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Background: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied., Methods: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP., Results: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20)., Conclusion: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted., (© 2024. Society of Surgical Oncology.)

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Open and robotic-assisted transthoracic approaches for diaphragm plication are accepted surgical interventions for diaphragm paralysis and eventration. However, long-term patient-reported symptom improvement and quality of life (QOL) remains unclear., Study Design: A telephone-based survey was developed focusing on postoperative symptom improvement and QOL. Patients who underwent open or robotic-assisted transthoracic diaphragm plication (2008-2020) across three institutions were invited to participate. Patients who responded and provided consent were surveyed. Likert responses on symptom severity were dichotomized and rates before and after surgery were compared using McNemar's test., Results: Forty-one percent of patients participated (43 of 105 responded, mean age 61.0 years, 67.4% male, 37.2% robotic-assisted surgery), with an average time between surgery and survey of 4.1 ± 3.2 years. Patients reported significant improvement in dyspnea while lying flat (67.4% pre- vs 27.9% postoperative, p < 0.001), dyspnea at rest (55.8% pre- vs 11.6% postoperative, p < 0.001), dyspnea with activity (90.7% pre- vs 55.8% postoperative, p < 0.001), dyspnea while bending over (79.1% pre- vs 34.9% postoperative, p < 0.001), and fatigue (67.4% pre- vs 41.9% postoperative, p = 0.008). There was no statistical improvement in chronic cough. 86% of patients reported improved overall QOL, 79% had increased exercise capacity, and 86% would recommend surgery to a friend with a similar problem. Analysis comparing open and robotic-assisted approaches found no statistically significant differences in symptom improvement or QOL responses between the groups., Conclusions: Patients report significantly improved dyspneic and fatigue symptoms after transthoracic diaphragm plication, regardless of open or robotic-assisted approach. The majority of patients report improved QOL and exercise capacity., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak., Methods: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020., Results: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]., Conclusions: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings., (© 2023. Society of Surgical Oncology.)

Diaphragm paralysis and eventration are rare conditions in adults. Symptomatic patients may benefit from surgical plication of the elevated hemidiaphragm. The objective of this study was to compare short-term outcomes and length of stay following robotic-assisted vs. open diaphragm plication. A multicenter retrospective study was conducted that identified patients undergoing unilateral hemidiaphragm plication from 5/2008 to 12/2020. The first RATS plication was performed in 11/2018. Electronic medical records were reviewed, and outcomes were compared between RATS and open approach. One hundred patients underwent diaphragm plication, including thirty-nine (39.0%) RATS and sixty-one (61.0%) open cases. Patients undergoing RATS diaphragm plication were older (64 years vs. 55 years, p = 0.01) and carried a higher burden of comorbidities (Charlson Comorbidity Index: 2.0 vs. 1.0, p = 0.02). The RATS group had longer median operative times (146 min vs. 99 min, p < 0.01), but shorter median hospital length of stays (3.0 days vs. 6.0 days, p < 0.01). There was a non-significant trend toward a decreased rate of 30-day postoperative complications (20.5% RATS vs. 32.8% open, p = 0.18) and 30-day unplanned readmissions (7.7% RATS vs. 9.8% open, p > 0.99). RATS is a technically feasible and safe option for performing diaphragm plications. This approach increases the surgical candidacy of older patients with a higher burden of comorbid disease without increasing complication rates, while reducing length of hospital stay., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Early recognition of esophageal perforation may prevent morbidity and mortality, and accurate diagnostic imaging facilitates triage. Stable patients with suspected perforation may be transferred to higher levels of care before appropriate work-up and diagnosis confirmation. We reviewed patients transferred for esophageal perforation to critically analyze the diagnostic workflow., Methods: We performed a retrospective review of patients transferred to our tertiary care institution from 2015-2021 for suspected esophageal perforation. Demographics, referring site characteristics, diagnostic studies, and management were analyzed. Bivariate comparisons were performed using Wilcoxon-Mann-Whitney tests for continuous variables and chi-squared or Fisher's exact tests for categorical variables., Results: Sixty-five patients were included. Etiology of suspected perforation was spontaneous in 53.8% and iatrogenic in 33.8%. Most patients were transferred within 24 hours from time of suspected perforation (66.2%). Transferring sites included seven states and were 101-300 miles (32.3%) or >300 miles (26.2%) away. CT imaging was obtained in 96.9% before transfer, most commonly demonstrating pneumomediastinum (46.2%). Only 21.5% of patients had an esophagram before transfer. Following transfer, 36.9% (n=24) were ultimately not found to have esophageal perforation, demonstrated by negative arrival esophagram in 79.1%. In patients with confirmed perforation (n=41), 58.5% had surgery, 26.8% endoscopic intervention, and 14.6% supportive care., Conclusions: After transfer a proportion of patients were ultimately found to not have esophageal perforation, typically demonstrated by negative esophagram upon arrival. We conclude that a recommendation of performing esophagram at the presenting site, when possible, may prevent unnecessary transfers, and will likely reduce costs, conserve resources, and decrease management