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Background: Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution.Methods: The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS).Results: Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051).Conclusions: In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC).Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment.Results: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims.Conclusions: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC. [ABSTRACT FROM AUTHOR]

Background: Trimodality therapy (TMT; chemoradiation plus surgery) has level-1 evidence for survival advantage for TMT-eligible esophagogastric cancer patients. Some patients, however, decline surgery after preoperative chemoradiation. The question of which patient should have esophagectomy and which one should not is unlikely to be answered by a prospective comparison; therefore, we matched the clinical covariates of several patients who had surgery with those who declined surgery (DS). Methods: Between 2002 and 2011, we identified 623 patients in our databases. Of 623 patients, 244 patients had TMT and 61 TMT-eligible patients were in the DS group. Using the propensity-score method, we matched 16 covariates between 36 DS patients and 36 TMT patients. Results: Baseline characteristics between the two groups were balanced (p = NS). The median overall survival times were: 57.9 months (95% CI: 27.7 to not applicable, NA) for the DS group and 50.8 months (95% CI: 30.7 to NA) for the TMT group (p = 0.28). The median relapse-free survival times were: 18.5 (95% CI: 11.5-30.4) for the DS group and 26.5 months (95% CI: 15.5-NA) for the TMT group (p = 0.45). Eleven (31%) of 36 patients in the DS group had salvage surgery. Conclusions: Our results are intriguing but skewed by the patients who had salvage surgery in the DS group. Until highly reliable predictive models are developed for esophageal preservation, TMT must be encouraged for all TMT-eligible gastroesophageal cancer patients. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Data, data everywhere. The diversity and magnitude of the data generated in the Life Sciences defies automated articulation among complementary efforts. The additional need in this field for managing property and access permissions compounds the difficulty very significantly. This is particularly the case when the integration involves multiple domains and disciplines, even more so when it includes clinical and high throughput molecular data. Methodology/Principal Findings: The emergence of Semantic Web technologies brings the promise of meaningful interoperation between data and analysis resources. In this report we identify a core model for biomedical Knowledge Engineering applications and demonstrate how this new technology can be used to weave a management model where multiple intertwined data structures can be hosted and managed by multiple authorities in a distributed management infrastructure. Specifically, the demonstration is performed by linking data sources associated with the Lung Cancer SPORE awarded to The University of Texas MDAnderson Cancer Center at Houston and the Southwestern Medical Center at Dallas. A software prototype, available with open source at www.s3db.org, was developed and its proposed design has been made publicly available as an open source instrument for shared, distributed data management. Conclusions/Significance: The Semantic Web technologies have the potential to addresses the need for distributed and evolvable representations that are critical for systems Biology and translational biomedical research. As this technology is incorporated into application development we can expect that both general purpose productivity software and domain specific software installed on our personal computers will become increasingly integrated with the relevant remote resources. In this scenario, the acquisition of a new dataset should automatically trigger the delegation of its analysis. [ABSTRACT FROM AUTHOR]

Objective: To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave., Summary of Background Data: The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years., Methods: The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients., Results: We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas., Conclusions: Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

