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Background: In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy.Methods: Thirty patients were treated with 12 weeks of ledipasvir/sofosbuvir and ribavirin. We evaluated the rate of sustained virological response 12 weeks after the end of treatment (SVR12) and examined the incidence of adverse events during ledipasvir/sofosbuvir and ribavirin treatment. NS5A and NS5B resistance-associated variants (RAVs) in treatment failure cases were examined.Results: The overall SVR12 rate was 86.7% (26/30). Large decreases in mean log10 HCV RNA levels were observed in patients without cirrhosis, and the SVR12 rate for these patients was 100% (12/12). In cases of cirrhosis, SVR12 rate was 72.2% (13/18). The common factors in treatment failure cases were the presence of liver cirrhosis and both NS5A L31M/I and Y93H RAVs. The frequency of RAVs did not change before and after treatment among patients who relapsed.Conclusion: Ledipasvir/sofosbuvir with ribavirin is an effective retreatment option for patients with chronic hepatitis C who failed to respond to prior daclatasvir and asunaprevir therapy. [ABSTRACT FROM AUTHOR]

Thermal spray (TS) coatings have been extensively utilized for various surface modifications such as enhancing wear/erosion resistance and thermal protection. In the present study, a new function of TS material is explored by studying its load-carrying capability. Due to the inherent microstructures containing voids and interfaces, it has been presumed TS materials were not suitable to bear loads. However, the recent advances in TS technology to manufacture near fully dense TS coatings have expanded their potential applications. In the current experiments, TS nickel coatings are deposited onto metallic substrates, and their mechanical behaviors are closely examined. Based on the measured data, the estimated elastic modulus of TS Ni is about 130 GPa (35% less than bulk value), and the maximum tensile strength is about 500 MPa (comparable to bulk value). It was found that such a high value is attainable because the coating is deposited onto a substrate, enabling a load-transfer mechanism and preventing coating failure at a much lower stress level. Three distinct deformation stages are identified to describe this behavior. Such a clarification is critical for enabling TS process to restore structural parts as well as to additively manufacture load-bearing components. [ABSTRACT FROM AUTHOR]

Dongrae and Haeundae are representative hot spring areas that have been used as spas for more than 1,000 years in the southern Korean Peninsula. These hot springs have water temperatures >58 °C and are located along the southeast coastal area of the peninsula. We used C, H, δO, δH, and Sr/Sr isotope data for the Dongrae and Haeundae hot spring waters collected over 2004-2014 to investigate the groundwater cycle and heat source for these hot springs. The stable isotope compositions of O and H suggested meteoric origin of the hot spring waters. The Sr/Sr ratios for the Dongrae and Haeundae hot spring waters have been steady for 11 years at 0.70567 ± 0.00002 and 0.70607 ± 0.00002, respectively, suggesting that they are in a near equilibrium state. The C age of the Dongrae hot spring waters ranges from 1,401 to 2979 years BP, and that of the Haeundae hot spring waters from 1930 to 6687 years BP. We observed a strong correlation between 87Sr/86Sr and C, as well as δO. Therefore, the hot springs in the Busan area were supposed to be heated by a paleo-heat source, suggesting that there may be no current heat source under the present crustal conditions. This study also demonstrates that monitoring of the Sr/Sr ratio and C in the groundwater and deep thermal water can be used as a proxy for tracing the heat source of geothermal waters such as hot springs and an indicator of groundwater mixings between upper and lower aquifers in granite area. [ABSTRACT FROM AUTHOR]

We report a rare case of pancreatic serous cystadenoma, which shrank remarkably from 6 to 1.5 cm in diameter, with cystic degeneration, over a period of only 3 weeks. A 29-year-old woman who presented with epigastric pain and jaundice underwent computed tomography, which showed a 6-cm monolocular cystic tumor in the pancreatic head. Endoscopic retrograde cholangiopancreatography showed stenosis and deviation of the inferior part of the extrahepatic bile duct. We performed surgery 3 weeks later for suspected mucinous cystadenoma or macroscopic serous cystadenoma of the pancreas. At laparotomy, the tumor in the pancreatic head was found to have shrunk remarkably. We excised the tumor completely by performing the Whipple procedure. Macroscopically, the mass was a 1.5-cm monolocular cyst. Microscopically, the cystic tumor was composed of a thick fibrous wall with granulation tissue and hemorrhage. Although epithelial cells were not found inside the cystic wall, numerous grossly invisible microcysts with glycogen-containing epithelial cells were seen at its periphery. Based on these findings, the tumor was diagnosed as a serous cystadenoma with cystic degeneration. [ABSTRACT FROM AUTHOR]

