A case of bronchopulmonary sequestration combined with congenital pulmonary airway malformation prenatally diagnosed as having two aberrant arteries originating from the celiac artery.

We report a case of BPS combined with CPAM prenatally diagnosed as having two aberrant arteries from the celiac artery by fetal 3D-US. Although the pattern of arterial feeding vessels was extremely rare in our case, the vasculature images obtained using fetal 3D-US were comparable to those obtained using postnatal CT angiography.

An 11-Beta Hydroxysteroid Dehydrogenase Type 1 Inhibitor, JTT-654 Ameliorates Insulin Resistance and Non-obese Type 2 Diabetes.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is the only enzyme that converts inactive glucocorticoids to active forms and plays an important role in the regulation of glucocorticoid action in target tissues. JTT-654 is a selective 11ß-HSD1 inhibitor and we investigated its pharmacological properties in cortisone-treated rats and non-obese type 2 diabetic Goto-Kakizaki (GK) rats because Asians, including Japanese, are more likely to have non-obese type 2 diabetics. Systemic cortisone treatment increased fasting plasma glucose and insulin levels and impaired insulin action on glucose disposal rate and hepatic glucose production assessed by hyperinsulinemic-euglycemic clamp, but all these effects were attenuated by JTT-654 administration. Cortisone treatment also reduced basal and insulin-stimulated glucose oxidation in adipose tissue, increased plasma glucose levels after administration of the pyruvate, the substrate of gluconeogenesis, and increased liver glycogen content. Administration of JTT-654 also inhibited all of these effects. Cortisone treatment decreased basal and insulin-stimulated 2-deoxy-D-[1-3H]-glucose uptake in 3T3-L1 adipocytes and increased the release of free fatty acids and glycerol, a gluconeogenic substrate, from 3T3-L1 adipocytes, and JTT-654 significantly attenuated these effects. In GK rats, JTT-654 treatment significantly reduced fasting plasma glucose and insulin levels, enhanced insulin-stimulated glucose oxidation in adipose tissue, and suppressed hepatic gluconeogenesis as assessed by pyruvate administration. These results demonstrated that glucocorticoid was involved in the pathology of diabetes in GK rats, as in cortisone-treated rats, and that JTT-654 ameliorated the diabetic conditions. Our results suggest that JTT-654 ameliorates insulin resistance and non-obese type 2 diabetes by inhibiting adipose tissue and liver 11ß-HSD1.

Current Treatment Options for Cutaneous Adnexal Malignancies.

OPINION STATEMENT: Cutaneous adnexal malignancies include various types of malignant tumors that show differentiation of cutaneous appendages. They can be classified into sweat gland, hair follicle, and sebaceous gland differentiations. All types of cutaneous adnexal tumors are rare and standard treatment options based on valid evidence have not been established. Although prognosis differs depending on the type of cutaneous adnexal malignancy, surgery is the mainstay of treatment. In surgical treatment, an adequate surgical margin is unclear for wide local excision. Mohs micrographic is a better option than wide local excision in terms of margin control and cosmetic outcome because the face, head, and neck are favorable sites for some cutaneous adnexal malignancies. There has been no randomized trial of radiation therapy and chemotherapy for any cutaneous adnexal malignancies. Radiation therapy should be considered if the tumor cannot be removed surgically. Chemotherapy is one of the options for metastatic cases in some types of cutaneous adnexal malignancies, but evidence of the effectiveness of chemotherapy is lacking. Recent studies have revealed genetic mutations in this field, and target therapy and immunotherapy may be promising treatment options for unresectable cutaneous adnexal malignancies in the future.

Interstitial granuloma after interferon-gamma and narrowband UVB therapy in a patient with mycosis fungoides: Immunological and histopathological considerations.

