Laparoscopic-cholangioscopic cooperative modified tunnel technique for hepatolithiasis combined with dilated common bile duct: A case report and literature review.

INTRODUCTION: Intrahepatic and extrahepatic lithiasis, a condition characterized by the presence of stones in the liver and bile ducts, is a common disease in Asia, particularly in East and Southeast Asia. We report a case with laparoscopic exploration of the common bile duct using a flexible cholangioscope and modified trans-common bile duct tunnel for hepatolithiasis combined with the dilated common bile duct. PRESENTATION OF CASE: A 35-year-old male patient has had chronic epigastric and right upper quadrant pain. The common bile duct was 11 mm dilated, and hepatolithiasis was also present, according to an upper abdomen MRI. The largest stone measured between 14 and 21 mm. A modified trans-common bile duct tunnel from the abdominal wall into the common bile duct was used in a laparoscopic procedure to examine the common bile duct. Complications during the procedure or following it were not present. The procedure took 120 min, and the blood loss was about 50 ml. The patient was discharged on the sixth postoperative day, and a follow-up visit one month later revealed that single-session stone clearance had been accomplished. DISCUSSION: Laparoscopic exploration of the common bile duct using a cholangioscope and modified trans-choledochal tube is applicable in selected patients and can be effectively and safely used to treat hepatolithiasis combined with the dilated common bile duct. CONCLUSION: In this case, we present an innovative approach for hepatolithiasis when combined with dilated common bile duct.

Results from 228 Patients with Hemifacial Spasm Undergoing Microvascular Decompression without Intraoperative Neuroelectrophysiology Monitoring.

BACKGROUND: Intraoperative neuroelectrophysiology monitoring (IONM) has been used to decrease complications and to increase the successful rate of microvascular decompression (MVD) MVD for hemifacial spasm (HFS). Still, it is not available at limited resource centers. We report the outcome of patients undergoing MVD for HFS without using IONM. METHODS: The variables concerning the patients' demographics (age and gender), clinical characteristics, offending vessels (vertebral artery type and non-vertebral artery type), postoperative grade of HFS, and postoperative complications of HFS patients undergoing MVD were retrospectively reviewed and collected. The scoring system provided by the Japan Society for MVD was used to evaluate the postoperative outcome of HFS. Postoperative hearing ability was evaluated according to a subjective assessment of the patients. RESULTS: A total of 228 patients were recruited. Their median age was 51.0 (44.0-57.0) years old. The total cure effect was observed in 207 (90.8%) patients within the first week after the surgery and in 200 (96.1%) patients in a 2-year follow-up. Permanent hearing disturbance happened in 2 patients (0.9%). No patient had permanent unilateral deafness (0%). No postoperative permanent facial paralysis was reported. CONCLUSIONS: MVD without IONM may be performed safely and effectively to treat patients with HFS.

Ancient Schwannoma of the Radial Nerve: A Case Report.

Ancient schwannoma is a very rare subtype of schwannoma. In this report, a case of ancient schwannoma in the upper extremity is reported. A 40-year-old man presented with a slowly growing tumor in the right forearm. He underwent surgery to remove the tumor. Investigation revealed an ancient schwannoma originated from the right radius. Careful preoperative imaging evaluation is important for correct preoperative diagnosis and surgical strategy.

Preliminary results of laparoscopic cholecystectomy using real-time indocyanine green fluorescence: a cross-sectional study.

Evaluating the results of laparoscopic cholecystectomy (LC) using indocyanine green (ICG) fluorescence. Materials and methods: This is a cross-sectional study of patients with LC using real-time fluorescent ICG to treat gallbladder disease from May 2021 to May 2022 in the 108 Military Central Hospital. Results: There were 68 patients who underwent LC using intraoperative ICG fluorescence for bile duct visualization. The mean age of the patients was 55.4±16.2, and the male/female ratio was 1.52. Chronic cholecystitis caused by stones accounted for the majority (51.47%). The authors detected 7.35% of cases with anatomical changes of the extrahepatic biliary tract using ICG fluorescence and clearly identified the anatomy of the common bile duct and the cystic duct at 100 and 92.65%, respectively. The average surgical time was 42.8±14.6 min. There were no postoperative complications or side effects from ICG; the average hospital stay was 2.8±1.5 days. Conclusions: ICG fluorescence cholangiography allows surgeons to easily identify critical anatomical landmarks in the LC. Thereby helping the surgery to be performed safely, avoiding severe complications due to damage to the biliary tract.

Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition.

Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients' responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation.

PD-1 inhibition in patient derived tissue cultures of human gastric and gastroesophageal adenocarcinoma.

