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Robin I Dewalt,1 Kenneth A Kesler,2 Zane T Hammoud,3 LeeAnn Baldridge,4 Eyas M Hattab,4 Shadia I Jalal1,5 1Division of Hematology/Oncology, Department of Medicine, 2Cardiothoracic Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; 3Henry Ford Hospital, Detroit, MI, USA; 4Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 5Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA Objective: Esophageal adenocarcinoma (EAC) continues to be a disease associated with high mortality. Among the factors leading to poor outcomes are innate resistance to currently available therapies, advanced stage at diagnosis, and complex biology. Platinum and ionizing radiation form the backbone of treatment for the majority of patients with EAC. Of the multiple processes involved in response to platinum chemotherapy or ionizing radiation, deoxyribonucleic acid (DNA) repair has been a major player in cancer sensitivity to these agents. DNA repair defects have been described in various malignancies. The purpose of this study was to determine whether alterations in DNA repair are present in EAC compared with normal gastroesophageal tissues. Methods: We analyzed the expression of genes involved in homologous recombination (HR), nonhomologous end-joining, and nucleotide excision repair (NER) pathways in 12 EAC tumor samples with their matched normal counterparts. These pathways were chosen because they are the main pathways involved in the repair of platinum- or ionizing-radiation-induced damage. In addition, abnormalities in these pathways have not been well characterized in EAC. Results: We identified increased expression of at least one HR gene in eight of the EAC tumor samples. Alterations in the expression of EME1, a structure-specific endonuclease involved in HR, were the most prevalent, with messenger (m)RNA overexpression in six of the EAC samples. In addition, all EAC samples revealed decreased expression of at least one of numerous NER genes including XPC, XPA, DDB2, XPF, and XPG. Conclusion: Our study identified DNA repair dysregulation in EAC involving two critical pathways, HR and NER, and is the first demonstration of EME1 upregulation in any cancer. These DNA repair abnormalities have the potential to affect a number of processes such as genomic instability and therapy response, and the consequences of these defects deserve further study in EAC. Keywords: esophageal adenocarcinoma, DNA repair, MUS81/EME1

Background: Paraesophageal hernias may produce a variety of clinical sequelae including anemia and esophagogastric ulcerations or erosions. We examined the prevalence of anemia in patients with paraesophageal hernias and frequency of anemia resolution with hernia repair.Methods: Patients undergoing paraesophageal hernia repairs from July 1996 to September 2010 were included. Data gathered included age, gender, type of hernia, presence of symptomatic anemia, presence of esophagogastric ulcer/erosion, type of repair, and anemia resolution.Results: One hundred eighty-three patients underwent paraesophageal hernia repair; of these, 68 (37%) were anemic. Of these anemic patients, 39 (57%) were symptomatic from their anemia or specifically referred for anemia, and 20 (29%) had esophagogastric ulceration/erosion. Fifty-eight had documented follow-up. Overall, of these, 35 (60%) had resolution of their anemia. Seventy percent of symptomatic patients had resolution of their anemia, compared to 48% of asymptomatic patients (p = 0.1). Of patients with esophagogastric ulceration/erosion, 85% were symptomatic and 88% had resolution of anemia, compared to 50% of patients without ulceration/erosion (p = 0.015).Conclusions: Anemia was a common finding in patients with paraesophageal hernia and most patients were symptomatic because of their anemia. Those patients with esophageal or gastric ulceration/erosion were very likely to have symptomatic anemia, and, interestingly, these patients were more likely to have their anemia resolve with paraesophageal hernia repair. [ABSTRACT FROM AUTHOR]

Giant cell tumor is a relatively uncommon bone tumor rarely originating from the chest wall. Given its proximity to vital structures in the thoracic cavity, treatment options may be challenging. We report the case of a patient with a giant cell tumor of the posterolateral chest wall with invasion of the thoracic spine treated with neoadjuvant denosumab, followed by surgical resection., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

N-Linked glycans, extracted from patient sera and healthy control individuals, are analyzed by Matrix-assisted laser desorption ionization (MALDI) in combination with ion mobility spectrometry (IMS), mass spectrometry (MS) and pattern recognition methods. MALDI-IMS-MS data were collected in duplicate for 58 serum samples obtained from individuals diagnosed with Barrett's esophagus (BE, 14 patients), high-grade dysplasia (HGD, 7 patients), esophageal adenocarcinoma (EAC, 20 patients) and disease-free control (NC, 17 individuals). A combined mobility distribution of 9 N-linked glycans is established for 90 MALDI-IMS-MS spectra (training set) and analyzed using a genetic algorithm for feature selection and classification. Two models for phenotype delineation are subsequently developed and as a result, the four phenotypes (BE, HGD, EAC and NC) are unequivocally differentiated. Next, the two models are tested against 26 blind measurements. Interestingly, these models allowed for the correct phenotype prediction of as many as 20 blinds. Although applied to a limited number of blind samples, this methodology appears promising as a means of discovering molecules from serum that may have capabilities as markers of disease.