Background: Advances in perioperative and operative management hold great promise for improving perioperative outcomes in patients undergoing resection for early stage non-small cell lung cancer (NSCLC). The objective of this study was to evaluate time trends in the incidence of perioperative outcomes and to identify predictors of pulmonary complication in early stage NSCLC resection patients., Methods: An institutional database was reviewed to identify patients with primary, clinical stage I and II NSCLC who underwent resection from 1998 to 2016. Rates of perioperative pulmonary complication, pneumonia, and cardiovascular complication; and 30-day and 90-day mortality were calculated for each year. Joinpoint regression was used to calculate annual percentage change (APC) and to evaluate time trends in rates of these outcomes. Multivariable logistic regression was conducted to identify predictors of pulmonary complication., Results: Of the 3045 patients identified, 80% had stage I and 20% had stage II NSCLC. From 1998 to 2016, there was no trend in the rate of pulmonary complication, but there was a significant downward trend in the rates of pneumonia (APC -3.7), cardiovascular complication (APC -3.5), 30-day mortality (APC -9.8), and 90-mortality (APC -7.4). Older age, male sex, smoking status, percentage of predicted forced expiratory volume in 1 second and percentage of diffusion capacity of lung for carbon monoxide, and intraoperative blood transfusion were identified as predictors of pulmonary complication., Conclusions: Decrease in the rates of perioperative outcomes parallels improvements in patient selection and perioperative management of early stage NSCLC resection patients. Predictors of pulmonary complication could be used to improve selection criteria for surgery and to reduce the incidence of pulmonary complication in these patients., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: High tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are leading biomarkers in metastatic non-small cell lung cancer (NSCLC) and predict favorable response to checkpoint inhibitors. We sought to identify clinicopathologic characteristics associated with elevated TMB and PD-L1 expression among patients who underwent resection for NSCLC., Methods: NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project. Multiplex immunofluorescence quantified densities (cells/mm 2 ) of CD3 + , CD3 + CD8 + , CD3 + CD8 + PD-1 + , malignant cells (MCs), MCsPD-L1 + , CD68 + , CD68 + PD-L1 + , and CD20 + cells. Whole-exome sequencing quantified TMB (mutations/megabase). TMB and MCsPD-L1 + were dichotomized according to the median of each., Results: A total of 55 patients completed multiplex immunofluorescence and whole-exome sequencing profiling. In this sample, 41.8% (23 of 55) had pathologic stage I disease. Median TMB and MCsPD-L1 + were 3.91 and 0.62 cells/mm 2 , respectively. TMB was higher among smokers (P = .001) and tumors with lymphovascular invasion (LVI) (P = .051). TMB was positively correlated with densities of MCsPD-L1 + (r = 0.293, P = .030), CD68 + PD-L1 + (r = 0.289, P = .033), and CD20 + (r = 0.310, P = .043) cells. The density of MCsPD-L1 + was associated with increased CD3 + CD8 + (r = 0.319, P = .018) and CD68 + PD-L1 + (r = 0.371, P = .005) cells. Patients with PD-L1 High TMB High tumors (30.9%, 17 of 55) had higher intratumoral densities of CD3 + , CD3 + CD8 + , CD68 + , CD68 + PD-L1 + , and CD20 + cells. On multivariable analysis LVI was associated with synchronous elevated TMB and PD-L1 expression (odds ratio 3.53, P = .039)., Conclusions: NSCLC tumors with elevated TMB and PD-L1 expression are associated with LVI and increased intratumoral immune cell infiltration. These findings may potentially improve patient selection for checkpoint inhibitor therapy trials in the adjuvant setting., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Ground glass opacities (GGOs) on computed tomography (CT) have gained significant recent attention, with unclear incidence and epidemiologic patterns. Natural language processing (NLP) is a powerful computing tool that collects variables from unstructured data fields. Our objective was to characterize trends of GGO detection using NLP., Methods: Patients were identified at a large quaternary referral center who underwent chest CT from 2000 to 2016 via query of institutional databases. NLP was used to identify imaging reports with GGOs and to obtain additional demographic data. Incidence of reported GGOs was tracked over time. Multivariate regression was used to identify predictors of GGOs identified on chest CT., Results: A total of 244,391 chest CTs were included, with 35,386 (14.5%) revealing GGOs. There was a significant relationship between advancing year of chest CT and likelihood of reported GGOs (p < 0.001). GGOs were more likely to occur in older subjects (60.5 vs 58.5 years, p < 0.001), males (54.6% vs 51.5%, p < 0.001), and nonwhite races (21.2% Asian, 15.6% Hispanic, 14.4% black, 14.0% white; p < 0.001). Certain occupational histories predicted more frequent GGOs (p < 0.001), including transportation labor (47.4%), metal workers (42.3%), iron workers (33.3%), cabinetry (32.6%), and foremen (29.6%). Multivariate regression revealed