HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies.

Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+ T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.

Transport and storage of serotonin by thrombin-treated platelets.

Repeated thrombin treatment of washed platelets prepared from rabbits can decrease the serotonin content of the platelets by about 80%. When these platelets are deaggregated they reaccumulate serotonin but their storage capacity for serotonin is reduced by about 60%. If thrombin-pretreated platelets are allowed to equilibrate with a high concentration of serotonin (123 mu M), they release a smaller percentage of their total serotonin upon further thrombin treatment, in comparison with the percentage of serotonin released from control platelets equilibrated with the same concentration of serotonin calculations indicate that in thrombin-treated platelets reequilibrated with serotonin, two-thirds of the serotonin is in the granule compartment and one-third is in the extragranular compartment, presumably the cytoplasm. Analysis of the exchange of serotonin between the suspending fluid and the platelets showed that thrombin treatment does not alter the transport rate of serotonin across the platelet membrane and does not cause increased diffusion of serotonin from the platelets into the suspending fluid. The primary reason for the reduced serotonin accumulation by the thrombin-treated platelets appears to be loss of amine storage granules or of the storage capacity within the granules.

Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma.

PURPOSE: To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS: Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/microL). Paclitaxel was initially administered at 135 mg/m2 over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to a maximum of 175 mg/m2. Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. RESULTS: Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. CONCLUSION: Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease.

Characterisation and evaluation of metal-loaded iminodiacetic acid-silica of different porosity for the selective enrichment of phosphopeptides.

Silica particles of different porosity were functionalised with iminodiacetic acid (IDA) and loaded with Fe(III) to yield immobilised metal affinity chromatography stationary phases (Fe(III)-IDA-silica) for phosphopeptide enrichment. The elution step of bound phosphopeptides was optimised with a 32P radioactive labelled peptide by a comprehensive study. Several elution systems, including phosphate buffers of different pH and concentration and ethylenediaminetetraacetic acid solutions were employed. Furthermore the effect of support porosity on elution behaviour was investigated. Under best conditions recoveries higher than 90% were achieved. A solid-phase extraction (SPE) protocol was developed for fractionation of phosphorylated and non-phosphorylated peptides and desalting of the fractions which is essential for subsequent mass spectrometric analysis by the combination of Fe(III)-IDA-silica and C18-silica particles. The pH of the loading buffer was found to be a critical parameter for the efficiency of the SPE protocol. As tryptic digests of alpha-lactalbumin, lysozyme and ribonuclease A mixed with three synthetic phosphopeptides were fractionated, pH 2.5 provided minimal proportion of unspecific bound peptides when comparing the fractions after mu-LC-electrospray ionization MS separation. The effect of a sample derivatisation reaction (methylation) on the efficiency of phosphopeptide enrichment was further investigated. Blocking carboxylate groups by methyl ester formation totally prevented unspecific interaction with the immobilised Fe(III) ions, but generated partially methylated phosphopeptides that increased the complexity of the phosphorylated fraction.

Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma.

CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate.

Successful surgical management of neutropenic enterocolitis in two patients with severe aplastic anemia. Case reports and review of the literature.

We describe two patients with severe aplastic anemia in whom neutropenic enterocolitis developed while they were undergoing treatment at the National Institutes of Health. Both patients had progressive symptoms while receiving optimal medical management and both underwent and survived surgical intervention despite continued prolonged neutropenia in the perioperative period. This experience contrasts with six cases reported in the literature and suggests that surgery can be employed even in patients with profound neutropenia. Thus, in patients who remain persistently septic or who develop clinical deterioration despite medical management or who have other indications for surgical intervention, neutropenia should not be a contraindication to the appropriate or necessary procedure.

Thyrotropin-secreting pituitary carcinoma.