Changes in glycosylation have been shown to have a profound correlation with development/malignancy in many cancer types. Currently, two major enrichment techniques have been widely applied in glycoproteomics, namely, lectin affinity chromatography (LAC)-based and hydrazide chemistry (HC)-based enrichments. Here we report the LC-MS/MS quantitative analyses of human blood serum glycoproteins and glycopeptides associated with esophageal diseases by LAC- and HC-based enrichment. The separate and complementary qualitative and quantitative data analyses of protein glycosylation were performed using both enrichment techniques. Chemometric and statistical evaluations, PCA plots, or ANOVA test, respectively, were employed to determine and confirm candidate cancer-associated glycoprotein/glycopeptide biomarkers. Out of 139, 59 common glycoproteins (42% overlap) were observed in both enrichment techniques. This overlap is very similar to previously published studies. The quantitation and evaluation of significantly changed glycoproteins/glycopeptides are complementary between LAC and HC enrichments. LC-ESI-MS/MS analyses indicated that 7 glycoproteins enriched by LAC and 11 glycoproteins enriched by HC showed significantly different abundances between disease-free and disease cohorts. Multiple reaction monitoring quantitation resulted in 13 glycopeptides by LAC enrichment and 10 glycosylation sites by HC enrichment to be statistically different among disease cohorts.

Background: Esophagectomy is associated with significant morbidity and mortality. This retrospective study examined use of a modified frailty index as a potential predictor of morbidity and mortality in esophagectomy patients., Methods: National Surgical Quality Improvement Program Participant Use Files were reviewed for 2005 through 2010. Patients undergoing esophagectomy were selected based on CPT codes. A modified frailty index with 11 variables was used to determine correlation between frailty and postesophagectomy morbidity and mortality. Data were analyzed using χ(2) test and logistic regression., Results: A total of 2,095 patients were included in the analysis. Higher frailty scores were associated with a statistically significant increase in morbidity and mortality. A frailty score of 0, 1, 2, 3, 4, and 5 had associated morbidity rates of 17.9% (142 of 795 patients), 25.1% (178 of 710 patients), 31.4% (126 of 401 patients), 34.4% (48 of 140 patients), 44.4% (16 of 36 patients), and 61.5% (8 of 13 patients), respectively. A frailty score of 0, 1, 2, 3, 4, and 5 had associated mortality rates of 1.8% (14 of 795 patients), 3.8% (27 of 710 patients), 4% (16 of 401 patients), 7.1% (10 of 140 patients), 8.3% (3 of 36 patients), and 23.1% (3 of 13 patients), respectively. When using multivariate logistic regression for mortality comparing age, functional status, prealbumin, emergency surgery, wound class, American Society of Anesthesiologists score, and sex, only age and frailty were statistically significant. The odds ratio was 31.84 for frailty (p = 0.015) and 1.05 (p = 0.001) for age., Conclusions: Using a large national database, a modified frailty index was shown to correlate with postesophagectomy morbidity and mortality. Such an index may be used to aid in improving risk assessment and patient selection for esophagectomy., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Frailty has yet to be explored as a risk factor for thoracic surgery. We hypothesized that our modified frailty index (mFI) may be a predictor of morbidity and mortality following lobectomy., Materials: National Surgical Quality Improvement Program (NSQIP) participant use files were reviewed (2005-2010). Patients undergoing lobectomy were identified based on Current Procedural Terminology code 32480. We used an mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities. Data were analyzed using χ(2) test, independent sample t-test, Jonckheere-Terpstra test, and logistic regression., Results: Of 1940 open lobectomy patients identified, morbidity and mortality uniformly increased as the mFI increased; 14.9% of patients (75/504) with mFI of 0 had at least one complication, compared with 32% of patients (91/284) with mFI of 0.27 (P < 0.001). An mFI of 0 was associated with a mortality rate of 1% (5/504), compared with 5.6% (16/284) for mFI of 0.27 (P < 0001). Failure to wean from the ventilator, reintubation, surgical site infections, pneumonia, and Clavien 4 and above complications occurred in 1.8% (9/504), 2.6% (13/504), 2.2% (11/504), 5.4% (27/504), and 4.2% (21/504), respectively, in patients with an mFI of 0, compared with 7.4% (21/284), 7% (22/284), 3.2% (9/284), 10.9% (31/284), and 14.4% (41/284), respectively, in patients with mFI of 0.27., Conclusions: This study demonstrates that the mFI may identify patients at higher risk for morbidity and mortality post-lobectomy. With the aging population, preoperative selection is important in minimizing morbidity and mortality and improving risk stratification for informed decision-making., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Three disease phenotypes, Barrett's esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS), and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including 7 characterized as BE, 12 as HGD, 56 as EAC, and 61 as NC. In typical data sets, it was possible to assign ∼20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for 11 N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution.

