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Transplantation of pancreatic islets is becoming a promising therapy for people with type I diabetes. In this study, we present a compact fluidic system that enables assessment of islet functionality ex vivo for efficient islet transplantation. The fluidic system includes a micromesh sheet-embedded chip. Islets can be loaded easily on the micromesh sheet and observed clearly by microscopy. Islets on the mesh sheet mainly remained in place during perfusion and did not get damaged by hydraulic pressure because of high porosity of the micromesh sheet. The fluidic system was assembled with a sample fraction chip of polydimethylsiloxane. The chip includes a channel and columns, both having surfaces that were super-hydrophilized so that solutions could flow smoothly within the chip by gravity. Using mouse pancreatic islets, a dynamic glucose-stimulated insulin secretion test was performed to examine the performance of the fluidic system. The system successfully analyzed levels and patterns of insulin secretion upon exposure of the islets to low- and high-glucose solutions in turns, thus demonstrating its capacity to assess islet functions more easily and cost-effectively.

Objective: Tsumura Suzuki Obese Diabetes (TSOD) mice exhibit early age-associated hearing loss. Histopathological analysis of these mice shows narrowing of capillaries in the stria vascularis and chronic reduction of blood flow in the cochlea. In this study, we investigated the effect of oral administration of a herbal medicine or calorie restriction on hearing in TSOD mice., Methods: TSOD mice were divided into 4 groups: CR (calorie restriction), BF and DS (treated with the herbal medicines, Bofutsushosan and Daisaikoto, respectively), and the control group. Body weight, blood glucose levels, and auditory brainstem responses (ABRs) were measured. The cochleae were excised and evaluated histopathologically., Results: Blood glucose levels were suppressed in the CR, BF, and DS groups. In addition, the elevation of ABR thresholds was inhibited in the CR, BF, and DS groups. Cochlear blood vessels remained wide in the three treatment groups compared with the control group. These results suggested that the administration of these herbal medicines improved glucose tolerance and yielded results similar to those on calorie restriction., Conclusion: Oral administration of 2 herbal medicines can prevent hearing function disorder in a model mouse of diabetes. The results may clarify the possibility of clinical application., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We report a case of gastrointestinal stromal tumor(GIST)with long-term survival treated by multidisciplinary therapy, including surgery and imatinib to prevent repeated recurrence. A 76-year-old woman visited our hospital with difficulty in defecation and bloody bowel discharge. She was diagnosed with rectal GIST and underwent transanal partial resection of the rectum. Local recurrence occurred 1 year after the operation, and the tumor was resected transanally. Hepatic metastasis occurred 8 months after the second operation. The patient was administered imatinib for 2 months, which caused the tumor to shrink, and extended left lobectomy was performed. Imatinib was administered for 2 years after hepatectomy. After another 2 years, metastasis to the liver and thoracic and lumbar vertebrae occurred. The recurrent tumors reverted to cystic lesions after 6 months of imatinib treatment. She has been alive without tumor progression during re-treatment with imatinib for 7 years(13 years after the first surgery).

In vitro 3D cultures of hepatocytes are increasingly being used to assess human hepatic metabolism and toxicity in drug development. Here, we developed an in vitro 3D cell culture method with a microstructured mesh sheet and applied it to culturing human hepatoma HepG2 cells. The micromesh sheet is constituted of fine mesh strands and apertures that are each much larger than a single cell in size. Proliferating on a micromesh sheet, HepG2 cells spread out in a planar manner and then formed a multilayered cell sheet, so that cell-cell adhesion was dominant over cell-substrate adhesion as being different from 2D cultures. In micromesh cultures, the increase rate in thickness of the cell mass was visually slower than that in spheroid cultures, enabling us to clearly observe inside cells of the cell population by microscopy. Micromesh-cultured HepG2 cells showed higher viability compared with spheroid-cultured cells. The multilayered HepG2 cell sheet increased expression of hepatic marker genes and induced cell polarization with bile canalicular membranes. Furthermore, a combination of micromesh cultures with medium perfusion further induced expression of hepatic marker genes in HepG2 cells; especially CYP1A1 and CYP1A2 mRNA increased 86-fold and 43-fold compared with 2D controls, respectively, which were much higher than those in spheroid cultures. Thus, this simple and versatile micromesh culture method holds some advantages over traditional spheroid cultures and is expected to be instrumental in culturing more differentiated hepatic cells such as HepaRG cells and primary hepatocytes for future preclinical testing.

