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Buffalo, New York, United States

Chanan-Khan A.,Roswell Park Cancer Center
Clinical advances in hematology & oncology : H&O | Year: 2010

Chronic lymphocytic leukemia (CLL) is a B-cell leukemia mainly affecting older adults. Historically, CLL has been regarded as an incurable disease, and treatment has been confined to cytotoxic chemotherapy regimens. However, prognosis for patients treated with these agents remained poor, prompting the development of new, targeted agents. The introduction of rituximab, a CD20-targeted monoclonal antibody, revolutionized the treatment for this disease. Rituximab in combination with fludarabine improved response rates and length of progression-free survival. The success of rituximab in this setting has prompted the development of many more investigational agents for CLL, including other antibody agents. However, as with any medication, the potential benefit achieved with CLL therapies is mitigated by the safety risk for the patient. These agents have been associated with adverse events such as immunosuppression, reactivation of cytomegalovirus, and infusion-related reactions that can occur with antibody administration. Adverse events can greatly affect the patient's quality of life and ability to tolerate therapy. Management of adverse events is a critical component of the overall treatment strategy for CLL, particularly in elderly patients. In this clinical roundtable monograph, 3 expert physicians discuss the latest clinical studies evaluating the treatment of CLL, focusing on the adverse events associated with each agent and the potential interventions that can be used to manage their occurrence.

Krivak T.C.,University of Pittsburgh | Darcy K.M.,Roswell Park Cancer Institute | Tian C.,Roswell Park Cancer Institute | Tian C.,Precision Therapeutics Inc. | And 4 more authors.
Gynecologic Oncology | Year: 2011

Objective: This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. Methods: Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS). Results: The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077). Conclusions: The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant. © 2011 Elsevier Inc. All rights reserved.

Parameswaran A.,State University of New York at Buffalo | Attwood K.,Roswell Park Cancer Center | Sato R.,State University of New York at Buffalo | Seiffert-Sinha K.,State University of New York at Buffalo | Sinha A.A.,State University of New York at Buffalo
British Journal of Dermatology | Year: 2015

Background Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering skin disease. It is known that individuals with autoimmune diseases such as PV, as well as their family members, are at increased risk of developing other autoimmune diseases. However, it is unknown whether there are specific autoimmune diseases that cluster with PV. Objectives To investigate the frequency of coexisting autoimmune diseases in patients with PV and their relatives, to determine the prevalence of specific autoimmune diseases in patients with PV vs. the general population and to identify statistically significant clinical clusters linking PV with other autoimmune disorders. Methods We performed a cross-sectional study and meta-analysis of patient data from our own patient database (n = 230), an anonymous online survey conducted by our laboratory (n = 171) and the International Pemphigus & Pemphigoid Foundation registry (n = 393). Results We found that the prevalences of autoimmune thyroid disease (AITD), rheumatoid arthritis and type 1 diabetes were significantly increased in patients with PV compared with the general population. These diseases were also among the most frequent in family members of patients with PV, in addition to systemic lupus erythematosus (SLE). Descriptive cluster analysis using basic principle components methods revealed that PV forms a distinct cluster with AITD, rheumatoid arthritis and type 1 diabetes, and another cluster with SLE, AITD and rheumatoid arthritis. Conclusions PV belongs to an established autoimmune disease cluster that includes AITD, rheumatoid arthritis and type 1 diabetes. Our data suggest the possibility of common genetic elements across clinically distinct diseases that might underlie autoimmune susceptibility. © 2014 British Association of Dermatologists.

Alexiev B.A.,University of Maryland, Baltimore | Levea C.M.,Roswell Park Cancer Center
International Journal of Surgical Pathology | Year: 2012

Nephrogenic adenoma (NA) is an uncommon and intriguing lesion in the urinary tract. The pathogenesis of NA is not entirely clear. NA was considered to be a metaplastic process of the urothelium in response to chronic irritation of the urinary tract. However, recent evidence has shown that NA is not a metaplastic lesion but rather a proliferation of exfoliated and implanted renal epithelial cells in the urinary tract. Histologically, NAs exhibit, singly or in combination, tubules, small papillae, and microcystic structures lined by cells with little cytological atypia and focal hobnail changes. Solid formations and compressed spindled cells within a fibromyxoid background are rarely observed. Differential diagnosis includes, but is not limited to, malignant neoplasms occurring at the same sites, in particular urothelial carcinoma with deceptively bland morphology (with small tubules, microcystic and nested variants), prostatic adenocarcinoma, and clear cell adenocarcinoma. Immunohistochemical studies with antibodies targeting members of the paired box gene family (PAX2 and/or PAX8) in NAs may be helpful in the differential diagnosis of urothelial lesions and prostatic adenocarcinoma. NAs are most likely to be confused with clear cell adenocarcinoma, especially in small biopsy specimens. This is confounded by both lesions being frequently positive for PAX2, PAX8, and CK7 and not infrequently positive for p504S (α-methylacyl-CoA-racemase, AMACR) by immunohistochemistry. Recognition of its characteristic morphological patterns and awareness of its unusual architectural and cytological features are important in making the diagnosis of NA and distinguishing this lesion from its mimickers. © 2012 The Author(s).

Greenberg C.C.,Dana-Farber Cancer Institute | Greenberg C.C.,Brigham and Womens Hospital | Lipsitz S.R.,Brigham and Womens Hospital | Hughes M.E.,Dana-Farber Cancer Institute | And 7 more authors.
Annals of Surgery | Year: 2011

Objective: To investigate the relationship between supply of subspecialty care and type of procedure preferentially performed for early stage breast cancer. Background: Three surgical options exist for early stage breast cancer: (1) breast conserving surgery (BCS), (2) mastectomy with reconstruction (RECON), and (3) mastectomy alone. Current guidelines recommend that surgical treatment decisions should be based on patient preference if a patient is eligible for all 3. However, studies demonstrate persistent variation in the use of BCS and RECON. Methods: Patients undergoing an operation for DCIS or stage I or II breast cancer at NCCN institutions between 2000 and 2006 were identified. Institutional procedure rates were determined. Spearman correlations measured the association between procedure types. Patient-level logistic regression models investigated predictors of procedure type and association with institutional supply of subspecialty care. Results: Among 10,607 patients, 19% had mastectomy alone, 60% BCS, and 21% RECON. The institutional rate of BCS and RECON were strongly correlated (r = -0.80, P = 0.02). Institution was more important than all patient factors except age in predicting receipt of RECON or BCS. RECON was more likely for patients treated at an institution with a greater supply of reconstructive surgeons or where patients live further from radiation facilities. RECON was less likely at institutions with longer waiting times for surgery with reconstruction. Conclusions: Even within the NCCN, a consortium of multidisciplinary cancer centers, the use of BCS and mastectomy with reconstruction substantially varies by institution and correlates with the supply of subspecialty care. Copyright © 2011 by Lippincott Williams & Wilkins.

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