Real-time diagnosis of Barrett's esophagus: a prospective, multicenter study comparing confocal laser endomicroscopy with conventional histology for the identification of intestinal metaplasia in new users.

INTRODUCTION: Endoscopic evaluation with high-definition white light endoscopy and random 4-quadrant biopsy (Seattle Protocol) is the current standard of care for the detection of Barrett's esophagus (BE). Recently, enhanced imaging technologies have become available to provide real-time diagnosis of intestinal metaplasia (IM) and dysplasia, reducing the need for tissue biopsy. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic microscopic mucosal views, rapidly capturing digital images that become optical biopsies. This study examined the role of pCLE in BE screening and surveillance as compared to the Seattle Protocol. METHODS: Patients undergoing BE screening or surveillance endoscopy were enrolled at eight US centers. Optical biopsy using pCLE was interpreted in real time. Endoscopists performing pCLE were new users with a median experience of 8.5 months and no formal training in surgical pathology. Seattle Protocol biopsies were then taken. Recorded pCLE images were reviewed by a blinded expert in optical biopsy interpretation. RESULTS: Early pCLE users identified significantly more patients with IM than the Seattle Protocol overall (99/172 vs. 46/172, p < 0.0001). Early users of pCLE also identified significantly more patients with IM than the Seattle Protocol in the patients with visible columnar lined esophagus (75 vs. 31, p < 0.0001), but not in the 76 patients without columnar lined esophagus (24 vs. 15, p = 0.067). There was no statistically significant difference between early pCLE users and expert review. CONCLUSION: Optical biopsy using pCLE technology allows for the real-time evaluation of entire segments of columnar lined esophagus. Consequently, pCLE is considerably more sensitive in the detection of BE than the Seattle Protocol, which leaves a majority of epithelium unexamined. This effect is seen even in new users and increases with experience. Overall, pCLE provides a promising advance in Barrett's detection which will likely result in superior identification of individuals at risk for esophageal adenocarcinoma.

Bromination and accompanying rearrangement of the polycyclic oxetane 2,4-oxytwistane.

Bromination of the polycyclic oxetane 2,4-oxytwistane (rac-(1R,3S,4R,7S,9R,11S)-2-oxatetracyclo[5.3.1.0(3,11).0(4,9)]undecane) was undertaken in order to form 2,4-dibromotwistane. The oxetane was subjected to the mild reagent combination CBr4/Ph3P in a fashion similar to that for the Appel and Corey-Fuchs reactions. NMR spectroscopy revealed that the isomeric dibromo compound 2,8-dibromoisotwistane (2,8-dibromotricyclo[4.3.1.0(3,7)]decane) was inadvertently formed. The conversion was prevented by migration of a C-C bond within the geometrically stressed C10 framework. Computational chemistry was used to model the structure of the polycyclic oxetane and to assess the component of total ring strain energy due to the four-membered heterocycle. Mechanistic aspects behind the skeletal rearrangement are also discussed.

Mild one-step synthesis of dibromo compounds from cyclic ethers.

A novel one-step method for mildly converting cyclic ethers into dibromo compounds is reported. Alcohols, oximes, aldehydes, and ketones are known to react under Appel or Corey-Fuchs reaction conditions, but apparently these have never been applied to oxetanes or larger cyclic ethers. Treatment of 3,3-dimethyloxetane (1) with tetrabromomethane and triphenylphosphine gave the corresponding dibromo compound 1,3-dibromo-2,2-dimethylpropane (2). The less-strained homologue oxolane (6) was also reacted giving 1,4-dibromobutane (7) in a 93% yield. Mechanistic interpretations are offered to explain the observed reaction rates of the conversions described.

Safety and efficacy of outpatient sleeve gastrectomy: 2534 cases performed in a single free-standing ambulatory surgical center.

