A nationwide assessment comparing nonelective open with minimally invasive complex colorectal procedures.

AIM: The use of minimally invasive colorectal surgery has increased greatly for both benign and malignant disease. Studies evaluating complex procedures have been largely limited to elective indications. We aimed to compare the outcome of a laparoscopic with an open transverse (TC) and total abdominal colectomy (TAC) in the nonelective setting. METHOD: Comparative analysis was made using the Nationwide Inpatient Sample (2008-11) of patients undergoing a nonelective TC or TAC identified by ICD-9-CM procedure codes. The risk-adjusted 30-day outcome was assessed using regression modelling accounting for patient characteristics, comorbidity and surgical procedure. RESULTS: We identified 7261 admissions including 818 laparoscopic and 6443 open procedures. The mean age of the population was 65 ± 17 years and patients in the laparoscopic group were younger (56 ± 20 vs. 66 ± 17 years; P < 0.05). The rate of a single complication was lower in the laparoscopic group (26% vs. 38%; P < 0.01), but this did not remain significant following a logistic regression analysis. Mortality was significantly lower in the laparoscopic group (3.1% vs. 17%; P < 0.01) and this remained true after adjusting for covariates (OR = 0.62; P < 0.05). Laparoscopic cases were associated with a shorter median length of stay (10 vs. 13 days; P < 0.01) and hospital charge ($75,758 vs. $98,833; P < 0.01). CONCLUSION: A nonelective laparoscopic TC or TAC is associated with an equivalent complication rate and lower mortality compared with an open operation. The results should encourage surgeons with the appropriate skills to consider a laparoscopic approach for nonelective pathology requiring a complex colectomy.

Long-term cost-effectiveness of weight management in primary care.

BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

A simple method for assaying colistimethate sodium in pharmaceutical aerosol samples using high performance liquid chromatography.

A rapid and simple reversed-phase high performance liquid chromatography (HPLC) method for the quantitation of colistimethate sodium in pharmaceutical formulations has been developed. The chromatographic separation was performed using a Phenomenex Kinetex XB-C18 column with gradient elution using a mobile phase containing acetonitrile and 32mM sodium sulphate. Quantitation is based on the sum of the areas of two prominent peaks in the chromatogram, which produces a total peak area that is stable for 120 sample injections. The HPLC method was validated over the range 0.05-7mg/mL, and was shown to be suitable for the analysis of aerosolised pharmaceuticals in terms of aerosol output onto filter and for the analysis of samples from a cascade impactor, which is used for the determination of aerosol particle size.

Variability in Delivered Dose from Pressurized Metered-Dose Inhaler Formulations Due to a Delay Between Shake and Fire.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) should be shaken before use to prevent creaming or sedimentation of the drugs in solution; however, data published on this topic are limited, and it is rarely specified how soon after shaking the device should be actuated. Delays between shaking and firing the pMDI have previously been shown to cause significant inhomogeneity in delivered dose. We studied the effect of various shake-fire delays on the drug delivered from five commercially available pMDIs commonly prescribed for asthma and chronic obstructive pulmonary disease to assess the potential variability in delivered dose. METHODS: The pMDI formulations tested were the Flovent HFA, Ventolin Evohaler, Airomir Inhaler, and Symbicort (suspension pMDIs), and the QVAR 100 Inhaler (solution pMDI). Each pMDI was shaken for 5 seconds before attachment to a dosage unit sampling apparatus collection tube and filter, and it was actuated once with shake-fire delays of 0, 5, 10, 20, 30, 40, 50, and 60 seconds. Analysis of the eluates from the collection tubes and filters was performed by using high-performance liquid chromatography. Three of each pMDI were tested twice with each time delay. RESULTS: All of the suspension pMDIs produced variable amounts of drug over the shake-fire delays tested. A comparison of the delivered doses after the 0- and 60-second delays showed that the drug delivered increased for the Flovent HFA (320%), Ventolin Evohaler (346%), and Airomir Inhaler (230%) pMDIs; decreased for the Symbicort budesonide (75%) and formoterol fumarate (76%) pMDI; and remained consistent for the QVAR 100 Inhaler pMDI. CONCLUSIONS: The amount of drug delivered can vary widely over different shake-fire delays with suspension pMDIs. Therefore, guidance should be given to users/caregivers on the timing of firing after shaking their device, particularly with pediatrics, who may take time to become receptive to accepting their medication after pMDI shaking and before dose administration.

