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Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.

Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone.

Lung cancer has been transformed from a rare disease into a global problem and public health issue. The etiologic factors of lung cancer become more complex along with industrialization, urbanization, and environmental pollution around the world. Currently, the control of lung cancer has attracted worldwide attention. Studies on the epidemiologic characteristics of lung cancer and its relative risk factors have played an important role in the tertiary prevention of lung cancer and in exploring new ways of diagnosis and treatment. This article reviews the current evolution of the epidemiology of lung cancer.

Objective Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non–small cell lung cancer. Methods Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non–small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. Results One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). Conclusions Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.

Esophageal cancer is a male-dominant aggressive malignancy and a leading cause of cancer-related mortality worldwide. Squamous cell carcinoma and adenocarcinoma are the two predominant histological subtypes with varying geographical and racial distribution. Globally, squamous cell carcinoma remains the most common histological type. In Western countries, however, adenocarcinoma has become the leading histological subtype, corresponding to a rise in the incidence of obesity, gastro-esophageal reflux disease and Barrett’s esophagus. The risk of esophageal adenocarcinoma conferred by Barrett’s esophagus depends on factors such as genomic instability, race and gender of the patient. Treatment requires a multidisciplinary team approach and optimal therapy is still debated. Endoscopic therapies, including radiofrequency ablation, endoscopic mucosal resection and endoscopic sub mucosal dissection, have become the standard treatment modality for Barrett’s esophagus and early carcinoma. Multimodal treatment, which includes chemotherapy, radiation therapy followed by surgical resection or without surgical resection, in varying orders remains the main mode of treatment for most patients. Minimally invasive surgical approaches have become the standard for esophagectomy and the current literature has demonstrated similar oncological outcomes with reduced morbidity. Recently, there has been a modest improvement in the overall survival of patients with esophageal cancer.

Department of Surgery, University of Arizona, Tucson, Arizona; Department of Thoracic Surgery, University Hospital Leuven, Leuven,Belgium; Department of Surgery, Duke University Medical Center, Durham, North Carolina; M.D. Anderson Cancer Center,Universityof Texas, Houston, Texas; Division of Cardiothoracic Surgery, University of Colorado Denver School of Medicine, Aurora, Colorado;Weill Cornell Medical College, New York, New York; Jersey Shore University Medical Center, Neptune, New Jersey

William H. Allum,1 Luigi Bonavina,2 Stephen D. Cassivi,3 Miguel A. Cuesta,4 Zhao Ming Dong,5 Valter Nilton Felix,6 Edgar Figueredo,7 Piers A.C. Gatenby,1,8,9 Leonie Haverkamp,10 Maksat A. Ibraev,11 Mark J. Krasna,12 Rene Lambert,13 Rupert Langer,14 Michael P.N. Lewis,15 Katie S. Nason,16 Kevin Parry,10 Shaun R. Preston,8 Jelle P. Ruurda,10 Lara W. Schaheen,16 Roger P. Tatum,7 Igor N. Turkin,11 Sylvia van der Horst,10 Donald L. van der Peet,4 Peter C. van der Sluis,10 Richard van Hillegersberg,10 Justin C.R. Wormald,15 Peter C. Wu,7 and Barbara M. Zonderhuis4 1Division of Surgery and Interventional Science, University College London, London, United Kingdom. 2Department of Biomedical Sciences for Health, Division of General Surgery, University of Milan School of Medicine, Milano, Italy. 3Department of Surgery, Mayo Clinic, Rochester, Minnesota. 4Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands. 5Department of Pathology, University of Washington, Seattle, Washington. 6Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. 7Department of Surgery, VA Puget Sound and University of Washington, Seattle, Washington. 8Royal Surrey County Hospital, Guildford, United Kingdom. 9Academic Department of Surgery, Royal Marsden Hospital, London, United Kingdom. 10Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. 11N.N.Blokhin Russian Cancer Research Center, RAMS, Moscow, Russia. 12Department of Oncology, Jersey Shore University Medical Center, Neptune, New Jersey. 13Screening Group at WHO, International Agency for Research on Cancer, Lyon, France. 14Institute of Pathology, University of Bern, Bern, Switzerland. 15Department of General Surgery, Norfolk and Norwich University Hospital, Norwich, United Kingdom. 16Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

Objective Clinical T2N0 esophageal carcinoma is a heterogenous disease frequently complicated by inaccurate staging. Incorrect staging may lead to suboptimal treatment for patients with unidentified local-regionally advanced disease. Therapeutic options for these patients remain controversial. We sought to evaluate the outcomes of patients with cT2N0 who underwent esophagectomy as either primary therapy or after neoadjuvant treatment. Methods This was a multi-institutional collaboration of 26 high-volume esophageal centers. Patients with complete staging who underwent elective resection from 2002 to 2012 were included. Three treatment groups were identified; primary esophagectomy, preoperative chemotherapy, and preoperative chemoradiation (CXRT). Pretreatment variables were explored for independent predictors of long-term outcomes. The primary esophagectomy subgroup was evaluated for stage migration. Results In total, 767 patients were evaluated; 35% (268) had preoperative therapy (195 CXRT, 73 chemotherapy). Staging accuracy was 14% (70/499), with pT 0 in 39% (195). Preoperative treatment modality (none, CXRT, chemotherapy) was not identified as a predictor of outcome (median survival 63, 70, 71 months, respectively, P = .956). Longitudinal tumor length >3.25 cm was predictive of pN+ for the primary esophagectomy cohort as well as adenocarcinoma histology only (odds ratio 2.2 and 2.4, respectively, P Conclusions Current treatment options for patients with cT2N0M0 do not reveal a comparative survival advantage to preoperative therapy. Pretreatment tumor length can identify a subgroup of patients at risk for understaging (pN+). The incidence of overstaging suggests that organ-sparing approaches (endoscopic resection) may play a future role in appropriately selected patients.

