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Checkpoint inhibitors (eg, programmed cell death protein 1 [PD-1], programmed cell death ligand 1 [PD-L1], cytotoxic T-lymphocyte associated protein 4 [CTLA-4] antibodies) are changing how we understand cancer and provide a means to develop modern immunotherapies. An emergent notion relates success with checkpoint inhibitors with high mutational load tumors. There are few studies that examine checkpoint protein expression and relate these to clinical outcomes after the conventional treatment of patients with esophageal cancer, which has a high mutational load. The objective of this review is to summarize the literature that examines checkpoint expression and clinical outcomes, as well as propose an accelerated approach to introducing these therapies into the clinic to treat patients with esophageal cancer., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: [corrected] In an effort to reduce the morbidity and mortality associated with open esophagectomy, a minimally invasive approach to esophagectomy was introduced at the University of Pittsburgh Medical Center (UPMC) in 1996. The objective of this article is to discuss the optimization and refinement of minimally invasive esophagectomy (MIE) techniques over the 15-year experience at UPMC. We also reviewed the literature on technical improvements in MIE., Method: Literature highlights for MIE and related meta-analyses comparing open esophagectomy and MIE were reviewed. The rationale and outcomes of techniques refinements were discussed in detail., Results: Most meta-analyses and systematic reviews confirm the feasibility and safety of MIE and suggest similar oncologic outcomes as compared with open esophagectomy. Since 1996, over 1,000 minimally invasive esophagectomies have been performed at UPMC. We have made several refinements to the MIE procedure that we believe significantly improved our surgical outcomes. It included adjustment of width of the gastric conduit, application of omental flap, and conversion from minimally invasive, three-hole esophagectomy to minimally invasive Ivor Lewis esophagectomy., Conclusion: MIE became a mainstay in the surgical treatment of esophageal cancer at UPMC. The technical improvements detailed above make the UPMC approach to MIE a feasible, safe, and efficient procedure.

Hypothesis: Screening for esophageal adenocarcinoma has focused on identifying Barrett esophagus (BE) in patients with severe, long-standing symptoms of gastroesophageal reflux disease (GERD). Unfortunately, 95% of patients who develop esophageal adenocarcinoma are unaware of the presence of BE before their cancer diagnosis, which means they never had been selected for screening. One possible explanation is that no correlation exists between the severity of GERD symptoms and cancer risk. We hypothesize that severe GERD symptoms are not associated with an increase in the prevalence of BE, dysplasia, or cancer in patients undergoing primary endoscopic screening., Design: Cross-sectional study., Setting: University hospital., Patients: A total of 769 patients with GERD., Interventions: Primary screening endoscopy performed from November 1, 2004, through June 7, 2007., Main Outcomes Measures: Symptom severity, proton pump inhibitor therapy, and esophageal adenocarcinogenesis (ie, BE, dysplasia, or cancer)., Results: Endoscopy revealed adenocarcinogenesis in 122 patients. An increasing number of severe GERD symptoms correlated positively with endoscopic findings of esophagitis (odds ratio, 1.05; 95% confidence interval, 1.01-1.09). Conversely, an increasing number of severe GERD symptoms were associated with decreased odds of adenocarcinogenesis (odds ratio, 0.94; 95% confidence interval, 0.89-0.98). Patients taking proton pump inhibitors were 61.3% and 81.5% more likely to have adenocarcinogenesis if they reported no severe typical or atypical GERD symptoms, respectively, compared with patients taking proton pump inhibitors, who reported that all symptoms were severe., Conclusions: Medically treated patients with mild or absent GERD symptoms have significantly higher odds of adenocarcinogenesis compared with medically treated patients with severe GERD symptoms. This finding may explain the failure of the current screening paradigm in which the threshold for primary endoscopic examination is based on symptom severity.