We report analysis of N-glycans derived from disease-free individuals and patients with Barrett's esophagus, high-grade dysplasia, and esophageal adenocarcinoma by microchip electrophoresis with laser-induced fluorescence detection. Serum samples in 10 μL aliquots are enzymatically treated to cleave the N-glycans that are subsequently reacted with 8-aminopyrene-1,3,6-trisulfonic acid to add charge and a fluorescent label. Separations at 1250 V/cm and over 22 cm yielded efficiencies up to 700,000 plates for the N-glycans and analysis times under 100 s. Principal component analysis (PCA) and analysis of variance (ANOVA) tests of the peak areas and migration times are used to evaluate N-glycan profiles from native and desialylated samples and determine differences among the four sample groups. With microchip electrophoresis, we are able to distinguish the three patient groups from each other and from disease-free individuals.

Non-small cell pulmonary carcinomas represent the majority of tumors located in the superior sulcus. However, only 5% of all non-small cell pulmonary carcinomas present in the superior sulcus. Other causes of superior sulcus tumors include metastatic tumors, hematologic malignancies, infectious causes, and amyloid nodules, as well as other lesions. We report a case in which a venous hemangioma presented as a superior sulcus tumor., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Atrial fibrillation is common after esophagectomy. The objective of this study was to determine the efficacy and safety of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy., Methods: Eighty patients undergoing transthoracic esophagectomy were randomly, prospectively assigned to receive amiodarone (n = 40) or no prophylaxis (control group, n = 40). Amiodarone-treated patients received the drug by continuous infusion, initiated at the time of induction of anesthesia, at a rate of 0.73 mg/min (43.75 mg/h), and continued for 96 hours (total dose 4200 mg). The primary end point was atrial fibrillation requiring treatment. Secondary end points included any atrial fibrillation lasting longer than 30 seconds and postoperative hospital and intensive care unit stays., Results: There were no significant differences between the amiodarone and control groups in demographic characteristics, comorbid conditions, or preoperative or postoperative use of beta-blockers or calcium-channel blockers. The incidence of atrial fibrillation requiring treatment was lower in the amiodarone group than in the control group (15% vs 40%, P = .02, relative risk reduction 62.5%). There were no significant differences between the amiodarone and control groups in median hospital stay (11 days vs 12 days, P = .31) or median intensive care unit stay (68 hours vs 77 hours, p = .097). There were no significant difference between the groups in the incidences of adverse effects., Conclusions: Amiodarone prophylaxis significantly reduced the incidence of atrial fibrillation after transthoracic esophagectomy., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Although glycoproteomic studies provide unique opportunities for cancer research, it has been necessary to develop specific methods for analysis of oncologically interesting glycoproteins. We describe a general, multimethodological approach for quantitative glycoproteomic analysis of fucosylated glycoproteins in human blood serum. A total of 136 putative fucosylated glycoproteins were identified with very high confidence in three clinically relevant sample pools (N=5 for each), with a mean CV of 3.1% observed for replicate analyses. Two samples were collected from subjects diagnosed with esophagus disease states, high-grade dysplasia plus esophageal adenocarcinoma, while the third sample was representative of a disease-free condition. Some glycoproteins, observed to be significantly upregulated in esophageal adenocarcinoma, i.e. more than twofold higher than in the disease-free condition, are briefly discussed. Further investigation will be necessary to validate these findings; however, the method itself is demonstrated to be an effective tool for quantitative glycoproteomics of clinical samples.