R- spondin ( RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4 %) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population. [ABSTRACT FROM AUTHOR]

Large-scale landslides along the Kubusu and Besso rivers in Toyama Prefecture are developed in the Miocene Iwaine Formation, which is composed of andesitic lava, tuff, and tuff breccia. In the middle member of this formation, the tuff is easily altered to montmorillonite-bearing rock, and subsequently plays an important role in the development of landslides events, which tend to be large-scale events, as the massive lava of the upper member forms a cap rock over the tuff. The Kiritani and Koinami basins, which are flat intermontane basins located along the Kubusu and Besso rivers, respectively, are interpreted as landslide-dammed lakes, later filled with sediment. Accelerator mass spectrometry C ages show that the landslides forming each dam occurred simultaneously, at approximately 2500 BP. These ages were measured from wood fragments embedded in the landslide material of Kiritani, and from an in situ stump drowned during the impoundment of Koinami. If the trigger of these landslides was an earthquake, it is most likely to have been the penultimate event along the Atotsugawa fault zone. [ABSTRACT FROM AUTHOR]

Real-time curvature measurement of a coating-substrate system during deposition has facilitated the monitoring of coating stresses and provided additional insights into thermal spray deposition mechanisms. However, the non-equilibrium state of coating formation along with harsh spray booth environment introduces complexity not only in data interpretation but also in the coating properties estimation. In this paper, a new procedure is proposed to estimate the elastic modulus of thermal sprayed ceramic coatings using in situ curvature and temperature measurements. In order to correlate the measurable parameters to coating elastic modulus, a systematic study is conducted to develop a suitable methodology. First, various finite element model analyses are carried out to formulate suitable relations between the measurements and elastic modulus. Subsequently, experiments are conducted to validate the procedure to estimate coating moduli. The results are compared with more accurate measurements obtained from post-deposition characterization technique under low temperature thermal cycles. The comparison suggests that the moduli estimated using the proposed procedure are in good agreements with those obtained from the post-deposition technique. Further, the nonlinear response of coatings are evaluated from the estimated moduli during deposition and cool down, which offer additional information on the characteristics of thermal spray coatings. [ABSTRACT FROM AUTHOR]

The diagnostic significance of single-balloon enteroscopy (SBE) in patients presenting with Crohn's disease (CD)-like anorectal fistula is unknown. We experienced 11 cases undergoing SBE due to CD-like fistulas between December 2007 and April 2013. The mean interval from fistula onset to SBE was 19.2 months with a range of 1.3−44.7. Prior to SBE, all patients underwent anorectal examination under anesthesia (EUA), and 9 patients underwent total colonoscopy with terminal ileal cannulation (TCS-I). One of 7 patients undergoing upper gastrointestinal endoscopy had CD-like gastritis. EUA revealed CD fissures in 7 patients, 1 of whom had no intestinal lesion. Primary TCS-I identified early lesions, such as aphthes and small ulcers, in 4 patients. Among the other 5 patients without any intestinal lesions with TCS-I, SBE indicated early lesions in 3 patients. One of 2 patients who initially underwent SBE without TCS-I showed multiple aphthes. Of the 11 patients, only 4 patients fulfilled the definitive Japanese diagnostic criteria for CD and 7 remained 'suspected CD' cases. Intrinsic anorectal fistulas as a presenting symptom of CD may be an early predictor of bowel lesions. SBE has the potential to reveal incipient disease because an early ileal lesion is not rare for patients with anorectal fistulas. [ABSTRACT FROM AUTHOR]