age, sex, nonsmokers, increasing year of chest CT, and race as significant independent predictors of identifying GGOs., Conclusions: NLP explored a large cohort of patients who underwent chest CT over the study period. Demographic features predicting reported GGOs include age, sex, race, and occupation. GGO recognition continues to increase with time, and further studies investigating etiology and prognostic implications are necessary., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have highlighted important biologic and survival-related differences among men and women with non-small cell lung cancer (NSCLC). However, differences in perioperative or short-term outcomes have not been as well characterized. In this study, we investigated differences in the perioperative period and postoperative emergency department (ED) visits among men and women after lobectomy for stage I NSCLC., Methods: A retrospective review was performed of patients who underwent a lobectomy for clinical stage I NSCLC at a single institution from 2010 to 2015., Results: We identified 559 patients for inclusion, including 293 women (52%) and 266 men (48%). Women were more likely to present with clinical T1 status (p = 0.005) and to undergo a minimally invasive operation (p = 0.058). To reduce confounding, 206 case-matched pairs were identified. After matching, no differences were found in length of stay (p = 0.551) or pulmonary complications (p = 0.509); however, men experienced more cardiac complications (18% versus 7%, p = 0.001). Of importance, although rates of 30- and 90-day ED visits between sexes were similar (p = 0.531, p = 0.890, respectively) and no sex-related differences were found in presenting symptom on return to the ED (p = 0.478), women were more likely to be readmitted after presenting to the ED within 30 days (p = 0.038)., Conclusions: Women demonstrated an increased likelihood of being admitted after presenting to the ED within 30 days after discharge, indicating important differences between men and women in the short-term period after lobectomy. Further research will be required to further understand the cause for these differences., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Enhanced recovery after surgery (ERAS) pathways aim to improve postoperative recovery through evidence-based practices, including early ambulation, multimodal opioid-sparing analgesia, and reduction of surgical stress. This study evaluated outcomes after implementation of ERAS in patients undergoing resection for pulmonary malignancy., Methods: A retrospective review compared outcomes for patients undergoing pulmonary resection for primary lung cancer. Analysis was performed between three periods: pre-ERAS (January 1, 2006, to December 31, 2011), transitional period with elements of ERAS (January 1, 2012, to August 31, 2015), and full implementation of ERAS (September 1, 2015, to December 31, 2016)., Results: We analyzed 2,886 lung resections (pre-ERAS, n = 1615; transitional, n = 929; ERAS, n = 342). For all patients, length of stay decreased in the ERAS and transitional periods compared with pre-ERAS (4 [3] versus 4 [3] versus 5 [3] days, p < 0.001). Pulmonary complications were decreased with ERAS compared with transitional and pre-ERAS (19.9% versus 28.2% versus 28.7%, p = 0.004). Cardiac complications decreased with ERAS (12.3% versus 13.1% versus 18.1%, p = 0.001). There was less thoracic epidural use (2.9% versus 44.5% versus 75.5%, p < 0.001). There were no differences in hospital readmission (p = 0.772) or mortality rates (p = 0.417). After thoracotomy, ERAS was associated with decreased length of stay, fewer intensive care unit readmissions, and decreased frequency of pneumonia, atrial arrhythmias, and need for home oxygen (all p < 0.05). ERAS was independently associated with decreased pulmonary (p = 0.046) and cardiac (p = 0.001) complications on logistic regression after thoracotomy but not minimally invasive operations., Conclusions: ERAS was associated with improved postoperative outcomes, including decreased length of stay and pulmonary and cardiac morbidity after thoracotomy, but not after minimally invasive operations. ERAS safety was demonstrated by low rates of adverse events without effect on hospital readmission or perioperative deaths., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Among patients with previous lung cancer, the malignant potential of subsequent ground-glass opacities (GGOs) on computed tomography remains unknown, with a lack of consensus regarding surveillance and intervention. This study sought to describe the natural history of GGO in patients with a history of lung cancer., Methods: A retrospective review was performed of 210 patients with a history of lung cancer and ensuing computed tomography evidence of pure or mixed GGOs between 2007 and 