PubMed Health⌕ Search

Biomedical subjects

David J Sugarbaker

Publications and source records attributed to David J Sugarbaker.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation.

OBJECTIVE: There is a strong association between reflux and end-stage lung disease, especially idiopathic pulmonary fibrosis. The presence of reflux after lung transplantation might predispose to the development of bronchiolitis obliterans. We evaluated the risk and physiologic effect of laparoscopic fundoplication in patients on the lung transplant waiting list. METHODS: One hundred forty-nine patients on the lung transplant waiting list between March 2001 and January 2005 were evaluated. Nineteen were found to have a history of reflux, continued symptoms, and severe reflux by means of pH and manometric studies and underwent laparoscopic fundoplication. The postoperative course of these 19 patients, including lung function, was retrospectively reviewed. Postoperatively, the lung function of the 14 patients with idiopathic pulmonary fibrosis who underwent the laparoscopic Nissen procedure was compared with that of 31 patients with idiopathic pulmonary fibrosis on the transplant waiting list who did not undergo fundoplication. RESULTS: There were no perioperative complications and no decrease in lung function over the 15-month average follow-up. Exercise capacity remained stable, as determined on the basis of 6-minute walk distance. Patients with idiopathic pulmonary fibrosis treated with fundoplication had stable oxygen requirements, whereas control patients with idiopathic pulmonary fibrosis on the waiting list had a statistically significant deterioration in oxygen requirement. CONCLUSIONS: Laparoscopic fundoplication can be performed safely in patients with end-stage lung disease awaiting lung transplantation. Overall, these patients maintained stable lung function during the follow-up period. When compared with a control group of patients with idiopathic pulmonary fibrosis not undergoing fundoplication, there was stabilization of oxygen requirement. A larger prospective trial evaluating the effect of laparoscopic fundoplication on underlying lung function in this patient population is warranted.

Bronchiolitis Obliterans↗
PubMed2006

Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma.

c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, c-Met was overexpressed and activated in most of the mesothelioma cell lines tested. Expression in MPM tissues by immunohistochemistry was increased (82%) in MPM in general compared with normal. c-Met was internalized with its ligand hepatocyte growth factor (HGF) in H28 MPM cells, with robust expression of c-Met. Serum circulating HGF was twice as high in mesothelioma patients as in healthy controls. There was a differential growth response and activation of AKT and extracellular signal-regulated kinase 1/2 in response to HGF for the various cell lines. Dose-dependent inhibition (IC50 < 2.5 micromol/L) of cell growth in mesothelioma cell lines, but not in H2052, H2452, and nonmalignant MeT-5A (IC50 > 10 micromol/L), was observed with the small-molecule c-Met inhibitor SU11274. Furthermore, migration of H28 cells was blocked with both SU11274 and c-Met small interfering RNA. Abrogation of HGF-induced c-Met and downstream signaling was seen in mesothelioma cells. Of the 43 MPM tissues and 7 cell lines, we have identified mutations within the semaphorin domain (N375S, M431V, and N454I), the juxtamembrane domain (T1010I and G1085X), and an alternative spliced product with deletion of the exon 10 of c-Met in some of the samples. Interestingly, we observed that the cell lines H513 and H2596 harboring the T1010I mutation exhibited the most dramatic reduction of cell growth with SU11274 when compared with wild-type H28 and nonmalignant MeT-5A cells. Ultimately, c-Met would be an important target for therapy against MPM.

Aged↗
PubMed2006

Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.

