Adverse effects of trimethoprim-sulfamethoxazole for the prophylaxis of Pneumocystis pneumonia in dermatology.

Trimethoprim-sulfamethoxazole (TMP/SMX) combination is used for the prophylaxis of Pneumocystis pneumonia (PCP). Although TMP/SMX is frequently used in dermatology for cases treated with corticosteroids and/or immunosuppressants, it is often difficult to continue the administration of TMP/SMX due to adverse events. There are only a few reported studies on the prophylaxis of PCP in dermatology. This is the first review focused on adverse events of TMP/SMX among patients with dermatological diseases compared with previous reports. In this study, we retrospectively investigated 132 cases treated with TMP/SMX and examined the adverse events. Adverse events occurred in 32 cases (24.2%) and the incidence in this study was higher than in previous reports. Thrombocytopenia occurred in 17 cases (12.5%), which was the most frequent adverse event. The possible causes of adverse events were that the standard dose of TMP/SMX may be excessive for most Japanese, in addition to the long administration period, and the concomitant use of corticosteroids and/or immunosuppressants in almost all cases. We must consider the risks of PCP and adverse events of TMP/SMX in each case. It is desirable to examine possible administration methods that can be continued by adjusting the dose and interval of TMP/SMX

Histological and quantitative polymerase chain reaction-based analysis of Buruli ulcer using mapping biopsy method.

Background:In Japan, Buruli ulcer cases are often advanced, requiring surgical treatment. However, extensive debridement is often difficult because of cosmetic and functional sequelae. Moreover, the lesions are complicated and composed of edematous erythema, necrotic ulcer, and erythematous skin lesions caused by a paradoxical reaction, which also make it difficult to perform adequate debridement.Methodology/principal findings:We performed quantitative polymerase chain reaction (PCR) analysis for IS2404 using 29 samples taken from mapping biopsy. We evaluated the relationship among mycobacterial burden, histopathological findings, and clinical outcomes using 83 tissue samples taken from mapping biopsy and debrided Buruli ulcer. On quantitative PCR, the Cp values of IS2404 amplification were substantially different in each site. The major histological findings could be divided into massive subcutaneous necrosis with scant inflammatory cell infiltration and dense inflammatory cell infiltration. Of the 84 sites, 34 were subjected to repeated histological evaluations. In these sites, histological necrosis did not disappear over time despite standard antibiotic treatment. In contrast, the ulcers were cured and no recurrences were observed without resecting the 11 biopsied sites that lacked histological necrosis. Although quantitative PCR revealed that a lower Cp value of IS2404 was associated with histological massive necrosis, sites that showed lower Cp values clinically did not always need debridement.Conclusion/significance:Our descriptive study revealed that the histological findings and amounts of mycobacterial DNA differed according to the sites despite being found in one lesion. Our results showed that the need for surgical debridement in each site was correlated with histological necrosis without inflammatory cell infiltration, as the inflammation is supposed to represent an active host immune response rather than mycobacterial burden. We suggest that the debridement of lesions with histological necrosis in mapping biopsy may be useful for Japanese cases with unsuccessful standard antibiotic treatment to achieve sufficient clinical improvement

Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

BackgroundAnti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.Patients and methodsThe study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.ConclusionNivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma

Mechanisms and Clinical Significance of Tumor Lymphatic Invasion

Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges

Mechanisms and clinical significance of tumor lymphatic invasion

Tumor-associated lymphatic vessels play an important role in tumor progression, medi-ating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes “hijacked” by tumor cells to gain access to the lymphatic system. Furthermore, we summarize the prognostic value of lymphatic invasion, discuss its relationship with local recurrence, lymph node and distant metastasis, and highlight potential therapeutic options and challenges.ISSN:2073-440

Analysis about the regulatory function of B1-B cells

科学研究費補助金研究成果報告書研究種目: 若手研究(B)研究期間: 2009～2011課題番号: 21791072研究代表者: 藤本 徳毅（滋賀医科大学・医学部・講師

Necrosis of Pedunculated Lipofibroma by Nab-Paclitaxel

We present a rare phenomenon of a soft tumor hanging on the woman’s left upper arm that underwent necrosis from the distal aspect during chemotherapy for pancreatic cancer. The benign tumor, pedunculated lipofibroma, originally had normal color for 10 years and then became necrotic when she was treated with gemcitabine and nab-paclitaxel. Necrosis stopped in conjunction with chemotherapy cessation. Dermatologists must remember that nab-paclitaxel could develop necrosis of a skin tumor