Biomedical subjects

Mark Smolkin

Publications and source records attributed to Mark Smolkin.

6 recordsLinked to original sources

PubMed2006

Radical cystectomy with ileal conduit diversion: early prospective evaluation of the impact of robotic assistance.

OBJECTIVE: To compare the performance of radical cystectomy with ileal conduit diversion by standard methods with that using the assistance of the daVinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA). PATIENTS AND METHODS: From November 2003 to August 2005, we performed 30 radical cystectomies with ileal conduit urinary diversions on patients with bladder cancer. Seven patients (one woman) had a cystectomy with the daVinci system and 23 (nine women) had a standard cystectomy. Data were collected prospectively, including estimated blood loss (EBL), transfusion requirement, operative duration, hospital stay and body mass index (BMI), and compared. RESULTS: The mean EBL and transfusion requirements for standard and daVinci-assisted cases was 1109 and 479 mL (P = 0.002) and 2.7 and 1.6 units (P = 0.14), respectively. Four of seven patients received a transfusion in the robotic group, and 20 of 23 in the standard group (P = 0.084). The mean operative duration was 638 and 507 min (P = 0.005) for the daVinci and standard group, respectively, with respective mean hospital stays of 11 and 13 days (P = 0.52). There was no difference in patient BMI between the groups (P = 0.22). CONCLUSION: The daVinci-assisted cystectomy appears to offer some advantages over standard cystectomy. Larger randomized studies are needed to confirm these findings.

Aged↗

PubMed2006

Accuracy of assigned BI-RADS breast density category definitions.

RATIONALE AND OBJECTIVES: Quantitative criteria for the Breast Imaging Reporting and Data System (BI-RADS) mammographic density categories have recently been defined as <25% dense for almost entirely fatty, 25%-50% dense for scattered fibroglandular densities, 51%-75% for heterogeneously dense, and >75% dense for the extremely dense category. The purpose of this study is to compare the range of percent mammographic densities with radiologist-assigned BI-RADS mammographic density categories and compare with the recently issued definitions. MATERIALS AND METHODS: In this study, 200 consecutive negative analog screening mammograms were assigned BI-RADS mammographic density categories independently by three radiologists blinded to the other readers' density assignment. Quantitative assessment of percent mammographic density was performed using previously validated software. RESULTS: All three readers agreed on BI-RADS mammographic density categories in 98 cases (49%), and two of three readers agreed in all 200 cases. Using two reader's consensus, median mammographic density (range) was 6.0% (0.5%-19.2%) for fatty, 14.8% (1.2%-52.7%) for scattered densities, 51.2% (15.9%-82.2%) for heterogeneously dense, and 78.4% (60.1%-87.9%) for extremely dense breasts. The percent mammographic density ranges for fatty and extremely dense breasts correlated well with BI-RADS definitions, whereas the ranges of densities in the scattered and heterogeneously dense categories were considerably broader. CONCLUSION: Fatty and extremely dense BI-RADS categories compare relatively well to defined criteria, and therefore may be helpful in breast cancer risk models. Scattered fibroglandular densities and heterogeneously dense categories have broad percent mammographic density ranges and may not function well in breast cancer risk models.

Absorptiometry, Photon↗

PubMed2006

Immunity to melanoma antigens: from self-tolerance to immunotherapy.

The development of effective immune therapy for cancer is a central goal of immunologists in the 21st century. Our laboratories have been deeply involved in characterization of the immune response to melanoma and translation of laboratory discoveries into clinical trials. We have identified a cohort of peptide antigens presented by Major Histocompatibility Complex (MHC) molecules on melanoma cells and widely recognized by T cells from melanoma patients. These have been incorporated into peptide-based vaccines that induce CD8(+) and CD4(+) T-cell responses in 80-100% of patients. Major objective clinical tumor regressions have been observed in some patients, and overall survival in vaccinated patients exceeds expected stage-specific survival. New clinical trials will determine the value of combination of melanoma helper peptides (MHP) into multipeptide vaccines targeting CD8 cells. New trials will also evaluate new approaches to modulating the host-tumor relationship and will develop new combination therapies. Parallel investigations in murine models are elucidating the immunobiology of the melanoma-host relationship and addressing issues that are not feasible to approach in human trials. Based on the fact that the largest cohort of melanoma antigens are derived from normal proteins concerned with pigment production, we have evaluated the mechanisms of self-tolerance to tyrosinase (Tyr) and have determined how T cells in an environment of self-tolerance are impacted by immunization. Using peptide-pulsed dendritic cells as immunogens, we have also used the mouse model to establish strategies for quantitative and qualitative enhancement of antitumor immunity. This information creates opportunities for a new generation of therapeutic interventions using cancer vaccines.