Phenobarbital, a nongenotoxic hepatocarcinogen, induces hepatic proliferation and promotes development of hepatocellular carcinoma (HCC) in rodents. Nuclear receptor constitutive active/androstane receptor (NR1I3/CAR) regulates the induction and promotion activities of phenobarbital. Here, it is demonstrated that phenobarbital treatment results in dephosphorylation of a tumor suppressor p38 MAPK in the liver of C57BL/6 and C3H/HeNCrlBR mice. The molecular mechanism entails CAR binding and inhibition of the growth arrest and DNA-damage-inducible 45 beta (GADD45B)-MAPK kinase 6 (MKK6) scaffold to repress phosphorylation of p38 MAPK. Phenobarbital-induced hepatocyte proliferation, as determined by BrdUrd incorporation, was significantly reduced in both male and female livers of GADD45B knockout (KO) mice compared with the wild-type mice. The phenobarbital-induced proliferation continued until 48 hours after phenobarbital injection in only the C57BL/6 males, but neither in males of GADD45B KO mice nor in females of C57BL/6 and GADD45B KO mice. Thus, these data reveal nuclear receptor CAR interacts with GADD45B to repress p38 MAPK signaling and elicit hepatocyte proliferation in male mice. Implications: This GADD45B-regulated male-predominant proliferation can be expanded as a phenobarbital promotion signal of HCC development in future studies. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/8/1309/F1.large.jpg Mol Cancer Res; 16(8); 1309-18. ©2018 AACR ., (©2018 American Association for Cancer Research.)

A 93-year-old woman was admitted to the hospital because of respiratorydiscomfort. A chest CT scan indicated aspiration pneumonitis and, simultaneously, intussusception was observed in the splenic flexure region. Abdominal enhance CT scan revealed a tumor in the advanced region of intussusception. Laparoscopy-assisted ileocecal resection was performed. Since the intussusception was difficult to reduce laparoscopically, the ileocecum was mobilized and the intussusception was reduced manually. In the resected specimen, a type 1 tumor was observed in the cecum and histopathologic ally diagnosed as cercal cancer. We report a case with intussusception due to colorectal cancer treated bylaparoscopic surgery.

Myxoid liposarcoma (MLPS) is the second most common histologic subtype of liposarcoma. However, cartilaginous differentiation within MLPS is an extremely rare phenomenon, with only 7 cases of MLPS with cartilaginous differentiation reported to date. The majority of MLPS cases show the t(12;16)(q13;p11) translocation, resulting in the fused in sarcoma-DNA damage-inducible transcript 3 ( FUS-DDIT3 ) fusion gene. This fusion gene as a hallmark of MLPS is very useful for differential diagnosis from other soft tissue sarcomas, and the associated protein, FUS-DDIT3, performs an important role in the phenotypic selection of targeted multipotent mesenchymal cells during oncogenesis. In this report, a case of MLPS with cartilaginous differentiation that occurred in the thigh of a 44-year-old woman is described. Histopathologically, the tumor was composed of a typical myxoid liposarcoma area and a mature hyaline cartilaginous area. Using fluorescence in situ hybridization analysis, rearrangement of the DDIT3 gene was detected in not only the liposarcomatous area but also in the chondrocytes of the cartilaginous area. Based on these findings, the cartilaginous differentiation area appears to be partially associated with oncogenesis through the specific fusion gene FUS-DDIT3 .