Pituitary tumors rarely metastasize outside the central nervous system. Of the more than 100 reported TSH-secreting adenomas, we now describe the first carcinoma. A 40-yr-old woman had transsphenoidal surgery for a large TSH-secreting pituitary adenoma in 1984. She had increased thyroid hormone levels with a TSH that varied from 16-31 microU/mL, and an unusually high alpha-subunit that ranged from 125-150 ng/mL. Because of residual tumor, she had a left craniotomy in 1985 followed by radiation. Despite these therapies, she had a residual tumor that remained stable until January 1989 when her tumor nearly doubled in size. She received radiation therapy and octreotide with marked diminution of the tumor and clinical improvement. In August 1989, she presented with leg weakness, and magnetic resonance imaging revealed a large sacral mass. A biopsy confirmed that the sacral mass was a metastasis from the pituitary tumor. Due to additional metastases in the lung, she received 5-fluorouracil, cytoxan, and adriamycin, with marked decrease in her lesions. Further substantiation of the metastatic pituitary tumor was made when the patient returned in December 1989 with a pleural effusion containing pituitary tumor cells. Of all the reported cases of TSH-secreting adenomas, this case had the highest alpha-subunit portending future metastases. Furthermore, the apparent response to octreotide and response to chemotherapy are encouraging and suggest that new therapies should be explored. Finally, since TSH-secreting adenomas tend to be more invasive than other pituitary tumors, this case underscores the need for early diagnosis and aggressive treatment of these tumors.

The causes of death in patients with human immunodeficiency virus infection: a clinical and pathologic study with emphasis on the role of pulmonary diseases.

The clinical records and autopsy data of 75 patients dying with AIDS were reviewed to determine the frequency of individual diseases diagnosed premortem and postmortem, the significance of pulmonary processes found in the lungs at autopsy, and the clinical and pathologic causes of death. Cytomegalovirus (CMV) infection was identified histologically either premortem or postmortem in 81% of patients. The lungs and adrenal glands were infected most commonly. Only one-half of CMV infections were recognized premortem. Pneumocystis pneumonia and Kaposi sarcoma occurred in 68% and 59% of patients, respectively, but were not unsuspected premortem in any patient. Visceral involvement with Kaposi sarcoma, however, was frequently recognized only at autopsy. While disseminated M. avium-intracellulare infection was common (31% of patients), histologically documented pulmonary disease was uncommon (3% of patients). Cryptococcal infection, diagnosed in 10 patients, was confined to the central nervous system in only 1 patient. Toxoplasma, in contrast, infected the brain of only 6 patients. All 75 patients had one or more disease processes identified in their lungs or pleurae at autopsy. These processes included opportunistic infections in 76% of patients, neoplasms in 37% (Kaposi sarcoma in 36% and lymphoma in 3%), and other processes in 60%. The most prevalent pathogen, CMV was found in pulmonary tissue from 44 patients and caused significant disease in 21 patients. Five patients died due to CMV pneumonia. Pneumocystis carinii was found at autopsy in 24 patients. In spite of treatment, pneumocystis pneumonia was fatal in 11 patients. One patient died with concomitant CMV and pneumocystis pneumonia. Kaposi sarcoma, identified in the lungs of 23 patients, led to death in 5 patients via upper airway obstruction, hemorrhage, or parenchymal destruction. Other fatal pulmonary processes included bacterial pneumonia in 9 patients, idiopathic diffuse alveolar damage in 5, cryptococcosis in 2, and pulmonary hemorrhage in 1. Specific clinical criteria were used to determine the cause of death due to organ system failure. Fifty-one percent of patients died due to respiratory failure; 16% from neurologic disease; 17% from hypotension that was not caused by respiratory, neurologic, or cardiac disease; and 3% from cardiac dysfunction. Thirteen percent of deaths did not meet the clinical criteria defining these 4 categories. This clinical assessment was combined with autopsy data to identify specific diseases as causes of death.(ABSTRACT TRUNCATED AT 400 WORDS)

Sinusitis in HIV-1 infection.

