Biomedical subjects

Richard L White

Publications and source records attributed to Richard L White.

9 recordsLinked to original sources

PubMed2006

Method of biopsy and incidence of positive margins in primary melanoma.

BACKGROUND: The staging of patients with primary melanoma is dependent on adequate sampling of the tumor thickness. Initial biopsies with a positive deep margin suggest inadequate sampling, potentially limiting accurate staging and affecting treatment decisions. METHODS: To determine the efficacy of shave biopsy to adequately sample the tumor, we retrospectively reviewed our pathology database for original pathology reports of primary melanomas accessioned between 01/01/04 and 6/30/05. The biopsies were evaluated by technique, the presence of tumor at the margins of the specimen, and specimen thickness. RESULTS: We identified 240 cases of primary melanoma; 223/240 were analyzable. The specimens were divided by biopsy technique (excisional, n = 51; punch, n = 44; and shave, n = 128). Shave and punch specimens had a significantly higher percentage of positive margins than excisional specimens (50, 68, and 16%, respectively; P < 0.0001). Shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (22, 7, and 2%, respectively; P = 0.0009). For melanomas <or=1 mm, shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (17, 0, and 0%, respectively; P = 0.0014). There was a significant difference in specimen thickness (P = 0.0005), with shave specimens being the thinnest. CONCLUSIONS: The presence of tumor at the lateral margin of punch biopsies is an expected result, since this method is often used to diagnose lesions with a large diameter. The presence of positive deep margins in 22% of shave biopsy specimens compromises the ability of this technique to properly stage patients.

Biopsy↗

PubMed2006

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Adult↗

PubMed2006

Detection of human MCP-4/CCL13 isoforms by SELDI immunoaffinity capture.

Monocyte Chemoattractant Proteins 4 (MCP-4/CCL13) is a member of a distinct, structurally-related subclass of CC chemokines mainly involved in recruitment of eosinphils to inflammatory sites. Recent evidence demonstrates that serum level of this protein strongly increases following high dose IL-2 immunotherapy. The physiological form of human MCP-4/CCL13 has yet to be purified. Therefore, the primary structure of the biologically relevant (mature) form has not been established. By using SELDI immunoaffinity capture technology we describe two mature isoforms both present in serum before and after high-dose IL-2 immunotherapy.

Journal Article↗

PubMed2006

Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients.

OBJECTIVE: To determine the impact of sentinel lymph node (SLN) status and other risk factors on recurrence and overall survival in head and neck melanoma patients. DESIGN: The SLN Working Group, based in San Francisco, Calif, with its 11 member centers, the John Wayne Cancer Institute, and The University of Texas M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma patients who had selective sentinel lymphadenectomy. A total of 614 subjects were analyzable. All centers obtained internal review board approval and adhered to the Health Insurance Portability and Accountability Act of 1996 regulations. A Cox proportional hazards model was used to identify factors associated with overall and disease-free survival. SETTING: Tertiary care medical centers. MAIN OUTCOME MEASURE: Clinical outcome of head and neck melanoma patients undergoing selective sentinel lymphadenectomy. RESULTS: Overall, 10.1% (n = 62) of the subjects had at least 1 positive node. Subjects with positive SLN status had significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were more likely to have ulcerated tumors (P = .004). During the median follow-up of 3.3 years, the overall mortality from head and neck melanoma was 10%, with more than 20% experiencing at least 1 recurrence. Multivariate analysis showed that tumor site was an independent predictor of mortality; location on the scalp had a more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor thickness was also an independent predictor of overall survival, and SLN status was the most important predictor of disease-free survival in the multivariate model (P < .001). Tumors on the scalp had the highest rate of recurrence, while those on the neck had the lowest. Tumor ulceration was the significant predictor of time to recurrence or disease-free survival (P < .001). CONCLUSION: In this multicenter study, SLN status and other risk factors have an effect on recurrence and/or overall survival.

Adult↗

PubMed2006

Inflammatory protein profile during systemic high dose interleukin-2 administration.

Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were down-regulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers.

Biomarkers↗

PubMed2004

A large population of 'Lyman-break' galaxies in a protocluster at redshift z approximately 4.1.

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.

Journal Article↗

PubMed2004

A retrospective study of columnar alteration with prominent apical snouts and secretions and the association with cancer.