We report an 85-year-old female suffered Paget-type recurrence at right remnant breast. The patient had undergone breast conserving surgery(BCS)20 years ago in another hospital for invasive ductal carcinoma of the right breast(pT1N0M0, Stage I ). Her chief complain was a skin ulcer of the right nipple. The pathological diagnosis for biopsy specimen from the areola was Paget's disease. She underwent total mastectomy. Paget cells were detected pathologically in the epidermis of the nipple and nearby mammary duct connected with fibrous tissue after BCS, suggesting Paget-type recurrence of invasive breast carcinoma.

Study Design: Case series., Objective: To clarify the following questions How long after cervical laminoplasty did the patients die? What were the causes of the death? Was the severity of the neurological dysfunction related to early death?, Summary of Background Data: Life expectancy in patients with cervical myelopathy is unclear. Cervical laminoplasty was performed in 216 patients between 1981 and 1994. It was possible to follow 148 patients for more than 20 years. We used the data of the 68 survivors and the 80 patients had already died., Methods: As for the patients who died by the final follow-up, the survival rate was analyzed by a Kaplan-Meier plot; the results were compared between the patients with cervical spondylosis (CS) and the patients with ossification of the posterior longitudinal ligament (OPLL). The causes of the death were assessed. The neurological evaluation was graded using the score devised by the Japanese Orthopaedic Association (JOA). The pre- and postoperative scores were compared between the patients in the died group (D group) and the surviving patients group (S group)., Results: The mean period from surgery to death was 13.4 ± 7.4 years. There was no difference in the survival rate between patients with CS and patients with OPLL. The most frequent cause of death was malignant tumor followed by ischemic heart disease. Preoperative JOA score in the D group was lower than that in the S group. There was no statistical difference in postoperative JOA score between the two groups., Conclusion: The patients who underwent cervical laminoplasty caused by compression myelopathy due to CS and OPLL had a long life expectancy, averaging more than 13 years. Life expectancy did not differ between patients with CS and patients with OPLL. Neurological deficit did not directly affect the life expectancy., Level of Evidence: 4.

Purpose: In Japan, the majority of early gastric cancers (EGCs) are now treated with endoscopic submucosal dissection (ESD). Patients with non-curative lesions treated by ESD are advised to undergo additional surgical resection (ASR) based on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and Japanese Gastric Cancer Association (JGCA). However, many studies have demonstrated that residual cancer and lymph node metastasis are only rarely found in ASR specimens. Here we retrospectively analyzed the conditions that could enable the avoidance of unnecessary ASR., Methods: The ESD data for 114 absolute indication lesions and 26 lesions of expanded indication lesions were analyzed. The indications and the curability were evaluated according to the JGES/JGCA guidelines., Results: The rates of non-curative resection and ASR were significantly higher in the expanded indication group compared to the absolute indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was performed for six patients. Three of their ARS specimens contained neither residual cancer nor lymph node metastasis, and the pathological findings of the preceding ESD specimens deviated slightly from the curative criteria defined by the guidelines. The conditions of the lesions that did not meet the curative criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal resection with a horizontal margin positive for the mucosal differentiated-type., Conclusions: These data suggest that a close follow-up without ASR might be appropriate for patients in the above-mentioned three categories after non-curative ESD for EGC., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

A 62-year-old woman was admitted to our hospital because of bloody stool. Colonoscopy revealed stenosis by a type 2 tumor of the recto-sigmoid colon. A biopsy specimen contained moderately differentiated adenocarcinoma. Thoraco-abdominal computed tomography (CT) showed liver metastasis (S7, 10 mm) and enlargement of Virchow's lymph node (17 mm) and several para-aortic lymph nodes (15 mm on average). Because of oozing from the tumor and severe stenosis of the recto-sigmoid colon, we performed laparoscopic-assisted high anterior resection of the primary lesion. After surgery, 3 courses of mFOLFOX6, 20 courses of mFOLFOX6 plus bevacizumab, and 5 courses of infusional 5-FU plus Leucovorin plus bevacizumab were administered. Thoraco-abdominal CT demonstrated complete response to the 1 year 2 months of chemotherapy. The patient has been alive without relapse for 2 years after surgery.

