4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress

4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds.     

Cutaneous squamous cell carcinoma,thyroid cancer and Langerhans cell histiocytosis in a patient with X‐linked recessive Mendelian susceptibility to mycobacterial diseases with a nuclear factor‐κB essential modifier mutation

Nuclear factor (NF)‐κB essential modifier (NEMO), also known as IκB kinase subunit‐γ (IKKγ), is a pivotal molecule in the NF‐κB signaling pathway. Mutations of NEMO cause incontinentia pigmenti and X‐linked ectodermal dysplasia with immunodeficiency. Mendelian susceptibility to mycobacterial diseases (MSMD), which confers an almost selective predisposition to mycobacterial infection, is also caused by NEMO mutations. We herein report the first case of a patient with X‐linked recessive (XR) MSMD who developed cutaneous squamous cell carcinoma, thyroid cancer and Langerhans cell histiocytosis. The relationship between NEMO mutation and oncogenesis is discussed.     

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.     

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.     

Proliferative fasciitis mimicking a sarcoma in a child: A case report

Proliferative fasciitis (PF) is a benign, discrete proliferation of fibroblasts or myofibroblasts in soft tissue. Proliferative fasciitis mostly occurs in adults and is often confused with a sarcoma because of its rapid growth and peculiar histological features. We report a case of PF mimicking a sarcoma which developed in a 13‐year‐old boy, who noticed a painful tumor, with gradual enlargement, in his right lower leg. Magnetic resonance imaging revealed that the tumor measured 34 mm × 20 mm × 41 mm and was located in the subcutaneous tissue. The tumor was surgically resected. Pathologically, the tumor was composed of a proliferation of atypical spindle cells, admixed with larger ganglion‐like cells. Immunohistochemically, the tumor cells were positive for vimentin, cytokeratin, smooth muscle actin, HHF‐35 and Fli‐1. The tumor was subsequently diagnosed as a PF, although it was difficult to differentiate from a sarcoma. Five years after surgery, the postoperative course has been uneventful with no recurrence or metastasis.     

Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An interim analysis of a postmarketing surveillance

A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for Japanese patients with malignant melanoma and accumulate data on all adverse events (AE) and efficacy. In this interim analysis, we evaluated data from approximately 100 Japanese medical institutions obtained from the nivolumab approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored during the first 12 months of treatment. Nivolumab was administrated by i.v. infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated for safety and efficacy, respectively. The incidences of adverse drug reactions (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%), alkaline phosphatase (6.18%) and γ‐glutamyltransferase (5.44%). Grade 3 or higher ADR of special interest with an incidence of 1% or higher were hepatic function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special interest, were observed. The estimated median overall survival was 379 days (95% confidence interval [CI], 290–not reached [NR]) in the overall population, NR (95% CI, 305–NR) for cutaneous melanoma and 340 days (95% CI, 275–NR) for mucosal melanoma. The improvement rate based on the antitumor response at the last evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and serious ADR of special interest were infrequent. Nivolumab showed equivalent efficacy in patients with mucosal melanoma and those with cutaneous melanoma.