BACKGROUND: A well-known histone deacetylase inhibitor, trichostatin A, was applied to non-small-cell lung cancer cells to determine whether inhibition of histone deacetylase leads to the production of proteins that either arrest tumor cell growth or lead to tumor cell death. METHODS: Trichostatin A (0.01 to 1.0 micromol/L) was applied to one normal lung fibroblast and four non-small-cell lung cancer lines, and its effect was determined by flow cytometry, annexin-V staining, immunoprecipitation, and Western blot analysis. RESULTS: Trichostatin A demonstrated tenfold greater growth inhibition in all four non-small-cell lung cancer lines compared with normal controls, with a concentration producing 50% inhibition ranging from 0.01 to 0.04 micromol/L for the tumor cell lines and 0.7 micromol/L for the normal lung fibroblast line. Trichostatin A treatment reduced the percentage of cells in S phase (10% to 23%) and increased G1 populations (10% to 40%) as determined by flow cytometry. Both annexin-V binding assay and upregulation of the protein, gelsolin (threefold to tenfold), demonstrated that the tumor cells were apoptotic, whereas normal cells were predominantly in cell cycle arrest. Trichostatin A increased histone H4 acetylation and expression of p21 twofold to 15-fold without significant effect on p16, p27, CDK2, and cyclin D1. CONCLUSIONS: Collectively, these data suggest that inhibition of histone deacetylation may provide a valuable approach for lung cancer treatment. We evaluated trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.

Antineoplastic Agents↗
PubMed2005

Validation of genomics-based prognostic tests in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme. EXPERIMENTAL DESIGN: Gene expression data using high-density oligonucleotide microarrays (approximately 22,000 genes) were obtained for a new cohort of human MPM tumors from patients undergoing similar treatments (n = 39). The relative expression levels for specific genes were also determined using real-time quantitative reverse transcription-PCR. We also used a subset of these tumors associated with widely divergent patient survival (n = 23) as a training set to identify new treatment-specific candidate prognostic molecular markers and gene ratio-based prognostic tests. The predictive nature of these newly discovered markers and gene ratio-based prognostic tests were then examined in an independent group of tumors (n = 52) using microarray data and quantitative reverse transcription-PCR. RESULTS: Previously described MPM prognostic genes and gene ratio-based prognostic tests predicted clinical outcome in 39 independent MPM tumor specimens in a statistically significant manner. Newly discovered treatment-specific prognostic genes and gene ratio-based prognostic tests were highly accurate and statistically significant when examined in an independent group of 52 tumors from patients undergoing similar treatment. CONCLUSIONS: The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM.

Adult↗
PubMed2005

High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation.

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000. PATIENTS AND METHODS: The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients. RESULTS: The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years. CONCLUSION: Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N(0). Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC.

Adult↗
PubMed2005

Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.

Blotting, Western↗
PubMed2005

Percutaneous treatment of high-output chylothorax with embolization or needle disruption technique.

Surgical ligation of the thoracic duct is associated with a high degree of morbidity; therefore, a minimally invasive approach is desirable. Herein, eight percutaneously treated patients are described. In four patients, the thoracic duct was embolized with use of coils and glue. In the other four patients, lymphatic ducts were disrupted by multiple needle punctures. The median chest tube drainage substantially decreased in both patient groups from more than 1,300 mL the day before the procedure to less than 300 mL 2 days after the procedure. The median times to chest tube removal were 7 days in the embolization group and 3.5 days in the needle disruption group.

Adhesives↗
PubMed2005

Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.

STUDY OBJECTIVE: To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs). DESIGN: A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE. MEASUREMENTS: The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed. RESULTS: Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. CONCLUSIONS: Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.

Adult↗
PubMed2005

Lung resection in patients with preoperative FEV1 < 35% predicted.