In mycosis fungoides (MF), cutaneous granuloma formation is unusual. Furthermore, MF showing interstitial granuloma, a rare type, after combination therapy with interferon-gamma (IFN-γ) and narrowband UVB (nbUVB) has not been previously reported. A 77-year-old man was referred to our hospital with a 2-month history of erythroderma. Biopsied specimens revealed infiltration of atypical lymphocytes and eosinophils. A diagnosis of an erythrodermic variant of MF was made. He was treated with combination therapy of IFN-γ and nbUVB. After the therapy, papules newly appeared and a histopathological specimen revealed interstitial granuloma. There were several CXCR3-positive cells around the granuloma. We speculated that the combination therapy made T-helper 1 cells migrate to the cutaneous lesion and resulted in the granuloma formation. Furthermore, judging from the disappearance of elastic fibers around the interstitial granuloma, we considered that IFN-γ may induce the infiltration of histiocytes interstitially after damage of elastic fibers caused by nbUVB therapy, and both IFN-γ and nbUVB may thus play an important role in the histogenesis. Not only histopathology but also immunological observations are needed to elucidate the mechanisms underlying the development of different types of granuloma in MF.

Nodules on the Knee in a Child: A Quiz.

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Implication of Perifollicular Clusters and Folliculotropic Distribution of Dendritic Cells in the Pathogenesis of Seborrhoeic Dermatitis.

The pathogenesis of seborrhoeic dermatitis is controversial and remains unclear. Malassezia is considered to be a commensal fungi and is found not only in the stratum corneum but also in hair follicles. It is an important pathogenic factor in seborrhoeic dermatitis. The aim of this study was to clarify the pathogenesis of seborrhoeic dermatitis, morphologically, through comparison with psoriasis vulgaris. Fifteen cases of seborrhoeic dermatitis, 7 of psoriasis, and 6 of normal skin were examined using routine histopathology, immunohistochemistry, and electron microscopy. Macrophages were found to be diffusely distributed in the upper dermis of seborrhoeic dermatitis and psoriasis. In contrast, a significant increase in the number of dendritic cells in the follicular epithelium and dendritic cell clusters in the perifollicular dermis were found only in seborrhoeic dermatitis. Ultrastructural examination of the clusters demonstrated that dendritic cells interacted with lymphocytes, macrophages, and other dendritic cells. In conclusion, folliculotropic distribution of dendritic cells as well as dendritic cell-immune cell clusters play an important role in the pathogenesis of seborrhoeic dermatitis.

Symptoms of and Palliative Treatment for Unresectable Skin Cancer.

OPINION STATEMENT: The symptom prevalence in patients with advanced cancer depends on the type of primary cancer, and the palliative treatment varies according to the nature of the primary cancer. Palliative treatment for unresectable skin cancer has not been fully discussed. Patients with unresectable skin cancer sometimes show the primary lesion in the skin and metastases to the lung, skin, liver, and bone. Pain, anorexia, and dyspnea commonly occur in such patients, and bleeding, exudate, and offensive odor are characteristically observed. For the last three symptoms, surgery and radiation are effective therapeutic options, and cryotherapy, Mohs' chemosurgery, electrochemotherapy, and some topical ointments and dressing materials are also additional options. For pain due to bone metastasis, pharmacotherapy with opioid and/or non-opioid agents is the most basic treatment, and radiation and bisphosphonate therapies are other options. For dyspnea, which is an intractable and uncomfortable symptom, morphine and oxygen play a leading role in treatment. Red blood cell transfusions may be effective for some patients with dyspnea induced by anemia. Nutritional supports and pharmacotherapy are therapeutic options for anorexia. As nutritional supports, enteral nutrition is better than parenteral nutrition. There is some evidence of progestins and corticosteroids having supportive effects for anorexia. Dermatologic oncologists should be skilled with symptom managements to maintain the quality of life in patients with unresectable skin cancer and their families.

Aggressive surgery based on an anatomical subclassification of craniopharyngiomas.