Background: The development of anastomotic leaks and/or strictures can be associated with considerable morbidity and impairment of quality of life. In the current study, we evaluated the outcomes of patients who developed anastomotic complications after esophagectomy to elucidate the impact of these events on morbidity, mortality, and subsequent need for dilation., Methods: We analyzed retrospectively the clinical course of 235 patients who underwent transhiatal esophagectomy for cancer from 2001 to 2009. Patients with confirmed anastomotic leaks were identified and classified with the following scale: class 1: Radiographic leak only, no intervention; class 2: leak requiring opening of the wound, cervical and/or percutaneous drainage; class 3: disruption of anastomosis (10-50% circumference) with perianastomotic abscess requiring video-assisted thoracoscopic surgery or thoracotomy; and class 4: gastric tip necrosis with anastomotic separation (>50% circumference)., Results: Anastomotic leaks were encountered in 30 patients (13%). Anastomotic leaks were associated with greater morbidity (70% vs 47%; P = .02) and stricture formation (57% vs 19%; P = .0001). Mortality was not different. Increasing leak class was associated with an increased need for postoperative anastomotic dilations (P = .016)., Conclusion: Anastomotic integrity after esophagectomy has a substantial impact on perioperative course and long-term swallowing. A more formal radiographic and endoscopic leak classification system seems justified., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objectives: Esophagectomy is the standard treatment for T1 esophageal cancer (EC). Interest in endoscopic therapies, particularly for T1 EC, is increasing. We evaluated the long-term outcomes after esophagectomy and examined the pathologic features of T1 cancer to determine the suitability for potential endoscopic therapy., Methods: We reviewed the outcomes of esophagectomy in 100 consecutive patients with T1 EC. The primary end points studied were overall survival (OS) and disease-free survival (DFS). In addition to detailed pathology review, we evaluated prognostic variables associated with survival., Results: Esophagectomy was performed in 100 patients (79 men, 21 women; median age, 68 years) for T1 EC, comprising adenocarcinoma, 91; squamous, 9; intramucosal (T1a), 29; and submucosal (T1b), 71. The 30-day mortality was 0%. Resection margins were microscopically negative in 99 patients (99%). N1 disease was present in 21 (T1a, 2 of 29 [7%]; T1b, 19 of 71 [27%]), associated high-grade dysplasia in 64 (64%), and angiolymphatic invasion in 19 (19%). At a median follow-up of 66 months, estimated 5-year OS was 62% and 3-year DFS was 80% for all patients (including N1). Nodal status and tumor size were significantly associated with OS and DFS, respectively., Conclusions: Esophagectomy can be performed safely in patients with T1 EC with good long-term results. Many patients with T1 EC have several risk factors that may preclude adequate treatment with endoscopic therapy. Further prospective studies are required to evaluate endoscopic therapies. Esophagectomy should continue to remain the standard treatment in patients with T1 EC.

Background: Abnormal body mass index has been targeted as a predictor of complications after major surgery. The aim of this study was to review the impact of obesity on perioperative outcomes after minimally invasive esophagectomy., Methods: This study was a single-institution retrospective review of patients undergoing minimally invasive esophagectomy for high-grade dysplasia or cancer of the esophagus between 1999 and 2004. A body mass index of 30 or greater was considered obese. Patients with a body mass index less than 18.5 were excluded because of the potentially adverse effects of malnutrition on outcomes., Results: A total of 282 eligible patients were identified. There were 84 obese and 198 nonobese patients (mean body mass index = 34.5 versus 25.5; p < 0.0001). Preoperative demographics, comorbidities, and cancer status were similar, except for a higher prevalence of diabetes (p = 0.002), lower prevalence of peripheral vascular disease (p = 0.045), and lower prevalence of stage III disease in the obese group (p = 0.044). Operative time was significantly longer in obese patients (375 versus 301 minutes; p = 0.0001), and estimated blood loss was similar (433 versus 377 mL, obese versus nonobese, respectively). There were 5 (1.8%) overall 30-day perioperative mortalities, with no differences between the groups. Overall major (obese, 23 [27.5%] versus nonobese, 68 [34.3%]) and minor (obese, 23 [27.5%] versus nonobese, 65 [32.8%]) complication rates were also similar. Furthermore, there were no significant differences in any individual complications. There was no difference in median intensive care unit stay (obese, 1 day versus nonobese, 2 days) or overall hospital stay (obese, 7 days versus nonobese, 8 days)., Conclusions: Obesity was associated with longer operative times. Our review suggests that obesity is not a risk factor for mortality, postoperative complications, or length of hospitalization after minimally invasive esophagectomy.