delays., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1798/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Introduction: Retrograde cerebral perfusion (RCP) is a safe and effective technique to augment cerebral protection during lower body circulatory arrest in patients undergoing elective hemiarch replacement. However, recommendations guiding optimal temperature, flow rate, and perfusion pressure are outdated and potentially overly limiting. We report our experience using RCP for elective hemiarch replacement with parameters that challenge the currently accepted paradigm., Methods: This was a single-center, retrospective analysis of 319 adult patients who underwent elective hemiarch replacement between February 2010 and 2021 using hypothermic lower body circulatory arrest with RCP alone, RCP followed by antegrade cerebral perfusion (ACP), or ACP alone. Flow rates were adjusted to maintain cerebral perfusion pressure between 30 and 50 mm Hg for RCP and between 40 and 60 mm Hg for ACP., Results: RCP was used in 22.6% (n = 72) of cases, whereas ACP alone was performed in 77.4% (n = 247) of cases. Baseline patient characteristics were similar between groups. Patients undergoing RCP demonstrated shorter cross-clamp time (97.0 min versus 100.0 min, P = 0.034) and shorter lower body circulatory arrest time (7.0 min versus 10.0 min, P < 0.0001) compared with ACP alone. Nadir bladder temperature was equivalent between groups (27.3°C versus 27.5°C, P = 0.752). There were no significant differences in postoperative complications, neurologic outcomes, or mortality., Conclusions: Moderate hypothermic lower body circulatory arrest combined with RCP at target perfusion pressures of 30-50 mm Hg in patients undergoing elective hemiarch replacement results in equivalent neurologic outcomes and overall morbidity to cases using ACP alone. These results challenge the currently accepted paradigm for RCP, which typically uses deep hypothermia while keeping perfusion pressures below 25 mm Hg., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: A new postoperative esophagectomy care pathway was recently implemented at our institution. Practice pattern change among provider teams can prove challenging; therefore, we sought to study the barriers and facilitators toward pathway implementation at the provider level., Methods: This qualitative study was guided by the Theoretical Domains Framework (TDF) to study the adoption and implementation of a post-esophagectomy care pathway. Sixteen in-depth interviews were conducted with providers involved with the pathway. Matrix analysis was used to analyze the data., Results: Providers included attending surgeons (n = 6), advanced practice providers (n = 8), registered dietitian (n = 1), and clinic staff (n = 1). TDF domains that were salient across our findings included knowledge, beliefs about consequences, social influences, and environmental context and resources. Identified facilitators included were electronic health record tools, such as note templates including pathway components and a pathway-specific order set, patient satisfaction, and preliminary data indicating clinical benefits such as a reduced anastomotic leak rate. The major barrier reported was a hesitance to abandon previous practice patterns, most prevalent at the attending surgeon level., Conclusion: The TDF enabled us to identify and understand the individuals' perceived barriers and facilitators toward adoption and implementation of a postoperative esophagectomy pathway. This analysis can help guide and improve adoption of surgical patient care pathways among providers., (© 2022. The Society for Surgery of the Alimentary Tract.)

Dysregulation of toll-like receptor (TLR) signaling within the gastrointestinal epithelium has been associated with uncontrolled inflammation and tumorigenesis. We sought to evaluate the role of TLR4 in the development of gastroesophageal reflux-mediated inflammation and mucosal changes of the distal esophagus. Verified human esophageal Barrett's cells with high grade dysplasia (CPB) and esophageal adenocarcinoma cells (OE33) were treated with deoxycholic acid for 24 hours. Cells were pretreated with a TLR4-specific inhibitor peptide 2 hours prior to deoxycholic acid treatment. Inflammatory markers were evaluated using immunoblotting and enzyme-linked immunosorbent assay. A surgical reflux mouse model was generated by performing a side-to-side anastomosis between the second portion of the duodenum and the gastroesophageal junction. Control animals underwent laparotomy with incision and closure of the esophagus superior to the gastroesophageal junction (sham procedure). Esophageal sections were evaluated using hematoxylin and eosin staining and immunohistochemistry. Deoxycholic acid increased expression of inflammatory markers including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin 8. Pretreatment with a TLR4 inhibitor significantly decreased deoxycholic acid-induced inflammatory marker expression. C3H/HeNCrl mice demonstrated a significant increase in mucosal hyperplasia and proliferation following DGEA compared to sham procedure. TLR4 mutant mice (C3H/HeJ) undergoing DGEA demonstrated an attenuated hyperplastic and proliferative response compared to C3H/HeNCrl mice. Inhibition of TLR4 signaling attenuates reflux-induced inflammation in vivo. These findings identify TLR4 inhibition as a potential therapeutic target to halt the progression of pathologic esophageal changes developing in the setting of chronic gastroesophageal reflux disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to analyze injury characteristics and stroke rates between blunt cerebrovascular injury (BCVI) with delayed vs non-delayed medical therapy. We hypothesized there would be increased stroke formation with delayed medical therapy., Methods: This is a sub-analysis of a 16 center, prospective, observational trial on BCVI. Delayed medial therapy was defined as initiation >24 hours after admission. BCVI which did not receive medical therapy were excluded. Subgroups for injury presence were created using Abbreviated Injury Scale (AIS) score >0 for AIS categories., Results: 636 BCVI were