Adhesive strength of the plasma-sprayed thermal barrier coating is one of the most important parameters which influence their durability and reliability during service. While many methods exist to measure the adhesive strength, in general, they require cumbersome and time-consuming specimen preparation. Furthermore, considerations of the adhesion strength from the point-of-view of fracture toughness or for that matter, their systematic correlation to both processing variances are limited. Consequently, there is an opportunity to both simplify the measurement procedure and establish correlations among methods and linkages between processing parameters and interfacial fracture toughness. In this paper, we report results on adhesion strength of plasma-sprayed yttria-stabilized zirconia (YSZ) coating on aluminum substrates based on both interfacial indentation test (to measure interfacial fracture toughness) and the modified tensile adhesive test. Carrier gas flow for powder injection into the plasma torch was systematically varied to introduce variances in particle melting with concomitant impact on the measured adhesive strength. The results indicate the correlation between the particle melting index and the measured interfacial fracture toughness. [ABSTRACT FROM AUTHOR]

The properties and performance of plasma-sprayed thermal barrier coatings (TBCs) are strongly dependent on the microstructural defects, which are affected by starting powder morphology and processing conditions. Of particular interest is the use of hollow powders which not only allow for efficient melting of zirconia ceramics but also produce lower conductivity and more compliant coatings. Typical industrial hollow spray powders have an assortment of densities resulting in masking potential advantages of the hollow morphology. In this study, we have conducted process mapping strategies using a novel uniform shell thickness hollow powder to control the defect microstructure and properties. Correlations among coating properties, microstructure, and processing reveal feasibility to produce highly compliant and low conductivity TBC through a combination of optimized feedstock and processing conditions. The results are presented through the framework of process maps establishing correlations among process, microstructure, and properties and providing opportunities for optimization of TBCs. [ABSTRACT FROM AUTHOR]

A 380-cm-long sediment core was acquired from the deep water area of Pumoyum Co, southern Tibet. Twenty-five plant residue samples were selected, and organic carbon stable isotopes were obtained using the AMS C chronological method. The C age and carbon reservoir effect were calibrated with surface sedimentation rate measurements using Pb dating. Results showed that the core sediment deposited over 19 cal ka BP. Based on a multi-proxy analysis of TOC and IC contents, grain size and pollen assemblage data, the palaeoclimatic evolution of Pumoyum Co was reconstructed since the last glacial. Pumoyum Co was a shallow lake prior to 16.2 cal ka BP; although the glacier around the lake began to melt due to increasing temperatures, climate was still cold and dry. In the interval of 16.2-11.8 cal ka BP, the sedimentary environment fluctuated drastically and frequently. Two cold-events occurred at 14.2 and 11.8 cal ka BP, and these may correspond to the Older Dryas and the Younger Dryas events, respectively. After 11.8 cal ka BP, Pumoyun Co developed into the deep lake as it is now. The lake water temperature was relatively lower at that time because of influx of cold water from glacial meltwater entering the lake. As a result, the multi-proxy indicators showed no sign of warm conditions. Comparisons between the sedimentary record of Pumoyum Co with that of other lakes of the same age in southern Tibet indicate a warmer climate following the last deglaciation influenced the southeastern Tibetan Plateau. These results imply that the southwest Asian monsoon gradually became stronger since the deglaciation during its expansion to the inner plateau. The glacial-supplied water of the lake responded sensitively to cold-events. The entire southern Tibet region was dominantly influenced climatically by the southwest Asian monsoon during the Holocene. [ABSTRACT FROM AUTHOR]

A total number of 328 groundwater samples are analysed to evaluate the groundwater flow systems in Bengal Delta aquifers, Bangladesh using environmental isotope (H, O, C, H, and C) techniques. A well-defined Local Meteoric Water Line (LMWL) δH = 7.7 δO + 10.7 ‰ is constructed applying linear correlation analyses to the monthly weighted rainfall isotopic compositions (δO and δH). The δO and δH concentrations of all groundwater samples in the study area are plotted more or less over the LMWL, which provides compelling evidence that all groundwaters are derived from rainfall and floodwater with a minor localized evaporation effects for the shallow groundwaters. Tritium concentration is observed in 40 samples out of 41 with values varying between 0.3 and 5.0 TU, which represents an evidence of young water recharge to the shallow and intermediate aquifers. A decreasing trend of C activity is associated with the heavier δC values, which indicates the presence of geochemical reactions affecting the C concentration along the groundwater flow system. Both vertical and lateral decrease of C activity toward down gradient show the presence of regional groundwater flow commencing from the unconfined aquifers, which discharges along the coastal regions. Finally, shallow, intermediate, and deep groundwater flow dynamics has revealed in the Bengal Delta aquifers, Bangladesh. [ABSTRACT FROM AUTHOR]

