Search

Anastomotic leak is an important cause of morbidity and mortality after esophagectomy. Few studies have targeted risk factors for the development of leak after esophagectomy. The purpose of this study is to use The Society of Thoracic Surgeons Database to identify variables associated with leak after esophagectomy.The Society of Thoracic Surgeons Database was queried for patients treated with esophagectomy for esophageal cancer between 2001 and 2011. Univariate and multivariate analysis of variables associated with an increased risk anastomotic leak was performed.There were 7,595 esophagectomies, with 804 (10.6%) leaks. Thirty-day mortality and length of stay were higher for patients with anastomotic leak. Mortality in patients requiring surgical management was 11.6% (38 of 327) compared with 4.4% (20 of 458) in medically managed leaks (p0.001). The leak rate was higher in patients with cervical anastomosis compared with those with intrathoracic anastomoses, 12.3% versus 9.3%, respectively (p = 0.006). There was no difference in leak-associated mortality between the two approaches. Factors associated with leak on univariate analysis include obesity, heart failure, coronary disease, vascular disease, hypertension, steroids, diabetes, renal insufficiency, tobacco use, procedure duration greater than 5 hours, and type of procedure (p0.05). Multivariable regression analysis associated heart failure, hypertension, renal insufficiency, and type of procedure as risk factors for the development of leak (p0.05).Anastomotic leak after esophagectomy is an important cause of postoperative mortality and increased length of stay. We have identified important risk factors for the development of esophageal anastomotic leak after esophagectomy. Further studies aimed at risk reduction are warranted.

MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In cancer, miRNAs may function as oncogenes or tumor suppressors. Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall cell lung cancers ( n = 81) and determined that miR-486 was the most down-regulated miRNA in tumors compared with adjacent uninvolved lung tissues, suggesting that miR-486 loss may be important in lung cancer development. We report that miR-486 directly targets components of insulin growth factor (IGF) signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer both in vitro and in vivo. Our findings support the role for miR-486 loss in lung cancer and suggest a potential biological link to p53.

In summary, patients with N2 disease constitute a heterogeneous population with differing treatments and prognoses. Subtleties in the presentation, method of diagnosis, extent of nodal involvement, and patterns of nodal involvement must be taken into consideration to determine prognosis and optimal therapy. Is the patient with an incidental, pathologically identified, single focus of mediastinal disease the same as the patient with clinically identified multilevel bulky unresectable disease? Clearly not, although both patients share a similar stage, grouping the data presented here clearly demonstrate that these patients differ considerable in their prognosis and in their treatment. The current staging system attempts at assigning a single unifying definition of N2 fails to take into account the numerous subtleties inherent in this patient population. Although it is unlikely that N2 disease will be subclassified to any significant extent, some of these factors may eventually find themselves into a modern revision of our current staging system. For now, the upcoming IASLC revisions to the Union Internationale Contre le Cancer (UICC) staging system will not alter the definitions of nodal disease or add distinct subsets. Therefore, it is imperative that physicians evaluating and treating patients with N2 disease recognize and appreciate the influence of these subtle differences in presentation. Decision making surrounding the treatment of N2-positive patients will continue to remain complex as long as the definition of the disease remains heterogeneous.

cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2'-deoxycytidine (DAC)/depsipeptide FK228 (DP) exposure in order to identify translational end points for clinical trials evaluating these agents. In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduction known to diminish the malignant phenotype of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell lines established from thoracic malignancies. Sequential DAC/DP treatment induced TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state. Promoter methylation coincided with loss of TFPI-2 expression in a number of cancer lines. TFPI-2 promoter methylation was observed in one of five pulmonary adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer cells deficient for TFPI-2 expression in the absence of promoter methylation. In these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling and PKC signaling strengthens the preclinical rationale for sequential administration of DNA demethylating agents and HDAC inhibitors in cancer patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of treatment response in individuals receiving sequential DAC/DP infusions.

Primary esophageal schwannomas are uncommon. We describe a case of a large asymptomatic primary esophageal schwannoma in a 65-year-old patient. Computed tomography and positron emission tomography revealed an (18)F-fluorodeoxyglucose-avid 11-cm mass arising from the esophagus. A preoperative diagnosis was made via endoscopic ultrasound. The patient underwent a three-field esophagogastrectomy with cervical esophagogastric anastomosis. He remains well and free of recurrence 10 months after treatment.

