State of transition to Ministry of Health governance of prison healthcare in the Council of Europe region.

OBJECTIVES: This study aimed to examine timebound prison healthcare governance amendments and current structures in Europe two decades after the World Health Organization (WHO) Declaration on Prison Health as part of Public Health adopted in Moscow on 24 October 2003 (Moscow Declaration), which recommended prison health care be closely linked with public health systems to ensure quality prison health care, connected health surveillance, and continuity of care. STUDY DESIGN: We present here a regional evolutionary mapping of the Council of Europe Member State transfer of prison healthcare governance to the auspices of the Ministry of Health. METHODS: The European Committee for the Prevention of Torture database and WHO Regional Office for Europe Health In Prison European Database were scrutinised for Council of Europe (CoE) Member State status regarding the Ministry responsible for prison healthcare governance and if this had changed since the adoption of the Moscow Declaration in 2003. RESULTS: As of October 2023, completed transfer of governance to the Ministry of Health nationally is documented in 13 CoE Member States and in one CoE Member State candidate (Kosovo). Partial transfer is documented in Spain (Catalonia and Basque Autonomous Community) and Switzerland (cantons of Geneva, Valais, Vaud, Neuchatel, and Basel-Stadt). Three CoE Member States operate joint governance of prison health care between Ministries (Malta, Portugal, Türkiye). Transfer is a lengthy process (up to 10 years). CONCLUSIONS: Successful transition requires political commitment, cooperation, needs assessment, resourcing, and evaluation. Monitoring of cost and prison healthcare standards, due process for complaints, and cooperation with independent/Committee against Torture inspections is critical.

[Intramammary use of antibiotics in dairy farms in the canton of Ticino before, during and after Staphylococcus aureus genotype B elimination]. / Intramammärer Antibiotikaeinsatz vor, während und nach einer Staphylococcus aureus Genotyp B Sanierung in Milchkuhbetrieben im Kanton Tessin.

INTRODUCTION: The aim of the study was to evaluate the use of intramammary antibiotics before, during and after the elimination of Staphylococcus aureus genotype B (SAGTB). Data on intramammary antibiotic use was collected in 65 dairy farms as part of a pilot project for SAGTB elimination in the canton of Ticino from 2017 to 2019. The investigated farms were divided into 46 affected farms (with at least one SAGTB-positive animal) and 19 control farms (SAGTB-free farms). Data on antibiotic use were requested from veterinarians and treatment incidence, as a measure of antibiotic use, was calculated based on medical records and veterinary prescriptions. In addition, the treatment incidence was calculated for 47 farms during alpine farming period. In 2018 (elimination year), the mean incidence of treatment during lactation in the SAGTB-positive farms was significantly higher than in the control farms (p=0,003). In 2019 no significantly lower antibiotic use during lactation or dry period was detected between 2017 (before elimination) and 2019 (after elimination). Alpine farming places where only S. aureus genotype B-negative animals had access to had a significantly lower antibiotic use during lactation (p=0,004). The new federal database (Antibiotics Information System in Veterinary Medicine, IS ABV) should allow continuous monitoring and to confirm the reduction of antibiotic use in the coming years.

