Kyle A. Perry

A Randomized Prospective Multicenter Trial of Pancreaticoduodenectomy With and Without Routine Intraperitoneal Drainage

Objective:To test by randomized prospective multicenter trial the hypothesis that pancreaticoduodenectomy (PD) without the use of intraperitoneal drainage does not increase the frequency or severity of complications. Background:Some surgeons have abandoned the use of drains placed during pancreas resection. Methods:We randomized 137 patients to PD with (n = 68, drain group) and without (n = 69, no-drain group) the use of intraperitoneal drainage and compared the safety of this approach and spectrum of complications between the 2 groups. Results:There were no differences between drain and no-drain cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, baseline quality of life, or operative technique. PD without intraperitoneal drainage was associated with an increase in the number of complications per patient [1 (0-2) vs 2 (1-4), P = 0.029]; an increase in the number of patients who had at least 1 ≥grade 2 complication [35 (52%) vs 47 (68%), P = 0.047]; and a higher average complication severity [2 (0-2) vs 2 (1-3), P = 0.027]. PD without intraperitoneal drainage was associated with a higher incidence of gastroparesis, intra-abdominal fluid collection, intra-abdominal abscess (10% vs 25%, P = 0.027), severe (≥grade 2) diarrhea, need for a postoperative percutaneous drain, and a prolonged length of stay. The Data Safety Monitoring Board stopped the study early because of an increase in mortality from 3% to 12% in the patients undergoing PD without intraperitoneal drainage. Conclusions:This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

Visceral Adipose Inflammation in Obesity Is Associated with Critical Alterations in Tregulatory Cell Numbers

Background The development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans. Methods and Findings Foxp3-green fluorescent protein (GFP) “knock-in” mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13) and lean controls (n = 7) were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3+CD4+, and CD3+CD8+ cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b+CD11c+ adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c+ ATMs and a decrease in foxp3 expression. Conclusions Our experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.

Comparison of perioperative outcomes after combined thoracoscopic-laparoscopic esophagectomy and open Ivor–Lewis esophagectomy

BACKGROUND Thoracoscopic-laparoscopic esophagectomy (TLE) has gained popularity in specialized centers. This study compares the perioperative outcomes of TLE and Ivor-Lewis esophagectomy (ILE). METHODS Forty-four consecutive TLEs were compared with 46 historical ILEs. Outcomes included surgical time and blood loss, hospital length of stay, 30-day mortality rate, and complications. RESULTS TLE took longer to perform (543 vs 437 min; P < .01) than ILE, but produced less blood loss (407 vs 780 mL; P < .01). The median length of stay and 30-day mortality did not differ between groups. Cardiovascular (41% for TLE vs 30% for ILE; P = .19) and pulmonary complications (31% TLE vs 30% ILE; P = 1.0) occurred frequently in both groups, but TLE patients had fewer wound complications (4% TLE vs 17% ILE; P = .05). CONCLUSIONS Despite longer surgical times, TLE produced decreased intraoperative blood loss and wound complications. These findings suggest that with further technical refinement TLE may ameliorate the morbidity seen with ILE.

Efficacy of Transoral Fundoplication vs Omeprazole for Treatment of Regurgitation in a Randomized Controlled Trial

BACKGROUND & AIMS Transoral esophagogastric fundoplication (TF) can decrease or eliminate features of gastroesophageal reflux disease (GERD) in some patients whose symptoms persist despite proton pump inhibitor (PPI) therapy. We performed a prospective, sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD. METHODS We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales, on and off PPIs. Those with at least troublesome regurgitation (based on the Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses. Patients with GERD and hiatal hernias ≤2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo (n = 87), or sham surgery and 6 months of once- or twice-daily omeprazole (controls, n = 42). Patients were blinded to therapy during follow-up period and reassessed at 2, 12, and 26 weeks. At 6 months, patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy. RESULTS By intention-to-treat analysis, TF eliminated troublesome regurgitation in a larger proportion of patients (67%) than PPIs (45%) (P = .023). A larger proportion of controls had no response at 3 months (36%) than subjects that received TF (11%; P = .004). Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores. Severe complications were rare (3 subjects receiving TF and 1 receiving the sham surgery). CONCLUSIONS TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.

Radiofrequency energy delivery to the lower esophageal sphincter reduces esophageal acid exposure and improves GERD symptoms: a systematic review and meta-analysis.

