Biomedical subjects

Mark D Iannettoni

Publications and source records attributed to Mark D Iannettoni.

At least 19 recordsLinked to original sources

PubMed2005

National trends in outcomes for esophageal resection.

BACKGROUND: Case-series reports from tertiary centers report improved outcomes for esophageal resection in recent years. The objective of the current study was to determine trends in short-term outcomes after esophageal resection in a representative sample of United States (US) hospitals. METHODS: Observational study of all adult patients in the Nationwide Inpatient Sample who underwent esophageal resection from 1988 to 2000 (N = 8,657). Temporal trends of in-hospital mortality and prolonged length of stay were determined. Analyses were performed for all hospitals after stratifying by hospital volume. The proportion of patients having surgery at high volume hospitals was used to assess changes in referral patterns. RESULTS: The overall mortality rate was 11.3% and revealed a modest but significant decline from 13.6% to 10.5% during the study period (p = 0.001). Low volume hospitals had markedly higher mortality rates and showed no improvement over time (15.3% vs 14.5%). In contrast, high volume hospitals indicated significant reduction in mortality over time (11.0% vs 7.5%, p = 0.003). Referral patterns changed over time with the proportion of esophageal resections performed at high volume hospitals increasing from 40% (1988 to 1991) to 57% (1997 to 2000). CONCLUSIONS: The operative mortality rate for esophageal resection has declined over the past 13 years, particularly at high volume hospitals. Efforts should be made to understand the processes of care underlying this improvement.

Adult↗

PubMed2005

Nontraumatic chest wall systemic-to-pulmonary artery fistula.

A congenital chest wall systemic-to-left pulmonary artery fistula fed by the left internal mammary and left gastric arteries in a 31-year-old man is reported. Attempted sclerosis was complicated by rupture of the communicating vessel, hemothorax, and deep vein thrombosis of the legs. Fistula resection and pulmonary decortication were successfully performed.

Adult↗

PubMed2005

Transhiatal esophagectomy.

Controversy still remains regarding the appropriateness of THE asa cancer operation. Critics argue that without an en bloc mediastinal lymphadenectomy, THE does not provide accurate staging or the potential for a curative procedure; however, operative margins are similar after transthoracic and transhiatal esophagectomy, and van Sandick and co-workers reported that 73% of margins were microscopically negative. In many cases, esophageal carcinoma appears to be a systemic disease at the time of diagnosis. According to Orringer and colleagues, 46% of patients have Stage III or IV disease at the time of operation, and Altorki and co-authors found that 35% of patients thought to be potentially curable were found to have occult cervical lymph node disease after three-field lymph node dissection. In addition, survival after THE is similar to that reported after transthoracic esophagectomy as well as radical esophagectomy with mediastinal lymphadenectomy. The most important determinants of survival appear to be the biologic behavior of the tumor and the stage at the time of resection rather than the operative approach, and esophageal carcinoma will likely require systemic therapy for a cure. Transhiatal esophagectomy has been used increasingly in the resection of benign and malignant disease, and has several potential advantages over transthoracic esophagectomy, including significantly decreased respiratory complications and mediastinitis due to the avoidance of thoracotomy and intrathoracic anastomosis. In a meta-analysis of fifty studies comparing transthoracic and transhiatal resection, Hulscher et al found significantly higher early morbidity and mortality rates after transthoracic resections, which was confirmed in a later randomized study of 220 patients(Table 2). Survival after THE is also equivalent to or better than that seen after transthoracic esophagectomy, and transhiatal esophagectomy should be considered in all patients requiring esophagectomy for benign or malignant disease.

Anastomosis, Surgical↗

PubMed2005

Fast-tracking: eliminating roadblocks to successful early discharge.

With continually increasing health care costs and limited medical resources, there has been increasing focus on shortening hospital stays. Many medical and nonmedical reasons can lead to a delay in hospital discharge after thoracic surgery despite technically successful procedures; common obstacles include inadequate pain control, prolonged air leaks, and social issues. Preoperative patient education, minimally invasive surgical techniques, aggressive pain control, and early resumption of physical activity and discontinuation of chest tubes and catheters are important in successful early discharge. Although many of these components can be combined in clinical pathways to optimize care with the input of various members of the patient care team, the thoracic surgeon must reassess outcomes constantly to ensure the maintenance of the quality of care.

Humans↗

PubMed2004

A 25-year experience with open primary transthoracic repair of paraesophageal hiatal hernia.

