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Objective: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC)., Background: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC., Methods: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS)., Results: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%., Conclusions: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence., Competing Interests: P.S.A. declares research funding from ATARA Biotherapeutics; Scientific Advisory Board Member and Consultant for ATARA Biotherapeutics, Abound Bio, Adjuvant Genomics, Bayer, Carisma Therapeutics, Imugene, ImmPactBio, Johnston and Johnston, Orion pharma, OutpaceBio; Patents, royalties and intellectual property on mesothelin-targeted CAR and other T-cell therapies, which have been licensed to ATARA Biotherapeutics, issued patent method for detection of cancer cells using virus, and pending patent applications on PD-1 dominant negative receptor, wireless pulse-oximetry device, and on an ex vivo malignant pleural effusion culture system. His laboratory work is supported by grants from the National Institutes of Health (P30 CA008748, R01 CA236615-01, R01 CA235667, and U01 CA214195), the U.S. Department of Defense (BC132124, LC160212, CA170630, CA180889, and CA200437), the Batishwa Fellowship, the Cycle for Survival fund, the Comedy versus Cancer Award, the DallePezze Foundation, the Derfner Foundation, the Esophageal Cancer Education Fund, the Geoffrey Beene Foundation, the Memorial Sloan Kettering Technology Development Fund, the Miner Fund for Mesothelioma Research, the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. Memorial Sloan Kettering Cancer Center has licensed intellectual property related to mesothelin-targeted CARs and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. David Restle and Jennie K. Choe are supported, in part, by the National Institutes of Health (T32CA009501-33). The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Robotic-assisted minimally invasive esophagectomy (RAMIE) is a safe alternative to open esophagectomy (OE). However, differences in quality of life (QOL) after these procedures remain unclear. We previously reported short-term QOL outcomes after RAMIE and OE and describe here our results from 2 years of follow-up., Methods: We conducted a prospective, nonrandomized trial of patients with esophageal cancer undergoing transthoracic resection by RAMIE or OE at a single institution. The primary outcomes were patient-reported QOL, measured by the Functional Assessment of Cancer Therapy-Esophageal (FACT-E), and pain, measured by the Brief Pain Inventory (BPI). Generalized linear models were used to assess the relationship between QOL outcomes and surgery cohort. P values were adjusted (P-adj) within each model using the false discovery rate correction., Results: Esophagectomy was performed in 170 patients (106 OE and 64 RAMIE). The groups did not differ significantly by any measured clinicopathologic variables. After covariates were controlled for, FACT-E scores were higher in the RAMIE cohort than in the OE cohort (parameter estimate [PE], 6.13; P-adj = .051). RAMIE was associated with higher esophageal cancer subscale (PE, 2.72; P-adj = .022) and emotional well-being (PE, 1.25; P-adj = .016) scores. BPI pain severity scores were lower in the RAMIE cohort than in the OE cohort (PE, -0.56; P-adj = .005), but pain interference scores did not differ significantly between groups (P-adj = .11)., Conclusions: During 2 years of follow-up, RAMIE was associated with improved patient-reported QOL, including esophageal symptoms, emotional well-being, and decreased pain, compared with OE., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: A review of the outcomes of patients who received our video-assisted thoracic surgery (VATS) lung lobectomy in 2015 revealed long lengths of stay, inefficient care transitions, and overuse of resources. Focused process redesign offers a proven method for instituting improvement and changes in health care. We sought to use systems process improvement to streamline VATS lobectomies at our institution, and we targeted cost drivers to optimize quality of care and minimize overuse of resources., Methods: We performed a retrospective review of perioperative practices between January 2015 and March 2016 for patients undergoing VATS lobectomy that helped establish a value stream map, used a granular cost database, and performed real-time analysis. We used an outcomes database, which allowed us to identify cost drivers, practice variability, and rent seeking. We implemented process redesign with constant review and formal value stream reanalysis at 6-month intervals over a 2-year period., Results: We ultimately experienced an overall 187% reduction of time in the operating room (297 v 159 minutes). Our process redesign also resulted in significantly fewer chest x-rays per patient (mean, 6.7 v 2), laboratory draws (100% v 5.7%), and consultations (100% v 5.7%), which resulted in a 234% reduction in mean length of stay (4.4 v 1.88 days) and an overall cost reduction of 40%. These changes did not have a detrimental effect on patient outcomes: pulmonary complications (16.9% v 8.6%), cardiac complications (13.2% v 8.6%), and readmission rates (13.6% v 2.9%) all decreased., Conclusion: By using value stream analysis and process redesign methodologies, closely paired with highly granular cost and outcomes data, we were able to achieve significant improvements in patient outcomes and use of resources.