To assess the prognostic significance of positive circumferential resection margin on overall survival in patients with esophageal cancer, a systematic review and meta-analysis was performed.Studies were identified from PubMed, EMBASE, and Web of Science. Survival data were extracted from eligible studies to compare overall survival in patients with a positive circumferential resection margin with patients having a negative circumferential resection margin according to the Royal College of Pathologists (RCP) criteria and the College of American Pathologists (CAP) criteria. Survival data were pooled with hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). A random-effects model meta-analysis on overall survival was performed.The pooled HRs for survival were 1.510 (95% CI, 1.329-1.717; p0.001) and 2.053 (95% CI, 1.597-2.638; p0.001) according to the RCP and CAP criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients with T3 stage disease according to the RCP (HR, 1.381; 95% CI, 1.028-1.584; p=0.001) and CAP (HR, 2.457; 95% CI, 1.902-3.175; p0.001) criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients receiving neoadjuvant therapy according to the RCP (HR, 1.676; 95% CI, 1.023-2.744; p=0.040) and CAP (HR, 1.847; 95% CI, 1.226-2.78; p=0.003) criteria, respectively.Positive circumferential resection margin is associated with poor prognosis in patients with esophageal cancer, particularly in patients with T3 stage disease and patients receiving neoadjuvant therapy.

The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies.

This paper presents commentaries on neoadjuvant treatment esophagectomy; the prognostic and predictive effects of single nucleotide polymorphisms (SNP) in the multimodality therapy of esophageal cancer; optimal preoperative treatment prior to surgery for esophageal cancer; a possible role for trastuzumab in treating esophageal adenocarcinoma or any esophageal dysplasia/intra-epithelial neoplasia; surgery after chemoradiation in resectable esophageal cancer; whether para-aortic lymph node dissection should be performed in esophagogastric junction (EGJ) tumors; and transhiatal esophagectomy in treatment of the esophageal cancer.

Because of video-assisted thoracic technology and increased patient awareness of treatment options for palmar hyperhidrosis, endoscopic thoracic sympathectomy (ETS) has become a well-accepted treatment for this disorder. Video assistance affords excellent visualization of thoracic anatomy, which allows the procedure to be done quickly with few complications. However, despite the ease of performing ETS, complications can occur unless thoracic anatomy and physiology are well-understood. Awareness of possible intraoperative and postoperative complications is essential if this procedure is gong to be performed safely.

The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation.

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.

Over the last 30 years neoadjuvant treatment of stage IIIA non-small cell lung cancer (NSCLC) followed by surgical resection for stage IIIB disease has significantly improved the overall results of treatment for patients with stage III NSCLC as well as for those with locally invasive tumors. Different chemotherapy regimens have been used, although in most studies some combination of drugs that include cisplatin is the standard. Radiation when given as part of the induction protocol appears to offer a higher rate of resection and complete resection, and higher doses of radiation are associated with better nodal downstaging. Resection in patients with persistent N2 disease and pneumonectomy following induction therapy remain controversial. Resection in patients with persistent N2 disease and pneumonectomy following induction therapy remain controversial.

The objective of this study was to evaluate the different pathological and clinical characteristics of thymomas with and without myasthenia gravis (MG) and to determine whether the presence of MG influences the prognosis in thymoma patients.We retrospectively studied data from 228 consecutive patients operated on from 1992 to 2007 in Beijing Tongren Hospital. These thymoma patients have been subdivided into two groups: group A with MG (n = 125) and group B without MG (n = 103).There were no perioperative deaths. There were 19 inoperable cases (6 in the group with MG, 13 without MG, P = 0.035). The proportions of types A, AB, B1, B2, B3, and C thymoma in this data were 0, 22.4, 26.4, 30.4, 20.8, and 0%, respectively, in the group with MG, and 10.5, 13.4, 23.6, 24.5, 16.4, and 11.6%, respectively in the group without MG. There was a significant difference between hyperplastic paraneoplastic thymus coexisting in 28.8% patients with MG and only 5.8% in patients without MG. Microthymoma was identified in the paraneoplastic thymus of three patients with MG. There were 198 patients followed up. There was no recurrence in patients with type A, and a few patients with types AB, B1, B2, B3, and C recurred. The actuarial 5- and 10-year survival rates were 89.3 and 81.2% for patients with MG, respectively, and 90 and 78.9% for patients without MG, respectively. Within 5 years postoperatively, 6 of 9 patients with MG died of myasthenia crisis, while 6 of 7 deaths in patients without MG were attributable to inoperable tumors (stage IV) and type C thymoma.MG seldom occurs in types A and C thymoma. MG of some thymoma patients was not caused by thymoma, but by the paraneoplastic thymus. The prognosis of thymomas with MG is similar to that without MG. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and/or type C for thymoma patients without MG.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling.Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema.Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life.After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life.BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).