We report a case of a villous tumor of the rectum with electrolyte depletion syndrome (EDS). A 76-year-old woman developed general fatigue, and on investigation, we found a large laterally spreading tumor of the rectum using bowel enema and colon fiber. Pathologically, the biopsy specimen was graded Group 4. We intended to perform a laparoscopy-assisted low anterior resection in the patient. However, the operation was interrupted by a short-run type of ventricular premature contraction (VPC) due to EDS-induced hypokalemia. After treating the hypokalemia, low anterior resection or laparotomy was performed. The tumor was 19 × 13 cm in size and occupied the circumference of the rectum. Histological examination revealed well differentiated tubular adenocarcinomas with tubulovillous adenoma. Pathological staging was pTis, pN0, M0, stage 0 according to the Japanese Classification of Colorectal Carcinoma (8th edition). It is now 6 months after the operation and hypokalemia has not recurred in the patient.

We report a case of a 60-year-old woman with abdominal distension who was treated with self-expandable metal stent (SEMS) placement in the proximal transverse colon. She was found to have severe bowel obstruction due to advanced transverse colon cancer on plain computed tomography (CT) and colonoscopy. We performed colonic stenting safely, and the symptom promptly improved. Defecation and flatus were observed on the same day of stenting, and the patient was able to start drinking and eating on the next day. Enhanced abdominal CT revealed multiple liver metastasis, peritoneal dissemination, ascites, and cystic ovarian tumor. After treatment with 1 course of 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6), the patient was discharged on day 14 after admission. The rapidly enlarging ovarian tumors and primary colonic lesion with SEMS were surgically removed after treatment with mFOLFOX6 for 4 months in an outpatient basis. The patient has been alive with a good quality of life (QOL) and being treated with bevacizumab plus mFOLFOX6/Leucovorin, 5-fluorouracil, and irinotecan( FOLFIRI) for 6 months. SEMS placement could be safe and effective for the treatment of obstruction of the right colon, and could maintain a good QOL in patients.

The patient was a 66-year-old male. He underwent sigmoidectomy with D1 for an advanced sigmoid colon cancer with massive metastasis to the para-aortic lymph nodes. After the resection he underwent chemotherapy, and CT showed that the para-aortic lymph node metastasis had disappeared. However, CT showed other lymph node(No. 252, No. 273 lt)swelling. We therefore resected No. 252 and No. 273 lt lymph nodes. Two years after the resection the patient is alive and shows no sign of recurrence while being without chemotherapy.

Extraskeletal myxoid chondrosarcomas (EMC) are relatively rare. We report a case of EMC of the thigh. A 41-year-old man presented with a tumor history of more than 4 months. Following open biopsy, wide resection of the tumor was performed. Histopathologically, the tumor had a multinodular architecture consisting of myxomatous areas demarcated by fibrous septa. Proliferation of uniform, round tumor cells with oval nuclei was observed. Well-formed hyaline cartilage and rhabdoid-like cells were not visible. Immunohistochemically, the tumor cells were positive for vimentin and S-100. The composite karyotype was 46,XY,t(9;17)(q22;q11),t(9;21)(q21;p13), and the diagnosis of EMC was made. No recurrence of the mass or metastasis was observed during a follow-up period of 4 years and 7 months. Only 50 cytogenetic cases of EMC, including our case, have been reported in the English literature thus far. Clinical presentation, radiological features and histopathological and cytogenetic findings are described, and the relevant literature is reviewed.