Background: Anastomotic leak following Ivor Lewis esophagectomy is associated with increased morbidity/mortality and decreased survival. Tissue oxygenation at the anastomotic site may influence anastomotic leak. Methods for establishing tissue oxygenation at the anastomotic site are lacking., Methods: Over a 2-year study period, 185 Ivor Lewis esophagectomies were performed. Study participants underwent measurement of gastric conduit tissue oxygenation at the planned anastomotic site using the wireless pulse oximetry device. Associations between anastomotic leaks or strictures and tissue oxygenation levels were analyzed using Wilcoxon rank sum test or Fisher's exact test., Results: Among study participants (n=114), median gastric conduit tissue oxygenation level was 92% (range, 62-100%). There were 8 (7.0%) anastomotic leaks and 3 (2.6%) strictures. Analysis of tissue oxygenation as a continuous variable showed no difference in median tissue oxygenation in patients with and without leaks (98% and 92%; P=0.2) and stricture formation (89% and 92%; P=0.6). Analysis of tissue oxygenation as a dichotomous variable found no difference in anastomotic leak rates [7.5% (n=93) in >80% vs. 0% (n=20) in ≤80%; P=0.3]. There were no significant differences in leak rates in concurrent study nonparticipants., Conclusions: No significant association was observed between intraoperative tissue oxygenation at the anastomotic site and subsequent anastomotic leak or stricture formation among patients undergoing Ivor Lewis esophagectomy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.02.58). PSA and MB have a pending patent application US20170172477A1 (wireless pulse-oximetry device). PSA has received research funding from ATARA Biotherapeutics and OSE Immunotherapies; has received research fees from ATARA Biotherapeutics; has an issued patent 10,538,588 licensed to Atara Biotherapeutics, EP1979000B1, and pending patent applications WO2018165228A1, CA3034691A1, CA3007980A1, and AU2016316033A1. PSA serves as an unpaid editorial board member of Journal of Thoracic Disease from Sep 2018 to Aug 2020. ISS serves as an unpaid editorial board member of Journal of Thoracic Disease from Sep 2018 to Aug 2020. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Minimally invasive esophagectomy may improve some perioperative outcomes over open approaches; effects on quality of life are less clear., Methods: A prospective trial of robotic-assisted minimally invasive esophagectomy (RAMIE) and open esophagectomy was initiated, measuring quality of life via the Functional Assessment of Cancer Therapy-Esophageal and Brief Pain Inventory. Mixed generalized linear models assessed associations between quality of life scores over time and by surgery type., Results: In total, 106 patients underwent open esophagectomy; 64 underwent minimally invasive esophagectomy (98% RAMIE). The groups did not differ in age, sex, comorbidities, histologic subtype, stage, or induction treatment (P = .42 to P > .95). Total Functional Assessment of Cancer Therapy-Esophageal scores were lower at 1 month (P < .001), returned to near baseline by 4 months, and did not differ between groups (P = .83). Brief Pain Inventory average pain severity (P = .007) and interference (P = .004) were lower for RAMIE. RAMIE had lower estimated blood loss (250 vs 350 cm 3 ; P < .001), shorter length of stay (9 vs 11 days; P < .001), fewer intensive care unit admissions (8% vs 20%; P = .033), more lymph nodes harvested (25 vs 22; P = .05), and longer surgical time (6.4 vs 5.4 hours; P < .001). Major complications (39% for RAMIE vs 52% for open esophagectomy; P > .95), anastomotic leak (3% vs 9%; P = .41), and 90-day mortality (2% vs 4%; P = .85) did not differ between groups. Pulmonary (14% vs 34%; P = .014) and infectious (17% vs 36%; P = .029) complications were lower for RAMIE., Conclusions: RAMIE is associated with lower immediate postoperative pain severity and interference and decreased pulmonary and infectious complications. Ongoing data accrual will assess mid-term and long-term outcomes in this cohort., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Finding of a significant replaced left hepatic artery (RLHA) during esophagectomy is relatively rare, with an incidence of approximately 5%. Sparing of the artery may be required to avoid complications of liver ischemia. Robotic assistance during esophagectomy may provide a technically superior method of artery preservation with minimally invasive approaches., Methods: This is a retrospective case series of patients undergoing robotic-assisted minimally invasive esophagectomy (RAMIE) identified to have a significant RLHA at time of surgery., Results: Five patients with a significant RLHA were identified from a series of over 100 RAMIE operations. Preservation of RLHA was accomplished in all cases without need for conversion, no intra-operative complications, and no post-operative liver dysfunction. The stomach was suitable and used for conduit reconstruction in all patients., Conclusions: Sparing of the RLHA during RAMIE is feasible and effective. The robotic assisted approach may obviate the need for open conversion during these complex minimally invasive operations., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes., Methods: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded., Results: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively ( P  < 0.001)., Conclusions: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: We have previously described our technique of robotic-assisted giant paraesophageal hernia repair (RA-GPEHR). The purpose of this study was to report our initial experience, early outcomes and learning curve with RA-GPEHR using a four-arm robotic platform., Methods: 24 consecutive patients presenting with symptomatic giant paraesophageal hernias (GPEH) underwent RA-GPEHR from April 2011 to February 2014. Peri-operative data and short-term patient outcomes were assessed by retrospective review of a prospectively maintained database., Results: Median age was 62 years (range 44-84). 15 (63%) patients underwent fundoplication and 9 (37%) gastropexy. Median procedure time was 277 min (range: 185-485) and decreased steadily over the experience. There were no intra-operative complications or surgical mortality. No patients experienced dysphagia in the early post-operative period., Conclusions: RA-GPEHR is safe, with reported short-term operative and functional outcomes similar to conventional laparoscopic approaches. The initial learning curve appears relatively short for experienced minimally invasive esophageal surgeons. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC)., Background: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons., Methods: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes., Results: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS., Conclusions: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment., Competing Interests: All authors declare no conflicts of interest.

In advanced stages, thymic tumors tend to spread locally. Distant metastatic disease is rare. We present the first report of single metastatic abdominal lymph node in a 37-year-old female patient and 5 years after an extrapleural pneumonectomy for stage IV thymoma followed by radiotherapy with no other evidence of abdominal disease successfully treated by robotic surgical resection.

Background: A standard-of-care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is pre-operative chemoradiation. Elevated levels of vascular endothelial growth factor (VEGF) have been associated with worse outcomes following chemoradiation and anti-VEGF therapies can potentiate radiation efficacy., Methods: In this single-arm phase II study, we added bevacizumab to induction chemotherapy and concurrent chemoradiation with cisplatin/irinotecan for locally advanced esophageal and GEJ adenocarcinomas., Results: Thirty-three patients were enrolled, with all evaluable. All tumors involved the GEJ and 67% were node-positive by endoscopic ultrasound (EUS) and imaging. Twenty-eight patients completed chemoradiation and 26 patients underwent surgery (25 R0 resections). Toxicities were not clearly increased. The pathologic complete response (pCR) rate was 15%. Median progression-free survival (PFS) and overall survival (OS) were 15.1 and 30.5 months respectively. Higher baseline VEGF-A levels were associated with a trend toward improved OS (not reached vs . 21.0 months, P=0.11). Response on positron emission tomography (PET) scan after induction chemotherapy was predictive of PFS and showed trends toward improved OS and pCR rate., Conclusions: The addition of bevacizumab to chemoradiation was not associated with clear worsening of toxicities but also led to no improvement in outcomes, when compared to a prior phase II study of 55 patients. Higher baseline VEGF-A levels correlated with a trend toward improved survival and might be used to stratify or select patients for future studies incorporating this or similar agents. PET scan to assess response following induction chemotherapy and change chemotherapy in non-responders during chemoradiation is the subject of a fully-accrued national trial (NCT01333033)., Competing Interests: The authors have no conflicts of interest to declare.

Background: Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen., Methods: A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease)., Results: Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis., Conclusions: Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders., Methods: Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m(2), cisplatin 60 mg/m(2) day 1, and capecitabine 625 mg/m(2) bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m(2), irinotecan 50 mg/mg(2) day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders., Results: Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30-85%] in responders compared with 56% in the non-responder group (95% CI, 20-80%, P=0.93)., Conclusions: The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial.

Objective: Robotic-assisted minimally invasive esophagectomy (RAMIE) is an emerging complex operation with limited reports detailing morbidity, mortality, and requirements for attaining proficiency. Our objective was to develop a standardized RAMIE technique, evaluate procedure safety, and assess outcomes using a dedicated operative team and 2-surgeon approach., Methods: We conducted a study of sequential patients undergoing RAMIE from January 25, 2011, to May 5, 2014. Intermedian demographics and perioperative data were compared between sequential halves of the experience using the Wilcoxon rank sum test and the Fischer exact test. Median operative time was tracked over successive 15-patient cohorts., Results: One hundred of 313 esophageal resections performed at our institution underwent RAMIE during the study period. A dedicated team including 2 attending surgeons and uniform anesthesia and OR staff was established. There were no significant differences in age, sex, histology, stage, induction therapy, or risk class between the 2 halves of the study. Estimated blood loss, conversions, operative times, and overall complications significantly decreased. The median resected lymph nodes increased but was not statistically significant. Median operative time decreased to approximately 370 minutes between the 30th and the 45th cases. There were no emergent intraoperative complications, and the anastomotic leak rate was 6% (6/100). The 30-day mortality was 0% (0/100), and the 90-day mortality was 1% (1/100)., Conclusions: Excellent perioperative and short-term patient outcomes with minimal mortality can be achieved using a standardized RAMIE procedure and a dedicated team approach. The structured process described may serve as a model to maximize patients' safety during development and assessment of complex novel procedures.

