Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.     

Behandlung des hyperammonämischen Komas bei Neugeborenen und Säuglingen durch Hämodialyse oder Hämofiltration

Zusammenfassung Das hyperammon?mische Koma ist eine akut lebensbedrohliche Stoffwechselentgleisung. Die h?ufigsten kongenitalen Ursachen sind Enzymdefekte im Harnstoffzyklus und im Abbau von organischen S?uren. Die Frühdiagnose und eine sofortige aggressive Therapie sind die entscheidenden Voraussetzungen zur Vermeidung irreversibler Hirnsch?den und letaler Verl?ufe. Das Therapieziel ist eine rasche Senkung des Ammoniaks und anderer neurotoxischer Metaboliten. Die therapeutischen Grundprinzipien beinhalten 1. eine restriktive Proteinzufuhr unter dem Erhalt essentieller Aminos?uren, 2. die Unterbrechung des Proteinkatabolismus mittels hochkalorischer Ern?hrung, 3. eine medikament?se Aktivierung alternativer Wege der Stickstoffausscheidung sowie 4. apparative Blutreinigungsverfahren. Das optimale Dialyseverfahren ist umstritten. Wir haben 4 Neugeborene und S?uglinge in einem hyperammon?mischen Koma im Rahmen von Stoffwechselerkrankungen mittels H?modialyse oder H?mofiltration behandelt. Die Kasuistiken best?tigen die Effektivit?t und Komplikationsarmut beider Verfahren. Diskussion: In der Behandlung von lebensbedrohlichen Hyperammon?mien bei Neugeborenen und S?uglingen sind H?modialysen und H?mofiltrationen die Behandlungsmethoden der Wahl. Die invasive Blutreinigung ist mit einer konsequenten di?tetischen und medikament?sen Therapie zu optimieren. Der prognostische Nutzen einer effizienten Blutreinigung bei ausgepr?gter Hyperammon?mie rechtfertigt einen unverzüglichen Transport in das n?chstgelegene p?diatrische Dialysezentrum.      

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

Improvement of lipophilicity and membrane transport of cefuroxime using in vitro models.

Most beta-lactam antibiotics cannot be absorbed orally and, therefore, must be administered intravenously (i.v.) or intramuscularly (i.m.). Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefuroxime exhibiting significant advantages in the parental treatment of common infections, was used as model drug in the present study. The effect of the cationic absorption enhancers (four quaternary ammonium salts) on the lipophilicity of cefuroxime was investigated by means of the n-octanol/water system. The results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in vitro transport model with artificial (dodecanol collodium membrane) and biological membranes (Charles-River guinea pig).     

Sulfemodin 8-O-beta-D-glucoside,a new sulfated anthraquinone glycoside,and antioxidant phenolic compounds from Rheum emodi

A sulfated emodin glucoside, emodin 8-O-beta-D-glucopyranosyl-6-O-sulfate (1), was isolated from the roots of Rheum emodi in an investigation of the active constituents of this Nepalese medicinal plant, and its structure was determined by spectroscopic and chemical methods. Additionally, two rare auronols, carpusin (2) and maesopsin (3), besides other anthraquinones and phenolics, were isolated and identified. Compounds 2 and 3 showed significant antioxidant activity in the DPPH assay, while chrysophanol, physcion, and emodin and their 8-O-glucosides were found to be inactive.     

Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.     

Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on physiological development,reflexes, locomotor activity and learning behaviour in Wistar rats

 Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat offspring were studied after administration of a loading dose of 300 or 1000 ng TCDD/kg body wt on day 19 of pregnancy, followed by weekly maintenance doses of 120 or 400 ng TCDD/kg body wt. The dose regimens led to a fluctuation of average TCDD concentrations in the liver of the offspring of 4.9–14.9 ng/g (TCDD1000/400 group) or 1.4–6.3 ng/g (TCDD300/120 group) during the course of the experiment. In both TCDD-exposed groups the body weight of the offspring was significantly lower on postnatal day 7 (PND 7); in the high dose group from PND 7 to PND 31. Some landmarks of postnatal development were retarded in the exposed groups; in particular, the vaginal opening was delayed for several days in both TCDD-exposed groups. The TCDD-exposed animals revealed a reduced ability to remain on a rotating rod. During reflex testing, the rate of successfully responding animals was higher in the exposed groups. No statistically significant differences in the locomotor activity between controls and TCDD-exposed offspring were detectable under our experimental conditions. In a discrimination learning test no effects on the learning ability were found. However, TCDD-exposed offspring showed an increase in unanswered trials during critical phases of the task. They also exhibited increased locomotor activity in a novel environment; prior to an amphetamine challenge dose of 1 mg/kg body weight. Amphetamine-induced activity was decreased in a dose-dependent manner. Received: 2 May 1994 / Accepted: 13 July 1994     

Three years of routine vitrification of human zygotes: is it still fair to advocate slow-rate freezing?

Cryopreservation of human oocytes and embryos is a necessary tool in assisted reproduction treatment that leads to an increased cumulative outcome while decreasing costs. Vitrification is a cryopreservation technique that leads to a glass-like solidification, with rapid cooling of cells or tissues. Nowadays vitrification is claimed to be the future of cryopreservation of human embryos due to improved survival rates and clinical outcomes. This study was conducted at a university clinic to assess the safety and efficiency of vitrification of human zygotes as a routine procedure. A total of 849 pronuclear-stage (PN) zygotes were vitrified between March 2004 and July 2006. During this period, 103 cycles of cryopreserved embryo transfer were completed. In total, 339 PN zygotes were thawed resulting in an 89% survival rate (302 PN zygotes). The mean number of embryos per transfer was 2.2. The pregnancy rate obtained was three times higher (36.9%) than that obtained with the slow-rate freezing method (10.2%) used previously in the same centre. In conclusion, vitrification of human zygotes at the pronuclear stage seems to be a successful and reliable method with favourable outcomes and can be recommended as a routine technique for cryopreservation of human embryos.     

Buchbesprechungen

Ohne Zusammenfassung