AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity.

BACKGROUND/OBJECTIVES: The incidence of obesity continues to increase worldwide and while the underlying pathogenesis remains largely unknown, nutrient excess, manifested by "Westernization" of the diet and reduced physical activity have been proposed as key contributing factors. Western-style diets, in addition to higher caloric load, are characterized by excess of advanced glycation end products (AGEs), which have been linked to the pathophysiology of obesity and related cardiometabolic disorders. AGEs can be "trapped" in adipose tissue, even in the absence of diabetes, in part due to higher expression of the receptor for AGEs (RAGE) and/or decreased detoxification by the endogenous glyoxalase (GLO) system, where they may promote insulin resistance. It is unknown whether the expression levels of genes linked to the RAGE axis, including AGER (the gene encoding RAGE), Diaphanous 1 (DIAPH1), the cytoplasmic domain binding partner of RAGE that contributes to RAGE signaling, and GLO1 are differentially regulated by the degree of obesity and/or how these relate to inflammatory and adipocyte markers and their metabolic consequences. SUBJECTS/METHODS: We sought to answer this question by analyzing gene expression patterns of markers of the AGE/RAGE/DIAPH1 signaling axis in abdominal subcutaneous (SAT) and omental (OAT) adipose tissue from obese and morbidly obese subjects. RESULTS: In SAT, but not OAT, expression of AGER was significantly correlated with that of DIAPH1 (n = 16; [Formula: see text], [0.260, 1.177]; q = 0.008) and GLO1 (n = 16; [Formula: see text], [0.364, 1.182]; q = 0.004). Furthermore, in SAT, but not OAT, regression analyses revealed that the expression pattern of genes in the AGE/RAGE/DIAPH1 axis is strongly and positively associated with that of inflammatory and adipogenic markers. Remarkably, particularly in SAT, not OAT, the expression of AGER positively and significantly correlated with HOMA-IR (n = 14; [Formula: see text], [0.338, 1.249]; q = 0.018). CONCLUSIONS: These observations suggest associations of the AGE/RAGE/DIAPH1 axis in the immunometabolic pathophysiology of obesity and insulin resistance, driven, at least in part, through expression and activity of this axis in SAT.

Usefulness of Omentoplasty to Reduce Perineal Wound Complications in Abdominoperineal Resection After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Omentoplasty is sometimes used to prevent perineal wound complications after abdominoperineal resection (APR) following neoadjuvant chemoradiotherapy (NACRT). However, recent studies have raised some controversy about its clinical benefit. PATIENTS AND METHODS: Outcomes for rectal cancer patients who received APR after NACRT were retrospectively compared between the groups with omentoplasty (n=28) and without omentoplasty (n=14). RESULTS: The operative time was significantly longer in the omentoplasty group (575 vs. 404 min, p<0.001). Laparoscopic surgery was performed more frequently in the omentoplasty group. Perineal wound problems including dehiscence and infection were significantly reduced in the omentoplasty group (46.4% vs. 78.6%, p<0.001). Univariate and multivariate analyses revealed that omentoplasty was the most important factor in reducing perineal wound complications (odds ratio=0.020, 95% confidence intervaI=0.001-0.393; p=0.001). CONCLUSION: Omentoplasty was useful in reducing perineal wound complications after APR following NACRT.

Collagen-rich omentum is a premetastatic niche for integrin α2-mediated peritoneal metastasis.

The extracellular matrix (ECM) plays critical roles in tumor progression and metastasis. However, the contribution of ECM proteins to early metastatic onset in the peritoneal cavity remains unexplored. Here, we suggest a new route of metastasis through the interaction of integrin alpha 2 (ITGA2) with collagens enriched in the tumor coinciding with poor outcome in patients with ovarian cancer. Using multiple gene-edited cell lines and patient-derived samples, we demonstrate that ITGA2 triggers cancer cell adhesion to collagen, promotes cell migration, anoikis resistance, mesothelial clearance, and peritoneal metastasis in vitro and in vivo. Mechanistically, phosphoproteomics identify an ITGA2-dependent phosphorylation of focal adhesion kinase and mitogen-activated protein kinase pathway leading to enhanced oncogenic properties. Consequently, specific inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion signaling may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.