Objective: Induction therapy is often recommended for patients with clinical stage IIIA-N2 (cIIIA/pN2) lung cancer. We examined whether postinduction positron emission tomography (PET) scans were associated with ypN2 disease and survival of patients with cIIIA/pN2 disease., Methods: We performed a retrospective review of a prospectively maintained database to identify patients with cIIIA/pN2 non-small cell lung cancer treated with induction chemotherapy followed by surgery between January 2007 and December 2012. The primary aim was the association between postinduction PET avidity and ypN2 status; the secondary aims were overall survival, disease-free survival, and recurrence., Results: Persistent pathologic N2 disease was present in 61% of patients (61 out of 100). PET N2-negative disease increased from 7% (6 out of 92) before induction therapy to 47% (36 out of 77) afterward. The sensitivity, specificity, and accuracy of postinduction PET for identification of ypN2 disease were 59%, 55%, and 57%, respectively. Logistic regression analysis indicated that postinduction PET N2 status was not associated with ypN2 disease. Of the 39 patients with both pre- and postinduction PET N2-avidity, 25 (64%) had ypN2 disease. The 5-year overall survival was 40% for ypN2 disease versus 38% for N2-persistent disease (P = .936); the 5-year overall survival was 43% for postinduction PET N2-negative disease versus 39% for N2-avid disease (P = .251). The 5-year disease-free survival was 34% for ypN2-negative disease versus 9% for N2-persistent disease (P = .079)., Conclusions: Postinduction PET avidity for N2 nodes is not associated with ypN2 disease, overall survival, or disease-free survival in patients undergoing induction chemotherapy for stage IIIA/pN2 disease., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Neoadjuvant therapy is commonly administered to patients with localized disease who have T3-4 esophageal disease as staged by endoscopic ultrasound (EUS). Previously, we noted that patients who present with dysphagia have a higher EUS T stage. We hypothesized that the presence of dysphagia is predictive of EUS T3-4 disease and that staging EUS could be forgone for esophageal cancer patients with dysphagia., Methods: We performed a prospective, intent-to-treat, single-cohort study in which patients with potentially resectable esophageal cancer completed a standardized four-tier dysphagia score survey. EUS was performed as part of our standard evaluation. To determine whether the presence of dysphagia predicted EUS T3-4 disease, the dysphagia score was compared with EUS T stage., Results: The study enrolled 114 consecutive patients between August 2012 and February 2014: 77% (88 of 114) received neoadjuvant therapy, 18% (20 of 114) did not, and 5% (6 of 114) pursued treatment elsewhere. In total, 70% (80 of 114) underwent esophagectomy; of these, 54% (61 of 114) had dysphagia and 46% (53 of 114) did not. Dysphagia scores were 66% (40 of 61) grade 1, 25% (15 of 61) grade 2, and 10% (6 of 61) grade 3 to 4. Among patients with dysphagia, 89% (54 of 61) had T3-4 disease by EUS; among those without dysphagia, only 53% (28 of 53) had T3-4 disease by EUS (p < 0.001)., Conclusions: The presence of dysphagia in patients with esophageal cancer was highly predictive of T3-4 disease by EUS. On the basis of this finding, approximately 50% of patients currently undergoing staging EUS at our institution could potentially forgo EUS before neoadjuvant therapy. Patients without dysphagia, however, should still undergo EUS., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Esophageal anastomotic leaks after cancer surgery remain a major cause of morbidity and mortality. Endoscopic interventions, including covered metal stents (cSEMS), clips, and direct percutaneous endoscopic jejunostomy (dPEJ) tubes are increasingly used despite limited published data regarding their utility in this setting. This study aimed to determine the efficacy and safety of a multimodality endoscopic approach to anastomotic leak management after operation for esophageal or gastric cancer., Methods: We performed a retrospective review of prospectively maintained databases of gastric and esophageal operations at our hospital between January 2003 and December 2012. Included patients had an operation for esophageal or gastric cancer, demonstrated evidence of an anastomotic leak at the esophageal anastomosis, and underwent attempted endoscopic therapy. Healing was defined as clinical and radiographic leak resolution., Results: Forty-nine patients with leaks underwent endoscopic management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a combined approach. Overall, 88% of patients achieved healing in a median of 83 days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic approach healed. Only 1 patient had a major complication associated with stent erosion into the pulmonary artery, which was successfully treated with operative repair., Conclusions: Esophageal anastomotic leaks after esophageal and gastric cancer operations can be managed successfully and safely with endoscopic therapy. Combining cSEMS for leak control and dPEJ tube placement for nutritional support was highly effective in achieving healing, without the need for surgical repair., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Current eligibility criteria for lung cancer screening may underestimate the risk of malignancy for some individuals. We compared the predicted risk of lung cancer among patients who would have met screening criteria to those who would not have despite being at moderate-risk., Methods: A retrospective cohort study of resected lung cancer patients was performed. The screen eligible group was based on criteria provided by the United States Preventive Services Task Force; age 55 to 80 and a 30 or greater pack-year smoking history. The screen ineligible group was based on criteria provided by the National Comprehensive Cancer Network for a moderate-risk individual not recommended screening; age greater than 50 years, greater than 20 pack-year smoking history, and no history of asbestos exposure or chronic obstructive pulmonary disease. A recently validated risk-prediction model was used to compare the risk of lung cancer across eligibility groups based on measured and imputed patient-level variables., Results: Screen ineligible patients (n = 88) had a lower estimated probability of lung cancer than screen eligible patients (n = 419); 1.3% versus 3.1%, p value less than 0.001. However, 20% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the prevalence of lung cancer (3.7%) among National Lung Screening Trial participants; 17% of screen ineligible patients had a predicted probability of lung cancer greater than or equal to the American Association for Thoracic Surgery threshold (5%) defining high-risk individuals., Conclusions: Current eligibility criteria for lung cancer screening underestimate the risk of lung cancer for some individuals who might benefit from lung cancer screening., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated the role of the 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) classification in predicting occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma., Methods: We reviewed lung adenocarcinoma patients who had clinically N2-negative status, were evaluated by preoperative positron emission tomography combined with computed tomography (PET/CT) and had undergone lobectomy or pneumonectomy at Memorial Sloan Kettering Cancer Center (n = 297). Tumours were classified according to the 2011 IASLC/ATS/ERS classification. The associations between occult lymph node metastasis and clinicopathological variables were analysed using Fisher's exact test and logistic regression analysis., Results: Thirty-two (11%) cN0-1 patients had occult mediastinal lymph node metastasis (pN2) whereas 25% of cN1 patients had pN2 disease. Increased micropapillary pattern was associated with increased risk of pN2 disease (P = 0.001). On univariate analysis, high maximum standard uptake value of the primary tumour on PET/CT (P = 0.019) and the presence of micropapillary (P = 0.014) and solid pattern (P = 0.014) were associated with occult pN2 disease. On multivariable analysis, micropapillary pattern was positively associated with risk of pN2 disease (odds ratio = 3.41; 95% confidence intervals = 1.42-8.19; P = 0.006)., Conclusions: The presence of micropapillary pattern is an independent predictor of occult mediastinal lymph node metastasis. Our observations have potential therapeutic implications for management of early-stage lung adenocarcinoma., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Unlabelled: Thoracic lymph nodes with marginally elevated maximum standardized uptake value (SUVmax) on PET/CT a diagnostic challenge in staging non-small-cell lung cancer. We evaluated the ratio of lymph node to primary tumor SUVmax (SUVN/T) in predicting nodal malignancy among 132 sampled nodes from 85 patients both a primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0. SUVN/T was more accurate than SUVmax for this subset of patients., Introduction/background: Among non-small-cell lung cancers with appreciable functional activity, positron emission tomography/computed tomography (PET/CT) is the most accurate imaging modality for clinical staging. However, lymph nodes (LN) with marginally elevated standardized uptake value (SUV) present a diagnostic challenge. In this retrospective study, we hypothesized that normalizing the LN SUV by using the ratio of the LN to primary tumor SUVmax (SUVN/T) may be a better predictor of nodal malignancy than using SUVmax alone for nodes with low to intermediate SUV., Patients and Methods: We identified 172 patients with newly diagnosed non-small-cell lung cancer who underwent pathologic LN staging and PET/CT within 31 days before biopsy. Receiver operating characteristic curves with area under the curve (AUC) calculations were used to evaluate SUVmax and SUVN/T for their ability to predict nodal malignancy for both the entire cohort of 504 LNs and a subset of 132 LNs from 85 patients who had both primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0., Results: In patients with primary tumor SUVmax > 2.5 and LN SUVmax 2.0 to 6.0, SUVN/T was significantly more accurate in predicting nodal malignancy (AUC, 0.846; 95% confidence interval, 0.775-0.917) than SUVmax (AUC, 0.653; 95% confidence interval, 0.548-0.759). The optimal cutoff value of SUVN/T to predict nodal malignancy was 0.28 (90% sensitivity, 68% specificity). Sensitivity was > 95% for SUVN/T < 0.21, whereas specificity was > 95% for SUVN/T > 0.50., Conclusion: The ratio of LN SUV to primary tumor SUV on PET/CT is more accurate than SUVmax when assessing nodes of low to intermediate SUV., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS)., Patients and Methods: We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated., Results: Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS., Conclusion: In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma., (© 2015 by American Society of Clinical Oncology.)

