Ki67 as a biologic marker of basal cell carcinoma: a retrospective study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biological markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histological variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation. OBJECTIVES: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables. METHODS: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up. Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histological analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion. RESULTS: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes. CONCLUSIONS: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histological subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

Novel rat model of methicillin-resistant Staphylococcus aureus-infected silicone breast implants: a study of biofilm pathogenesis.

BACKGROUND: Clinical infection of breast implants occurs in 7 to 24 percent of breast reconstructions. It may persist over time in the form of biofilm without overt manifestation and is extremely difficult to eradicate. The authors' aim was to establish a novel model for biofilm infection of silicone breast implants in rats. METHODS: Fifty-six rats underwent implantation of miniature silicone breast implants and/or methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Group A received implants covered with MRSA biofilm. Group B received implants and free planktonic MRSA. Group C received free planktonic MRSA without implants. A control group received sterile implants without MRSA. Each group was divided to receive either saline or vancomycin injections between days 4 and 11. Clinical evaluation, bacterial counts, and scanning electron microscopy were performed. RESULTS: The mortality rate in group B (implants infected with free planktonic MRSA) was significantly higher than that in all other groups [37 percent versus groups A and D (0 percent) and group C (7 percent)]. Treatment with vancomycin lowered temperature in groups B and C (p < 0.05) and improved wound healing in group B (p < 0.01). Vancomycin treatment reduced wound bacterial counts in free planktonic MRSA groups B and C but had no significant effect on biofilm MRSA-infected group A. CONCLUSIONS: The model successfully induced persistent breast implant infection. Free planktonic MRSA produced in situ biofilm on silicone implants. Biofilm infection has milder manifestations than free planktonic MRSA infection, which has higher rates of systemic infections and death when compared with either isolated biofilm infection or free planktonic MRSA infection without implant. Vancomycin has limited effect against mature biofilm.

Protective effect of human recombinant copper-zinc superoxide dismutase on zone of stasis survival in burns in rats.

Superoxide dismutase, acting as a scavenger of oxygen free radicals, has shown mixed results in increasing burn wound survival. Originally, we demonstrated that human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) could increase the survival of failing ischemic flaps in a rat model. Because of the possible similar pathophysiology of tissue ischemia in flaps and the zone of stasis in burns, we conducted a later study using 2 groups of rats with standardized intermediate burns, to ascertain whether Hr-CuZnSOD could increase zone of stasis survival in rats. The results showed that postburn Hr-CuZnSOD failed to improve zone of stasis survival in burns. We decided to undertake a new controlled study to ascertain whether there is a protective effect of Hr-CuZnSOD in cases of intermediate burns. We used 2 groups of rats, one of which received prophylactic treatments with Hr-CuZnSOD before the induction of standardized intermediate burns. Results showed that preburn Hr-CuZnSOD also failed to improve zone of stasis survival in burns. Further studies are needed to adequately understand the effect of oxygen free radicals in burn wound pathophysiology and to determine whether Hr-CuZnSOD has a role in the clinical management of burns or should be abandoned.

Lack of complications in skin surgery of patients receiving clopidogrel as compared with patients taking aspirin, warfarin, and controls.

Clopidogrel, a new antiplatelet agent that irreversibly inhibits platelet aggregation, is widely used today. This prospective work was conducted to evaluate the safety of performing skin surgery on patients taking clopidogrel. Patients undergoing surgery for excision of skin or subcutaneous lesions under local anesthesia taking clopidogrel were the study group. The control group comprised 2073 historical patients who had undergone a similar procedure. Data collected included: age, sex, past medical history, medications, and late complications. Follow-up was done at 1 to 2 weeks and 3 to 6 months. There were 32 patients on clopidogrel, having 38 lesions removed. Of these, seven patients were on aspirin and clopidogrel combined. The groups taking clopidogrel, aspirin, and warfarin had significantly more males, were older, and had significantly more comorbid medical conditions. There was no significant difference in the incidence of any of the complications in any of the groups. This study shows that patients taking clopidogrel before skin surgery, though older and with more associated medical conditions, do not experience a greater rate of complications. We conclude that patients undergoing minor excisional cutaneous surgery should continue taking clopidogrel because there is no apparent risk for increased complications when good meticulous surgical techniques are used.

Pemphigus variant associated with penicillin use: a case-cohort study of 363 patients from Israel.

OBJECTIVE: To determine whether medication use is associated with the development of a pemphigus variant. DESIGN: Population-based case-cohort study. SETTING: Health maintenance organization in Israel. METHODS: All incident pemphigus variant cases diagnosed from January 1, 1997, through December 31, 2001, among 1.5 million members were identified. A cohort of 150,000 was randomly selected from the health maintenance organization population as the control group. Data on case patients and control subjects, including all medication purchased during the 6 months before the diagnosis, were obtained using the health maintenance organization's central database. RESULTS: We identified a total of 363 case patients diagnosed as having pemphigus during the 5-year study (6,961,853 person-years of follow-up). The mean age at diagnosis was 49.8 (SD, 22.7) years, and 53% of the cases were women. Results of a multivariate analysis showed that increased risk for pemphigus was associated with purchasing penicillin during the 6 months before the diagnosis (odds ratio, 2.03; 95% confidence interval, 1.56-2.64). Compared with individuals with no penicillin purchases, we calculated increased risks of 1.84 (95% CI, 1.36-2.49) and 3.02 (95% CI, 1.41-6.49) in those with 1 and 3 or more purchases, respectively. None of the other examined medications, including cephalosporins, angiotensin-converting enzyme inhibitors, dipyrone, anticonvulsants, and nonsteroidal anti-inflammatory drugs, showed similar risks. CONCLUSIONS: To our knowledge, the present research is one of the largest published epidemiological studies on pemphigus variant. The use of computerized medical and administrative databases allowed the detection of case patients in the community, resulting in a higher calculated incidence rate than previously reported. The findings suggest a relationship between the use of penicillin and pemphigus variant. Further studies to assess the nature of this statistical association are warranted.

Reduced hospitalizations and death associated with influenza vaccination among patients with and without diabetes.

OBJECTIVE: To assess whether the influenza vaccination of community-dwelling, diabetic, elderly individuals is associated with reduced rates of hospitalization and death. RESEARCH DESIGN AND METHODS: In this outcome-research study, we compared mortality and hospitalization rates of 15,556 patients aged >or=65 years followed using a diabetes registry in a large health maintenance organization to that of 69,097 members not suffering from chronic disease who were considered as a reference group. The study outcomes included all-cause death and hospitalization in internal medicine or geriatric wards for any reason over winter and summer (control) periods. RESULTS: Vaccination rates were 48.8 and 42.0% among patients with diabetes and the reference population, respectively. Influenza vaccination was associated with a 12.3% reduction in hospitalization rates for patients with diabetes compared with 23.0% in the reference group (P = 0.08). The reduction in hospitalization rates was similar in both sexes among patients with diabetes. In addition, there was a significant reduction in mortality for the vaccinated group of patients with diabetes when compared with the nonvaccinated group except for female patients aged >or=85 years. CONCLUSIONS: The study results support the use of influenza vaccine among an elderly population. However, there does not appear to be an additional benefit for patients with diabetes.