Oesophageal and gastric cancers are amongst the most frequent and lethal of cancers worldwide. In the US alone, some 13 000 individuals are affected each year, and mortality is particularly high in elderly patients with advanced stage disease and multiple co-morbidities. Patients usually do not present until later in the disease when symptoms occur, once the tumour is sufficiently large to cause obstruction or invasion of adjacent structures. Oesophageal cancer can metastasize to almost any organ, and widespread distant metastases are almost always present at the time of death. Overall mortality from this cancer is around 80-90%. Curative treatment of oesophageal cancer must achieve local control of the primary lesion as well as control and/or prevention of metastases. These are important contributors to overall results when therapy is undertaken in elderly patients, as are the significant risks of adverse effects such as morbidity from chemoradiation and the morbidity and mortality of oesophagectomy. Surgical resection affords the best chance for local control and the best means of palliation of dysphagia for most patients with localized disease, although both local and systemic recurrence of disease are common when surgery is used alone. Because of the low cure rates associated with the use of surgery alone, other modalities have been added to the treatment regimen. Elderly patients with significant cardiac and pulmonary co-morbidity are candidates for nonoperative therapy, even at an early disease stage. There are few data to support a survival advantage from adjuvant radiotherapy or chemotherapy following complete resection, in the absence of documented metastatic disease. Chemotherapy and radiotherapy have both been reported to improve survival when administered preoperatively in patients with oesophageal cancer, while current data using trimodal therapy show a trend towards increased treatment-related mortality with only a slight increase in overall survival. There is currently no completely reliable preoperative method for restaging patients following neoadjuvant chemoradiation in order to assess pathological complete response. Novel restaging techniques are therefore required, in addition to further study of the risks and benefits of neoadjuvant chemoradiotherapy for this disease.

As cardiothoracic surgeons, we face many difficult problems in our professional lives, and base most decisions on clinical judgment developed and honed during many years of training and experience. Some decisions, however, are based on more than weighing scientific evidence and outcome probabilities, and they require value judgments on such matters as the desirability of alternative outcomes. Among the most difficult judgments we make are those that conflict with the views of the patient or the patient’s proxy (ie, agent appointed in advance by the patient) or surrogate (ie, agent authorized by law) decision maker. In cases of critical illness with low survival probability, discordant judgments about withdrawing life support are often based on perceived acceptability of the projected quantity and quality of life if the patient survives. The surgeon and the proxy or surrogate might find themselves on either of the opposing sides of the issue.

The objective of lung volume reduction surgery (LVRS) is the safe, effective, and durable palliation of dyspnea in appropriately selected patients with moderate to severe emphysema. Appropriate patient selection and preoperative preparation are prerequisites for successful LVRS. An effective LVRS program requires participation by and communication between experts from pulmonary medicine, thoracic surgery, thoracic anesthesiology, critical care medicine, rehabilitation medicine, respiratory therapy, chest radiology, and nursing. The critical analysis of perioperative outcomes has influenced details of the conduct of the procedure and has established a bilateral, stapled approach as the standard of care for LVRS. The National Emphysema Treatment Trial (NETT) remains the world's largest multi-center, randomized trial comparing LVRS to maximal medical therapy. NETT purposely enrolled a broad spectrum of anatomic patterns of emphysema. This, along with the prospective, audited collection of extensive demographic, physiologic, radiographic, surgical and quality-of-life data, has positioned NETT as the most robust repository of evidence to guide the refinement of patient selection criteria for LVRS, to assist surgeons in providing optimal intraoperative and postoperative care, and to establish benchmarks for survival, complication rates, return to independent living, and durability of response. This article reviews the evolution of current LVRS practice with a particular emphasis on technical aspects of the operation, including the predictors and consequences of its most common complications.

Thoracoscopy or video-assisted thoracic surgery (VATS) has become an important tool in the management of thoracic diseases. Most thoracic procedures are first attempted using a VATS technique. Thoracoscopy has an important role in managing malignancies that present with symptoms or lesions in the chest. Although the primary role is diagnostic, in the case of non-thoracic malignancies, VATS also has an important palliative treatment role, as in dealing with pleural and pericardial effusions and metastatic deposits.

Purpose Outcomes after resection of stage I non–small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. Materials and Methods Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. Results Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. Conclusion NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.

Although staple line buttressing is advocated to reduce air leak after lung volume reduction surgery (LVRS), its effectiveness is unknown. We sought to identify risk factors for air leak and its duration and to estimate its medical consequences for selecting optimal perioperative technique(s), such as buttressing technique, to preempt or treat post-LVRS air leak.Detailed air leak data were available for 552 of 580 patients receiving bilateral stapled LVRS in the National Emphysema Treatment Trial. Risk factors for prevalence and duration of air leak were identified by logistic and hazard function analyses. Medical consequences were estimated in propensity-matched pairs with and without air leak.Within 30 days of LVRS, 90% of patients developed air leak (median duration = 7 days). Its occurrence was more common and duration prolonged in patients with lower diffusing capacity (p = 0.06), upper lobe disease (p = 0.04), and important pleural adhesions (p = 0.007). Duration was also protracted in Caucasians (p0.0001), patients using inhaled steroids (p = 0.004), and those with lower 1-second forced expiratory volume (p = 0.0003). Surgical approach, buttressing, stapler brand, and intraoperative adjunctive procedures were not associated with fewer or less prolonged air leaks (p/= 0.2). Postoperative complications occurred more often in matched patients experiencing air leak (57% vs 30%, p = 0.0004), and postoperative stay was longer (11.8 +/- 6.5 days vs 7.6 +/- 4.4 days, p = 0.0005).Air leak accompanies LVRS in 90% of patients, is often prolonged, and is associated with a more complicated and protracted hospital course. Its occurrence and duration are associated with characteristics of patients and their disease, not with a specific surgical technique.

