Plasma Metabolomic and Lipidomic Profiling of Metabolic Dysfunction-Associated Fatty Liver Disease in Humans Using an Untargeted Multiplatform Approach.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies.

Modulatory Effect of Silymarin on Apoptosis in Testosterone -Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is considered a normal part of the aging process in men, and is characterized by an imbalance between cell proliferation and apoptosis. Our study aimed to investigate the potential protective role of silymarin (SIL) against testosterone-induced BPH in rats and to elucidate the molecular mechanisms underlying SIL pro-apoptotic and anti-proliferative effects. Forty adult male Wistar rats were divided equally into four groups: control group, BPH group (3 mg/kg testosterone propionate, s.c. for 14 days, SIL group (50 mg/kg SIL, orally, once daily concomitantly with 3 mg/kg testosterone propionate s.c.) and inhibitor group (50 mg/kg SIL orally concomitantly with 3 mg/kg testosterone, s.c. and 0.5 mg/rat Z-VAD-FMK, i.p.). Silymarin induced caspase-dependent apoptosis in BPH as SIL significantly reduced prostatic Bcl-2 protein and increased Bax protein concentration. Also, SIL down-regulated survivin (Inhibitor of apoptosis protein (IAPs) gene expression in rat prostate assisting mainly caspase-dependent pathway. Silymarin significantly decreased cytochrome-c cytosolic concentration and increased caspase 3 activity compared to BPH group. Silymarin significantly increased the content of p27/kip1 (Cyclin dependent kinase inhibitor (CDKIs) promoting cell cycle arrest. The histological features of BPH such as hypertrophy, papillary projections formation, improved in SIL group. Silymarin showed a significant anti-proliferative and pro-apoptotic role in BPH and accordingly it could be effectively and safely used as a treatment tool in cases of BPH or prostatic disorders.

Timing of laparoscopic elective surgery for acute left colonic diverticulitis. Retrospective analysis of 332 patients.

PURPOSE: The optimal time to perform elective surgery remains to be determined. We analyzed the impact of time interval to surgery on short-terme outcome parameters in patients undergoing elective laparoscopic left colonic resection for diverticulitis. MATERIALS AND METHODS: Retrospective analysis of two series of case-matched patients according to the timing of operation after the last episode of diverticulitis: group A (within 90 days) and group B (beyond 90 days). RESULTS: 332 patients had left colonic resection for diverticulitis. 117 patients were included in group A vs 114 patients in group B. Overall abdominal morbidity in Group A was 21% vs 5% in group B (p = 0.02). Mean hospital stay was 7.7 days in group A vs 5 days in group B (p = 0.08). Residual inflammation was significantly increased in group A (31%) as compared to group B (11%) (p = 0.01). CONCLUSIONS: Laparoscopic left colonic resection for acute diverticulitis is best performed beyond the third month after the last acute episode.

Two stages conversion of failed laparoscopic adjustable gastric banding to laparoscopic roux-en-y gastric bypass. A study of one hundred patients.

INTRODUCTION: Conversion to laparoscopic gastric bypass (LRYGB) appears to be the treatment of choice after failed LAGB. To reduce the risk of postoperative complications, some surgeons routinely adopt a two-stage strategy. The purpose of this study was to analyze our institution's experience with the two-stage procedure for LAGB conversion to LRYGB MATERIALS AND METHODS: The bariatric database of our institution was reviewed to identify patients who had undergone conversion of LAGB to LRYGB from November 2007 to June 2012. RESULTS: One hundred patients were included. Of these, 62 (62%) required conversion to LRYGB for inadequate weight loss or weight regain and 38 for band-related complications. All the procedures were performed in two stages and laparoscopically. The average time between band removal and LRYGB was 17.3 months. The mean follow-up after LRYGB was 31 ± 18.7 months. The mean BMI prior to LRYGB conversion was 45.3 ± 5.2. Early complications occurred in 15 patients (15%), while late complications occurred in only 3 patients (3%). The average %EWL at 24 months and 48 months after conversion was 70.1 and 69.4%, respectively. CONCLUSION: Although a two-stage conversion strategy increases the number of operations and hospital stay without decreasing the rate of early complications compared to one-stage conversion; it has shown to be associated with low rates of GJA stenosis and excellent %EWL.

Oxidation of hydrogen sulfide by human liver mitochondria.

Hydrogen sulfide (H2S) is the third gasotransmitter discovered. Sulfide shares with the two others (NO and CO) the same inhibiting properties towards mitochondrial respiration. However, in contrast with NO or CO, sulfide at concentrations lower than the toxic (µM) level is an hydrogen donor and a substrate for mitochondrial respiration. This is due to the activity of a sulfide quinone reductase found in a large majority of mitochondria. An ongoing study of the metabolic state of liver in obese patients allowed us to evaluate the sulfide oxidation capacity with twelve preparations of human liver mitochondria. The results indicate relatively high rates of sulfide oxidation with a large variability between individuals. These observations made with isolated mitochondria appear in agreement with the main characteristics of sulfide oxidation as established before with the help of cellular models.