PURPOSE: To determine the clinical and radiographic characteristics of sinusitis in patients with human immunodeficiency virus type 1 (HIV-1) infection. PATIENTS AND METHODS: A retrospective study was performed that identified all HIV-1-infected patients with sinus radiographs, sinus computed tomograms, or magnetic resonance imaging of the head between 1982 and 1989 (n = 145). Medical record review detailed the clinical course and laboratory parameters in all patients. RESULTS: Eighty-nine patients had radiographic evidence of sinusitis; 75 patients had adequate clinical data and comprise the study group. Acute sinusitis was seen in 10 patients (13%), while all 75 patients had mucosal thickening indicative of chronic sinusitis. Fifty patients (67%) were symptomatic with fever, nasal congestion or discharge, and headache being the most common symptoms; nineteen patients (25%) were asymptomatic when their radiographs showed active disease. The mean CD4 count for the group was 276 cells/mm3; 32 (43%) had CD4 counts less than or equal to 100 cells/mm3. Twenty-three patients (31%) received antibiotics orally, parenterally, or both. CONCLUSIONS: Sinusitis appears to occur frequently in HIV-infected patients, is often asymptomatic, may be recurrent or refractory, and may be associated with declining immunocompetence in HIV-infected patients.

Pulmonary Langerhans cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases.

We report the clinical and histologic findings of lung biopsies from 48 patients with pulmonary Langerhans cell granulomatosis (PLCG) and show how special techniques such as immunohistochemistry, electron microscopy (EM), and high resolution computerized tomography (HRCT) of the lungs can be useful in diagnostically challenging cases. Nineteen patients were men and 29 were women. The median age was 33 years (range 15-54 years). Two had pituitary involvement. Bone lesions were observed in four patients and biopsy proven in two. All patients were cigarette smokers. In six patients HRCT revealed a combination of thin-walled cystic and nodular lesions. The pathologic diagnosis was established on the basis of open lung biopsy specimens in 44 cases and transbronchial biopsy specimens in 4 of 10 cases. In two transbronchial biopsies, diagnostic PLCG infiltrates were seen in toluidine blue-stained thick sections in the tissue processed for EM but not on the tissue processed for histology. EM in both of these cases revealed Birbeck granules within LCs. The diagnosis was supported by a positive bone biopsy in one of these patients and characteristic HRCT findings in the other. The antibody to S100 protein stained the LC infiltrates in the five cases studied. This staining and the characteristic findings on HRCT confirmed the diagnosis in one case in which the PLCG lesions were obscured by atelectasis. The frequent finding of intraluminal fibrosis (78% of open lung biopsies) supports the recent suggestion that this alteration plays an important role in the pathogenesis of fibrotic remodeling in PLCG. The strong association of PLCG with cigarette smoking and the frequent peribronchiolar location of PLCG lesions (87% of open lung biopsies) in our cases are consistent with the concept that in adults this disorder is associated with an abnormal response to cigarette smoke.

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas.

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.

Platelet adherence and detachment--in what ways is surface-bound albumin different from surface-bound fibrinogen?

The adhesion and detachment of platelets on surface-bound albumin and surface-bound fibrinogen were studied. Fluorescent video-microscopy of platelets labelled with mepacrine was used to provide continuous information. Glass tubes (I.D. 1.3 mm) were precoated with either human albumin or human fibrinogen before exposure to a suspension of washed platelets and red cells. Observations were made 0.5 cm from the tube's entrance over a 1370 micron 2 portion of lumen. The rate at which cells leave the measurement area and the percent of initially attaching cells which leave are independent of protein coating but increase with flow rate. The percent of initially attaching platelets which permanently adhere is equal for both protein coatings but the pathways leading to this result can be different. For the lower shear rate studied, 80 s-1, the percent of cells which permanently adhere on first contact is less for albumin than for fibrinogen; the percent of initially attaching cells which adhere and then move before permanent adhesion is greater for albumin. The mechanism of detachment and reattachment leads to the equality of the overall adhesion efficiencies for the two protein coatings at 80 s-1. For the higher shear rate studied, 456 s-1, the adhesion pathways for both coatings were the same.

Adhesion of polymorphonuclear leukocytes to protein-coated and platelet adherent surfaces.

