Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids.

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.

Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma.

We report the first use of endoscopic submucosal dissection (ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus (EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution, and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor, primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion, an 8 mm submucosal tumor. Immunohistologically, tumor cells differentiating into ductal epithelium and myoepithelium were observed, and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall, vertical stump or horizontal margin invasion with pT1b-SM2 staining (1800 µm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

In the non-cirrhotic stage of nonalcoholic steatohepatitis, angioarchitecture of portal veins and lobular architecture are maintained.

The morphogenesis of lobular restructuring to liver cirrhosis in nonalcoholic steatohepatitis (NASH) is yet to be clearly understood. Therefore, we observed tissue samples from three biopsies and one autopsy with NASH in the non-cirrhotic stage three-dimensionally to elucidate the evolution of fibrosis and the changes of angioarchitecture. Histologic reconstructions revealed that pericellular fibrosis developed around the central vein in the early stage and gradually progressed to arch-shaped band-like fibrosis connecting the central veins in the neighboring lobules. In contrast, the basic angioarchitecture of the portal vein in the portal tracts tended to be preserved in the non-cirrhotic stage, although the portal vein architecture was slightly altered as the portal tract underwent gradual fibrous expansion. In addition, a striking development of arteries originating from the portal tract was found in the fibrotic area around the central and sublobular veins. In summary, while central-central bridging fibrosis and ectopic arterial development were conspicuous, the lobular architecture was maintained relatively well in the non-cirrhotic stage of NASH because of only mildly damaged angioarchitecture of the portal veins. The process of lobular restructuring in NASH is considered to be different from that in chronic viral hepatitis in the non-cirrhotic stage.

Isolation and characterization of bone marrow-derived mesenchymal progenitor cells with myogenic and neuronal properties.

Sphere formation has been utilized as a way to isolate multipotent stem/progenitor cells from various tissues. However, very few studies on bone marrow-derived spheres have been published and assessed their multipotentiality. In this study, multipotent marrow cell populations were isolated using a three-step method. First, after elimination of hematopoietic cells, murine marrow-derived adherent cells were cultured in plastic dishes until small cells gradually appeared and multiplied. Cells were then cultured under non-adherent conditions and formed spheres that were immunopositive for a neural precursor marker, nestin. RT-PCR analysis also revealed that the spheres were positive for nestin in addition to PPARgamma, osf2, SOX9, and myoD, which are markers of precursors of adipocytic, osteoblastic, chondrocytic, and skeletal myeloblastic lineages, respectively. Finally, spheres were dissociated into single cells and expanded in adherent cultures. Under appropriate induction conditions, the sphere-derived cells acquired the phenotypic properties in vitro of neurons, skeletal myoblasts, and beating cardiomyocytes, as well as adipocytes, osteoblasts, and chondrocytes. Next, sphere-derived cells were transplanted into murine myocardial infarction models. One month later, they had become engrafted as cardiomyocytes, and cardiac catheterization showed significant functional improvements. Thus, sphere-derived cells represent a new approach to enhance the multi-differentiation potential of murine bone marrow.

Two different roles of purified CD45+c-Kit+Sca-1+Lin- cells after transplantation in muscles.

Recent studies have indicated that bone marrow cells can regenerate damaged muscles and that they can adopt phenotypes of other cells by cell fusion. Our direct visualization system gave evidence of massive muscle regeneration by green fluorescent protein (GFP)-labeled CD45+c-Kit+Sca-1+Lin- cells (KSL cells), and we investigated the role of KSL cells in muscle regeneration after transplantation with or without lethal irradiation. In the early phase, GFP signals were clearly observed in all the muscles of only irradiated mice. Transverse cryostat sections showed GFP+myosin+ muscle fibers, along with numerous GFP+ hematopoietic cells in damaged muscle. These phenomena were temporary, and GFP signals had dramatically reduced 30 days after transplantation. After 6 months, GFP+ fibers could hardly be detected, but GFP+c-Met+ mononuclear cells were located beneath the basal lamina where satellite cells usually exist in both conditioned mice. Immunostaining of isolated single fibers revealed GFP+PAX7+, GFP+MyoD+, and GFP+Myf5+ satellite-like cells on the fibers. Single-fiber cultures from these mice showed proliferation of GFP+ fibers. These results indicate two different roles of KSL cells: one leading to regeneration of damaged muscles in the early phase and the other to conversion into satellite cells in the late phase.