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T J Lynch

Publications and source records attributed to T J Lynch.

At least 55 records · Page 3Linked to original sources
PubMed1998

The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA 2 domain protein.

Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects in seed development, including decreased sensitivity to ABA inhibition of germination and altered seed-specific gene expression. This phenotype is consistent with a role for ABI4 in regulating seed responses to ABA and/or seed-specific signals. We isolated the ABI4 gene by positional cloning and confirmed its identity by complementation analysis. The predicted protein product shows homology to a plant-specific family of transcriptional regulators characterized by a conserved DNA binding domain, the APETALA 2 domain. The single mutant allele identified has a single base pair deletion, resulting in a frameshift that should disrupt the C-terminal half of the protein but leave the presumed DNA binding domain intact. Expression analyses showed that despite the seed-specific nature of the mutant phenotype, ABI4 expression is not seed specific.

Abscisic Acid↗
PubMed1997

Cocaine detoxification by human plasma butyrylcholinesterase.

The ability of human plasma butyrylcholinesterase (BChE) to detoxify cocaine in vivo was evaluated. Intravenous administration of BChE, at doses sufficient to increase the plasma levels of the enzyme as much as 800-fold, produced no adverse effects on the cardiovascular, autonomic, or central nervous systems of rats. Most of the enzyme could be recovered in the plasma immediately after administration and remained active with a beta-t(1/2) of 21.6 +/- 2.4 hr. Pretreatment of chloralose-urethane anesthetized rats with BChE, 0.1-7.8 mg/kg, decreased the hypertensive and arrhythmogenic effects produced by cocaine and increased the lethal dose of cocaine by three- to fourfold. Treatment of conscious rats with 1 and 10 mg/kg BChE decreased the incidence of seizures and deaths produced by a prior dose of cocaine (80 mg/kg, i.p.). These results suggest that BChE would provide a safe and highly efficacious treatment for cocaine intoxication.

Animals↗
PubMed1997

Therapeutic use of butyrylcholinesterase for cocaine intoxication.

The most common complications of cocaine ingestion are on the cardiovascular and central nervous systems and produce chest pain and generalized seizures. In humans, decreased levels of butyrylcholinesterase (BChE) (EC 3.1.1.8) have been associated with sustained effects of cocaine and life-threatening complications. Administration of purified human BChE has previously been demonstrated to protect against cocaine-associated cardiovascular toxicity in rats. A shift in the metabolism of cocaine as well as enhanced metabolism may be the underlying mechanism of the enzyme. Therefore, levels of the parent drug and four metabolites were determined in rat plasma after i.p. administration of a lethal cocaine dose, followed by i.v. administration of BChE. Plasma and brain concentrations of cocaine were lowered by 80% after BChE administration. Furthermore, the metabolic profile of cocaine in the plasma was altered. The concentration of ecgonine methylester was doubled although the concentration of ecgonine, a secondary metabolite of cocaine, was reduced. The level of benzoylecgonine was reduced by one-half while norcocaine was absent. Cocaine-associated effects upon the central nervous system were also shown to be reduced by administration of BChE to conscious rats. Furthermore, our studies in the cat have also shown that purified BChE shifts the metabolic profile of cocaine (1 mg/kg) to the pharmacologically inactive products ecgonine methylester and ecgonine. Pretreatment with BChE (0.27, 1.0, and 10.0 mg/kg) ameliorated the hypertensive effects of cocaine (1 mg/kg) by reducing the duration and the extent of BP elevation by 66%. Administration of the enzyme, 1 min after cessation of cocaine infusion, resulted in an immediate attenuation in the cocaine-induced broadening of the QRS complex. These results suggest that BChE could be an effective and rapid therapy for the treatment of life-threatening cocaine-induced cardiovascular effects in human while clearing the total body burden of cocaine.

Animals↗
PubMed1997

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study.

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.

Adenocarcinoma↗
PubMed1997

The middle ear of a lion: comparison of structure and function to domestic cat.

Acoustic and anatomical measurements were made on the middle ear of a deceased lion and compared with measurements from the domestic cat. The acoustic input impedance and sound-transmission ratios measured in the two species have similar features but differ quantitatively. Three-dimensional anatomical reconstructions show that the middle-ear structures of the lion and cat are similarly arranged but have large differences in absolute and relative size. In all fields, a bony septum divides the middle-ear air space into two cavities that are coupled through a small opening. A six-element analog-circuit model based on this distinctive structure captures the main features of both sets of middle-ear frequency responses, except at high frequencies. The element values are consistent with the structural dimensions of the cavities. The results suggest that quantitative measures of middle-ear cavity structure could allow prediction of frequency-dependent features of acoustic sensitivity for the entire cat family.

