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Biomedical subjects

Michael E Ming

Publications and source records attributed to Michael E Ming.

18 recordsLinked to original sources

Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma.

BACKGROUND: Sentinel lymph node (SLN) status is an important prognostic factor for survival for patients with primary cutaneous melanoma. To address the issue of selecting patients at high and low risk for a positive SLN, prognostic factors were sought that predict SLN involvement by examining characteristics of both the primary tumor and the patient within the context of a biological model of melanoma progression. METHODS: The study included 682 patients with primary vertical growth phase (VGP) melanoma and no clinical evidence of metastatic disease who underwent SLN biopsy (1995-2003). Logistic regression and classification tree analyses were used to investigate the association between SLN positivity and Breslow thickness, Clark level, tumor infiltrating lymphocytes (TIL), ulceration, mitotic rate (MR), lesion site, gender, and age. RESULTS.: In all, 88 of the 682 patients had > or =1 positive SLN (12.9%). In the multivariate analysis, MR, TIL, and thickness were found to be independent prognostic factors for SLN positivity. In the classification tree, four different risk groups were defined, ranging from minimal risk (2.1%) to high risk (40.4%). In lesions < r =2.0 mm, MR was important in risk-stratifying patients, and in lesions >2.0 mm TIL was important. CONCLUSIONS: By incorporating biologically based variables such as VGP, TIL, and MR along with thickness into a prognostic model, both patients at high risk and minimal risk for SLN positivity can be identified. If validated, this model can be used in patient management and trial design to select patients to undergo or be spared SLN biopsy.

Adult↗

Melanoma chemoprevention.

BACKGROUND: Despite efforts to promote sun protection behaviors, melanoma incidence continues to increase. The prognosis of advanced melanoma remains extremely poor in spite of treatment advances, emphasizing the importance of exploring additional preventive measures. OBJECTIVE: We sought to summarize the results of published research on candidate chemoprevention agents for melanoma. METHODS: We conducted a narrative review of the literature. RESULTS: Investigation into a possible role in melanoma chemoprevention continues for multiple agents, including sunscreen, lipid-lowering medications, nonsteroidal anti-inflammatory drugs, dietary nutrients, immunomodulators, and other drugs, including retinoids, difluoromethylornithine, and T4 endonuclease V. LIMITATIONS: Systematic review of the literature was not performed. CONCLUSION: Because no agent yet emerges as a clear choice for effective melanoma chemoprevention, sun avoidance and sun protection remain the mainstay of melanoma prevention for persons at high risk.

Anti-Inflammatory Agents, Non-Steroidal↗

Predictors of regional nodal disease in patients with thin melanomas.

BACKGROUND: Most melanoma patients present with thin ( 0, vertical growth phase (VGP), male sex, and ulceration were statistically significant predictors of RND. Patients at the highest risk according to a classification tree analysis (VGP and MR>0) had an RND rate of 11.9%. The regression model developed predicted well the SLN status in the validation sample. CONCLUSIONS: Investigation of a large pre-SLN population identified MR>0, ulceration, VGP, and male sex as independently predictive of RND in patients with thin melanomas. These factors may help to identify subgroups of these patients that have clinically significant risks of SLN positivity.

Female↗

Diagnosing and managing cutaneous pigmented lesions: primary care physicians versus dermatologists.

BACKGROUND: Primary care physicians (PCPs) are often expected to screen for melanomas and refer patients with suspicious pigmented lesions to dermatologists. OBJECTIVE: To assess whether there is a difference between dermatologists and PCPs in accurately diagnosing melanoma and appropriately managing (based on decisions to refer/biopsy) suspicious pigmented lesions. DESIGN, PARTICIPANTS: A survey based on a random sample of 30 photographs of pigmented lesions with known pathology was administered to 101 dermatologists and 115 PCPs from October 2001 to January 2003. MEASUREMENTS: Likelihoods that a photographed lesion was melanoma and that the lesion should be biopsied/referred were scored on a 1 to 10 scale. Accuracy of melanoma diagnosis and appropriateness of pigmented lesion management were compared between dermatologists and PCPs by using the areas under (AUC) the receiver operating characteristic (ROC) curves. RESULTS: Dermatologists were superior to PCPs in diagnosing melanomas (AUC 0.89 vs 0.80, P<.001) and appropriately managing pigmented lesions (AUC .84 vs 0.76, P<.001). PCPs who tended to biopsy lesions themselves did better at managing pigmented lesions than PCPs who did not perform biopsies. Dermatology training during residency did not significantly improve the diagnostic accuracy of PCPs nor their management of pigmented lesions. CONCLUSIONS: Dermatologists have both better diagnostic accuracy and ability to manage pigmented lesions than PCPs. Yet, there is a shortage of dermatologists to meet the demand of accurate melanoma screening. More innovative strategies are needed to better train PCPs and enhance skin cancer screening.