Antarctic climate changes influence environmental changes at both regional and local scales. Here we report Holocene paleolimnological changes in lake sediment core Sk4C-02 (length 378.0 cm) from Lake Skallen Oike in the Soya Kaigan region of East Antarctica inferred from analyses of sedimentary facies, a range of organic components, isotope ratios of organic carbon and nitrogen, and carbon-14 dating by Tandetron accelerator mass spectrometry. The sediment core was composed of clayish mud (378.0–152.5 cm) overlain by organic sediments (152.5 cm-surface). The age of the surface and the core bottom were 150 (AD1950-1640) and ca. 7,030 ± 73 calibrated years before present (cal BP), respectively, and the mean sedimentation rate was estimated to be 0.55 mm/year. Multi-proxy analyses revealed that the principal environmental change in the core is a transition from marine to lacustrine environments which occurred at a depth of 152.5 cm (ca. 3,590 cal BP). This was caused by relative sea level change brought about by ongoing retreat of glaciers during the mid-Holocene warming of Antarctica, and ongoing isostatic uplift which outpaced changes in global (eustatic) sea level. The mean isostatic uplift rate was calculated to be 2.8 mm/year. The coastal marine period (378.0–152.5 cm, ca. 7,030–3,590 cal BP) was characterized by low biological production with the predominance of diatoms. During the transition period from marine to freshwater conditions (152.5-approximately 135 cm, ca. 3,590–3,290 cal BP) the lake was stratified with marine water overlain by freshwater, with a chemocline and an anoxic (sulfidic) layer in the bottom of the photic zone. Green sulfur bacteria and Cryptophyta were the major photosynthetic organisms. The Cryptophyta appeared to be tolerant of the moderate salinity and stratified water conditions. The lacustrine period (approximately 135 cm-surface, ca. 3,290 cal BP-present) was characterized by high biological production by green algae (e.g. Comarium clepsydra and Oedegonium spp.) with some contributions from cyanobacteria and diatoms. Biological production during this period was 8.7 times higher than during the coastal marine period. [ABSTRACT FROM AUTHOR]

Thermal spray in general, plasma spray in particular, is a highly complex process with numerous interacting variables associated with generation of the spray stream, deposit formation dynamics, and the resultant property linkages. Compounding this variability further are both the spatial (different booths and different locations) and temporal (process start-stops, hardware degradation, operator etc.) effects. As such, an understanding of process and coating consistency and variability offers significant challenges. Recent scientific advances as well as measurement tools have enabled elucidation of the intrinsic variabilities associated with each of the process sub-steps; however, integrated understanding of the system level reliability is still lacking. This article seeks an integrated assessment of process and coating reliability through systematic measurements of variabilities during each stage of the process subjected to different operating parameters. Through critical examination of first-order process maps, the influence of process parameters on particle state is reviewed for repeated spray runs with a single parameter effect as well as across a spectrum of process parameters. In addition, influence of these changes on design-relevant coating properties were obtained for plasma-sprayed zirconia through recourse to novel in situ and ex situ substrate curvature measurements. Finally, the implications of such integrated reliability studies have been explored through collaborative experiments conducted in the industrial sites. [ABSTRACT FROM AUTHOR]

