Systemic therapy in pediatric-type soft-tissue sarcoma.

Soft-tissue sarcoma (sts) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (rms) is most prevalent in children less than 10 years of age and peaks again during adolescence (16-19 years of age). Multi-agent chemotherapy constitutes the mainstay of treatment for rms. In other non-rhabdomyosarcoma soft-tissue tumours, such as synovial sarcoma, evidence for routine use of chemotherapy is less robust, and alternative treatment options, including targeted agents and immunotherapy, are being explored. In this review, we focus on chemotherapy for pediatric-type rms and discuss the advances and challenges in systemic treatment for select non-rhabdomyosarcoma soft-tissue tumours in children and adolescents. We support an increasingly cooperative approach for treating pediatric and adult sts.

Listening through narratives: using a narrative approach when discussing fertility preservation options with young cancer patients.

Despite clinical practice guideline recommendations mandating that fertility preservation be discussed with young cancer patients, many providers fail to initiate such discussions with adolescents. Researchers and clinicians often focus on system-level changes to improve access to fertility preservation for adolescents and young adults in Canada. However, little of the available information considers the way in which health care providers approach those discussions. Research has shown that, even when fertility preservation options are broached with adolescents, survivors often report dissatisfaction with those conversations, thus raising additional concerns about their content and quality. Here, we consider how a narrative approach-and the Frank narrative typology in particular-could improve the quality of such conversations by helping providers to more accurately and thoughtfully respond to the needs of adolescent patients when discussing the possibility of fertility preservation. Based on findings from a qualitative research project, we provide concrete suggestions for how to more sensitively approach fertility preservation conversations with male adolescent cancer patients and survivors.

A systematic review of active treatment options in patients with desmoid tumours.

INTRODUCTION: We conducted a systematic review to determine the optimal treatment options in patients with desmoid tumours who have declined observational management. METHODS: A search was conducted of the medline and embase databases (1990 to September 2012), the Cochrane Library, and relevant guideline Web sites and conference materials. RESULTS: One systematic review and forty-six studies met the preplanned study selection criteria; data from twenty-eight articles were extracted and analyzed. For local control, three studies reported a statistically significant difference in favour of surgery plus radiotherapy (rt) compared with surgery alone, and one study did not; two studies reported the lack of a statistical difference between surgery plus rt and rt alone in maintaining local control. Multivariate risk factors for local recurrence included positive surgical margins and young patient age. Single-agent imatinib led to a progression-free survival rate of 55% at 2 years and 58% at 3 years. Methotrexate plus vinblastine led to a progression-free survival rate of 67% at 10 years. Significant toxicities were reported for all treatment modalities, including surgical morbidity, and rt- and chemotherapy-related toxicities. CONCLUSIONS: In patients who have declined observational management, the local control rate was higher with surgery plus rt than with surgery alone. However, the additional rt-related complications should be considered in treatment decision-making. Surgery, rt, and systemic therapy are all reasonable treatment options for patients with desmoid tumours.

Treatment and follow-up strategies in desmoid tumours: a practice guideline.

OBJECTIVES: We set out to determine the optimal treatment options-surgery, radiation therapy (rt), systemic therapy, or any combinations thereof-for patients with desmoid tumours once the decision to undergo active treatment has been made (that is, monitoring and observation have been determined to be inadequate).provide clinical-expert consensus opinions on follow-up strategies in patients with desmoid tumours after primary interventional management. METHODS: This guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and the Sarcoma Disease Site Group. The medline, embase, and Cochrane Library databases, main guideline Web sites, and abstracts of relevant annual meetings (1990 to September 2012) were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Sarcoma Disease Site Group. RECOMMENDATIONS TREATMENTS: Surgery with or without rt can be a reasonable treatment option for patients with desmoid tumours whose surgical morbidity is deemed to be low.The decision about whether rt should be offered in conjunction with surgery should be made by clinicians and patients after weighing the potential benefit of improved local control against the potential harms and toxicity associated with rt.Depending on individual patient preferences, systemic therapy alone or rt alone might also be reasonable treatment options, regardless of whether the desmoid umours are deemed to be resectable. RECOMMENDATIONS FOLLOW-UP STRATEGIES: Undergo evaluation for rehabilitation (occupational therapy or physical therapy, or both).Continue with rehabilitation until maximal function is achieved.Undergo history and physical examinations with appropriate imaging every 3-6 months for 2-3 years, and then annually.

Chemotherapy (gemcitabine, docetaxel plus gemcitabine, doxorubicin, or trabectedin) in inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma: a clinical practice guideline.

