A vision of individualized medicine in the context of global health.

The Three Musketeers' slogan of solidarity-"All for one, and one for all"-aptly describes how the emerging science of individualized medicine (IM) promises to transform the value of the medical care we deliver to specific individuals as well as global populations.

Multiple lung abscesses due to Ochroconis gallopavum, a dematiaceous fungus, in a nonimmunocompromised wood pulp worker.

An occurrence of multiple chronic lung abscesses managed by lobectomy is described. These abscesses were present for 13 years in the patient, a nonimmunocompromised wood pulp worker. The patient had hemoptysis at presentation. The organism isolated was Ochroconis gallopavum, a dematiaceous fungus known to cause disease in immunocompromised patients and epidemic encephalitis in poultry. The fungus is typically found in warm environments and in decaying compost; for this reason, we postulate that his illness was occupationally acquired.

Contrast transesophageal echocardiography in the diagnosis and localization of diffuse pulmonary telangiectasias.

Pulmonary arteriovenous fistulas are rare, usually related to the Rendu-Osler-Weber syndrome, and are detected by chest CT scan or pulmonary angiography. In a 14-year-old boy without Rendu-Osler-Weber syndrome, but with clinical evidence of a right-to-left shunt, ancillary diagnostic studies were negative for pulmonary arteriovenous fistulas, and the final diagnosis was made by contrast transesophageal echocardiography. Saline echo-contrast medium injected peripherally was seen emerging from each pulmonary vein and filling the left chambers. These findings, in light of other negative test results, established the diagnosis of diffuse telangiectasias at the capillary level in both lungs. After 6 years of medical therapy, the patient remains cyanotic but functions well.

Photodynamic therapy for early stage squamous cell carcinoma of the lung.

OBJECTIVE: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

An unusual case of carcinoma polyarthritis with associated vasculitis.

This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and "rheumatoid-like" nodules. Two months after the administration of combined-modality therapy for stage IIIA non-small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.

Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients.

OBJECTIVE: To characterize the pulmonary hemodynamics and identify predictors of pulmonary hypertension in a group of patients before liver transplantation and to determine whether pulmonary hypertension in these patients is related to survival. MATERIAL AND METHODS: In 362 patients before their first liver transplantation (between 1985 and 1993), the clinical history, laboratory data, and results of pulmonary function tests were recorded. Pulmonary artery (PA) catheterization was performed after induction of anesthesia at the time of transplantation. Monthly follow-up was maintained. RESULTS: A hyperdynamic circulation was often present -- an increased mean cardiac output (7.6 L/min), increased mean PA pressure (20.9 mm Hg), correlation of mean PA pressure with cardiac output (r = 0.25; P<0.001), and decreased mean pulmonary vascular resistance (60 dynes times s/cm5). Mean PA pressures were more than 25 mm Hg in 72 patients (20%). Pulmonary hypertension (defined as mean PA pressure of more than 25 mm Hg and pulmonary vascular resistance in excess of 120 dynes times s/cm5) occurred in 15 patients (4%). Pulmonary function tests revealed obstruction in 7%, restriction in 18%, and low diffusing capacity in 46%. By univariate analysis, lower forced expiratory volume in 1 second, forced vital capacity, and total lung capacity were the only preoperative factors associated with pulmonary hypertension (P<0.05). Survival was significantly lower in patients with acute fulminant hepatitis (P<0.001), the group with the highest mean PA pressure, than in those with other diagnoses. Increased PA pressures or mild to moderate pulmonary hypertension was not found to be associated with a worse survival by univariate or multivariate analysis. CONCLUSION: Increased PA pressure is common in liver transplant patients (20%). "True" pulmonary hypertension occurred in only 4% of our patients and was not associated with an adverse outcome.

Photodynamic therapy. Its use in the management of bronchogenic carcinoma.

Photodynamic therapy is an investigational treatment of various types of carcinoma. It involves a photosensitizing agent which, when exposed to light of the proper wavelength, forms toxic oxygen radicals that result in cell death. This article describes its current use in the management of bronchogenic carcinoma.

Failure of hepatopulmonary syndrome to resolve after liver transplantation and successful treatment with embolotherapy.

The hepatopulmonary syndrome is an uncommon accompaniment of chronic liver disease. The outcome of this disorder after orthotopic liver transplantation is variable. We describe a patient with the hepatopulmonary syndrome who underwent orthotopic liver transplantation for autoimmune hepatitis. Her platypnea and orthodeoxia failed to improve postoperatively. Pulmonary angiography showed large pulmonary arteriovenous shunts that were successfully treated with coil embolotherapy.

Referral selection bias in the Medicare hospital mortality prediction model: are centers of referral for Medicare beneficiaries necessarily centers of excellence?