Prevention by nerve growth factor (NGF) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low-affinity (p75) or high-affinity (trkA) receptor or to a cooperative interaction between the two. In a series of studies using, in turn, neuroblastoma cell lines that express only p75, mutant NGF species that bind selectively to either p75 or trkA, and a polyclonal antibody that binds to the NGF-binding domain of p75, we demonstrate that NGF binding to p75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents.

Background The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. Methods A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. Results There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X = 2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. Conclusions Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted.

Cardiac myxoma represents the most common primary cardiac tumor, which accounts for 75% of all benign cardiac tumors. Embolization is a well-known hazard of myxoma and can be a presenting feature. Resection is generally recommended for cardiac myxomata; once identified but less understood is what to do with systemic emboli. Although extremely uncommon, the literature contains a number of examples of metastatic myxomata with active growth at the site of embolic implantation, with most cases being cerebral. We present an unusual case of embolic occlusion of the right renal artery from a left ventricular myxoma. Excision of the tumor required cardiac autotransplantation and mitral valve replacement. Subsequent right nephrectomy revealed renal artery occlusion with pathologically viable myxoma tissue.

Objective DNA methyltransferase (DNMT)1, DNMT3b, or both, facilitate malignant transformation through chromatin remodeling mechanisms. The present study was undertaken to examine the effects of antisense-mediated inhibition of DNMT expression in cultured thoracic malignancies. Methods CALU-6 and A549 lung cancer, SKGT5 and BIC esophageal adenocarcinoma, and H2373 and H2052 malignant pleural mesothelioma (MPM) cells, as well as normal human bronchial epithelial (NHBE) cells, were transfected with phosphorothioate-modified antisense oligos targeting DNMT1, DNMT3b, or both, or mismatch oligos. Quantitative reverse transcription–polymerase chain reaction, Western blotting, trypan blue exclusion, and ApoBrdU techniques were used to evaluate DNMT expression, proliferation, and apoptosis after antisense oligo transfections. Gene expression profiles were assessed by using long-oligo array techniques. Results Antisense oligos mediated specific and dose-dependent depletion of DNMT1 and DNMT3b, resulting in pronounced inhibition of proliferation of all thoracic cancer lines, but not NHBE cells. Depletion of DNMT1 or DNMT3b coincided with dramatic, caspase-dependent, p53-independent apoptosis in 4 of the 6 thoracic cancer lines. The antiproliferative effects of the antisense oligos were not attributable to induction of RASSF1A, p16, or p21 tumor suppressor genes, and did not coincide with demethylation of genes encoding cancer-testis antigens. DNA methyltransferase knockdown mediated induction of numerous genes regulating response to genotoxic stress. Gene expression profiles after DNMT1, DNMT3b, or combined DNMT1/3b depletion were remarkably similar, yet distinctly different from expression profiles mediated by 5 aza 2′ deoxycytidine. Conclusions Antisense oligos targeting DNMT1 and DNMT3b induce genomic stress, and mediate potent growth inhibition in lung and esophageal cancer and MPM cells. These findings support further evaluation of DNMT knockdown strategies for cancer therapy.

Bronchoesophageal fistula is a rare complication of Hodgkin's disease. We report a case of Hodgkin's disease presenting with a bronchoesophageal fistula that was successfully treated with bipolar esophageal exclusion and substernal gastric bypass. Direct invasion from mediastinal lymph nodes was the probable cause. Although bronchoesophageal fistula can result as a complication during the course of treatment for Hodgkin's disease, it rarely occurs as the presenting feature. Early recognition and surgical treatment are key aspects of management.

The incidence of esophageal cancer in the United States has been increasing in recent years. Since multimodality therapy for esophageal cancer has produced discouraging results, recent approaches have focused on molecular biological techniques, positron emission tomography, and minimally invasive surgery to improve pretreatment staging which will facilitate a more accurate assessment of new treatment. This article summarizes the results of studies investigating these approaches and outlines the strategy currently used at the University of Pittsburgh Medical Center.