Drug Delivery in Asthmatic Children Following Coordinated and Uncoordinated Inhalation Maneuvers: A Randomized Crossover Trial.

BACKGROUND: Valved holding chambers (VHCs) are used in children to deliver pressurized metered dose inhalers (pMDI). In vitro data suggest that uncoordinated use decreases the amount of drug available for inhalation. We hypothesize that in an ex vivo study, the coordinated maneuver will deliver more drug than the uncoordinated one. PATIENTS AND METHODS: Thirty-two clinically stable asthmatic children, ages 5-8 years, completed the study. An aerosol filter was interposed between a small-volume nonelectrostatic VHC and a mouthpiece to capture the drug emitted by one puff of Flovent® 220 mcg during tidal breathing. Inhalation and actuation parameters were measured by an electronic monitor, and the number of breaths required to empty the VHC was calculated. Subjects completed three coordinated and three uncoordinated (actuation at the beginning of inhalation and exhalation, respectively) runs in random order. Drug content from the filter and VHC was measured by high-performance liquid chromatography and expressed as percentage of emitted dose. RESULTS: [mean (99% confidence interval)] Filter dose was higher during coordinated technique 46% (43%-50%) than during uncoordinated technique 41% (37%-44%) (p < 0.001). Peak inspiratory flow and tidal volume were 23.2 L/min (21.3-25.1 L/min) and 281 mL (251-311 mL), respectively. Subjects required three breaths to empty the VHC in 96% of the tests. CONCLUSIONS: Actuating the pMDI into a small-volume nonelectrostatic VHC during exhalation reduced by 11% the amount of fluticasone captured at the exit of the VHC. Asthmatic children (5-8 years old) need three or less breaths to empty the small-volume VHC (NCT01714063).

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme.

OBJECTIVE: To improve the management of obese adults (18-75 y) in primary care. DESIGN: Cohort study. SETTINGS: UK primary care. SUBJECTS: Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. INTERVENTION: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. MAIN OUTCOME MEASURES: Proportion of practices trained and recruiting patients, and weight change at 12 months. RESULTS: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. CONCLUSION: The Counterweight programme provides a promising model to improve the management of obesity in primary care.

Priming for T-cell-mediated rejection of established tumors by cutaneous DNA immunization.

DNA immunization has been shown to elicit both antibody and CTL responses against antigens expressed by infectious organisms. Because CTL responses have been implicated in rejection of cancer, we investigated whether DNA immunization by particle bombardment using a gene gun could induce CTL responses that were capable of rejecting tumors in mice. DNA immunization by particle bombardment using genes encoding beta-galactosidase and ovalbumin primed mice to generate CTLs in two genetic backgrounds (DBA/2 and C57BL/6 strains, respectively). DNA immunization was more potent in inducing CTLs than immunization with an optimized regimen of ovalbumin peptide plus immune adjuvant. Immunity induced by DNA immunization protected mice against s.c. challenge with tumors expressing the beta-galactosidase antigen. Tumors were rejected even when DNA immunization was started 3 or 7 days after tumor challenge as tumors were becoming established. Tumor rejection required CD8(+) T cells, confirming a role for CTLs in vivo. These studies show that DNA immunization by particle bombardment can efficiently induce CTL responses that are capable of rejecting even established tumors.

Factors to consider when selecting a nebulizer for a new inhaled drug product development program.

INTRODUCTION: Nebulizers are a common device choice for use when developing a new drug product, but the range of nebulizer devices available can make it difficult to select the right device. Increasingly, companies are only able to promote a drug with the device that was used during the development program; therefore, choosing the best device at an early stage is important in order to achieve commercial success. Selecting a device that is inappropriate for the intended drug can result in poor drug delivery from the nebulizer to the patient, which would have obvious implications for the development program. As device performance varies, it is important to ensure that the most appropriate device is chosen for the intended drug to ensure optimal drug delivery to the patient population. AREAS COVERED: In this review, the types of nebulizer devices available are highlighted, and the factors that should be taken into consideration when selecting the most appropriate device for a new drug are discussed. The review is broadly divided into drug, device, patient and trial characteristics. EXPERT OPINION: Efficient nebulizer devices that combine electronic monitoring capabilities as a form of telehealth are likely to provide superior drug delivery to patients and accurate clinical trial data. Their use in adaptive clinical trials may help to vastly reduce the time and costs associated with achieving drug approval.