Emerging immunotherapies quest for better patient stratification in cancer treatment decisions. Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers urge for meaningful human model systems that allow for investigating immune responses ex vivo. Here, the standardized patient-derived tissue culture (PDTC) model was applied to investigate tumor response to the PD-1 inhibitor Nivolumab and the CD3/CD28 t-lymphocyte activator ImmunoCultTM. Resident t-lymphocytes, tumor proliferation and apoptosis, as well as bulk gene expression data were analyzed after 72 h of PD-1 inhibition either as monotherapy or combined with Oxaliplatin or ImmunoCultTM. Individual responses to PD-1 inhibition were found ex vivo and combination with chemotherapy or t-lymphocyte activation led to enhanced antitumoral effects in PDTCs. T-lymphocyte activation as well as the addition of pre-cultured peripheral blood mononuclear cells improved PDTC for studying t-lymphocyte and tumor cell communication. These data support the potential of PDTC to investigate immunotherapy ex vivo in gastric and esophagogastric junction cancer.

FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo.

Diagnosis in an advanced state is a major hallmark of ovarian cancer and recurrence after first line treatment is common. With upcoming novel therapies, tumor markers that support patient stratification are urgently needed to prevent ineffective therapy. Therefore, the transcription factor FOXM1 is a promising target in ovarian cancer as it is frequently overexpressed and associated with poor prognosis. In this study, fresh tissue specimens of 10 ovarian cancers were collected to investigate tissue cultures in their ability to predict individual treatment susceptibility and to identify the benefit of FOXM1 inhibition. FOXM1 inhibition was induced by thiostrepton (3 µM). Carboplatin (0.2, 2 and 20 µM) and olaparib (10 µM) were applied and tumor susceptibility was analyzed by tumor cell proliferation and apoptosis in immunofluorescence microscopy. Resistance mechanisms were investigated by determining the gene expression of FOXM1 and its targets BRCA1/2 and RAD51. Ovarian cancer tissue was successfully maintained for up to 14 days ex vivo, preserving morphological characteristics of the native specimen. Thiostrepton downregulated FOXM1 expression in tissue culture. Individual responses were observed after combined treatment with carboplatin or olaparib. Thus, we successfully implemented a complex tissue culture model to ovarian cancer and showed potential benefit of combined FOXM1 inhibition.

Ruptured liver abscess presenting as pneumoperitoneum caused by Klebsiella pneumoniae: a case report.

BACKGROUND: Spontaneous gas-forming pyogenic liver abscess (GFPLA) is a rare complication with a high fatality rate in spite of aggressive management. Clinical spectrum of GFPLA can mimic hollow viscus perforation as it usually accompanied by pneumoperitoneum and peritonitis. Up to now, GFPLA has not been well studied in Vietnam. CASE PRESENTATION: We reported here a case with pneumoperitoneum caused by ruptured liver abscess in a 41-year-old man with a history of treated duodenal ulcer and uncontrolled type II diabetes mellitus. He had an epigastric pain associated with a high fever. Patient was diagnosed peritonitis and pneumoperitoneum presumed to be secondary to perforation of a hollow viscus and subjected to emergency laparotomy. We did not find any gastrointestinal perforation. Surprisingly, we detected a 4 cm × 4 cm pus-containing abscess in the left liver lobe of the liver. The abscess was ruptured. Pus was running into abdominal cavity through one hole. The abscess and abdominal cavities were cleaned up and abscess and abdominal drainages were performed. K. pneumoniae was isolated from culture of the abscess. The histopathological examination of the abscess did not yield any evidence of malignancy. Blood glucose levels were controlled. Antibiotic therapy was used according to antibiogram. A reassessment chest X-ray showed no air-fluid level or subdiaphragmatic air by the hospital day 14. Patient eventually made a full recovery and was discharged home 23 days after the operation. CONCLUSIONS: Ruptured GFPLA is a life-threatening complication. It is usually accompanied by peritonitis and pneumoperitoneum and can imitate hollow viscous perforation. In these cases, CT scan should be performed whenever it is possible to make a correct diagnosis. When the abscess has small size, partial hepatectomy might not be necessary and could be replaced by a careful cleaning and drainage of the abscess. Patient could show a good postoperative recovery following an appropriate antibiotic therapy.

Willingness to pay for a quality-adjusted life year among advanced non-small cell lung cancer patients in Viet Nam, 2018.

To examine the willingness to pay (WTP) for a quality-adjusted life year (QALY) gained among advanced non-small cell lung cancer (NSCLC) patients in Viet Nam and to analyze the factors affecting an individual's WTP.A cross-sectional, contingent valuation study was conducted among 400 NSCLC patients across 6 national hospitals in Viet Nam. Self-reported information was recorded from patients regarding their socio-demographic status, EQ-5D (EuroQol-5 dimensions) utility, EQ-5D vas, and WTP for 1 QALY gained. To explore the factors related to the WTP, Gamma Generalized Linear Model and multiple logistic regression tools were applied to analyze data.The overall mean and median of WTP/QALY among the NSCLC patients were USD $11,301 and USD $8002, respectively. Strong association was recorded between WTP/QALY amount and the patient's education, economic status, comorbidity status, and health utility.Government and policymakers should consider providing financial supports to disadvantaged groups to improve their access to life saving cancer treatment.