INTRODUCTION: L'objectif de l'étude était d'évaluer la consommation d'antibiotiques intramammaires avant, pendant et après l'assainissement de Staphylococcus aureus génotype B (SAGTB). Dans le cadre d'un projet pilote d'assainissement SAGTB dans le canton du Tessin, l'étude a recueilli des données sur la consommation d'antibiotiques intramammaires de 2017 à 2019 dans 65 exploitations laitières réparties en 46 exploitations test (avec au moins un animal positif au SAGTB) et 19 exploitations témoins (exploitations exemptes de SAGTB). Les données relatives à la consommation d'antibiotiques ont été demandées aux vétérinaires et, grâce aux enregistrements et aux prescriptions des vétérinaires, il a été possible de calculer l'incidence du traitement en tant que mesure de la consommation d'antibiotiques. En outre, l'incidence des traitements pendant l'alpage a également pu être calculée pour 47 exploitations. En 2018 (année d'assainissement), l'incidence des traitements pendant la lactation était en moyenne significativement plus élevée dans les exploitations SAGTB-positives que pour les exploitations de contrôle (p=0,003). En comparant 2017 (avant l'assainissement) et 2019 (après l'assainissement), il n'y a pas eu de baisse significative de la consommation d'antibiotiques pendant la lactation et le tarissement en 2019. Dans les exploitations d'estivage, on a constaté l'année suivant l'assainissement (2019) une consommation d'antibiotiques significativement plus faible pendant la lactation pour les alpages qui n'accueillaient que des animaux négatifs à S. aureus génotype B (p=0,004). Il faut espérer qu'avec l'aide de la nouvelle base de données fédérale (Système d'information sur les antibiotiques en médecine vétérinaire, IS ABV), le monitoring pourra être poursuivi dans les années à venir et que la réduction de la consommation d'antibiotiques sera confirmée dans les années suivantes.

[Economic importance of antibiotic sale for private food animal practices in Switzerland - example veal production]. / Ökonomische Bedeutung des Umsatzes mit Antibiotika für private Nutztierpraxen in der Schweiz ­ Beispiel Kälbermast.

INTRODUCTION: The use of antibiotics in Swiss veal production is considered an established method for controlling bacterial infectious diseases. Although the veterinary profession aims to ensure animal welfare, the veterinary business income needs to be ensured at the same time. Against the background of increasing problems with resistant pathogens in human and veterinary medicine, the use of antibiotics should be significantly reduced and used more selectively. The associated economic consequences for food animal practitioners are unknown. The aim of this study was to determine the economic importance of antibiotic sale volume for private food animal practitioners in veal production. An anonymized questionnaire was sent to 120 mixed veterinary practices in Switzerland, which offered services to veal and beef cattle farmers. Questions involved the pharmaceutical sale volume, details on veterinary invoices from three farms with average, below and above average animal health throughout 2017. Twenty-nine complete questionnaires (response rate: 24.2%) and veterinary invoices of 84 farms were returned. The study is not representative, but it allows a rough assessment of the economic framework in Swiss livestock practice. The majority of the total turnover with livestock farms was generated by the sale of antibiotics (54%). Antibiotic sales per animal were higher as expected in farms with a below-average animal health than in farms with an average or above-average animal health. Consulting services turnover contributed only 0.5% to the total sale volume in veal farming. The results document, that antibiotic reduction measurements in veal and beef production will have economic consequences for veterinary livestock practices. In the medium term, the profitable existence of livestock veterinary practice requires a change to cost based consulting services.