The metabolic response to opportunistic infections in AIDS.

OBJECTIVE: The metabolic response to AIDS-defining opportunistic infections was examined to provide a logical basis for the management of associated weight loss. DESIGN: A prospective study of metabolism in AIDS. SETTING: HIV outpatients' department and wards at the Chelsea and Westminster Hospital, London. PATIENTS: Ten asymptomatic Centers for Disease Control and Prevention stage II HIV-seropositive control subjects and 36 HIV-seropositive patients with a single newly diagnosed and untreated opportunistic infection [10 with microsporidial or cryptosporidial diarrhoea, 10 with Pneumocystis carinii pneumonia, nine with cytomegalovirus enteritis and seven with systemic Mycobacterium avium-intracellulare]. MAIN OUTCOME MEASUREMENTS: Subjects had measurements of resting energy expenditure using indirect calorimetry and of body composition using dual energy X-ray absorptiometry. RESULTS: Subjects with protozoal diarrhoea had a decreased resting energy expenditure (P < 0.05) and decreased body fat (P < 0.01). Subjects with P. carinii pneumonia had an elevated resting energy expenditure (P < 0.05). Subjects with systemic M. avium-intracellulare had an elevated resting energy expenditure (P < 0.05) and decreased skeletal muscle mass (P < 0.05). Subjects with cytomegalovirus enteritis had a non-significant elevation of resting energy expenditure with a non-significant loss of both fat and lean tissue. CONCLUSION: Subjects with protozoal diarrhoea show a starvation response to infection and subjects with systemic M. avium-intracellulare show a cachectic response. Since there is a variation in the metabolic response to opportunistic infection in AIDS patients, nutritional management should be directed according to the specific cause.

Short-term growth hormone administration at the time of opportunistic infections in HIV-positive patients.

OBJECTIVES: A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss. METHODS: HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety. RESULTS: There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group. CONCLUSIONS: A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.

Energy balance in asymptomatic HIV infection.

OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

Absorbed dose to man from the Se-75 labeled conjugated bile salt SeHCAT: concise communication.

The absorbed radiation dose that would result from the oral or intravenous administration of SeHCAT (23-[75Se]selena-25-homotaurocholate) has been calculated using the MIRD tables and formulas and data from measurements of whole-body distribution and from long-term whole-body counting in rats, mice, and man. When SeHCAT is administered to normal subjects, the gallbladder is the critical organ, receiving 12 mrad (oral dose) or 22 mrad (i.v.) per microcurie. The whole-body dose is 1 mrad/microCi, whatever the route of administration. In severe hepatic failure the liver might receive 200 mrad/microCi. The activity likely to be used in routine clinical practice is 10 microCi. Where a whole-body counter is used, an activity of 1 microCi has proved adequate. Even at an administered activity of 25 microCi, the absorbed dose is small compared with established techniques of investigating the gastrointestinal tract.

Enterohepatic circulation in man of a gamma-emitting bile-acid conjugate, 23-selena-25-homotaurocholic acid (SeHCAT).

A conjugated bile acid, 23-selena-25-homotaurocholic acid (SeHCAT), labeled with the gamma emitter Se-75, has been evaluated in man. Absorption and excretion were compared with that of simultaneously administered [23-14C]cholic acid. SeHCAT is absorbed quantitatively following oral administration, secreted into the bile at the same rate as cholic acid, reabsorbed from the small intestine, and resecreted. It is not absorbed when the terminal ileum has been excised or bypassed. SeHCAT is therefore the first of a new class of radiopharmaceuticals, namely, gamma-emitting tracers of the complete cycle of the enterohepatic circulation. Its use will simplify investigation of the functional state of the terminal ileum by eliminating the need to collect and process feces.