included. Median time to first medical therapy was 62 hours in the delayed group and 11 hours in the non-delayed group (p < 0.001). The injury severity score (ISS) was greater in the delayed group (24.0 vs the non-delayed group 22.0, p <  0.001) as was the median AIS head score (2.0 vs 1.0, p <  0.001). The overall stroke rate was not different between the delayed vs non-delayed groups respectively (9.7% vs 9.5%, p = 1.00). Further evaluation of carotid vs vertebral artery injury showed no difference in stroke rate, 13.6% and 13.2%, p = 1.00 vs 7.3% and 6.5%, p = 0.84. Additionally, within all AIS categories there was no difference in stroke rate between delayed and non-delayed medical therapy (all N.S.), with AIS head >0 13.8% vs 9.2%, p = 0.20 and AIS spine >0 11.0% vs 9.3%, p = 0.63 respectively., Conclusions: Modern BCVI therapy is administered early. BCVI with delayed therapy were more severely injured. However, a higher stroke rate was not seen with delayed therapy, even for BCVI with head or spine injuries. This data suggests with competing injuries or other clinical concerns there is not an increased stroke rate with necessary delays of medical treatment for BCVI., Competing Interests: Conflict of interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The appropriate stent length in frozen elephant trunk replacements (FET) remains debated relative to the risk for paraplegia. However, landing the distal end of the stent beyond the curve of the arch facilitates distal reintervention, which is commonly beyond the 10 cm stent coverage when deployed proximal to the left subclavian artery. The aim of this study was to evaluate outcomes following the use of 15 cm stent grafts in zone 2 (z2, distal to the left common carotid)., Methods: Using our single institution-maintained database, 103 zone 2 FET performed from 2016 to 2020 were reviewed., Results: Of the 103 z2, a 15 cm stent graft was used in 51 operations. The indications for FET included acute and chronic aortic dissection, arch aneurysms, and pseudoaneurysms. The incidence of SCI was 0%. Seven deaths (13.7%) occurred., Conclusions: The data demonstrates the incidence of post-operative paraplegia to be 0% with 15 cm z2 FET. The understanding of SCI in FET should not only include the stent length but also from where it begins., Competing Interests: Declaration of competing interest Our group has no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: Glypican 1 (GPC1) is a heparan sulphate proteoglycan cell membrane protein. It is implicated in driving cancers of the breast, brain, pancreas, and prostate; however, its role in esophagogastric cancer (EGAC) remains unexplored. The aim of the study was to investigate and elucidate the molecular mechanistic of GPC1 in human EGAC., Methods: Thirty tissue and 120 microarray sections of EGAC were evaluated with Anti-GPC1 immunohistochemistry. Loss and gain of GPC1 function were performed using lentivirus transfection in EGAC cell lines. Mechanistically, AKT/GSK/β-catenin pathway was evaluated using AKT inhibitor MK-2206 and Wnt/β-catenin stimulant LiCl., Results: GPC1 overexpression was found in 102 cases (68%). Overexpression of GPC1 correlated with lymph node metastasis, poor differentiation and decreased overall survival. Lentivirus mediated GPC1 knockdown resulted in decreased cell proliferation, migration, invasion, and colony formation. Knockdown caused G0/G1 cell cycle arrest, increased apoptosis, and reduced epithelial mesenchymal transition (EMT). GPC1 mediated its effects by activation of AKT/GSK/β-catenin pathway., Conclusions: This is the first descriptive study to decipher the role of GPC1 in EGAC. Our results suggest that GPC1 regulates cell proliferation and growth and may serve as an attractive oncotarget in EGAC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-240/coif). AP reports that he receives robotic intuitive foundation fellowship grant, which is awarded for training minimal invasive surgery fellows. Paul O Hara and Academic enrichment fund were awarded for this project. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Observational studies demonstrate a protective effect of statins on the development and progression of esophageal adenocarcinoma. The role of statins in the prevention of reflux-induced esophageal changes remains unknown., Aims: Using a mixed gastroduodenal reflux mouse model, we hypothesized that oral administration of simvastatin would attenuate reflux-induced mucosal changes of the distal esophagus., Methods: Human Barrett's (CPB) and esophageal adenocarcinoma (FLO1 and OE19) cells were treated with simvastatin. Cell proliferation and apoptosis were evaluated using the MTS proliferation and annexin V apoptosis assays, respectively. A reflux mouse model was generated by performing a side-to-side anastomosis between the gastroesophageal junction and first portion of the duodenum (duodeno-gastroesophageal anastomosis, DGEA). DGEA mice were fed a standard or simvastatin-containing diet following surgery. Mice were euthanized 6 weeks post-operatively., Results: Simvastatin significantly decreased proliferation and increased apoptosis in all cell lines. Compared to control animals, mice undergoing DGEA who were fed a standard diet demonstrated a fourfold increase in mucosal thickness and significant increase in proliferating cells (p < 0.0001). DGEA mice fed a simvastatin-containing diet had an attenuated response to reflux, with a significant reduction in mucosal hyperplasia and proliferation (p < 0.0001). DGEA mice fed a simvastatin-containing diet demonstrated significant upregulation of procaspase-3 (p = 0.009) and cleaved caspase-3 (p = 0.034) in the distal esophagus., Conclusions: We demonstrate for the first time a reduction in reflux-induced histologic changes of the distal esophagus following oral administration of simvastatin in vivo. These findings identify simvastatin as a potential preventative agent to inhibit the development and progression of reflux-induced esophageal injury., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: There is a paucity of data describing opioid prescribing patterns for trauma