[A Case of Spindle Cell Tumor in the Gastric Mucosa Treated with Laparoscopic Local Gastrectomy].

The patient was a 43-year-old man. An upper gastrointestinal endoscopic examination revealed a gastric submucosal tumor(SMT)-like, elevated 8-mm lesion in the greater curvature of the upper body of the stomach. It was diagnosed as spindle cell tumor on the basis of biopsy findings, and a gastrointestinal stromal tumor(GIST)was suspected. Various immunohistochemical staining techniques were used; however, a definitive diagnosis could not be achieved. There was no evidence of distant metastasis even on thoracoabdominal computed tomography imaging; thus, the patient was referred to our department for definitive diagnosis and surgical treatment. Laparoscopic local gastrectomy with concomitant intraoperative gastroscopy was performed. Pathological examination of the resected specimen showed a type Ⅱc-like lesion with a maximum diameter of 6 mm in the mucosal layer along with spindle cell proliferation. Immunostaining was negative for c- kit, DOG1, CD34, S-100, SMA, WT-1, desmin(N), EMA, and keratin(pan)and positive for ß-catenin, Bcl-2, and vimentin; furthermore, low Ki-67(MIB-1)expression was detected. Therefore, GIST, solitary fibrous tumor, leiomyoma, leiomyosarcoma, desmoid tumor, spindle cell carcinoma, and synovial sarcoma were excluded, and an unclassifiable spindle cell tumor arising from the gastric mucosa was diagnosed. The patient has remained recurrence-free for 1 year and 8 months post-operatively and is currently under careful outpatient follow-up.

Interaction between SDF1 and CXCR4 Promotes Photoreceptor Differentiation via Upregulation of NFκB Pathway Signaling Activity in Pax6 Gene-Transfected Photoreceptor Precursors.

BACKGROUND: CCL2 (also known as monocyte chemoattractant protein 1) and CX3CR1 (also known as Fractalkine receptor)-deficient mice have damaged photoreceptors. OBJECTIVES: We examined the interaction of SDF1 and CXCR4 on the differentiation of retinal progenitors into rhodopsin-positive photoreceptors. METHODS: Cloned retinal progenitors were obtained by Pax6 gene transfection of mouse iPS cells followed by serial dilution. Clones were selected by expression of nestin, Musashi1, Six3, and Chx10 mRNA. Cell surface protein expression was analyzed by flow cytometry. The levels of mRNA and intracellular protein were examined by real-time PCR and immunochemistry, respectively. Transient transfection experiments of retinal progenitors were conducted using a human rhodopsin promoter luciferase plasmid. RESULTS: We selected 10 clones that expressed Six3, Chx10, Crx, Rx1, Nrl, CD73, and rhodopsin mRNA, which, except for rhodopsin, are photoreceptor precursor markers. Clones expressed both CD73 and CXCR4 on the cell surface and differentiated into rhodopsin-positive photoreceptors, which was reinforced by the addition of exogenous SDF1. A CXCR4 inhibitor AMD3100 blocked SDF1-mediated differentiation of progenitors into photoreceptors. SDF1 enhanced human rhodopsin promoter transcription activity, possibly via the NFκB pathway. Addition of SDF1 to the cell culture induced nuclear translocation of NFκB on retinal progenitor cell clones. Neonatal and newborn mouse retinas expressed SDF1 and CXCR4. Cells in the outer nuclear layer where photoreceptors are located expressed CXCR4 at P14 and P56. Cells in the inner nuclear layer expressed SDF1. CONCLUSIONS: These findings suggest that retinal progenitor cell differentiation was at least partly regulated by SDF1 and CXCR4 via upregulation of NFκB activity.

[A Case of Large Cell Neuroendocrine Carcinoma of the Ampulla of Vater].

