The outcome of local excision of large rectal polyps by transanal endoscopic microsurgery.

Introduction: Local excision of large rectal polyps can be an alternative for radical rectal resection with total mesorectal excision. We aim to report the functional and oncological outcomes of transanal endoscopic microsurgery (TEM) for patients with large rectal polyps. Methods: All demographic and clinical data of patients who underwent TEM for rectal polyp of 5 cm or more at the Hasharon Hospital from 2005 to 2018 were retrospectively reviewed. Results: Twenty-eight patients were included. The mean age was 66 years. The mean polyp size was 6.2 cm (range: 5-8.5 cm) with a mean distance of 8.3 cm from the anal verge. Peritoneal entry during TEM was observed in five patients and additional laparoscopy after the completion of the TEM was performed in four patients. There were no major perioperative complications. Seven patients had minor complications. Final pathology revealed T1 carcinoma in five patients and T2 carcinoma in three patients. Re-TEM was performed in one patient with involved margins with adenoma. After a median follow-up of 64 months, one patient had local recurrence. Conclusion: TEM is an acceptable technique for the treatment of large polyps with minor complications and a reasonable recurrence rate. TEM may be considered regardless of the size of the rectal polyp.

A Comparison of One- and Two-Stage Laparoscopic Sleeve Gastrectomy Following Failed Laparoscopic Adjustable Gastric Banding Using the BAROS Score.

INTRODUCTION: Revision of a failed band can be done by laparoscopic sleeve gastrectomy (LSG). It can be performed synchronously with band removal or during two separate procedures. AIM: Comparing single- and two-staged LSG following a failed LAGB in terms of short- and mid-term outcomes, with an emphasis on postoperative quality of life. METHODS: A retrospective cohort study comparing revisional LSG's safety and efficacy after failed LAGB removal. Data included patients' medical files, as telephone interviews. We compared demographics, weight loss, complications, long-term outcomes, and quality-of-life measures, including the Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: Ninety-three patients were enrolled, of which 68 (73.1%) underwent a single-stage revisional LSG. Of these, 40 were males (35.1%) with a mean age of 44.9 years (± 12.9). The two-staged group were older. The reasons for band removal differed between the groups: whereas in the two-stage surgery, the common causes were slippage (29.2%) or band intolerance (25%); in the single-stage group, it was weight gain (51%). There were no differences in short- and mid-term complications, weight loss, and quality of life. CONCLUSION: In selected cases, laparoscopic sleeve gastrectomy as a revision of failed gastric banding in one stage is as safe as a two-stage procedure in terms of short- and mid-term complications, weight loss, and quality of life. We believe that there is little benefit in performing elective surgery in two stages unless there are clinical indications. Exceptions for two-stage revision should include cases of band erosion and acute slippage with patient preference for band removal.

Circulating Cell-free DNA in Patients With Acute Biliary Pancreatitis: Association With Disease Markers and Prolonged Hospitalization Time-A Prospective Cohort Study.

OBJECTIVE: To evaluate cfDNA as an indicator of pancreatitis severity. BACKGROUND: Acute pancreatitis severity scores have limited proficiency, and are complex and challenging to use clinically. Elevation of circulating cfDNA concentration has been shown to be associated with hospital length of stay (LOS) and mortality. METHODS: In a prospective study, cfDNA concentration was measured by a simple fluorometric test, at admission and for 2 consecutive days, in patients with acute biliary pancreatitis (ABP). Ranson and APACHE II scores were used as measures of pancreatitis severity. Hospital LOS and mortality were used as outcome measures. RESULTS: Seventy-eight patients were included. Patients with severe disease according to Ranson's Criteria (n = 24) had elevated median admission cfDNA compared to patients with mild disease (n = 54, 2252ng/ml vs 1228 ng/ml, P < 0.05 ). Admission cfDNA levels correlated with Ranson and APACHE II scores and markers of bile duct obstruction. LOS did not differ between patients with mild and severe disease according to Ranson and APACHE II scores. Patients with cfDNA at 24 hours concentrations above the cutoff value of healthy patients (>850 ng/ml) had a significantly longer LOS compared to those with normal cfDNA levels ( P < 0.001 ). CONCLUSIONS: cfDNA, measured by a rapid simple assay, proved a valuable early marker of severity in ABP with clear advantages for prediction of LOS over Ranson and APACHE II. Measurement of cfDNA has the potential to be an effective practical approach to predict the course of ABP and should be further evaluated in larger trials.

STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery.

INTRODUCTION: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. METHODS: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. RESULTS: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. CONCLUSION: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

Human adipose tissue is a putative direct target of daytime orexin with favorable metabolic effects: A cross-sectional study.

OBJECTIVE: Orexin/hypocretin (Ox) and its receptors (OxR), a neuroendocrine system centrally regulating sleep/wakefulness, were implicated in the regulation of peripheral metabolism. It was hypothesized that human adipose tissue constitutes a direct target of the OxA/OxR system that associates with distinct metabolic profile(s). METHODS: Serum Ox levels and abdominal subcutaneous and visceral adipose tissue expression of Ox/HCRT, OxR1/HCRTR1, and OxR2/HCRTR2 were measured in n = 81 patients. RESULTS: Higher morning circulating Ox levels were associated with improved lipid profile and insulin sensitivity, independently of BMI (ß = -0.363, p = 0.018 for BMI-adjusted homeostatic model of insulin resistance). Adipose HCRT mRNA was detectable in <20% of patients. Visceral HCRT expressers were mostly (80%) males and, compared with nonexpressers, had lower total and LDL cholesterol. HCRTR1 was readily detectable, and HCRTR2 was undetectable. HCRTR1 mRNA and OxR1 protein expression were higher in subcutaneous than visceral adipose tissue, and among nonobese patients, patients with obesity, and patients with obesity and T2DM were 3.4 (1.0), 0.7 (0.1), 0.6 (0.1) (AU) (p < 0.001) and 1.0 (0.2), 0.5 (0.1), 0.4 (0.1) (AU) (p = NS), respectively. Higher visceral HCRTR1 expression was associated with lower fasting insulin and homeostatic model of insulin resistance, also after adjusting for BMI. In human adipocytes, HCRTR1 expression did not exhibit significant oscillation. CONCLUSIONS: Human adipose tissue is a putative direct target of the OxA-OxR1 system, with higher morning input being associated with improved metabolic profile.

Laparoscopic Sleeve Gastrectomy Following Failed Laparoscopic Adjustable Gastric Banding-a Comparison Between One- and two-Stage Procedures, an Israeli National Database Study.

PURPOSE: The optimal revisional bariatric surgery procedure following a previous failed gastric band surgery is yet to be determined. The aim of our study was to compare single- and two-stage laparoscopic sleeve gastrectomy (LSG) following laparoscopic adjustable gastric banding (LAGB) in terms of short- and mid-term outcomes. MATERIALS AND METHODS: Patients who underwent LSG after a failed LAGB in Israel during 2014-2017 were included. Data were obtained from the Israeli National Bariatric Surgery Registry. Data analyzed included comorbidities, postoperative complications, and anthropometric outcomes. RESULTS: Of 595 patients included in the data analysis, 381 (64%) underwent one-stage and 214 (36%) had two-stage LSG. No differences were observed between the groups in complication rates (5.0 vs. 5.1%, p=0.93). Percent of total weight loss was lower following one-stage than two-stage procedure at both 6 months (19.3±9.3 vs. 21.5±8.1%; p=0.02) and 1 year postoperative (24.9±10.4 vs. 27.8±9.9%; p=0.02). No difference was observed in the percent excess weight loss (51 vs. 56%; p=0.34 and 66 vs. 72%; p=0.38, at 6 months and 12 months postoperative, respectively). In a regression analysis, percent excess weight loss was greater in the two-stage procedure (p=0.02), with no difference in the complication rates (p=0.98). CONCLUSION: Single-step LSG had a similar safety profile as two-stage LSG following a failed LAGB. Better weight loss was seen following two-stage LSG. Further prospective studies should investigate long-term follow-up after one- and two-stage procedure.