The exact mechanism of blood vessel thrombus formation remains to be defined. Here, we introduce a new approach to probe thrombus formation in blood vessels of living animals using intravital microscopy in green fluorescent protein (GFP)-transgenic mice to simultaneously monitor platelet aggregation and procoagulant activity. To this end, GFP-expressing platelets and annexin A5 labeled with a fluorescent dye were employed to visualize and analyze platelet aggregation and markers of procoagulant activity (platelet surface phosphatidylserine (PS)). Laser-induced thrombi increased and then decreased in size with time in vessels of living animals, whereas platelet surface PS initiated at the site of injury and then penetrated into the thrombus. PS-positive platelets were predominantly localized in the center of the thrombus, as was fibrin generation. The experimental system proposed here is a valuable tool not only for investigating mechanisms of thrombus formation but also to assess the efficacy of antithrombotic drugs within the vasculature. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Anal fistulas are common in individuals with Crohn's disease (CD). We sought to evaluate the efficacy of oral spherical adsorptive carbon (AST-120) (Kremezin®; Kureha Corporation, Tokyo, Japan) for the treatment of intractable anal fistulas in patients with CD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, patients with CD and at least one active anal fistula under treatment were assigned to receive either AST-120 or placebo for 8 wk. Improvement was defined as a reduction of 50% or more from baseline in the number of draining fistulas observed at both 4 and 8 wk. Remission was defined by closure of all draining fistulas at both 4 and 8 wk. The Perianal Disease Activity Index (PDAI) and Crohn's Disease Activity Index (CDAI) were also assessed. RESULTS: In total, 62 patients were randomized, of whom 57 received AST-120 (N = 27) or placebo (N = 30). The improvement rate in the AST-120 group (37.0%) was significantly greater than that in the placebo group (10.0%) ( P= 0.025). The corresponding remission rates were 29.6% and 6.7%, respectively ( P= 0.035). PDAI significantly improved at both 4 and 8 wk with AST-120, compared to placebo ( P= 0.004 and P= 0.005, respectively). CDAI was also significantly improved at both 4 and 8 wk in the AST-120 group, compared to the placebo group ( P= 0.007 and P= 0.001, respectively). AST-120 treatment was well tolerated and no life-threatening adverse events were observed. CONCLUSION: AST-120 is useful for the control of intractable anal fistulas in CD patients. [ABSTRACT FROM AUTHOR]

We report four cases of Crohn’s disease (CD)-associated colorectal cancer (CRC) in our department. A 42-year-old Japanese man had a 14-year history of ileocolon CD. He had a history of an ileocecal resection and a stricture plasty. At the age of 42, sigmoid colostomy was performed because of the deterioration of the anal stenosis. After this operation, the perianal pain had remained, and a magnetic resonance imaging scan revealed a rectal tumor. A 30-year-old Japanese man had a 13-year history of ileocolon CD. He had a history of an ileostomy, a subtotal colectomy, and ileo-rectal anastomosis. At the age of 30, he had perianal pain, and a colonoscopy revealed a rectal cancer. An abdomino-perineal resection of the remnant rectum was performed. A 46-year-old Japanese man had a 9-year history of ileocolon CD. He experienced abdominal fullness. Colonoscopy revealed an ascending colon cancer. He underwent a subtotal colectomy and ileo-rectal anastomosis. A 33-year-old Japanese woman had a 16-year history of ileocolon CD. She had no changes in symptoms of CD. Surveillance colonoscopy revealed a transverse colon cancer. She underwent a subtotal colectomy and ileo-rectal anastomosis. As the number of patients with CD and with CD-associated CRC has increased in Japan, CD-associated CRC, as noted in these patients, should be kept in mind in the management of patients with CD. In addition, a surveillance system of patients with CD should be established and should prompt further study about CD-associated CRC. [ABSTRACT FROM AUTHOR]

A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription–polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P=0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 downregulation in colorectal cancer, we examined the methylation status of the 5′CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2′-deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P=0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P=0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P=0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5′CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.Oncogene (2005) 24, 5637–5647. doi:10.1038/sj.onc.1208720; published online 11 July 2005 [ABSTRACT FROM AUTHOR]

The integrity of a composite laminate can be greatly affected by an existence of embedded interlaminar flaw. In general, identification of such a flaw often requires expensive tools and tedious processes. The aim of the present work is to develop a novel method with the aid of an intelligent post-processing scheme, thereby not relying on those sophisticated experiments. Essentially the proposed procedure utilizes an inverse analysis to estimate unknown delamination parameters from limited measurements. The procedure first constructs approximate functions relating the delamination parameters to measurement parameters. Then, a multi-dimensional minimization technique is adopted to search for the best estimates of unknown parameters corresponding to the lowest value of error objective function. In the present verification and simulation analyses, surface strains at discrete locations on a composite laminate under three-point bending are selected as the input measurements. Although reasonable estimates are obtained with these measurements, to increase their accuracy, the deflection at load point is also included as measurement input. Additional improvements are observed when those measurements under multiple loading conditions are included. A detailed error sensitivity analysis is also carried out to confirm the method’s robustness. These results suggest the current method to be one of the alternate identification approaches for detecting a single embedded delamination in composite laminates. [ABSTRACT FROM AUTHOR]