An 80-year-old women admitted to our hospital with jaundice. Abdominal contrast-enhanced CT scan revealed an enhanced tumor, measuring 10 mm, at the duodenal ampulla. Upper endoscopy showed a submucosal tumor-like lesion at the duodenal ampulla. Immunohistochemical findings showed positive for chromogranin A and synaptophysin, and neuroendocrine carcinoma was diagnosed. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed. The final diagnosis was large cell neuroendocrine carcinoma(LCNEC). Multiple metastases of liver, lung and bone were occurred 14 months after the surgery, and she died 21 months after the surgery. LCNEC of the duodenal ampulla is very rare, and its prognosis is poor.

[A Case of Omental Desmoid Tumor after a Small Bowel Resection for Gastrointestinal Stromal Tumor].

An intra-abdominaldesmoid tumor, especially omentaldesmoid tumor, is rare. Here, we report a case of omentaldesmoid tumor after a smallbowelresection for gastrointestinalstromaltumor (GIST). A 73-year-old man underwent a partial resection of smallbowelfor GIST. He received adjuvant therapy with imatinib due to high risk of recurrence. After 2.5 years of treatment, a follow-up CT showed a 15mm nodule in the omentum near the splenic flexure. We considered the possibility of recurrence and imatinib failure, and laparoscopic tumor resection was performed for differential diagnosis. Immunohistochemicalstaining showed negative for c-kit, CD34, desmin, and S100. However, it was diagnosed as desmoid tumor because of positive b-catenin. Intra-abdominal desmoid tumor should be a differential diagnosis for a new single lesion in patients with GIST.

Deep-Sea Phylogeographic Structure Shaped by Paleoenvironmental Changes and Ongoing Ocean Currents Around the Sea of Japan in a Crangonid Shrimp, Argis lar.

The deep-sea crangonid shrimp, Argis lar, is a highly abundant species from the northern Pacific Ocean. We investigated its phylogeographic and demographic structure across the species' extensive range, using mitochondrial DNA sequence variation to evaluate the impact of deep-sea paleoenvironmental dynamics in the Sea of Japan on population histories. The haplotype network detected three distinct lineages with allopatric isolation, which roughly corresponded to the Sea of Japan (Lineage A), the northwestern Pacific off the Japanese Archipelago (Lineage B), and the Bering Sea/Gulf of Alaska (Lineage C). Lineage A showed relatively low haplotype and nucleotide diversity, a significantly negative value of Tajima's D, and a star-shaped network, suggesting that anoxic bottom-water in the Sea of Japan over the last glacial period may have brought about a reduction in the Sea of Japan population. Furthermore, unexpectedly, the distributions of Lineage A and B were closely related to the pathways of the two ocean currents, especially along the Sanriku Coast. This result indicated that A. lar could disperse across shallow straits through the ocean current, despite their deep-sea adult habitat. Bayesian inference of divergence time revealed that A. lar separated into three lineages approximately 1 million years before present (BP) in the Pleistocene, and then had been influenced by deep-sea paleoenvironmental change in the Sea of Japan during the last glacial period, followed by a more recent larval dispersal with the ocean current since ca. 6 kilo years BP.

[Long-Term Disease-Free Survival by Curative Resection in a Case of Remnant Gastric Cancer with Peritoneal Recurrence].

The patient was 69-year-old man. For the remnant gastric cancer, partial resection of the remnant stomach with combined resection of mesentery of transverse colon was performed. Pathological diagnosis was adenocarcinoma(tub2>tub1), M, B- 50-AJ, type 3, pT4b(mesentery of transverse colon), pN0, CY0. A CT scan of 6 months after the surgery showed a tumor on the left side abdomen and diagnosed as peritoneal recurrence. Chemotherapy consisted of 1 course of TS-1(100mg/body) plus cisplatin(70mg/body), 4 courses(2 weeks administration and 1 week break)of TS-1(100mg/body), 8 courses of docetaxel(80mg/body). Tumor shrinkage and internal necrosis were observed. Peritoneal tumor was resected 19 months after the first surgery, and partial resection of the invaded transverse colon and jejunum was performed. Pathological diagnosis was metastasis of remnant gastric cancer. After that, it is 61 months since the first surgery and 42 months from the recurrence surgery without relapse.