Introduction: Accurate assessment of lymph node (LN) involvement with malignancy is critical to staging and management of non-small-cell lung cancer. The goal of this retrospective study was to determine the tumor and imaging characteristics independently associated with malignant involvement of LNs visualized on positron emission tomography/computed tomography (PET/CT)., Methods: From 2002 to 2011, 172 patients with newly diagnosed non-small-cell lung cancer underwent PET/CT within 31 days before LN biopsy. Among these patients, 504 anatomically defined, pathology-confirmed LNs were visualized on PET/CT. Logistic regression analysis was used to determine the associations between nodal involvement with malignancy and several clinical and imaging variables, including tumor histology, tumor grade, LN risk category in relation to the primary tumor location, pathologic findings from additional biopsied LNs, interval between PET/CT and biopsy, primary tumor largest dimension, primary tumor standardized uptake value (SUVmax), LN short-axis dimension, and LN SUVmax., Results: On univariate analysis, adenocarcinoma histology (p = 0.010), high LN risk category (p < 0.001), larger LN short-axis dimension (p < 0.001), and higher LN SUVmax (p < 0.001) all correlated with nodal involvement. On multivariate analysis, adenocarcinoma histology (p = 0.003), high LN risk category (p = 0.005), and higher LN SUVmax (p < 0.001) correlated with nodal involvement, whereas LN short-axis dimension was no longer statistically significant (p = 0.180). A nomogram developed for clinical application based on this analysis had excellent concordance between predicted and observed results (concordance index, 0.95)., Conclusion: Adenocarcinoma histology, higher LN SUVmax, and higher LN risk category independently correlate with nodal involvement with malignancy and may be used in a model to accurately predict the risk of a node's involvement with malignancy.

Prosthetic reconstruction of the chest wall after oncologic resection is performed by means of various techniques using different materials. We describe a new technique of chest wall reconstruction that includes the use of Marlex mesh and the creation of a neo-rib from a Steinmann pin and methyl methacrylate., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We sought to determine the prognostic variables associated with overall survival (OS) and recurrence-free probability (RFP) in patients with primary and secondary sternal tumors treated with surgical resection., Methods: A retrospective analysis of patients who underwent resection of primary or secondary sternal tumors at 2 cancer institutes between 1995 and 2013 was performed. OS and RFP were estimated using the Kaplan-Meier method, and predictors of OS and RFP were analyzed using the Cox proportional hazards model., Results: Sternal resection was performed in 78 patients with curative (67 [86%]) or palliative (6 [8%]) intent. Seventy-three patients (94%) had malignant tumors, of which 28 (36%) were primary and 45 (57%) were secondary malignancies. Sternal resections were complete in 13 patients (17%) and partial in 65 (83%). There were no perioperative deaths, and grade III/IV complications were noted in 17 patients (22%). The 5-year OS was 80% for patients with primary malignant tumors, 73% for patients with nonbreast secondary malignant tumors, and 58% for patients with breast tumors (p = 0.85). In the overall cohort, R0 resection was associated with prolonged 5-year OS (84% vs 20%) on univariate (p = 0.004) and multivariate (adjusted hazard ratio, 3.37; p = 0.029) analysis. On subgroup analysis, R0 resection was associated with improved OS and RFP only for patients with primary malignant tumors., Conclusions: Sternal resection can achieve favorable OS for patients with primary and secondary sternal tumors. R0 resection is associated with improved 5-year OS and RFP in patients with primary malignant tumors. We did not detect a similar effect in patients with breast or nonbreast secondary tumors., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Although the technical aspects of robotic video-assisted thoracic surgery (RVATS) for lung resections may be advantageous, compared with standard thoracoscopy, complications of chylothorax and recurrent laryngeal nerve injury (RLNI) associated with mediastinal lymph node dissection (MLND) may be significant., Methods: Consecutive patients who underwent RVATS anatomic lung resection for suspected or confirmed cancer and experienced RLNI or chylothorax were identified and reviewed from a prospectively maintained database. Complications were graded according to the Common Terminology Criteria for Adverse Events version 3.0., Results: From July 28, 2010, to December 20, 2013, 251 patients underwent RVATS segmentectomy, lobectomy, or bilobectomy with MLND. Eleven patients (4.4%) experienced MLND-related complications and composed the study group; 81.8% were right-sided resections, and the median lymph node counts in right station IV and station VII were 9 (range, 1-23) and 5.5 (range, 1-10); 72.7% of the cases were performed for early-stage I and II lung cancers. Chylothorax [6/251 (2.4%)] and RLNI [6/251 (2.4%)] were significantly more common in the RVATS group than in the open thoracotomy and standard VATS groups. Complications requiring procedural intervention (Grade 3) are as follows: 4 cases of RLNI in patients undergoing percutaneous vocal cord medialization and 3 cases of chylothorax in patients undergoing image-guided thoracic duct embolization or maceration. No operative interventions were required., Conclusions: RVATS MLND may be associated with increased rates of chylothorax and RLNI. Attention must be paid to identifying potential technical pitfalls with RVATS lung resections, adjusting surgical techniques accordingly, and minimizing patient morbidity.