INTRODUCTION: En Suisse, dans le cadre de la pratique de l'engraissement des veaux, l'utilisation d'antibiotiques est principalement considérée comme une méthode éprouvée pour lutter contre les maladies infectieuses bactériennes. L'activité vétérinaire vise à prévenir ou minimiser les souffrances chez les animaux. Mais pour autant, les vétérinaires restent des entrepreneurs qui doivent assurer un revenu adéquat de leur pratique. Dans un contexte de problèmes croissants rencontrés avec les agents pathogènes résistants en médecine humaine et vétérinaire, l'utilisation d'antibiotiques devrait être considérablement réduite et ciblée. Les conséquences économiques associées pour la pratique vétérinaire rurale sont peu connues. Le but de la présente étude était de déterminer l'importance économique des ventes d'antibiotiques pour les pratiques vétérinaires rurales privées en utilisant l'exemple de l'engraissement des veaux. À cet effet, un questionnaire anonymisé a été envoyé à 120 cabinets vétérinaires mixtes en Suisse, qui s'occupent entre autres d'exploitations d'engraissement de veaux, de broutards et de taurillons. Les participants ont été interrogés sur le niveau des ventes de médicaments. En outre, nous les avons invités à envoyer des factures vétérinaires concernant trois entreprises d'engraissement avec un niveau de santé animale inférieur, égal et supérieur à la moyenne tout au long de l'année 2017. Vingt-neuf questionnaires complets (taux de réponse: 24,2%) ainsi que des factures vétérinaires concernant au total 84 exploitations d'engraissement de veaux, de broutards ou de taurillons nous ont été retournés. L'étude n'est certes pas représentative, mais elle permet une évaluation approximative du cadre économique des pratiques rurales en Suisse. La majorité du chiffre d'affaires total sur les exploitations d'engraissement de veaux, de broutards ou taurillons a été générée par la vente d'antibiotiques (54%). Il apparait que les ventes d'antibiotiques étaient plus élevées dans les exploitations où la santé animale était inférieure à la moyenne que dans les établissements où elle était supérieure ou égale à la moyenne. Le chiffre d'affaires des prestations de conseil ne représentait que 0,5% du chiffre d'affaires total dans le domaine des veaux. Ces résultats montrent que les mesures visant à réduire les antibiotiques dans les conditions actuelles de production de veau et de boeuf auront probablement des conséquences économiques non négligeables sur la part des exploitations d'engraissement dans les revenus des pratiques vétérinaire rurales. A moyen terme, afin d'assurer la rentabilité d'une pratique rurale, une nouvelle orientation de l'activité vétérinaire sera nécessaire: la mise en place d'un service de conseils payants pour les exploitations d'engraissement, ayant pour but l'établissement de concepts de prévention.

Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain.

BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS.

[Prostatitis and fertility: the biologist's point of view]. / Prostatite, fertilité : le point de vue du biologiste.

There are two leukocytospermia: the leukocytospermia below 10(6) cells/ml comes from the epididymis. It is physiological, improves sperm quality and ART outcomes and therefore must be respected. Leukocytospermia above 10(6) cells/ml are of prostatic origin and reflect a chronic prostatitis. The results of IVF and ICSI with these sperm are always surprisingly improved when compared to those obtained using semen without leukocytes at all. But this improvement is offset by a dramatic increase in the miscarriage rate. Should we treat this leukocytospermia or its cause? A clinical trial is conducted in Cochin hospital with the PHRC Sigma (Male Genital Track Inflammatory Syndrome) that will help us answer this question. It seems, a priori, that it is better to treat the cause and to respect the leukospermia.

[Pre-washing catheter dramatically improves the post intrauterine insemination pregnancy rate]. / Le rinçage des cathéters avant insémination intra-utérine augmente considérablement les taux de grossesses.

OBJECTIVE: To analyze the effectiveness of pre-washing the intrauterine insemination catheters on IUI outcome. PATIENTS AND METHODS: Infertile couples (n=322) involved in a IUI program were included in the study. IUI indications were cervical factors, ovulation dysfunction, cryopreserved semen and unexplained infertility. Every other week for two years, IUI catheters were washed with culture medium prior to intrauterine sperm insemination. RESULT(S): Only the first IUI for each couple were analyzed. Washing the catheter, prior to use, resulted in a 49.7% increase in clinical pregnancy rate (22.0% vs 14.7% P<0.05). This result is observed with fresh sperm (15.7% vs 11.1%) and frozen-thawed sperm as well (31.1% vs 19.8%). The early pregnancy termination rate was similar in all groups. DISCUSSION AND CONCLUSION: Pre-washing the catheter before IUI should be recommended in Good Laboratory Practice Guidelines as it is already the case for embryo transfer catheters. This raises the problem of washing all single-use devices, in contact with gametes or embryos during IVF.