Selenium-binding protein 1 (SELENBP1) is a marker of mature adipocytes.

Selenium-binding protein 1 (SELENBP1) has recently been reported to catalyse the oxidation of methanethiol, an organosulfur compound produced by gut microbiota. Two of the reaction products of methanethiol oxidation, hydrogen peroxide and hydrogen sulphide, serve as signalling molecules for cell differentiation. Indeed, colonocyte differentiation has been found to be associated with SELENBP1 induction. Here, we show that SELENBP1 is induced when 3T3-L1 preadipocytes undergo terminal differentiation and maturation to adipocytes. SELENBP1 induction succeeded the up-regulation of known marker proteins of white adipocytes and the intracellular accumulation of lipids. Immunofluorescence microscopy revealed predominant cytoplasmic localisation of SELENBP1 in 3T3-L1 adipocytes, as demonstrated by co-staining with the key lipogenic enzyme, acetyl-CoA-carboxylase (ACC), located in cytosol. In differentiating 3T3-L1 cells, the mTOR inhibitor rapamycin and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α) likewise suppressed SELENBP1 induction, adipocyte differentiation and lipid accumulation. However, lipid accumulation per se is not linked to SELENBP1 induction, as hepatic SELENBP1 was down-regulated in high fructose-fed mice despite increased lipogenesis in the liver and development of non-alcoholic fatty liver disease (NAFLD). In conclusion, SELENBP1 is a marker of cell differentiation/maturation rather than being linked to lipogenesis/lipid accumulation.

Differential capability of metabolic substrates to promote hepatocellular lipid accumulation.

PURPOSE: Excessive storage of triacylglycerides (TAGs) in lipid droplets within hepatocytes is a hallmark of non-alcoholic fatty liver disease (NAFLD), one of the most widespread metabolic disorders in Western societies. For the purpose of exploring molecular pathways in NAFLD development and testing potential drug candidates, well-characterised experimental models of ectopic TAG storage in hepatocytes are needed. METHODS: Using an optimised Oil Red O assay, immunoblotting and real-time qRT-PCR, we compared the capability of dietary monosaccharides and fatty acids to promote lipid accumulation in HepG2 human hepatoma cells. RESULTS: Both high glucose and high fructose resulted in intracellular lipid accumulation after 48 h, and this was further augmented (up to twofold, as compared to basal levels) by co-treatment with the lipogenesis-stimulating hormone insulin and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α), respectively. The fatty acids palmitic and oleic acid were even more effective than these carbohydrates, inducing significantly elevated TAG storage already after 24 h of treatment. Highest (about threefold) increases in lipid accumulation were observed upon treatment with oleic acid, alone as well as in combinations with palmitic acid or with high glucose and insulin. Increases in protein levels of a major lipid droplet coat protein, perilipin-2 (PLIN2), mirrored intracellular lipid accumulation following different treatment regimens. CONCLUSIONS: Several treatment regimens of excessive fat and sugar supply promoted lipid accumulation in HepG2 cells, albeit with differences in the extent and rapidity of steatogenesis. PLIN2 is a candidate molecular marker of sustained lipid accumulation in HepG2 cells.

Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of nicotinic acetylcholine receptor.

Azemiopsin, a novel polypeptide, was isolated from the Azemiops feae viper venom by combination of gel filtration and reverse-phase HPLC. Its amino acid sequence (DNWWPKPPHQGPRPPRPRPKP) was determined by means of Edman degradation and mass spectrometry. It consists of 21 residues and, unlike similar venom isolates, does not contain cysteine residues. According to circular dichroism measurements, this peptide adopts a ß-structure. Peptide synthesis was used to verify the determined sequence and to prepare peptide in sufficient amounts to study its biological activity. Azemiopsin efficiently competed with α-bungarotoxin for binding to Torpedo nicotinic acetylcholine receptor (nAChR) (IC(50) 0.18 ± 0.03 µm) and with lower efficiency to human α7 nAChR (IC(50) 22 ± 2 µm). It dose-dependently blocked acetylcholine-induced currents in Xenopus oocytes heterologously expressing human muscle-type nAChR and was more potent against the adult form (α1ß1εδ) than the fetal form (α1ß1γδ), EC(50) being 0.44 ± 0.1 µm and 1.56 ± 0.37 µm, respectively. The peptide had no effect on GABA(A) (α1ß3γ2 or α2ß3γ2) receptors at a concentration up to 100 µm or on 5-HT(3) receptors at a concentration up to 10 µm. Ala scanning showed that amino acid residues at positions 3-6, 8-11, and 13-14 are essential for binding to Torpedo nAChR. In biological activity azemiopsin resembles waglerin, a disulfide-containing peptide from the Tropidechis wagleri venom, shares with it a homologous C-terminal hexapeptide, but is the first natural toxin that blocks nAChRs and does not possess disulfide bridges.