The National Lung Screening Trial was a large, multicenter, randomized controlled trial published in 2011. It found that annual screening with low-dose CT (LDCT) in a high-risk population was associated with a 20% reduction in lung cancer-specific mortality compared with conventional chest radiography. Several leading professional organizations have since put forth lung cancer screening guidelines that include the use of LDCT, largely on the basis of this study. Broad adoption of these screening recommendations, however, remains a challenge., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Tumor invasion in lung adenocarcinoma is defined as infiltration of stroma, blood vessels, or pleura. Based on observation of tumor spread through air spaces (STAS), we considered whether this could represent new patterns of invasion and investigated whether it correlated with locoregional versus distant recurrence according to limited resection versus lobectomy., Methods: We reviewed resected small (less than or equal to 2 cm) stage I lung adenocarcinomas (n = 411; 1995-2006). Tumor STAS was defined as tumor cells-micropapillary structures, solid nests, or single cells-spreading within air spaces in the lung parenchyma beyond the edge of the main tumor. Competing risks methods were used to estimate risk of disease recurrence and its associations with clinicopathological risk factors., Results: STAS was observed in 155 cases (38%). In the limited resection group (n = 120), the risk of any recurrence was significantly higher in patients with STAS-positive tumors than that of patients with STAS-negative tumors (5-year cumulative incidence of recurrence, 42.6% versus 10.9%; P < 0.001); the presence of STAS correlated with higher risk of distant (P = 0.035) and locoregional recurrence (P = 0.001). However, in the lobectomy group (n = 291), the presence of STAS was not associated with either any (P = 0.50) or distant recurrence (P = 0.76). In a multivariate analysis, the presence of tumor STAS remained independently associated with the risk of developing recurrence (hazard ratio, 3.08; P = 0.014)., Conclusion: The presence of STAS is a significant risk factor of recurrence in small lung adenocarcinomas treated with limited resection. These findings support our proposal that STAS should formally be recognized as a pattern of invasion in lung adenocarcinoma.

Background: Operative mortality rates are of great interest to surgeons, patients, policy makers, and payers as a metric for quality assessment. Thirty-day mortality and discharge mortality have been presumed to capture procedure-related deaths. However, many patients die after the 30-day mark or are transferred to other facilities or to home and die there, leading to the underreporting of surgically related deaths. We hypothesized that a longer period of observation would address these concerns and provide a more accurate measure of operative mortality., Methods: We retrospectively reviewed institutional databases of patients undergoing resection for lung cancer, esophageal cancer, and mesothelioma. Mortality rates at 30 and 90 days were calculated with 95% confidence intervals (CIs)., Results: From 1999 to 2012, 7,646 surgical resections were performed: 6,119 for lung cancer, 1,258 for esophageal cancer, and 269 for mesothelioma. Among the different cancers and across operations, the additional mortality from day 31 to 90 (1.4%; 95% CI, 1.2% to 1.8%; n=111) was similar to that by day 30 (1.2%; 95% CI, 1.0% to 1.5%; n=95), resulting in overall 90-day mortality (2.7%; 95% CI, 2.3% to 3.1%; n=206) that was more than double the 30-day mortality., Conclusions: Among patients who have undergone operations for thoracic malignancies, mortality attributable to the operation occurs beyond the first 30 postsurgical days as well as after hospital discharge. Because cancer operations constitute a large portion of general thoracic surgery, we recommend national databases consider the inclusion of 90-day mortality in their data collection., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive lung lobectomy and segmentectomy by video-assisted thoracic surgery (VATS) are assumed to result in better quality of life and less postoperative pain compared with standard open approaches. To date, few prospective studies have compared the two approaches. We performed a prospective cohort study to compare quality of life and pain scores during the first 12 months after VATS or open anatomic resection., Methods: Patients were prospectively enrolled from May 2009 to April 2012. Patients with clinical stage I lung cancer who were scheduled to undergo anatomic lung resection were eligible. The Brief Pain Index and Medical Outcomes Study 36-Item Short Form Health Survey were conducted perioperatively and at four assessments during the first 12 months after the operation. Intent-to-treat analyses using mixed-effects models were used to longitudinally assess the effect of treatment on quality of life components (physical component summary and mental component summary) and pain., Results: In total, 74 patients underwent thoracotomy, and 132 underwent VATS (including 19 patients who were converted to thoracotomy); 40 and 80 patients, respectively, completed the 12-month surveys. Baseline characteristics were similar between the two groups. Physical component summary and Brief Pain Index scores were similar between the two groups throughout the 12 months of follow-up. The mental component summary score, however, was consistently worse in the VATS group., Conclusions: Patient-reported physical component summary and pain scores after VATS and thoracotomy were similar during the first 12 months after surgical resection., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

During esophagectomy, identification and preservation of the right gastroepiploic vascular arcade are critical and may be challenging with minimally invasive approaches. We assessed the use of near-infrared fluorescence imaging fluorescence angiography (NIFI-FA) during robotic-assisted minimally invasive esophagectomy (RAMIE) as an aid to visualize the gastric vasculature with mobilization. After intravenous administration of 10 mg of indocyanine green, a robotic platform with near-infrared optical fluorescence capability was used to examine the gastric vasculature in patients undergoing RAMIE. Thirty (71%) of 42 patients undergoing RAMIE were assessed using NIFI-FA during mobilization of the greater gastric curve and fundus; 11 were excluded because the system was not available, and 1 was excluded because of documented allergy to iodinated contrast. The median time from indocyanine green administration to detectable fluorescence was 37.5 seconds (range, 20-105 seconds). Near-infrared fluorescence imaging FA identified or confirmed termination of the vascular arcade in all 30 cases. Subjectively, NIFI-FA often identified otherwise unvisualized small transverse vessels between the termination of the vascular arcade and the first short gastric artery, as well as between the short gastric arteries. Identification and/or confirmation of the vascular arcade position during mobilization of the greater curve/omentum were also aided by NIFI-FA. Although there are limitations to the current technology, NIFI-FA may be a useful adjunct to confirm and identify the position of gastroepiploic vessels, allow for safer and more confident dissections during gastric mobilization, as well as potentially decrease serious intraoperative vascular misadventures.

