James S. Michaelson

American Cancer Society lung cancer screening guidelines

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Predicting the survival of patients with breast carcinoma using tumor size

Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method.

Occult Nipple Involvement in Breast Cancer: Clinicopathologic Findings in 316 Consecutive Mastectomy Specimens

PURPOSE Although breast-conserving surgery is a standard approach for patients with breast cancer, mastectomy often becomes necessary. Surgical options now include nipple-sparing mastectomy but its oncological safety is still controversial. This study evaluates frequency and patterns of occult nipple involvement in a large contemporary cohort of patients with the retroareolar margin as possible indicator of nipple involvement. PATIENTS AND METHODS Three hundred sixteen consecutive mastectomy specimens (232 therapeutic, 84 prophylactic) with grossly unremarkable nipples were evaluated by coronal sections through the entire nipple and subareolar tissue. Extent and location of nipple involvement by carcinoma was assessed with the tissue deep to the skin as potential retroareolar en-face resection margin. RESULTS Seventy-one percent of nipples from therapeutic mastectomies showed no pathologic abnormality, 21% had ductal carcinoma in situ (DCIS), invasive carcinoma (IC), or lymphovascular invasion (LVI), and 8% lobular neoplasia (lobular carcinoma in situ). Human epidermal growth factor receptor 2 amplification, tumor size, and tumor-nipple distance were associated with nipple involvement by multivariate analysis (P = .0047, .0126, and .0176); histologic grade of both DCIS (P = .002) and IC (P = .03), LVI (P = .03), and lymph node involvement (P = .02) by univariate analysis. Nipple involvement by IC or DCIS was identified in the retroareolar margin with a sensitivity of 0.8 and a negative predictive value of 0.96. None of the 84 prophylactic mastectomies showed nipple involvement by IC or DCIS. CONCLUSION Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy.

Melanoma in the young: Differences and similarities with adult melanoma : A case-matched controlled analysis

Melanoma in the first 2 decades of life is rare and is less well characterized than melanoma in adults. Previously published comparisons of melanoma of the young (age ≤20 years) and in adults have been biased by the observation that primary melanomas of the young are significantly thicker on average than adult melanomas. In this study, the use of an adult control group that was matched for tumor thickness adjusted for this bias and allowed for a comparison of the biology of pediatric melanoma and adult melanoma.

Matched Pair Analyses of Stage IV Breast Cancer with or Without Resection of Primary Breast Site

BackgroundReports demonstrate improved survival of stage IV breast cancer patients with primary cancer resection. This may result from selection for surgery, rather than biological processes.MethodsWe performed matched-pair analysis that minimized potential bias in selecting surgery for primary cancer. Chart review was also performed of 5-year survivors to assess selection bias affecting breast surgery.Results19,464 breast cancer patients were identified; 808 (4.2%) were stage IV: 622 were analyzed after eliminating wrong diagnoses or staging, and limiting patients to Massachusetts residents.Matched-pair analysis narrowed or eliminated apparent survival benefit associated with primary site surgery in several comparisons. When the impact of the sequence of systemic and surgical treatments was studied in stage IV patients, 90% 2-year survival occurred in patients receiving chemotherapy first, in contrast to receiving chemotherapy simultaneously with or after surgery, suggesting selection for delayed surgery after excellent response to initial chemotherapy. In bone metastases, the 2-year survival advantage occurred with chemotherapy before surgery; no difference in survival with or without surgery occurred when these treatments were simultaneous.Among 5-year survivors, frequency of primary site surgery after excellent response to systemic therapy, breast surgery in stage III patients incorrectly classified as stage IV, and frequency of oligo metastases all indicated selection bias.ConclusionsCase selection bias in primary breast cancer resection in state IV patients may explain most, if not all, the apparent survival advantage of such surgery.

Analysis of the structure and expression of the Augmenter of Liver Regeneration (ALR) gene

BackgroundThe gene encoding the hepatotrophic factor Augmenter of Liver Regeneration (ALR) has recently been cloned in the rat. The availability of the mouse form of ALR would allow the analysis of the role of this factor in the physiology of liver and other organs, while the identification of the human homolog would allow the transfer of the great wealth of information that has been generated in animal models to clinically oriented pilot trials, and eventually the therapeutic application of this information.Materials and MethodsStandard molecular biology approaches have been used to determine the genomic structure of the ALR gene in the mouse, and to characterize the ALR transcript and its protein product. The human ALR cDNA was also isolated and the amino acid sequence of the human gene product deduced. The mapping of mouse and human ALR genes on mouse and human chromosomes was then completed.ResultsThe protein coding portion of the mouse ALR gene is comprised of three exons, the first containing the 5′ untranslated sequence and the initial 18 bases after the ATG translation initiation codon, the second exon encompasses 198 bases, and the third exon contains the remaining portion of the protein coding sequence. Rat, mouse, and human ALR genes (and protein products) were found to be highly conserved and preferentially expressed in the testis and in the liver. The ALR gene maps to the mouse chromosome 17, in a region syntenic with human chromosome 16, where the T/t region has also been mapped.ConclusionsALR appears to be a protein with important physiologic properties, not exclusively limited to liver regeneration, with roles that are involved in the synthesis or stability of the nuclear and mitochondrial transcripts that are present in actively regenerating cells, particularly the germ cells of the testes.

Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis

BACKGROUND Burkitts lymphoma (BL) is a highly aggressive B-cell non-Hodgkins lymphoma (NHL) that may be cured with intensive chemotherapy. The addition of the CD20-directed monoclonal antibody rituximab to CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, alternating with ifosfamide, etoposide, and cytarabine) has not been studied despite efficacy in other aggressive CD20-positive NHLs. PATIENTS AND METHODS Eighty adult BL patients treated with or without rituximab were identified at our institutions. Response rate, overall survival (OS), and progression-free survival (PFS) are calculated. RESULTS There were fewer relapses in rituximab-treated patients (3 of 40 versus 13 of 40, P = 0.01). There was a trend for improvement in outcome favoring rituximab-containing therapy, with 3-year PFS (74% versus 61%) and 3-year OS (77% versus 66%), although these did not reach statistical significance. Advanced age and central nervous system involvement were associated with poorer OS on multivariable Cox regression analysis, adjusting for treatment, human immunodeficiency virus (HIV) involvement, and risk group. CONCLUSIONS CODOX-M/IVAC, with or without rituximab, is a highly effective regimen for the treatment of adult BL. Rituximab decreased the recurrence rate and showed a trend in favor of improvement in PFS and OS. HIV-infected patients achieved outcomes comparable with those of their non-HIV-infected counterparts.

The pattern of breast cancer screening utilization and its consequences

The objective of this study was to describe the pattern of screening utilization and its consequences in terms of tumor size and time of tumor appearance of invasive breast carcinoma among a population of women who were examined at a large service screening/diagnostic program over the last decade.

Biology of Desmoplastic Melanoma: A Case-Control Comparison With Other Melanomas

PURPOSE Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. PATIENTS AND METHODS From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. RESULTS Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. CONCLUSION Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness.

Development and validation of a model predictive of occult nipple involvement in women undergoing mastectomy

This prospective study aimed to build a predictive model using preoperative information to aid selection for nipple‐sparing mastectomy.