A TRAIL-TL1A Paracrine Network Involving Adipocytes, Macrophages, and Lymphocytes Induces Adipose Tissue Dysfunction Downstream of E2F1 in Human Obesity.

Elevated expression of E2F1 in adipocyte fraction of human visceral adipose tissue (hVAT) associates with a poor cardiometabolic profile. We hypothesized that beyond directly activating autophagy and MAP3K5 (ASK)-MAP kinase signaling, E2F1 governs a distinct transcriptome that contributes to adipose tissue and metabolic dysfunction in obesity. We performed RNA sequencing of hVAT samples from age-, sex-, and BMI-matched patients, all obese, whose visceral E2F1 protein expression was either high (E2F1high) or low (E2F1low). Tumor necrosis factor superfamily (TNFSF) members, including TRAIL (TNFSF10), TL1A (TNFSF15), and their receptors, were enriched in E2F1high While TRAIL was equally expressed in adipocytes and stromal vascular fraction (SVF), TL1A was mainly expressed in SVF, and TRAIL-induced TL1A was attributed to CD4+ and CD8+ subclasses of hVAT T cells. In human adipocytes, TL1A enhanced basal and impaired insulin-inhibitable lipolysis and altered adipokine secretion, and in human macrophages it induced foam cell biogenesis and M1 polarization. Two independent human cohorts confirmed associations between TL1A and TRAIL expression in hVAT and higher leptin and IL6 serum concentrations, diabetes status, and hVAT-macrophage lipid content. Jointly, we propose an intra-adipose tissue E2F1-associated TNFSF paracrine loop engaging lymphocytes, macrophages, and adipocytes, ultimately contributing to adipose tissue dysfunction in obesity.

Higher Mast Cell Accumulation in Human Adipose Tissues Defines Clinically Favorable Obesity Sub-Phenotypes.

The identification of human obesity sub-types may improve the clinical management of patients with obesity and uncover previously unrecognized obesity mechanisms. Here, we hypothesized that adipose tissue (AT) mast cells (MC) estimation could be a mark for human obesity sub-phenotyping beyond current clinical-based stratifications, both cross-sectionally and prospectively. We estimated MC accumulation using immunohistochemistry and gene expression in abdominal visceral AT (VAT) and subcutaneous (SAT) in a human cohort of 65 persons with obesity who underwent elective abdominal (mainly bariatric) surgery, and we validated key results in two clinically similar, independent cohorts (n = 33, n = 56). AT-MC were readily detectable by immunostaining for either c-kit or tryptase and by assessing the gene expression of KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase), TPSB2 (tryptase beta 2), and CMA1 (chymase 1). Participants were characterized as VAT-MClow if the expression of both CMA1 and TPSB2 was below the median. Higher expressers of MC genes (MChigh) were metabolically healthier (lower fasting glucose and glycated hemoglobin, with higher pancreatic beta cell reserve (HOMA-ß), and lower triglycerides and alkaline-phosphatase) than people with low expression (MClow). Prospectively, higher MC accumulation in VAT or SAT obtained during surgery predicted greater postoperative weight-loss response to bariatric surgery. Jointly, high AT-MC accumulation may be used to clinically define obesity sub-phenotypes, which are associated with a "healthier" cardiometabolic risk profile and a better weight-loss response to bariatric surgery.

The Clinical Outcome of Postoperative Invasive Fungal Infections Complicating Laparoscopic Sleeve Gastrectomy.