[A Case of Perforation Peritonitis with Multiple Duodenal and Intestinal Malignant Lymphomas].

Malignant lymphomas of the duodenum and small intestine are relatively rare, but are clinically important, as they may result in perforation peritonitis. Here, we report a case of perforation peritonitis caused by multiple duodenal and small intestinal malignant lymphomas. An 84-year-old man was diagnosed with malignant lymphoma of the duodenum. Although chemotherapy was planned, emergency surgery was performed to treat perforation peritonitis. Laparoscopic observation revealed that the perforation was not in the duodenum, but in the ileum. In addition, numerous lymphoma lesions were revealed throughout the small intestine. Partial resection of the small intestine including the perforation was performed. Primary gastrointestinal malignant lymphoma may exist over multiple digestive tracts and it is necessary to carefully diagnose and treat, even in emergency surgery.

[Two Cases of Colorectal Cancer with Tumor Thrombus in the Inferior Mesenteric Vein].

In colorectal cancer, progression with an intravenous tumor thrombus is very rare. Here, we report 2 cases of colorectal cancer which showed a tumor thrombus in the inferior mesenteric vein (IMV). Case 1: A 69-year-old woman was admitted for the treatment of advanced rectal cancer, and underwent a low anterior resection. Six months of post-operative therapy was carried out with mFOLFOX6, but a metachronous lung metastasis was detected and a lung partial resection was performed. Case 2: A 67-year-old man was admitted for the treatment of advanced sigmoid colon cancer with simultaneous liver metastasis, and underwent a laparoscopic high anterior resection. Four courses of mFOLFOX6+bevacizumab chemotherapy were carried out after surgery, and subsequently he underwent a partial hepatectomy. In both cases IMV tumor thrombus was suspected from abdominal contrast-enhanced computed tomography (CT). Tumor thrombus filling the lumen of the IMV was confirmed on histopathological examination. Colorectal cancer with IMV tumor thrombus is a form of advanced cancer with advanced vascular invasion, and there is a high risk of simultaneous or metachronous hematogenous metastasis. Combined modality therapy should therefore be given to improve the prognosis.

[A case of HER2-positive advanced gastric cancer successfully treated via capecitabine, cisplatin, and trastuzumab combination chemotherapy].

We report a case of human epidermal growth factor receptor 2 (HER2) -positive advanced gastric cancer effectively treated via capecitabine, cisplatin, and trastuzumab (XPT) chemotherapy followed by curative gastrectomy. The patient was a 66- year-old man with type 2 gastric cancer in the greater curvature of the gastric angle. Biopsy revealed that the tumor was a well or moderately differentiated adenocarcinoma, and immunohistochemistry showed positive expression of HER2(3+). Chest and abdominal computed tomography(CT)showed a liver tumor 21×9 mm in size in the caudate lobe and swollen lymph nodes in the paragastric, para-aortic, and left supraclavicular regions. After 4 courses of XPT, a clinical complete response was obtained. The patient received additional 13 courses of trastuzumab and capecitabine and underwent Billroth I distal gastrectomy with D2 lymph node dissection and resection of the para-aortic and left supraclavicular lymph nodes. Liver metastasis was not detected. No residual cancer cells were found in the stomach or lymph nodes except for the left supraclavicular lymph nodes. Pathological classification according to the Japanese Classification of Gastric Carcinoma, 14 th edition, was ypT0, ypN0, ypM1(LYM), Grade 2, ypStage IV. The patient developed a post-operative anastomotic leakage that required drainage via laparotomy, but was discharged 76 days after surgery in good condition.

Contrasting population histories of the deep-sea demersal fish, Lycodes matsubarai, in the Sea of Japan and the Sea of Okhotsk.