OBJECTIVES: To determine the morbidity, mortality, and feasibility of lung resection in patients with tumors and preoperative FEV1 < 35% predicted. DESIGN: Retrospective review. SETTING: A 734-bed, tertiary care, academic hospital with a dedicated general thoracic surgery unit performing > 2,000 operations per year. PATIENTS: One hundred consecutive patients with discrete lung tumors and with preoperative FEV1 < 35% predicted undergoing lung resection between September 1997 and May 2003. Only operations with curative intent were included. Average preoperative predicted FEV1 was 26%. Sixteen percent of the patients were oxygen dependent prior to the operation. RESULTS: Open and thoracoscopic wedge resections, segmentectomies, lobectomies, and combined lung resections with lung volume reduction were performed. Sixty-six of the lesions were malignant, and 57 were primary lung cancers. Only one patient left the operating room with positive margins. There was one in-hospital or 30-day mortality. Thirty-six percent of the patients had one or more complications. Twenty-two percent of the patients had prolonged air leaks requiring a chest tube for > 7 days. One patient left the hospital ventilator dependent, 3 additional patients required intubation > 48 h, and 11 patients were discharged with a new oxygen requirement. There were four pneumonias, one myocardial infarction, and two reoperations for bleeding. Male gender (p = 0.003), preoperative oxygen dependence (p = 0.03), and pack-year history (p = 0.006) were associated with a higher overall incidence of complications, while age, incision, diabetes, coronary artery disease, duration of smoking cessation, amount of lung resected, size of lesion, and preoperative percentage of predicted FEV1 did not correlate with the overall incidence of complications. CONCLUSIONS: In a large academic center, minimally invasive surgical techniques, intensive pulmonary care, and advanced anesthetic techniques allow for curative lung tumor resections in patients with very low preoperative FEV1 with a very low mortality and very low incidence of ventilator dependence. Other serious complications such as pneumonia, myocardial infarction, and bleeding are uncommon. An extended hospital stay and a high incidence of prolonged air leak should be expected, especially in patients with preoperative FEV1 < or = 20% predicted.

Adult↗
PubMed2005

Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database.

STUDY OBJECTIVES: To determine the effect of age and type of surgery on long-term survival in patients with early-stage non-small cell lung cancer (NSCLC). DESIGN AND PATIENTS: A total of 14,555 patients who were > or = 20 years of age with stage I or II primary NSCLC and had been registered in the Surveillance, Epidemiology, and End Results Database from 1992 to 1997 were analyzed. Age was grouped into the following three categories: < 65 years (n = 5,057; 35%); 65 to 74 years (n = 6,073; 42%); and > or = 75 years (n = 3,425; 23%). Log-rank tests and Cox regression models were used for crude and adjusted survival analyses. MEASUREMENTS AND RESULTS: A total of 8,080 men (55%) and 6,475 women (mean [+/- SD] age, 67.3 +/- 9.8 years) with stage I NSCLC (83%) or stage II NSCLC were analyzed. Curative surgery was performed in 4,669 patients (92%) who were < 65 years of age (youngest), 5,219 patients (86%) who were 65 to 74 years of age (intermediate age), and 2,382 patients (70%) who were > or = 75 years of age (elderly) [p < 0.0001]. Thirty percent of the elderly patients were denied surgery or were offered only palliative surgery, in contrast with 8% among the youngest patients (p < 0.0001). Limited resections increased from 8% in young patients to 17% in the elderly (p < 0.0001). Survival decreased with age. The median survival times were 71, 47, and 28 months, respectively, for patients < 65, 65 to 74, and > or = 75 years of age (p < 0.0001). The results were unchanged after adjusting for sex, type of surgery, histology, and stage of disease. For the young patients, lobectomies conferred better survival times than limited resections after 2 years. However, there was no difference in survival between lobectomies and limited resections in terms of survival time for the elderly patients. The statistical difference in long-term survival between those patients undergoing lobectomies and those undergoing limited resections disappeared at 71 years. CONCLUSIONS: Age is an independent predictor of postsurgical survival in NSCLC patients, even after adjustment for significant covariates. Curative surgery is performed less frequently in elderly patients. Among younger patients undergoing curative surgery, lobectomies are more commonly performed and confer a significant survival benefit over limited resections. This benefit, however, is not evident for patients > 71 years of age.

Aged↗
PubMed2005

Diameter of non-small cell lung cancer correlates with long-term survival: implications for T stage.