Background: Recent advances have improved the likelihood of long-term survival for patients with lung cancer. However, little attention has been given to the growing need for dedicated survivorship care for these patients. To address this unmet need, we developed a unique follow-up care model., Methods: In 2006, we convened a multidisciplinary working group to design a thoracic survivorship program (TSP) that provides follow-up by a nurse practitioner (NP) trained in survivorship care. Patients with early-stage lung cancer who were disease free for at least 1 year after resection were eligible for the program, which incorporates a standardized approach to cancer surveillance. Data on symptoms and outcomes were prospectively collected. Real-time electronic medical documentation was developed to optimize communication with primary physicians., Results: Data were analyzed for the initial phase of the program, which comprised 655 patients. Ninety-two percent of eligible survivors who remained disease free chose to continue their care in the TSP, rather than receive follow-up with their thoracic surgeon. Clinically significant posttreatment symptoms were common, including fatigue (46%), anxiety (32%), chronic pain (25%), dyspnea (14%), and depression (12%). The majority of recurrences (72%) and second primary cancers (91%) in this cohort were identified by scheduled chest computed tomography at TSP visits., Conclusions: Survivorship care for patients with lung cancer, delivered in our NP-led TSP, is feasible, effective, and well accepted by patients. Through the implementation of a uniform self-sustaining patient-centered system, the TSP model improves on the variation of physician-led follow-up care., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Smokers have a higher risk of developing non-small cell lung cancer (NSCLC) than never-smokers, but the relative risk of developing second primary lung cancer (SPLC) is unclear. Determining the risk of SPLC in smokers versus never-smokers after treatment of an initial cancer may help guide recommendations for long-term surveillance., Methods: Patients who underwent resection for stage I adenocarcinoma were identified from a prospectively maintained institutional database. Patients with other histologies, synchronous lesions, or who received neoadjuvant or adjuvant therapy were excluded. The SPLCs were identified based on Martini criteria., Results: From 1995 to 2012, a total of 2,151 patients underwent resection for stage I adenocarcinoma (308 never-smokers [14%] and 1,843 ever-smokers [86%]). SPLC developed in 30 never-smokers (9.9%) and 145 ever-smokers (7.8%). The SPLC was detected by surveillance computed tomography scan in the majority of patients (161; 92%). In total, 87% of never-smokers and 83% of ever-smokers had stage I SPLC. There was no significant difference in the cumulative incidence of SPLC between never-smokers and ever-smokers (p = 0.18) in a competing-risks analysis. The cumulative incidence at 10 years was 20.3% for never-smokers and 18.2% for ever-smokers., Conclusions: Although smokers have a greater risk of NSCLC, the risk of a second primary cancer developing after resection of stage I lung cancer is comparable between smokers and never-smokers. The majority of these second primary cancers are detectable at a curable stage. Ongoing postoperative surveillance should be recommended for all patients regardless of smoking status., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Robotic-assisted minimally invasive esophagectomy (RAMIE) is emerging as a potential alternative approach to standard minimally invasive esophagectomy (MIE). However, early reports vary widely in operative approach, method, and reporting of outcomes, including operative complications. A formal, prospective academic program to evaluate RAMIE was initiated at the authors' institution, with the primary goal of maximizing patient safety during the introduction of new technology into the operating room. The standardized RAMIE Ivor Lewis approach developed through this program is described in detail. The available literature is reviewed, with early reports suggesting outcomes similar to those of MIE and standard open esophagectomy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rates of pathological complete response. A pathological complete response is recognized to be an important predictor of improved survival, to the extent that observation rather than surgery is advocated by some in patients with presumed pathological complete response based on their clinical response. The goal of this study was to look at the ability of clinical variables to predict pathological complete response after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients with locally advanced esophageal squamous cell carcinoma who underwent chemoradiotherapy followed by surgery and compared those with pathological complete response to patients with residual disease. Between January 1996 and December 2010, 116 patients met inclusion criteria. Fifty-six percent of patients had a pathological complete response and a median survival of 128.1 months versus 28.4 months in patients with residual disease. When compared with patients with residual disease, patients with a pathological complete response had a lower post-neoadjuvant positron emission tomography (PET) maximum standardized uptake value (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post-chemoradiotherapy computed tomography and a higher rate of normal appearing post-chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of these characteristics alone was able to correctly identify patients with a pathological complete response, and none has significant specificity. Although the rate of pathological complete response after chemoradiotherapy is high in patients with esophageal squamous cell carcinoma, the ability of identifying patients with pathological complete response is limited. A reduction of the PET SUVmax by >70%, a normal appearing endoscopic examination, and no residual disease on biopsy all were seen in >65% of the patients with a pathological complete response. Even if these findings were unable to confirm the absence of residual disease in the primary tumor, they can help guide expectant management in high-risk patients., (© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Purpose: Limited resection is an increasingly utilized option for treatment of clinical stage IA lung adenocarcinoma (ADC) ≤2 cm (T1aN0M0), yet there are no validated predictive factors for postoperative recurrence. We investigated the prognostic value of preoperative consolidation/tumor (C/T) ratio [on computed tomography (CT) scan] and maximum standardized uptake value (SUVmax) on (18)F-fluorodeoxyglucose-positron emission tomography (PET) scan., Methods: We retrospectively reviewed 962 consecutive patients who underwent limited resection for lung cancer at Memorial Sloan-Kettering between 2000 and 2008. Patients with available CT and PET scans were included in the analysis. C/T ratio of 25 % (in accordance with the Japan Clinical Oncology Group 0201) and SUVmax of 2.2 (cohort median) were used as cutoffs. Cumulative incidence of recurrence (CIR) was assessed., Results: A total of 181 patients met the study inclusion criteria. Patients with a low C/T ratio (n = 15) had a significantly lower 5-year recurrence rate compared with patients with a high C/T ratio (n = 166) (5-year CIR, 0 vs. 33 %; p = 0.015), as did patients with low SUVmax (n = 86) compared with patients with high SUVmax (n = 95; 5-year CIR, 18 vs. 40 %; p = 0.002). Furthermore, within the high C/T ratio group, SUVmax further stratified risk of recurrence [5-year CIR, 22 % (low) vs. 40 % (high); p = 0.018]., Conclusions: With the expected increase in diagnoses of small lung ADC as a result of more widespread use of CT screening, C/T ratio and SUVmax are widely available markers that can be used to stratify the risk of recurrence among cT1aN0M0 patients after limited resection.

Introduction: After definitive treatment of esophageal cancer, patients are at high risk for recurrence. Consistent follow-up is important for detection and treatment of recurrence. The optimal surveillance regimen remains undefined. We investigated posttreatment recurrence patterns and methods of detection in survivors of esophageal cancer., Methods: We retrospectively studied a cohort of patients who had undergone surgical resection for esophageal cancer at our institution between 1996 and 2010. Routine computed tomography scan and upper endoscopy were performed for surveillance., Results: In total, 1147 patients with resected esophageal adenocarcinoma or squamous cell carcinoma were included (median follow-up, 46 months). Of these, 723 patients (63%) had received neoadjuvant therapy before surgery. During follow-up, there were 595 deaths (52%) and 435 recurrences (38%) (distant [55%], locoregional [28%], or both [17%]). Half of recurrences were detected as a result of symptoms (n = 217), 45% by routine chest and abdominal computed tomography scan (n = 194), and 1% by surveillance upper endoscopy (n = 6). The recurrence rate decreased from 27 per 100 person-years in posttreatment year 1 to 4 per 100 person-years in year 6. In the first 2 years, the rate of recurrence was higher among patients who had received neoadjuvant therapy (35 per 100 person-years) than among those who had not (14 per 100 person-years) (p < 0.001)., Conclusions: The incidence of recurrence is high after esophagectomy for cancer. Surveillance endoscopy has limited value for detection of asymptomatic local recurrence. The yield from follow-up scans diminishes significantly after the sixth year; surveillance scans after that point are likely unnecessary.

