In situ breast carcinomas: A population-based study on frequency,growth pattern,and clinical aspects

This study comprises 78 consecutive women, within situ carcinoma of the breast and no evidence of invasion, who were diagnosed and treated surgically from October, 1979 to June, 1986. Lobular carcinoma in situ (LCIS) was found in 30 patients (38%) and ductal carcinoma in situ (DCIS) was identified in 48 patients (62%). The series is a study based in the county of Funen, which has a total female population of 230,028 inhabitants.Epidemiological calculations were carried out in 5 municipalities in the area of Odense University Hospital with 77,477 female inhabitants 20+ years of age according to a predetermined referral scheme and diagnostic procedures. This sub-study revealed a frequency of 9.0 cases ofin situ carcinomas per 10⁵ woman-years and a cumulated risk of 0.53% of havingin situ carcinoma demonstrated within the age range of 20–75 years.In situ lesions made up about 6% of all newly diagnosed breast carcinomas in the region. Furthermore, in about 3% of all breast biopsies and in about 0.3% of all women having mammography due to breast symptoms, anin situ finding was the only malignant change.Pathoanatomically, a distinction could be made between 3 different growth patterns: microfocal, tumor-forming, and diffuse growths. Microfocal lesions comprised a major part (60%) of in situ carcinomas. With one exception, the microfocal cases were chance findings in an otherwise benign breast biopsy, whereas the more aggressive growth patterns (tumor-forming and diffuse) were predominantly clinical and/or mammographic findings, all belonging to the DCIS type. Excisional biopsy or partial mastectomy was performed in 85% of the women with microfocal cases, while such breast preservation procedures were used in only 27% of patients with tumor-forming or diffuse growths.

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Resumen El presente estudio comprende 78 mujeres consecutivas con carcinoma mamarioin situ y sin evidencia de invasíon, quienes fueron diagnosticadas y tratadas quirúrgicamente durante el período 1979 a 1986. Se encontró carcinoma lobular in situ (CLIS) en 30 pacientes (38%) y carcinoma ductal in situ (CDIS) en 48 pacientes (62%). La serie proviene de la región de la isla de Funen, Dinamarca, con una población de 230,028 habitantes.Se realizaron determinaciones epidemiológicas en 5 municipalidades correspondientes a la región del Hospital de la Universidad de Odense, con 77,477 habitantes mujeres de acuerdo a un esquema predeterminado de referencia y a procedimientos de diagnóstico estandarizados. Este subanálisis reveló una frecuencia de 9.0 casos de carcinomasin situ por 10⁵ mujer-años y un riesgo de 0.53% de tener carcinomain situ para las mujeres entre los 20 y los 75 años. Las lesionesin situ representaron alrededor del 6% de la totalidad de los nuevos carcinomas mamarios diagnosticados en la región. Además, en alrededor de 3% de todas las biopsias mamarias y en alrededor de 0.3% de todas las mujeres sometidas a mamografía por razón de presentar síntomas mamarios, el hallazgoin situ fue el único hallazgo de malignidad.Se pudo hacer la diferenciación anatomopatológica entre 3 diferentes patrones de crecimiento: microfocal, formación tumoral, y crecimiento difuso. Las lesiones microfocales comprenden la mayor parte (60%) de los carcinomasin situ. Con una excepción, los casos del tipo microfocal fueron hallazgos fortuitos en biopsias mamarias por lo demás benignas, en tanto que los patrones de crecimiento de tipos más agresivos (formación tumoral y crecimiento difuso) fueron predominantemente hallazgos clínicos y/o mamográficos, todos CDIS. Se realizó biopsias excisional o mastectomía parcial en 85% de las mujeres con el tipo microfocal, en tanto que tales procedimientos de conservación mamaria fueron utilizados en solo 27% de las pacientes con los patrones de formación tumoral de crecimiento difuso.

