abdominal incision and complications of anastomosis including stenosis and leakage, were compared between the groups undergoing LATG with OrVil™ and the group undergoing mini-laparotomy. RESULTS: The operations were successfully performed on all the patients without intraoperative complications or conversion to open surgery. Two (10%) patients received palliative procedure under laparoscope who were prepared for LATG preoperatively. One case had hepatic metastatic carcinoma and 1 case had tumor recurrence near the anastomosis 8 mo after surgery. The mean follow-up duration was 10 mo (range, 2-24 mo). Operation time was significantly reduced by the use of OrVil™ (198.42 ± 30.28 min vs 240.83 ± 8.23 min). The postoperative course with regard to occurrence of stenosis and leakage was not different between the two groups. There were no significant differences in estimated blood loss. The upper abdominal incision was smaller in OrVil™ group than in mini-laparotomy group (4.31 ± 0.45 cm vs 6.43 ± 0.38 cm). CONCLUSION: LATG using OrVil™ is a technically feasible surgical procedure with sufficient lymph node dissection, less operation time and acceptable morbidity.

A successful treatment of traumatic bronchobiliary fistula by endoscopic retrograde biliary drainage.

Bronchobiliary fistula (BBF) is a rare condition in which there is a nonnatural communication between the biliary tract and the bronchial trees. It is usually aroused by the complications of hepatic hydatidosis, hepatic amebic, biliary obstruction, trauma, neoplasm and hepatic abscess formation. In this paper, we described a patient suffering from BBF that is secondary to trauma or surgery. Especially, BBF was detected in the left lung. Finally, we managed this case successfully without an open surgery.

Management of acquired bronchobiliary fistula: A systematic literature review of 68 cases published in 30 years.

AIM: To outline the appropriate diagnostic methods and therapeutic options for acquired bronchobiliary fistula (BBF). METHODS: Literature searches were performed in Medline, EMBASE, PHMC and LWW (January 1980-August 2010) using the following keywords: biliobronchial fistula, bronchobiliary fistula, broncho-biliary fistula, biliary-bronchial fistula, tracheobiliary fistula, hepatobronchial fistula, bronchopleural fistula, and biliptysis. Further articles were identified through cross-referencing. RESULTS: Sixty-eight cases were collected and reviewed. BBF secondary to tumors (32.3%, 22/68), including primary tumors (19.1%, 13/68) and hepatic metastases (13.2%, 9/68), shared the largest proportion of all cases. Biliptysis was found in all patients, and other symptoms were respiratory symptoms, such as irritating cough, fever (36/68) and jaundice (20/68). Half of the patients were treated by less-invasive methods such as endoscopic retrograde biliary drainage. Invasive approaches like surgery were used less frequently (41.7%, 28/67). The outcome was good at the end of the follow-up period in 28 cases (range, 2 wk to 72 mo), and the recovery rate was 87.7% (57/65). CONCLUSION: The clinical diagnosis of BBF can be established by sputum analysis. Careful assessment of this condition is needed before therapeutic procedure. Invasive approaches should be considered only when non-invasive methods failed.