This paper presents the features of the “eleven-year” cycle of radiocarbon content during the period of prolonged sunspot minimum called the Maunder Minimum (1645-1715AD). Whether or not the Sun had maintained the cyclic polarity reversal even during the Maunder Minimum has been a controversial topic for a long time. Although persistency of the cyclicity has been investigated by using cosmogenic isotopes or by calculations, a consistent description has not been obtained so far. Hence, we have obtained a new record of carbon-14 content in tree rings from 1631-1739AD, and made a comparison with the record previously obtained. Periods of 13-15 and 24-29 years detected in the variation of carbon-14 content seem to be suggesting that the Sun had retained periodic polarity reversal during this prolonged minimum with slightly longer periodicity than that of recent intense solar activity. Our results seem to support the inverse correlation between the intensity and the cycle length of solar activity. [ABSTRACT FROM AUTHOR]

We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third portion of the duodenum extending into the pancreas head. As the tumor was pathologically determined to be adenocarcinoma at the time of surgery, pylorus-preserving pancreaticoduodenectomy was performed. We carried out molecular analyses of this patient to examine the pathway of carcinogenesis in PJS. The tumor did not show somatic mutation of the APC and K-ras genes, which is a critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a germline mutation of the STK11 gene was detected at codon 281 delC in exon 6. Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11 and somatic mutation of the p53 gene. These findings suggest that STK11 is a tumor suppressor gene regulating the development of hamartomas, and that somatic mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in PJS. [ABSTRACT FROM AUTHOR]

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor that preferentially involves the pelvic and perineal regions, and is characterized by frequent local recurrences. We describe here a case of large AA in a 31-year-old woman. The patient was admitted to our hospital with a mass in the perineal region, associated with severe menstrual pain. Although her past medical history was unremarkable, she had spotty pigmentation on the lips. Magnetic resonance imaging showed a large mass in the abdominal pelvis traversing the pelvic diaphragm just to the right of the anus, and the border between the tumor and the rectal wall was indistinct. Pathology examination of a frozen intraoperative specimen suggested AA, and, therefore, we completely resected the tumor, using a combined abdominoperineal approach. The tumor was attached to the right wall of the rectum and the pelvic diaphragm between the anus and the puborectalis. The patient recovered uneventfully and there has not been any evidence of local recurrence for 3 years postoperatively. We consider that abdominoperineal resection may be an appropriate treatment for a large AA infiltrating to the perirectal tissues, because the high recurrence rate of this disease has been attributed to incomplete surgical excision. [ABSTRACT FROM AUTHOR]

This study was conducted to determine whether stapled ileal pouch-anal canal anastomosis (IACA) preserving the anal transitional zone (ATZ) or hand-sewn ileal pouch-anal anastomosis with mucosectomy (IPAA) is more beneficial in achieving disease eradication and better postoperative function. IACA was performed in 10 patients with ulcerative colitis (UC) and 10 patients with familial adenomatous polyposis (FAP), 15 of whom were examined proctoscopically. IPAA was performed in 4 patients with UC and 8 patients with FAP. The mean maximum resting pressure (MRP) was 55 mmHg in the IACA group and 34 mmHg in the IPAA group ( P < 0.01). The anorectal inhibitory reflex was positive in 18 patients (90%) from the IACA group and 5 (42%) from the IPAA group ( P < 0.05). The pre- and postoperative MRPs were 61 mmHg and 55 mmHg, respectively, in the IACA group vs 63 mmHg and 34 mmHg, respectively, in the IPAA group ( P < 0.01). Whereas 16 (80%) of the 20 IACA patients could discriminate feces from gas, only 4 (33%) of the 12 IPAA patients could ( P < 0.05). The mean observation period was 2.3 years, the mean length of the columnar cuff was 2.8 cm, and no case of dysplasia or adenoma was seen. Postoperative function is more favorable following IACA than following IPAA, both physiologically and symptomatically. However, long-term surveillance of the residual mucosa is necessary before making a final recommendation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 57-year-old man presented with a perianal fistula after restorative proctocolectomy for refractory ulcerative colitis (UC). He underwent through ileal pouch-anal anastomosis (IPAA) and his histological findings of excised colorectum were compatible with UC and ruled out Crohn's disease (CD). He was treated with metronidazole and his computed axial tomography failed to reveal an intraabdominal abscess.