The occurrence of primary extraskeletal Ewing's sarcoma (EES) of the spinal epidural space has been rarely reported in the literature. The clinical, radiologic and pathologic features of a case of EES occurring in the thoracic epidural space are presented. A 37-year-old woman presented with a one-year history of back pain. Magnetic resonance imaging demonstrated an epidural mass at the T8-9 level. Laminectomy and partial resection of the tumor were performed. The differential diagnosis of a spinal epidural mass is broad. Histopathological and molecular cytogenetic examinations confirmed an EES arising from the thoracic epidural space. Despite receiving both chemotherapy and radiotherapy, the patient died of respiratory insufficiency due to medulla oblongata metastasis 22 months after the initial consultation. Awareness of this entity will allow this rare diagnosis to be considered and facilitate appropriate management. A review of the literature on spinal epidural EES is also presented.

The patient, a 58-year-old woman, underwent a partial excision of the right breast and an axillary lymph node dissection in October 2004. The histopathological findings were: solid tubular carcinoma with metastasis to 17 axillary lymph nodes; triple negative-type breast cancer. As adjuvant therapy, FEC60 was administered 6 times, followed by radiotherapy applied to the residual breast and the right supraclavicular fossa. In Novermber 2007, she noted a tumorous growth above the right clavicle. The pathological diagnosis via fine needle biopsy was adenocarcinoma. An oral antineoplastic agent was given for about 6 months, but did not alter the lymph nodes. No distant recurrence was noted during this time. In August 2008, the right supraclavicular lymph nodes were dissected. The patient has been under observation without treatment, but no signs of recurrence have been noted. It was thought that excision of the recurrent supra-clavicular lymph nodes should be considered after careful examination in some individual cases.

Eight patients with inoperable advanced gastric cancer were treated with combination chemotherapy of S-1, low-dose cisplatin(CDDP)and Lentinan. S-1 80 mg/ m² was orally administered for 2 weeks followed by 1-week rest, CDDP 15 mg/ m² and Lentinan 2 mg/body were given intravenously on day 1 and 8. One complete response and four partial responses were observed for an overall response rate of 63%(5 of 8 patients). Only one patient developed over grade 3 toxicity leukocytopenia. Many patients could be maintained by long-term continuous treatment. Since combination chemotherapy of S-1/low-dose CDDP/Lentinan for advanced gastric cancer was very tolerable, it could be used for a long time.

Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and ionizing radiation (IR) on human OS cells were investigated. IR and TRAIL treatment synergistically decreased the cell viability and enhanced apoptosis in OS cell lines. IR pretreatment enhances TRAIL-induced Bid and caspase-3 activations. Decreases in the expression levels of the antiapoptotic proteins c-FLIP and XIAP also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced DR4 and DR5 expressions at the transcription stage. These results can become the basic lines of evidence for the future treatment of OS using TRAIL with IR., ((c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit the p53-MDM2 interaction and activate p53 signaling. The expressions of DR4 and DR5, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, are regulated by p53. In this study, the combined effects of nutlin-3 and TRAIL on apoptosis were investigated in HOS and HCT116 cells, which express wild-type p53. Nutlin-3 and TRAIL synergistically enhanced apoptosis owing to their intrinsic and extrinsic pathway signals, respectively. The increase in the Bid expression level and the decrease in the expression levels of anti-apoptotic proteins, c-FLIP and XIAP, were involved in this apoptosis enhancement. Furthermore, nutlin-3 activated the DR5 promoter and increased the expression levels of DR5 at mRNA and protein levels. These results indicate that the combination, treated with nutlin-3 and TRAIL, is useful for apoptosis induction in malignant cells expressing wild-type p53., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

A 61-year-old man with esophagus invasive advanced gastric cancer and peritoneum dissemination underwent three courses of S-1/CDDP/Lentinan (LNT) combination neoadjuvant chemotherapies (T3N1P1H0, Stage IV) (It is S-1 80 mg/m2,CDDP 15 mg/m2 and LNT 2 mg/body twice/week for two weeks) since down staging was obtained. We performed the surgery of total gastrectomy, splenectomy, D2 lymph node dissection, and Roux-en Y reconstruction in March 2008. With the surgical examination, there was no ascites and peritoneal dissemination. Although there was serious infiltration, we were able to remove it. In the histopathological effect judgment, it was Grade 1b. We changed the therapy to S-1 alone after the same chemotherapy for six months. One year after the operation, he is still alive one year after the surgery.