BACKGROUND: Sleeve gastrectomy (SG) is currently the most widely performed operation for treatment of morbid obesity. SG leads to significant weight loss and reduction in weight related comorbidities. Procedures performed in ambulatory surgical centers (ASC) can provide several advantages over hospital-based surgery. We present results of 2,534 consecutive patients who underwent SG in an ASC. OBJECTIVE: Assess the safety and efficacy of outpatient SG in a freestanding ASC. SETTING: Free-standing ASC, Eviva Bariatrics, Seattle WA. METHODS: Data was collected retrospectively for all patients undergoing SG from January 2008 - January 2018, n = 2,534. Revisional procedures were not excluded from this study. Patients were excluded from the ASC if they weighed >450 pounds, if anticipated surgery time was > 2 hours, if the patient had impaired mobility limiting early ambulation, or if there were medical problems requiring postoperative monitoring beyond 23 hours. RESULTS: Mean age was 45.9 years. Mean preoperative body mass index (BMI) was 41.9. Mean operative time was 70 minutes. 30-day complications included 3 mortalities (0.12%), 60 (2.53%) re-admissions, 35 (1.42%), re-operations, and 31 (1.22%) direct transfers from the ASC to a nearby hospital. There were 25 staple line leaks (0.99%). There were no open conversions. At 6 months average excess body weight loss (EWL) was 56.3% and total weight loss (TWL) was 20.9% (n = 1,758/2,303). At 1 year, EWL was 70.1% and TWL was 26.4% (n = 1,199/2,125). CONCLUSION: With experienced surgeons, appropriate protocols, and a consistent operative team, SG can be performed safely in a free-standing ASC.

Does the future of laparoscopic sleeve gastrectomy lie in the outpatient surgery center? A retrospective study of the safety of 3162 outpatient sleeve gastrectomies.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a safe and effective procedure that can be performed as an outpatient procedure. OBJECTIVES: The aim of the study was to determine whether same-day discharge LSG is safe when performed in an outpatient surgery center. SETTING: Outpatient surgery centers. METHODS: The medical records of 3162 patients who underwent primary LSG procedure by 21 surgeons at 9 outpatient surgery centers from January 2010 through February 2018 were retrospectively reviewed. RESULTS: Three thousand one hundred sixty-two patients were managed with enhanced recovery after surgery protocol and were included in this analysis. The mean age and preoperative body mass index were 43.1 ± 10.8 years and 42.1 ± 7.1 kg/m2, respectively. Sleep apnea, type 2 diabetes, gastroesophageal reflux disease, hypertension, and hyperlipidemia were seen in 14.4%, 13.5%, 24.7%, 30.4%, and 17.6% patients, respectively. The mean total operative time was 56.4 ± 16.9 minutes (skin to skin). One intraoperative complication (.03%) occurred. The hospital transfer rate was .2%. The 30-day follow-up rate was 85%. The postoperative outcomes were analyzed based on the available data. The 30-day readmission, reoperation, reintervention, and emergency room visit rates were .6%, .6%, .2%, and .1%, respectively. The 30-day mortality rate was 0%. The total short-term complication rate was 2.5%. CONCLUSIONS: Same-day discharge seems to be safe when performed in an outpatient surgery center in selected patients. It would appear that outpatient surgery centers are a viable option for patients with minimal surgical risks.

High acuity sleeve gastrectomy patients in a free-standing ambulatory surgical center.

BACKGROUND: Procedures performed in ambulatory surgical centers (ASC) can provide several advantages over hospital-based surgery. Understandably, concerns have been raised regarding "high acuity" cases in the ASC setting. Recently the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) presented protocols for ASCs to follow, requiring them to perform only "low acuity" cases to be compliant with accreditation. OBJECTIVE: Assess the safety and efficacy of outpatient sleeve gastrectomy (SG) on the "high acuity patient" in a free-standing ASC. SETTING: Free-standing ASC, Eviva Bariatrics, Seattle, Washington. METHODS: Data were collected retrospectively for all patients who underwent sleeve gastrectomy from January 1, 2013 to December 31, 2015, n = 1112. Of those patients, 120 were classified as "high acuity." RESULTS: Mean age was 51.7 years (24-73), mean body mass index was 42.4 (26.2-65.9). Mean operative time was 91 minutes. Five patients (4.2%) were readmitted within 30 days. Causes of re-admission were portal vein thrombosis (n = 2), intra-abdominal abscess (n = 1), infected hematoma (n = 1), and postoperative bleeding (n = 1). One patient (0.83%) was transferred from the ASC to a nearby hospital due to a postoperative bleed. One patient (0.83%) had a re-operation to evacuate a hematoma. One patient had a re-operation to wash out an infected hematoma. There were 0 confirmed staple line leaks. There were no open conversions and no deaths within 30 days or at 1 year. Follow-up was 83% (n = 100) at 6 months, and 65.0% at 1 year (n = 78). CONCLUSION: Criteria such as age, body mass index, or prior bariatric surgery did not reflect worse outcomes in a specialized ASC. With experienced surgeons, appropriate protocols, and a consistent operative team, SG can be performed safely in a free-standing ASC on select "high acuity" patients.