Since protein adsorption and platelet adhesion are likely to precede significant contact of leukocytes with the surfaces of artificial organs, we have chosen to study polymorphonuclear leukocyte (PMN) adhesion in a sequential manner. The work presented here deals with the effects of flow and surface type on PMN adhesion to fibrinogen- and albumin-coated glass. We compared direct adhesion to adsorbed protein with adhesion to adsorbed protein having adherent platelets. These experiments were designed to see if PMN's might preferentially adhere to albumin or fibrinogen and whether a particular morphological form of adherent platelet could promote PMN adhesion. The adhesion of PMN's to spread platelets on albumin or fibrinogen occurs to a greater extent than in the absence of platelets. Adhesion of PMN's to spread platelets may be an important mechanism for their depletion from the circulation during artificial organ use.

Adhesion and aggregation of thrombin prestimulated human platelets on surface-bound fibrinogen: evidence for involvement of ADP and arachidonic acid pathways.

The purpose of this study was to examine the influence of substances released from human platelets upon their accumulation on human fibrinogen-coated glass tubes. After prestimulation with thrombin for one minute or in the absence of prestimulation, washed human platelets suspended in Eagle's medium with RBC were drawn through the tubes at 1 ml/min, 80 s-1, for 1, 2 or 6 min. Thrombin prestimulation (0.02, 0.05 or 0.25 U/ml) was followed by inactivation with hirudin (0.1, 0.25 or 1.25 U/ml) before flow. Singly adherent platelets were observed in the absence of thrombin or with thrombin for exposure times of 1 and 2 min. At 6 min after at least 0.05 U/ml of thrombin, surface-bound aggregates were observed. The initial rate of adhesion increased with the amount of thrombin used for prestimulation. For adhesion to fibrinogen in the absence of prestimulation, platelet-derived ADP was a stimulator. Adhesion was shown to be independent of the ADP and arachidonic acid pathways in response to prestimulation with a low level of thrombin, 0.02 U/ml. For adhesion and cohesion, aggregation, in the presence of sufficient thrombin for prestimulation, 0.05 U/ml, ADP, serotonin and substances from arachidonic acid metabolism acted jointly to stimulate platelets.

Platelet accumulation on collagen: drugs which inhibit arachidonic acid metabolism and affect intracellular cyclic AMP levels.

We have studied the accumulation of washed platelets on collagen-coated glass from flowing platelet-red blood cell suspensions in the presence and absence of drugs. Glass tubes were 10 cm long and the flow rate was 1 ml/min, 80 s-1. For all experiments, platelet accumulation was greatest near the tube's inlet with a continuous decrease to the exit. A common feature, of those drug treatments which lead to reduced accumulation at the inlet, was an increase in outlet accumulation when compared with outlet control values. Platelet-collagen adhesion resulted in maximal release of 3H-serotonin in the presence of agents that prevent platelet aggregation on collagen. Only drug treatment known to raise cAMP levels (PGE1 and dipyridamole) or prevent the formation of prostaglandins and thromboxanes (sulfinpyrazone, indomethacin and ASA) were found to inhibit aggregate growth. Platelet aggregation on collagen in the absence of thrombin likely proceeds through the liberation of prostaglandins and thromboxanes from surface-bound platelets into the flow where they may stimulate flow-born cells. An alternate hypothesis is that such treatments affect the release of alpha-granule components necessary for aggregation.

Aortic hypoplasia in homozygous familial hypercholesterolemia.

Diagnosis of hypoplastic aortic root with ultrafast computed tomography provides important clinical information in homozygous familial hypercholesterolemic patients with supravalvular aortic stenosis.

Relation of cholesterol-year score to severity of calcific atherosclerosis and tissue deposition in homozygous familial hypercholesterolemia.

