Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Prognostic factors for satellitosis or in-transit metastasis in cutaneous squamous cell carcinoma: A multicentric cohort study.

BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.

Physical activity reduces intradermal bacterial load in a murine model submitted to forced swim training - a pilot study.

Regular exercise is beneficial to health. This study evaluated the effects of moderate and intense physical exercise modalities on intradermal infection by Staphylococcus aureus in a murine model. Mice that practiced moderate exercise had lower bacterial load on lymph nodes and less inflammatory infiltrate in dermis. They presented greater weight, however, less amount of epididymal fat: the weight was increased while they had fat diminished. A positive correlation was observed between lipid content and bacterial load in mice trained at moderate intensity. Animals that were under high intensity exercises presented superior bacterial load on the lymph nodes, increased neutrophil count and circulating lymphocytes, and had leukocyte recruitment to the dermis augmented, when compared to the ones in moderate exercise. These findings suggest that moderate physical activity modulates the immune response in dermal infection caused by S. aureus in a murine model.

Photodynamic therapy controls of Staphylococcus aureus intradermal infection in mice.

Infections caused by Staphylococcus aureus lead to skin infections, as well as soft tissues and bone infections. Given the communal resistance to antibiotics developed by strains of this bacterium, photodynamic therapy emerges as a promising alternative treatment to control and cure infections. Females of the Balb/C mice were infected with 108 CFU of methicillin-resistant S. aureus (MRSA) and divided into four distinct groups: P-L- (negative control group), P+L- (group exposed only to curcumin), P-L+ (group exposed only to LED incidence of 450 nm, 75 mW/cm2, and 54 J/cm2 for 10 min), and P+L+ (group exposed to curcumin followed by 10 min of LED irradiation) (n = 24). The mice were euthanized 48 and 72 h after infection, and biologic materials were collected for analysis of the bacterial load, peripheral blood leukocyte counts, and draining lymph nodes cell counts. The normalization of data was checked and the ANOVA test was applied. The bacterial load in the draining lymph node of P+L+ group was lower when compared to the control groups 72 h post infection (p < 0.0001), indicating that the LED incidence associated with curcumin controls of the staphylococci intradermal infection. The number of the total lymph node cells shows to be lower than control groups in the two availed times (p < 0.01). The histological analysis and the counting of white blood cells did not show differences among cells in the blood and in the tissue of infection. This is the first report showing that photodynamic therapy may be effective against MRSA infection in a murine model of intradermal infection.

A report of 4 years of experience of a multidisciplinary unit of psoriasis and psoriatic arthritis.

INTRODUCTION AND OBJECTIVES: Up to 30% of patients with psoriasis develop joint disease, the course of which can be improved by early diagnosis and treatment. The aim of this study was to describe our experience with a new multidisciplinary psoriasis and psoriatic arthritis unit over a period of 4 years (2009-2012). MATERIAL AND METHODS: Implementation of a PSOriasis Rheumatology and Dermatology unit (PSORD) to provide patient care and physician training. In the first phase of the project, referral criteria for the unit were defined and several meetings were organized to train and prepare the specialists involved in the program. In the second phase, a schedule was drawn up for monthly patient visits with the PSORD team. Starting in 2011, training was offered to dermatologists and rheumatologists from other hospitals interested in implementing a similar model. RESULTS: A total of 259 visits (71% first visits, 8% no-shows) were scheduled during the period analyzed, with a median of 8 visits (range, 2-14 visits) per session. Sixty-three percent of the patients were referred from the rheumatology department. Diagnosis and treatment were modified in 32% and 47% of cases, respectively. Three training courses were held with 15 physicians from 6 hospitals, 3 of which created similar units. CONCLUSIONS: The PSORD model improved the management of difficult-to-diagnose and/or uncontrolled disease, the early diagnosis and treatment of psoriatic arthritis, and collaboration between dermatologists and rheumatologists. Finally, the model lends itself to being exported to other settings.

Refractory childhood pemphigoid successfully treated with rituximab.

Bullous pemphigoid is an acquired autoimmune blistering disorder affecting mostly elderly people that is rare in children. There have been fewer than 100 cases of childhood bullous pemphigoid reported. Childhood bullous pemphigoid (CBP) generally has a good prognosis. Remission is usually achieved within several weeks to a few months, and relapses are rare, although refractory cases can occur, and the disease may be life threatening, particularly when lesions generalize. Herein we describe the case of an infant with severe CBP refractory to multiple treatments. In our case, therapy with azathioprine and intravenous immunoglobulin resulted in a slight clinical response, but only combined with high doses of prednisolone. Administration of rituximab led to a complete clinical response and allowed almost complete steroid tapering. There are no current guidelines indicating what doses and frequency of rituximab are safest or most effective in children with blistering diseases.