PURPOSE: Peritonitis is a major complication of bariatric surgery due to direct damage to the natural barriers to infection. Most such secondary peritoneal infections are caused by Gram-negative microorganisms; however, under certain conditions, Candida species can infect the peritoneal cavity following bariatric surgery. MATERIALS AND METHODS: We retrospectively analyzed the clinical and microbiological data of morbidly obese patients who suffered infectious complications following laparoscopic sleeve gastrectomy (LSG) at the Soroka Medical Center between January 2010 and June 2015. RESULTS: Out of 800 patients who underwent LSG, 43 (5.3%( developed secondary peritonitis and were admitted to our General Intensive Care Unit during the study period. Intraperitoneal leaks, intraabdominal abscesses and pleural effusions were significantly more common in patients with fungal infection than in those with non-fungal infections (p values 0.027, < 0.001, and < 0.014, respectively). Leaks situated at the suture line of gastro-esophageal area occurred much more frequently in the fungal infection group than in the non-fungal infection group (94.7 vs 41.7%, p < 0.001). Microbiological analysis of the abdominal and pleural fluids of patients with invasive fungal infectious complications showed the presence of commensal polymicrobial bacterial infections-mainly Streptoccocus constellatus and coagulase negative Staphylococcus spp. Leakage at the suture line of gastro-esophageal area (upper suture part) and administration of parenteral nutrition were found to be independent predictors for invasive fungal infections after LSG. CONCLUSION: Our study demonstrates that invasive fungal infection is a significant postoperative infectious complication of bariatric LSG surgery in morbidly obese patients.

Single Port and Conventional Laparoscopy in Colorectal Surgery: Comparison of Two Techniques.

BACKGROUND: Single-incision laparoscopic surgery (SILS) was introduced to further the enhanced outcome of conventional multiport laparoscopy (CML). We compared their short- and long-term outcomes in colorectal surgery. MATERIALS AND METHODS: Retrospective review of patients who underwent elective laparoscopic colorectal surgery during 3-year period. Patients' data, surgery outcomes, and oncological results were compared. RESULTS: Sixty-one patients (33 male, 28 female), mean age 67.4 years, underwent laparoscopic colonic resections: 28 SILS and 33 CML. Twenty-three (37.7%) patients had previous abdominal surgery. There were 19 (31.2%) right, 9 (14.7%) left, and 2 (3.3%) total colectomies, 16 (26.2%) sigmoidectomies, 13 (21.3%) anterior and 2 (3.3%) abdominoperineal resections. Colonic malignancy was a main indication for the surgery in 51 (83.6%) patients. Mean surgery time and postoperative stay were 92.0 minutes and 9 days, respectively. Pathological examination revealed stage I colon cancer in 16 (32%), stage II in 22 (44%), stage III in 10 (20%), and stage IV in 2 (4%) patients. Mean number of retrieved lymph nodes was 19 ± 13.5. No differences were found between groups in demographic data, type of surgery, surgery time and hospital stay, pathological results and tumor staging, and disease-free and overall survivals. In the SILS group, placement of additional trocar was required in 7 (25%) and conversion in 3 (10.7%) cases compared with 1 (3%) case of conversion to formal laparotomy in the CML group. Overall postoperative morbidity was 16.4%. There was no mortality in both the groups. During the study period, 3 patients from the CML group had cancer recurrence. CONCLUSIONS: SILS is a feasible and safe technique compared with CML in terms of surgical and oncological outcomes.

Comparison of the Long-Term Oncological Outcomes of Stent as a Bridge to Surgery and Surgery Alone in Malignant Colonic Obstruction.

BACKGROUND: Self-expanding metallic stents (SEMS) insertion is an alternative to emergency surgery in malignant colonic obstruction. However, the long-term oncological outcome of stents as a bridge to surgery is limited and controversial. OBJECTIVES: To determine the long-term oncological outcome of stents as a bridge to surgery. METHODS: Data of patients who underwent emergency surgery and endoscopic stent insertion as a bridge to surgery due to obstructing colon cancer at Soroka Medical Center during a 14 year period were collected retrospectively. Preoperative data, tumor staging, and oncological outcomes in terms of local recurrence, metastatic spread, and overall survival of the patients were compared. RESULTS: Sixty-four patients (56% female, mean age 72 years) were included in the study: 43 (67%) following emergency surgery, 21 stent inserted prior to surgery. A stent was inserted within 24-48 hours of hospital admission. The mean time between SEMS insertion and surgery was 15 days (range 0-30). Most of the patients had stage II (41%) and stage III (34%) colonic cancer. There was no difference in tumor staging and localization between groups. There was no significant difference in disease recurrence between SEMS and surgery groups, 24% and 32%, respectively. Disease-free survival rates were similar between the SEMS group (23.8%) and surgery group (22%). Four year and overall survival rates were 52.4% vs. 47.6%, 33.3% vs. 39.5%, respectively. CONCLUSIONS: SEMS as a bridge to surgery in patients with obstructing colon cancer provide an equivalent long-term oncological outcome to surgery alone.