The St.16 core obtained from the Academician Ridge of Lake Baikal in eastern Siberia may span about 260 000 years, and some physical properties of the core samples are closely related to aquatic paleoproductivity and climatic change. The median of grain size, grain density, and water content fluctuate synchronously. They also are connected with change in the abundance of biogenic silica (diatoms). The physical parameters indicate that there were high aquatic productivity periods around ‘interglacial’ periods (MIS 5 and 7; 70 000-125 000 yr B.P. and 180 000-250 000 yr B.P.). Comparatively large clastics were transported from outside of the lake through various routes (ice rafting, etc.) in addition to fluvial routes during the ‘glacials‘ or 'stadials’. There are ca. 20 000 yr, 40 000 yr and 100 000 yr periods in the variations of physical properties. These are related to the three Milankovitch parameters of solar insolation. [ABSTRACT FROM AUTHOR]

The present study was conducted to clarify whether endotoxin-induced liver injury could be improved by modulating the function of hepatic macrophages using OK432, an immunostimulant derived from Streptococcus. OK432 elevated the capacity of hepatic macrophages to produce superoxide and tumor necrosis factor (TNF), and enhanced the mRNA expression of interleukin-1-α, -β, and TNF-α in liver nonparenchymal cells (NPC). However, intravenous (iv) preadministration of OK432 reduced the mRNA expression of TNF-α in liver NPC enhanced by the endotoxin injection, decreased the serum level of GOT and lactic dehydrogenase (LDH), and improved the survival rate of endotoxin-injected rats. Histological examination revealed a significant reduction in cell vacuolization and focal necrosis in the livers of the endotoxin-injected rats pretreated with OK432. These results indicate that hepatic macrophages play a crucial role in endotoxin-induced liver injury, and that TNF-α is one of the factors most likely to be implicated in the development of endotoxin-induced liver injury. Thus, it is suggested that the administration of OK432 provides liver protection by modulating the responsiveness of hepatic macrophages against endotoxin. [ABSTRACT FROM AUTHOR]

Increases in 14C concentrations in tree rings could be attributed to cosmic-ray events, as have increases in 10Be and nitrate in ice cores. The record of the past 3,000 years in the IntCal09 data set, which is a time series at 5-year intervals describing the 14C content of trees over a period of approximately 10,000 years, shows three periods during which 14C increased at a rate greater than 3‰ over 10 years. Two of these periods have been measured at high time resolution, but neither showed increases on a timescale of about 1 year (refs 11 and 12). Here we report 14C measurements in annual rings of Japanese cedar trees from ad 750 to ad 820 (the remaining period), with 1- and 2-year resolution. We find a rapid increase of about 12‰ in the 14C content from ad 774 to 775, which is about 20 times larger than the change attributed to ordinary solar modulation. When averaged over 10 years, the data are consistent with the decadal IntCal 14C data from North American and European trees. We argue that neither a solar flare nor a local supernova is likely to have been responsible. [ABSTRACT FROM AUTHOR]