patients. We investigated pain medication regimens prescribed at discharge for patients with traumatic rib fractures, as well as potential variables predictive of opioid prescribing., Methods: A single-center, retrospective analysis was performed of 337 adult patients presenting with ≥1 traumatic rib fractures between January and December 2019. The primary outcome was oral morphine milligram equivalents (MME) prescribed on discharge. A multivariable logistic regression analysis was performed to determine factors independently associated with above median (150) MME prescription at discharge., Results: The majority of patients were male (68.8%) with a median age of 53 y. Blunt trauma accounted for 97.3% of cases with a median Injury Severity Score(ISS) of 10. Locoregional pain procedures were utilized in 16.9% of patients. Opioids were the most common analgesic prescribed at discharge, and 74.1% of patients prescribed opioids on discharge were also prescribed a non-opioid adjunct. On multivariable analysis, daily MME prescribed during hospitalization (OR 1.01, 95% CI 1.01-1.02, P < 0.01) and number of rib fractures (OR 2.26, 95% CI 1.36-3.74, P < 0.01) were predictive of high MME prescribed on discharge., Conclusions: For patients with traumatic rib fractures, daily MME during hospitalization and number of rib fractures were predictive of high MME prescribing on discharge. Further prospective studies evaluating strategies for pain management and protocolized approaches to opioid prescribing are needed to reduce unnecessary and inappropriate opioid use in this patient population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There is a tremendous need for affordable and accessible surgical simulators in the United States and abroad. Our group developed a portable, modular, inexpensive surgical simulator designed for all levels of surgical trainees, from medical students to cardiothoracic surgery fellows, and adaptable to a variety of surgical specialties. Our goal is to provide a platform for innovative surgery simulation that applies to any learner or resource setting. We describe the development, assembly, and future directions for this simulator., (© Lin et al.)

Introduction: Data is limited on hybrid transoral incisionless fundoplication (TIF) and hiatal hernia repair in giant paraoesophageal hernia (GPEH). We aimed to assess the safety, patient satisfaction, and symptom resolution following a hybrid paraoesophageal hernia (PEH) repair and TIF in patients with GPEH., Patients and Methods: All single-session hybrid TIF combined with minimally invasive PEH repair performed between February 2020 and June 2021 were evaluated. Procedures were performed in the operating room under general anesthesia with robotic or laparoscopic PEH repair followed by TIF., Results: Twelve patients underwent combined surgical hiatal hernia repair and TIF. Primary presenting symptoms included heartburn (75.0%), dysphagia (41.7%), and chronic anemia from Cameron's ulcers (16.7%). The mean hernia defect size was 5.0 cm (range 3.0 to 6.0 cm). Hiatal hernia repairs were performed robotically in 7 patients and laparoscopically in 5 patients. The total mean operative time was 254 minutes (range: 180 to 390 min). One patient reported postoperative dysphagia requiring endoscopic dilation postdischarge with a resolution of symptoms. No gas-bloat symptoms were reported. All patients reported complete resolution of presenting symptoms at the time of follow-up. Postoperative mean follow-up for 4 patients at 6 months with upper endoscopy and pH testing showed an intact valve with no evidence of esophagitis or acid reflux., Conclusions: In our experience, hybrid hiatal hernia repair and TIF is a safe and effective therapeutic option for patients with GPEH. This hybrid procedure allows for more expeditious completion of the repair and results in lower rates of postfundoplication dysphagia and gas-bloat. Furthermore, this approach requires a less extensive surgical dissection on the greater curvature of the stomach, thereby minimizing the risk of vagal nerve injury and bleeding from the short gastric vessels., Competing Interests: A.P. reports grant funding from the Intuitive Foundation for a minimally invasive surgery fellowship program. M.S.W. is a consultant for Boston Scientific, Olympus, Medtronic, Incyte, Fujifilm, and Conmed. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lung transplantation is the mainstay of treatment for patients with end-stage respiratory failure. This study sought to evaluate survival following transplantation compared to the general population and quantify standardized mortality ratios (SMRs) using a nested case-control study design., Methods: Control subjects were nonhospitalized inhabitants of the United States identified through the National Longitudinal Mortality Study. Case subjects were adults who underwent lung transplantation between 1990 and 2007 and identified through the Organ Procurement and Transplantation Network. Propensity-matching (5:1, nearest neighbor, caliper = 0.1) was utilized to identify suitable control subjects based on age, sex, race, and location of residency. The primary study endpoint was 10-year survival., Results: About 14,977 lung transplant recipients were matched to 74,885 nonhospitalized US residents. The 10-year survival rate of lung transplant recipients was 28% (95% confidence interval [CI] = 27%-29%). The population expected mortality rate was 19 deaths/100 person-years while the observed ratio was 104 deaths/100 person-years (SMR = 5.39, 95% CI = 5.35-5.43). The largest discrepancies between observed and expected mortality rates were in females (SMR = 5.97), Hispanic (SMR = 10.70), and single lung recipients (SMR = 5.92). SMRs declined over time (1990-1995 = 5.79, 1996-2000 = 5.64, and 2001-2007 = 5.10). Standardized mortality peaks in the first year after transplant and decreases steadily over time., Conclusions: Lung transplant recipients experience a fivefold higher SMR compared to the nonhospitalized population. Long-term mortality rates have experienced consistent decline over time., (© 2022 Wiley Periodicals LLC.)