Objective We sought to identify predictors of operative mortality, pulmonary morbidity, and cardiovascular morbidity after lung volume reduction surgery. Methods Univariate and multivariate logistic regression analyses were performed. Candidate predictors included demographic characteristics, physical condition characteristics, pulmonary function measures, measures of the distribution of emphysema as determined by radiologists and by means of computerized analysis of chest computed tomographic scans, and measures of exercise capacity, dyspnea, and quality of life. End points analyzed were operative mortality (death within 90 days of the operation), major pulmonary morbidities (tracheostomy, failure to wean, reintubation, pneumonia, and ventilator for ≥3 days), and cardiovascular morbidities (infarction, pulmonary embolus, or arrhythmia requiring treatment). Results Five hundred eleven patients in the non–high-risk group of the National Emphysema Treatment Trial underwent lung volume reduction. The incidence of operative mortality was 5.5%, major pulmonary morbidity occurred in 29.8% of patients, and cardiovascular morbidity occurred in 20.0% of patients. Predictors for these end points are as follows: Relative oddsP valueOperative mortalityNon–upper-lobe predominance (radiologist)2.99.009Pulmonary morbidityAge in years1.05.02FEV 1 % predicted0.97.05Dlco % predicted0.97.01Cardiovascular morbidityAge in years1.07.004Oral steroid use1.72.04Non–upper-lobe predominance (QIA α measure)2.67 FEV 1 , Forced expiratory volume in 1 second; D lco, diffusion capacity; QIA , quantitative image analysis. Conclusions Although lung volume reduction can be performed in selected patients with acceptable mortality, the incidence of major cardiopulmonary morbidity remains high. The lone predictor for operative mortality of lung volume reduction was the presence of non–upper-lobe-predominant emphysema, as assessed by the radiologist. Pulmonary morbidity can be expected in elderly patients who have a low diffusing capacity for carbon monoxide and forced expiratory volume in 1 second. When assessing morbidity, the computer-assisted chest computed tomographic analysis proved useful only in predicting cardiovascular complications.

Background and Objectives CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. Methods Failure-free survival was calculated from a landmark 3 months after resection to account for heterogeneity in adjuvant therapy. Results Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9 had a median failure-free interval of 47.8 months from landmark, whereas the 33 patients (79%) with persistent N2 disease had a median failure-free survival of 8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete resection (positive highest resected node and/or margin), completeness of resection did not influence failure-free survival. There were 3 distant and no local recurrences among the N2 negative group, and 12 local recurrences among patients with residual N2 disease (P=0.041). Conclusions These data suggest: (1) persistent N2 disease following induction chemotherapy is unfavorable; (2) patients downstaged to N2 negative may benefit from surgical resection; however, (3) 33% of N2 negative patients suffered disease relapse. J. Surg. Oncol. 2006;94:599–606. © 2006 Wiley-Liss, Inc.

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non–small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of γ-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy γ-radiation, and harvested at 3 hours after γ-radiation treatment. γ-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in γ-radiation-treated cultures from the same subject. The mean percentage of γ-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of γ-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (Ptrend = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (Ptrend < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage–induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage–induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.

Background The purpose of this study is to evaluate the safety and efficacy of thoracoscopic sympathectomy for the treatment of hyperhidrosis, blushing, reflex sympathetic dystrophy, and digital ischemia. Methods We conducted a retrospective review of 202 patients who underwent thoracoscopic sympathectomy at the University of Maryland from March 1992 to April 2003. Results Three hundred ninety-seven procedures were performed on 202 patients (105 women, 97 men). Mean age was 29 years (range, 9 to 65). Indications for surgery included hyperhidrosis, facial blushing, digital ischemia, and reflex sympathetic dystrophy. Synchronous bilateral sympathectomies were performed in 194 patients; right side alone (n = 6); left side alone (n = 1); 1 patient had staged bilateral sympathectomies. Single incision with lung isolation technique was used. There was no mortality. Preoperative symptoms resolved completely or significantly improved in greater than 90% of patients. One patient with reflex sympathetic dystrophy recurred and 1 patient with hyperhidrosis complained of significant compensatory sweating. Compensatory sweating to a lesser degree occurred in approximately one third of patients. Complications included asymptomatic pleural effusion (n = 1), pneumothorax (n = 1), and reoperation for chylothorax that was identified early (n = 1). In 2 patients treated for facial blushing, Horner's syndrome developed postoperatively; 1 of them subsequently underwent blepharoplasty. In 3 patients, hyperesthesias developed at the incision. Conclusions Thoracoscopic sympathectomy can be performed safely and with excellent results. Compensatory sweating is the main side effect, although significant complaints from this are rare. Horner's syndrome remains an extremely uncommon complication as a result of thoracoscopic sympathectomy at our institution.