Recent studies have revealed the impact of the drastic climate change during the last glacial period on coastal marine and anadromous species in the marginal seas of the northwestern Pacific Ocean; however, its influence on deep-sea species remains poorly understood. To compare the effects of the last glacial period on populations from the Sea of Japan and the Sea of Okhotsk, we examined the mitochondrial control region and cytochrome b gene sequences of Lycodes matsubarai, a deepsea demersal fish that inhabits these two seas. Our results showed clear genetic differentiation of populations between the two seas. The populations may have diverged during the last glacial period, probably as a result of vicariance due to the drastic sea level change. The population in the Sea of Okhotsk was larger than that in the Sea of Japan, but suddenly decreased after the last glacial period. However, the Sea of Japan population expanded after the last glacial period, coincident with high levels of oxygenation in deep-sea areas. These results elucidate regional-scale impacts of climate change on deep-sea organisms.

Improving drug adherence using fixed combinations caused beneficial treatment outcomes and decreased health-care costs in patients with hypertension.

We enrolled 196 patients with hypertension who were already being treated with free-drug combinations of angiotensin-II receptor blocker (ARB) and amlodipine. The free-drug combinations of ARB and amlodipine were replaced with the same dose of the fixed-dose combinations. The average home blood pressure (BP) in all patients receiving fixed-dose combinations was significantly lower than those receiving free-drug combinations (131 ± 10/75 ± 8 vs. 136 ± 11/77 ± 9 mm Hg, P < .01) accompanied with increasing drug adherence. After lowering BP by fixed-dose combinations, the costs for medications decreased by 31% over the 3 months.

(-)-Benzyl 2,3-dide-oxy-ß-d-erythro-hex-2-eno-pyran-oside.

In the title compound, C13H16O4, the six-membered ring of the sugar moiety shows a half-chair conformation. In the crystal, mol-ecules are connected via O-H⋯O hydrogen bonds, forming columns around twofold screw axes along the b-axis direction. There is a disorder of the benz-yloxy group, which has two possible orientations with the phenyl group lying on a common plane [site-occupancy factors = 0.589 (9) and 0.411 (9)].

Role of SDF1/CXCR4 interaction in experimental hemiplegic models with neural cell transplantation.

Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES) cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1) in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

Ventricular fibrillation during carotid endarterectomy and bailout stenting: a case report.

BACKGROUND: Carotid artery manipulation is not a special technique but reports of intraoperative ventricular fibrillation are rare. The risk of fatal arrhythmias may be hidden behind routine surgical techniques and anesthetic management. We focused on QT prolongation and QT dispersion. CASE PRESENTATION: A 77-year-old man underwent carotid endarterectomy and bailout stenting. Although there were no obvious preoperative risk factors for intraoperative ventricular tachyarrhythmia, ventricular fibrillation (VF) had occurred during a maneuver of the carotid artery under hypercapnia. QTc was prolonged from 317 ms before surgery to 458 ms before the onset of VF. QTc dispersion between leads II and III was also increased to 50 ms. Hypomagnesemia was noted after resuscitation by electrical defibrillation, adrenaline, and noradrenaline. CONCLUSIONS: We considered that the combination of multiple risk factors led to the development of ventricular fibrillation. It should be noted that carotid artery manipulation has the potential to cause arrhythmias.

Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy in patients with advanced gastric cancer.

BACKGROUND: A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer. METHODS: Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2) on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.d. on days 1 to 14 followed by 2 weeks off, in a 28-day cycle. RESULTS: A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confirmed, giving an overall response rate of 46.3%. At a final follow up of 3 years, the median progression-free survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatment-related deaths. CONCLUSION: A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confirmation.

Transfection with pax6 gene of mouse embryonic stem cells and subsequent cell cloning induced retinal neuron progenitors, including retinal ganglion cell-like cells, in vitro.