Tratamiento endovascular de un caso de priapismo de alto flujo / Endovascular treatment of a case of high-flow priapism

Objetivo. Presentar nuestra experiencia en un caso de priapismo de alto flujo tratado con éxito mediante laembolización selectiva de la arteria cavernosa. Caso clínico. Varón de 43 años con priapismo de alto flujo secundario aun traumatismo perineal. El tiempo desde la presentación de la sintomatología hasta el momento del tratamiento fue de157 días. El diagnóstico se confirmó mediante ecografía Doppler del pene y angiorresonancia aortoilíaca. En el primermomento fue tratado con una embolización supraselectiva y se utilizó un coágulo autólogo. Tres semanas después de laprimera intervención, el priapismo reapareció. La segunda embolización se realizó con micropartículas de polivinilo y microcoils.A corto plazo, el paciente recuperó la flacidez y la erección del pene. A largo plazo mostró como única secuela unamoderada fibrosis de los cuerpos cavernosos. Conclusiones. La embolización de la arteria lacerada es un procedimientoseguro para tratar el priapismo de alto flujo y proporciona excelentes resultados

Aim. To present our experience in a case of high-flow priapism successfully treated by superselectiveembolization of the internal pudendal artery. Case report. A 43 year-old male with high-flow priapism secondary to aperineal trauma. The time from the filing of the symptoms until the time of treatment was 157 days. The diagnosis wasconfirmed by Doppler ultrasound of the penis and aorto-iliac angioresonance. The first time, it was treated bysupraselective embolization with autologous blood clot. Three weeks after the first intervention, priapism reappeared.The second embolization was performed using polyvinyl microparticles and microcoils. In the short term, the patientregained flaccidity and the erection of the penis. In the long term, the only sequel was a moderate fibrosis of the corporacavernosa. Conclusions. The embolization of the lacerated artery is a safe procedure for treating the high flow priapismand provides excellent results

A novel breast tissue density classification methodology.

It has been shown that the accuracy of mammographic abnormality detection methods is strongly dependent on the breast tissue characteristics, where a dense breast drastically reduces detection sensitivity. In addition, breast tissue density is widely accepted to be an important risk indicator for the development of breast cancer. Here, we describe the development of an automatic breast tissue classification methodology, which can be summarized in a number of distinct steps: 1) the segmentation of the breast area into fatty versus dense mammographic tissue; 2) the extraction of morphological and texture features from the segmented breast areas; and 3) the use of a Bayesian combination of a number of classifiers. The evaluation, based on a large kappa = 0.81 and 0.67 for the two data sets) between automatic and expert-based Breast Imaging Reporting and Data System mammographic density assessment.

Well or poorly differentiated nonfunctioning neuroendocrine carcinoma of the pancreas: a single institution experience with 17 cases.

AIM: To evaluate the influence of distinguishing between well and poorly differentiated nonfunctioning neuroendocrine pancreatic carcinomas (PC). METHOD: Six well differentiated and 11 poorly differentiated nonfunctioning neuroendocrine PC were retrospectively analyzed for differences and compared with 340 ductal PC. RESULTS: 1. There was no difference in pT categories between well differentiated and, poorly differentiated nonfunctioning neuroendocrine PC and ductal PC. 2. The rate of the pN1 category was lower in well differentiated lesions (20%) than in poorly differentiated lesions (66%) and in the ductal PC group (75%). 3. The outcome of patients with R0 resections was significantly better for well differentiated neuroendocrine PC with all patients alive than for poorly differentiated ones and for ductal PC (5-year survival rate 0% and 18%, respectively). 4. The outcome following R1/R2 resections for poorly differentiated neuroendocrine PC tended to be similar than for ductal PC (1-year survival rate 20% vs. 33%). 5. There was no difference in mean survival time (9 months) between poorly differentiated lesions and ductal PC after palliative procedures. CONCLUSIONS: The better outcome of surgical treatment of nonfunctioning neuroendocrine PC vs. that of ductal PC was confined to well differentiated neuroendocrine lesions. For poorly differentiated lesions the outcome was as poor as for ductal PC. These results underscore the importance to distinguish between well and poorly differentiated nonfunctioning neuroendocrine PC.

[Importance of nocturia and its impact on quality of sleep and quality of life in patient with benign prostatic hyperplasia]. / Importancia de la nocturia y su impacto en la calidad del sueño y en la calidad de vida en el paciente con hiperplasia benigna de próstata.