Long-term success and failure with SG is predictable by 3 months: a multivariate model using simple office markers.

INTRODUCTION: Despite being the most common surgery in the United States, little is known about predicting weight loss success and failure with sleeve gastrectomy (SG). Papers that have been published are inconclusive. We decided to use multivariate analysis from 2 practices to design a model to predict weight loss outcomes using data widely available to any surgical practice at 3 months to determine weight loss outcomes at 1 year. SETTING: Two private practices in the United States. METHODS: A retrospective review of 613 patients from 2 bariatric institutions were included in this study. Co-morbidities and other preoperative characteristics were gathered, and %EWL was calculated for 1, 3, and 12 months. Excess weight loss (%EWL)<55% at 1 year was defined as weight loss failure. Multiple variate analysis was used to find factors that affect %EWL at 12 months. RESULTS: Preoperative sleep apnea, preoperative diabetes, %EWL at 1 month, and %EWL at 3 months all affect %EWL at 1 year. The positive predictive value and negative predictive value of our model was 72% and 91%, respectively. Sensitivity and specificity were 71% and 91%, respectively. CONCLUSION: One-year results of the SG can be predicted by diabetes, sleep apnea, and weight loss velocity at 3 months postoperatively. This can help surgeons direct surgical or medical interventions for patients at 3 months rather than at 1 year or beyond.

The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans.

CONTEXT: The mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood. OBJECTIVE: To investigate whether a reduction in adipose tissue inflammation plays a role in the metabolic improvements seen after bariatric/metabolic surgery, both in the short-term and longer-term. DESIGN: Fasting blood and subcutaneous abdominal adipose tissue were obtained before (n=14), at one month (n=9), and 6-12months (n=14) after bariatric/metabolic surgery from individuals with obesity who were not on insulin or anti-diabetes medication. Adipose tissue inflammation was assessed by a combination of whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes. RESULTS: One month after surgery, body weight was reduced by 13.5±4.4kg (p<0.001), with improvements in glucose tolerance reflected by a decrease in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105±98mmol/L * min; p=0.009) and enhanced pancreatic ß-cell function (insulinogenic index: +0.8±0.9pmol/mmol; p=0.032), but no change in estimated insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p=0.720). Furthermore, although biomarkers of systemic inflammation and pro-inflammatory gene expression in adipose tissue remained unchanged, the number of neutrophils increased in adipose tissue 15-20 fold (p<0.001), with less substantial increases in other leukocyte populations. By the 6-12month follow-up visit, body weight was reduced by 34.8±10.8kg (p<0.001) relative to baseline, and glucose tolerance was further improved (AUC glucose -276±229; p<0.001) along with estimated insulin sensitivity (Matsuda ISI: +4.6±3.2; p<0.001). In addition, improvements in systemic inflammation were reflected by reductions in circulating C-reactive protein (CRP; -2.0±5.3mg/dL; p=0.002), and increased serum adiponectin (+1358±1406pg/mL; p=0.003). However, leukocyte infiltration of adipose tissue remained elevated relative to baseline, with pro-inflammatory cytokine mRNA expression unchanged, while adiponectin mRNA expression trended downward (p=0.069). CONCLUSION: Both the short- and longer-term metabolic improvements following bariatric/metabolic surgery occur without significant reductions in measures of adipose tissue inflammation, as assessed by measuring the expression of genes encoding key mediators of inflammation and by flow cytometric immunophenotyping and quantification of adipose tissue leukocytes.