The high concentrations of low-density lipoprotein cholesterol in plasma lead to accelerated atherosclerosis in patients homozygous for familial hypercholesterolemia (FH). We addressed the hypothesis that lipid deposition in the arterial vasculature and in nonvascular tissues in these patients correlates with both the duration and severity of their hypercholesterolemia. The severity of calcific atherosclerosis was defined by calcification scores and a calcified volume determined by electron beam tomography. The extent of tendinous xanthomatosis was quantitated by computed tomography. A cholesterol-year score was calculated based on the age and the yearly mean serum cholesterol concentration of each patient. Seventeen patients homozygous for FH were followed up. The average total cholesterol concentration in the study group was 780 +/- 231 mg/dl (20.2 mmol/L), and the cholesterol-year scores ranged from 2,172 mg-year/dl (56 mmol-year/L) to 32,260 mg-year/dl (834 mmol-year/L). Achilles tendon width (r=0.86) and cross-sectional area (r=0.81; both p <0.001) were best correlated with the cholesterol-year score. In addition, the coronary (r=0.61; p<0.05), ostial (r=0.45; p<0.05), and total (r= 0.77; p<0.001) calcification atherosclerosis scores all were best correlated with the cholesterol-year score. Calcific atherosclerosis was not observed in these patients until the cholesterol-year score exceeded 10,000 mg-year/dl (260 mmol-year/L). These findings establish a direct association of cholesterol-year with extravascular lipid deposition in tissues of patients with FH. The cholesterol-year score may be useful in defining the risk of atherosclerosis in patients with more common forms of hypercholesterolemia.

Hypoxia and cyanosis in alpha-1-antitrypsin deficiency. Cirrhosis as an unusual etiologic factor.

A patient with type PiZZ alpha-1-antitrypsin deficiency was found to have severe hypoxia despite normal pulmonary function testing and a normal chest radiograph. A nuclear medicine ventilation-perfusion study revealed a right-to-left shunt. Computed tomography showed minimal bleb formation, no diffuse changes, and hepatic changes of cirrhosis with portal hypertension. No nodular pulmonary masses or enlarged peripheral pulmonary vessels were found. The diagnosis of diffuse intrapulmonic arteriovenous shunts ("pulmonary spiders of cirrhosis") was suggested and then confirmed with a dynamic radionuclide flow study.

Computed tomography appearance of a right cervical aortic arch.

The clinical diagnosis of cervical aortic arch rests on the detection of a pulsatile mass in the supraclavicular fossa. Unfortunately, clinical differentiation of a cervical arch from an aneurysm of the great vessels can be difficult. Dynamic computed tomography (CT) can aid in this differentiation and avert the need for angiography.

Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma.

OBJECTIVES: Our objective was to analyze the impact of preoperative and postresection solid tumor volumes on outcomes in 47 of 48 consecutive patients undergoing resection for malignant pleural mesothelioma who were treated prospectively and randomized to photodynamic therapy or no photodynamic therapy. METHODS: From July 1993 to June 1996, 48 patients with malignant pleural mesothelioma had cytoreductive debulking to 5 mm or less residual tumor by extrapleural pneumonectomy (n = 25) or pleurectomy/decortication (n = 23). Three-dimensional computed tomographic reconstructions of preresection and postresection solid tumor were prospectively performed and the disease was staged postoperatively according to the new International Mesothelioma Interest Group staging. RESULTS: Median survival for all patients is 14.4 months (extrapleural pneumonectomy, 11 months; pleurectomy/decortication, 22 months; p2 = 0.07). Median survival for preoperative volume less than 100 was 22 months versus 11 months if more than 100 cc, p2 = 0.03. Median survival for postoperative volume less than 9 cc was 25 months versus 9 months if more than 9 cc, p2 = 0.0002. Thirty-two of forty-seven (68%) had positive N1 or N2 nodes. Tumor volumes associated with negative nodes were significantly smaller (median 51 cc) than those with positive nodes (median 166 cc, p2 = 0.01). Progressively higher stage was associated with higher median preoperative volume: stage I, 4 cc; stage II, 94 cc; stage III, 143 cc; stage IV, 505 cc; p2 = 0.007 for stage I versus II versus III versus IV. Patients with preoperative tumor volumes greater than 52 cc had shorter progression-free intervals (8 months) than those 51 cc or less (11 months; p2 = 0.02). CONCLUSIONS: Preresection tumor volume is representative of T status in malignant pleural mesothelioma and can predict overall and progression-free survival, as well as postoperative stage. Large volumes are associated with nodal spread, and postresection residual tumor burden may predict outcome.