Surgical resection is the mainstay of therapy for patients presenting with Stage I and II non-small-cell lung cancer (NSCLC). Despite optimal staging and surgery, these patients are still at significant risk for failure. The purpose of this study is to report a retrospective analysis of the outcome of patients treated with surgery alone, as well as to analyze prognostic factors associated with survival.From May 2000 to November 2002, there was a total of 125 patients who were treated with surgery for NSCLC at University of Maryland Medical Center. Of these, 82 Stage I and II patients who received surgery alone as the definitive therapy were identified. The median age of the entire cohort was 68 years (range, 43-88 years). There were 48 males and 34 females. Sixty-three patients (76.8%) underwent lobectomies whereas 19 patients (23.2%) underwent nonlobectomy (wedge resection or segmentectomy) procedures. Patients who received neoadjuvant or adjuvant radiation therapy or chemotherapy were excluded from the study. Factors included in univariate and multivariate analyses were age, sex, tumor histology, pathologic stage, p53 status, preoperative hemoglobin (Hgb), and type of surgery performed. Endpoints of the study were relapse-free survival (RFS) and overall survival (OS).Median follow-up was 20.8 months (range, 0.4-43.2 months). For the entire cohort, the 2-year RFS was 66.0% and 2-year OS was 76.3%. Median survival for the entire cohort has not been achieved. In univariate analysis, the only factor that achieved statistical significance was preoperative Hgb level. Patients who had preoperative Hgb12 mg/dL experienced significantly worse RFS (mean RFS: 26.6 months vs. 34.9 months, p = 0.043) and OS (median OS: 27 months vs. 42.5 months, p = 0.011). For Stage I patients (n = 72), the 2-year RFS and OS were 66.4% and 77.1%, respectively. In the subgroup of stage IA patients (n = 37), there was a trend toward decreased overall survival in the anemic patients (2-year OS of 65.6% vs. 90.9%, p = 0.07). For Stage II patients (n = 10), the 2-year RFS and OS were 60.0% and 66.7%. In the Cox multivariate regression analysis, the only factor that achieved statistical significance was preoperative Hgb, with patients with Hgb12 mg/dL having decreased RFS (RR 4.1, p = 0.020) and OS (RR 2.9, p = 0.026). There was a trend toward worse RFS (p = 0.056) and OS (p = 0.068) in p53-negative patients (n = 39). Stage, histologic type, type of surgery performed, age, and sex did not affect outcome.In our cohort of mostly Stage I NSCLC patients treated with surgery only, preoperative Hgb12 mg/dL predicted for worse outcome. This effect was observed even in the traditionally low-risk subgroup of completely resected stage IA patients. Much has been written in the literature about anemia causing possible worsening of tumor hypoxia within solid tumors, thereby increasing radio-resistance. This has been a popular argument to explain poorer outcomes of anemic patients with solid tumors who undergo radiotherapy. However, our data suggest that anemia may be a sign of a more aggressive tumor that is at an increased risk of failure independent of the treatment modality.

Patients with Barrett's esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EAC). Clinical neoplastic progression risk factors, such as age and the length of the esophageal BE segment, have been identified. However, improved molecular biomarkers predicting increased progression risk are needed for improved risk assessment and stratification. Using real-time quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens. A subset of genes manifesting significant differences in methylation frequencies between BE and EAC was then analysed in 20 dysplastic specimens. All 10 genes except p14 were frequently methylated in EACs, with RUNX3, HPP1, CRBP1, RIZ1, and OST-2 representing novel methylation targets in EAC and/or BE. p16, RUNX3, and HPP1 displayed increasing methylation frequencies in BE vs EAC. Furthermore, these increases in methylation occurred early, at the interface between BE and low-grade dysplasia (LGD). To demonstrate the silencing effect of hypermethylation, we selected the EAC cells BIC1, in which the HPP1 promoter is natively methylated, and subjected them to 5-aza-2'-deoxycytidine (Aza-C) treatment. Real-time RT-PCR indicated increased HPP1 mRNA levels after 3 days of Aza-C treatment, as well as decreased levels of methylated HPP1 DNA. Hypermethylation of a subset of six genes (APC, TIMP3, CRBP1, p16, RUNX3, and HPP1) was then tested in a retrospective longitudinal study of 99 BE and nine LGD specimens obtained from 53 BE patients undergoing surveillance endoscopy. Only high-grade dysplasia (HGD) or EAC were defined as progression end points. Two patient groups were compared: eight progressors (P) and 45 nonprogressors (NP), using Cox proportional hazards models to determine the relative progression risks of age, BE segment length, and methylation events. Multivariate analyses revealed that only hypermethylation of p16 (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.33-2.20), RUNX3 (OR 1.80, 95% CI 1.08-2.81), and HPP1 (OR 1.77, 95% CI 1.06-2.81) were independently associated with an increased risk of progression, whereas age, BE segment length, and hypermethylation of TIMP3, APC, or CRBP1 were not independent risk factors. In combined analyses, risk was detectable up to, but not earlier than, 2 years preceding neoplastic progression. Hypermethylation of p16, RUNX3, and HPP1 in BE or LGD may represent independent risk factors for the progression of BE to HGD or EAC. These findings have implications regarding risk stratification, early EAC detection, and the appropriate endoscopic surveillance interval for patients with BE.

Purpose A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. Methods A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. Results Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. Conclusion Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.