Background: T1 (≤ 3 cm) tumors with visceral pleural invasion (VPI) are upstaged to T2a (stage IB) in the TNM classification. We investigated the effect of VPI on the cumulative incidence of recurrence (CIR) and overall survival (OS) of lung adenocarcinoma (ADC) ≤ 2 cm (T1a) and 2 to 3 cm (T1b)., Methods: OS and CIR among patients with or without VPI were examined by tumor size (≤ 2 and 2-3 cm) in 777 patients with node-negative lung ADC ≤ 3 cm who underwent resection., Results: Among patients with tumors ≤ 2 cm, VPI was not associated with either increased CIR (P = .90) or decreased OS (P = .11). Among patients with tumors 2 to 3 cm in size, the presence of VPI was associated with increased CIR (P = .015) and decreased OS (P &lt; .001), even after adjusting for histologic subtype. When stage I lung ADCs ≤ 3 cm were regrouped as either new stage IA (≤ 2 cm with or without VPI, 2-3 cm without VPI) or new stage IB (2-3 cm with VPI), there was a statistically significant difference in 5-year CIR and OS between new stage IA and new stage IB tumors (CIR, 18% vs 40% [P = .004]; OS, 76% vs 51% [P &lt; .001])., Conclusions: VPI stratifies prognosis in patients with lung ADC 2 to 3 cm but not in those with tumors ≤ 2 cm. Our proposed regrouping of a new stage IB better stratifies patients with poor prognosis, similar to published outcomes in patients with stage II disease, who may benefit from adjuvant chemotherapy.

Introduction: Guidance is limited for invasive staging in patients with lung cancer without mediastinal disease by positron emission tomography (PET). We developed and validated a prediction model for pathologic N2 disease (pN2), using six previously described risk factors: tumor location and size by computed tomography (CT), nodal disease by CT, maximum standardized uptake value of the primary tumor, N1 by PET, and histology., Methods: A cohort study (2004-2009) was performed in patients with T1/T2 by CT and N0/N1 by PET. Logistic regression analysis was used to develop a prediction model for pN2 among a random development set (n = 625). The model was validated in both the development set, which comprised two thirds of the patients and the validation set (n = 313), which comprised the remaining one third. Model performance was assessed in terms of discrimination and calibration., Results: Among 938 patients, 9.9% had pN2 (9 detected by invasive staging and 84 intraoperatively). In the development set, univariate analyses demonstrated a significant association between pN2 and increasing tumor size (p < 0.001), nodal status by CT (p = 0.007), maximum standardized uptake value of the primary tumor (p = 0.027), and N1 by PET (p < 0.001); however, only N1 by PET was associated with pN2 (p < 0.001) in the multivariate prediction model. The model performed reasonably well in the development (c-statistic, 0.70; 95% confidence interval, 0.63-0.77; goodness of fit p = 0.61) and validation (c-statistic, 0.65; 95% confidence interval, 0.56-0.74; goodness-of-fit p = 0.19) sets., Conclusion: A prediction model for pN2 based on six previously described risk factors has reasonable performance characteristics. Observations from this study may guide prospective, multicenter development and validation of a prediction model for pN2.

Background: We sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO)., Methods: Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification on all consecutive patients who underwent LR or LO for small lung ADC between 1995 and 2009 at Memorial Sloan-Kettering Cancer Center. Clinical characteristics and pathologic data were retrospectively evaluated for 734 consecutive patients (LR: 258; LO: 476). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Grey's test. All statistical tests were two-sided., Results: Application of IASLC/ATS/ERS lung ADC histologic subtyping to predict recurrence demonstrates that, in the LR group but not in the LO group, micropapillary (MIP) component of 5% or greater was associated with an increased risk of recurrence, compared with MIP component of less than 5% (LR: 5-year CIR = 34.2%, 95% confidence interval [CI] = 23.5% to 49.7% vs 5-year CIR = 12.4%, 95% CI = 6.9% to 22.1%, P < .001; LO: 5-year CIR = 19.1%, 95% CI = 12.0% to 30.5% vs 15-year CIR = 12.9%, 95% CI = 7.6% to 21.9%, P = .13). In the LR group, among patients with tumors with an MIP component of 5% or greater, most recurrences (63.4%) were locoregional; MIP component of 5% or greater was statistically significantly associated with increased risk of local recurrence when the surgical margin was less than 1cm (5-year CIR = 32.0%, 95% CI = 18.6% to 46.0% for MIP ≥ 5% vs 5-year CIR = 7.6%, 95% CI = 2.3% to 15.6% for MIP < 5%; P = .007) but not when surgical margin was 1cm or greater (5-year CIR = 13.0%, 95% CI = 4.1% to 22.1% for MIP ≥ 5% vs 5-year CIR = 3.4%, 95% CI = 0% to 7.7% for MIP < 5%; P = .10)., Conclusions: Application of the IASLC/ATS/ERS classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.

Objectives: This study reports an early, single-institution experience of combined thoracoscopic and laparoscopic robotic-assisted minimally invasive esophagectomy (RAMIE) using a four-arm robotic platform, with special attention given to the pitfalls and complications during procedure development., Methods: We conducted a prospective, single-cohort, observational study of patients undergoing RAMIE at a single institution., Results: A total of 21 patients (median age, 62 years [range, 37-83 years]) underwent RAMIE with a four-arm robotic platform (17 by Ivor Lewis and 4 by McKeown). Of the patients, 17 (81%) had a complete (R0) resection, and 16 (76%) received induction treatment, the majority (14/21 [67%]) with combined chemoradiation. The median operative time was 556 min (range, 395-807 min), which decreased to 414 min (range, 405-543 min) for the last 5 cases in the series. The median estimated blood loss was 307 cm(3) (range, 200-500 cm(3)), and the median length of hospital stay was 10 days (range, 7-70 days). The median number of lymph nodes resected was 20 (range, 10-49). Five (24%) patients were converted to open procedures. Five patients (24%) had major complications. One (5%) died of complications on postoperative Day 70, and 3 (14%) had clinically significant anastomotic leaks (Grade II or greater, by Common Terminology Criteria for Adverse Events version 3.0). Three patients (14%) in this early experience developed airway fistulas., Conclusions: While four-arm RAMIE may offer advantages over standard minimally invasive esophagectomy approaches, its adoption in a structured program, with critical evaluation of adverse events and subsequent adjustment of technique, is paramount to maximize patient safety, minimize complications and improve the conduct of operation early in the learning curve. Particular technical consideration should be given to prevention of airway complications.