STUDY OBJECTIVES: To determine the effect of tumor diameter on the long-term survival of patients with stage I non-small cell lung cancer (NSCLC) within a large multi-institutional database, and to assess the accuracy of the T-descriptor threshold of 3 cm. DESIGN AND PATIENTS: A total of 9,191 patients > or = 20 years old with surgically treated stage I NSCLC < or = 6 cm registered in the Surveillance, Epidemiology, and End Results database from 1992 to 1997 were included. The size of the nodule was grouped into six categories: < 1 cm (n = 191, 2%), 1 to 1.9 cm (n = 2,130, 23%), 2 to 2.9 cm (n = 2,851, 31%), 3 to 3.9 cm (n = 1,984, 22%), 4 to 4.9 cm (n = 1,161, 13%), and 5 to 6 cm (n = 874, 9%). Due to its limited sample size, subcentimeter nodules were not included in the survival analysis. Survival analyses were performed with Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models. MEASUREMENTS AND RESULTS: A total of 4,904 (53%) men and 4,287 women (mean +/- SD age, 66.6 +/- 9.4 years) with stage I NSCLC were analyzed. The use of lobectomies and pneumonectomies as surgical treatment instead of limited resections increased with the size of the tumor, from 62% in subcentimeter nodules to 96% in 5- to 6-cm tumors (p < 0.0001). Survival decreased with increasing size of the tumor (p < 0.0001). There was a significant survival difference when size groups were compared to tumors 1.0 to 1.9 cm: 2.0 to 2.9 cm (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.16 to 1.47), 3.0 to 3.9 cm (HR, 1.49; 95% CI, 1.32 to 1.69), 4.0 to 4.9 cm (HR, 1.82; 95% CI, 1.59 to 2.08), and 5.0 to 6.0 cm (HR, 2.04; 95% CI, 1.77 to 2.36). Survival was similar in tumors between 2.0 to 2.9 cm and 3.0 to 3.9 cm, and in tumors between 4.0 to 4.9 cm and 5.0 to 6.0 cm. CONCLUSIONS: The T descriptor should be changed so that T1 is reserved for tumors < 2 cm. Further refinement of larger tumors into T2a (2 to 3.9 cm) and T2b (> or = 4 cm) should be considered.

Adenocarcinoma↗
PubMed2005

Radiofrequency ablation of thoracic lesions: part 2, initial clinical experience--technical and multidisciplinary considerations in 30 patients.

OBJECTIVE: The purpose of our study was to report our initial experience with patients who underwent percutaneous imaging-guided radiofrequency ablation of thoracic lesions, and to emphasize technical and multidisciplinary issues and adjunctive procedures specific to thoracic tumor ablation. MATERIALS AND METHODS: Our cohort consisted of 30 patients with a spectrum of primary (n=18) and secondary (n=11) lung tumors, mesothelioma (n=1), and five secondarily eroded, painful ribs who underwent ablation of 36 total lesions (one patient had two ablations). Patients either were nonsurgical candidates because of medical comorbidities or extent of disease, or had exhausted chemotherapy and radiation therapy options, or had refused surgery or undergone unsuccessful surgery. Patients were treated with radiofrequency ablation after agreement among oncologists, thoracic surgeons, and interventional radiologists. An array-style electrode under impedance control was used to treat 29 thoracic tumors and the adjacent rib metastases (n=5). A cool-tip radiofrequency probe was used for two patients. CT guidance and general anesthetic were used for all but one patient. Sonographic guidance and IV conscious sedation were used in one patient. Pain (n=11) and tumor cure or control (n=19) were the primary indications for the procedures. Adjunctive procedures to the radiofrequency ablations included the creation of saline or water windows (n=3); establishment of transosseous and transchondral routes (n=4); use of intercostal and paravertebral nerve blocks (n=15); and use of an intraprocedural catheter (n=1), needle (n=1), or sheath (n=3) for treatment of pneumothoraces. Follow-up was from 2 to 26 months. RESULTS: All ablations were technically successful. No periprocedural mortality occurred. Necrosis of tumor was greater than 90% in 26 of 30 lesions based on short-term follow-up imaging (CT, PET, MRI). In the 11 patients who underwent ablation for pain, relief was complete in four and partial in the other seven. One patient developed a local skin burn, four patients had self-limited hemoptysis up to 4 days after ablation, one had transient atrial fibrillation, one developed hoarseness, and two patients were transiently reintubated after extubation. Eight pneumothoraces developed; one patient underwent placement of a chest tube. Four patients died within 1 year of ablation from extrathoracic spread of tumor. CONCLUSION: Radiofrequency ablation for a variety of thoracic tumors can be performed safely and with a high degree of efficacy for pain control and tumor killing. The effect of ablation can be assessed with CT, MRI, or PET. Various technical issues differentiate thoracic tumor ablation from standard abdominal ablations. Numerous other thoracic interventional radiology procedures are beneficial to assist the radiofrequency ablation. A multidisciplinary approach offers valuable expertise for patient care.