A case of laparoscopic resection of myxoid liposarcoma of the greater omentum.

Primary omental liposarcoma is a rare clinical entity with less than 20 cases being reported in the literature. Laparotomy has been the traditional approach for resection, with no reports of laparoscopic resection. A 39-year-old lady presented at the Sarawak General Hospital, Kuching, Malaysia with a history of a progressive, painless left upper quadrant abdominal swelling for a year. CT scan showed a well-defined heterogeneously enhancing cystic mass measuring 7.5x7.5x8.1cm with a poor plane with the adjacent greater curvature of stomach and transverse colon. Upper and lower endoscopy was normal. The tumour was completely dissected from the adjacent transverse colon and removed laparoscopically. Histopathological examination of the resected specimen revealed a myxoid liposarcoma. She had an uneventful recovery and was discharged well on the third postoperative day. She subsequently underwent adjuvant chemotherapy and was well at 1-year follow-up with PET CT showing no evidence of recurrence or metastases.

Lesser Omental Panniculitis.

A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum between the liver and stomach. Esophagogastroduodenoscopy revealed a submucosal tumor-like change, and endoscopic ultrasonography (EUS) revealed that the mass was located outside of the stomach wall. We performed EUS fine-needle aspiration and diagnosed panniculitis of the lesser omentum. Based on these findings, we suggest that mass-like lesions in the lesser omentum and submucosal tumor-like changes in the anterior wall on the lesser curvature side of the stomach be evaluated for the possibility of panniculitis of the lesser omentum.

Reducing the occurrence rate of catheter dysfunction in peritoneal dialysis: a single-center experience about CQI.

To reduce the occurrence rate of peritoneal dialysis (PD) catheter dysfunction caused by catheter displacement or plugging, this study screened all patients with peritoneal dialysis catheterization from 2002 to 2015 from the Third Xiangya Hospital of Central South University. There were 256 patients before continuous quality improvement (CQI) (from 2002 to 2007) and 813 patients after CQI (from 2008 to 2015). The occurrence rate of catheter dysfunction was 5.9% in the preCQI group: seven cases were associated with peritonitis, six cases were involved in omentum wrapping, one case was blocked by oviduct, and one case was blocked by blood clot. Through PDCA (plan-do-check-act) four-step of CQI, the following measures were adopted: (1) Preoperative: treat complications, enema and urine catheterization (2) Intraoperative: strengthen analgesia, Lower the insert position of catheter to 7.5 ∼ 8.5 cm above the pubic symphysis, extending the straight distance of catheter in rectus abdominis and decrease the times of peritoneal dialysis catheter implantation. (3) Postoperative: strengthen the training of nurses, patients and their families. (4) strengthen anticoagulation therapy during peritonitis treatment. (5) use laparoscopic technology for refractory patients, and so on. The occurrence of catheter dysfunction was 1.5% in the postCQI group (p < 0.05): two cases were associated with peritonitis, ten cases were involved in omentum wrapping. The measures we adopted in CQI reduce the occurrence rate of catheter displacement or plugging in peritoneal dialysis.

A method for voltage measurements of cancerous vs non-cancerous omentum.

This paper presents and elaborates upon the practicalities of a method which enables the recording of voltage measurements from omental tissue in patients with advanced ovarian cancer. The key components of the proposed low-cost experimental setup are a tungsten electrode, a Ag/AgCl reference electrode and an instrumentation amplifier. Intriguingly, potential difference recordings between cancerous omentum and tissue culture media and between non-cancerous omentum and media, differ for tissue samples coming from the same patient. Further studies are warranted to assess the potential prognostic value of voltage measurements in cancerous tissue.

