Mucin gel formed by tumorigenic squamous lung carcinoma cells has Le(a)-X oligosaccharides and excludes antibodies from underlying cells.

Cells of cloned lines of human squamous lung carcinomas elaborate large glycoproteins that are associated with their tumorigenic potential. Two groups of clones (called Le(a)-X-positive and Le(a)-X-negative) were studied that either do or do not express the Le(a)-X oligosaccharide associated with large glycoproteins and mucins secreted by these clones. Le(a)-X-positive cells elaborate a mucin gel complex associated with their apical surfaces, which appears as a mosaic of extracellular plates. Clones of this type are tumorigenic in nude rodents when injected s.c. or when introduced into the lungs via intrabronchial aerosol. By contrast, the Le(a)-X-negative clones do not form extracellular plates and are not tumorigenic in the lungs or subcutaneously. We demonstrate that the extracellular plates of Le(a)-X-positive cells exclude antibodies from interacting with the underlying squamous lung carcinoma cells and may therefore exert an immunoprotective effect. In support of this possibility it was found that: (a) There is a substantial inflammatory cell infiltrate associated with regressing nodules of Le(a)-X-negative cells in nude rodent lung and subcutaneous nodules, while there is no observable infiltration associated with progressing Le(a)-X-positive tumors. (b) In the brain (an immunoprivileged site) tumors develop and progress when either Le(a)-X-negative or -positive cells are introduced.

Irradiated nude rat model for orthotopic human lung cancers.

The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.

Malignant fibrous histiocytoma of the heart presenting as unilateral pulmonary thromboembolism and infarct.

A malignant fibrous histiocytoma of the heart located at the pulmonic valve and thrombotic occlusion of branches of the left pulmonary artery with pulmonary infarct were found at autopsy in a 77-year-old man. The thrombi contained malignant cells. The patient had undergone left upper lobectomy four years earlier for thromboembolism with infarct, and review of the slides from that procedure revealed similar malignant cells within thrombi. This case is remarkable for the slow growth of the neoplasm and the prolonged survival of the patient, without specific therapy.

A Markov model of the natural history of prostate cancer.

The objective of this study was to lay a foundation for future cost-benefit analyses evaluating the public health impact of treatment and screening protocols for prostate cancer. Specifically we wanted to define the relative impact on cancer-specific mortality rates of the individual epidemiological components: pathological incidences by age groups, cancer progression rates, and the effect of competing causes of death, assuming expectant management (i.e. no definitive treatment). A biological model of prostate cancer incidence and progression was converted into a standard Markov tree where competing causes of death could occur. Weighted averages of progression rates were obtained from clinical studies. Separate cohorts of 30 year old black and white men were followed for 50 years. The model yielded cancer-specific mortality rates, overall mortality rates, and pathologic prevalences for both white and black males, consistent with the literature. Sensitivity analyses showed that of all the parameters studied, the pathological incidence of cancer in men under 50 years of age had the greatest impact on the cancer-specific mortality rates. Also important was the annual probability of progression of A1 lesions. However the other parameters including pathological incidence in older males, and progression from locally-extensive to metastatic lesions had much smaller effects. In summary, this model correlates the clinical literature with the epidemiology of prostate cancer and can be used for further decision analyses. We recommend that future research be done to more precisely quantify the pathological incidence of prostate cancer in men under 50-60 years of age. More certainty is also needed before generalizing the results of relatively small A1 series to millions of men, since A1 progression rates critically affect the eventual cancer-specific mortality. Enough uncertainty remains at this point however, that we cannot advocate widespread screening for prostate cancer until its merit be demonstrated either by the definitive long term study, or by examination of costs and quality-of-life-adjusted benefits.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

Pharmaceutical cost growth under capitation: a case study.

Rising drug spending has generated concern among purchasers and policymakers. This paper compares drug cost growth in a capitated system with that in managed care systems that generally did not place physicians directly at risk for drug spending. We focus on cost growth because a substantial body of literature indicates that managed care interventions that reduce the level of costs may not influence the rate of cost growth. Drug cost growth under capitation initially was below that of other systems but still above targeted rates. Over time the capitation rates rose, the amount of risk transferred to physicians declined, and spending growth accelerated.

The danger of applying group-level utilities in decision analyses of the treatment of localized prostate cancer in individual patients.

The optimal management strategy for men who have localized prostate cancer remains controversial. This study examines the extent to which suggested treatment based on the perspective of a group or society agrees with that derived from individual patients' preferences. A previously published decision analysis for localized prostate cancer was used to suggest the treatment that maximized quality-adjusted life expectancy. Two treatment recommendations were obtained for each patient: the first (group-level) was derived using the mean utilities of the cohort; the second (individual-level) used his own set of utilities. Group-level utilities misrepresented 25-48% of individuals' preferences depending on the grade of tumor modeled. The best kappa measure achieved between group and individual preferences was 0.11. The average quality-adjusted life years lost due to misrepresentation of preference was as high as 1.7 quality-adjusted life years. Use of aggregated utilities in a group-level decision analysis can ignore the substantial variability at the individual level. Caution is needed when applying a group-level recommendation to the treatment of localized prostate cancer in an individual patient.