Invasive Candida Infection after Upper Gastrointestinal Tract Surgery for Gastric Cancer.

Upper gastrointestinal tract (GIT) surgical procedures are more likely to cause nosocomial Candida peritonitis than lower GIT procedures and they thus constitute an independent risk factor for mortality. Because of the severity of postsurgical fungal infections complications, intensivists and surgeons need to be extremely aware of their clinical importance in critically ill postsurgical intensive care unit (ICU) patients. We analyzed the clinical and microbiological data of 149 oncologic patients who were hospitalized in the ICU at Soroka Medical Center between January 2010 and January 2015 after undergoing upper GIT surgery for gastric cancer. Invasive fungal infections related to secondary peritonitis following oncologic upper GIT surgery had a higher mortality rate than patients with nonfungal postoperative infectious complications. The presence of gastroesophageal junction leakage and advanced age were found to be independent risk factors for invasive fungal infection after oncologic upper GIT surgery.

Cell-free deoxyribonucleic acid as a prognostic marker of bowel ischemia in patients with small bowel obstruction.

BACKGROUND: Patients with strangulation small bowel obstruction are at a high risk for serious morbidity and mortality due to ischemic bowel. Measuring serum, cell-free deoxyribonucleic acid levels could help recognize early cell death. Our hypothesis was that small bowel ischemia or necrosis is associated with increases in serum cell-free deoxyribonucleic acid and that recovery is associated with a decrease in cell-free deoxyribonucleic acid levels. METHODS: A prospective cohort study in addition to standard treatment of patients admitted with a diagnosis of small bowel obstruction. The participants were divided into groups depending on the presence of ischemic or necrotic bowel according to operative and clinical outcome. Clinical data and serum-based cell-free deoxyribonucleic acid levels were compared. Cell-free deoxyribonucleic acid levels from these 2 groups also were compared with a third group of healthy controls. RESULTS: In the study, 58 patients were enrolled, and 18 patients (31%) underwent operation. During the operative procedure, ischemic or necrotic bowel was found in 10 cases (17%). Serum levels of cell-free deoxyribonucleic acid at the time of admission in the ischemic/necrotic bowel group were increased compared with patients with well perfused or spontaneously recovered bowel (P = .03). Cell-free deoxyribonucleic acid levels decreased on the day after admission in 88% of the nonoperated patients. No significant differences were found in demographics, medical background, imaging performed, and cause of obstruction nor in clinical admission data. CONCLUSION: Surgeons currently rely on imprecise clinical parameters, including degree of pain, abdominal tenderness, leukocytosis etc to decide when operative intervention is needed. The association of cell-free deoxyribonucleic acid with small bowel obstruction, ischemia, and recovery supports our hypothesis and suggests that this biomarker is a potential surrogate of small bowel perfusion.

ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tissue in obesity, molecularly defining a human dys-metabolic obese phenotype.