OBJECTIVE: The optimal surgical treatment of paraesophageal hiatal hernia is in debate. Our experience with a traditional transthoracic approach was reviewed to provide "benchmark" data against which newer surgical techniques can be measured. METHODS: Between 1977 and 2001, 240 patients had primary transthoracic repair of paraesophageal hiatal hernia. Presenting complaints included reflux (69%), pain (67%), dysphagia (36%), and bleeding or anemia (33%). Preoperative esophageal function testing showed abnormal reflux in 86%. Hernia types were combined (type III) in 92% and type IV in 8%. All patients had reduction of the hernia and a concomitant antireflux procedure. An esophageal lengthening Collis gastroplasty was performed in 96%. RESULTS: There were 3 perioperative deaths (1.7%). The median length of hospital stay was 7 days. Early complications requiring reoperation occurred in 12 patients (5%) and included recurrent hernia in 4, leak in 3, and a tight hiatal closure in 3. Mean follow-up in 226 patients was 42 months (median 27.8 months). Satisfactory results were obtained in 86% of patients. Follow-up complaints (moderate or persistent symptoms) included dysphagia (4), reflux (1), dumping (3), and post-thoracotomy pain (1). Routine postoperative barium radiographs showed intact repair in 71% (108/153). Of 19 patients with an anatomic recurrence, 4 (2%) had more than a partial asymptomatic migration of the fundoplication and required reoperation. Postoperative esophageal function testing, obtained in 28% of the patients, showed abnormal gastroesophageal reflux in 2. CONCLUSION: Open transthoracic repair of paraesophageal hiatal hernia provides good to excellent long-term control of both the hernia and gastroesophageal reflux with relatively low early morbidity.

Adult↗

PubMed2004

Closure of bronchopleural fistulas using albumin-glutaraldehyde tissue adhesive.

Bronchopleural fistulas are a life-threatening complication of pulmonary resection. A 21-year-old woman developed a large bronchopleural fistula after undergoing a pneumonectomy for carcinoid tumor. Despite bronchial stump revision and omental coverage, the fistula recurred. The second patient is a 42-year-old woman with a history of multiple thoracotomies who developed a bronchopleural fistula following aortic root replacement. Using either rigid bronchoscopy or thoracoscopy, these fistulas were evaluated and sealed with an albumin-glutaraldehyde tissue adhesive that may have improved strength and biocompatibility compared with other tissue sealants. This approach may be an effective alternative in the treatment of bronchopleural fistulas.

Adult↗

PubMed2004

Management of chyle fistula utilizing thoracoscopic ligation of the thoracic duct.

OBJECTIVES: To document the treatment of refractory chyle leaks using thoracoscopic thoracic duct ligation and provide systematic guidelines to manage chyle leaks. METHODS: The medical records of 2 patients with chyle leaks are reviewed, followed by a review of the literature on chyle leaks and their thoracoscopic management. CONCLUSIONS: Initial treatment of chyle fistula is aimed at conservative medical management. Persistent high-output fistulas (>500 cm(3)) should be considered for neck reexploration as conservative management is likely to fail. Thoracoscopic thoracic duct ligation provides a safe and efficient means of treating chyle leaks refractory to repeated surgical and medical intervention. It should also be considered as a primary surgical intervention for patients with: (1) chyle output exceeding 500 cm(3)/day where prior intraoperative attempts at ligation have failed, (2) severe metabolic and nutritional complications, (3) coexisting chylothorax with respiratory compromise, and (4) low-output fistulas (<500 cm(3)/day) of long duration (>14 days).

Chyle↗

PubMed2004

Genomic and proteomic analyses of vascular endothelial growth factor and insulin-like growth factor-binding protein 3 in lung adenocarcinomas.