INTRODUCTION: Nocturia is the main cause of insomnia or sleep interruption in adult men, which has a negative impact on daily activities, quality of life (QoL) and quality of sleep (QoS). The assessment of nocturia and its impact on QoL and QoS in patients suffering from benign prostatic hyperplasia (BPH) has been poor in terms of clinical research, moreover there is a lack of specific methods to assess this impact. OBJECTIVES: The objectives of BPH treatment should include the improvement of patient's QoL by controlling both diurnal and nocturnal symptoms. In order to assess how nocturia affects QoL and also QoS, some specific tools, such as N-QoL questionnaire or the number of Hours of Undisturbed Sleep (HUS), have been recently developed. Therefore, it would be interesting to assess how nocturia reduction due to LUTS/BPH treatment can impact on some objective parameters such as HUS and also how nocturia reduction improves QoS and QoL. This assessment should be developed during the application of pharmacological treatments in clinical practice by means of these specific tools. With the aim of tackling nocturia as an urologic problem in patients with LUTS/BPH, as well as knowing the physiology of sleep and the effect of nocturia on the sleep and QoL, a meeting of expert urologists, that gathered about fifty specialists of all around Spain, was held in Madrid. This article presents the main ideas and concepts exposed in this meeting. CONCLUSIONS: Nocturia is a symptom with a high prevalence in older patients with STUI/BPH. The PreNoc study has showed a Nocturia prevalence in Spain of 83% in patients > or =60 years old diagnosed of BPH. Nocturia is the most bothersome symptom in patients with STUI/BPH.

Importancia de la nocturia y su impacto en la calidad del sueño y en la calidad de vida en el paciente con hiperplasia benigna de próstata / Importance of nocturia and its impact on quality of sleep and quality of life in patient with benign prostatic hyperplasia

Introducción: La nocturia es la principal causa de insomnio o de interrupción del sueño en varones adultos, ello se traduce en un efecto negativo sobre la actividad diaria, la calidad de vida y la calidad del sueño. La valoración de la nocturia y su impacto en la Calidad de Vida (CdV) y en la Calidad del Sueño (CdS) en el paciente con HBP ha sido escasa desde el punto de vista de la investigación clínica, además de la falta de métodos específicos que evaluasen dicho impacto. Objetivos: Entre los objetivos del tratamiento de la HBP debería procurarse la mejora de la calidad de vida del paciente mediante el control de los síntomas tanto de día como de noche. Recientemente se han desarrollado instrumentos específicos para valorar la afectación de la nocturia en la CdV, como es el cuestionario N-QoL, así como la afectación en la CdS, por medio de las horas de sueño ininterrumpido (HUS). Sería interesante evaluar cómo la reducción de la nocturia originada por el tratamiento sobre los STUI/HBP puede influir en parámetros objetivos como las HUS, y cómo se traduce en una mejora de la calidad del sueño y de la calidad de vida. Esta valoración debería realizarse, con la ayuda de estas herramientas específicas, durante el desarrollo clínico de los tratamientos farmacológicos. Con objeto de abordar la nocturia como problema urológico en los pacientes con STUI/HBP, así como de conocer la fisiología del sueño y el efecto de la nocturia sobre el sueño y sobre la calidad de vida, se celebró en Madrid una reunión de expertos urólogos que congregó a una cincuentena de profesionales de toda España. Este artículo presenta los principales conceptos expuestos en esta reunión. Conclusiones: La nocturia es un síntoma de alta prevalencia en la población masculina de edad avanzada con STUI / HBP. El estudio PreNoc mostró una prevalencia de nocturia en España del 83% en pacientes ≥60 años diagnosticados de HBP. La nocturia es el síntoma más molesto en los pacientes con STUI/HBP