Biopsy↗

Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma.

PURPOSE: Tumor cell proliferation is a central feature of melanoma progression. In this study, we characterized three biomarkers of proliferation (Ki67 expression, dermal mitotic rate [MR], and tumorigenicity) in thin (< or = 1.00 mm) primary cutaneous melanomas and examined their association with prognosis. PATIENTS AND METHODS: We used immunohistochemistry to determine Ki67 expression using the monoclonal antibody MIB-1 in lesions from a prospective cohort that included 396 patients with thin invasive primary melanomas seen between 1972 and 1991. A multivariate Cox proportional hazards model was used to define independent prognostic factors, and recursive partitioning was used to develop a prognostic tree identifying risk groups. RESULTS: Dermal Ki67 expression was lower than epidermal Ki67 expression in radial growth phase (RGP) melanomas (n = 171), and dermal Ki67 expression and MR were higher in tumorigenic vertical growth phase (VGP) melanomas (n = 193) compared with RGP and nontumorigenic VGP melanomas (n = 42). Dermal Ki67 expression, MR greater than 0, growth phase, thickness, ulceration, tumor-infiltrating lymphocytes, and sex were associated with metastasis at 10 years, however, only dermal Ki67 expression, MR greater than 0, and sex were independent prognostic factors. Two high-risk groups were identified: men and women with dermal MR greater than 0 and dermal Ki67 expression > or = 20% in tumor cells and men with MR greater than 0 and Ki67 expression less than 20%, with 10-year metastasis rates of 39% and 20%, respectively. CONCLUSION: Proliferation slows as melanoma cells enter the dermis and then increases with the onset of tumorigenic VGP. Ki67 expression and dermal MR provide independent prognostic information that can potentially be used in risk-based management of patients.

Adult↗

Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas.

BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) provide important prognostic information for patients with early-stage melanoma. Although the use of this technique in patients with thin melanomas (< or =1.00 mm) is not routine, risk factors that may predict sentinel lymph node (SLN) positivity in this patient population are under investigation. We sought to determine whether mitotic rate (MR) is associated with SLN positivity in thin-melanoma patients and, therefore, whether it may be used to risk-stratify and select patients for LM/SL. METHODS: Clinical and histopathologic variables were reviewed for 181 patients with thin melanomas who underwent LM/SL from January 1996 through January 2004. Univariate and multivariate logistic regression analyses were performed to identify factors associated with SLN positivity. Risk groups were defined on the basis of the development of a classification tree. RESULTS: The overall SLN positivity rate was 5%. All patients with positive SLNs had an MR of >0. By univariate analysis, MR and thickness were significant predictors of SLN positivity. The association between MR and SLN positivity remained significant controlling for each of the other variables evaluated. On the basis of a classification tree, patients with an MR >0 and tumor thickness > or =.76 mm were identified as a higher-risk group, with an SLN positivity rate of 12.3%. CONCLUSIONS: In patients with thin melanomas, MR >0 seems to be a significant predictor of SLN positivity that may be used to risk-stratify and select patients for LM/SL. To confirm these results, the predictive value of MR for SLN positivity needs to be validated in other populations of thin-melanoma patients.

Female↗

Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging.