The objective of this study was to evaluate the educational impact following the implementation of a robotic thoracic surgery program on cardiothoracic (CT) surgery trainees. We hypothesized that the introduction of a robotic thoracic surgery program would adversely affect the CT surgery resident experience, decreasing operative involvement and subsequent competency of surgical procedures. CT surgery residents and thoracic surgery attendings from a single academic institution were administered a recurring, electronic survey from September 2019 to September 2020 following each robotic thoracic surgery case. Surveys evaluated resident involvement and operative performance. This study was exempt from review by our Institutional Review Board. Attendings and residents completed surveys for 86 and 75 cases, respectively. Residents performed > 50% of the operation independently at the surgeon console in 66.2 and 73.3% of cases according to attending and resident responses, respectively. The proportion of trainees able to perform > 75% of the operation increased with each increasing year in training (p = 0.002). Based on the Global Evaluative Assessment of Robotic Skills grading tool, third-year residents averaged higher scores compared to first-year residents (22.9 versus 17.4 out of 30 possible points, p < 0.001), indicating that more extensive prior operative experience could shorten the learning curve of robotic thoracic surgery. CT surgery residents remain actively involved in an operative role during the establishment of a robotic thoracic surgery program. The transition to a robotic thoracic surgery platform appears feasible in a large academic setting without jeopardizing the educational experience of resident trainees., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Various adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), have been shown to play a role in inflammation as well as contribute to tumor progression and prognosis. We hypothesized that gastroduodenal reflux upregulates ICAM-1 and VCAM-1 expression in the distal esophagus, serving as possible early markers of pathologic esophageal disease., Methods: Normal human esophageal epithelial cells (HET1A), Barrett cells (CPB), and esophageal adenocarcinoma cells (FLO1 and OE33) were treated with deoxycholic acid at increasing concentrations for 24 hours. Adhesion molecule expression was assessed using immunoblotting. A surgical mouse reflux model was generated by performing a side-to-side anastomosis between the gastroesophageal junction and the first portion of the duodenum (duodenum-gastroesophageal anastomosis). Esophageal sections were evaluated using hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence., Results: Deoxycholic acid induced a significant increase in ICAM-1 and VCAM-1 expression in HET1A, CPB, FLO1, and OE33 cells. Animals undergoing duodenum-gastroesophageal anastomosis demonstrated a significant increase in mucosal hyperplasia (P < .0001) and cellular proliferation (P < .0001) compared with control animals. Immunofluorescence and Western blot analysis of the lower esophagus demonstrated significant upregulation of ICAM-1 (P = .005), with no change in VCAM-1 expression (P = .82)., Conclusions: Our results reveal that ICAM-1 and VCAM-1 are upregulated in response to in vitro reflux treatment of normal esophageal epithelial cells. However, our investigation using a mouse reflux model found ICAM-1 is noticeably upregulated without a concomitant increase in VCAM-1. These findings identify ICAM-1, but not VCAM-1, as a potential player in early esophageal disease developing from chronic reflux exposure., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent clinical evidence suggests an association between warfarin use and calcification of the aortic valve. We sought to determine the effect of warfarin on aortic valve interstitial cell (AVIC) osteogenic protein expression and the signaling pathways by which this effect is mediated., Methods: Human AVICs were isolated from normal aortic valves of patients undergoing cardiac transplantation, whereas diseased AVICs were isolated from patients undergoing aortic valve replacement for aortic stenosis. AVICs were treated with various anticoagulants, and osteogenic protein expression was evaluated using immunoblotting. Phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and extracellular signal-regulated kinase 1/2 (ERK1/2) was evaluated after treatment with warfarin. AVICs were pretreated with LRP6 inhibitor dkk1 and ERK1/2 inhibitor PD98059 followed by treatment with warfarin, and osteogenic protein expression was evaluated., Results: Warfarin, but not heparin or dabigatran, significantly increased Runx-2 and Osx expression in both normal and diseased human AVICs. Upregulation of β-catenin protein expression and nuclear translocation occurred in diseased AVICs but not normal AVICs after warfarin treatment. Warfarin induced phosphorylation of LRP6 in diseased AVICs only and phosphorylation of ERK1/2 in both normal and diseased AVICs. LRP6 inhibition attenuated warfarin-induced Runx-2 expression in diseased AVICs. ERK1/2 inhibition attenuated warfarin-induced Runx-2 expression in both normal and diseased AVICs., Conclusions: Warfarin induces osteogenic activity in normal and diseased isolated human AVICs. This effect is mediated by ERK1/2 in both diseased and normal AVICs, but in diseased AVICs β-catenin signaling also plays a role. These results implicate the role of warfarin in aortic valve calcification and highlight potential mechanisms for warfarin-induced aortic stenosis., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background:  Selective antegrade cerebral perfusion (SACP) has become our preferred method for cerebral protection during open arch cases. While the initial approach involved sewing a graft to the innominate artery as the arterial cannulation site, our access strategy has since evolved to central aortic cannulation with use of a percutaneous cannula in the innominate for SACP. We hypothesized that SACP delivered via direct innominate cannulation using a 12- or 14-Fr cannula results in