Evidence for infanticide in bottlenose dolphins: an explanation for violent interactions with harbour porpoises?

Most harbour porpoises found dead on the north-east coast of Scotland show signs of attack by sympatric bottlenose dolphins, but the reason(s) for these violent interactions remain(s) unclear. Post-mortem examinations of stranded bottlenose dolphins indicate that five out of eight young calves from this same area were also killed by bottlenose dolphins. These data, together with direct observations of an aggressive interaction between an adult bottlenose dolphin and a dead bottlenose dolphin calf, provide strong evidence for infanticide in this population. The similarity in the size range of harbour porpoises and dolphin calves that showed signs of attack by bottlenose dolphins suggests that previously reported interspecific interactions could be related to this infanticidal behaviour. These findings appear to provide the first evidence of infanticide in cetaceans (whales, dolphins and porpoises). We suggest that infanticide must be considered as a factor shaping sociality in this and other species of cetaceans, and may have serious consequences for the viability of small populations.

Isolated lung perfusion with melphalan for the treatment of metastatic pulmonary sarcoma.

OBJECTIVE: Isolated lung perfusion allows the delivery of high-dose chemotherapy to the perfused lung and is an efficacious modality in the treatment of pulmonary metastases in the rat. Melphalan activity in this model was investigated. METHODS: TOXICITY STUDY: Maximum tolerated dose of melphalan delivered by means of isolated lung perfusion was determined by survival after contralateral pneumonectomy. PHARMACOKINETICS STUDY: Nineteen rats were treated with melphalan administered either by isolated lung perfusion (2 mg) or intravenously (2 mg or 1 mg). Lung, pulmonary effluent, and serum melphalan were analyzed by high-pressure liquid chromatography. EFFICACY STUDY: On day 0, 41 rats received an intravenous injection of 5 x 10(6) methylcholanthrene induced sarcoma cells. On day 7, rats either received intravenous melphalan (2 mg [n = 10]; 1 mg [n = 8]) or underwent left isolated lung perfusion with 2 mg of melphalan (n = 12). Isolated lung perfusion with buffered hetastarch in sodium chloride (Hespan, n = 11) was used as control. On day 14, pulmonary nodules were counted. TOXICITY: Maximum tolerated dose of melphalan delivered buy means of isolated lung perfusion was 2 mg. PHARMACOKINETICS: Left lung melphalan level was significantly higher in the isolated lung perfusion group (62.2 +/- 34.3 microg/gm lung) than in the intravenous treatment groups (6.9 +/- 1.9 microg/gm lung and 3.3 +/- 0.9 microg/gm lung, respectively) (p = 0.0002). EFFICACY: Significantly fewer left lung nodules were found in animals receiving melphalan by means of isolated lung perfusion (7 +/- 10) than in the groups receiving intravenous melphalan (60 +/- 21) or buffered hetastarch by isolated lung perfusion (84 +/- 52) (p = 0.01 and p = 0.0001, respectively). CONCLUSION: Isolated lung perfusion with melphalan is safe and effective in the treatment of pulmonary sarcoma metastases in the rat.

Establishment of an experimental intrapulmonary tumor nodule model.

BACKGROUND: A pulmonary tumor model is necessary to study the biology and therapy of lung cancer. Methods to establish a solitary intrapulmonary nodule are not well defined. Two methods for solitary intrapulmonary tumor nodule development in the Fischer rat are described. METHODS: Methylcholanthrene-induced sarcoma cell suspensions were introduced into lung parenchyma of Fischer rats via limited thoracotomy and lung puncture, or instilled into a distal airway after tracheal puncture and catheterization. Intrapulmonary tumor location, implantation mortality, procedure length, and animal survival were recorded. RESULTS: Single pulmonary nodules developed at the implanted position in 100% (n = 320) and 95% (62/65) of animals after direct injection into the pulmonary parenchyma or via tracheal puncture and instillation. Operative mortality was 2% and 5% via lung or tracheal implantation, respectively. Less than 5 minutes was required for each implantation. Mean survival time was 24 +/- 2 and 26 +/- 6 days after lung or tracheal implantation in animals allowed to survive until tumor-induced death. CONCLUSIONS: These easily performed, reproducible methods of establishing solitary intrapulmonary tumors are useful tools for lung cancer research.