Acoustic Impedance Tests↗
PubMed1997

Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin.

PURPOSE: Immunotoxins could improve outcome in small-cell lung cancer (SCLC) by targeting tumor cells that are resistant to chemotherapy and radiation. N901 is a murine monoclonal antibody that binds to the CD56 (neural cell adhesion molecule [NCAM]) antigen found on cells of neuroendocrine origin, including SCLC. N901-bR is an immunoconjugate of N901 antibody with blocked ricin (bR) as the cytotoxic effector moiety. N901-bR has more than 700-fold greater selectivity in vitro for killing the CD56+ SCLC cell line SW-2 than for an antigen-negative lymphoma cell line. Preclinical studies suggested the potential for clinically significant cardiac and neurologic toxicity. We present a phase I study of N901-bR in relapsed SCLC. PATIENTS AND METHODS: Twenty-one patients (18 relapsed, three primary refractory) with SCLC were entered onto this study. Successive cohorts of at least three patients were treated at doses from 5 to 40 microg/kg/d for 7 days. The initial three cohorts received the first day's dose (one seventh of planned dose) as a bolus infusion before they began the continuous infusion on the second day to observe acute toxicity and determine bolus pharmacokinetics. Toxicity assessment included nerve-conduction studies (NCS) and radionuclide assessment of left ventricular ejection fraction (LVEF) before and after N901-bR administration to fully assess potential neurologic and cardiac toxicity. RESULTS: The dose-limiting toxicity (DLT) of N901-bR given by 7-day continuous infusion is capillary leak syndrome, which occurred in two of three patients at the dose of 40 microg/kg (lean body weight [LBW])/d. Detectable serum drug levels equivalent to effective in vitro drug levels were achieved at the 20-, 30-, and 40-microg/kg(LBW)/d dose levels. Specific binding of the immunotoxin to tumor cells in bone marrow, liver, and lung was observed. Cardiac function remained normal in 15 of 16 patients. No patient developed clinically significant neuropathy. However, a trend was noted for amplitude decline in serial NCS of both sensory and motor neurons. One patient with refractory SCLC achieved a partial response. CONCLUSION: N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 microg/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study.

Adult↗
PubMed1997

Ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer: update and preliminary survival analysis.

The primary objective of this study was to define the maximum tolerated dose and toxicity profile of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), given as a 24-hour infusion, in conjunction with ifosfamide/carboplatin/etoposide (ICE) chemotherapy in patients with advanced lung cancer. Paclitaxel was escalated from 75 to 225 mg/m2 in 25-mg/m2 increments. All patients received granulocyte colony-stimulating factor 5 microg/kg/d from day 4 until the neutrophil count was > or = 10,000/microL. The study population consisted of 41 patients with a median age of 60 years and a median follow-up of 20.7 months. Stage distribution included 5% stage IIIA, 46% stage IIIB, and 49% stage IV. Histology consisted of 61% adenocarcinoma, 12% squamous cell carcinoma, 10% large cell carcinoma, 15% small cell carcinoma, and 2% mixed. The predominant toxicity was hematologic; 63% of patients experienced grade 4 neutropenia and 49% developed grade 4 thrombocytopenia. Fever and neutropenia occurred in 34% of patients. Hematologic toxicity was, in all cases, short-term and reversible and was not dose related. With few exceptions, nonhematologic toxicity was not clinically important. Among 39 patients evaluable for response, 36% achieved a remission (8% complete, 28% partial, 41% had stable disease, and 23% experienced disease progression). Among 33 patients with non-small cell lung cancer, the response rate was 27% (one complete response, eight partial responses, 15 had stable disease, and nine had progressive disease). Among six patients with small cell carcinoma, the response rate was 83% (two complete responses, three partial responses, and one had stable disease). The median survival of all 41 patients was 13.6 months. Survival was almost identical between stage IIIA and stage IV subsets. We conclude that it is possible to safely administer full-dose single-agent paclitaxel with granulocyte colony-stimulating factor support in conjunction with full-dose ifosfamide/carboplatin/etoposide chemotherapy. While response rates observed were not particularly notable, median survival is considerably longer than that usually achieved with combination chemotherapy in advanced lung cancer.