OBJECTIVE: Although the Health Care Financing Administration (HCFA) uses Medicare hospital mortality data as a measure of hospital quality of care, concerns have been raised regarding the validity of this concept. A problem that has not been fully evaluated in these data is the potential confounding effect of illness severity factors associated with referral selection and hospital mortality on comparisons of risk-adjusted hospital mortality. We address this issue. DATA SOURCES AND STUDY SETTING: We analyzed the 1988 Medicare hospitalization data file (MEDPAR). We selected data on patients treated at the two Mayo Clinic-associated hospitals in Rochester, Minnesota, and a group of seven other hospitals that treat many patients from large geographic areas. These hospitals have had observed mortality rates substantially lower than those predicted by the HCFA model for the period 1987-1990. STUDY DESIGN: Using the multiple logistic regression model applied by HCFA to the 1988 data, we evaluated the relationship between distance from patient residence to the admitting hospital and risk-adjusted hospital mortality. PRINCIPAL FINDINGS: Among patients admitted to Mayo Rochester-affiliated hospitals, residence outside Olmsted County, Minnesota was independently associated with a 33 percent lower 30-day mortality rate (p < .001) than that associated with residence in Olmsted County. When patients at Mayo hospitals were stratified by residence (Olmsted County versus non-Olmsted County), the observed mortality was similar to that predicted for community patients (9.6 percent versus 10.2 percent, p = .26), whereas hospital mortality for referral patients was substantially lower than predicted (5.0 percent versus 7.5 percent, p = < .001). After incorporation of the HCFA risk adjustment methods, distance from patient residence to the hospitals was also independently associated with mortality among the Mayo Rochester-affiliated hospitals and seven other referral center hospitals. CONCLUSIONS: The HCFA Medicare hospital mortality model should be used with extreme caution to evaluate hospital quality of care for national referral centers because of residual confounding due to severity of illness factors associated with geographic referral that are inadequately captured in the extant prediction model.

The use of prosthetic stents in tracheobronchial, gastrointestinal, and genitourinary diseases.

The concept of using a stent to maintain patency of a lumen is not new. As early as 1969, stents were being investigated in the peripheral arterial system as a means of preventing restenosis after dilatation by balloon angioplasty (Dotter, 1969). Since then, numerous reports have demonstrated the use of stents in both the peripheral and coronary artery systems (Maass et al., 1982; Dotter et al., 1983; Wright et al., 1985; Palmaz et al., 1987). Concomitant with the investigation of expandable endovascular metal prosthesis has been the development of prosthetic devices for management of tracheobronchial, gastrointestinal, and genitourinary diseases. We will review the use of endoscopically placed prosthetic devices in the management of diseases affecting these systems.

Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue.

We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.

Ancillary therapies in the management of lung cancer: photodynamic therapy, laser therapy, and endobronchial prosthetic devices.

Endoscopic therapy for cancer that involves the tracheobronchial tree is currently available for two distinct types of lesions: radiographically occult superficial squamous cell carcinoma and advanced malignant tumors that cause severe airway obstruction. Photodynamic therapy, which uses a photosensitizing agent, is effective for managing early superficial squamous cell carcinoma. Neodymium:yttrium-aluminum-garnet laser therapy has been effective in the palliative management of patients with advanced or recurrent malignant obstructive airway lesions, either alone or in combination with intraluminal radiation therapy. Most recently, endobronchial prosthetic devices (stents) have been used in patients with advanced airway obstruction. The use of each of these modalities in the management of lung cancer is reviewed.

Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection.

Photodynamic therapy has been used since 1980 at our institution for the management of cancer of the tracheobronchial tree. We identified 13 patients (14 cancers) who were thought to be surgical candidates but who elected to have photodynamic therapy. Thirteen cancers (93 percent) had a complete response to hematoporphyrin-derivative phototherapy. Ten cancers (71 percent) showed a complete response after single treatment, and three (21 percent) required a second course of therapy to achieve a complete response. Ten (77 percent) of 13 cancers have shown no local recurrence. Three patients with persistent cancer underwent surgical resection and were found not to have nodal involvement. We concluded that photodynamic therapy is an alternative to surgical resection in the management of early superficial squamous cell carcinoma.

A prospective study of pulmonary function and gas exchange following liver transplantation.

Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.

Endothelium-derived relaxing factor in pulmonary and renal circulations during hypoxia.

The pulmonary and renal vasculatures, in contrast to the systemic vasculature, constrict during hypoxia. The endothelium has been implicated in mediating these vascular responses to acute hypoxia via the production of endothelium-derived vasoactive factors. The present study, performed in anesthetized dogs, was designed to investigate the role of endothelium-derived relaxing factor (EDRF) to attenuate the vasoconstrictor response of the pulmonary and renal circulations during acute hypoxia. In response to hypoxia, pulmonary (2.2 +/- 0.3 to 4.5 +/- 0.6 mmHg.l-1.min) and renal (0.60 +/- 0.07 to 0.90 +/- 0.14 mmHg.ml-1.min) vascular resistances increased. Inhibition of endogenous EDRF with NG-monomethyl-L-arginine resulted in similar increases in pulmonary (3.0 +/- 0.1 to 4.8 +/- 0.4 mmHg.l-1.min) and renal (0.67 +/- 0.07 to 0.90 +/- 0.09 mmHg.ml-1.min) vascular resistances as in hypoxia. However, in the presence of both hypoxia and EDRF inhibition, an exaggerated pulmonary vascular response was observed (2.2 +/- 0.2 to 7.4 +/- 0.9 mmHg.l-1.min), in contrast to the renal vascular response to EDRF inhibition during hypoxia (0.61 +/- 0.05 to 0.95 +/- 0.10 mmHg.ml-1.min), which was not different from hypoxia or EDRF inhibition individually. The endothelium-derived contracting factor endothelin, which modestly increased during hypoxia (11.7 +/- 1.9 to 15.6 +/- 2.4 pg/ml), may also contribute to this vasoconstrictive response to hypoxia. This study suggests in the intact animal that EDRF serves to oppose the pulmonary vasoconstrictor response to hypoxia and further characterizes the role of endothelium-derived factors in the regulation of vascular function during hypoxia.