Purpose To evaluate possible clinical and dosimetric predictors of acute esophagitis in patients with locally advanced non–small-cell lung carcinoma treated in a prospective Phase I-II trimodality protocol. Methods and materials The data from 36 patients with Stage III non–small-cell lung carcinoma treated in a Phase I-II high-dose concurrent chemoradiotherapy protocol were analyzed for possible predictors of acute esophagitis. The median age was 58 years (range, 38–77 years). Patients included in this study had either Stage IIIA ( n = 24) or IIIB ( n = 12) disease. All patients were treated with induction concurrent carboplatin (area under the plasma concentration-time curve 1), vinorelbine (5–15 mg/m 2 ), and hyperfractionated radiotherapy (69.6 Gy) followed by consolidation chemotherapy (carboplatin area under the plasma concentration-time curve 6, vinorelbine 25 mg/m 2 , docetaxel 75 mg/m 2 ) or surgery ( n = 19) plus consolidation chemotherapy. Acute toxicities were graded using the Radiation Therapy Oncology Group criteria. The following clinical and dosimetric parameters were analyzed: age, gender, race, T stage, N stage, pretreatment body mass index, percentage of weight lost during therapy, pretherapy serum albumin, tumor location, length of esophagus in treatment field, percentage of esophagus volume treated to >40, >45, >50, >55, >60, and >65 Gy. These parameters were coded and analyzed against Grade 2 and worse esophagitis using univariate and multivariate regression analyses. Results Of the 36 patients, Grade 1, 2, and 3 acute esophagitis was observed in 16 (44%), 12 (33%), and 2 (5.5%) patients, respectively. Grade 4 or 5 toxicity was not observed in this patient cohort. Only the pretreatment body mass index (ρ = −0.431, p = 0.004) and percentage of esophagus volume treated to >50 Gy (ρ = 0.297, p = 0.040) demonstrated a statistically significant correlation with the incidence of Grade 2 or worse esophagitis on univariate analysis. These parameters retained their statistical significance on multivariate regression analysis ( p = 0.029 and 0.049, respectively). Conclusion In patients undergoing concurrent high-dose chemotherapy and hyperfractionated radiotherapy, a low pretherapy body mass index and percentage of esophagus volume treated to >50 Gy were significantly associated with acute Grade 2 or worse esophagitis.

Recently, LVRS has received renewed public interest. Various surgical approaches and techniques exist, and each has challenges, advantages, and disadvantages. Stapled techniques have been used more commonly than plication techniques or lasers. The choice of staple buttressing material has not been shown to affect outcome. For most patients who are suitable for LVRS, a bilateral procedure is appropriate. Minimally invasive techniques are gaining in popularity and have demonstrated good results. Of the approaches discussed above, bilateral thoracoscopy in the supine position is likely to be the most expeditious with the lowest incision-related morbidity and dysfunction.

Background With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. Methods Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53 , an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. Results 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. Conclusions Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.

BACKGROUND Esophageal adenocarcinoma (EAC) is increasing at the most rapid rate of any cancer in the United States. An esophagogastroduodenal anastomosis (EGDA) surgical model in rats mimics human gastroesophageal reflux and results in EAC. Leukotriene A4 hydrolase (LTA4H), a protein overexpressed in EAC in this model, is a rate-limiting enzyme in the biosynthesis of leukotriene B4 (LTB4), a potent inflammatory mediator. We used this model and human EAC and non-tumor tissues to elucidate the expression pattern of LTA4H and to evaluate it as a target for chemoprevention. METHODS LTA4H expression was examined by western blotting and immunohistochemistry. The functional role of LTA4H in carcinogenesis was investigated by use of an LTA4H inhibitor, bestatin, in the rat EGDA model. All statistical tests were two-sided. RESULTS LTA4H was overexpressed in all 10 rat EACs examined, compared with its level in normal rat tissue; it was also overexpressed in four of six human EAC tumor samples, compared with its level in adjacent non-tumor tissue. In tissue sections from 20 EGDA rats and 92 patients (86 with EAC, one with dysplasia, and five with columnar-lined esophagus), LTA4H was expressed in infiltrating inflammatory cells and overexpressed in the columnar cells of preinvasive lesions and cancers, especially in well-differentiated EACs, as compared with the basal cells of the normal esophageal squamous epithelium. Bestatin statistically significantly inhibited LTB4 biosynthesis in the esophageal tissues of EGDA rats (without bestatin = 8.28 ng/mg of protein; with bestatin = 4.68 ng/mg of protein; difference = 3.60, 95% CI = 1.59 to 5.61; P = .002) and reduced the incidence of EAC in the EGDA rats from 57.7% (15 of 26 rats) to 26.1% (6 of 23 rats) (difference = 31.6%, 95% CI = 0.3% to 56.2%; P = .042). CONCLUSION LTA4H overexpression appears to be an early event in esophageal adenocarcinogenesis and is a potential target for the chemoprevention of EAC.

Environmental exposure to carcinogens and individual susceptibility play significant roles in cancer risk. Suboptimal DNA repair capability, measured by quantifying mutagen-induced chromosome breaks, might explain variable host susceptibility to environmental carcinogens. In an ongoing lung cancer case-control study, we compared individual sensitivity to bleomycin-induced chromosome breaks in 152 non-small cell lung cancer patients with 94 population controls and 85 hospital controls with no history of cancer. Mutagen sensitivity was measured by mean number of chromatid breaks per cell in cultured peripheral blood lymphocytes treated with bleomycin. Non-parametric tests and chi(2) tests were used to determine the statistical significance of the crude case-control comparisons, followed by logistic regression to adjust for important covariates. The mean number of bleomycin-induced breaks per cell was 1.01 for the cases compared with 0.86 for hospital controls (P0.01) and 0.89 for population controls (P0.01). The mean number of breaks per cell was 1.01 for those65 years old and 0.81 for thoseor = 65 years old (P0.01) among population controls. Defining bleomycin sensitive as0.84 break/cell (the median level in population controls), 67% of the cases were bleomycin sensitive compared with 49% of the hospital controls [adjusted odds ratio (OR) = 2.69, 95% confidence interval (CI) = 1.44, 5.04], and 51% of the population controls (adjusted OR = 2.18, 95% CI = 1.13, 4.21). Our data indicate that the increased number of bleomycin-induced chromosome breaks was significantly associated with an increased risk of lung cancer in the first 331 subjects.