Primary omental pregnancy with secondary implantation into posterior cul-de-sac: laparoscopic treatment using hemostatic matrix.

Primary omental pregnancy is a rare form of ectopic pregnancy. Only a few reported cases have been treated using laparoscopy. Hemostasis after trophoblast removal can be challenging. A 25-year-old primigravida in week 8 of pregnancy was admitted to our hospital with a diagnosis of missed abortion. An ultrasound scan showed an empty uterine cavity and a gestational sac with a 15-mm embryo dorsal to the uterus, indicative of an ectopic pregnancy. The preoperative serum concentration of human chorionic gonadotropin was 33 600 U/mL. Laparoscopy was performed, which revealed an omental pregnancy invading the peritoneum of the Douglas pouch. After laparoscopic removal of the ectopic pregnancy with partial omentectomy, diffuse bleeding from the crater between both sacrouterine ligaments was treated using the gelatin-thrombin matrix (FloSeal). The final histologic analysis confirmed the omentum as the primary site of the ectopic pregnancy (multiple chorionic villi and decidua within the omental fat). The postoperative period was uneventful. This case expands the classic Studdiford criteria. Secondary peritoneal ectopic pregnancy implantation can occur not only after tubal rupture or expulsion of tubal ectopic pregnancy but also after primary implantation at any other ectopic site. The laparoscopic approach to abdominal pregnancy is safe and feasible if there is sufficient intraoperative hemostasis. The hemostatic matrix facilitates quick and effective control of bleeding.

Omental torsion, a rare cause of acute surgical abdomen.

Torsion of the greater omentum is a rare cause of acute abdominal pain. The symptoms of this pathology are non-specific and abdominal CT is usually necessary to make the diagnosis. Treatment is surgical and can often be performed laparoscopically.

Ulcus péptico perforado: revisión de 102 casos en el Hospital Dr. "Domingo Luciani" / Perforated peptic ulcer: a review of 102 cases at the Hospital Dr. Domingo Luciani

Determinar los aspectos epidemiológicos y el tratamiento quirúrgico en los pacientes con ulcus péptico perforado atendidos en el Departamento de Cirugía General del Hospital Domingo Luciani. IVSS, Caracas. Estudio retrospectivo, transversal, descriptivo y observacional, realizado en el período correspondiente de julio de 1989 a julio de 2007, mediante la revisión de historias clínicas de pacientes intervenidos quirúrgicamente por ulcus péptico perforado. Un total de 102 pacientes fueron intervenidos por ulcus péptico perforado, en su mayoría hombres (90 por ciento), con edad promedio de 40 años. El principal síntoma fue el dolor. Los pacientes acudieron en las primeras 24 horas del inicio de los síntomas. Los antecedentes más importantes fueron el hábito tabáquico y alcohólico (62 por ciento y 56 por ciento). La localización más frecuente de la úlcera fue prepilórica (64 por ciento). La técnica de reparación quirúrgica más empleada fue la rafia de la úlcera más parche de epiplón (44 por ciento). La morbilidad fue de 27.5 por ciento y la mortalidad de 5 por ciento. El ulcus péptico perforado se presenta con mayor frecuencia en hombres fumadores. La raparación quirúrgica con rafia y parche de epiplón es segura.

Laparoscopic diagnosis and treatment of primary torsion of the greater omentum.

Clinical presentation of primary torsion of the greater omentum is nonspecific, thus rarely allowing for a preoperative diagnosis. Three patients presented with acute but nonspecific abdominal symptoms. Because ultrasonographic and radiologic findings were unclear, all patients underwent diagnostic laparoscopy. In all cases, laparoscopy enabled us to achieve the diagnosis and to perform a resection of necrotic omentum. The mean duration of the procedure was 56 minutes (range: 42 to 76). The postoperative course was uneventful and the patients were discharged on postoperative day 1 (2) and 3. The value of diagnostic laparoscopy increases when the disease can be treated laparoscopically. The laparoscopic vision allowed us to explore the whole peritoneal cavity, so achieving the diagnosis, and to place the operative trocars at the most convenient sites. The laparoscopic resection of the greater omentum is an easy task even for inexperienced laparoscopic surgeons, allowing patients to benefit from the advantages of a mini-invasive approach.