Vascular endothelial growth factor (VEGF) is regulated by the hypoxia-inducible factor 1 (HIF1) pathway and is implicated in tumor progression and patient survival in many types of cancer. Insulin-like growth factor-binding protein 3 (IGFBP3) is also regulated by HIF1 but works in a completely different manner by modulating the activities of insulin-like growth factors and inducing apoptosis. In this study, 2-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) was used to analyze the protein expression profiles of VEGF and IGFBP3 isoforms in 93 lung adenocarcinomas and 10 uninvolved lung samples. The same samples were examined for messenger RNA (mRNA) expression with use of oligonucleotide arrays. Correlation analysis in the lung adenocarcinomas between mRNA expression levels of VEGF and all 4966 other genes was used to identify other biologic processes that may be associated with increased VEGF expression. Two-dimensional gel separations revealed 7 VEGF protein isoforms and 5 isoforms of IGFBP3. VEGF and IGFBP3 mRNA were found to be overexpressed in bronchial-derived lung adenocarcinomas (P < 0.0001), and expression was decreased in well-differentiated lung adenocarcinomas (P < 0.0002). There was a significant correlation (P < 0.01) between VEGF and IGFBP3 mRNA in lung adenocarcinomas; however, no correlation was detected in uninvolved lung samples. Forty genes were identified as the most significantly associated with VEGF expression (r > 0.38, P < 0.001), 17 of which were also associated with IGFBP3, and 12 were known to be induced through the HIF1 pathway. Among other highly correlated genes, several, including bradykinin receptor B2, suggest additional cellular processes that were not previously known to be associated with VEGF expression in lung adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Protein profiles associated with survival in lung adenocarcinoma.

Morphologic assessment of lung tumors is informative but insufficient to adequately predict patient outcome. We previously identified transcriptional profiles that predict patient survival, and here we identify proteins associated with patient survival in lung adenocarcinoma. A total of 682 individual protein spots were quantified in 90 lung adenocarcinomas by using quantitative two-dimensional polyacrylamide gel electrophoresis analysis. A leave-one-out cross-validation procedure using the top 20 survival-associated proteins identified by Cox modeling indicated that protein profiles as a whole can predict survival in stage I tumor patients (P = 0.01). Thirty-three of 46 survival-associated proteins were identified by using mass spectrometry. Expression of 12 candidate proteins was confirmed as tumor-derived with immunohistochemical analysis and tissue microarrays. Oligonucleotide microarray results from both the same tumors and from an independent study showed mRNAs associated with survival for 11 of 27 encoded genes. Combined analysis of protein and mRNA data revealed 11 components of the glycolysis pathway as associated with poor survival. Among these candidates, phosphoglycerate kinase 1 was associated with survival in the protein study, in both mRNA studies and in an independent validation set of 117 adenocarcinomas and squamous lung tumors using tissue microarrays. Elevated levels of phosphoglycerate kinase 1 in the serum were also significantly correlated with poor outcome in a validation set of 107 patients with lung adenocarcinomas using ELISA analysis. These studies identify new prognostic biomarkers and indicate that protein expression profiles can predict the outcome of patients with early-stage lung cancer.

Adenocarcinoma↗

PubMed2003

Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade dysplasia.

PURPOSE: The purpose of this study was to determine the frequency and overall contribution of specific gene amplification events in the formation of Barrett's adenocarcinomas. The relationship of gene amplification to clinical-pathological variables and its potential usefulness as a marker for early cancer detection were also examined. EXPERIMENTAL DESIGN: We used quantitative PCR and Southern blot analysis to screen 87 cases of Barrett's adenocarcinoma for the presence or absence of 13 distinct gene amplification events. Gene amplification was then examined for correlation with other amplification events and clinical variables (survival, stage, nodal involvement, tumor invasion, smoking history, and gender). Additionally, 22 specimens of Barrett's with high-grade dysplasia (HGD) were examined for the presence of gene amplification. RESULTS: One or more amplification events were present in 50 of 87 (57%) adenocarcinomas. The ERBB2 gene was amplified in 19 of 87 (21.8%), CCNE1 in 11 of 87 (12.6%), GATA4 in 9 of 87 (10.3%), KRAS in 9 of 87 (10.3%), EGFR in 7 of 87 (8.0%), CCND1 in 6 of 87 (6.8%), HNF3alpha in 5 of 87 (5.7%), PIK3CA in 5 of 87 (5.7%), C-MYC in 4 of 87 (4.6%), DYRK2 in 2 of 87 (2.3%), and AIB1, AKT1, and IGF1R were amplified in 0 of 87 (0%) of the tumors. CCND1 amplification was found to correlate negatively with survival (P < 0.05). In addition, the ERBB2 amplicon positively correlated (P < 0.05) with GATA4 amplification. Increased copy number of the ERBB2 (1 of 22), GATA4 (1 of 22), KRAS (2 of 22), C-MYC (1 of 22), CCNE1 (2 of 22), and CCND1 (2 of 22) genes was also observed in one or more Barrett's adenocarcinomas with HGD. CONCLUSIONS: The high frequency of gene amplification in esophageal adenocarcinomas and HGD indicates the important role of these events in esophageal adenocarcinoma development. Additionally, these results underscore the possible usefulness of early detection approaches and chemotherapeutic strategies (ErbB2 and cyclin D1) targeted against amplified gene products.