Adult↗
PubMed1996

Considerations of pool size in the manufacture of plasma derivatives.

BACKGROUND: The pooling of human plasma from many donors for the purpose of manufacturing therapeutic proteins increases the risk of exposing recipients of these proteins to pathogens that may contaminate 1 or a few units included in the pool. STUDY DESIGN AND METHODS: This risk is estimated for a range of manufacturing scales that would derive material from a varied number of donors and for a number of hypothetical infectious agents that may exist in the donor population over a wide range of prevalence. Risk is also calculated both for recipients of single doses of a plasma protein and for those who depend on long-term treatment with plasma derivatives. RESULTS: Risk of exposure increases with pool size and the prevalence of the agent in question and accumulates with repeated treatments with material manufactured from different pools. CONCLUSION: Reducing pool size would at best decrease this risk in proportion to the reduction in manufacturing scale. However, for individuals requiring repeated or continuous treatments, the risk of exposure to all but the rarest infectious agents would be only minimally affected, even by large reductions in manufacturing scale.

Blood Proteins↗
PubMed1996

Identification, mapping and linkage analysis of randomly amplified DNA polymorphisms in Tetrahymena thermophila.

Using the random amplified polymorphic DNA (RAPD) technique and exploiting the unique genetics of Tetrahymena thermophila, we have identified and characterized 40 DNA polymorphisms occurring between two inbred strains (B and C3) of this ciliated protozoan. These RAPD markers permit the PCR amplification of a DNA species using template DNA from SB1969 (B strain) but fail to do so using DNA from C3-368-5 (C3 strain). Polymorphisms were mapped to chromosomes using a panel of monosomic strains constructed by crossing B strain-derived nullisomic strains to inbred strain C3. They map to all five chromosomes and appear to be evenly distributed throughout the genome. Chromosomal groups were then analyzed for linkage using meiotic segregants; four linkage groups were identified in chromosomes 1R 2L, 3 and 5. The RAPD method appears useful for the construction of a genetic map of the Tetrahymena genome based on DNA polymorphisms.

Animals↗
PubMed1995

Genetic map of randomly amplified DNA polymorphisms closely linked to the mating type locus of Tetrahymena thermophila.

We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosome segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome.

Animals↗
PubMed1995

Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.

PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.

Biomarkers↗
PubMed1995

A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.

A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.

Adult↗
PubMed1994

Continuous-infusion cisplatin, 5-fluorouracil, and leucovorin for advanced non-small cell lung cancer.

BACKGROUND: Cisplatin, 5-fluorouracil, and leucovorin (PFL) have demonstrated synergistic activity in preclinical models. Continuous infusion of these agents maximizes the potential for synergistic interaction and forms the basis of the PFL regimen. METHODS: Sixty-one patients with advanced (Stages IIIB and IV) non-small cell lung cancer were entered into the study. Thirty-one were treated with cisplatin 25 mg/m2/day on days 1-5, 5-fluorouracil 800 mg/m2/day on days 2-6, and calcium leucovorin 500 mg/m2/day on days 1-6. Because of severe mucositis, the final 30 patients were treated with the same dosage of cisplatin but with the deletion on day 6 of leucovorin and 5-fluorouracil. Cycles were repeated every 28 days. Response was assessed after two cycles. Responding patients received an additional two cycles. Patients with Stage IIIB disease received radiation therapy to the mediastinum and sites of involved disease. RESULTS: PFL had an overall response rate of 41%. Median survival was 8.1 months, and median time to treatment failure was 4.2 months. Importantly, 68% (17 of 25) of responses were maximal after just two cycles of chemotherapy. Notable toxicities included mucositis (43% > or = Grade 3) and myelosuppression. Response, time to failure, or survival did not differ between the two schedules. Mucositis was less severe with 4-day PFL. CONCLUSIONS: PFL as given in this manner is an active regimen for the treatment of patients with advanced non-small cell lung cancer. The rapidity of response makes it a regimen for incorporation into protocols for Stage IIIA disease. A neoadjuvant study using PFL is underway.

Adult↗
PubMed1994

Measurements of the acoustic input impedance of cat ears: 10 Hz to 20 kHz.

