CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

Simulation of the Fissureless Technique for Thoracoscopic Segmentectomy Using Rapid Prototyping

The fissureless lobectomy or anterior fissureless technique is a novel surgical technique, which avoids dissection of the lung parenchyma over the pulmonary artery during lobectomy by open thoracotomy approach or direct vision thoracoscopic surgery. This technique is indicated for fused lobes. We present two cases where thoracoscopic pulmonary segmentectomy was performed using the fissureless technique simulated by three-dimensional (3D) pulmonary models. The 3D model and rapid prototyping provided an accurate anatomical understanding of the operative field in both cases. We believe that the construction of these models is useful for thoracoscopic and other complicated surgeries of the chest.     

Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full‐thickness cutaneous wound model in rats

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic‐pituitary‐adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full‐thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6‐epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6‐EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = ?.630). Finally, the mechanical withdrawal threshold in the 5,6‐EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6‐EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.     

Wound,pressure ulcer and burn guidelines – 4: Guidelines for the management of connective tissue disease/vasculitis-associated skin ulcers

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.     

Utility of preoperative imaging diagnosis for a malignant tumor of the mandible: a malignant tumor of the mandible is difficult to discriminate from bisphosphonate-related osteonecrosis of the jaw

We report our experience of a case with a malignant tumor of the mandible in which diagnostic imaging played an important role in the differential diagnosis and therapeutic strategy decisions. The patient was a 78-year-old woman who visited our hospital because of poor healing after tooth extraction. Multiple cytological diagnoses provided class II results, and a histopathological diagnosis of a biopsy also failed to show malignant findings. Therefore, a definitive diagnosis could not be made. Although the patient had a history of osteoporosis treatment, details of her medications were unclear. Therefore, bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be excluded, causing difficulty in management of the patient’s condition. Eventually, we mainly focused on the diagnostic imaging and planned the therapeutic strategy in accordance with treatment for a malignant tumor. A postoperative histopathological examination of the surgical specimen revealed squamous cell carcinoma. It is sometimes difficult to differentiate among atypical diseases such as malignant tumors of the mandible and BRONJ, based solely on clinical or diagnostic imaging results. However, in the present patient, diagnostic imaging suggested a malignant tumor, and the appropriate treatment could be selected.     

Three cases of pigmented cosmetic dermatitis‐like eruptions associated with primary Sjögren's syndrome or anti‐SSA antibody

Pigmented cosmetic dermatitis‐like (Riehl's melanosis‐like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti‐SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle‐aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA‐A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3‐ and few IL17‐positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti‐SSA antibody.