Background . This study compares the health care costs and effectiveness of multiple staging options for patients with esophageal cancer. Techniques studied included computed tomographic (CT) scan, endoscopic ultrasound with fine-needle aspiration biopsy (EUS-FNA), positron emission tomography (PET), thoracoscopy/laparoscopy, and combinations of these. Methods . A decision-analysis model was constructed to compare different staging strategies. Costs were derived from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases and from other Medicare reimbursement rates. Life expectancies were obtained from the 1973–1996 SEER database and adjusted for quality of life. Cost and effectiveness measures were discounted at 0% and 3% per year. Sensitivity and specificity measures were obtained from the published literature and a parallel prospective clinical trial, and all key variables were subjected to sensitivity analyses. Results . Under baseline assumptions, CT + EUS-FNA was the most inexpensive strategy and offered more quality-adjusted life-years, on average, than all other strategies with the exception of PET + EUS-FNA. The latter was slightly more effective but also more expensive. The marginal cost-effectiveness ratio for PET + EUS-FNA was $60,544 per quality-adjusted life-year. These findings were robust and changed very little in all of the sensitivity analyses. Conclusions . The combination of PET + EUS-FNA should be the recommended staging procedure for patients with esophageal cancer, unless resources are scarce or PET is unavailable. In these instances, CT + EUS-FNA can be considered the preferred strategy.

Precise clinical staging of esophageal cancer before treatment is important. Thoracoscopic/laparoscopic (Ts/Ls) staging has been proposed as a promising staging method. This study was conducted to evaluate the potential benefits of Ts/Ls staging over conventional noninvasive clinical staging in patients with esophageal cancer. From 1991 to 1999, 111 patients with esophageal cancer underwent Ts/Ls staging by the University of Maryland Medical System. Pretreatment staging workup included computed tomography, magnetic resonance imaging, and esophageal ultrasonography, followed by Ts/Ls surgical staging. Thoracoscopy was successfully performed in 102 patients and was aborted in 4 patients because of pleural adhesions. Laparoscopy was successfully done in 76 patients and was aborted in 1 patient because of peritoneal adhesion. Sixty-seven patients had both Ts and Ls staging, whereas 35 patients and 9 patients, respectively, had only Ts or Ls staging. Thirteen of 19 patients with clinical T4 disease were downstaged to T3 disease, and 8 patients with clinical T3 disease were upstaged to T4 by Ts/Ls staging. No clinical T1-2 disease was found to be associated with local invasion (T4) by Ts/Ls. Forty-eight and 19 patients had mediastinal and celiac lymph node metastases clinically diagnosed, respectively. Nine (18.8%) and 12 (63.2%) of them were proved by Ts and Ls, respectively. An additional 5 and 16 patients were found to have unexpected mediastinal and celiac lymph node metastases, respectively, by Ts/Ls. Biopsy specimens of pleura, lung, or liver were obtained by Ts/Ls procedures in 17 patients because of suspicious findings of routine imaging studies or unexpected findings during the staging operation. Five patients were found to have distant metastasis, and the presence of metastases in others was excluded. The correlation between Ts/Ls staging and conventional noninvasive clinical staging in the diagnosis of T4 disease, mediastinal lymph node metastasis, celiac lymph node metastasis, and M1 disease was 18.8%, 14.5%, 25.5%, and 20.0%, respectively. Ts/Ls provides more accurate information for evaluating local invasion, lymph node metastasis, and distant metastasis. The poor correlation of staging diagnosis between Ts/Ls and conventional noninvasive clinical examinations suggests that the accuracy of current noninvasive clinical staging is questionable and needs to be improved.

Background . This study was performed to evaluate the pattern of lymphatic metastases found by combined thoracoscopic (TS) and laparoscopic (LS) lymph node staging in esophageal cancer, and ascertain whether clinicopathologic factors may be used to guide the clinical practice of combined TS and LS staging. Methods . A retrospective study was performed in a series of 76 esophageal cancer patients who had undergone both TS and LS staging before treatment. The correlation of TS and LS lymph node metastases with clinicopathologic factors was analyzed, including the clinical T stage, clinical N stage, tumor location, and histology. Results . Thirty-one patients (40.8%) were found to have lymphatic metastasis by TS and LS staging. Among them, 22 patients had abdominal lymph node metastases, 7 patients had mediastinal lymph node metastases, and 2 patients had both. Patients with advanced T stage (T3 to T4) or adenocarcinoma had a higher frequency of abdominal lymphatic metastases than patients with early T stage (T1 to T2) (39% vs 16%; p = 0.04) or squamous cell carcinoma (39% vs 20%; p = 0.079), respectively. Patients with clinical abdominal N1 stage had a higher incidence of positive laparoscopic finding than patients with clinical abdominal N0 stage (67% vs 23%; p = 0.001). There was no significant correlation between lymphatic metastases and the location of the primary tumor. Conclusions . Clinicopathologic factors, including the histologic type, the clinical T stage, and abdominal N stage, may affect the outcome of TS and LS lymph node staging in esophageal cancer patients. This clinicopathologic impact may play a role for the selection of candidates for TS and LS staging, and also allows surgeons to focus their attention on the most likely high-yield biopsy targets.