The aim of this study was to examine whether, a new synthesized class of benzocycloalkene derivatives (BCs), enhances apoptosis induced by hyperthermia. The combined effects of hyperthermia (44 degrees C, 20 min) and BCs on apoptosis in human lymphoma U937 cells were investigated. Among the tested compounds (BC1 approximately 9), the combined treatment of 10 muM BC2 or BC4 and hyperthermia showed the largest potency to induce DNA fragmentation at 6 h after hyperthermia. And enhancement of hyperthermia-induced apoptosis by BC2 or BC4 in a dose-dependent manner was observed. When the cells were treated first with BC2 or BC4 at a nontoxic concentration of 20 muM, and exposed to hyperthermia afterwards, a significant enhancement of heat-induced apoptosis was evidenced by DNA fragmentation, morphological changes and phosphatidylserine externalization. Flow cytometry revealed an increase of intracellular superoxide due to BC2 or BC4, which was further increased when hyperthermia was combined. Mitochondrial membrane potential was decreased and the activation of caspase-3 and caspase-8 was enhanced in the cells treated with the combination. The activation of Bid, but no change of Bax and Bcl-2 were observed after the combined treatment. The release of cytochrome c from mitochondria to cytosol, which was induced by hyperthermia, was enhanced by BC2 or BC4. An increase in the intracellular Ca2+ concentration [Ca2+](i), externalization of Fas, and decrease in Hsp70 were observed following the combined treatment. These results indicate that the intracellular superoxide generated by BC2 or BC4 is involved in the enhancement of apoptosis through Fas-mitochondria caspase and [Ca2+](i)-dependent pathways, and a decrease in Hsp70 also contributed to the enhancement of apoptosis.

A 28-year-old woman was given a diagnosis of gastric endocrine cell carcinoma with multiple liver metastases in 1997. Chemotherapy was administered for treatment after a distal gastrectomy and hepatic tumor resection, and she had shown no sign of relapse after 2002. In February 2004, she was in the third month of pregnancy, and experienced recurrent liver metastasis. Although the tumor grew rapidly from 3cm to 10cm during her pregnancy, its size was significantly reduced with systemic chemotherapy after delivery. This is a rare case in which a liver metastasis of a gastric endocrine cell carcinoma grew during the course of pregnancy.

Background: Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels., Objective: The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders., Methods: This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement., Results: A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1 patient each). Administration of rabeprazole was discontinued in 5 patients due to the occurrence of the following ADRs: constipation (1 patient); epigastric pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y-glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients achieving improvement with either dose was 30/33 (90.9%). The relief rates assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for epigastric pain and heartburn, respectively. The proportion of patients achieving global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other hepatic diseases [alcoholic hepatitis, fatty liver])., Conclusion: In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.

We experienced a case of bone metastatic recurrence from gastric carcinoma that responded to TS-1 combined with low-dose cisplatin (CDDP) therapy. A 63-year-old male patient presented with multiple bone metastases 5 years after radical surgery for advanced gastric carcinoma. The titer of serum CEA showed extremely high levels of 18,000 ng/ml. The uptake area was found at all vertebrae, ribs, and pelvis by scintigraphy 99mTc-HMDP. The chemotherapy regimen, performed in the outpatient clinic, comprised daily oral administration of 80 mg/m2 of TS-1 for 14 days and CDDP 20 mg/m2 infusion (day 1). This regimen was repeated every 3 weeks for 9 months. After that, severe pain diminished and the titer of serum showed CEA had improved to 599 ng/ml. The uptake at the multiple bone metastasis was found to have decreased by scintigraphy. The patient was able to resume his full social activities. TS-1/low-dose CDDP therapy seems to be applicable for the treatment of gastric carcinoma with bone metastasis.