Adenocarcinoma↗

PubMed2003

Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas.

We examined the expression of oncoprotein 18 (Op18) in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional PAGE analysis with confirmation by mass spectrometry and two-dimensional Western blot analysis. mRNA expression was examined using oligonucleotide microarrays, and the cellular localization of the Op18 protein was examined using immunohistochemical analysis of tissue microarrays. Three phosphorylated forms and one unphosphorylated form of the Op18 protein were identified and found to be overexpressed in lung adenocarcinomas as compared with normal lung. The percentage of phosphorylated to total Op18 protein isoforms increased from 3.2% in normal lung to 7.9% in lung tumors. Both the phosphorylated and unphosphorylated Op18 proteins were significantly increased in poorly differentiated tumors as compared with moderately or well differentiated lung adenocarcinomas (p<0.03), suggesting that up-regulated expression of Op18 reflects a poor differentiation status and higher cell proliferation rates. This was further verified in A549 and SKLU1 lung adenocarcinoma cell lines by examining Op18 levels and phosphorylation status following treatment that altered either cell proliferation or differentiation. The increased expression of Op18 protein was significantly correlated with its mRNA level indicating that increased transcription likely underlies elevated expression of Op18. The overexpression of Op18 proteins in poorly differentiated lung adenocarcinomas and the elevated expression of the phosphorylated forms of Op18 may offer a new target for drug- or gene-directed therapy and may have potential utility as a tumor marker.

Adenocarcinoma↗

PubMed2003

Proteomic analysis of eIF-5A in lung adenocarcinomas.

We examined the eIF-5A protein expression in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis with identification by mass spectrometry and 2-D Western blots. The same tissue samples were examined for the eIF-5A mRNA expression using oligonucleotide microarrays, and the cellular localization of the eIF-5A protein was examined using immunohistochemical analysis on tissue arrays. Higher eIF-5A protein expression was present in tumors showing poor differentiation, 12/13(th) codon K-ras mutations, p53 nuclear accumulation, and tumors with positive lymphocytic response. The eIF-5A mRNA was also significantly increased in lung adenocarcinomas compared to normal lung, but the eIF-5A protein expression was not correlated to its mRNA levels indicating that the increase in the eIF-5A protein expression in lung tumors is post-transcriptionally/translationally/post-translationally regulated. Patients having a higher eIF-5A protein expression showed a relatively poorer survival suggesting the use of eIF-5A as prognostic marker in lung adenocarcinoma. Moreover, the investigation on agents that inhibit eIF-5A function is encouraged.

Adenocarcinoma↗

PubMed2003

Challenges in reversing esophageal discontinuity operations.

BACKGROUND: After catastrophic esophageal or gastric disruption results in esophageal discontinuity, operations to restore swallowing are surgical challenges. METHODS: A retrospective review and assessment of functional results was performed in 40 patients (average age 59.9 years) who had 42 operations to reverse esophageal discontinuity between 1973 and 2002. RESULTS: Esophageal discontinuity resulted from gastric necrosis after esophagectomy and esophagogastrostomy (n = 10) or hiatal hernia repair (n = 4), esophageal perforation complicating dilatation (n = 5), failed colonic or jejunal interpositions (n = 5), caustic ingestion (n = 4), Boerhaave syndrome (n = 4), esophagogastric anastomotic leak (n = 3), and other causes (n = 6). Eighteen patients (43.9%) required prolonged mechanical ventilation. Thirty-one (75.6%) had an end cervical esophagostomy; 6, an anterior thoracic esophagostomy; 2, lateral esophagostomy and in situ native esophagus stapled and divided distally; and 1 each, a stapled, divided esophagus without esophagostomy and a stapled undivided esophagus without esophagostomy. Twenty-six patients (63.4%) had undergone partial or total gastrectomy. Ten (24.4%) had vocal cord paralysis. Operations reestablishing continuity included colonic interposition in 23 (56.1%), substernal gastric interposition in 7 (17.1%), esophagectomy and cervical anastomosis in 6, esophageal reanastomosis in 3, staged jejunal interposition in 1, and Roux-en-Y esophagojejunostomy in 1. There were no hospital deaths. Twenty-eight patients (68.3%) had postoperative complications. Length of stay averaged 20.6 days. Follow-up for 40 patients averaged 54.5 months. Functional results (39 patients) were excellent in 12 (30.8%), good in 15 (38.5%), fair in 10 (25.6%), and poor in 2 (5.1%). CONCLUSIONS: Successful reversal of esophageal discontinuity requires individualized assessment and ingenuity. Despite appreciable morbidity, the ultimate result is generally gratifying.