Lung tolerance to hyperthermia by in vivo perfusion.

In vivo isolated lung perfusion is a novel technique for targeting anticancer therapy to the lung while avoiding systemic toxicity as normal lung toxicity from the antitumour therapy becomes the limiting factor. This study was performed to investigate the effects of hyperthermia on lung function in an intact animal model in which both acute and subacute toxicity could be monitored. Dogs underwent in vivo isolated lung perfusion. A control group was perfused to a lung temperature of 37 degrees C (group 1) and two other groups were treated in an identical manner except that the perfusion temperature was 43 degrees-44.8 degrees C in group 2 and greater than 45 degrees C in group 3. An assessment of lung injury was performed pre-perfusion, immediately post-perfusion and 2 weeks post-perfusion by measurement of extravascular lung water (Qev), serotonin uptake and wet weight to dry weight ratio. Our findings showed that the lung was tolerant to hyperthermia up to about 44 degrees C for 1 h. Analysis of 4 animals who survived perfusion above 3/44.0 degrees C showed a highly significant decrease in serotonin uptake between pre- and post-perfusion values (82.4 +/- 1.2 vs 40.4 +/- 3.9, P less than 0.02); at 2 weeks serotonin uptake had returned to normal in all 3 dogs. Fulminating pulmonary oedema developed at temperatures over 45 degrees C. Serotonin uptake may be a sensitive predictor of thermal lung injury.

Thoracic empyema: causes, diagnosis, and treatment.

Thoracic empyema is a disease that has been recognized for centuries. The principles of management as stated by Hippocrates remain more or less unchanged. Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases. With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis. When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay. The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered. If the original infection is adequately treated, empyema rarely occurs. Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention. These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment. Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management.

Right ventricular needle embolus in an injecting drug user: the need for early removal.

This case report describes an unusual cardiac complication in a 22 year old, female injecting drug user. The retention of two fractured injection needles at the site of intravenous injection in the groin, and the subsequent embolisation of one to the right ventricle, predisposed to recurrent local and systemic infections, and endocarditis. Two years later, the needle was completely embedded in the wall of the right ventricle and not suitable for transvenous removal. Removal of the retained and/or embolised needle at an earlier stage would have precluded these complications.

Methods for analyzing referral patterns.

OBJECTIVE: To develop a sound method to identify patient and physician characteristics that influence specialty referrals. DESIGN: A retrospective cohort analysis of medical claims data from 1996 supplemented with surveys of primary care physicians. SETTING: A 600-member independent practice association in southeastern Michigan that provided care for 90,000 members of an HMO. PATIENTS: Five cohorts, each of 2,000 to 6,000 patients with diagnoses that could be referred to cardiologists, ophthalmologists, pulmonologists, orthopedists, or general surgeons. MAIN RESULTS: The referral rates for the different cohorts ranged from 1% to 7%. The discriminatory ability of the multivariate logistic models (c-statistic) ranged from 0.66 to 0.79. The likelihood of referral was associated with the patient's diagnoses and medications and with the referring physician's age, years out of medical school, satisfaction with the specialty being referred to, and the importance of making or confirming a diagnosis. CONCLUSIONS: Because these methods were not difficult to implement and the results were credible, we believe that other organizations should be able to use them.

A decision analysis for treatment of clinically localized prostate cancer.

OBJECTIVE: To determine the preferred treatment of clinically localized prostate cancer. DESIGN: Cancer grade, patient age, and comorbidities are considered in a Markov model with Monte Carlo sensitivity analyses. Large and recent pooled analyses and patient-derived utilities are included. RESULTS: Principal findings suggest benefit for radical prostatectomy relative to watchful waiting for men under 70 years of age with low to moderate comorbidity. Men older than 70 with high comorbidity and disease of low to moderate grade do better with watchful waiting. CONCLUSIONS: Cohort-level sensitivity analyses suggest a quality-based treatment benefit for radical prostatectomy for younger men and treatment harm for older men. Tailored patient and clinician decisions remain necessary, especially for men older than 70 in good health but with aggressive cancers.

Survival estimates for patients with abnormal swallowing studies.

OBJECTIVE: To better understand the life expectancy of patients who have an abnormal videofluoroscopic swallowing study. DESIGN: Retrospective cohort study. The common starting point was the time of the severely abnormal swallowing study. Hospital charts were reviewed for clinical variables of potential prognostic significance by reviewers blinded to the outcome of interest, survival time. SETTING: A university-affiliated, community teaching hospital. PATIENTS: One hundred forty-nine hospitalized patients who were deemed nonoral feeders based on their swallowing study. Patients excluded were those with head, neck, or esophageal cancer, or those undergoing a thoracotomy procedure. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic variables and time until death or censoring were measured. Overall 1-year mortality was 62%. Multivariable Cox proportional hazards analyses identified four variables that independently predicted death: advanced age, reduced serum albumin concentration, disorientation to person, and higher Charlson comorbidity score. Eighty patients (54%) subsequently underwent placement of a percutaneous endoscopic gastrostomy (PEG) tube after their swallowing study. CONCLUSIONS: Mortality is high in patients with severely abnormal swallowing studies. Common clinical variables can be used to identify groups of patients with particularly poor prognoses. This information may help guide discussions regarding possible PEG placement.