OBJECTIVE: It is theoretically possible to induce various cell types, including retinal neurons, from embryonic stem cells (ESCs). pax6 regulates early events in eye development, including the generation of retinal ganglion cells (RGCs). We previously reported the successful induction of corneal epithelial cells from ESCs transfected with the pax6 gene. Here, we attempted to establish cloned RGC-like cells from ESCs transfected with the pax6 gene. METHODS: Undifferentiated mouse ESCs were transfected with pax6 cDNA by electroporation, followed by selection with G418. We conducted limiting-dilution culture of pax6-transfected cells. We expanded the cloned pax6-transfected cells, which expressed nestin and musashi-1, for further characterization in culture media containing fibronectin. The cells were characterized using RT-PCR, immunostaining, electron microscopy, renal subcapsular transplantation assay and Ca imaging. RESULTS: We obtained clonally expanding pax6-transfected cells, all of which were positive for six3, sonic hedgehog (shh), math5, brn3, thy1 and melanopsin, by using several ESCs. When transplanted into a mouse renal capsule, they differentiated into neurons with elongated axons, expressing betaIII tubulin and neurofilament middle chain, and were free from teratoma development. Electron-microscopic examination showed neurotubules and neurofilaments in the axon-like processes of the cloned pax6-transfected cells. High KCl stimulation increased free Ca influx on Ca2+ imaging. CONCLUSIONS: ESCs were applicable for the induction of retinal progenitor cells, including RGC-like cells, by transfection with the pax6 gene and subsequent limiting-dilution culture. Cloned cell lines may be useful to analyze the requirements for retinal progenitor cell differentiation, and our study suggests the clinical application of this cell type.

Mechanisms Associated with the Adverse Vascular Consequences of Rapid Posthypothermic Rewarming and Their Therapeutic Modulation in Rats.

We previously demonstrated that rapid posthypothermic rewarming in noninjured animals was capable of damaging cerebral arterioles both at endothelial and smooth muscle levels. Such adverse consequences could be prevented with antioxidants, suggesting the involvement of free radicals. In this study, we further investigate the mechanisms associated with free radicals production by using two radical scavengers, superoxide dismutase (SOD) and catalase. Employing rats, the cerebral vascular response was evaluated at 2, 3, and 4 hours after onset of hypothermia. Before rapid rewarming, SOD treatment, but not catalase, preserved the NO-mediated dilation induced by acetylcholine (ACh). On the contrary, catalase preserved the hypercapnia-induced relaxation of the smooth muscle cells, whereas SOD offered only partial protection. Adding SOD to catalase treatment offered no additional benefit. These results suggest that rapid posthypothermic rewarming impairs ACh- and hypercapnia-induced vasodilation through different subcellular mechanisms. In the case of diminished vascular response to ACh, it appears to act on the endothelial front primarily by superoxide anions, as evidenced by its full preservation after SOD treatment. In terms of impaired dilation to hypercapnia, hydrogen peroxide and/or its derivatives are the likely candidates in targeting the smooth muscle cells. The partial protection of SOD to hypercapnia-induced dilation is believed to be the reduced amount of superoxide that would otherwise spontaneously dismutate to produce hydrogen peroxide. Although SOD exerts some indirect influence on the hydrogen peroxide production downstream, catalase apparently has no influence on upstream superoxide production.

A case of poorly differentiated adenocarcinoma with lymphoid stroma originated in the ascending colon diagnosed as lymphoepithelioma-like carcinoma.

An 86-year-old woman's stool sample was positive for blood. Computed tomography (CT) showed wall thickening of the ascending colon at the hepatic flexure. Colonoscopy showed near-complete obturation by colon cancer. Since she was asymptomatic, elective surgery was planned. Laparoscopic right hemicolectomy was performed. Histopathological examination showed poorly differentiated carcinoma cells proliferating in a solid pattern with marked lymphocyte infiltration. The diagnosis was lymphoepithelioma-like carcinoma (LELC) associated with Epstein-Barr virus (EBV) infection; however, EBV-encoded small RNA-in situ hybridization was negative. Microsatellite instability was not assessed. The postoperative course was uneventful and she was discharged on the 15th postoperative day. She remains recurrence-free at 2 years after surgery. Past reports note that colorectal carcinomas with dense lymphoid stroma may be related to LELC or medullary carcinoma (MC). Gastrointestinal LELC is rare, with some reports on LELC of the esophagus and stomach. Reports on LELC of the large intestine are very rare. MC of the large intestine is relatively new concept, firstly described in the WHO Classification of Tumours of the Digestive System 3rd Edition in 2000. We herein present a case of lymphoepithelioma-like carcinoma of the ascending colon and relevant case reports about LELC and MC of the large intestine.