Incidental gastric mesenchymal tumors identified during laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a well-tolerated and effective procedure for sustained weight loss and amelioration of weight-related co-morbidities. Rarely, unexpected pathology may be identified intraoperatively, which may alter the surgical plan. Gastrointestinal stromal tumors (GISTs) are among the more frequently encountered tumors and pose a particular concern because of their malignant potential. We review our findings of incidental tumors encountered during 1415 consecutive SGs. METHODS: Abnormal pathology records from all patients who underwent SG at our institution between 2009 and 2014 were reviewed. Patient demographic characteristics and clinical characteristics, tumor characteristics, including immunohistochemistry, operative course, and patient follow-up were reviewed. RESULTS: There were 17 incidental gastric mesenchymal tumors identified (1.2%) in 1415 SG procedures. This included 12 GISTs (.8%), 2 schwannomas (.1%), and 3 leiomyomas (.3%). In the majority of cases (1210/1415), the gastric specimens were not reviewed by a pathologist because there were no gross abnormalities appreciated by the surgeon. The GISTs were between .3 and 2.9 cm, and all were low grade with negative margins. Patients with GISTs tended to be older (mean age 55±9.3 y) than the rest of the patients. There was no evidence of recurrence on follow-up. CONCLUSION: Incidental gastric mesenchymal tumors are rarely encountered during SG. The vast majority were GISTs with an incidence of .8% in this population. Concomitant SG and tumor resection were feasible, without compromising the objectives of each. Complete tumor excision is necessary for tumors>2 cm.

Outpatient laparoscopic sleeve gastrectomy in a free-standing ambulatory surgery center: first 250 cases.

BACKGROUND: A growing body of evidence supports the laparoscopic sleeve gastrectomy (LSG) as a safe and effective procedure for sustained weight loss and amelioration of weight-related co-morbidities. Procedures performed in ambulatory surgery centers (ASC) can provide several advantages over hospital-based surgery. We present our results of 250 consecutive patients undergoing LSG in an ASC. The objective of this study was to assess the safety and efficacy of outpatient LSG in a freestanding ASC. METHODS: Data was collected prospectively from 250 consecutive patients who underwent LSG at a freestanding ASC. Patients were excluded from the ASC if they weighed>450 pounds, if anticipated operative time was>2 hours, if the patient had impaired mobility limiting early ambulation, or if there were medical problems requiring postoperative monitoring beyond 23 hours. Revisions were not included in this study. RESULTS: Mean age was 47 years (range, 23-74 yr). Mean preoperative body mass index (BMI) was 43 kg/m² (29-71 kg/m²). Mean operative time was 60 minutes (31-161 min). Mean recovery room time was 131 minutes (30-385 min). Mean percent excess weight loss (%EWL) was 60% at 1 year and 63% at 2 years. Nine patients (3.6%) were readmitted within 30 days. Two patients (.8%) were transferred from the ASC to a hospital. There was 1 staple line leak (.4%). There were no open conversions and no deaths. CONCLUSIONS: LSG can be performed safely in a freestanding ASC in select patients with outcomes comparable to the inpatient standard. Additional studies are needed to formulate selection criteria and guidelines to maximize patient safety and outcomes.

Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages.

Adipose tissue macrophage (ATM)-driven inflammation plays a key role in insulin resistance; however, factors activating ATMs are poorly understood. Using a proteomics approach, we show that markers of classical activation are absent on ATMs from obese humans but are readily detectable on airway macrophages of patients with cystic fibrosis, a disease associated with chronic bacterial infection. Moreover, treating macrophages with glucose, insulin, and palmitate-conditions characteristic of the metabolic syndrome-produces a "metabolically activated" phenotype distinct from classical activation. Markers of metabolic activation are expressed by proinflammatory ATMs in obese humans/mice and are positively correlated with adiposity. Metabolic activation is driven by independent proinflammatory and anti-inflammatory pathways, which regulate balance between cytokine production and lipid metabolism. We identify PPARγ and p62/SQSTM1 as two key proteins that promote lipid metabolism and limit inflammation in metabolically activated macrophages. Collectively, our data provide important mechanistic insights into pathways that drive the metabolic-disease-specific phenotype of macrophages.