equivalent outcomes to cases utilizing a side graft., Methods:  This was a single-center, retrospective analysis of 211 adult patients who underwent elective hemiarch replacement using hypothermic circulatory arrest with SACP via the innominate artery between 2012 and 2020. Urgent and emergent cases were excluded., Results:  A side graft sutured to the innominate was utilized in 81% ( n  = 171) of patients, while direct innominate artery cannulation was performed in 19% ( n  = 40) of patients. Baseline patient characteristics were similar between groups aside from a higher baseline creatinine in the direct cannulation group (1.3 vs. 0.9, p  = 0.032). Patients undergoing direct cannulation demonstrated shorter cardiopulmonary bypass time (132.7 vs. 154.9 minutes, p  = 0.020) and shorter circulatory arrest time (8.1 vs. 10.9 minutes, p  = 0.004). Nadir bladder temperature did not significantly differ between groups (27.2°C for side graft vs. 27.6°C for direct cannulation, p  = 0.088). There were no significant differences in postoperative outcomes., Conclusion:  Direct cannulation of the innominate artery with a 12- or 14-Fr cannula for SACP during hemiarch replacement is a safe alternative to using a sutured side graft. While cardiopulmonary bypass and circulatory arrest times appear improved, this is likely attributable to accumulation of experience and proficiency in technique. However, direct innominate artery cannulation may facilitate quicker completion of these procedures by eliminating the time necessary to suture a graft to the innominate artery., Competing Interests: The authors declare no conflict of interest related to this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: The objective of this study was to evaluate the impact of unplanned conversion to open esophagectomy during minimally invasive esophagectomy (MIE) on postoperative morbidity and mortality for patients with esophageal cancer, as well as to evaluate the variables that influence the need for conversion., Methods: This study was a retrospective analysis of patients with esophageal cancer who underwent open esophagectomy or MIE by either a laparothoracoscopic approach or a robotic approach from 2016 to 2018 by using the esophagectomy-specific American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Poisson regression models were used to analyze 30-day outcomes and risk factors for conversion to open esophagectomy during attempted MIE., Results: A total of 2616 patients were identified. The overall conversion rate for MIE was 6.3%. Compared with completed MIE, patients requiring conversion to open esophagectomy had a significantly increased risk of 30-day mortality (risk ratio, 2.63; 95% confidence interval, 1.03 to 6.69) and experienced a variety of other postoperative complications. Patients requiring conversion to open esophagectomy during MIE also experienced worse perioperative outcomes when compared to patients who underwent planned open esophagectomy. Estimated surgical risk on the basis of the ACS NSQIP Surgical Risk Calculator was the only variable found to be independently associated with conversion from minimally invasive to open esophagectomy (risk ratio, 1.03; 95% confidence interval, 1.01 to 1.04, for each 10% increase in risk score)., Conclusions: Unplanned conversion to open esophagectomy during MIE is associated with significantly greater morbidity and a 2.6-fold increased risk of death when compared with both completed MIE and planned open esophagectomy. The ACS NSQIP Surgical Risk Calculator may help identify patients preoperatively who are at higher risk for conversion to open esophagectomy during MIE., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Perforated peptic ulcer is a morbid emergency general surgery condition. Best practices for postoperative care remain undefined. Surgical dogma preaches practices such as peritoneal drain placement, prolonged nil per os, and routine postoperative enteral contrast imaging despite a lack of evidence. We aimed to evaluate the role of postoperative enteral contrast imaging in postoperative perforated peptic ulcer care. Our primary objective was to assess effects of routine postoperative enteral contrast imaging on early detection of clinically significant leaks., Methods: We conducted a multicenter retrospective cohort study of patients who underwent repair of perforated peptic ulcer between July 2016 and June 2018. We compared outcomes between those who underwent routine postoperative enteral contrast imaging and those who did not., Results: Our analysis included 95 patients who underwent primary/omental patch repair. The mean age was 60 years, and 54% were male. Thirteen (14%) had a leak. Eighty percent of patients had a drain placed. Nine patients had leaks diagnosed based on bilious drain output without routine postoperative enteral contrast imaging. Use of routine postoperative enteral contrast imaging varied significantly between institutions (30%-87%). Two late leaks after initial normal postoperative enteral contrast imaging were confirmed by imaging after a clinical change triggered the second study. Two patients had contained leaks identified by routine postoperative enteral contrast imaging but remained clinically well. Duration of hospital stay was longer in those who received routine postoperative enteral contrast imaging (12 vs 6 days, median; P = .000)., Conclusion: Routine postoperative enteral contrast imaging after perforated peptic ulcer repair likely does not improve the detection of clinically significant leaks and is associated with increased duration of hospital stay., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Morgagni hernia (MH) is a rare diaphragmatic hernia which needs surgical repair. The conventional reconstruction involves reduction of hernia, closure of the defect and placement of an intraperitoneal onlay mesh often using robotic platform for ease of dissection and suturing the mesh (r-IPOM). We propose a novel robotic preperitoneal repair (r-TAPP) of MH in four cases and compare them with conventional r-IPOM technique. Between August 2017 and August 2020 