Practical management of patients with non-small-cell lung cancer treated with gefitinib.

PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.     

Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts.

The first superior vena cava-pulmonary artery shunt (Glenn shunt) in our series was performed in February 1958. From then through September 1988, 91 patients have undergone this procedure for a wide variety of congenital defects. We here report follow-up data available on all patients. Ages ranged from 2 days to 46 years (mean 6.8). Diagnoses were as follows: tricuspid atresia, 27; single ventricle, 22; tetralogy of Fallot, 14; D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis, 9; D-transposition, 5; Ebstein's anomaly, 4; pulmonary atresia + intact septum, 4; and others, 6. The hospital mortality rate was 7.7% (one death in the last 53 patients, 1.9%). Five deaths occurred in patients less than 6 months old. There were 20 late deaths (22%) with actuarial survival rates of 84% and 66% at 10 and 20 years, respectively. Pulmonary arteriovenous fistula formation was seen in 18 patients (19.7%), six of whom have undergone therapeutic embolization with improvement in saturation. The prevalence of pulmonary arteriovenous fistula increases with time after shunt. No long-term shunt thrombosis or stricture formation was seen. Fifty percent of shunts were still functioning at 20 years. Palliation was limited because of decrease in blood flow to the contralateral pulmonary artery, collaterals between the inferior and superior venae cavae, and pulmonary arteriovenous fistula formation. Improvement in saturation was obtained in eight otherwise inoperable patients by creation of a right axillary arteriovenous fistula up to 19 years after the Glenn shunt. Three patients had conversion of a Blalock-Taussig shunt to a Glenn shunt with improvement in congestive heart failure. Twenty-six patients have undergone a Fontan procedure with two deaths. Compared with the group having a Fontan procedure without a prior Glenn operation, there was no difference in early or late mortality. Thirty years after a Glenn shunt, the first patient in this series is working full time after having undergone a modified Fontan procedure in 1981. We conclude that the Glenn connection, usually with supplemental procedures to enhance oxygenation, has provided excellent physiologic palliation with low mortality up to 30 years with no late thrombosis or stricture formation. The incidence of pulmonary arteriovenous fistula increases with time and can be effectively treated with embolization. Physiologic repair after the Glenn shunt carries a low mortality. Although currently used infrequently, superior vena cava-pulmonary artery shunting remains a useful method of palliation in selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Induction of an invasive phenotype in benign tumor cells with a laminin A-chain synthetic peptide.

K-1735 clones 10 and M2 are cell lines cloned from a UV-induced murine melanoma. While both lines are highly tumorigenic, only the M2 cells are highly invasive in vitro and metastatic in vivo. Here we have exposed the clone 10 cells to the synthetic peptide PA22-2, which contains the IKVAV sequence from the A chain of laminin and which, like laminin, induces collagenase IV production and enhances metastasis formation by B16F10 cells. Zymogram analysis of conditioned media from clone 10 cells cultured on the peptide demonstrated a dose-dependent increase in collagenase IV activity. When clone 10 cells were cultured on a reconstituted basement membrane (Matrigel), this peptide caused an invasive phenotype comparable to the M2 cells. The invasive clone 10 cells were, however, unable to form lung colonies in vivo in the presence of this peptide. We conclude that this peptide represents an active site on laminin which is able to stimulate the invasiveness of this tumor cell line, but that this activity is not sufficient to confer metastatic potential.     

Industrial hygiene, chemical and biological assessments of exposures to a chlorinated phenolic sapstain control agent

A two-year study of the occupational exposure of workers in a lumber mill to a wood preservative containing chlorophenol has been conducted. The methods were biological (urine) monitoring, industrial hygiene assessment and a questionnaire related to worker-perceived health effects. Approximately 40 workers exposed to the wood preservative and 40 unexposed controls working in other locations of the plant participated in the study. Evaluation of work conditions, assessment of urinary levels of tetra- and pentachlorophenol, and administration of a medical questionnaire were performed at a six-month intervals over a two-year period. Industrial hygiene ratings of exposures and adequacy of protection were evaluated in relation to the results of biological monitoring. Workers who came into contact with freshly treated and still wet wood had consistently higher urinary levels of tetrachlorophenol. Workers stationed adjacent to the spray applicator also had higher tetrachlorophenol levels. There was no statistically significant relationship between the subjective ratings by the industrial hygienist of exposure and adequacy of worker protection with the urinary levels of tetrachlorophenol. Nor was there a consistent pattern linking exposure ratings with adequacy of protection. The short half-life of tetrachlorophenol in the urine makes this a good indicator of only the most recent exposure. The differences in urinary levels between controls and exposed workers were large, with averages of 240.4 ppb for exposed workers and 14.6 for controls. Traditional industrial hygiene evaluation techniques, in conjunction with biological monitoring, proved to be the most effective method of assessing both exposure and work practices. Exposed workers reported a statistically significant increase of positive answers to known signs and symptoms of chlorophenol exposure compared with the controls. There was no statistically significant relationship between the number of these health problems reported and the mean urinary levels of tetra- or pentachlorophenol for the exposed group; however, for certain variables (heavy vs. light exposure, inadequate vs. adequate protection, greater than 100 ppb urinary tetrachlorophenol vs. less than 100 ppb), those with heavier exposure, inadequate protection or higher urinary tetrachlorophenol reported on the average more health problems over the two-year period. Firm statistical conclusions could not be drawn because of the small size of the study population.     

Sonography of hypertrophic pyloric stenosis: frequency and cause of nonuniform echogenicity of the thickened pyloric muscle.

In hypertrophic pyloric stenosis, the muscle is typically described as hypoechoic on sonography. However, we have frequently noted a nonuniform pattern; the pyloric muscle seen in the transverse plane is more echogenic in the near and far fields and less echogenic on the sides. The muscle also appears almost as echogenic as the liver on midline longitudinal sonograms. To establish the frequency of these findings, we reviewed the sonograms of 71 infants with hypertrophic pyloric stenosis. The muscle was imaged directly during surgery in three patients. In an in vitro experiment, muscle arranged to stimulate the pyloric ring was scanned in a water bath. Then, using two sections of muscle, we compared the echogenicity when scanning in a plane perpendicular to the long axis of the muscle fibers with that seen with the beam parallel to the long axis of the muscle fibers. In the transverse plane, nonuniform echogenicity of the pyloric muscle was seen in 59 (98%) of 60 patients. In the midline longitudinal plane, the muscle was equal to or slightly less echogenic than the liver in all patients. Both the in vivo and in vitro studies show that the echogenicity varies with the relationship of the ultrasound beam to the orientation of the circular muscle fibers; this phenomenon is known as the anisotropic effect. Our results show that nonuniform echogenicity of the hypertrophied pyloric muscle is a characteristic sonographic finding caused by the anisotropic effect, which is related to the orientation of the ultrasound beam with respect to the circular fibers of the pyloric muscle.