In order to identify and contrast global gene expression profiles defining the premalignant syndrome, Barrett's esophagus, as well as frank esophageal cancer, we utilized cDNA microarray technology in conjunction with bioinformatics tools. We hybridized microarrays, each containing 8000 cDNA clones, to RNAs extracted from 13 esophageal surgical or endoscopic biopsy specimens (seven Barrett's metaplasias and six esophageal carcinomas). Hierarchical cluster analysis was performed on these results and displayed using a color-coded graphic representation (Treeview). The esophageal samples clustered naturally into two principal groups, each possessing unique global gene expression profiles. After retrieving histologic reports for these tissues, we found that one main cluster contained all seven Barrett's samples, while the remaining principal cluster comprised the six esophageal cancers. The cancers also clustered according to histopathological subtype. Thus, squamous cell carcinomas (SCCAs) constituted one group, adenocarcinomas (ADCAs) clustered separately, and one signet-ring carcinoma was in its own cluster, distinct from the ADCA cluster. We conclude that cDNA microarrays and bioinformatics show promise in the classification of esophageal malignant and premalignant diseases, and that these methods can be applied to small biopsy samples.

e18015 Background: The Rutgers Cancer Institute of New Jersey (CINJ) is conducting an ongoing, prospective, observational clinical trial that is evaluating use of comprehensive genomic profiling (CGP) and molecular tumor board (MTB) review to assist in caring for patients with rare or refractory cancers. As part of this precision medicine approach to cancer care, CINJ has formed a partnership with community hospitals (Meridian Health) to enroll patients in this study, and to actively participate in MTB meetings. The purpose of this cohort analysis is to evaluate the feasibility of using CGP to identify clinically-relevant genomic alterations as an aid to guiding point-of-care management in a community hospital setting. Methods: Meridian Health staff was trained in patient selection, enrollment, and follow-up. CGP was performed by Foundation Medicine, Inc. The patient case’s clinical history, pathology, and CGP results were presented at an MTB meeting. The enrolling physicians (n = 11) were invited to attend the MTB in person or through web-accessible video conferencing. A letter listing MTB consensus recommendations on potential treatment options was sent to the referring physician, and patient follow-up was scheduled at regular intervals. Results: 35 patients were enrolled by Meridian Health. Gyn and GI cancers were the most common types at enrollment (each 26%, 9 out of 35), followed by breast cancer (20%, 7 out of 35). At study enrollment, the mean KPS was 91%, and 23 patients (66%) had stage IV disease. The median duration between study enrollment and MTB presentation was 44 days. 3 patients were excluded because of deteriorated clinical status at the time of the MTB. MTB-based treatment options were implemented in 9 of 32 patients (28%). This result is similar to those reported in published analyses of patients enrolled at CINJ. Conclusions: Collaborations between an academic cancer center and a community hospital is a feasible approach to facilitating access to precision medicine for cancer patients treated in the community. A larger cohort is needed to determine the impact on patient’s outcomes.

Background Recurrent laryngeal nerve (RLN) lymph node metastasis used to be shown a predictor for poor prognosis in esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prognostic impact of RLN node metastasis and the number of metastatic lymph nodes in node-positive patients with squamous cell carcinoma of middle thoracic esophagus. Methods A cohort of 235 patients who underwent curative surgery for squamous cell carcinoma of middle thoracic esophagus was investigated. The prognostic impact was evaluated by univariate and multivariate analyses. Results Lymph node metastasis was found in 133 patients. Among them, 81 had metastatic RLN nodes, and 52 had at least one positive node but no RLN nodal involvement. The most significant difference in survival was detected between patients with metastatic lymph nodes below and above a cutoff value of six (P

Objective: Prediction of responders to induction therapy in esophageal cancer (EC) patients is important. In this study, we evaluated the role of thoracoscopic/laparoscopic (Ts/Ls) staging in prediction of treatment response and survival in EC patients with trimodality treatment. Methods: Retrospective study of EC patients who had undergone Ts/Ls staging and received trimodality treatment at the University of Maryland Medical Center and the Baltimore Veterans Administration Hospitals from July, 1991 to December, 1999. Preoperative therapy consisted of concurrent chemotherapy (5-FU 1 cisplatinum) and radiotherapy. Results: Forty-four EC patients who underwent pretreatment Ts/Ls staging during the study period were able to complete concurrent chemoradiotherapy followed by surgical resection. There were 36 men and 8 women aged 40 to 77 (median age 62). Twenty-seven (61.4%) patients were found to have lymph node metastasis by surgical staging. Fourteen patients (31.8%) had a pathologic complete response. Patients with positive lymph nodes had a lower response rate than those with negative lymph nodes (14.8% vs. 58.8%, Pa 0:006). Other clinicopathologic features including gender, weight loss, clinical TNM stage, surgical T stage, and histology did not correlate with treatment response. Univariate analysis showed that weight loss and treatment response were important prognostic factors for disease-free survival (Pa 0:01 and Pa 0:02, respectively). Histology, surgical N stage and surgical TNM stage appeared to be associated with prognosis (Pa 0:067‐0.097). Multivariate analysis revealed that only surgical N status and weight loss were significant prognostic factors (Pa 0:05, and Pa 0:006, respectively). Conclusions: Surgical Ts/Ls staging provides accurate evaluation of tumor spread in EC patients. Pretreatment N status was the single most important predictor of response to induction treatment as well as a reliable prognosticator of survival. q 2001 Elsevier Science B.V. All rights reserved.

Objective: To investigate the expression of novel multidrug resistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients’ RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients’ RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it’s overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

Noninvasive staging of esophageal cancer (EC) is often inaccurate, and this fact has compromised clinical trials of treatment for EC. Prognostic evaluation might allocate chemotherapy and radiation more appropriately. Thoracoscopy and laparoscopy has recently shown promising results, and molecular analysis of the recovered tissue may further improve staging accuracy.