Animals↗

PubMed2004

Allelic imbalance of 8p indicates poor survival in gastric cancer.

Gastric cancer is a common tumor worldwide and a tremendous health burden. However, the underlying mechanisms of tumorigenesis in this cancer's development are primarily undefined. Allelic imbalance (AI) of 8p has been reported in many cancers, yet, the target(s) of alteration and the importance of allelic imbalance on this chromosomal arm in gastric carcinoma development remained to be characterized. Our findings confirmed a high rate of AI on 8p in gastric cancers. Moreover, we demonstrated that AI on 8p, either overall or at marker D8S560, was associated with poorer survival in patients with gastric cancer. Finally, gastric cancers with a high rate of microsatellite instability were significantly associated with noncardia tumors and with female gender.

Adult↗

PubMed2003

Cluster stability scores for microarray data in cancer studies.

BACKGROUND: A potential benefit of profiling of tissue samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Hierarchical clustering has been the primary analytical tool used to define disease subtypes from microarray experiments in cancer settings. Assessing cluster reliability poses a major complication in analyzing output from clustering procedures. While most work has focused on estimating the number of clusters in a dataset, the question of stability of individual-level clusters has not been addressed. RESULTS: We address this problem by developing cluster stability scores using subsampling techniques. These scores exploit the redundancy in biologically discriminatory information on the chip. Our approach is generic and can be used with any clustering method. We propose procedures for calculating cluster stability scores for situations involving both known and unknown numbers of clusters. We also develop cluster-size adjusted stability scores. The method is illustrated by application to data three cancer studies; one involving childhood cancers, the second involving B-cell lymphoma, and the final is from a malignant melanoma study. AVAILABILITY: Code implementing the proposed analytic method can be obtained at the second author's website.

Algorithms↗

PubMedDate not supplied

Autoimmune toxicities associated with the administration of antitumor vaccines and low-dose interleukin-2.

The purpose of this investigation was to evaluate the occurrence of autoimmune toxicities associated with the administration of low-dose IL-2 in conjunction with vaccines for melanoma. Ninety-three patients with stage IIB, III, or IV melanoma were enrolled in three clinical trials and received anti-melanoma vaccines on days 1, 8, 15, 29, 36, and 43. The vaccines comprised peptide-pulsed dendritic cells, autologous tumor cells with GM-CSF in Montanide ISA-51, or synthetic peptides with GM-CSF in Montanide ISA-51. In conjunction with the vaccines, all patients were administered 3 x 10(6) IU/m2/d IL-2 subcutaneously for 42 days, either days 8 to 49 or 29 to 70. Clinical and laboratory data from these studies were reviewed in aggregate to evaluate the occurrence of autoimmune toxicities. Of 91 evaluable patients, vitiligo was documented in 6 patients (7%). In addition, one patient experienced transient severe insulin-dependent diabetes that resolved after discontinuing IL-2, and another experienced an exacerbation of his pre-existing diabetes; these occurrences are consistent with an autoimmune insulitis. Four occurrences (4%) of transient minor ocular toxicity were documented, but no autoimmune ocular toxicities or changes in visual acuity were found. Of 55 evaluable patients, 14 experienced thyroid abnormalities (25%). These were attributed to an autoimmune thyroiditis, which was supported by findings of antithyroid antibodies in three of the seven patients evaluated. Overall, autoimmune toxicities affecting several organ systems were observed in patients receiving melanoma vaccines in conjunction with low-dose IL-2. None of these toxicities caused major long-term effects, though one was acutely life-threatening and others contributed to treatment-related morbidity. Peptide- or cell-based vaccines administered in combination with low-dose IL-2 appear to be capable of breaking tolerance to self-antigens; despite the associated toxicities, these combinations may still be useful to administer as an immunotherapy for cancer. However, careful monitoring for autoimmune toxicities should be incorporated in future clinical studies incorporating low-dose IL-2.

Adult↗