The acoustic input impedence of the ear is a useful measure of the behavior of the middle ear and of its effect on the acoustics of the external ear. A high-impedance acoustic source with an integral microphone was designed for acoustic-impedance measurements. The source's Norton equivalent circuit was determined from measurements of the sound pressure it generated in known acoustic loads. Tests on simple acoustic configurations show errors in impedance measurements of less than 10% in magnitude and 7 degrees in angle over a frequency range from 10 Hz to 10 kHz with increasing errors at higher frequencies. Measurements at the tympanic membrane (TM) on five cat ears with widely opened middle-ear cavities show an impedance that is compliance-like below 0.3 kHz and approximately resistive above 2 kHz. With the cavities intact the impedance magnitude is somewhat larger for low frequencies, has a sharp maximum near 4 kHz, and at the highest frequencies is little affected by the state of the cavities. Impedance magnitude varies among ears by a factor of 3. The pressure reflection-coefficient that is determined from the impedance is frequency dependent with magnitude between 0.2 and 1. To characterize the motion transformation of the TM we calculate the ratio of tympanic-membrane volume velocity to the velocity of the mallear umbo, called here the kinematic area ATK. This complex quantity is constant with an angle of zero for frequencies below 0.6 kHz, but at higher frequencies both magnitude and angle of ATK vary with frequency.

Acoustic Impedance Tests↗
PubMed1994

Phase II study of topotecan in metastatic non-small-cell lung cancer.

PURPOSE: Topotecan is an inhibitor of topoisomerase I that has shown preclinical activity against non-small-cell lung cancer (NSCLC). This phase II study was designed to determine the clinical activity and toxicity spectrum of topotecan in untreated patients with metastatic NSCLC. PATIENTS AND METHODS: Twenty previously untreated patients received topotecan every 21 days at the dose of 2 mg/m2/d intravenously (IV) for 5 days for two cycles, at which point response was assessed. Patients with either clinical response or stable disease (SD) received additional cycles of the drug until toxicity developed or disease progression (PRG) occurred. RESULTS: This study was designed to enter 30 patients. However, because no clinical responses were seen in the first 20 patients entered onto the study, the early-stopping rule was invoked and patient accrual was halted. Eleven patients (55%) had SD on topotecan, and nine (45%) had PRG. Toxicity included neutropenia and rash. The median survival duration for all patients was 7.6 months. CONCLUSION: We observed no objective clinical responses despite producing high-grade neutropenia. Phase II trials of topotecan using different schedules or higher doses supported by growth factors may clarify the role of topotecan in the treatment of NSCLC. The combination of topotecan with cisplatin and topoisomerase II inhibitors such as etoposide should be explored. Finally, the median survival duration of 7.6 months for 20 patients treated with an agent that failed to produce any obvious clinical responses compares favorably to the survival obtained with combinations of existing agents. This supports the further study of novel compounds in this clinical setting.

Aged↗
PubMed1993

Cisplatin, 5-fluorouracil, and etoposide for advanced non-small cell lung cancer.

BACKGROUND: Cisplatin and etoposide combination chemotherapy is the most commonly used regimen for advanced non-small cell lung cancer (NSCLC). 5-Fluorouracil (5-FU) is an agent with little intrinsic activity against NSCLC: However, there is increasing evidence that 5-FU is synergistic with cisplatin and vice versa. In an effort to improve on the traditional chemotherapeutic approach to NSCLC, a treatment regimen consisting of cisplatin, 5-FU, and etoposide (PFE) was developed. METHODS: Thirty-five patients with advanced NSCLC were treated with the PFE regimen (cisplatin 25/mg/m2/d and 5-FU 1000 mg/m2/d by continuous infusion and etoposide 60 mg/m2/d, each for 4 days). The cycles were repeated every 28 days. RESULTS: The patients received a mean of 2.8 cycles of PFE. Ten patients had a partial response to chemotherapy for an overall response rate of 28.6%. The median survival was 7.0 months. Toxicities included myocardial infarction (2 of 35), congestive heart failure (2 of 35), fatal pulmonary embolus (1 of 35), and a cerebrovascular accident (1 of 35). The incidence of Grade 4 neutropenia (5.7%) and thrombocytopenia (8.5%) was acceptable. CONCLUSIONS: The response rate, duration of response, and survival in this group of 35 patients treated with PFE was similar to that reported for cisplatin and etoposide. The increased cardiovascular toxicity may be the result of the infused 5-FU.

Adult↗
PubMed1993

Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.

PURPOSE: We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy. RESULTS: Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years. CONCLUSION: Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment.

Adult↗