Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Infectious complications and managements for surgical site infections in genital Paget's disease.

BACKGROUND: Extramammary Paget's disease is an intra-epidermal carcinoma that occurs preferentially in genital areas. Patients with genital Paget's disease (GPD) sometimes develop severe post-surgical infections because of this anatomical disadvantage. OBJECTIVE: To study perioperative micro-organisms and surgical site infection (SSI) in GPD. METHODS: We examined micro-organisms isolated from preoperative lesions, necrotic sites and infected wounds in 60 adult patients with GPD who underwent surgery at our hospital between November 1990 and December 2005. Based on the obtained microbiological data, we assessed the incidence, risk factors and treatment of SSI. RESULTS: The colonized organisms found in preoperative GPD were Enterobacteriaceae (27.6%), methicillin-sensitive Staphylococcus aureus (MSSA) (22.4%) and coagulase-negative staphylococci (CNS) (15.5%), among others. In the postoperative necrotic sites, the frequency of MSSA isolation was reduced to 9.4%, while Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA) both increased in frequency from 3.4% and 0% upon preoperative examination to 18.8% and 9.4%, respectively. The incidence of SSI was 15%. In 7 of 9 SSIs, MRSA and/or P. aeruginosa were isolated. CONCLUSION: We have successfully identified a number of perioperative micro-organisms in GPD. The present observations may be extremely useful in choosing appropriate antimicrobial agents for use in the surgical treatment of GPD.

Koebner phenomenon on skin graft donor site in cutaneous angiosarcoma.

An 81-year-old woman developed a necrotic plaque and a surrounding purple-red, irregularly shaped macule on her scalp. The diagnosis of angiosarcoma was confirmed histologically. A wide surgical excision was made followed by a split-thickness skin graft from her right buttock. Nine months later, she noticed a dark purple-red lesion on the donor site which grew rapidly into a large mass. Histological examination revealed irregular clefts and vascular channels lined by atypical endothelial cells. Lung metastasis and pneumothorax were also noted. The secondary tumor appeared to represent Koebner phenomenon in a patient with angiosarcoma of the scalp.

Adherence characteristics and susceptibility to antimicrobial agents of Staphylococcus aureus strains isolated from skin infections and atopic dermatitis.

We examined the adherence characteristics and susceptibility to various antimicrobial agents of 130 strains of Staphylococcus aureus isolated from infective skin lesions and 135 strains of S. aureus isolated from non-infective eczematous lesions of atopic dermatitis (AD) patients. The isolation rate of methicillin-resistant S. aureus (MRSA) was 27.7% in strains from clinical sources excluding AD and 31.1% in those from AD. Coagulase type II strains were most frequently observed in MRSA strains isolated from all sources excluding AD, and coagulase type III strains were most frequently observed in those isolated from AD. We proposed that antimicrobial treatment for AD patients should be carefully designed to prevent MRSA infection. Plasma coagulation ability was lowest in S. aureus strains isolated from abscesses, suggesting that the lower production of fibrin observed in abscesses may assist the infiltration of neutrophils into skin tissues and that a decrease in plasma coagulation ability may enable abscess formation. Adherence to polypropylene tubes with slime production was most evident in S. aureus strains isolated from felon and least evident in those isolated from cellulitis and lymphangitis. Tube adherence was characteristic of the S. aureus strains attached to superficial skin tissues, but not necessarily for strains that had infiltrated the deep skin tissues. Fusidic acid demonstrated significant antimicrobial activity against the MRSA strains, but rifampicin was the strongest antimicrobial agent.

Nasal and nasal-type natural killer/T-cell lymphoma.

Nasal and nasal-type natural killer (NK)/T-cell lymphomas follow an aggressive course and have a poor prognosis. Recent pathologic studies suggest that the disease is a malignant proliferation of NK cells, which often express CD56. An association with the Epstein-Barr virus has also been reported. Skin involvement occurred in each of the 3 patients studied. Radiation therapy provided some benefit to the patients in the early stages. Conventional chemotherapies were not effective. To overcome this multiple-drug resistance of the tumor cells, cyclosporine and high-dose chemotherapy was combined with peripheral-blood stem-cell transplantation. The average life span from the onset of the disease for our patients was 9.6 months. Further improvement in the management of nasal and nasal-type NK/T-cell lymphomas is necessary.

[Percutaneous transhepatic portal vein embolization for hepatocellular carcinoma].

We report on the significance of percutaneous transhepatic portal vein embolization (PTPE) for hepatocellular carcinoma based on the results in 111 patients who underwent PTPE in our hospital. All patients tolerated the procedure without major complications, although transient elevations in serum transaminase levels were noted. Immediately after PTPE, the portal pressure increased. Portal venous flow at the main portal trunk decreased, but the flow in the nonembolized part of the liver increased. PTPE produced regenerative hypertrophy in the nonembolized part of the liver, which was mainly predicted by the volume of the embolized area and the morphological score of the hepatitis or cirrhosis. PTPE increased the safety of subsequent hepatectomy and expanded the indications for hepatectomy. PTPE is also useful as a type of multiplicative therapy for hepatocellular carcinoma.

[Percutaneous microwave coagulation therapy for hepatocellular carcinoma--study on its therapeutic effect in surgical cases].

Six patients with hepatocellular carcinoma were subjected to percutaneous microwave coagulation therapy (PMCT) by ultrasonic guiding. The size of the main tumor in the present cases was limited to not more than 2 cm. From 18 to 48 days after PMCT, each patient was subjected to surgery and pathological examination. By macroscopic observation, the PMCT area including both non-tumor and tumor regions looked yellowish white, and the boundary was clearly recognized. In the histological examination, the coagulation area surrounded by fibrous capsule was found, and deletion of nuclei and changes in stainability were observed in the marginal region. These changes indicated obvious coagulation necrosis, but the changes became less intense toward the center in the area, and in some portions, the tissue was indistinguishable from viable cells by light microscopy. In 2 cases out of the 6, part of the tumor remained outside the coagulation area. Since only the area determined by the microwave electrode is coagulated to cause necrosis on PMCT, sufficient safety margin should be required.