Objective: Aberrant glycosylation has been implicated in various types of cancers. Cancerous cells with altered glycosylation of their surface proteins shed such proteins into the circulating fluids. Glycomic profiling of such fluids shows the altered glycosylation. We performed glycomic profiling of serum from patients with no known disease, Barrett's without dysplasia, with high-grade dysplasia, and with esophageal adenocarcinoma in an attempt to delineate distinct differences in glycosylation among these groups., Methods: Serum samples from patients with Barrett's metaplasia (N = 5), high-grade dysplasia (N = 11), and esophageal adenocarcinoma (N = 50) were collected; samples from 18 healthy volunteers were used as control. Serum N-glycans were enzymatically released and then applied to both C18 Sep-Pak (Waters, Milford, MA) cartridges and activated charcoal cartridges. N-glycans were permethylated and then spotted directly onto a matrix-assisted laser desorption ionization plate. Mass spectra were acquired using the Applied Biosystems 4800 MALDI TOF/TOF Analyzer (Applied Biosystems Inc, Framingham, Mass). The obtained matrix-assisted laser desorption ionization-mass spectrometry data were processed using DataExplorer files (Applied Biosystems Inc) listing m/z values and intensities., Results: The intensities of 98 glycans were significantly different among the 3 groups; 26 of these corresponded to known glycan structures. Pairwise comparisons showed that 8 glycans were significantly different in all 3 pairwise comparisons., Conclusion: We demonstrated that comparative glycomic profiling of esophageal adenocarcinoma reveals a subset of glycans that can be selected as candidate biomarkers. These markers can differentiate normal from high-grade dysplasia, normal from esophageal adenocarcinoma, and high-grade dysplasia from esophageal adenocarcinoma. Further validation will be necessary to determine the clinical utility of these glycan biomarkers., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: We examined the early and late prognostic significance of DLCO and forced expiratory volume in 1 sec (FEV1) in patients who underwent surgical resection of lung cancer., Methods: From 1997 to 2004, 462 patients underwent successful complete resection of their lung cancer and had full pulmonary function testing including DLCO performed. Mean follow-up was over 5 years (64.8 months--range: 0-158 months)., Results: Postoperative 90-day mortality was 2.6% (12/462). At last follow-up, of the remaining 450 patients, 182 patients were alive, 130 had died of cancer, and 138 have died of other causes and did not have recurrent cancer. Mean DLCO values were 69.4%, 66.8%, and 53.9%, respectively. Mean FEV1 values were 81.3%, 78.1%, and 71.5%, respectively. Mean DLCOs and FEV1s between patients who died of cancer versus other causes were significantly different (P < 0.0001 and P = 0.0157). When cause-specific survival was analyzed for both DLCO and FEV1 simultaneously, DLCO had a very significant effect on survival from other causes (HR 0.966, P < 0.0001) when adjusted for FEV1. However, when adjusted by DLCO, FEV1 had no significant effect. A DLCO <40% best predicted decreased survival from causes other than cancer within stage I lung cancers (stage IA HR 0.953, P < 0.0001; stage IB HR 0.968, P < 0.0001)., Conclusions: DLCO was found to be a significant prognostic factor for long-term survival after lung cancer surgery. This may serve as a surrogate for competing morbidities with declining values predicting a higher risk of late non-cancer-related death., (Copyright 2009 Wiley-Liss, Inc.)

Background: Atrial fibrillation (AF) occurs commonly after anatomic pulmonary resection. In this study, the efficacy of amiodarone for prevention of post-pulmonary resection AF was investigated., Methods: One hundred thirty patients undergoing lobectomy, bilobectomy, or pneumonectomy were randomly assigned prospectively to receive amiodarone (n = 65) or no prophylaxis (control group, n = 65). The amiodarone group received 1,050 mg by continuous intravenous infusion over 24 hours, initiated at the time of anesthesia induction, followed by 400 mg orally twice daily until hospital discharge or for a maximum of 6 days. The primary endpoint was AF requiring treatment during hospitalization. Secondary endpoints included postoperative length of hospital and intensive care unit stays., Results: There were no significant differences between the amiodarone and control groups in demographics, comorbid conditions, extent of pulmonary resection, or preoperative or postoperative use of beta-blockers or calcium-channel blockers. The incidence of AF was lower in the amiodarone group than in the control group (13.8% versus 32.3%, p = 0.02; relative risk reduction = 57%). There was no difference between the amiodarone and control groups in median length of hospital stay (7 versus 8 days, p = 0.79), but median length of intensive care unit stay was shorter in the amiodarone group (46 versus 84 hours, p = 0.03). There was no significant difference between the amiodarone and control groups in the incidence of pulmonary complications or other adverse effects., Conclusions: Amiodarone prophylaxis significantly reduces the incidence of AF after anatomic pulmonary resection, and is associated with a significant reduction in length of intensive care unit stay.

Background: Histoplasmosis may result in a spectrum of complications that require thoracic surgical intervention. We reviewed our 17-year experience in the management of histoplasmosis to determine outcomes as well as gain insight into the distribution of complications requiring surgical intervention., Methods: The hospital records of patients who underwent surgical treatment for complications related to histoplasmosis from 1991 to 2008 were reviewed. Based on the predominant presentation, patients were categorized with complications secondary to broncholithiasis, granulomatous disease, or fibrosing mediastinitis. Patients who underwent diagnostic surgery and were found to have histoplasmosis were excluded., Results: Of the 49 patients who underwent surgery for histoplasmosis-related complications, 27 (55%) had granulomatous disease, 13 (27%) had broncholithiasis, and 9 (18%) had fibrosing mediastinitis. The most common clinical presentations were recurrent pneumonia (n = 16) and hemoptysis (n = 13); less common presentations included dysphagia (n = 3) and superior vena cava syndrome (n = 1). Two patients required cardiopulmonary bypass for resection; 1 of these died postoperatively (series mortality 2%). Seven patients (14%) had complications. Relief of symptoms was achieved in all surviving patients., Conclusions: Complications of histoplasmosis requiring thoracic surgical intervention are diverse with pulmonary complications predominating. Although surgically challenging, excellent short- and long-term outcomes may be expected.