2013. Computed tomography reports were reviewed to determine the fate of the GGOs, by classifying all lesions as stable, resolved, or progressive over the course of the study. Multivariable analysis was performed to identify predictors of GGO progression and resolution., Results: The mean follow-up time was 13 months. During this period, 55 (26%) patients' GGOs were stable, 131 (62%) resolved, and 24 (11%) progressed. Of the 24 GGOs that progressed, three were subsequently diagnosed as adenocarcinoma. Patients of black race (odds ratio [OR], 0.26) and other races besides white (OR, 0.89) had smaller odds of GGO resolution (p = 0.033), whereas patients with previous lung squamous cell carcinoma (OR, 5.16) or small cell carcinoma (OR, 5.36) were more likely to experience GGO resolution (p < 0.001). On multivariable analysis, only a history of adenocarcinoma was an independent predictor of GGO progression (OR, 6.9; p = 0.011)., Conclusions: Among patients with a history of lung cancer, prior adenocarcinoma emerged as a predictor of GGO progression, whereas a history of squamous cell carcinoma or small cell carcinoma and white race were identified as predictors of GGO resolution., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Immune checkpoint inhibitors that target the programmed cell death protein ligand 1 (PD-L1) pathway have shown benefit for the treatment of metastatic non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 independent of immunotherapy is still unclear, with conflicting results reported between PD-L1 expression and patient survival. Our aim was to correlate PD-L1 mRNA level with clinical and pathologic factors and to investigative the prognostic value of PD-L1 mRNA in all stages of NSCLC., Methods: Gene expression and clinical data were obtained from public repositories in The Cancer Genome Atlas from the National Cancer Institute. Genotype-Tissue Expression was used to compare with normal tissue expression analysis., Results: A total of 985 patients met inclusion criteria, among whom 79.6% were stage I to II, 16.5% were stage III, and 3.5% were stage IV, representing 495 adenocarcinoma and 490 squamous cell carcinoma (SCC). PD-L1 mRNA gene expression in lung cancers was higher than in most other tumor and normal tissue types and was significantly higher in lung SCC than adenocarcinoma (p < 0.001). PD-L1 mRNA expression was associated with pathologic stage in SCC and with smoking status in adenocarcinoma of the lung. However, none of the cutoff values of PD-L1 mRNA expression were prognostic of overall survival., Conclusions: Our results suggest that the value of PD-L1 mRNA in prognosticating outcome in lung cancer is limited. Further studies are needed to identify novel prognostic biomarkers other than PD-L1 that are associated with improved patient survival. Identification of further prognostically important biomarkers may prove useful in identifying patients suitable for immunotherapy., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Unlike infections related to chemotherapy-induced neutropenia, postoperative infections occurring in patients with solid malignancy remain largely understudied. Our aim is to evaluate the outcomes and the volume-outcomes relationship associated with postoperative infections following resection of common solid tumors., Methods: We used Texas Discharge Data to study patients undergoing resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum from 01/2002 to 11/2006. From their billing records, we identified ICD-9 codes indicating a diagnosis of serious postoperative infection (SPI), i.e., bacteremia/sepsis, pneumonia, and wound infection, occurring during surgical admission or leading to readmission within 30 days of surgery. Using regression-based techniques, we estimated the impact of SPI on mortality, resource utilization, and costs, as well as the relationship between hospital volume and SPI, after adjusting for confounders and data clustering., Results: SPI occurred following 9.4 % of the 37,582 eligible tumor resections and was independently associated with nearly 12-fold increased odds of in-hospital mortality [95 % confidence interval (95 % CI), 7.2-19.5, P < 0.001]. Patients with SPI required six additional hospital days (95 % CI, 5.9-6.2) at an incremental cost of $16,991 (95 % CI, $16,495-$17,497). Patients who underwent resection at high-volume hospitals had a 16 % decreased odds of developing SPI than those at low-volume hospitals (P = 0.03)., Conclusions: Due to the substantial burden associated with SPI following common solid tumor resections, hospitals must identify more effective prophylactic measures to avert these potentially preventable infections. Additional volume-outcomes research is needed to identify infection prevention processes that can be transferred from high- to lower-volume providers.