Introduction: Nocturia is the main cause of insomnia or sleep interruption in adult men, which has a negative impact on daily activities, quality of life (QoL) and quality of sleep (QoS). The assessment of nocturia and its impact on QoL and QoS in patients suffering from benign prostatic hyperplasia (BPH) has been poor in terms of clinical research, moreover there is a lack of specific methods to assess this impact. Objetives: The objectives of BPH treatment should include the improvement of patient’s QoL by controlling both diurnal and nocturnal symptoms. In order to assess how nocturia affects QoL and also QoS, some specific tools, such as N-QoL questionnaire or the number of Hours of Undisturbed Sleep (HUS), have been recently developed. Therefore, it would be interesting to assess how nocturia reduction due to LUTS/BPH treatment can impact on some objective parameters such as HUS and also how nocturia reduction improves QoS and QoL . This assessment should be developed during the application of pharmacological treatments in clinical practice by means of these specific tools. With the aim of tackling nocturia as an urologic problem in patients with LUTS/BPH, as well as knowing the physiology of sleep and the effect of nocturia on the sleep and QoL, a meeting of expert urologists, that gathered about fifty specialists of all around Spain, was held in Madrid. This article presents the main ideas and concepts exposed in this meeting. Conclusions: Nocturia is a symptom with a high prevalence in older patients with STUI/BPH. The PreNoc study has showed a Nocturia prevalence in Spain of 83% in patients ≥60 years old diagnosed of BPH. Nocturia is the most bothersome symptom in patients with STUI/BPH

[Plasma cell leukaemia]. / La leucémie à plasmocytes.

We report a case of primary plasma cell leukaemia, with an absolute count of plasma cells of 53 Giga/L, diagnosed in a 83-year-old woman. The patient's condition improved, with no circulating plasma cells after 3 weeks of treatment, in response to the combination of thalidomide and dexamethasone administered for 5 days followed by thalidomide alone. The clinical presentation, the morphological, flow cytometric and pathophysiological characteristics of the plasma cell leukaemia and the treatment are summarised in this paper.

Immunology of skin transplantation.

Untreated viable allogeneic skin is highly immunogenic. Epidermal Langerhans migrate after transplantation out of the donor skin into the lymph node of the recipient where they can activate T cells capable to mediate rejection. Allogeneic skin is used as a temporary coverage of burn wounds, often in combination with autologous skin grafts. Several methods to pretreat the allogeneic skin have been used to delay the rejection process. Processing of allogeneic skin in 85% glycerol results in a non-viable skin with a well-preserved structure. Experiments in a full thickness porcine wound model showed that rejection of glycerol treated allogeneic skin grafts was up to six days delayed. Viable, untreated allogeneic skin grafts were rejected predominantly by CD8 positive T cells whereas in the glycerol treated grafts the influx of host cells was lower and the majority of the cells were macrophages. The outgrowth of the autologous skin grafts underneath glycerol treated allogeneic skin was three days earlier completed when compared to grafts in combination with untreated allogeneic skin. Thus, by processing the allogeneic skin into 85% glycerol, the direct route to induce graft rejection is blocked since the Langerhans cells are non-viable. The glycerol-preserved skin grafts are finally rejected via an indirect route mediated by macrophages; this process is less disturbing for the outgrowth of autologous cells.

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors.