Adult↗

PubMed2003

The role of thoracoscopy in the management of lung cancer.

The use of video-assisted thoracic surgery (VATS) has allowed surgeons to perform complex procedures that previously required a thoracotomy. While VATS is well accepted in the management of benign thoracic disease, its role in the management of lung cancer continues to evolve. VATS is utilized in many aspects of the management of lung cancer including the evaluation of indeterminate pulmonary nodules and pleural effusions, staging of mediastinal lymph nodes, and the resection of primary and metastatic tumors. However, concerns regarding cost, training issues, and adherence to oncological principles have caused some surgeons to proceed more slowly. This review discusses the current role of thoracoscopy in the management of lung cancer.

Humans↗

PubMed2003

Patient selection for lung volume reduction surgery.

LVRS represents a valid surgical option for a limited number of patients who have symptomatic emphysema. The results of recent controlled studies have provided a realistic view of LVRS outcomes and yielded a validated algorithm for selection of optimal candidates for surgery. Furthermore, the NETT has provided simultaneously collected cost data that have provided a unique view of the costs and benefits of LVRS in patients who have advanced emphysema. Additional data collection will better define the long-term benefits of such surgical intervention in patients who have COPD.

Algorithms↗

PubMed2003

The solitary pulmonary nodule.

More than 150,00 patients a year present to their physicians with the diagnostic dilemma of a solitary pulmonary nodule (SPN) found either on chest radiography or chest CT. A thoughtful and timely workup of this finding is essential if lung cancer is to be recognized early and the chance for cure optimized. Based on the literature to date, recommendations are made for appropriate imaging modalities and diagnostic testing, as well as indications for obtaining preoperative tissue diagnosis for the patient with an SPN.

Biopsy, Needle↗

PubMed2003

Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis.

PURPOSE: The purpose of this study was to determine whether expression of migration inhibitory factor (MIF) is increased in non-small cell lung cancer, and whether it correlates with angiogenesis and/or prognosis. EXPERIMENTAL DESIGN: We measured vessel density, and levels of MIF, angiogenic CXC chemokines, and vascular-endothelial growth factor (VEGF; by ELISA) in tumor and normal lung tissue from 87 patients after resection of lung cancer. We compared vessel density with levels of MIF, VEGF, or angiogenic CXC chemokines in the corresponding tumor homogenate. Disease-free survival was analyzed in a Cox proportional hazards model. RESULTS: Levels of MIF in lung cancer demonstrated a bimodal distribution, with some having "normal" values (relative to normal lung tissue) and a second cluster with markedly high values. The increased levels of MIF in lung cancer were statistically significant in both paired and unpaired comparisons (P < 0.05). The strongest correlation of vessel density was with the sum of angiogenic CXC chemokines. MIF correlated very strongly with levels of angiogenic CXC chemokines. Tumors in the high MIF group had a strong correlation between MIF level and vessel density. Risk of recurrence was associated with high levels of glutamic acid-leucine-arginine amino acid motif CXC chemokines, MIF, and/or VEGF in a Cox proportional hazards model. CONCLUSIONS: MIF expression in non-small cell lung cancer occurs in a bimodal distribution, and is closely associated with tumor levels of angiogenic CXC chemokines and with vessel density. High levels of tumor-associated CXC chemokines, MIF, or VEGF are associated with risk of recurrence after resection of lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

Gene-expression profiles predict survival of patients with lung adenocarcinoma.

Histopathology is insufficient to predict disease progression and clinical outcome in lung adenocarcinoma. Here we show that gene-expression profiles based on microarray analysis can be used to predict patient survival in early-stage lung adenocarcinomas. Genes most related to survival were identified with univariate Cox analysis. Using either two equivalent but independent training and testing sets, or 'leave-one-out' cross-validation analysis with all tumors, a risk index based on the top 50 genes identified low-risk and high-risk stage I lung adenocarcinomas, which differed significantly with respect to survival. This risk index was then validated using an independent sample of lung adenocarcinomas that predicted high- and low-risk groups. This index included genes not previously associated with survival. The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.

Adenocarcinoma↗