Spontaneous pneumothorax in a patient with an azygos lobe.

The association between a spontaneous pneumothorax and an azygos lobe is surprisingly rare. A case is reported in which surgical management was difficult; it is suggested that thoracotomy is preferable to video-assisted thoracoscopic surgery in this situation. It is possible that the presence of an azygos lobe might protect against the subsequent development of a spontaneous pneumothorax, and the possible mechanism of this is discussed.

Endoscopy assisted microthoracotomy: initial experience.

BACKGROUND: Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures, which have traditionally required formal thoracotomy. METHODS: Twenty one patients (M:F 1.2:1; mean (SD) age 47.1 (18.8), range 17-75 years) underwent endoscopic intrathoracic surgery. Eight had unidentified peripheral masses on the chest radiograph, eight required lung biopsy, and five had recurrent or persisting pneumothoraces. Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. RESULTS: There were no complications or deaths, though one patient developed a second pneumothorax seven days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home from two to six days after surgery (mean (SD) 3.7 (1.2) days). CONCLUSION: Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment.

A guide for planning community-oriented health care: the health sector resource allocation model.

The objective of this study was to demonstrate the value of a planning model for the design and evaluation of community health services. The health status of Washtenaw County, Michigan was modeled. Data were obtained from the Michigan Department of Public Health, Medstat Systems, and the medical literature for 32 diseases or conditions, representing approximately 85% of causes of death and 56% of medical payments (excluding medication costs). An expanded life-table approach was used for 16 age-and sex-matched cohorts exposed to a disease attack rate, access-to-care rate, case fatality rate, morbidity, and costs. Rates can be modified to reflect changes due to treatment, secular trends, or prevention programs. Two alternative delivery methods were considered to show the potential impact of reducing cardiovascular deaths (worksite initiative), or increasing utilization of services (lay health promotion) on county health status and costs over time. Deaths, bed days, and annual medical payments were the main outcome measurements. Cardiovascular and cancer conditions are and will be the primary causes of death in this population. The most important causes of bed days are musculoskeletal conditions, chronic obstructive pulmonary disease, accidents, strokes, and depression. The major health-care payments are for angina pectoris and/or other cardiac conditions, musculoskeletal conditions, accidents, prenatal care, and/or childbirth, and depression. The two alternative scenarios illustrate how reductions in mortality are not necessarily equated with similar improvements in morbidity or costs. This model presents an overview of the current and projected health status of a community. With such a planning tool, a community can better understand the impact of potential prevention or intervention programs, and help design its health-care system within the constraints of available resources.

An unusual combination of diaphragmatic hernias in a patient presenting with the clinical features of restrictive pulmonary disease: report of a case.

The combination of a Morgagni hernia and a paraesophageal hernia in adults is very rarely encountered in clinical practice. In fact, to our knowledge, only three cases of this condition, which is probably a coincidental occurrence, have been reported in the medical literature. We discuss the management of a 74-year-old man found to have combined Morgagni and paraesophageal hernia who presented with clinical features of a restrictive pulmonary disease.

Serial prostate specific antigen screening for prostate cancer: a computer model evaluates competing strategies.

PURPOSE: We compare prostate specific antigen (PSA) screening strategies in terms of expected years of life saved with screening, number of screens, number of false-positive screens and rates of over diagnosis, defined as detection by PSA screening of patients who would never have been diagnosed without screening. MATERIALS AND METHODS: A computer model of disease progression, clinical diagnosis, PSA growth and PSA screening was used. Under baseline conditions, when screening is not considered, the model replicates clinical diagnosis and disease mortality rates recorded by the Surveillance, Epidemiology and End Results Program of the National Cancer Institute in the mid 1980s. RESULTS: Biannual screening with PSA greater than 4.0 ng./ml. was projected to reduce the number of screens and false-positive tests by almost 50% relative to annual screening while retaining 93% of years of life saved. With annual screening use of an age specific bound for PSA to consider a test positive instead of the standard 4.0 ng./ml. was projected to reduce false-positive screens by 27% and over diagnosis by a third while retaining almost 95% of years of life saved. Sensitivity analyses did not change the relative efficacy of biannual screening. CONCLUSIONS: Under the model assumptions biannual PSA screening is a cost-effective alternative to annual PSA screening for prostate cancer. With annual screening use of an age specific bound for PSA positivity appears to reduce false-positive results and over diagnosis rates sharply relative to a bound of 4 ng./ml. while retaining most of the survival benefits.