Possible role of milky spots in mesothelial transplantation.

Milky spots are very small omental organs, in contact with peritoneal membrane, devoid of capsule and consisting of macrophages, lymphocytes and a few plasma cells supported by blood and lymphatic vessels. The exact role of these particular organs is still not clear, but they are similar to lymphatic structures and it is clear that they play a role in peritoneal infection and abdominal tumors. Peritoneal dialysis seems to activate the milky spots changing their morphology. The authors try to formulate some hypotheses on the role played by these little omental organs during autologous mesothelial transplant.

Novel role for mast cells in omental tissue remodeling and cell recruitment in experimental peritoneal dialysis.

Because of its dynamic structure, the omentum plays a key role in the immunity of the peritoneal cavity by orchestrating peritoneal cell recruitment. Because mast cells accumulate in the omentum upon experimental peritoneal dialysis (PD) and may produce angiogenic/profibrotic factors, it was hypothesized that mast cells mediate omental tissue remodeling during PD. Daily treatment with conventional PD fluid (PDF) for 5 wk resulted in a strong omental remodeling response, characterized by an approximately 10-fold increase in mast cell density (P < 0.01), an approximately 20-fold increase in vessel density (P < 0.02), an approximately 20-fold increase in the number of milky spots (P < 0.01), and a four-fold increase in submesothelial matrix thickness (P < 0.0003) in wild-type rats. In contrast, all PDF-induced omental changes were significantly reduced in mast cell-deficient Ws/Ws rats or in wild-type rats that were treated orally with a mast cell stabilizer cromoglycate. A time-course experiment showed mast cell accumulation immediately before the formation of blood vessels and milky spots. Functionally, PDF evoked a peritoneal cell influx, which was significantly reduced in Ws/Ws rats (P < 0.04) and in wild-type rats that were treated with cromoglycate (P < 0.03). Cromoglycate treatment also completely prevented PDF-induced omental adhesions to the catheter tip (P = 0.0002). Mesothelial damage, angiogenesis, and fibrosis of mesentery and parietal peritoneum as well as glucose absorption rate and ultrafiltration capacity proved to be mast cell independent. Data strongly support the hypothesis that mast cells mediate PDF-induced omental tissue remodeling and, subsequently, peritoneal cell influx and adhesion formation, providing therapeutic possibilities of modulating omental function.

Complicated umbilical hernia in childhood.

Umbilical hernias occur frequently in children but complications are rarely reported. This study assessed the incidence of complicated umbilical hernias in our patients, evaluated data for risk factors and reviewed our management in the light of these findings. We conducted a prospective study of all children needing umbilical hernia repair for complications over a period of 15 years. Patients with para-umbilical and other ventral wall hernias were excluded. In total, 389 children had umbilical hernias repaired during this period (average age 6 years); 28 (7%) of these had complicated hernias. Symptoms included umbilical pain (100%), vomiting (71%) and constipation (28%). The average age of the complicated group was 3 years. All cases had a painful irreducible umbilical mass. Eleven of the 19 children who had an abdominal radiograph showed radiological evidence of small-bowel obstruction and in 5 children there was radiological evidence of pica. Two patients had ischaemic omentum that required resection. Patients who present with localised abdominal pain or an irreducible umbilical mass should be operated on promptly.

Omental milky spots and peritoneal dialysis--review and personal experience.