Adult↗
PubMed2004

Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia.

The SH2 domain-containing protein-tyrosine phosphatase PTPN11 (Shp2) is required for normal development and is an essential component of signaling pathways initiated by growth factors, cytokines, and extracellular matrix. In many of these pathways, Shp2 acts upstream of Ras. About 50% of patients with Noonan syndrome have germ-line PTPN11 gain of function mutations. Associations between Noonan syndrome and an increased risk of some malignancies, notably leukemia and neuroblastoma, have been reported, and recent data indicate that somatic PTPN11 mutations occur in children with sporadic juvenile myelomonocytic leukemia, myelodysplasic syndrome, B-cell acute lymphoblastic leukemia, and acute myelogenous leukemia (AML). Juvenile myelomonocytic leukemia patients without PTPN11 mutations have either homozygotic NF-1 deletion or activating RAS mutations. Given the role of Shp2 in Ras activation and the frequent mutation of RAS in human tumors, these data raise the possibility that PTPN11 mutations play a broader role in cancer. We asked whether PTPN11 mutations occur in other malignancies in which activating RAS mutations occur at low but significant frequency. Sequencing of PTPN11 from 13 different human neoplasms including breast, lung, gastric, and neuroblastoma tumors and adult AML and acute lymphoblastic leukemia revealed 11 missense mutations. Five are known mutations predicted to result in an activated form of Shp2, whereas six are new mutations. Biochemical analysis confirmed that several of the new mutations result in increased Shp2 activity. Our data demonstrate that mutations in PTPN11 occur at low frequency in several human cancers, especially neuroblastoma and AML, and suggest that Shp2 may be a novel target for antineoplastic therapy.

Adult↗
PubMed2004

Integrin-dependent protein tyrosine phosphorylation is a key regulatory event in collagen-IV-mediated adhesion and proliferation of human lung tumor cell line, Calu-1.

BACKGROUND: The clinical phenomenon of lung cancer metastasis to specific target organs is believed to be a direct interaction between tumor cells and extracellular matrix components. During invasion, tumor cells attach to the basement membrane protein, collagen type IV, degrade it, migrate through blood vessels, and adhere to extracellular matrix proteins. METHODS: Four nonsmall-cell lung cancer cells were tested for adhesion, proliferation, migration and morphologic alterations on collagen type IV matrix by immunoprecipitation, Western blotting, phase contrast and time lapse video microscopy. RESULTS: Collagen type IV promoted Calu-1 cell adhesion (< 15 minutes) and motility (< 6 hours) without any significant effect on proliferation. beta(1)-integrin is essential for collagen type IV adhesion and 8 to 10 fold higher expression of beta1-integrin on the surface of Calu-1 cells was identified. A protein tyrosine phosphatase inhibitor, peroxyvanadate, caused 50% inhibition in the adhesion process within 5 minutes but exposure to 60 micromol/L genistein for 72 hours, a protein tyrosine kinase inhibitor, drastically inhibits Calu-1 cell proliferation (> 70%). We examined the influence of beta1-integrin, peroxyvanadate and genistein on the spreading morphogenesis of Calu-1 cells on Collagen type IV. Use of either 1 microg of anti beta1-integrin inhibitory antibody (P5D2), 100 micromol/L peroxyvanadate or 60 micromol/L genistein had dramatic influence on the spreading of Calu-1 cells. Finally, Focal adhesion kinase was identified as a phosphoprotein target. CONCLUSIONS: We have characterized an in vitro model of matrix-specific binding of a lung cancer cell line, Calu-1 to Coll IV. Calu-1 cells use primarily a beta1-integrin mediated intracellular tyrosine phosphorylation phenomenon as the key regulatory mechanism for its binding advantage to Coll IV matrix.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Pleural biopsy: a reliable method for determining the diagnosis but not subtype in mesothelioma.