Aberrant glycosylation has been implicated in various types of cancers and changes in glycosylation may be associated with signaling pathways during malignant transformation. Glycomic profiling of blood serum, in which cancer cell proteins or their fragments with altered glycosylation patterns are shed, could reveal the altered glycosylation. We performed glycomic profiling of serum from patients with no known disease (N = 18), patients with high grade dysplasia (HGD, N = 11) and Barrett's esophagus (N = 5), and patients with esophageal adenocarcinoma (EAC, N = 50) in an attempt to delineate distinct differences in glycosylation between these groups. The relative intensities of 98 features were significantly different among the disease onsets; 26 of these correspond to known glycan structures. The changes in the relative intensities of three of the known glycan structures predicted esophageal adenocarcinoma with 94% sensitivity and better than 60% specificity as determined by receiver operating characteristic (ROC) analysis. We have demonstrated that comparative glycomic profiling of EAC reveals a subset of glycans that can be selected as candidate biomarkers. These markers can differentiate disease-free from HGD, disease-free from EAC, and HGD from EAC. The clinical utility of these glycan biomarkers requires further validation.

Background: Differential gene expression offers an attractive means by which to study genes that may be involved in disease development and/or progression. We performed quantitative gene expression in various stages of esophageal adenocarcinoma, treated exclusively by surgery with complete 2-field lymphadenectomy, in an attempt to discern genes involved in disease progression as well as genes that may predict survival., Methods: Gene expression profiling was accomplished by cDNA-mediated annealing, selection, extension, and ligation (DASL) assay. RNA was extracted from 89 archived formalin-fixed, paraffin-embedded esophageal adenocarcinoma tissues. DASL assay was performed with the Sentrix Universal Array (Illumina Corp, San Diego, Calif) of 502 known cancer-related genes. Bioinformatics tools were used to determine significant differential gene expression in T1-2 versus T3-4 tumors and tumors without lymph node involvement (N0) versus tumors with lymph node involvement (N+). Gene expression was also correlated with overall survival., Results: Twenty-one genes were overexpressed in T1-2 compared with T3-4 tumors (false discovery rate of 0). Underexpression of 1 gene was seen in N+ compared with N0 tumors (false discovery rate of 0). For overall survival, underexpression of 9 genes correlated with long survival., Conclusions: Using differential gene expression of 502 known cancer genes, we identified genes that may be involved at various stages in the progression of esophageal adenocarcinoma. We also identified genes that may correlate with prolonged survival and, thus, may serve as prognostic markers. These findings may provide further insight into the mechanisms of development and/or progression of esophageal adenocarcinoma. Prospective studies are needed to verify the prognostic value of these genes.

Background: Bronchopleural fistula remains a significant source of morbidity and mortality after right pneumonectomy. We reviewed our initial experience with a novel "carinaplasty" airway closure technique aimed at reducing the risks of bronchopleural fistula., Methods: Since 2003, 51 consecutive patients who required right pneumonectomy at our institution underwent carinaplasty airway closure. Malignancy was the indication for pneumonectomy in all but 2 patients. Eighteen patients received preoperative radiation therapy, including 5 patients who received 6000 cGy or more. Postoperatively, 17 patients required mechanical ventilation for an average of 13 days (range, 3 to 42 days)., Results: Six operative deaths occurred, four (8.6%) of which were in the 46 patients who did not receive preoperative bleomycin. All deaths were secondary to respiratory failure. None of these patients demonstrated bronchopleural fistula despite mechanical ventilation for up to 30 days. In 2 patients, a small (< or = 2 mm) bronchopleural fistula developed at 3 and 4 months after operation, respectively. Both patients presented with minor symptoms and spontaneously healed within 1 month after open drainage., Conclusions: These data suggest that the carinaplasty airway closure may reduce the morbidity and mortality of bronchopleural fistula after right pneumonectomy. We speculate mechanisms include elimination of the bronchial stump diverticulum in combination with more submucosal blood supply at the suture line compared with the standard bronchial closures. We currently consider carinaplasty airway closure the technique of choice at our institution and plan continued evaluation.