Sequential bilateral isolated lung perfusion in the rat: an experimental model.

BACKGROUND: A model of isolated single-lung perfusion in the rat has been established in our laboratory to study the chemotherapeutic treatment of pulmonary metastases. A sequential bilateral isolated lung perfusion model was designed to investigate the feasibility of staged perfusions in the rat. METHODS: Twenty-four Fischer rats were randomized into three experimental groups of 8 rats each. All rats underwent left isolated lung perfusion. One, 2, or 3 weeks later, the rats in groups I, II, and III, respectively, underwent contralateral (right) perfusion. Five control animals (group IV) underwent sequential bilateral sham thoracotomies 1 week apart. Arterial blood gas analysis was performed 1 week after the second operation in the rats in groups I and IV. RESULTS: All animals survived the first operation, with 100% (8/8), 75% (6/8), and 100% (8/8) of the animals in perfusion groups I, II, and III, respectively, surviving the second operation. All control animals (group IV) survived the second sham thoracotomy. Arterial blood gas analysis did not show a significant difference in the oxygen or carbon dioxide partial pressure or the pH between group I and IV (p = 0.32, 0.96, and 0.76, respectively). CONCLUSIONS: Our experiments demonstrate that sequential bilateral isolated lung perfusion is safe in and well tolerated by the rat. This model can be used to investigate the safety and efficacy of staged perfusions with chemotherapeutic agents in the treatment of bilateral pulmonary metastases in the rat.

Nonoperative management of tracheal laceration during endotracheal intubation.

Tracheal laceration is a rare but potentially devastating complication of endotracheal intubation. Traditional management of intubation-related tracheal laceration is operative. Nonoperative management of a woman noted to have a tracheal laceration during intubation is described. Criteria by which nonoperative treatment can be considered are outlined.

Isolated lung perfusion for patients with unresectable metastases from sarcoma: a phase I trial.

BACKGROUND: In patients with unresectable pulmonary metastases from sarcoma, systemic chemotherapy has had limited efficacy possibly because of dose-limiting toxicities. Isolated lung perfusion is an alternative method of delivering high-dose chemotherapy to the lungs while minimizing systemic toxicities. We present the results of our Phase I trial of isolated lung perfusion with doxorubicin hydrochloride in such a group of patients. METHODS: From May 1995 to June 1997, 8 patients with unresectable metastases from sarcoma limited to the lungs underwent isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at 40 mg/m2 was used. Seven patients were treated with a dose of 40 mg/m2 or less, and 1 patient received 80 mg/m2. Blood, tumor, and normal lung samples were obtained at various time points during the operation. Patients were evaluated for cardiac, pulmonary, and other toxicities. RESULTS: The doxorubicin concentrations in both normal lung and tumor correlated directly with the amount of doxorubicin in the perfusate. The tumors took up less doxorubicin than the lung. All patients had minimal or undetectable systemic levels of doxorubicin at the conclusion of the perfusion. There were no cardiac or other systemic toxicities. In the 7 patients perfused with 40 mg/m2 or less of doxorubicin, there was a significant decrease in the forced expiratory volume in 1 second and a trend toward a significant decrease in diffusing capacity. The patient who received 80 mg/m2 underwent lung scanning postoperatively, and scans showed no ventilation or perfusion in the perfused lung. There were no perioperative deaths. Two patients are alive with disease, and 6 patients died of disease. The median follow-up is 11 months and the longest, 31 months. There were no partial or complete responses. One patient had stabilization of disease in the perfused lung, whereas the lesions in the untreated lung progressed markedly. CONCLUSION: Isolated lung perfusion is well tolerated by patients and effectively delivers high doses of doxorubicin to the lung and tumor tissues while minimizing systemic toxicities. A single dose of 80 mg/m2 resulted in substantial injury to the lung. There were no partial or complete responses in patients perfused with doxorubicin at the maximum tolerated dose of 40 mg/m2. Isolated lung perfusion remains a model for testing new and innovative therapies for metastatic sarcoma.