Análise imunoistoquímica do ki-67 em 140 pacientes com câncer de mama - correlação com fatores clínico-patológicos e sobrevida / Immunohistochemical analysis of ki-67 in 140 patients with breast cancer- correlation with clinicopathological factors and survival

O antígeno Ki-67 é utilizado para avaliar a atividade proliferativa em vários tumores. No entanto, o papel do Ki-67 como fator prognóstico em câncer de mama é ainda indefinido. O objetivo do trabalho foi analisar a expressão do antígeno Ki-67 correlacionando com fatores clínico-patológicos e sobrevida em pacientes com câncer de mama. Realizou-se a análise imunoistoquímica utilizando anticorpos monoclonais MIB-1 em 140 amostras de câncer de mama de mulheres com idade entre 27 e 90 anos, atendidas no Hospital Araújo Jorge da Associação de Combate ao Câncer de Goiás. O ponto de corte para a análise foi de 25%. A sobrevida global em cinco anos foi de 77,1%. Houve sobrevida significativamente pior nos casos com linfonodos positivos (p < 0,0001), tumores maiores (p < 0,0001), estádios mais avançados (p < 0,0001) e pacientes com receptores hormonais negativos (p = 0,019). Pacientes com imunodetecção de Ki-67 em mais de 25% das células tiveram pior sobrevida quando comparadas àquelas que expressaram Ki-67 em menos de 25% das células examinadas (70,8% x 82,7%), porém essa diferença não foi estatisticamente significativa (p = 0,094). A hiperexpressão do Ki-67 não se correlacionou com pior sobrevida no grupo de pacientes analisadas.

The Ki-67 antigen is used to evaluate proliferative activity in several tumors. However the role of the Ki-67 as a prognostic factor in breast cancer is still undefined. The aim of present study was to analyze the expression of Ki-67 antigen correlating with clinicopathological factors and survival in patients with breast cancer. We carried out an immunohistochemical analysis using MIB-1 monoclonal antibody in 140 specimen of breast cancer of women with age between 27 and 90 years. The cut-off point was 25%. The five year overall survival was 77.1%. There was a significant worse survival of patients with node positive (p < 0.0001), larger tumors (p < 0.0001), more advanced stages (p < 0.0001) and with negative hormonal receptors (p = 0.019). Patients with Ki-67 immunodetection in more than 25% of the tumors cells showed a poorer outcome when compared with those that express Ki-67 in less than 25% of the cells examined (70.8% x 82.7%), however this difference was not statistically significative (p = 0,094). The overexpression of Ki-67 did not correlate with a worse survival in the group of patients analyzed.

Reduced GABA neurotransmission underlies hyperalgesia induced by repeated forced swimming stress.

We determined if cutaneous hyperalgesia and pain-induced c-Fos overexpression in the spinal cord produced by repeated forced swimming (FS) stress in the rat were related to changes in GABA neurotransmission by studying spinal release of GABA and the effect of positive modulation of GABA-A receptors with diazepam. Male rats were daily submitted to 10-20 min of either forced swimming or sham swimming (SS) for 3 consecutive days. Two days later, spinal GABA release was estimated by in vivo microdialysis. In other set of rats, either diazepam (2 mg/kg, i.p.) or saline was administered 1h before either SS or FS and inflammatory nociception was assessed with the formalin test; it was followed by removal of lumbar spinal cords for c-Fos immunocytochemistry. Basal and pain-evoked release of GABA in the spinal cord was lower in FS rats than in SS rats. In contrast, pain scores during formalin test late phase and pain-induced c-Fos expression in laminae I-VI of ipsilateral dorsal horn were significantly higher in FS rats than in SS rats. In FS rats, diazepam did not have effect on GABA release but reduced pain scores and overexpression of c-Fos whereas flumazenil (0.1 mg/kg, i.p.), an antagonist of the benzodiazepine binding site, reversed these effects. When diazepam was given only 1h before the formalin test, it slightly but significantly reduced pain scores during late phase in FS rats but not in SS rats. In conclusion, stress-induced reduction in GABA-A receptor activation is involved in the development of FS stress-induced hyperalgesia.