Background: We investigated the association between the newly proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), and whether the combination of these radiologic and pathologic factors can further prognostically stratify patients with stage I lung adenocarcinoma., Methods: We retrospectively evaluated 222 patients with pathologic stage I lung adenocarcinoma who underwent FDG-PET scanning before undergoing surgical resection between 1999 and 2005. Patients were classified by histologic grade according to the IASLC/ATS/ERS classification (low, intermediate, or high grade) and by maximum standard uptake value (SUVmax) (low <3.0, high ≥3.0). The cumulative incidence of recurrence (CIR) was used to estimate recurrence probabilities., Results: Patients with high-grade histology had higher risk of recurrence (5-year CIR, 29% [n = 25]) than those with intermediate-grade (13% [n = 181]) or low-grade (11% [n = 16]) histology (p = 0.046). High SUVmax was associated with high-grade histology (p < 0.001) and with increased risk of recurrence compared to low SUVmax (5-year CIR, 21% [n = 113] vs. 8% [n = 109]; p = 0.013). Among patients with intermediate-grade histology, those with high SUVmax had higher risk of recurrence than those with low SUVmax (5-year CIR, 19% [n = 87] vs. 7% [n = 94]; p = 0.033). SUVmax was associated with recurrence even after adjusting for pathologic stage (p = 0.037)., Conclusions: SUVmax on FDG-PET correlates with the IASLC/ATS/ERS classification and can be used to stratify patients with intermediate-grade histology, the predominant histologic subtype, into two prognostic subsets.

Background: The National Quality Forum endorses prolonged length of stay of more than 14 days (PLOS) as a quality metric for lobectomy for lung cancer. Because PLOS rates are lower than complication rates, we hypothesized that PLOS misses a significant proportion of clinically important events., Methods: A retrospective study was performed on patients undergoing lobectomy (2000 to 2009). The severity of adverse events was based on the National Cancer Institute common terminology criteria for adverse events (grade 2 or higher indicates symptoms or need for medical intervention; grade 5 indicates death)., Results: Among 2,667 patients, 163 (6%) experienced PLOS and 773 (29%) experienced an adverse event. Although the frequency of adverse events was higher among the PLOS group (99% [161 of 163] versus 24% [612 of 2504]), 79% (612 of 773) of adverse events occurred in the non-PLOS group. Whereas PLOS was associated with more severe events, 89% of those in the non-PLOS group experienced a grade 2 or higher event. Likewise, although PLOS was associated with the lowest 5-year survival rate (31%), patients in the non-PLOS group who had an adverse event had significantly lower survival rates than patients in the non-PLOS group who did not have any adverse events (55% versus 68%, p<0.001; adjusted hazard ratio 1.3 [95% confidence interval: 1.1 to 1.6])., Conclusions: The PLOS missed a high proportion of adverse events defined by the need for ongoing inpatient therapy and an association with poor long-term survival. These findings have implications for efficient and fair performance assessment in the setting of a quality improvement program., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Mesothelin is overexpressed in several malignancies and is purportedly a specific marker of malignant transformation. In this pilot study, we investigated whether tissue and serum mesothelin are potential markers of neoplastic progression in Barrett's esophagus (BE) and in esophageal adenocarcinoma (EAC)., Methods: Mesothelin expression was retrospectively evaluated in normal, BE, and EAC tissue from surgically resected esophageal specimens (n = 125). In addition, soluble mesothelin-related peptide (SMRP) levels were measured in serum., Results: Normal esophageal mucosa did not express mesothelin. BE tissue with high-grade dysplasia specifically expressed mesothelin, whereas BE tissue with low-grade or without dysplasia did not. Fifty-seven (46%) EAC tumors were positive for mesothelin. EAC tumors with BE expressed mesothelin more often than those without BE (58% vs. 35%, P = 0.01). SMRP levels were elevated in 70% of EAC patients (mean = 0.89 nmol/L; range: 0.03-3.77 nmol/L), but not in patients with acid reflux and/or BE., Conclusions: Mesothelin is commonly expressed in BE-associated EAC. On the basis of this pilot study, a prospective study is under way to evaluate tissue and serum mesothelin which are potential markers of neoplastic progression in BE and in EAC (NCT01393483)., Impact: Current surveillance methods in Barrett's esophagus are invasive and neither cost-effective nor sensitive. This pilot study suggests that serum mesothelin is a marker of neoplastic transformation in BE and may provide a noninvasive method to improve identification of malignant transformation., (©2012 AACR.)

Objective: Large case series have demonstrated that video-assisted thoracoscopic surgery (VATS) lobectomy is feasible and safe. However, catastrophic intraoperative complications during VATS lobectomy requiring thoracotomy can be overlooked and are not reported in the current literature. We reviewed our experience to determine the frequency, management, and outcome of these complications., Methods: A systematic review of a prospective database was performed after institutional review board approval. All patients who underwent VATS lobectomy or a combination of any VATS procedure plus a thoracotomy were identified. A catastrophic complication was defined as an event that resulted in an additional unplanned major surgical procedure other than the planned lobectomy., Results: From 2002 to 2010, a total of 633 VATS lobectomies were performed and 610 patients had any VATS procedure plus a thoracotomy. Thirteen catastrophic complications were identified in 12 (1%) patients. We included all cases in which a VATS was performed as well as a thoractomy since this would include conversions as well. These cases included 3 main pulmonary arterial and 1 main pulmonary venous transection requiring reanastomosis, 3 unplanned pneumonectomies, 1 unplanned bilobectomy, 1 tracheoesophageal fistula, 1 membranous airway injury to the bronchus intermedius, 1 complete staple line disruption of the inferior pulmonary vein injury to the azygos/superior vena cava junction, and 1 splenectomy. There were no intraoperative deaths., Conclusions: Catastrophic intraoperative complications of VATS lobectomy are uncommon. However, awareness of the possibility of such injuries is critical to avoid them, and development of specific management strategies is necessary to limit morbidity should they occur., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma., Methods: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and disease-specific survival were analysed., Results: From 1985 to 2009, 714 patients received preoperative therapy for localised gastric/GEJ adenocarcinoma, and 609 (85%) underwent a subsequent R0 resection. There were 60 patients (8.4%) with a pCR. Median follow-up was 46 months. Recurrence at 5 years was significantly lower for pCR vs non-pCR patients (27% and 51%, respectively, P=0.01). The probability of recurrence for patients with pCR was similar to non-pCR patients with pathologic stage I or II disease. Although the overall pattern of local/regional (LR) vs distant recurrence was comparable (43% LR vs 57% distant) between pCR and non-pCR groups, there was a significantly higher incidence of central nervous system (CNS) first recurrences in pCR patients (36 vs 4%, P=0.01)., Conclusion: Patients with gastric or GEJ adenocarcinoma who achieve a pCR following preoperative therapy still have a significant risk of recurrence and cancer-specific death following resection. One third of the recurrences in the pCR group were symptomatic CNS recurrences. Increased awareness of the risk of CNS metastases and selective brain imaging in patients who achieve a pCR following preoperative therapy for gastric/GEJ adenocarcinoma is warranted.