BACKGROUND: Little research has been dedicated to milky spots (MS), except for their role in oncology. In the field of peritoneal dialysis (PD), studying MS could help in understanding peritoneal defenses. METHODS: We reviewed the methods for detecting and counting omental MS and studied modifications induced by chemical and inflammatory stimuli. The reactions of MS to peritoneal catheters, PD solutions, and infection were studied in 32 rabbits. We also evaluated changes in MS in 39 serial omental biopsies from 16 patients with different histories of PD, and examined peritoneal biopsies from 38 patients with sclerosing peritonitis. RESULTS: The catheter provoked an immediate increase in the number and size of MS in rabbits. Intraperitoneal infusion of commercial PD solution containing 1.38% or 3.86% glucose for 30 days led to a slight but significant increase in the number and size of MS, without differences between the two glucose concentrations. Peritonitis caused a sharp increase in the number of MS in rabbits and humans, and a particular transformation. In patients with simple sclerosis, we observed normal MS having the same number and size as in patients without simple sclerosis. A few MS were found in only 2 patients with sclerosing peritonitis. CONCLUSIONS: Peritoneal dialysis activates omental MS. Peritoneal infection leads to a marked increase in the activity of MS, some of which undergo a singular transformation, casting doubt on previous theories about differentiation of MS from other lymphatic organs. Comparison with oncological studies indicates certain contact points. The presence of MS in PD patients with simple sclerosis is in contradiction to other morphological studies sustaining that MS act only when in contact with a fenestrated mesothelial basement membrane. Finally, the shortage of MS in patients with sclerosing peritonitis raises certain questions about etiopathogenesis.

Laparoscopic management of an internal double omental hernia: a rare cause of intestinal obstruction.

INTRODUCTION: Internal hernia is a very rare cause of intestinal obstruction (0.2-0.9% of cases), associated with 45% mortality. A review of the literature revealed just eight reported cases of double omental hernia since 1950 of which our patient is the first case successfully treated laparoscopically. CASE PRESENTATION: We report on a 29-year-old man who presented with signs and symptoms of intestinal obstruction. The patient underwent emergent exploratory laparoscopy. This revealed herniation of a 20-cm jejunal loop through the gastrocolic ligament and reemergence through a defect in the gastrohepatic ligament. The strangulated loop was reduced with slight traction, and the defect was repaired. The patient was discharged from hospital in just 5 days' time, and after 6 months of follow-up, the general condition of the patient was normal. CONCLUSIONS: Laparoscopy is a good technique with minimal complications compared with laparotomy. As many cases are missed due to nonspecific signs and symptoms, an urgent laparoscopy or laparotomy is highly recommended in such a situation.

Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells.

BACKGROUND: Menstrual effluent affects mesothelial cell (MC) morphology. We evaluated whether these changes were consistent with epithelial-mesenchymal transitions (EMT). METHODS: Monolayer cultures of MC were incubated overnight in conditioned media, prepared from cells isolated form menstrual effluent, with or without kinase and ATP inhibitors. Changes in cell morphology were monitored using time-lapse video microscopy and immunohistochemistry. Effects on the expression of EMT-associated molecules were evaluated using real-time RT-PCR and/or Western blot analysis. RESULTS: Incubation in conditioned media disrupted cell-cell contacts, and increased MC motility. The changes were reversible. During the changes the distribution of cytokeratins, fibrillar actin and alpha-tubulin changed. Sodium azide, an inhibitor of ATP production, and Genistein, a general tyrosine kinase inhibitor, antagonized these effects. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, and SU6656, an Src tyrosine kinase inhibitor, only partially antagonized the effect. The expression of Snail and vimentin was markedly up-regulated, whereas the expression of E-cadherin was decreased and cytokeratins were altered. CONCLUSIONS: In MC, menstrual effluent initiates a reversible, energy-dependent transition process from an epithelial to a mesenchymal phenotype. Involvement of the (Src) tyrosine kinase signalling pathway and the changes in the expression of cytokeratins, Snail, vimentin and E-cadherin demonstrate that the morphological changes are EMT.

In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.

Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.