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Grobmyer S.R.,University of Florida | Kooby D.,Emory University | Blumgart L.H.,Memorial Sloan Kettering Cancer Institute | Hochwald S.N.,University of Florida
Journal of the American College of Surgeons | Year: 2010

Background: Pancreatic anastomotic failure has traditionally been a source of significant morbidity and potential mortality after pancreaticoduodenectomy. Both patient-derived and technical factors contribute to pancreatic anastomotic failure. From a technical standpoint, an "ideal" pancreaticojejunal anastomosis would meet the following criteria: applicable to all patients, easy to teach, and associated with a low rate of pancreatic anastomotic failure-related complications. The pancreaticojejunostomy described by one of the authors (LHB) meets the criteria for an "ideal" pancreaticojejunostomy. Study Design: We performed an audit of results of a consecutive series of patients at two institutions who underwent pancreaticojejunostomy using the described technique. Pancreaticojejunostomy after pancreaticoduodenectomy was performed in all cases using a novel two-layer technique consisting of an outer full thickness pancreas-to-seromuscular jejunal anastomosis and an inner duct-to-mucosal anastomosis. Incidences of pancreatic anastomotic failure (measured using the International Study Group of Pancreatic Fistula definition) and perioperative pancreatic anastomotic failure-related complications were analyzed. Results: One hundred eighty-seven patients underwent pancreaticojejunostomy after pancreaticoduodenectomy using the described technique. Overall mortality was 1.6%. The rate of clinically significant pancreatic anastomotic failure (International Study Group of Pancreatic Fistula grade B or C) was only 6.9%. There was no bleeding, reoperation, or mortality secondary to pancreatic anastomotic failure among patients in this series. Conclusions: The novel pancreaticojejunostomy is applicable to all patients in whom the pancreatic duct can be identified, and it is associated with very low rates of significant postoperative morbidity and mortality. These findings support its routine use for pancreaticojejunal reconstruction after pancreaticoduodenectomy. © 2010 American College of Surgeons.


Shiyko M.P.,Northeastern University | Burkhalter J.,Memorial Sloan Kettering Cancer Institute | Li R.,Pennsylvania State University | Park B.J.,Hackensack University Medical Center
Journal of Consulting and Clinical Psychology | Year: 2014

Objective: The goal of this article is to introduce to social and behavioral scientists the generalized time-varying effect model (TVEM), a semiparametric approach for investigating time-varying effects of a treatment. The method is best suited for data collected intensively over time (e.g., experience sampling or ecological momentary assessments) and addresses questions pertaining to effects of treatment changing dynamically with time. Thus, of interest is the description of timing, magnitude, and (nonlinear) patterns of the effect. Method: Our presentation focuses on practical aspects of the model. A step-by-step demonstration is presented in the context of an empirical study designed to evaluate effects of surgical treatment on quality of life among early stage lung cancer patients during posthospitalization recovery (N = 59; 61% female, M age = 66.1 years). Frequency and level of distress associated with physical symptoms were assessed twice daily over a 2-week period, providing a total of 1,544 momentary assessments. Results: Traditional analyses (analysis of covariance [ANCOVA], repeated-measures ANCOVA, and multilevel modeling) yielded findings of no group differences. In contrast, generalized TVEM identified a pattern of the effect that varied in time and magnitude. Group differences manifested after Day 4. Conclusions: Generalized TVEM is a flexible statistical approach that offers insight into the complexity of treatment effects and allows modeling of nonnormal outcomes. The practical demonstration, shared syntax, and availability of a free set of macros aim to encourage researchers to apply TVEM to complex data and stimulate important scientific discoveries. © 2014 American Psychological Association.


Duhamel K.,Memorial Sloan Kettering Cancer Institute | Jandorf L.,Mount Sinai School of Medicine
Cancer Causes and Control | Year: 2010

Background: Despite the acknowledged importance of colorectal cancer (CRC) screening and its proven prognostic benefit, African American men and women simultaneously possess the highest rates of CRC-related incidence and mortality (Swan et al. in Cancer 97(6):1528-1540, 2003) and lowest screening rates in the United States (Polite et al. in Med Clin N Am 89(4):771-793, 2005). Effective, targeted interventions that promote CRC screening for this community are therefore critical. The current study evaluated the impact of a print-based educational intervention on screening behavior and associated patient-based factors, including cancer-related knowledge, fatalism, worry, and decisional balance (pros-cons). Methods: One hundred and eighteen individuals (mean age = 56.08, SD = 5.58) who had not undergone screening were recruited from two health clinics in New York City. Each participant received educational print materials regarding the need for screening, the process of undergoing screening, and the benefits of regular CRC screening. Results: One in four individuals had undergone post-intervention screening at a three-month follow-up. Whereas all participants reported a decrease in cancer-related worry (p < .05), it was a decrease in fatalism (p < .05) and an increase in decisional balance (p < .05) that was associated with post-intervention screening behavior. Discussion: These preliminary results suggest that fatalistic beliefs and an individual's assessment of the benefits and barriers of screening may be critical in the decision to undergo CRC screening. Future interventions to increase CRC-screening rates for this community may be improved by focusing on these patient-based factors. © 2010 Springer Science+Business Media B.V.


Heidel F.H.,Otto Von Guericke University of Magdeburg | Arreba-Tutusaus P.,Otto Von Guericke University of Magdeburg | Armstrong S.A.,Memorial Sloan Kettering Cancer Institute | Fischer T.,Otto Von Guericke University of Magdeburg
Clinical Cancer Research | Year: 2015

Acute myelogenous leukemia stem cells (AML-LSC) give rise to the leukemic bulk population and maintain disease. Relapse can arise from residual LSCs that have distinct sensitivity and dependencies when compared with the AML bulk. AML-LSCs are driven by genetic and epigenomic changes, and these alterations influence prognosis and clonal selection. Therapies targeting these molecular aberrations have been developed and show promising responses in advanced clinical trials; however, so far success with LSCs has been limited. Besides the genetic diversity, AML-LSCs are critically influenced by the microenvironment, and a third crucial aspect has recently come to the fore: A group of evolutionarily conserved signaling pathways such as canonical Wnt signaling, Notch signaling, or the Hedgehog pathway can be essential for maintenance of AML-LSC but may be redundant for normal hematopoietic stem cells. In addition, early reports suggest also regulators of cell polarity may also influence hematopoietic stem cells and AML biology. Interactions between these pathways have been investigated recently and suggest a network of signaling pathways involved in regulation of self-renewal and response to oncogenic stress. Here, we review how recent discoveries on regulation of AML-LSC-relevant evolutionarily conserved pathways may open opportunities for novel treatment approaches eradicating residual disease. © 2015 American Association for Cancer Research.


Wingard J.R.,University of Florida | Carter S.L.,EMMES Corporation | Walsh T.J.,U.S. National Cancer Institute | Kurtzberg J.,Duke University | And 14 more authors.
Blood | Year: 2010

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P =.09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803. © 2010 by The American Society of Hematology.

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