Immune-mediated Drug-induced Liver Injury Caused by Laninamivir Octanoate Hydrate.

We herein report the first case of immune-mediated drug-induced liver injury that may have been caused by laninamivir. A 15-year-old girl was diagnosed with influenza and prescribed 40 mg laninamivir. Six weeks later, she was admitted to our hospital because of jaundice and fatigue. Laboratory examinations revealed elevated levels of hepatobiliary enzymes, and acute liver injury was suspected. Laboratory examinations and histological findings were characteristic of autoimmune hepatitis. Steroid treatment was ineffective, and azathioprine was added to the treatment. Twenty-two months after the onset, a second biopsy revealed the absence of inflammatory infiltrations, and the drugs were withdrawn. Liver function tests remained normal nine months after withdrawal.

Effects of implant surface on bone healing around titanium screw implants in ovariectomized rats.

PURPOSE: The aim of this study was to investigate whether estrogen deficiency interrupts bone healing around titanium implants and to evaluate whether bone healing around implants under a condition of estrogen deficiency is affected by variations in implant surface characteristics. MATERIALS AND METHODS: Forty-eight female rats were divided into two groups: ovariectomized rats (OVX; n = 24) and sham-operated rats (SHAM; n = 24). Each group was further divided into two groups: a machine-polished implants group and a sandblasted implants group. One implant was placed into the left femur of each rat 84 days after OVX or sham surgery. After 28 or 56 days, the rats were killed, and nondecalcified sections were obtained. Bone-to-implant contact (BIC) and bone area (BA) around the implants were assessed for cortical and cancellous bone. Furthermore, bone density (BD) was evaluated in a 500-mm-wide zone of cancellous bone lateral to the implants. RESULTS: At 28 and 56 days after implantation, no significant differences were found between the OVX and SHAM groups for BIC and BA in cortical bone. BIC, BA, and BD with cancellous bone were lower in the OVX group than in the SHAM group. However, BIC and BA tended to increase with the sandblasted implant surface. CONCLUSIONS: Estrogen deficiency affected bone healing and bone density around titanium implants, especially in cancellous bone, but the sandblasted surface has the possibility to improve osseointegration. However, the positive effect of this rough surface is limited at the implant surface.

An experimental study of bone healing around the titanium screw implants in ovariectomized rats: enhancement of bone healing by bone marrow stromal cells transplantation.

PURPOSE: : This study is to evaluate the bone quality of surrounding areas of implants with bone marrow stromal cells (BMSCs) transplantation to rat femur, which have become osteoporosis-induced models. MATERIALS AND METHODS: : The Sprague-Dawley rats were divided into 3 groups: the first group where their ovaries were removed (OVX group), the second group where a sham surgery was given (SHAM group), and the third group where BMSCs were transplanted to an OVX group (OVX-BMSCs group). In the OVX-BMSCs group, 1 × 10 BMSCs were transplanted into femur with implant. Each value of the bone to implant contact and the bone area of each cortical bone and cancellous bone was obtained. Bone density of the width of 500 µm from the implants was measured. RESULTS: : Each ratio of bone to implant contact, bone area, and bone density in the OVX-BMSCs group was significantly higher than those of OVX group as to the cancellous bone. CONCLUSION: : The BMSCs transplantation therapy improved local bone healing in the cancellous bone surrounding implants and also significantly improved bone binding with implants.

Colonic lipoma with florid vascular proliferation and nodule-aggregating appearance related to repeated intussusception.