PURPOSE: The majority of invasive primary melanomas are thin (< or = 1.00 mm). Since the current staging system imperfectly predicts outcome in patients with such lesions, we sought to develop a more effective classification scheme to better identify both patients at high risk of metastasis who are candidates for further staging and therapy and those with little risk. PATIENTS AND METHODS: This prospective cohort study included 884 patients who had thin invasive melanomas. A tree-structured analysis of 10-year metastasis was used to develop a new classification scheme. RESULTS: The overall 10-year metastasis rate was 6.5% (95% CI, 4.8% to 8.1%). The prognostic tree defined four risk groups: high-risk: men with vertical growth phase (VGP) lesions that had mitotic rates (MRs) greater than 0, and for whom the 10-year metastasis rate was 31% (22% to 42%; n = 90); moderate-risk: women with VGP lesions that had MRs greater than 0 and for whom the rate was 13% (9% to 18%; n = 136); low-risk: patients with VGP lesions that had MR of 0 for whom the rate was 4% (2% to 7%; n = 247); and minimal-risk: patients with invasive lesions without VGP for whom the rate was 0.5% (0% to 1.2%; n = 411). Survival curves differed significantly among the four groups (P <.001). CONCLUSION: Growth phase, mitotic rate, and sex are important prognostic factors for patients with thin melanomas, and they identify subgroups at substantial risk for metastasis. After validation in other populations, the proposed prognostic tree will be useful in the design of clinical trials and clinical management.

Aged↗

Validity of patient self-reported history of skin cancer.

OBJECTIVE: To determine the validity of patient self-report of skin cancer history. DESIGN: A cohort of patients was randomly selected from the case group in a prior case-control study involving skin cancer, and a second cohort was randomly selected from the controls of that study. Patient self-reported history (as determined by responses to a survey) was compared with the gold standard of chart documentation of a pathology report or a procedure note from Mohs micrographic surgery demonstrating skin cancer. SETTING: University-based outpatient dermatology clinic. PATIENTS: Three hundred patients were selected. MAIN OUTCOME MEASURES: Patients were considered to have correctly classified their skin cancer history if their self-reported history was consistent with chart documentation. RESULTS: We obtained chart information for 258 patients.Of those patients, 183 (70.9%) had chart documentation of nonmelanoma skin cancer, and 16 (6.2%) had chart documentation of a melanoma. Using chart documentation as the gold standard, we found that patients correctly identified their basal cell carcinoma status in 84.3% of cases; their squamous cell carcinoma status in 81.5% of cases; their overall nonmelanoma skin cancer status in 91.8% of cases; their melanoma status in 94.8% of cases; and their overall skin cancer status in 92.6% of cases. Patients' self-reported history of skin cancer of any type had a positive predictive value of 95.1% and a negative predictive value of 85.9%. CONCLUSIONS: Self-reported history of skin cancer had a high degree of sensitivity and specificity and a high positive and negative predictive value within the study population. Obtaining medical information by patient report appears to be a useful tool for determining medical history of skin cancer.

Adult↗

Merkel cell carcinoma.

Merkel cell carcinoma is a rare cutaneous neoplasm most commonly affecting the head and neck of elderly white patients. Even with treatment, Merkel cell carcinoma has a strong propensity toward local recurrence, lymphatic spread, and distant metastasis. Because of its rarity and the subsequent lack of well-controlled clinical trials, no single standard of care exists for the treatment of this aggressive tumor. In our institution, primary lesions are excised with wide margins or by Mohs' micrographic surgery. After local removal, the excision site is treated locally with external radiation therapy. Sentinel lymph node mapping and biopsy are performed. Patients with tumor within a sentinel lymph node undergo lymph node dissection and radiation to the lymphatic basin. Adjuvant chemotherapy is offered to high-risk patients with local disease and to patients with metastases. Patients with distant metastases are treated with a combination of salvage chemotherapy and radiation therapy.

Carcinoma, Merkel Cell↗

The lack of a relationship between atopic dermatitis and nonmelanoma skin cancers.