nine patients underwent repair of MH. Five cases underwent repair by r-IPOM (group I). For the other four cases, r-TAPP was used (group II). Among the nine cases, the mean age was 53 years in group I and 55 years in group II, mean defect size was 33 mm in group I and 55 mm in group II. Operative time was longer in group II compared to group I (220 min vs 135 min, p = 0.022). Mean length of hospital stay was 1.3 days in group I compared to group II (4.5 and 4.5 vs 1.3 days, p = 0.03). There was statistically significant difference in reduced post-operative pain and time to return to work in group II compared to group I. There was no difference in complications, 30-day readmissions or recurrence of hernia between the two groups. We conclude that compared to the conventional r-IPOM repair, the r-TAPP technique is associated with less pain, early discharge, and faster return to work, translating into overall cost savings for the hospital., (© 2021. Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Morgagni hernia (MH) is a rare, congenital diaphragmatic hernia. We developed a novel robotic-assisted technique to repair MH which enables dissection into the preperitoneal space, facilitating closure of the diaphragmatic defect and placement of a synthetic mesh., Materials and Surgical Technique: Between August 2017 and August 2020, 8 consecutive patients with MH were repaired by robotic-assisted transabdominal preperitoneal (r-TAPP) approach. A preperitoneal plane is developed at the level of the falciform ligament and extended toward the diaphragmatic defect. The pocket is dissected inferior to the defect to allow 3 to 5 cm overlap of synthetic mesh. Excision of the hernia sac followed by closure of defect is performed. A synthetic mesh is deployed in the preperitoneal space with wide overlap. This technique using the robot provides superior optics and ergonomics for dissection while isolating the mesh from underlying viscera and avoiding the need for suturing or tacking of the mesh. Data of patients who underwent r-TAPP were reviewed. Mean operating time was 113 minutes. Mean pain visual analog scale score was 5/2 on post-operative days 1/7. Average hospital stay was 1.8 days. One patient developed superficial cellulitis related to the abdominal drain. There were no procedure-related complications, 30-day readmissions, or hernia recurrences at a mean follow-up of 10 months., Discussion: A robotic-assisted preperitoneal approach is a novel, safe, and anatomically justified alternative technique for MH repair that may lead to improved post-operative outcomes., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Esophageal adenocarcinoma (EAC) is a lethal malignancy with poor prognosis. Pharmacologic inhibitors of inflammation, such as statins, have been shown to decrease the risk of development and progression of esophageal cancer, but the mechanism of this protection is unclear. The objective of this study was to elucidate the effect of statins on toll-like receptor 4-mediated-proliferation of human EAC cells and identify the mechanism responsible for these observed effects., Methods: Human EAC cells (OE33 and FLO1) were treated with simvastatin or atorvastatin for increasing doses and time periods. Toll-like receptor 4 (TLR4) expression was assessed. Cells were pretreated with statin followed by lipopolysaccharide (LPS). Cell proliferation and expression of signaling proteins were evaluated. FLO1 cells were injected into the flank of nude mice. Mice received intraperitoneal injections of simvastatin, atorvastatin, or control solution and tumor volume was measured., Results: OE33 and FLO1 cells demonstrated decreased TLR4 expression after treatment with simvastatin or atorvastatin for 8 h (P < 0.05). LPS increased proliferation, whereas pretreatment with statin abolished this response (P < 0.05). Statins decreased expression and activation of LPS-induced signaling proteins, including MyD88, TRAF6, Akt, and NF-κB (P < 0.05). Mice receiving daily statin injections demonstrated smaller tumors than control mice (P < 0.001 at day 33)., Conclusions: Treatment of EAC cells with simvastatin or atorvastatin decreases TLR4-mediated proliferation and in vivo tumor growth. Decreased TLR4 expression and subsequent reduction in MyD88-dependent signaling could be a mechanism by which statins act to reduce tumor growth rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Gastroesophageal reflux and Barrett's esophagus are significant risk factors for the development of esophageal adenocarcinoma. Group IIa secretory phospholipase A 2 (sPLA 2 ) catalyzes the production of various proinflammatory metabolites and plays a critical role in promoting reflux-induced inflammatory changes within the distal esophagus. We hypothesized that inhibition of sPLA 2 in human Barrett's cells would attenuate adhesion molecule expression via decreased activation of nuclear factor kappa B (NF-κB) and decrease cell proliferation, possibly mitigating the invasive potential of Barrett's esophagus., Materials and Methods: Normal human esophageal epithelial cells (HET1A) and Barrett's cells (CPB) were assayed for baseline sPLA 2 expression. CPB cells were treated with a specific inhibitor of sPLA 2 followed by tumor necrosis factor-α. Protein expression was evaluated using immunoblotting. Cell proliferation was assessed using an MTS cell proliferation assay kit. Statistical analysis was performed using the Student's t-test or analysis of variance, where appropriate., Results: CPB cells demonstrated higher baseline sPLA 2 expression than HET1A cells (P = 0.0005). Treatment with 30 μM sPLA 2 inhibitor significantly attenuated intercellular adhesion molecule-1 (P = 0.004) and vascular cell adhesion molecule-1 (P < 0.0001) expression as well as decreased NF-κB activation (P = 0.002). sPLA 2 inhibition decreased cell proliferation in a dose-dependent manner (P < 0.001 for 15, 20, and 30 μM doses)., Conclusions: sPLA 2 inhibition in human Barrett's cells decreases cellular adhesive properties and NF-κB activation as well as decreases cell proliferation, signifying downregulation of the inflammatory