Purpose: Studies of endoscopic application of radiofrequency energy to the lower esophageal sphincter for gastroesophageal reflux control have produced conflicting reports of its effectiveness. This study aimed to conduct a meta-analysis of randomized controlled trials and cohort studies to assess the impact of this treatment. Methods: Twenty studies were included. Outcomes analyzed included gastroesophageal reflux disease (GERD) symptom assessment, quality of life, esophageal pH, and esophageal manometry. Results: A total of 1441 patients from 18 studies were included. Radiofrequency treatment improved heartburn scores (P=0.001), and produced improvements in quality of life as measured by GERD–health-related quality-of-life scale (P=0.001) and quality of life in reflux and dyspepsia score (P=0.001). Esophageal acid exposure decreased from a preprocedure Johnson-DeMeester score of 44.4 to 28.5 (P=0.007). Conclusions: Radiofrequency ablation of the lower esophageal sphincter produces significant improvement in reflux symptoms and may represent an alternative to medical treatment and surgical fundoplication in select patients.

Long-term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux

BACKGROUND & AIMS Based on results from year 2 of a 5-year trial, in 2012 the US Food and Drug Administration approved the use of a magnetic device to augment lower esophageal sphincter function in patients with gastroesophageal reflux disease (GERD). We report the final results of 5 years of follow-up evaluation of patients who received this device. METHODS We performed a prospective study of the safety and efficacy of a magnetic device in 100 adults with GERD for 6 months or more, who were partially responsive to daily proton pump inhibitors (PPIs) and had evidence of pathologic esophageal acid exposure, at 14 centers in the United States and The Netherlands. The magnetic device was placed using standard laparoscopic tools and techniques. Eighty-five subjects were followed up for 5 years to evaluate quality of life, reflux control, use of PPIs, and side effects. The GERD-health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device; patients served as their own controls. A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs off PPI were compared. RESULTS Over the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs; 5 years after device placement this score decreased to 4. All patients used PPIs at baseline; this value decreased to 15.3% at 5 years. Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years. CONCLUSIONS Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD. ClinicalTrials.gov no: NCT00776997.

Decreased Conduit Perfusion Measured by Spectroscopy Is Associated With Anastomotic Complications

BACKGROUND Gastric conduit ischemia during esophagectomy likely contributes to high anastomotic complication rates, yet we lack a reliable method to assess gastric conduit perfusion. We hypothesize that optical fiber spectroscopy (OFS) can reliably assess conduit perfusion and that the degree of intraoperative gastric ischemia is associated with subsequent anastomotic complications. METHODS During esophagectomy, OFS was used to measure oxygen saturation (SaO(2)) and blood volume fraction (BVF) in the distal gastric conduit at baseline and after gastric devascularization, conduit formation, and transposition. The SaO(2) and BVF readings were correlated to clinical outcomes. RESULTS The OFS measurements were obtained in 23 patients during esophagectomy, four of whom previously underwent gastric ischemic conditioning. Eight patients developed anastomotic complications. Compared with baseline, conduit creation produced a 29.4% reduction in SaO(2) (p < 0.01), while BVF increased by 28% (p = 0.06). Patients with subsequent anastomotic complications demonstrated a 52.5% decrease in SaO(2) upon conduit creation compared with 15.1% in patients without complications (p = 0.01). Patients who underwent ischemic conditioning did not develop significant changes in SaO(2) (p = 0.72) or BVF (p = 0.5) upon gastric conduit creation. CONCLUSIONS Intraoperative OFS demonstrates significant alterations in gastric conduit oxygenation during esophageal replacement, which may be tempered by gastric ischemic conditioning. The degree of intraoperative gastric ischemia resulting from gastric conduit creation is associated with the development of anastomotic complications, suggesting that OFS is useful for assessing changes in conduit oxygenation during esophagectomy. Further studies are needed to refine this technology and investigate the clinical utility of intraoperative conduit oxygenation data.

Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case–control study

Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Long-term cost-effectiveness of medical, endoscopic and surgical management of gastroesophageal reflux disease

BACKGROUND The long-term cost effectiveness of medical, endoscopic, and operative treatments for adults with gastroesophageal reflux disease (GERD) remains unclear. We sought to estimate the cost effectiveness of medical, endoscopic, and operative treatments for adults with GERD who require daily proton pump inhibitor (PPI) therapy. METHODS A Markov model was generated from the payers perspective using a 6-month cycle and 30-year time horizon. The base-case patient was a 45-year-old man with symptomatic GERD taking 20 mg of omeprazole twice daily. Four treatment strategies were analyzed: PPI therapy, transoral incisionless fundoplication (EsophyX), radiofrequency energy application to the lower esophageal sphincter (Stretta) and laparoscopic Nissen fundoplication. The model parameters were selected using the published literature and institutional billing data. The main outcome measure was the incremental cost-effectiveness ratio (cost per quality-adjusted life-year gained) for each therapy. RESULTS In the base case analysis, which assumed a PPI cost of

Esophageal Replacement Following Gastric Devascularization Is Safe, Feasible, and May Decrease Anastomotic Complications

234 over 6 months (