BACKGROUND: This investigation evaluates prognostic variables in patients with seminomatous and non-seminomatous extragonadal germ-cell tumors (EGCT) in order to identify relevant factors for long-term outcome following cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients from six countries treated at 11 centers in Europe and the USA from 1975 to 1996 were evaluated retrospectively. Uni- and multivariate analyses of prognostic variables for survival and for response to chemotherapy were performed. RESULTS: Data were available for 635 EGCT patients, 104 with seminomatous and 524 with non-seminomatous EGCT (n = 7 not specified). For non-seminomatous EGCT the following independent adverse factors were identified: presence of either liver, lung or central nervous system metastases, primary mediastinal tumor or elevation of pretreatment beta-human gonadotropin; for extragonadal seminoma (only univariate) adverse factors were: presence of liver metastases, two or greater metastatic sites or International Germ Cell Cancer Collaborative Group (IGCCCG) grouping (intermediate versus good). Integration of these variables produced the following prognostic risk groupings: 'excellent prognosis', all seminomatous EGCT (89% 5-year survival rate); 'intermediate low', 'intermediate high' and 'poor', all non-seminomatous EGCT with a 69, 55 and 17% 5-year survival rate, respectively. The decreased survival among the different groups was due to a lower rate of favorable objective remissions and a higher rate of relapses. Classification and regression tree (CART) modeling confirmed histology and location of primary tumor as the major prognosticators. For the subgroup of patients with mediastinal non-seminoma, the 2-year survival rate ranged from 34 to 84%. Multivariate testing for the probability to respond to chemotherapy revealed non-seminomatous histology, primary mediastinal tumor site, and the presence of liver, lung or CNS metastases as independent adverse factors. CONCLUSIONS: In EGCT, prognostic variables for the outcome and for the response to chemotherapy could be identified, which in part differ from gonadal GCT. The proposed model might help to better understand the specific prognosis of EGCT and to tailor risk-adapted treatment strategies. In addition, CART analysis demonstrated the heterogenous prognosis of patients with mediastinal non-seminoma.

Effective salvage therapy with carboplatin/mitomycin C in metastatic breast cancer.

BACKGROUND: Alternative and effective drug regimens in patients with metastatic breast cancer progressing after adriamycin- and taxoid-containing regimens are urgently needed. PATIENTS AND METHODS: In a phase II trial, 43 heavily pretreated patients with metastatic breast cancer were treated with both carboplatin 200 mg/m(2) i.v. and mitomycin C 10 mg/m(2) i.v. on day 1 every 4 weeks. In case of granulocytopenia or thrombocytopenia below grade 3 according to NCI-CTC, the carboplatin dosage was escalated to 300, 400, and 450 mg/m(2) in the next treatment cycle. RESULTS: During the first 3 cycles the dose intensity of carboplatin could be increased from a mean of 50 to 74 mg/m(2)/week. Beyond this value the carboplatin dose intensity decreased because of hematotoxicity. Based on an intention-to-treat analysis, 9 of 43 patients responded to therapy (21%; 95% CI = 10.04-36.04) including 2 complete and 7 partial responses. 15 patients had no change, 13 progressed, and 6 patients were considered nonevaluable. The median time to progression was 3 (range 0-12) months. NCI-CTC grade 3 or 4 granulocytopenia was observed in 14 patients, grade 3 or 4 thrombocytopenia occurred in 32, grade 3 infections in 3, grade 3 hemorrhage in 1, and grade 3 cardiac dysrhythmias in 1 of the patients. CONCLUSIONS: In anthracycline/ taxoid-pretreated patients, salvage treatment with a combination of carboplatin and mitomycin C seems to be effective and associated with foreseeable toxicity. Based on our results with an intraindividual dose escalation of carboplatin, a dosage of 300 mg/m(2) in combination with mitomycin C 10 mg/m(2) every 4 weeks seems to represent a recommendable starting dose for future studies.

Sodium-lithium countertransport is increased in normoalbuminuric type 1 diabetes but is not related to other risk factors for microangiopathy.