QUESTIONS: Does chemotherapy-that is, gemcitabine, gemcitabine plus docetaxel, doxorubicin, or trabectedin-improve clinical outcomes in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma (lms)? Is there a difference in the tumour response rate to chemotherapy between recurrent pelvic disease and extrapelvic metastases in the target patients? METHODS: This guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care, the Sarcoma Disease Site Group (dsg), and the Gynecologic Cancer dsg. The core methodology was the systematic review. The medline and embase databases (2004 to June 2011), the Cochrane Library, main guideline Web sites, and relevant annual meeting abstracts (2005-2010) were searched. Internal and external reviews were conducted, with final approval by the dsgs and the Program in Evidence-Based Care. CLINICAL PRACTICE GUIDELINE: Based on currently available evidence from the medical literature (four single-arm phase ii studies, one arm of a randomized controlled trial, and one abstract), doxorubicin alone, gemcitabine alone, or gemcitabine plus docetaxel may be treatment options in first- or second-line therapy (or both) for women with inoperable, locally advanced, recurrent, or metastatic uterine lms. Hematologic toxicity is common and should be monitored, and granulocyte colony-stimulating factor should be considered when gemcitabine plus docetaxel is used. Other toxicities, such as neurotoxicity, pulmonary toxicity, and cardiovascular toxicity should be monitored. No recommendation is made for or against the use of trabectedin in the targeted patients. No data were available concerning differences in response in recurrent pelvic disease or extrapelvic metastases, or concerning quality of life.

Systematic chemotherapy for inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma: a systematic review.

The goal of this systematic review was to investigate and compare the treatment effects of systemic chemotherapy (i.e. doxorubicin, gemcitabine, gemcitabine plus docetaxel, or trabectedin) in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma. A 2005 systematic review (searching the literature from 1980 to June 2004) on systemic therapy in advanced uterine sarcoma was used as the basis for this updated review. MEDLINE and EMBASE (from January 2004 to June 2011), the Cochrane Library, some main guideline websites and the American Society of Clinical Oncology and the Connective Tissue Oncology Society annual meeting abstracts were searched. One arm from a randomised controlled trial (RCT), four single-arm phase II trials and one abstract were included in this systematic review. The studies of gemcitabine plus docetaxel have reported numerically longer median overall survival (14.7-17.9 months versus 12.1 months) and numerically higher objective response rates (27-53% versus 25%) than those reported in the study of doxorubicin alone. The combination of gemcitabine plus docetaxel resulted in more toxicity than doxorubicin alone. The available study for single-agent gemcitabine reported a tumour response rate of 21%, which is not superior to the 25% response rate with doxorubicin alone. One abstract (pooling data from two RCTs) failed to show the superiority of gemcitabine plus docetaxel over gemcitabine alone for tumour response rate (23% versus 18%) and progression-free survival (6 versus 4.9 months). To date, there is insufficient evidence to support or refute the use of trabectedin in the target patients. Doxorubicin, gemcitabine, and gemcitabine plus docetaxel are treatment options in women with inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma as first- or second-line therapy. Well-designed and good-quality RCTs are required to investigate the efficacy of chemotherapy and quality of life in target patients with uterine leiomyosarcoma.

Topotecan and cyclophosphamide in adults with relapsed sarcoma.

UNLABELLED: Background. The combination of topotecan and cyclophosphamide (TC) has activity in pediatric patients with recurrent sarcoma, especially Ewing's sarcoma (EWS). We sought to determine the toxicity of and response to TC in adults with recurrent sarcoma. Patients and Methods. Adults treated with TC from 2005 to 2010 were reviewed who received T = topotecan at 0.75 mg/m(2)/day (days 1-5) and C = cyclophosphamide at 250 mg/m(2)/day (days 1-5) every 21 days. Results. Fifteen patients, median age 31 years (range 17.5-56) had nonpleomorphic rhabdomyosarcoma (RMS, n = 6), EWS, n = 5, synovial sarcoma (SS, n = 2) leiomyosarcoma (LMS, n = 1), and desmoplastic small round cell tumour (DSRCT, n = 1). Median time to progression was 2.5 months (range 1.6-13.0). Partial responses were seen in 2/6 RMS and 1/2 SS. Stable disease was seen in 2/5 EWS, 1/2 SS and 1 DSRCT. The most common reason for stopping treatment was progressive disease 12/15, (80%). Hematologic toxicity was common; 7 (47%) patients required blood product transfusion, 5 (33%) patients had fever/neutropenia. At median follow-up time of 7.7 months, all but 1 patient had died of disease. CONCLUSION: TC combination is tolerable but has only modest activity in adults with recurrent sarcoma. Other regimens deserve exploration for this high-risk group of patients.

Clinical features, treatment, and outcome in 102 adult and pediatric patients with localized high-grade synovial sarcoma.

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

Morphologic variation of the diaphragmatic crura: a correlation with pathologic processes of the esophageal hiatus?