Background: Resection of pulmonary colorectal carcinoma metastases may provide long-term benefit, but patient selection remains controversial. The objective of this study was to identify preoperative predictors of survival and lung recurrence for patients undergoing resection of such lesions., Methods: A prospectively collected database was retrospectively reviewed to identify patients who underwent their first colorectal carcinoma pulmonary metastasectomy. Two multivariate logistic analyses were performed to identify preoperative predictors of survival and lung recurrence. Preoperative factors, pathologic colorectal carcinoma stage, additional sites of metastases, timing of metastatic occurrence, and premetastasectomy disease-free interval were included in the univariate analyses., Results: From January 2000 to December 2010, 229 patients met inclusion criteria. The mean age was 60 years, and 100 patients (43.7%) were women. The overall median time and 5-year survival rate were 70.1 months and 55.4%, respectively, after the first pulmonary metastasectomy. Median follow-up was 37.2 months. Age older than 60 years (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.005 to 1.052; p=0.016), male sex (HR, 1.84; 95% CI, 1.089 to 3.094; p=0.023), and more than three lung metastases (HR, 1.15; 95% CI, 1.024 to 1.282; p=0.018) predicted survival at 5 years in one multivariate analysis. In the second, more than three lung metastases present at first metastasectomy (HR, 1.19; 95% CI, 1.071 to 1.321; p=0.001) and the preoperative disease-free interval of less than 3 years (HR, 0.99; 95% CI, 0.973 to 0.997; p=0.013) predicted lung recurrence., Conclusions: Older age, male sex, and more lung metastases predict poorer survival after resection of pulmonary colorectal cancer metastases. The number of lung metastases present at the first metastasectomy and the preoperative disease-free interval predicted recurrence in the lung., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: An uncontained thoracic anastomotic leak may cause severe morbidity or mortality. Thoracic transposition of an omental flap along with the gastric conduit may decrease leak incidence, severity, or need for reoperations after esophagectomy., Methods: We identified 607 patients who underwent esophagectomy with thoracic anastomosis between January 2001 and August 2011. All patients were studied for leak postoperatively. Four leak grades were defined, ranging from radiographic leak to conduit loss. Univariate and multivariate analyses were performed to identify variables associated with anastomotic leak., Results: Omental reinforcement was used in 215 of 607 patients (35%). Anastomotic leak occurred in 51 of 607 patients (8.4%). Patients with omentum had a significantly lower (odds ratio [OR], 0.4; P = .014) anastomotic leak rate (4.7%) compared with patients without omentum (10.5%). Salvage resections were performed in 69 patients and 23 (32%) received omentum; the leak rate with omentum was 4.6% compared with 15% without (OR, 0.27; P = .24). Patients undergoing planned esophagectomy with omentum had a significantly lower leak rate than patients without omentum (4.7% vs 9.8%) (OR, 0.43; P = .04). Reoperations to rescue an anastomotic leak (Grade 3) was less common with omentum (OR, 0.26; P = .024). Multivariate analysis identified omental reinforcement (OR, 0.45; P = .034) and surgeon (OR, 3.4; P = .001) as variables predictive of an anastomotic leak., Conclusions: Omental reinforcement of thoracic esophagogastric anastomoses decreases overall leak rate and need for reoperation. We recommend pedicled omental transposition to reinforce all thoracic anastomoses. Endoscopic evaluation of significant anastomotic leaks is still warranted., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Primary mediastinal germ-cell tumors are rare, and the effect of newer drugs and treatment strategies in this disease on overall survival is not known. We retrospectively assessed treatment outcomes at a single institution., Materials and Methods: We identified men seen at our institution from 1998 through 2005 for mediastinal germ-cell tumors. Medical records were reviewed for patient characteristics, histology, tumor markers, treatment, and survival outcome., Results: Thirty-four patients met study criteria, of whom 27 had nonseminomatous germ-cell tumor (NSGCT) and 7 had pure seminoma. Eleven patients (41%) with NSGCT were alive at last contact with a median overall survival time of 33.5 months. Among 13 patients with NSGCT referred to us at initial diagnosis, 7 (54%) were alive and recurrence-free at a median follow-up of 56.5 months. Progression-free survival was associated with absence of risk factors (any histology other than endodermal sinus tumor, β-hCG > 1000 mIU/mL, or disease outside the mediastinum). For the patients whose disease progressed (n = 5) or who had been referred to us for salvage treatment (n = 14), the 3-year overall survival from the date of first progression was 23%. Conversely, patients with seminoma did uniformly well with platinum-based chemotherapy; most did not undergo radiation or surgery., Conclusion: Chemotherapy given to maximum effect followed by surgical consolidation resulted in long-term progression-free survival for 54% of patients with mediastinal NSGCT. The number of risk factors present at diagnosis may be associated with survival outcome and should be studied in a larger test group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Outcomes of