Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Trigeminal Neuralgia Secondary to Intracranial Lesions: A Prospective Series of 17 Consecutive Cases

Object: The purpose of the study was to assess the role of Gamma Knife surgery (GKS) in secondary trigeminal neuralgia (TN) caused by space-occupying lesions. Methods: From July 2010 till January 2015, 17 patients had GKS for secondary TN caused by intracranial lesions. The primary outcome was tumor control. The secondary outcomes were the alleviation of pain and the eventual secondary effects. Covariates were the age, duration of symptoms, duration till alleviation etc. Results: The mean age in this series was 63.3 years (range 39-79). The mean follow-up period was 1.85 years (range 0.5-3). Nine (52.9%) were meningiomas, five (29.4%) trigeminal schwannomas, two (11.8%) brain metastases and one (5.9%) arteriovenous malformation (AVM). Eight were located on the right side and nine on the left side. The mean duration of TN was 13.5 months (range 0.5-160). Follow-up was available for 16 patients (94.1%). Pain alleviation appeared after a mean time of 4.6 months (1-11) in 15 patients (88.2%). Five (29.4%) patients completely stopped medication in a mean time of 7 months (range 1-13) and three (17.6%) decreased it at half of the initial doses. No patient developed new hypoesthesia or other cranial nerve complication. The marginal doses for meningiomas and trigeminal schwannomas were 12 Gy (12-14), for metastasis 20 (20-20) and for AVM 24 Gy. The mean target volume was 1.84 cc (range 0.12-8.10). The mean prescription isodose volume was 2.65 cc (0.19-11.90). The mean maximal diameter was 19.9 (range 9-36). The mean number of isocenters was 14.2 (4-27). The mean duration was 76.9 minutes (range 25-172). The mean conformity, selectivity, Paddick and gradient index were: 0.99 (range 0.955-1), 0.701 (range 0.525-0.885), 0.694 (range 0.525-0.885) and 2.904 (range 2.654-3.371). At last follow-up, tumor decreased in 10 (58.8%) patients, was stable in 6 (35.3%) and increased in one (5.9%), the latest at 6 months. Conclusions: Gamma Knife surgery is safe and effective in treating intracranial lesions presenting with secondary TN. The initial pain freedom response was close to 90%, while having no secondary effect. Pain alleviation is achieved even in the absence of a volume variation of the lesions.

Suomen TUL pyöräilymestaruuskilpailut Eläintarhan urheilukentällä 17-18.8.40

13 x 20 cm

Ohjelma ratsastuskilpailut 17-18.3.38

14 x 22 cm

Ohjelma Suomen Kenttäratsastusklubin ratsastuskilpailut 17 p:nä toukokuuta 1925

14 x 21 cm

Förteckning över näringsidkare, vilka avses i § 15 i statsrådets beslut av den 17 december 1942 om reglementering av hudar och vilka erhållit rättighet att bereda hudar till läder eller skinn

14 x 20 cm

17 turistrutter i Finland

kuv., 10 x 20 cm

17 Suomen matkailureittiä

kuv., 10 x 20 cm

Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued). Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins) also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05), and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05). There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l). Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

Cortisol and 17-a-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-a-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with £30 weeks of gestation and a birth weight £1250 g, with no postnatal use of corticosteroid or death in the first 48 h were studied. Mean arterial pressure was measured every 4 h during the first 48 h. Cortisol and 17-a-OH-progesterone were determined at 12 and 36 h and patients were divided into refractory hypotensive (N = 15) and control (N = 20) groups. The groups were not different regarding type of delivery, use of prenatal corticosteroid, requirement of mechanical ventilation, use of vasopressor drugs, morphine, fentanyl, prophylactic indomethacin, and mean sample timing. Although refractory hypotensive newborns were more immature, were smaller, suffered more deaths after 48 h of life and had a higher SNAPPE-2 score, their cortisol and 17-a-OH-progesterone levels were not different from controls at 12 h and at 36 h. The increase of cortisol in newborns with refractory hypotension 36 h after birth was significantly higher than in controls. Despite the fact that refractory hypotensive very low-birth weight neonates were submitted to a very stressful condition, their cortisol and 17-a-OH-progesterone levels were similar to controls.

Catalogue des planches gravées en tous genres par les plus célèbres graveurs du XVe au XIXe siècle, composant le fonds de commerce d'éditeur d'estampes de Mme Vve Auguste Jean. Deuxième partie dont la vente, par continuation et par suite de cessation de commerce, aura lieu les mardi 16, mercredi 17, jeudi 18 et vendredi 19 juin 1846 et le lundi suivant, 22 juin, pour les cartes géographiques... Hôtel de ventes mobilières, place de la Bourse, n° 2... / Me Merlin, commissaire-priseur ; M. J. Vallée, expert, rue de Chartres-Dt.-Honoré, 8

[Vente. Art. 1846-06-16 - 1846-06-22. Paris]

Sermón que en las solemnes honras celebradas en obsequio de los V.V.P.P. predicadores apostólicos: Fr. Francisco Tomás Hermenegildo Garcés : Fr. Juan Marcelo Díaz : Fr. José Matías Moreno : Fr. Juan Antonio Barreneche : misioneros del colegio de propaganda fide de la Santa Cruz de Querétaro fundadores de las conversiones de la Purísima Concepción, y de S. Pedro y S. Pablo del Río Colorado entre los gentiles Yumas, y muertos en ellas gloriosamente a manos de los mismos bárbaros en los días 17 y 19 de julio de 1781 ...

UANL