The contributions of muscle fibers from the right and left diaphragmatic crura to the formation of the esophageal hiatus have been documented in several studies, none coming to a complete consensus on the number of anatomic variations or the prevalence of these variations in the human population. These variations may play a role in the pathogenicity of specific diseases that involve the esophageal hiatus, such as hiatal hernias. We examined a total of two hundred adult cadavers during 2000-2007. The variations in the diaphragmatic crura, particularly their muscular contributions to the formation of the esophageal hiatus, were grossly examined and revealed a bilateral occurrence of diaphragmatic crura in all 200 specimens. The results of the various morphological patterns of circumferential muscle fibers forming the esophageal hiatus were classified into six groups. The most common type (Type I, 45%) formed the esophageal hiatus from muscular contributions arising solely from the right crus. In Type II (20%) the esophageal hiatus was formed by muscular contributions from the right and left crura. In Type III (15%), the right and left muscular contributions arose from the right crus with an additional band from the left crus. Type IV (10%) showed that the right and left muscular contributions arose from the right crus, with two additional (anterior and posterior) bands arising from the left crus. Type V (5%) demonstrated the contributions arising solely from the left crus. In Type VI (5%) the right and left contributions originated from the left crus with two additional bands, one from the right crus and one from the left crus. These variations may play a role in the pathogenicity of specific diseases that involve the esophageal hiatus such as hiatal hernia, gastroesophageal reflux disease and Dunbar's syndrome.

The first description of the palmaris brevis muscle.

Giovanni Battista Canano was born in Italy in 1515 and his work has gone mostly unknown. Very few copies of this anatomist and physician's book are known to exist. Interestingly, Canano reported and depicted what we believe, to be the first description of the palmaris brevis muscle. This description would be some 200 years prior to what is thought to be the earliest mention of this muscle by William Cheselden in his book, The Anatomy of the Human Body, published in 1713.

Sorption kinetics of As(V) with iron-oxide-coated cement-a new adsorbent and its application in the removal of arsenic from real-life groundwater samples.

In the search of alternative adsorbents for the removal of arsenic, a new adsorbent (iron-oxide coated cement) was examined under various conditions to evaluate its suitability in removing As(V). A removal of more than 99% was obtained within 2 h for an initial As(V) concentration of 1 mg/L. Kinetic studies showed a removal which became somewhat constant after 2 h. Thorough investigations to understand the mechanism of solute adsorption onto the new sorbent with the help of four kinetic models, viz. approximately first-order reversible kinetics model, pseudo-first-order kinetic model, second-order kinetic model, and pseudo-second-order kinetic model showed that the sorption kinetics is consistent with the pseudo-second-order model from which it can be inferred that the mechanism of adsorption is chemical interaction or chemisorption. The equilibrium data followed the Langmuir isotherm at low concentrations of As(V) (

Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children.

OBJECTIVES: In this study, we tried to determine the safety and outcomes of thrombolysis with tissue plasminogen activator of intravascular thrombus. STUDY DESIGN: Eighty consecutive children were treated between 1985 and 1999 in a tertiary care setting in a retrospective case series. There were 65 arterial thrombi (56 after cardiac catheterization) and 15 venous thrombi treated with tPA at an average dose of tPA of 0.5 mg/kg/hour for a median duration of 6 hours. RESULTS: Clot resolution was complete in 65% of children, partial in 20%, and there was no effect in 15%. There were major complications in 40%, minor complications in 30%, and no complications in 30%. Two patients had cerebral ischemia secondary to hypotension because of profound bleeding, with intracranial hemorrhage in 2 additional patients. Clot resolution was not related to patient age or weight, dose, and duration of tPA therapy and fibrinogen levels. However, complications were more likely in patients who weighed less, had a longer duration of therapy, a greater decrease in fibrinogen levels, and who failed to have resolution of their clot. CONCLUSIONS: tPA therapy can be effective in the thrombolysis of intravascular thrombus in children, but is associated with a low margin of safety and an unknown risk-benefit ratio.

An E3-like factor that promotes SUMO conjugation to the yeast septins.

Covalent attachment of the ubiquitin-related protein SUMO to other proteins participates in many processes including signal transduction, transcriptional regulation, and growth control. We report the characterization of Siz1 as an E3-like factor in the SUMO pathway. Siz1 is required for SUMO attachment to the S. cerevisiae septins in vivo and strongly stimulates septin sumoylation in vitro. Siz1 and the related protein Siz2 promote SUMO conjugation to different substrates at different stages of the cell cycle and, together, are required for most SUMO conjugation in yeast. Siz1, Siz2, and the PIAS (protein inhibitor of activated STAT) proteins form a conserved family defined by an unusual RING-related motif. Our results suggest that this family functions by promoting SUMO conjugation to specific substrates.

Rat peritoneal mast cells produce IFN-gamma following IL-12 treatment but not in response to IgE-mediated activation.

Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.