BACKGROUND: Very little has been published on whether a relationship exists between atopic dermatitis (AD) and skin cancer. OBJECTIVE: The goal of this study was to investigate whether individuals with AD are more likely than other patients with dermatologic conditions to develop nonmelanoma skin cancer. METHODS: This was a case-control, mailed-survey study. RESULTS: Of those contacted, 69.8% (3207 of 4591) filled out the survey. Of the control patients, 18.4% (254) had a history of AD as defined by the United Kingdom Working Party diagnosis criteria and composed 13.7% (210) of the cases. The unadjusted odds ratio of AD to nonmelanoma skin cancer was 0.70 (95% confidence interval 0.57-0.85). After fully adjusting for age, sex, ethnicity, and topical steroid use the odds ratio was 0.78 (0.61, 0.98). Using different definitions of AD had little effect on this result. CONCLUSIONS: It does not appear that patients with a history of AD are more likely to develop nonmelanoma skin cancers than other patients with dermatologic conditions.

Aged↗

Mail surveys can achieve high response rates in a dermatology patient population.

In order to understand the burden of skin disease on patient populations, researchers need to be able to measure exposures and outcomes of interest in a population-based study. One method of obtaining such information is mailed patient surveys. This method of obtaining information, however, raises concerns regarding possible low response rates, and to the best of our knowledge, this method has not been attempted in large dermatology patient populations with a high response rate. We sought to determine whether using a slightly modified version of the Dillman Total Design Method as a mailed survey protocol would result in a high response rate in a dermatology population. A mail survey was sent using a slightly modified version of Dillman's Total Design Method to 4894 patients seen in the Dermatology Department of the University of Pennsylvania, who were diagnosed with nonmelanoma skin cancer, dermatophytosis, acne rosacea, seborrheic keratosis, or warts; 74.1% of the subjects responded to the mailings; 69.8% (n=3203) of patients returned a completed survey. Response rates (both as overall response and as survey completers only) were high across a wide spectrum of dermatologic illnesses and did not vary significantly by entry diagnosis. Dillman's Total Design Method appears to be an effective tool for researchers studying the burden of skin disease in a large sample of dermatology patients.

Aged↗

Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi.

BACKGROUND: Desmoplastic melanoma (DMM) is an uncommon melanoma variant with a distinct morphology, including a prominent spindle cell component with fibrosis, as well as a distinct immunohistochemical profile. Histologically, the spindle cell component of DMM can be confused with sclerotic/desmoplastic nevi, nonpigmented blue nevi, scar, and neural tumors. The histological distinction between sclerotic/desmoplastic/blue nevi and DMM using standard light microscopic techniques can be exceedingly subtle. Therefore, we investigated whether immunohistochemical staining for Melan-A and Ki-67 expression can be used to discriminate these lesions, distinguishing between epithelioid and spindle cell compartments of the lesions. DESIGN: Fifty cases of DMM and 13 cases of sclerotic/desmoplastic/blue nevi were identified. Standard immunohistochemical techniques were used with antibodies towards HMB-45, Melan-A (A103), and Ki-67; 43 of 50 DMM cases were available for staining with Melan-A, 42 of 50 for HMB-45, and 31 of 50 cases were stained with Ki-67. All 13 nevi were stained for Melan-A and 8 for Ki-67. Immunoreactivity to Ki-67 antibody was scored as 0 to 5%, 6 to 10%, 11 to 30%, or greater than 30% positive tumor cells. RESULTS: Only 3 of 43 and 3 of 42 of spindle cell compartments of DMMs were positive for Melan-A and HMB-45, respectively. Focal staining of epithelioid cells in the junctional component or superficial dermis was observed in 33% (14/43). In contrast, 100% of the 13 nevi were strongly positive for Melan-A (P < 0.001). Seventeen melanomas (55%) were 0 to 5% positive for Ki-67, five (16%) fell into the 6 to 10% category, three (10%) were between 11 and 30%, and six (19%) were at least focally greater than 30% positive. All 8 nevi (100%) had less than 5% positive cells for Ki-67 (P = 0.02), with only 2 cases having more than 2% positive cells. CONCLUSION: The sclerotic/desmoplastic and hypopigmented blue nevi were uniformly positive for Melan-A, while the vast majority of DMM were negative in their spindle cell compartments. Melan-A is very useful in distinguishing between DMM and sclerotic nevi. Ki-67 appears to be an inconsistent marker for DMM. However, a high labeling index (over 5%) may be used as a clue in diagnosing DMM.

Antigens, Neoplasm↗

Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists.