Background: The treatment of primary mediastinal nonseminomatous germ cell tumors (PMNSGCT) with cisplatin-based chemotherapy, followed by surgical resection of residual disease, has been established. We reviewed our institution's 25-year experience in the cisplatin era to determine surgical risks and predictors of survival after surgery for PMNSGCT., Methods: A total of 158 patients (mean age, 29 +/- 8 years) who underwent postchemotherapy operations for PMNSGCT were reviewed and multiple variables analyzed., Results: Ten (6%) operative deaths occurred, nine of which were attributed to respiratory failure, and 26 (18%) patients experienced postoperative complications, including 9 with respiratory failure. None of 17 recent patients who received chemotherapy regimens that did not contain bleomycin experienced pulmonary complications (p = 0.12 vs patients who received bleomycin). Operative survivors were followed up a median of 34 months (range, 1 to 194 months). Multivariable analysis demonstrated that the postchemotherapy pathologic category of complete necrosis vs teratoma), persistent germ cell or nongerm cell cancer, and elevated serum tumor markers after operation were independently predictive of survival., Conclusions: Operative risks for PMNSGCT appear to be improved with the use of chemotherapy regimens that do not contain bleomycin. Patients pathologically demonstrating complete tumor necrosis in the residual mass after chemotherapy have excellent long-term survival, with decreasing survival after resection of teratoma and persistent germ cell or nongerm cell cancer. Patients pathologically demonstrating persistent germ cell or nongerm cell cancer have poor but possible long-term survival, which justifies an aggressive surgical approach in patients who are deemed operable.

Background: Atrial fibrillation occurs in up to 46% of patients following esophagectomy; amiodarone may be used for prophylaxis or treatment in these patients. There are few data regarding drug absorption following esophagectomy., Objective: The aim of this study was to determine serum amiodarone concentrations when the drug is administered into the stomach conduit following esophagectomy., Methods: Patients who underwent noncardiac thoracic surgery were enrolled in this prospective, controlled study. One group of patients underwent esophagectomy, and a second group of patients comprised a control group who underwent pulmonary resection (PR). A continuous IV amiodarone infusion (0.73 mg/min) was initiated at anesthesia induction and continued for 24 hours (total IV dose 1050 mg), followed by 400 mg via a nasogastric tube (in the esophagectomy group) or orally (in the PR group) every 12 hours for 6 days. Blood samples for determination of serum amiodarone concentrations were obtained at completion of the infusion (postoperative day [POD] 1), and before the third (POD 2) and seventh (POD 4) enteral doses., Results: A total of 27 patients were enrolled (esophagectomy group, 13 patients; PR group, 14 patients). Patients in the 2 groups had statistically similar ages (mean [SD], 60 [10] vs 53 [10] years; P = 0.07) and proportions of men (12/13 [92%] vs 8/14 [57%]; P = 0.08). Patients in the 2 groups were statistically similar with respect to race (white, 13/13 [100%] vs 13/14 [93%]) and preoperative weight (mean [SD], 83.3 [11.5] vs 77.7 [18.6] kg). On POD 1, age-adjusted and sex-adjusted serum amiodarone concentrations were not significantly different in the esophagectomy group versus the PR group (mean [SD] 0.65 [0.22] vs 0.84 [0.20] microg/mL). Mean (SD) serum amiodarone concentrations were significantly lower in the esophagectomy group on POD 2 (0.35 [0.27] vs 0.60 [0.18] microg/mL; P = 0.02) and on POD 4 (0.30 [0.34] vs 0.87 [0.16] microg/mL; P < 0.001). Serum amiodarone concentrations were undetectable in 33% and 50% of patients in the esophagectomy group on PODs 2 and 4, respectively, compared with 0% in the PR group (both, P = 0.03)., Conclusions: Serum amiodarone concentrations were significantly lower (and in some cases undetectable) when the drug was administered via a nasogastric tube into the stomach conduit in patients after esophagectomy compared with those concentrations after oral administration in a PR population. Nasogastric administration of amiodarone should probably be avoided for prophylaxis or treatment of postesophagectomy tachyarrhythmias.

Purpose: Prolonged air or fluid chest tube drainage may delay chest tube removal in thoracic surgery patients otherwise ready for discharge. We reviewed 20 months of experience at our institution with postoperative, outpatient chest tube management using a new portable chest tube device., Description: From May 2003 to December 2004, 457 major thoracic procedures were performed at our institution. Besides excessive chest tube output or air leak, 50 patients met the criteria for discharge. There were 36 patients who were discharged with a new portable chest tube system (Express Mini 500; Atrium Medical Corp, Hudson, NH). Patients received written instructions and demonstrated competence on system use. Patients returned for chest tube removal after satisfactory resolution of air leak or fluid drainage., Evaluation: Postoperative outpatient chest tube management accounted for 404 days. There were no major complications. Four patients experienced minor complications. Thirty-two patients (89%) experienced uneventful and successful outpatient chest tube management., Conclusions: These data suggest that successful postoperative outpatient chest tube management can be accomplished in select patients. This program resulted in substantial hospital cost reduction and enhanced patient satisfaction by allowing earlier discharge.