salvage esophagectomy after definitive chemoradiation (CRT) for squamous cell carcinoma are well defined. Previous reports of salvage esophagectomy in patients with recurrent adenocarcinoma after definitive CRT are limited by small numbers and high morbidity and mortality rates., Methods: We reviewed our experience of 65 patients with esophageal adenocarcinoma treated from 1997 to 2010 who underwent salvage esophagectomy after failed definitive CRT. We then compared this group to 65 matched patients of 521 total patients with esophageal adenocarcinoma who received preoperative CRT followed by planned esophagectomy. Propensity matching and multivariable analysis were performed., Results: Median time to surgery from completion of therapy for the salvage group was 216 days. Major postoperative events (major pulmonary event, conduit loss, leak, readmission to intensive care unit) occurred in 35% (23 of 65) of salvage patients and 31% (20 of 65) of the planned resection matched group. Anastomotic leak occurred in 18.5% (12 of 65) and 11.3 (59 of 521) of salvage and planned groups, respectively. Thirty-day mortality was 3.1% (2 of 65) after salvage resection and 4.6% (3 of 65) after planned resection. There was no difference in 3-year overall or median survival between the two groups of patients (32 months, 48% salvage, versus 40 months, 57% planned resection). Multivariable analysis did not identify salvage strategy or time from completion of therapy to resection as a predictor of major event or death., Conclusions: Postoperative morbidity, mortality, and overall survival of patients after salvage esophagectomy are comparable to matched patients after planned resection. These results suggest that patients with esophageal adenocarcinoma who fail definitive CRT and recur locoregionally should be considered for salvage esophagectomy at experienced esophageal centers., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The incidence and consequence of an isolated involved circumferential radial margin (CRM) after resection for esophageal adenocarcinoma in the setting of neoadjuvant chemoradiotherapy (CRT) has not been reported. We aimed to determine the frequency and significance of a close (<1 mm) or involved CRM in patients undergoing esophagectomy after CRT., Methods: We retrospectively analyzed the data from patients undergoing resection from 1997 to 2008 for esophageal adenocarcinoma after neoadjuvant CRT. A positive CRM was defined as microscopic tumor at or less than 1 mm of the radial margin. An R1 resection was tumor at the radial margin. Only patients with ypT3 or greater tumors were included. R2 resections were excluded. Statistical comparisons were performed using Cox regression and Kaplan-Meier analyses., Results: A total of 160 patients met the inclusion criteria, 42 (26%) had a positive CRM. The median survival did not significantly differ between the CRM-negative and -positive groups (28 vs 50 months, P = .84). A propensity score matching analysis also failed to find a significant difference in outcomes. When analyzed by tumor present at the margin (R1), R0 patients had a longer median survival compared with R1 patients (28 vs 8 months, P = .01). This difference, however, was not seen on propensity score matching., Conclusions: Resections of locally advanced esophageal adenocarcinoma with residual transmural viable tumor after CRT frequently showed involvement of the radial margin with tumor either close to or at the margin. Tumor close (<1 mm) to the radial margin did not result in a significant decrease in overall or disease-free survival or increase in local recurrence., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: After neoadjuvant chemoradiation (CXRT) for esophageal cancer, surgery has traditionally been recommended to be performed within 8 weeks. However, surgery is often delayed for various reasons. Data from other cancers suggest that delaying surgery may increase the pathologic complete response rate. However, there are theoretical concerns that waiting longer after radiation may lead to a more difficult operation and more complications. The optimal timing of esophagectomy after CXRT is unknown., Methods: From a prospective database, we analyzed 266 patients with resected esophageal cancer who were treated with neoadjuvant CXRT from 2002 to 2008. Salvage resections were excluded from this analysis. We compared patients who had surgery within 8 weeks of CXRT and those who had surgery after 8 weeks. We used multivariable analysis to determine whether increased interval between chemoradiation and surgery was independently associated with perioperative complication, pathologic response, or overall survival., Results: One hundred fifty patients were resected within 8 weeks and 116 were resected greater than 8 weeks after completing CXRT. Mean length of operation, intraoperative blood loss, anastomotic leak rate, and perioperative complication rate were similar for the two groups. Pathologic complete response rate and overall survival were also similar for the two groups (p=not significant). In multivariable analysis, timing of surgery was not an independent predictor of perioperative complication, pathologic complete response, or overall survival., Conclusions: The timing of esophagectomy after neoadjuvant CXRT is not associated with perioperative complication, pathologic response, or overall survival. It may be reasonable to delay esophagectomy beyond 8 weeks for patients who have not yet recovered from