Background: Hepatocyte growth factor (HGF) is involved in the proliferation and migration of various types of epithelial cells. HGF is produced as a single-chain precursor (pro-HGF) and functions after activation by HGF activator (HGFA). In this study, we aimed to examine the activation of pro-HGF to mature HGF and the expressions of HGF-related molecules, such as HGFA and HGFA inhibitor type 1 (HAI-1), in a monkey model of gastric mucosal injury., Methods: Gastric mucosal injury was induced in Japanese monkeys by administration of HCl using nasal-gastric tubes. HGF activation was evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA), and the expression of HGF, HGFA, HAI-1, and c-Met were examined by Northern blotting and immunohistochemistry., Results: Pro-HGF, but not mature HGF, was detected in normal gastric mucosa. When gastric mucosal injuries were induced, the expression of HGF significantly increased, and immunostaining of HGF was detected in fibroblasts in the gastric mucosa. In addition, conversion to mature HGF was observed in the injured gastric tissues, and mature HGF continued to increase for 48 h. HGFA was stably expressed in monkey livers, regardless of HCl administration. HAI-1 expression was detected in normal gastric mucosa, and its levels decreased after the induction of gastric mucosal injury., Conclusions: These results indicate that pro-HGF is stored in normal gastric tissues, and suggest that its conversion to mature HGF, associated with HGFA and HAI-1, is important for the repair of gastric mucosal injury.

Background: Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electron insertion., Methods: From February 1999 to September 2001, we treated 104 HCC tumors with an expandable needle with four hooks. Ninety-nine of the 104 tumors were successfully treated by single-session RFA with a single electrode insertion. We investigated the relationships between pretreatment factors (tumor size, tumor staining, tumor capsule, and tumor location) and local recurrence in these 99 tumors., Results: The mean size of the 99 tumors was 21.5 mm in diameter (range, 10 to 33 mm). The overall local recurrence rates were 9.7%, 15.4%, and 20.4%, at 1, 2, and 3 years, respectively. For small tumors (smaller than 25 mm), the local recurrence rates at 1, 2, and 3 years were 4.0%, 8.0%, and 14.6%, respectively. The local recurrence rates were 21.1% and 32.3% at 1 and 2 years, respectively, for large tumors (25 mm or larger), and at 3 years the rate was over 50% for tumors located close to the liver surface. Tumor size and tumor location relative to the liver surface were significantly associated with a higher local recurrence rate. However, other variables tested showed no significant relationship to the local recurrence rate., Conclusions: This study demonstrated that both tumor size and location relative to the liver surface influence the local efficacy of single-session RFA with a single electrode insertion.Radiofrequency ablation (RFA) is a new, minimally invasive treatment for hepatocellular carcinoma (HCC). However, there is little available information regarding local recurrence after a single session of RFA with a single electrode insertion.

A 65-year-old female had been taking analgesics containing phenacetin, because of severe headaches since 1958. The total dose of phenacetin that she had taken was calculated to be 8.0 kg. She visited the department of urology in our hospital in August, 1999 complaining of gross hematuria. A solid mass was detected in her left renal pelvis on the abdominal computed tomographic (CT) scan. Under the diagnosis of a left renal pelvic tumor, nephrouretectomy was performed in September, 1999. Histopathological diagnosis was grade 2 transitional cell carcinoma. Interstitial nephritis was also observed. Our case is the twenty-second report of an urinary tract tumor associated with phenacetin abuse in Japan.