Background: Currently, endoscopic biopsy is the only method used to diagnose esophageal adenocarcinoma. Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we sought to identify a potentially diagnostic serum protein pattern that can serve as a reliable blood test for the diagnosis of esophageal adenocarcinoma. In addition, we sought to identify potential biomarkers for esophageal adenocarcinoma., Methods: Whole serum was collected using standard techniques from subjects with a known diagnosis of esophageal adenocarcinoma as well as from subjects without any known esophageal disease. The samples were spotted onto a hydrophobic (H50) and immobilized metal affinity (IMAC30) chip surface and allowed to incubate. All samples were run in duplicate. After several washes, matrix was added and a mass range of 1500 to 30000 daltons was analyzed by SELDI-Time-of-Flight mass spectroscopy. Statistical analysis was performed using Biomarker Pattern Software (Bio-Rad Laboratories, Hercules, CA)., Results: For the H50 analysis, 3 peaks were identified that correctly diagnosed 42 of 43 cancers and 10 of 11 normals. For the IMAC30, 4 peaks were identified that correctly diagnosed 50 of 50 cancers and 10 of 10 normals., Conclusions: Serum proteomic pattern shows great promise in the diagnosis of esophageal adenocarcinoma. This technology may lead to the development of a noninvasive screening test as well as to the identification of potential novel biomarkers for esophageal adenocarcinoma.

Objectives: Proliferating cell nuclear antigen is a component of the DNA synthesome and functions in DNA replication and repair. Our group has recently identified an acidic isoform of proliferating cell nuclear antigen, cancer-specific proliferating cell nuclear antigen, that appears to be present only in malignant tissue. We sought to determine the presence of cancer-specific proliferating cell nuclear antigen in esophageal dysplasias and invasive adenocarcinomas to assess its potential utility in discriminating malignancy., Methods: With a polyclonal antibody to cancer-specific proliferating cell nuclear antigen, immunohistochemical staining was performed on samples from a total of 30 patients with Barrett esophagus with varying degrees of dysplasia and 18 patients with invasive adenocarcinoma. We also performed cancer-specific proliferating cell nuclear antigen immunohistochemical staining on a commercially available tissue microarray and on specimens obtained from endoscopic biopsies. As controls, immunohistochemical staining for cancer-specific proliferating cell nuclear antigen was performed on normal esophageal tissue and immunohistochemical staining for proliferating cell nuclear antigen was performed on all specimens with a commercially available antibody., Results: Of the Barrett esophagus specimen, 14 showed no dysplasia, 8 showed low-grade dysplasia, and 8 showed high-grade dysplasia. None of these specimens stained positively for cancer-specific proliferating cell nuclear antigen. Of the 18 adenocarcinoma specimens, all stained positively for cancer-specific proliferating cell nuclear antigen. There was no significant cancer-specific proliferating cell nuclear antigen expression in normal esophageal tissue, and proliferating cell nuclear antigen expression was noted to a high degree in all tissues., Conclusions: Cancer-specific proliferating cell nuclear antigen appears to demonstrate high specificity for esophageal adenocarcinoma. This marker therefore may prove useful in differentiating invasive cancer from high-grade dysplasia. Cancer-specific proliferating cell nuclear antigen also holds future promise as a biomarker for esophageal adenocarcinoma.

Hypoxic pulmonary vasoconstriction (HPV) and pulmonary hypertension present a common and formidable clinical problem for practicing thoracic, transplant, and trauma surgeons. The recent discovery of efficacious drugs that are selective for the pulmonary vasculature has brought about the potential for very powerful therapeutic agents. Inhaled nitric oxide (NO) therapy has already found broad clinical utility, yet its use is limited by potential toxicities. Rho kinase (ROK) has been discovered to play a very central role in the formation of hypoxia induced pulmonary hypertension, and the advent of very specific ROK inhibitors has shown positive clinical results. Finally, phosphodiesterase-5 inhibitors have been found to selectively vasodilate the pulmonary vasculature in the midst of HPV. The purposes of this review are to: 1) discuss the advantages and disadvantages of inhaled preparations of NO; 2) address experimental alternatives to inhaled preparations of NO to treat HPV; 3) explore potential therapeutic avenues associated with inhibition of Rho-kinase; and, 4) examine the use of phosphodiesterase-5 (PDE-5) inhibitors and combination therapy in the treatment of HPV.