chemoradiation., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Duplicated muscularis mucosae (MM) in early esophageal adenocarcinoma (EAC) can cause overstaging of the disease on endoscopic ultrasound and pathology specimens. No study has determined the correlation between lymph node metastasis and invasion in the space between duplicated MM in pathologic tumor stage (pT) 1 EAC. Hematoxylin and eosin-stained slides from surgically resected pT1 EAC (n=99) were reviewed for tumor configuration, grade, level of invasion (lamina propria/inner MM, space between duplicated MM, and submucosa), quantitative depth of invasion in millimeter, and lymphovascular invasion (LVI). These pathologic characteristics were correlated with lymph node status and recurrence-free survival (RFS). All specimens had duplicated MM with thick-walled blood vessels. Tumor differentiation was well in 37, moderate in 47, and poor in 15 specimens. EAC invaded the lamina propria/inner MM in 28 cases, duplicated MM space in 41 cases, and submucosa in 30 cases. LVI was identified in 23 tumors. Eleven patients had lymph node metastasis. Quantitative depth of invasion as a continuous variable (P=0.002), poorly differentiated histology (P=0.028), presence of LVI (P=0.001), and submucosal invasion versus duplicated MM/lamina propria invasion (P=0.02) were associated with increased risk of lymph node metastasis and shorter RFS by univariate analysis. By multivariate analysis, LVI was an independent predictor of lymph node status and RFS. EAC invasion into the space between duplicated MM confers a similar risk of lymph node metastasis and recurrence as those of intramucosal EAC, and LVI is the best predictor of lymph node status and RFS in pT1 EAC.

Background: Treatment strategy for patients with adequately staged cT2N0M0 carcinoma of the thoracic esophagus is currently a subject of debate. This study analyzed the largest series of consecutive cT2N0M0 esophageal cancer patients treated with preoperative chemoradiotherapy., Methods: Data from all patients with cT2N0M0 (assessment included endoscopic ultrasonography and computed tomography of the chest and abdomen) thoracic esophageal cancer who were treated with preoperative chemoradiation between 1997 and 2009 were analyzed. The Cox regression model and Kaplan-Meier plots were used to analyze the data., Results: Data from 49 patients were analyzed. The median follow-up was 28.46 months. Male sex and adenocarcinoma histology predominated. Pathologic complete response was observed 19 (39%) patients. The 10-year actuarial overall survival (OS) for adenocarcinoma patients was >60%. In the univariate analysis for OS, squamous histology (P = .006), smoking (P = .015), and alcohol consumption (P = .032) were found to be associated with poor OS. In the univariate analysis for disease-free survival (DFS), squamous histology (P = .009) and smoking (P = .014) were associated with poor DFS. In the multivariate analysis for OS, smoking was an independent prognosticator (P = .02). In the multivariate analysis for DFS, advanced pathologic stage (P = .05) and lymph node metastases (P = .006) were independent prognosticators. Patients with adenocarcinoma (P = .002) and those with pathologic N0 disease had better OS and DFS. Upward stage migration occurred in only 10% of patients., Conclusions: These data suggest that smoking and alcohol influence the long-term outcome of patients with cT2N0M0 disease. Adenocarcinoma patients treated with trimodality therapy had an excellent actuarial 10-year OS and a high rate of pathologic complete response. Trimodality therapy should be prospectively compared with primary surgery in these patients., (Copyright © 2010 American Cancer Society.)

Purpose: Esophageal cancer is the seventh leading cause of cancer death worldwide and is responsible for 4% of the cancer deaths in the United States annually. Changing epidemiologic patterns and expanded treatment options have brought this often deadly cancer to the forefront., Methods and Materials: To characterize epidemiological changes, the effect of treatment advances, and patient outcomes over time, we retrospectively reviewed 756 consecutive esophageal cancer cases treated between 1985 to 2003 at The University of Texas M. D. Anderson Cancer Center in Houston. For purposes of evaluation, cases were divided into four cohorts of approximately 5 years each. Men make up 75% or more of the patients with esophageal cancer, most patients have adenocarcinoma in the gastroesophageal junction, and almost 75% have stage II or III disease., Results: Three-year overall survival improved from 16.7% (1985-1989) to 35.2% (2000-2003). By multivariate Cox regression analysis, significant reductions in relative risk were associated with having good performance status (relative risk [RR] = 0.68 [95% confidence interval (CI) = 0.56-0.83]; p < 0.001), being treated in the most recent interval (2000-2003) than in the first (1985-1989) (RR = 0.63 [95% CI = 0.44-0.88]; p = 0.007), with improved therapies, including induction chemotherapy plus concurrent chemoradiotherapy (RR = 0.68 [CI = 0.56-0.84]; p < 0.001), explaining the reductions., Conclusion: Although fully delineated comparisons must await incorporation and study of data through 2007, this analysis suggests that multimodality management that has been adapted in recent years may be associated with the improvements in outcomes of these cases of largely stage II and III esophageal adenocarcinoma found at the gastroesophageal junction.

