Review of renal anastomosing hemangioma with focus on clinical and pathological aspects.

Renal anastomosing hemangiomas (RAH) has been recently proposed as a new entity. In this article, we summarize the clinicopathologic features of this tumor. RAH usually develops on a background of end-stage renal disease. Macroscopically, tumors are well-defined and their cut surface shows mahogany brown spongy tissue with epicenter in the renal medulla. Tumors are usually small, but larger lesions are reported. On microscopic examination, the tumor consists of sinusoid-like vascular channels lined by cuboidal endothelial cells with occasional hobnail-like appearance of endothelial cells closely mimicking splenic sinusoids. Eosinophilic hyaline globules may be present in the cytoplasm of neoplastic endothelial cells. Extramedullary hematopoiesis containing erythroid precursor and megakaryocytes may be present in the vascular lumens. Immunohistochemically, endothelial cells are positive for CD31 and CD34, but negative for D2-40, GLUT-1 and HHV8. The surrounding stroma around endothelial cells demonstrates positivity for  smooth muscle action. To date, there are no studies on molecular genetic aspects of RAH. This tumor is indolent based on site and size of the lesion, partial or nephrectomy is sufficient as a therapeutic modality.

Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects.

Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells.

[Off-pump coronary artery bypass for old myocardial infarction associated with jejunotomy for obstructive ileus due to gall bladder stone; report of a case].

In non-cardiac operative cases with inflammatory digestive organ disease, bacterial translocation (BT) often results from non-enteral nutrition postoperatively. If coronary artery bypass grafting (CABG) is performed in the case having old myocardial infarction (OMI) and inflammatory digestive organ disease at first before non-cardiac operation, he seems vulnerable to have severe complications such as multiple organ failure due to systemic inflammatory response syndrome (SIRS) and preexisting BT postoperatively. We performed a off-pump CABG (OPCAB) for OMI associated with jejunotomy for obstructive ileus due to gall bladder stone. No complication was found in the postoperative course. We conclude that combined operation, non-cardiac surgery after OPCAB is worth considering in those cases. And we think OPCAB is better than conventional CABG in such cases, because cardiopulmonary bypass is known to ponder comparable damages to immune system, coagulation system and others.

Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-kappa B-inducing kinase.

Alymphoplasia (aly) mice, a natural strain with a mutant NF-kappa B-inducing kinase (NIK) gene, manifest a unique phenotype; they lack lymph nodes and Peyer's patches, have a disturbed spleen architecture, and exhibit defects in both Ab and cellular immune responses. Although a stromal defect caused by impaired lymphotoxin-beta receptor signaling accounts for their abnormal lymphoid organogenesis, the exact mechanisms underlying the development of immunodeficiency in aly mice are poorly understood. We therefore investigated the contribution of hemopoietic cells with the aly NIK mutation to the development of immunodeficiency. Transfer of aly/aly bone marrow cells into aly/+ mice resulted in poorly developed B cell follicles and lack of support for the development of germinal centers and isotype switching, indicating that the hemopoietic cells of aly mice contain an autonomous defect. However, follicular dendritic cell clusters were maintained in the spleens of these bone marrow chimeras, suggesting that the lack of follicular dendritic cell clusters in aly mice is probably due to the stromal defect. The aly mice lacked marginal zone B cells in their spleens, and aly/aly B cells showed an impaired proliferative response after in vitro stimulation. IL-2 production by activated T cells was also impaired. By contrast, the dendritic cells of aly mice exhibited grossly normal development and function. Supporting the concept of an autonomous cell defect, Rel protein expression was altered in aly/aly spleens. Thus, the aly NIK mutation affects hemopoietic cell function in an intrinsic fashion and, together with the stromal defect, may contribute to the development of immunodeficiency in aly mice.