OBJECTIVE: Obesity variably disrupts human health, but molecular-based patients' health-risk stratification is limited. Adipose tissue (AT) stresses may link obesity with metabolic dysfunction, but how they signal in humans remains poorly-characterized. We hypothesized that a transcriptional AT stress-signaling cascade involving E2F1 and ASK1 (MAP3K5) molecularly defines high-risk obese subtype. METHODS: ASK1 expression in human AT biopsies was determined by real-time PCR analysis, and chromatin immunoprecipitation (ChIP) adopted to AT explants was used to evaluate the binding of E2F1 to the ASK1 promoter. Dual luciferase assay was used to measure ASK1 promoter activity in HEK293 cells. Effects of E2F1 knockout/knockdown in adipocytes was assessed utilizing mouse-embryonal-fibroblasts (MEF)-derived adipocyte-like cells from WT and E2F1-/- mice and by siRNA, respectively. ASK1 depletion in adipocytes was studied in MEF-derived adipocyte-like cells from WT and adipose tissue-specific ASK1 knockout mice (ASK1-ATKO). RESULTS: Human visceral-AT ASK1 mRNA (N = 436) was associated with parameters of obesity-related cardio-metabolic morbidity. Adjustment for E2F1 expression attenuated the association of ASK1 with fasting glucose, insulin resistance, circulating IL-6, and lipids (triglycerides, HDL-cholesterol), even after adjusting for BMI. Chromatin-immunoprecipitation in human-AT explants revealed BMI-associated increased occupancy of the ASK1 promoter by E2F1 (r2 = 0.847, p < 0.01). In adipocytes, siRNA-mediated E2F1-knockdown, and MEF-derived adipocytes of E2F1-knockout mice, demonstrated decreased ASK1 expression and signaling to JNK. Mutation/truncation of an E2F1 binding site in hASK1 promoter decreased E2F1-induced ASK1 promoter activity, whereas E2F1-mediated sensitization of ASK1 promoter to further activation by TNFα was inhibited by JNK-inhibitor. Finally, MEF-derived adipocytes from adipocyte-specific ASK1-knockout mice exhibited lower leptin and higher adiponectin expression and secretion, and resistance to the effects of TNFα. CONCLUSIONS: AT E2F1 -ASK1 molecularly defines a metabolically-detrimental obese sub-phenotype. Functionally, it may negatively affect AT endocrine function, linking AT stress to whole-body metabolic dysfunction.

Laparoscopic resection of duodenal gastrointestinal stromal tumour.

Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results.

Colorectal cancer in southern Israel: Comparison between Bedouin Arab and Jewish patients.

PURPOSE: Colorectal cancer (CRC) is the second most common malignancy and the third leading cause of cancer deaths in Israel; it is less common among the Arab than the Jewish population. This study compares the clinico-pathologic features, treatment, and prognosis between Bedouin-Arab (BA) and Jewish CRC patients treated at our medical centre. METHODS: The medical records of 56 BA patients with CRC were compared retrospectively to 115 Jewish patients. Collected data included age, gender, history of smoking, family history of cancer, presenting symptoms, laboratory tests, previous malignancy, tumor characteristics, surgery type, stoma formation and closure, types of adjuvant treatment, and outcome. RESULTS: BA patients were younger (mean age 68 versus 57 years, p < 0.001), showed a higher incidence in females (p = 0.045), and had a lower frequency of a family history of cancer (p = 0.005) compared to Jewish patients. BA patients had a higher presentation of rectal bleeding and a lower rate of anemia at tumor diagnosis (p = 0.05 and p = 0.004, respectively) with a more distal location of the tumor (p = 0.003). BA patients more often received chemotherapy and radiotherapy (p = 0.02 and p = 0.04, respectively). Disease-free survival was shorter among BA patients (p = 0.023); overall survival was similar in both groups. CONCLUSIONS: CRC in BAs is characterized by a higher proportion of female, younger age, and higher proportion of distal location compared to Jewish patients. These differences in biology may be related to differences in past lifestyles and diet of BA compared to Jewish patients, and are expected to decrease in the following years as the BA population continues to undergo "westernization" changes.

Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity.

BACKGROUND: Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient. METHODS: We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery. RESULTS: Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p<0.05) and ATM lipid content (r = 0.303,p<0.05). Among patients with BMI≥25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men. CONCLUSIONS: Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.

Laparoscopic adjustable gastric band removal and outcome of subsequent revisional bariatric procedures: A retrospective review of 214 consecutive patients.