The Lung Cancer SPORE at University Texas MDAnderson Cancer Center and Southwestern Medical School requires the integration of heterogeneous multi-institutional sources comprising both molecular and clinical data. In this report we describe a novel method for converging domain specific experimental ontologies that relies on propagating permissions in Resource Description Framework triplets rather than the single access point of conventional relational databases. We address this challenge by combining semantic web data reposition with code distribution.

Purpose: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus., Patients and Methods: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS., Results: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p <0.001), whereas sex was distributed similarly among SCC patients (55% male vs 45% female; p = 0.5). A significantly larger percentage of SCC patients were classified as lower TN and overall stage than ACA patients (T2 = 41% vs 28%, p <0.0001; N0 = 69% vs 48%, p = 0.01; stage II = 76% vs 55%, p <0.001). A significantly greater portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p = 0.02). Among the pathCR patients in clinical stage II, there were significantly greater proportion of SCC patients (77% vs 63%; p <0.001) than ACA patients. Among the pathCR patients in clinical stage III patients, a significantly greater proportion were ACA patients (38% vs 23%; p <0.001) than SCC patients. The median and 5-yr OS was 53 +/- 11 mo and 39% for ACA patients and 35 +/- 14 mo and 37% for SCC (median OS, p = 0.3). Among pathCR patients, median OS of ACA patients (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p = 0.07); results were similar for non-pathCR patients. DFS results were similar in all subgroups. Among the whole cohort, incidence of local-regional recurrence and distant metastases did not vary significantly. The median time to distant metastases did not vary significantly for pathCR and non-pathCR patients., Conclusions: We believe this is the first study that compares failure outcome of ACA and SCC patients with similar clinical stage after trimodality therapy. Our data suggest that significant differences in clinical stage and post-therapy pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes in the resected specimens of ACA patients resulted in a shorter time-to-metastases suggesting that ACA patients need better systemic control.

Objective: To assess the evolution of treatment and outcome for resected esophageal cancer at a single institution., Summary Background Data: Strategies for optimizing the treatment of resected esophageal cancer continue to evolve over time. The outcomes of these evolving treatments in the context of improved diagnostic staging and changing epidemiology have not been carefully analyzed in a single institution., Methods: One thousand ninety-seven consecutive patients with primary esophageal cancer underwent surgery during the period 1970 to 2001. Nine hundred ninety-four patients underwent curative esophagectomy and were analyzed for changing demographics. Eight hundred seventy-nine patients who did not have systemic metastases and survived the perioperative period were assessed by multivariate analysis for factors associated with long-term survival., Results: During the study period the overall median survival increased from 17 to 34 months, and combined hospital and 30-day mortality decreased from 12% to 6%. The R0 resection rate increased from 78 to 94%, and adenocarcinoma replaced squamous cell carcinoma as the predominant histology (83% vs. 17%). No change in survival with time was noted for patients treated with surgery alone having the same postoperative pathologic stage (pTNM). An increased proportion of patients had preoperative chemoradiation in the last 4 years of the study (59% vs. 2%). Preoperative chemoradiation was associated with a longer survival and increased likelihood of achieving a complete resection. Multivariate analysis showed that long-term survival was associated with a complete resection and the preoperative staging strategy used, while the use of preoperative chemoradiation was the most significant factor associated with ability to achieve an R0 esophageal resection., Conclusions: This study shows favorable trends in the survival of patients with resected esophageal cancer over time. The increased use of preoperative chemoradiation, better preoperative staging, and other time-dependent factors may have contributed to the observed increase in survival.