Retromuscular mesh repair of midline incisional hernia with polyester standard mesh: monocentric experience of 261 consecutive patients with a 5-year follow-up.

BACKGROUND: Midline incisional hernia (MIH) repair remains a major challenge for surgeons. Multiple procedures and types of mesh to treat incisional hernia are available. We evaluated outcomes of MIH treated by retromuscular mesh repair (RMR) using a polyester standard prosthesis. PATIENTS: A total of 262 patients were treated for MIH by RMR between June 2000 and November 2007 in an academic tertiary referral center using the same standardized surgical technique and one type of mesh. The early complications and recurrence rate were evaluated. RESULTS: The average patient age was 57 years; 51% were women. The mean width was 7.8 cm and defect size was 61 cm². Previous MIH repair had been performed in 23% of the patients. Average hospital stay was 7 days. Of the 262 patients studied, 34 patients (13%) developed early complications, and 16 required reoperation for various indications. Early mesh infection occurred in 2 patients (0.8%) requiring mesh removal. The mean follow-up was 58 months. Recurrence was observed in 8 patients (3%) with an average delay of 19 months. There was a significant difference in terms of recurrence in patients with mesh infection versus the group who did not develop infection (2/2 patients versus 6/259; P < 0.001). CONCLUSIONS: Our results suggest that RMR with a polyester standard prosthesis for MIH remains a safe "classic" treatment with a moderate complication rate and a low infection and recurrence rate, even in large incisional hernia.

Single-incision laparoscopic appendectomy for acute appendicitis: a preliminary experience.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is a major conceptual change in the field of modern surgery. However, corresponding technological refinements are not yet available to fill the gap separating the current laparoscopy from the NOTES of the future. Meanwhile, "hybrid" NOTES techniques, including single-port procedures, have been increasingly reported. This report describes a technique of single-incision laparoscopic appendectomy (SILA) for selected patients with acute appendicitis. METHODS: Patients with noncomplicated acute appendicitis, excluding those with abscess, perforation, peritonitis, previous surgery, or obesity, underwent SILA. The procedure was performed using a single 15-mm-diameter umbilical incision with two 5-mm-diameter port sites. RESULTS: The study enrolled 36 women and 19 men with a mean age of 28 years (range, 18-78 years). The procedure was achieved for 41 patients (74.5%). The mean operative time was 39 min (range, 14-111 min). There was no mortality. The postoperative complication rate was 5.4% (3 complications in 3 patients), and the median hospital stay was 39 h (range, 8-240 h). CONCLUSION: The SILA technique is safe and feasible for selected patients with noncomplicated acute appendicitis. Compared with other transumbilical techniques of appendectomy, SILA has the advantages of feasibility without endoscopic skills and an acceptable operative time. Technical refinements and accomplished learning probably will enable its wider use for more patients with acute appendicitis.

First description of the surgical anatomy of the cynomolgus monkey liver.

No detailed description of nonhuman primate liver anatomy has been reported and little is known about the similarity between such livers and human liver. The cynomolgus monkey (Macaca fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto transplantation. Here, we report information gleaned from careful observation and notes obtained from 59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical liver dissections after total resection at autopsy were performed and served to confirm peroperative observations and for photography to provide illustrations. Our results indicate that the cynomolgus monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes. In 60% (N=20) of individuals the portal bifurcates into right and left portal veins, in the remaining 40% (N=14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments. Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of any small or large nonprimate mammals that have been described.

Staged laparoscopic adjuvant intraperitoneal chemohyperthermia after complete resection for locally advanced colorectal or gastric cancer: a preliminary experience.

BACKGROUND: Cytoreductive surgery followed by intraperitoneal chemohyperthermia (IPCH) is a promising treatment for patients with peritoneal carcinomatosis, a disease with dismal prognosis. METHODS: We describe our preliminary experience with staged adjuvant laparoscopic IPCH after complete resection in patients with locally or regionally advanced colorectal or gastric cancer. RESULTS: Twenty-one patients underwent resection for colorectal (N = 16) or gastric cancer (N = 5) followed by staged laparoscopic IPCH. No conversion to laparotomy was required. No major operative incident occurred. Mean duration of hospital stay was 12 days (range 9-23 days). No mortality occurred in the 30-day postoperative period. Four patients developed major complications (19%). One patient (5%) was reoperated. Mean follow-up period was 15.5 months (range 9-29 months). Three patients died, including two of cancer-related causes. No patient developed peritoneal carcinomatosis during the follow-up period. CONCLUSION: Staged laparoscopic adjuvant IPCH after open or laparoscopic resection in selected patients with colorectal or gastric cancer is feasible and reasonably safe. However, additional data are required to determine the effect on long-term survival.