BACKGROUND: Laparoscopic adjustable gastric band (LAGB) removal is required in cases of slippage, erosion, infection, intolerance, or failure in weight loss. The aim of the study was to follow up the patients who underwent band removal and analyze the outcome of subsequent revisional bariatric procedures. PATIENTS AND METHODS: A retrospective review of consecutive patients who underwent LAGB removal during 3.5 years. All patients underwent a phone interview in early 2015. Patients were divided to three groups following band removal: without additional surgery, laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en Y gastric bypass (LRYGB), and Redo LAGB(Re-LAGB). Outcome of different revisional procedures was compared according to causes and symptoms before band removal, patient satisfaction, weight loss, quality of life (QOL) questionnaire, and the bariatric analysis and reporting outcome system II (BAROSII) score. RESULTS: Overall 214 patients (73.8% females) with mean age of 41.9 years were enrolled in the study. The mean time between LAGB placement and removal was 81.0 months. Mean % estimated weight loss (%EWL) was 29.6 at time of band removal. There was no difference between groups in patient age, gender, BMI before LAGB, and most co-morbidities. Patients with 1-5 outpatient visits preferred additional surgery. Patients suffering from vomiting from 1 to 10 times per week preferred revision as LSG or LRYGB. Patients with lower BAROS score underwent LSG or LRYGB. Most of the patients with band intolerance underwent conversion to another bariatric procedure, while patients with band erosion and infected band preferred Re-LAGB. Most of the patients without band gained weight. There was a significant improvement in %EWL (39.9 vs 29.6), QOL (1.08 vs 0.07), and BAROS(2.82 vs-0.11) in patients who underwent additional bariatric surgery before and after band removal irrespective of surgery type. CONCLUSIONS: Patient selection for different revisional bariatric procedures after LAGB removal is a main point for surgery success. This results in high patient satisfaction, EWL, and QOL. All options (Re-LAGB, LSG, LRYGB) are feasible and safe.

Elevated autophagy gene expression in adipose tissue of obese humans: A potential non-cell-cycle-dependent function of E2F1.

Autophagy genes' expression is upregulated in visceral fat in human obesity, associating with obesity-related cardio-metabolic risk. E2F1 (E2F transcription factor 1) was shown in cancer cells to transcriptionally regulate autophagy. We hypothesize that E2F1 regulates adipocyte autophagy in obesity, associating with endocrine/metabolic dysfunction, thereby, representing non-cell-cycle function of this transcription factor. E2F1 protein (N=69) and mRNA (N=437) were elevated in visceral fat of obese humans, correlating with increased expression of ATG5 (autophagy-related 5), MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 ß), but not with proliferation/cell-cycle markers. Elevated E2F1 mainly characterized the adipocyte fraction, whereas MKI67 (marker of proliferation Ki-67) was elevated in the stromal-vascular fraction of adipose tissue. In human visceral fat explants, chromatin-immunoprecipitation revealed body mass index (BMI)-correlated increase in E2F1 binding to the promoter of MAP1LC3B, but not to the classical cell cycle E2F1 target, CCND1 (cyclin D1). Clinically, omental fat E2F1 expression correlated with insulin resistance, circulating free-fatty-acids (FFA), and with decreased circulating ADIPOQ/adiponectin, associations attenuated by adjustment for autophagy genes. Overexpression of E2F1 in HEK293 cells enhanced promoter activity of several autophagy genes and autophagic flux, and sensitized to further activation of autophagy by TNF. Conversely, mouse embryonic fibroblast (MEF)-derived adipocytes from e2f1 knockout mice (e2f1-/-) exhibited lower autophagy gene expression and flux, were more insulin sensitive, and secreted more ADIPOQ. Furthermore, e2f1-/- MEF-derived adipocytes, and autophagy-deficient (by Atg7 siRNA) adipocytes were resistant to cytokines-induced decrease in ADIPOQ secretion. Jointly, upregulated E2F1 sensitizes adipose tissue autophagy to inflammatory stimuli, linking visceral obesity to adipose and systemic metabolic-endocrine dysfunction.