Background: Intersphincteric resection (IRS) is a surgical technique used to preserve sphincter function, mainly cases of low rectal cancer located less than 5 cm from the anal verge [, ]. There have been reports of laparoscopic ISR [, ], but discussion of the specific techniques used in this laparoscopic surgical procedure have not been sufficient. For better outcomes of this sophisticated procedure, extreme care must taken to prevent perforation of the rectal wall and to preserve the external sphincter muscle. The most difficult steps for ISR are the circular dissection and separation of the internal sphincter muscle from the external sphincter and puborectalis using the perineal approach. The authors' techniques and the advantages of laparoscopic ISR are shown by a video presentation of three rectal tumor cases. Also, the perioperative outcomes for the patients who underwent laparoscopic ISR with this technique are described. Methods: From January 2006 to September 2009, laparoscopic ISR with total mesorectal excision was performed for 15 patients (10 men and 5 women). The median age of the patients was 60.5 years. The T categories of the tumor node metastasis (TNM) classification for the rectal cancers were Tis for two patients, T1 for one patient, T2 for four patients, and T3 for eight patients. The median distance from the anal verge to the tumor in this series was 3.7 cm. The Tis cases had large laterally spreading tumors that could not be removed by endoscopic submucosal dissection. The T1 case presented in the video had a small tumor just above the dentate line that had developed in the presence of chronic ulcerative colitis. Because this case required total proctocolectomy and ileal pouch anal anastomosis, local resection was not used (Table 1). Cases: The 68-year-old man in case 1 had a large, laterally spreading rectal tumor. The 61-year-old man in case 2 had rectal cancer, with a tumor located 4 cm from the anal verge. Laparoscopic surgery was performed after neoadjuvant chemoradiotherapy. The 71-year-old woman in case 3 had T1 rectal cancer, with a tumor located just above the dentate line. After dissection of the intersphincteric space, the prolapsing technique was used. Methods: In the male patients, the rectum with the mesorectum was first dissected to the anal hiatus, initially on the posterior side along the avascular plane. Second, Denonvilliers' fascia was dissected, and the seminal vesicle was exposed. The third step was dissection of the lateral tissues followed by incision of Denonvilliers' fascia with the rectal wall exposure and care taken not to injure the neurovascular bundle (Fig. 1). Along this dissection plane, the puborectalis could be reached and intersphincteric space entered from the lateral side of the rectal wall (Fig. 2). The final step was dissection of the hiatal ligament at the posterior side of the rectum. Nearly circular dissection of the intersphincteric space could be completed. The difficulties associated with the perineal approach were reduced by this abdominal approach, and the tumor could be exteriorized easily. [Figure not available: see fulltext.][Figure not available: see fulltext.] Results: The mean duration of surgery was 386 min, and the mean blood loss was 108 ml. The mean postoperative hospital stay was 18 days. The diverting ileostomy was closed at a mean of 7.3 postoperative months. No remarkable perioperative complication was encountered (Table 2). Conclusion: Laparoscopic ISR enabled reduction of the difficulties associated with the perineal approach. An advantage of laparoscopic ISR is the ability clearly to visualize anatomic structures in the deep pelvic cavity. [ABSTRACT FROM AUTHOR]

A 67-year-old Japanese man complained of a painful lump in his anus. He had a 15-month history of myelodysplastic syndrome (MDS) and had been diagnosed with MDS overt leukemia. A solid lump measuring 1.0 cm in diameter was detected in the anal verge. Under a diagnosis of a thrombosed external hemorrhoid, thrombectomy was performed under local anesthesia. One week after thrombectomy, the wound had not healed, and grayish-green tissue was seen at the bottom. A biopsy of the wound revealed atypical mononuclear cell infiltration. Myeloperoxidase and lysozyme were positive on immunohistochemical staining. Finally, the diagnosis of granulocytic sarcoma (GS) was made. Though it is well known that perianal complications occur quite often in patients with leukemia, it is unusual for a diagnosis of GS of the anus to be definitely established. To our knowledge, there has not been a previous report of GS presenting as a thrombosed external hemorrhoid. The development of GS should be considered during the management of such lesions, especially in patients with bone marrow disorders, such as acute myeloid leukemia (AML) or high-risk MDS. [ABSTRACT FROM AUTHOR]

We report herein a rare case of diverticulitis causing a high serum level of carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital with lower abdominal pain. Laboratory data showed evidence of inflammation and a high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated thickening of the wall of the sigmoid colon. He was diagnosed as having diverticulitis of the sigmoid colon and was treated with antibiotics. Although his symptoms improved, the presence of a malignancy such as colorectal cancer could not be completely ruled out because of the persistently high serum level of CA19-9. A laparotomy was performed and the sigmoid colon was found to be adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was performed. Pathological examination revealed diverticulitis of the sigmoid colon, but there was no evidence of malignancy in the resected specimen. The serum CA19-9 level decreased to normal postoperatively and immunohistochemical staining revealed CA19-9 antigen in the cytoplasm of the diverticular epithelium. Therefore, a possible explanation for the high level of this tumor marker was diverticulitis of the sigmoid colon. [ABSTRACT FROM AUTHOR]