BACKGROUND: It has been reported that sodium-lithium countertransport (Na/Li CT) activity is increased in patients with diabetes mellitus and that this increased Na/Li CT activity is associated with the development of diabetic nephropathy. It is unclear however, whether Na/Li CT is related to other pathophysiological factors in diabetic patients. We studied kinetic parameters of Na/Li CT activity together with other putative risk factors for microangiopathy in normoalbuminuric type 1 diabetic patients and matched control subjects. SUBJECTS AND METHODS: We measured maximum velocity (Vmax) and sodium affinity (Km) of Na/Li CT in 53 diabetic patients and 45 healthy controls. Endothelial function was assessed by monitoring forearm vascular response to intrabrachial infusion of acetylcholine. Blood samples were collected for measurement of HbA1c, glucose, insulin and lipids. Blood pressure was measured intra-arterially. Renal haemodynamics were measured by inulin/p-aminohippurate clearance. Urinary albumin was measured by enzyme-linked immunosorbent assay. Transcapillary escape of albumin (TERalb) was calculated by the disappearance curve of 125I-labelled albumin. RESULTS: Vmax was increased in diabetic patients (779 +/- 36 micromol Li+ h-1 L-1 erythrocytes vs. 623 +/- 35 in controls, P < 0.01), whereas Km was decreased (64 +/- 16 mmol L-1 vs. 76 +/- 27 in controls, P = 0.03). The ratio of Vmax : Km was 12.4 +/- 0.6 in diabetic patients and 8.9 +/- 0.9 in controls (P < 0.001). When comparing diabetic patients in the lowest and highest quartile of Vmax or Km there were no differences in blood pressure, renal haemodynamics, urinary albumin excretion, TERalb, endothelial function, HbA1c, glucose, insulin, or lipid profile. CONCLUSION: Na/Li CT is increased in uncomplicated type 1 diabetes and characterized by an increase in Vmax and a decrease in Km. The increase in Na/Li CT is not associated with changes in endothelial function, degree of metabolic control, blood pressure or renal haemodynamics.

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Somatostatin-receptor scintigraphy for staging and follow-up of patients with extraintestinal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type.

The majority of lymphomas of the mucosa-associated lymphoid tissue (MALT)-type arise in the stomach, but extragastric locations are also frequently encountered. Due to previous results indicating that somatostatin receptor (SSTR)-expression distinguishes between gastric and extragastric MALT-type lymphoma, we have initiated a study to evaluate the role of SSTR-scintigraphy for staging and follow-up of patients with extragastric manifestations of MALT-type lymphoma. A total of 30 consecutive patients, including 24 with primary extragastric MALT-type lymphoma, 5 patients with dissemination to extragastric sites (including colon, lung, parotid, ocular adnexa and breast) following an initial gastric MALT-lymphoma and one patient with spread to stomach, lung and lymph nodes following parotid lymphoma were prospectively studied. All patients had histologically verified MALT-type lymphoma: 2 patients had lymphoma presenting in the lung, 9 in the ocular adnexa, 7 had lymphomas in the parotid, 2 patients had disease located in the breast, 3 patients had lymph-node relapse following MALT-type lymphoma of the parotid, the lacrimal gland and the thyroid, and 1 had primary MALT-lymphoma of the liver. All patients underwent SSTR-scintigraphy using (111)In-DTPA-D-Phe(1)-Octreotide ((111)In-OCT) before initiation of therapy, while 13 also had a second scan after treatment. The results of gamma camera imaging were compared to conventional staging. No positive scans could be obtained in patients with dissemination following gastric lymphoma, while all patients with primary extragastric lymphoma had positive scans at the site of histologically documented involvement before initiation of therapy. In addition, also the patient with secondary spread to stomach, lung and lymph nodes was positive in all documented lymphoma sites. In one patient, focal tracer uptake in projection to the maxillary sinus was documented, which was bioptically verified as inflammation. In the scans performed after therapy, focal tracer accumulation in the left orbit indicated persistence of disease following irradiation in one patient with otherwise negative work-up, which was verified by MRI and biopsy 6 months later. In another patient, a positive scan indicated disease relapse in the lacrimal gland 9 months before clinical verification by means of ultrasound. In one patient, a focus not present in the pretherapeutic scan was found in the ethmoidal sinus, corresponding to a hyperplastic polyp. Both SST-scan as well as CT indicated disease persistence in one case, while negative scans corresponding to complete remission as judged by conventional staging were obtained following therapy in the remaining patients, and absence of relapse has been confirmed for a median follow-up of 2 years. These results indicate that (111)In-OCT is an excellent tool for staging and non-invasive therapy-monitoring in extragastric MALT-type lymphomas. These data further confirm our initial finding that gastric MALT-type lymphomas do not express relevant amounts of respective SSTR, and that SSTR-scanning is able to distinguish between gastric vs extragastric origin of MALT-type lymphoma irrespective of the site of presentation.