response and possible attenuation of cellular malignant potential. These findings identify sPLA 2 inhibition as a potential chemopreventive target for premalignant lesions of the esophagus., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Approximately 5% of patients who have undergone prior Heller myotomy and Roux en Y gastric bypass progress to end-stage achalasia (ESA). Surgical options for ESA are often limited to esophagectomy for management of severe dysphagia or life-threatening aspiration episodes. Mediastinoscopy-assisted transhiatal esophagectomy (MATHE) by a small left neck incision combined with an abdominal incision, without using a transthoracic approach, has been reported to reduce pulmonary complications. We herein present the first report of MATHE in 2 consecutive patients with ESA and gastric bypass., Materials and Methods: Between August 2017 and September 2020, 2 patients who had undergone Heller myotomy and Roux en Y gastric bypass underwent MATHE for ESA. Transhiatal esophagectomy with mediastinoscopy-assisted dissection was performed. The remnant stomach was used as the conduit in both cases. The embedded Supplemental Digital Content 1 (http://links.lww.com/SLE/A269) reports our novel technique., Results: Both cases were completed laparoscopically without conversion to laparotomy or thoracotomy. Median length of hospital stay was 9 days (range, 6 to 11 d). Postoperatively, 1 patient developed a cervical anastomotic leak, which healed with conservative management. No other major complications were observed., Conclusions: MATHE can be safely performed in patients with a history of gastric bypass and ESA without requiring thoracoscopic mobilization of the esophagus. Further studies are required to validate reproducibility of our technique as an alternative to using a thoracic incision., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pulmonary segmentectomy provides an anatomic lung resection while avoiding removal of excess normal lung tissue. This may be beneficial in patients with minimal pulmonary reserve who present with early-stage non-small cell lung cancer (NSCLC). However, the operative performance of a segmentectomy using a video-assisted thoracoscopic approach can be technically challenging. We hypothesized that introduction of the robotic surgical system would facilitate the performance of a segmentectomy as measured by an increase in the proportion of segmentectomies being pursued., Methods: We completed a retrospective analysis of thoracoscopic and robotic anatomic lung resections, including lobectomies and segmentectomies, performed in patients with primary lung cancer from the time of initiation of the robotic thoracic surgery program in November 2017 to November 2019. We compared the proportion of thoracoscopic and robotic segmentectomies performed during the first year compared to the second year of the data collection period., Results: A total of 138 thoracoscopic and robotic anatomic lung resections were performed for primary lung cancer. Types of lung cancer resected (adenocarcinoma, squamous cell carcinoma, or other), tumor size based on clinical T staging (T1-T4), and tumor location were not significantly different between years (P=0.44, P=0.98, and P=0.26, respectively). The proportion of segmentectomies increased from 8.6% during the first year to 25.0% during the second year (P=0.01). One out of 6 (16.7%) segmentectomies were performed using the robot during the first year versus 15 out of 17 (88.2%) during the second year (P=0.003)., Conclusions: Use of the robot led to a significant increase in the number of segmentectomies performed in patients undergoing anatomic lung resection. With increasing lung cancer awareness and widely available screening, a greater number of small, early-stage tumors suitable for segmentectomy will likely be detected. We conclude that robotic-assisted surgery may facilitate the challenges of performing a minimally invasive segmentectomy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2249). CDS reports personal fees from Intuitive Surgical, Inc., outside the submitted work. The authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background/aim: The aim of this study was to evaluate the role of toll-like receptor 2 (TLR2) in the proliferation of human lung cancer cells and identify the signaling pathway that mediates this effect., Materials and Methods: Adenocarcinoma (A549 and H1650) and adenosquamous (H125) cells were treated with increasing doses of Pam3CSK4, a TLR2 agonist. Cell proliferation and NF-ĸB activation were evaluated. NF-ĸB was inhibited prior to treatment with Pam3CSK4 and proliferation was assessed., Results: TLR2 expression was significantly higher in A549 and H1650 cells compared to H125 cells (p<0.001). TLR2 stimulation induced proliferation in adenocarcinoma cells only and led to a corresponding increase in NF-ĸB activity (p<0.05). Inhibition of NF-ĸB prior to treatment with Pam3CSK4 attenuated this proliferative response., Conclusion: TLR2 activation induced proliferation of lung adenocarcinoma cells through activation of NF-ĸB. Thus, the TLR2 signaling pathway may be a potential therapeutic target in lung adenocarcinoma., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Small cell lung cancer (SCLC) is an aggressive tumor type characterized by rapid growth and overall poor prognosis. For the past several decades, chemotherapy and radiotherapy have served as the cornerstone of treatment. Recently, however, the role of surgery for early stage disease has gained considerable interest. Multiple retrospective and observational studies have shown excellent survival for early stage SCLC treated with surgical resection. We herein review the past and present evidence regarding surgical options for limited stage SCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.79). The series “Small Cell Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. JDM serves as the unpaid editorial board member of Journal of Thoracic Disease. Dr. JDM reports personal fees from Medtronic and Intuitive. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)