Developing leadership within an academic medical department in Canada: a road map for increasing leadership span.

Medicine is dependent on strong leaders to advance innovation in the clinical care of patients. In most academic medical streams, there is no explicit system-wide approach for succession planning and leadership development. In late 2009, it was clear to the authors' department that they were at risk of losing high-potential individuals and division heads.

Development and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing.

Intravenous (i.v.) busulfan (Bu) administered once daily in myeloablative transplant regimens is convenient, effective, and relatively well tolerated.

Influence of comorbidities on transplant outcomes in patients aged 50 years or more after myeloablative conditioning incorporating fludarabine, BU and ATG.

Non-myeloablative (MA) and reduced intensity allo-SCT regimens are offered to older patients and/or those with comorbidities because the morbidity and mortality attributable to fully MA conditioning is thought to be unacceptably high. A total of 207 patients aged 50-66 years were treated between 1999 and 2008 with SCT after MA conditioning with fludarabine 50 mg/m(2) daily × 5 and i.v.

Systematic review on the efficacy of multimodal treatment of sarcomatosis with cytoreduction and intraperitoneal chemotherapy.

Background: Peritoneal sarcomatosis carries a dismal prognosis with median survival of 12 months and no 5-year survivors. The treatment for sarcomatosis has mostly been chemotherapy and surgery for palliation. Recently, cytoreduction (CRS) and intraperitoneal chemotherapy (IPC) has been tried as an alternative for improving regional control and survival, but the efficacy of this combined treatment is difficult to determine.

Impairment of cognitive function reported by patients suffering from carcinoid syndrome.

Background: Carcinoid syndrome (CS) is characterized by symptoms of diarrhea, flushing, bronchospasm, and valvular heart disease. It has been our impression that patients with CS also exhibit features of cognitive impairment. The purpose of this pilot study was to evaluate if symptoms of cognitive impairment were reported by patients with CS.

The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia.

A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML).

pY-STAT3 and p53 expression predict outcome for poor prognosis diffuse large B-cell lymphoma treated with high dose chemotherapy and autologous stem cell transplantation.

The purpose of this study was to evaluate the ability of biomarkers to predict 5-year event-free survival (EFS) of poor prognosis patients with diffuse large B-cell lymphoma (DLBCL) who were treated on a prospective clinical trial with upfront high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). We previously reported 51 patients with DLBCL treated with one cycle each of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP), and carmustine, etoposide, Ara-C, and melphalan (BEAM)/ASCT. Of these patients, 33 had DLBCL and suitable tissue for immunohistochemical (IHC) biomarker evaluation.

Gamma-secretase represents a therapeutic target for the treatment of invasive glioma mediated by the p75 neurotrophin receptor.

The multifunctional signaling protein p75 neurotrophin receptor (p75(NTR)) is a central regulator and major contributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembrane proteolysis (RIP) of p75(NTR) is required for p75(NTR)-mediated glioma invasion, and identify a previously unnamed process for targeted glioma therapy. Expression of cleavage-resistant chimeras of p75(NTR) or treatment of animals bearing p75(NTR)-positive intracranial tumors with clinically applicable gamma-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival.

Relationship between tumor grade and computed architectural complexity in breast cancer specimens.

Breast cancer is the leading form of cancer diagnosed in women, and the second leading cause of cancer mortality in this group. A commonly accepted grading system for breast cancer that has proven useful for guiding treatment strategy is the modified Bloom-Richardson system. However, this system is subject to interobserver variability, which can affect patient management and outcome.

Sexual intimacy in heterosexual couples after prostate cancer treatment: What we know and what we still need to learn.

Receiving a diagnosis of and treatment for prostate cancer often results in significant physical side-effects and associated psychosocial stressors that can interfere with the experience of sexual intimacy for couples. Despite the fact that prostate cancer affects mainly older men, the maintenance of sexual intimacy is an important issue to consider, as the majority of older adults continue to value, engage in, and enjoy sexual activity throughout their lives. While the current research identifies the challenges that many men face, little is known about the strategies that couples use to successfully maintain sexual intimacy after prostate cancer treatment.

Overnight storage of autologous stem cell apheresis products before cryopreservation does not adversely impact early or long-term engraftment following transplantation.

To reduce costs and avoid inconvenient overtime work, our institution changed policy in September 2000 so that autologous stem cell apheresis products were stored overnight before cryopreservation rather than immediately processed. This retrospective review was conducted to evaluate the possible impact of this policy change on hematopoietic engraftment following autologous stem cell transplantation (ASCT). In total, 229 consecutive lymphoma patients who underwent a single, unpurged ASCT in Calgary between January 1995 and November 2003 were evaluated.

Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas.

Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.

Energy response of an aluminium oxide detector in kilovoltage and megavoltage photon beams: an EGSnrc Monte Carlo simulation study.

A Monte Carlo study of the energy response of an aluminium oxide (Al(2)O(3)) detector in kilovoltage and megavoltage photon beams relative to (60)Co gamma rays has been performed using EGSnrc Monte Carlo simulations. The sensitive volume of the Al(2)O(3) detector was simulated as a disc of diameter 2.85 mm and thickness 1 mm.

Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates.

Purpose: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates.

Experimental Design: Racine glioma cells 9L and RG2 were implanted s.

Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype?

Unlike most patients with glioblastoma multiforme who survive less than a year, approximately 2% have an unusually long survival after diagnosis and contemporary treatment (> or = 3 or more years); rarely, the disease appears to be "cured." Understanding these rare patients may tell us something important about the biology of glioblastoma multiforme. Patients who are young, have good performance status, and receive multimodalitytherapy (i.

Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma.

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus.

Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes.

The availability of an i.v. form of busulfan (Bu) has prompted investigation of administration schedules other than the 4-times-daily dosage commonly used with oral Bu.

Reovirus as an oncolytic agent against experimental human malignant gliomas.

Background: Reovirus is a naturally occurring oncolytic virus that usurps activated Ras-signaling pathways of tumor cells for its replication. Ras pathways are activated in most malignant gliomas via upstream signaling by receptor tyrosine kinases. The purpose of this study was to determine the effectiveness of reovirus as an experimental treatment for malignant gliomas.

Primary Central Nervous System Tumors in Adults.

It is important that before treatment is initiated, the precise diagnosis of brain tumor has been made and fits with the clinical, radiographic, and histologic findings. With low-grade gliomas, maximal surgical resection should be attempted. We delay radiation therapy unless the patient has significant neurologic symptoms that could be alleviated by treatment.

Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

Purpose: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy.

Patients And Methods: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.

Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

Background: Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy.

Procedure: An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy. Patients received dolasetron in single intravenous doses of 0.

Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group.

Background: Approximately 1% of children with unilateral Wilms tumor develop contralateral disease. The authors assessed the demographic and histologic features associated with metachronous bilateral Wilms tumor (BWT).

Methods: Characteristics of all children registered on the first four National Wilms Tumor Studies (NWTS) were recorded.

Long-term complications and post-treatment follow-up of patients with Wilms' tumor.

An increasing number of children with Wilms' tumor can expect to be cured, reflecting the undisputed progress made in the treatment of children with this renal cancer. However, it does underscore the need to screen survivors for late effects of cancer therapy. Some of the late effects, such as those following radiation therapy, should be expected after a considerable latent period.