OBJECTIVE Craniopharyngiomas remain a particularly formidable challenge in the neurosurgical field. Because these lesions involve the hypothalamus and ophthalmological systems, their resection is associated with either higher rates of mortality and recurrence or a lower rate of radical resection. The authors report the outcomes of aggressive surgeries based on an anatomical subclassification of craniopharyngiomas. METHODS Clinical and ophthalmological examinations, imaging studies, endocrinological studies, neuropsychological function, and surgical complications in all patients who had undergone microsurgical resection for craniopharyngioma at Osaka City University hospital between January 2000 and December 2014 were retrospectively reviewed through the medical records. Radical resections were planned in all of the patients. To help choose the correct surgical approach, craniopharyngiomas were classified based on tumor origin. The 4 possible groups included the intrasellar type, prechiasmatic type, retrochiasmatic type, and intra-third ventricle type. A multistage surgery was planned in some cases. RESULTS Seventy-two cases of craniopharyngioma were resected. Thirty-two patients (44.4%) had undergone previous surgical procedures at other institutions. Thirty-five cases (48.6%) were classified as retrochiasmatic, 19 (26.4%) as prechiasmatic, 12 (16.7%) as intra-third ventricle, and 6 (8.3%) as intrasellar. In 26 cases (36.1%), multistage surgery was required to complete the radical resection. Overall, 41 cases involved an orbitozygomatic approach; 21, a transpetrosal approach; 21, an interhemispheric approach; and 14, a transsphenoidal approach. In 3 cases, other approaches were applied. Gross-total resection was achieved in 43 patients (59.7%), near-total resection in 28 (38.9%), and partial resection in only 1 patient (1.4%). The mean follow-up period after resection was 4.7 years. Tumor recurrence or regrowth occurred in 15 (20.8%) of the 72 patients, with 14 of the 15 cases successfully controlled after additional resections and stereotactic radiosurgery. However, 1 patient died of uncontrollable tumor progression, and 2 patients died of unrelated diseases during the follow-up. Overall, disease in 69 (95.8%) of 72 patients was well controlled at the last follow-up. CONCLUSIONS Aggressive tumor resection is the authors' treatment policy for craniopharyngioma. Using an anatomical subclassification of craniopharyngioma to choose the most appropriate surgical approach is helpful in achieving that goal of aggressive resection.

Glioblastoma in long-term survivors of acute lymphoblastic leukemia: Report of two cases.

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Second neoplasms as late effects of therapy for ALL have been recognized as a significant clinical issue given the increasing number of long-term survivors of ALL, because they can be the cause of death in such cases. In contrast, glioblastoma (GBM) is the most common primary brain tumor in adults. It is a malignant brain tumor that most often occurs in elderly patients, and GBM in young adults or adolescents appears to be rare. Here, we describe our experience of two cases of GBM in young long-term survivors of ALL, and emphasize the necessity of careful follow up of patients treated for ALL for the potential occurrence of central nervous system second neoplasms, especially when the patients have previously undergone cranial radiotherapy.

Metal-mediated oxidative DNA damage induced by methylene blue.

BACKGROUND: Methylene blue (MB) is used for various clinical purposes, including chromoendoscopy and methemoglobinemia treatment. However, MB induces tumors of pancreatic islets and small intestine in experimental animals. This finding raises a possibility that MB induces carcinogenicity in these organs via light-independent mechanisms, although MB is known to cause light-dependent DNA damage. METHODS: We investigated the mechanism of MB-induced DNA damage using (32)P-5'-end-labeled DNA fragments of human tumor-relevant genes. We investigated the redox reaction of MB by UV-visible spectrometry. RESULTS: MB induced DNA damage at the 5'-ACG-3' sequence, a hot spot of the p53 gene, in the presence of NADH and Cu(II). DNA damage was inhibited by catalase and bathocuproine, a Cu(I)-specific chelator. MB induced DNA damage at every nucleotide in the presence of NADH and Fe(III)-ethylenediaminetetraacetic acid, which was inhibited by OH scavengers and catalase. MB significantly increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, in the presence of NADH and metal ions. UV-visible spectrometry revealed that the absorbance of oxidized form of MB at 668nm was decreased by NADH, and the addition of metal ions attenuated the spectral change. CONCLUSIONS: MB undergoes NADH-dependent reduction followed by metal ion-mediated reoxidation. Reduced metal ions [Cu(I) and Fe(II)] interact with H2O2, generated during the redox reaction, to produce Cu(I)OOH and OH that cause DNA damage, respectively. These findings suggest that metal-mediated DNA damage contributes to MB-mediated carcinogenesis. GENERAL SIGNIFICANCE: This study would provide an insight into the mechanism of MB-induced carcinogenesis and its safety assurance for clinical use.