BACKGROUND: Although a nevus with the microscopic features of a "dysplastic nevus" is commonly seen, the nomenclature used to describe such a lesion has been thought to be inconsistent. A 1992 National Institutes of Health (NIH) Consensus Conference sought to unify nomenclature and suggested that the term "nevus with architectural disorder" be used along with a comment on melanocytic atypia. METHODS: We performed a cross-sectional mail survey to determine preferred terminology as well as the level of adherence to the NIH-recommended nomenclature. All 856 active members of the American Society of Dermatopathology (ASDP) and 1100 (13.0%) of the 8471 active members of the American Academy of Dermatology (AAD) were surveyed. RESULTS: Five hundred and thirty-three ASDP members and 483 AAD members who fulfilled eligibility criteria completed the questionnaire. The term "dysplastic nevus" was favored by the largest number of responders (favored by 39.1% of ASDP members and 62.3% of AAD members), while the 1992 NIH Consensus Conference-recommended terminology was the second most popular term (25.3% of ASDP and 15.1% of AAD members). Dermatopathologists (OR = 1.9, p = 0.0001) and those who had dual training in dermatology and dermatopathology (OR = 1.6, p = 0.02 for ASDP members; OR = 2.3, p = 0.02 for AAD members) were more likely to adhere to the 1992 NIH Consensus Conference nomenclature. CONCLUSIONS: Despite attempts to unify nomenclature for microscopically dysplastic nevi through the NIH Consensus Conference, wide variation in terminology persists.

Consensus Statements as Topic↗

Psychosocial factors related to the correspondence of recipient and provider perceptions of social support among patients diagnosed with or at risk for malignant melanoma.

This study examined considered perceptions of social support and factors contributing to increased support among 18 patients diagnosed with or at risk for malignant melanoma and their partners. Partner support, perceived stress, emotional approach coping and partner empathy were evaluated. Results showed lack of correspondence between patient and partner reports of support. Greater correspondence between reports was associated with increased patient emotional approach coping. Partners reported increased empathy following the patients' diagnoses and more perceived stress than patients. Patients indicated greater use of emotional approach coping than their partners. Male partners reported engaging in less emotional expression than female partners. Interventions might incorporate partner participation to resolve misperceptions of support and to foster factors that promote increased support.

Adaptation, Psychological↗

Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?

To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly. Fifteen dermatopathologists examined the cases separately. Margin status was categorized as positive, negative, or indeterminate. Kappa statistics were calculated per dermatopathologist and per case. One case from each group was excluded because epidermis was not available in the routine sections. Of 330 evaluations (22 cases, 15 dermatopathologists), there were 132 diagnostic discrepancies (40.0%): 66 each for MM and NML (mean per case for both diagnoses, 6). In 9 instances (6.8%), the change was from positive (frozen) to negative (permanent) and in 43 (32.6%), from negative (frozen) to positive (permanent). There was poor agreement between frozen and permanent sections (kappa range per dermatopathologist, -0.1282 to 0.6615). If permanent histology is considered the "gold standard" for histologic evaluation, en face frozen sections are not suitable for accurate surgical margin assessment of melanocytic lesions.

Aged↗

Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus.

OBJECTIVES: To illustrate the potential for aggressive growth of cutaneous squamous cell carcinomas (SCCs) in patients infected with the human immunodeficiency virus (HIV) and to determine the factors associated with increased morbidity and mortality from aggressive SCCs in HIV-infected patients. DESIGN: Retrospective nonrandomized case series. SETTING: University-based dermatologic referral center. PATIENTS: A consecutive sample of 10 patients infected with HIV who had "aggressive" SCC based on the following criteria: diameter larger than 1.5 cm, rapid growth rate, local recurrence, and/or evidence of metastasis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Five patients died of metastatic SCC within 7 years of their initial diagnosis despite treatment. Human immunodeficiency virus stage and the degree of immunosuppression were not associated with increased morbidity and mortality. Patients initially undergoing combination surgery and radiation therapy or radical neck dissection had the best outcomes. CONCLUSIONS: Patients infected with HIV can develop rapidly growing cutaneous SCCs at a young age, with a high risk of local recurrence and metastasis. High-risk SCCs should be managed aggressively and not palliatively in patients infected with HIV.

Adult↗