BACKGROUND: Survival after tri-modality therapy with extrapleural pneumonectomy (EPP) and postoperative chemoradiotherapy is longer for patients with epithelial MPM versus mixed or sarcomatoid subtypes, leading some to decline aggressive therapy for patients with nonepithelial histology. However, pathologic diagnosis of malignant pleural mesothelioma (MPM) and subclassification into one of the three histologic subtypes (epithelial, mixed, sarcomatoid) can be challenging. Pleural biopsy has been proposed as the diagnostic gold standard. We investigated the accuracy of open pleural biopsy for diagnosis and subtype identification in MPM. METHODS: Patients with suspected MPM routinely undergo open pleural biopsy to establish diagnosis. Those diagnosed definitively by pleural biopsy or cytology are offered pleurectomy or EPP dependent on stage and cardiorespiratory status. We reviewed medical records for all patients undergoing EPP at our institution, comparing tissue and subtype diagnosis at initial diagnostic biopsy versus definitive resection. RESULTS: Between 1988 and 2000, 305 of 332 consecutive patients undergoing EPP had MPM. One patient diagnosed with MPM at pleural biopsy was misclassified. Subtype analysis at pleural biopsy proved correct in 80% (226/282). Most patients (174/192) with epithelial subtype at final diagnosis were diagnosed correctly at pleural biopsy. However, 44% (45/103) with pathologic diagnosis of nonepithelial subtype at resection were initially misdiagnosed with the epithelial subtype. The sensitivity of pleural biopsy for epithelial MPM was 97% with a specificity of 56%. CONCLUSIONS: Open pleural biopsy is accurate and should be considered the gold standard diagnostic method for MPM. It is less sensitive for determining histologic subclass, particularly with nonepithelial subtypes.

Biopsy↗
PubMed2004

Adenocarcinoma of the gastric cardia: what is the optimal surgical approach?

BACKGROUND: The incidence of adenocarcinoma of the gastric cardia is rising in Western countries. This study evaluates prognostic factors associated with surgical management of this cancer. STUDY DESIGN: Medical records of consecutive patients with gastric cardial cancer treated by surgical resection from 1991 through 2001 were reviewed. Survival was analyzed using the Kaplan-Meier method. Prognostic factors were evaluated using log-rank test and Cox regression. Mean followup period was 34 months. RESULTS: Eighty-two patients met study inclusion criteria. Median patient age was 65 years (range 86 to 22). Fifty-nine (72%) patients had type II tumors and 23 (28%) patients had type III tumors, according to the Siewert classification for gastroesophageal junction tumors. Twenty-seven (33%) patients underwent total esophagectomy, 24 (29%) patients underwent extended gastrectomy with thoracotomy, and 31 (38%) patients underwent extended gastrectomy without thoracotomy. Overall postoperative 5-year survival rate was 30%. On multivariate analysis, patient age 65 years and older, absence of lymph node metastasis, and R0 resection emerged as factors independently associated with improved postoperative survival. Frequency with which proximal resection margin was infiltrated with cancer was a function of gross margin length and T stage. Proximal gross margin length of at least 6 cm was required to achieve a microscopically negative proximal margin for T3 and T4 cancers. CONCLUSIONS: Achieving R0 resection should be the goal of surgical therapy for the gastric cardial cancer. The surgical approach should be tailored to individual patients to achieve this goal.

Adenocarcinoma↗