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Résumé On a étudié les résultats de soixante-dix-huit cancersin situ du sein chez la femme, sans évidence d'envahissement, diagnostiqué et traités chirurgicalement entre octobre 1979 et juin 1986. Il y avait 30 cas (38%) de cancer lobulaire (CL) et 48 cas (62%) de cancer cannalaire (CC). Cette série de patientes provenait du comté de Funen, Danemark, dont la population féminine est de 230,028.L'épidémiologie a été étudiée dans 5 municipalités dans la région de l'Hôpital Universitaire d'Odense où la population féminine est de 77,477 selon une méthode de consultation et de diagnostic standardisée. Cette étude a montré que l'incidence était de 9 cas de cancerin situ pour 10⁵ femmes-années; le risque d'avoir un cancerin situ était de 0.53% entre les âges de 20–75 ans. Six pour cent des cancers diagnostiqués dans la région étaitin situ. Un cancer in situ a été trouvé dans 3% de toutes les biopsies du sein, et 0.3% des femmes ayant une mammographie motivée par une Symptomatologie au niveau du sein.Histologiquement, on pouvait distinguer 3 types de croissance: microfocale, tumorale, et diffuse. Les lésions microfocales étaient responsables de 60% des cancersin situ. A une exception près, les microfoyers de cancer ont tous été découverts par hasard, alors que les formes tumorales et diffuses ont tous été décelés grâce à des signes cliniques et/ou mammographiques. Il s'agissait toujours d'un cancer cannalaire. Une biopsie d'exérèse ou mastectomie partielle a été effectuée chez 85% des femmes ayant un microcancer, mais seulement chez 27% des femmes ayant une forme tumorale ou diffuse.

     

Branch retinal vein occlusion. A clinicopathologic case report

The eyes of a 72-year-old woman with a history of two branch retinal vein occlusions involving the left eye, were obtained postmortem and studied histopathologically. Prior to her death, she had been enrolled in the multicentered, prospective, randomized clinical trial on branch vein occlusion and treated with peripheral argon laser photocoagulation for disc neovascularization. Routine fluorescein angiograms and fundus photographs were available for clinical correlation. Despite photocoagulation, the patient had frequent recurrent episodes of vitreous hemorrhage. On histologic examination, both venous occlusions were found at arteriovenous crossings and associated with moderately sclerotic retinal arterioles. One occlusion was recanalized. Retinal inner ischemic atrophy was observed distal to the site of both venous occlusions and corresponded to areas of nonperfusion. Cystoid macular edema was not present. Three areas of neovascularization were found; one at the optic nerve head, one at the peripapillary retina, and one at the fovea. It is likely the patient's repeated vitreous hemorrhages were from one or all three areas of neovascularization demonstrated histopathologically.     

Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B.

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maximum relaxation rate of the diaphragm during weaning from mechanical ventilation.

BACKGROUND--The maximum relaxation rate (MRR; percentage fall in pressure/10 ms) of oesophageal (POES) and transdiaphragmatic (PDI) pressure slows under conditions of loaded breathing, and has been measured previously in normal subjects. MRR has not been measured in intubated patients weaning from mechanical ventilation. METHODS--Five postoperative patients who were expected to wean and nine patients who had previously failed were studied. POES and PDI MRR, peak oesophageal pressure during spontaneous breathing, maximum oesophageal pressure, and the inspiratory duty cycle were measured at rest during mechanical ventilation, in the first two minutes of spontaneous breathing, and after reventilation in those patients who failed, or before extubation in those patients who succeeded. RESULTS--At rest POES MRR in intubated patients had a range of 5.6-11 and PDI MRR 6.9-10.0, with a coefficient of variation of 9.9% and 7.3% respectively. POES and PDI MRR were similar before and after extubation in five postoperative patients, and POES MRR was reflected by endotracheal MRR measured at the airway. In five patients who failed to wean POES and PDI MRR slowed by 47% and 44%, and fully recovered after 10 minutes reventilation. In four patients who were successfully weaned MRR was unchanged during spontaneous breathing. At the time when MRR decreased, the respiratory muscles were heavily loaded in relation to their strength. CONCLUSIONS--Weaning failure occurs when the applied load exceeds the capacity of the respiratory muscles, and this is associated with a slowing of respiratory muscle MRR.     

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.


     

Mucolytic agents and otitis media with effusion

Middle ear effusion was obtained from children with otitis media with effusion and separated into thick (mucoid) and thin (serous) pools. Both effusion types contained similar amounts of non-dialysable solids. However, the thick effusions contained more mucus glycoprotein than the thin effusions, 25% and 8.2% respectively. Amino acid and carbohydrate analysis of the CsCl purified mucus glycoproteins demonstrated that the glycoprotein from the thick and thin effusions differed in their protein core, those from the thick effusions possessing a higher percentage of serine and threonine, the amino acids to which the sugar side-chains attach. They are also more glycosylated. N-acetyl cysteine and mercaptoethanol caused a fall in the viscosity of solutions of purified middle ear glycoprotein and effusion homogenate. However, longer term incubation caused a rise above the starting viscosity. This effect was concentration-dependent, and was mediated by low molecular weight components in the effusion and not the mucus glycoprotein. S-carboxymethyl cysteine had no effect on the viscosity of either the purified mucus glycoprotein or the effusion homogenate. Therefore, to produce a decrease in effusion viscosity in vivo, the concentration of mucolytic reaching the middle ear and the time it remains there are critical factors.