Background: Standard nasogastric decompression following esophagectomy is associated with reduced patient comfort and mobility and impaired hypopharyngeal function--predisposing the patient to sinusitis, pharyngitis, and the risk of aspiration. In this study, we evaluate the results of the transcervical gastric tube drainage in the setting of esophagectomy., Methods: Transcervical gastric tube decompression was performed on 145 consecutive patients undergoing open esophagectomy between 2003 and 2007. Postoperative outcome variables include morbidity, mortality, esophagostomy duration, and length of stay., Results: There were 107 males and 38 females (median age = 66; range = 37-87). Perioperative mortality was 2.8%. Major complications included five anastomotic leaks (3.4%), ten pneumonias (6.9%), two myocardial infarctions (1.4%), and the need for reoperation in four patients (bleeding, dehiscence). Median duration of transcervical drainage was 8 days. No tubes were dislodged prematurely. There were no bleeding complications. Four patients developed cellulitis near the cervical gastric tube site and were treated successfully with antibiotics and/or tube removal., Conclusions: Transcervical gastric decompression can be performed safely with minimal complication risk. Inadvertent tube removal was not encountered in this series. The use of this technique may help to promote accelerated patient mobilization, greater patient comfort, and a durable means of gastric decompression.

Objective: The aim of this study was to evaluate the feasibility of using novel autoantibody and cancer-related protein arrays to identify potential biomarkers for the early detection of esophageal adenocarcinoma in serum., Methods: Sera from 18 patients with esophageal adenocarcinoma and 14 with gastroesophageal reflux disease were added to microarrays designed to detect circulating autoantibodies to 51 tumor-associated antigens. Sera from the same patients were also added to a 53-plex assay for various cancer-related proteins. Cutoff values at 3 standard deviations above the mean expression of gastroesophageal reflux disease were used as a boundary for positivity., Results: Nine proteins and 11 autoantibodies were able to individually segregate at least 1 esophageal adenocarcinoma sample from gastroesophageal reflux disease by means of cutoff values. The most discriminative marker was Fas ligand in the protein array, which was associated with 83.3% sensitivity and 100% specificity. The best performing autoantibody, NY-ESO-1, detected 3 esophageal adenocarcinoma samples. When both of these markers were combined, a sensitivity of 88.9% and specificity of 100% were attained., Conclusions: Cancer-related protein and autoantibody arrays provide a technically simple and rapid method of identifying potential biomarkers for the detection of esophageal adenocarcinoma in serum. Furthermore, combining these platforms improves the diagnostic power of either platform alone. Integrating technologies that detect the expression of multiple proteins and autoantibodies in serum may provide a noninvasive and accurate method of detecting early esophageal adenocarcinoma.

Background: We have previously reported our experience with minimally invasive esophagectomy. Our standard approach involves laparoscopic and thoracoscopic mobilization of the esophagus with a cervical esophagogastric anastomosis. In the present study we report our early experience with a modification of this technique, in which a high intrathoracic anastomosis is performed., Methods: From 2002 to 2005, a minimally invasive Ivor Lewis esophagectomy was performed in 50 patients. The planned approach included a totally laparoscopic abdominal procedure and either a minithoracotomy or thoracoscopy. Indications for esophagectomy included short segment Barrett's esophagus with high-grade dysplasia or resectable adenocarcinoma of the gastroesophageal junction (GEJ) with minimal proximal esophageal extension. ., Results: The median age was 62.3 years (range, 38 to 79). Twenty-five patients (50%) received either preoperative chemotherapy or chemoradiation. There was one nonemergent conversion to an open procedure during laparoscopy. Planned minithoracotomy was successful in 35 patients; an additional 15 patients had the entire thoracic component performed thoracoscopically. A circular stapled anastomosis was performed in all patients. The operative mortality was 6%. Three patients (6%) developed an anastomotic leak; all were successfully managed nonoperatively. Four patients (8%) developed postoperative pneumonia. There were no recurrent laryngeal nerve injuries., Conclusions: Minimally invasive Ivor Lewis esophagectomy was technically feasible and resulted in good initial results in our center, which is experienced in minimally invasive and open esophagectomy. This approach minimizes the degree of gastric mobilization, almost eliminates recurrent laryngeal nerve injury and pharyngeal dysfunction, and allows additional gastric resection margin in the case of cardia extension of GEJ tumors.