A variety of strategies, using chemotherapy, radiation therapy, and surgical resection have been employed in the treatment of locally advanced esophageal cancer. No strategy has proven superior, and poor long-term survival is anticipated. A survival benefit has been suggested for patients who achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation therapy. We examined the collective results at three institutions of patients who achieved a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based review was conducted. Kaplan-Meier calculations were used to determine overall and disease-free survival. Between 1995 and 2002, 229 patients were treated with neoadjuvant chemoradiation followed by surgery as a planned approach for locally advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and adenosquamous/undifferentiated in two patients. Forty patients were staged by endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in the perioperative period. The remaining patients have been followed for an average of 46 months. Overall survival at 5 years was 56.4% and a median survival has not been reached. Esophageal cancer patients who demonstrate a pCR following neoadjuvant chemoradiation are a select subset who demonstrate excellent long-term survival. Identification of clinical variables or biomarkers predictive of pCR may therefore optimize treatment strategies of patients with locally advanced esophageal cancer.

Background: Severe central airway obstruction due to expiratory collapse occurs with malacia of intrathoracic trachea and main bronchi, often with chronic obstructive pulmonary disease. Bronchoscopically observed, it is confirmed by inspiratory-expiratory computerized tomographic chest scans. Prior attempts at surgical stabilization have not given dependable results., Methods: Posterior tracheobronchial splinting with polypropylene mesh (Marlex) holds cartilages in more normal configuration, and fixes redundant membranous walls. Fourteen consecutive patients were so treated for severe dyspnea. Prior trials of various autologous and exogenous splints failed., Results: All felt subjectively improved early, with decreased dyspnea, cough, and secretion retention, and with increased activities. Mean forced expiratory volume in 1 second rose from 51% predicted to 73% (p = 0.009), and peak expiratory flow rate from 49% to 70% (p < 0.00001). One patient was lost to follow-up (1 year), 1 died of unrelated cause (5 years), 1 died of chronic obstructive pulmonary disease (3 years), and 1 had decreased respiratory function over 5 years. Ten patients were available for long-term follow-up: 6 were judged to have an excellent result, 2 were good, and 2 were poor due to collapse of unsplinted main bronchi., Conclusions: Complete splinting of all malacic central airways with Marlex restores anatomic configuration and permanently prevents expiratory collapse, with relief of extreme dyspnea, cough, and secretion retention.

Airway invasion by thyroid carcinoma is an uncommon but important clinical problem. The surgical management of airway invasion is somewhat controversial, with some studies suggesting that conservative shave procedures might be adequate; however, the standardization and safety of techniques of airway resection and reconstruction have made en bloc surgery a reasonable approach for the management of such carcinomas. Tracheal resection and reconstruction for thyroid carcinomas with airway invasion might provide long-lasting palliation and might even be curative in a significant number of patients suffering from this disease.

Objective: Mediastinoscopy is a common procedure used for the diagnosis of thoracic disease and the staging of lung cancer. We sought to determine the current role of mediastinoscopy in the evaluation of thoracic disease., Methods: We conducted a retrospective review of all mediastinoscopies performed by members of our service between January 1988 and September 1998., Results: We performed mediastinoscopies on 2137 patients. A total of 1745 patients underwent mediastinoscopy for known or suspected lung cancer. In 422 of these procedures, N2 or N3 disease was identified; only 28 of these patients underwent resection. The remaining 1323 had no evidence of metastatic disease. In these patients 947 had lung cancer. Only 76 of the patients with lung cancer were found to have N2 disease at exploration. Among the 1323 patients with a negative mediastinoscopy result, 52 underwent resection of a nonbronchogenic malignancy, and 217 had resection of a benign lesion. A total of 392 patients underwent mediastinoscopy for the evaluation of mediastinal adenopathy in the absence of any identifiable pulmonary lesion. Of these, 161 had a nonbronchogenic malignancy, 209 had benign disease, and 25 had no diagnosis established; mediastinoscopy established a definitive diagnosis in 93.6% of patients. In the entire group of 2137 patients, there were 4 perioperative deaths and 12 complications. Only one death was directly attributed to mediastinoscopy. No deaths or complications occurred in patients undergoing mediastinoscopy for benign disease., Conclusions: Mediastinoscopy is a highly effective and safe procedure. We believe that mediastinoscopy should currently be used routinely in the diagnosis and staging of thoracic diseases.

The incidence of esophageal adenocarcinoma has increased dramatically over the past 20 years. The causes for this change in incidence and the genetic defects that underlie tumorigenesis are unknown. We performed loss of heterozygosity (LOH) studies in esophageal adenocarcinomas in an effort to map the location of tumor suppressor genes involved in the initiation or progression of this cancer. A genome-wide search for LOH was undertaken using microsatellite repeat polymorphisms and a panel of 27 tumor and matched normal DNAs. This is the first report of an allelotype analysis of esophageal adenocarcinomas. We observed frequent loss of sequences on the short arm of chromosome 17 in the region of the TP53 gene. We also identified a region on 4q lost in more than half of the tumors investigated. The high rate of LOH for 4q sequences speaks to the involvement of an as yet unidentified tumor suppressor gene in esophageal adenocarcinoma tumorigenesis.