A unique case of repeatedly intussuscepted colonic lipoma mimicking an epithelial tumor in a 50-year-old man is reported. The tumor was located in the ascending colon and was approximately 5 cm in diameter. Colonoscopic and barium-enema examinations suggested a huge epithelial tumor because of its nodule-aggregating appearance. In contrast, computed tomography examination showed a fatty element in the core of the lesion. The biopsy specimens suggested a primary angiomatous lesion because of its pronounced vascular proliferation. Because the presumed diagnoses based on the examinations were different, the preoperative diagnosis was not confirmed. The tumor was composed of intramural lipoma with a multiple polypoid mucosa overlay. This lesion was unique in that the lipoma appeared to be within the muscularis propria and the multiple polypoid appearance of its covering mucosa. The mucosal changes including florid vascular proliferation, fibromuscular obliteration and epithelial regeneration suggested a reparative process, with ischemic damage due to the effects of intussusception being the most likely event. It should be kept in mind that even a simple lipoma can have a unique appearance reminiscent of epithelial tumor when it repeatedly experiences intussusception.

Extended indication criteria for endoscopic mucosal resection of early gastric cancer with special reference to lymph node metastasis--examination by multivariate analysis.

The purpose of this study was to clarify extended indication criteria of endoscopic mucosal resection (EMR) for early gastric cancer (EGC) by analyzing the independent risk factors involved in lymph node metastasis (LNM). Subjects were 422 patients who underwent gastrectomy with lymph node dissection for EGC at the Kurume University Hospital from 1994 to 2001. The EGCs were mucosal cancers (M) in 252 cases and submucosal cancers (SM) in 170 cases. Twelve clinico-pathological factors were assessed for their possible association with LNM. On univariate analysis, EGC with LNM showed the following characteristics: size; 3.1 cm or more, ulceration; present, heterogeneity; present, differentiation; poor, lymphatic vascular invasion; present, and invasion depth; SM2 (cancer penetration of submucosal layer, 0.5 mm or more from the muscularis mucosa). On multivariate analysis, the following four factors were identified as independent risk factors; invasion depth: Odds Ratio (OR) 10.9, lymphatic vascular invasion: OR 10.6, size: OR 3.2, and ulceration: OR 3.2. The incidence of LNM was 0% (0/141) (95% confidence interval, 0-2.6%) when these risk factors met the following four conditions: invasion depth; M or SM1 (cancer penetration of submucosal layer, less than 0.5 mm), lymphatic vascular invasion; absent, size; 3.0 cm or less, and ulceration; absent. It is concluded that EMR is a suitable radical treatment for EGC, and that the indication criteria for EMR can be extended depending on the results of the histological evaluation of the en bloc/total resected specimen concerning the above four factors for LNM.

Combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features: genetic analysis for histogenesis.

The histogenesis of sarcomatoid transformation in hepatocellular carcinomas (HCCs) and cholangiocellular carcinomas (CCCs) remains unclear. In the current case, microsatellite loss of heterozygosity (LOH) assay and mutational analysis of the p53 gene with immunohistochemical examination were performed to investigate the histogenesis of each component. The tumor was composed of two parts: one part comprised poorly differentiated HCC (HCC portion), while the other part included undifferentiated, sarcomatoid HCC and CCC (combined portion). LOH at D8S555 was detected in both portions. 1-bp cytosine was deleted at codon 241 of exon 7 of the p53 gene in the combined portion. Immunohistochemically, p53 accumulated in the nuclei of undifferentiated, sarcomatoid HCC and CCC cells, suggesting that the p53 gene mutation might be common in these components. These results support the hypothesis that undifferentiated, sarcomatoid HCC and CCC could be offspring from the original HCC.

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis.

BACKGROUND: Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique.METHODS: Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII.RESULTS: The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis.CONCLUSIONS: All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis.

Primary squamous cell carcinoma of the stomach.

Primary squamous cell carcinoma (SCC) of the stomach is extremely rare; only 32 cases are found in the Japanese literature. The pathogenesis of this neoplasm remains obscure and controversial. Furthermore, the optimal treatment, including adjuvant chemotherapy, remains unclear. We report herein a case of SCC of the stomach in a 70-year-old male with amazing effectiveness of neoadjuvant chemotherapy, low-dose FP chemotherapy. To our knowledge, no case of this disease has ever been reported that was given neoadjuvant chemotherapy and histologically showed its effectiveness. Our case demonstrated a striking effectiveness of chemotherapy in the neoplasm both radiologically and histologically.