Bathyraja (Arctoraja) sexoculata sp. nov., a new softnose skate (Rajiformes: Arhynchobatidae) from Simushir Island, Kuril Islands (western North Pacific), with special reference to geographic variations in Bathyraja (Arctoraja) smirnovi.

A new species of softnose skate (Arhynchobatidae), Bathyraja sexoculata Misawa, Orlov, Orlova, Gordeev and Ishihara is described on the basis of five specimens collected from off the east coast of Simushir Island, Kuril Islands, located in the western North Pacific. The specimens conformed to the genus Bathyraja by having the anteriormost pectoral-fin skeleton almost reaching the snout tip, and a slender unsegmented rostral cartilage. Within Bathyraja, the new species belongs to the subgenus Arctoraja (currently with four valid species) due to the relatively short tail (79-86% of disc width), high count of predorsal caudal vertebrae (more than 86), and large strong nuchal and scapular thorns. It is most similar to Bathyraja (Arctoraja) smirnovi, distributed in the Seas of Japan and Okhotsk, in having tail thorns not extending to the nuchal area, median thorns discontinuous from the nape to the tail, and no mid-dorsal thorns. However, B. sexoculata can be distinguished from B. smirnovi by the following characters: three pairs of white blotches on the dorsal disc surface (vs. blotches absent, or a pair of white or dark blotches in B. smirnovi), dark blotch around cloaca, dark bands along mid ventral line of tail (vs. dark blotch and band usually absent ventral disc surface in B. smirnovi), 86-93 predorsal caudal vertebrae (vs. 80-87 in B. smirnovi), and a unique mitochondrial DNA cytochrome c oxidase subunit I sequence. Proportional measurements, including disc width, disc length, head length, preoral length, prenarial length, internarial distance, eye diameter, and tail length, also differ between the two species. For the referential purpose, geographical variations of B. smirnovi distributed in the Seas of Japan and Okhotsk are analyzed and clarified based on morphological and genetic data. Significant morphological and genetic differences were found between local populations in the Seas of Japan and Okhotsk.

Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet's disease (210 characters).

OBJECTIVES: We have previously demonstrated that the phylum Actinobacteria, the family Lactobacillaceae, and the genus Bifidobacterium increased in relative abundance of gut microbiota in patients with Behcet's disease (BD). The phylum Firmicutes and the class Clostridia were predominant in the feces of normal individuals. The class Clostridia includes short-chain fatty acid-producing bacteria, important for the balance between regulatory T cells and helper T type 17 (Th17) cells. It is possible that the bacterial compositional alteration causes low intestinal short-chain fatty acid concentrations, leading to skewed immune functions in patients with BD. METHODS: To test the hypothesis, we examined species composition and gene functions from the 16S rRNA data by utilizing PICRUSt software. RESULTS: We have shown that relative abundance of Eggerthella lenta, Acidaminococcus species, Lactobacillus mucosae, Bifidobacterium bifidum, Lactobacillus iners, Streptococcus species, and Lactobacillus salivarius increased significantly in patients with BD. Relative abundance of Megamonas hypermegale, Butyrivibrio species, Streptococcus infantis, and Filifactor species increased significantly in normal individuals compared with BD patients. In the functional annotation analysis by PICRUSt, we found prevalent gene functions of the pentose phosphate pathway and the inosine monophosphate biosynthesis in patients with BD. The data suggested that BD gut microbes altered nucleic acid and fatty acid synthesis. CONCLUSIONS: These compositional and functional alterations of gut microbes may accompany unfavorable molecular exchanges between intestinal immunocompetent cells and gut microbes, and these interactions may have an association with the immune aberration in patients with BD.