BACKGROUND: Columnar alteration with prominent snouts and secretions (CAPSS) is routinely described on breast core needle biopsies (CNBs); however, its significance and appropriate treatment is unknown. This study evaluated the incidence of cancer (in situ/invasive) in core biopsies and in subsequent surgical biopsy specimens after an initial core biopsy identifying CAPSS. METHODS: Using our medical center's pathology database, we retrospectively identified lesions described as CAPSS on breast core needle biopsies performed between January 1998 and August 2003. The specimens were subdivided into CAPSS lesions with and without atypical features. We also identified lesions described as atypical ductal hyperplasia. RESULTS: Overall, 10 cancers were associated with 135 (7.4%) CAPSS lesions without atypia, and 11 (18.3%) were associated with 60 CAPSS lesions with atypia (P = 0.023). CAPSS lesions with atypical features had a slightly higher rate of coexisting cancer on initial biopsy than CAPSS without atypical features (7% vs 12%, P = 0.320). Specimens showing atypical ductal hyperplasia on initial biopsy had a greater rate of coexisting cancer than CAPSS with or without atypical features (P <0.0001). CONCLUSION: We support the existing recommendation that a patient with a CNB showing CAPSS with atypical features undergo surgical biopsy.

Biopsy, Needle↗

PubMed2004

Clinical use of fluorodeoxyglucose F 18 positron emission tomography for detection of renal cell carcinoma.

PURPOSE: We evaluate the role of fluorodeoxyglucose F 18 positron emission tomography (PET) in patients with renal cell carcinoma (RCC) by retrospective review. To our knowledge this series is the largest reviewing the use of PET in patients with RCC. MATERIALS AND METHODS: A total of 66 patients who underwent 90 PET scans for suspected or known RCC were identified. Dictated reports of PET, chest computerized tomography (CT), abdominal/pelvic CT and bone scan were examined with confirmation of results by histopathology or followup of at least 1 year. The accuracies of PET and conventional imaging modalities were compared. RESULTS: PET exhibited a sensitivity of 60% and specificity of 100% for primary RCC tumors (abdominal CT demonstrated 91.7% sensitivity and 100% specificity). For retroperitoneal lymph node metastases and/or renal bed recurrence, PET was 75.0% sensitive and 100.0% specific (92.6% sensitivity and 98.1% specificity for abdominal CT). PET had a sensitivity of 75.0% and a specificity of 97.1% for metastases to the lung parenchyma compared to 91.1% and 73.1%, respectively, for chest CT. PET had a sensitivity of 77.3% and specificity of 100.0% for bone metastases, compared to 93.8% and 87.2% for combined CT and bone scan. In 39 scans (32 patients) PET failed to detect RCC lesions identified by conventional imaging. CONCLUSIONS: The role of fluorodeoxyglucose F 18 PET in the detection of RCC is limited by low sensitivity. With superior specificity PET may have a complementary role as a problem solving tool in cases that are equivocal on conventional imaging.

Adult↗

PubMed2004

Update on the NSABP and ACOSOG breast cancer sentinel node trials.

Sentinel lymph node biopsy in women with breast cancer has become routine in many surgical practices; yet basic questions regarding the procedure remain unanswered. The National Surgical Adjuvant Bowel and Breast Project (NSABP) and the American College of Surgeons Oncology Group (ACOSOG) trials address the issues of morbidity, efficacy, safety, and the significance of low-volume disease. NSABP B-32 randomizes women to sentinel lymph node biopsy followed by a standard level I and II axillary dissection or sentinel lymph node biopsy without dissection unless metastatic disease is noted by H&E examination. Overall survival, disease-free survival, and morbidity serve as end points. Further pathologic evaluation of the lymph nodes with immunohistochemistry will be performed by the study center. This study is nearing its anticipated accrual goal. Patients enrolled in the now-closed ACOSOG Z0010 trial underwent bone marrow aspiration just prior to sentinel node biopsy. Immunocytochemical analysis of the marrow will be compared to sentinel lymph node (SLN) biopsy to determine prognostic accuracy. ACOSOG Z0011 randomizes women undergoing breast-conserving therapy with low-volume axillary disease to completion axillary dissection or observation. Overall survival, disease-free survival, local regional control, and morbidity serve as end points. This trial is currently enrolling patients.

Biopsy↗