Supplementary Table 2 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 2 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 5 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 1 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 4 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 6 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

Supplementary Table 3 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers

We present three cases of self-expandable metallic stent (SEMS) placement using a balloon enteroscope (BE) and its overtube (OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine.

Background Endoscopic retrograde cholangiopancreatography (ERCP) is technically more challenging in patients who have undergone gastrointestinal (GI) reconstruction. Aims The aim of this study was to evaluate the utility of the anterior oblique-viewing endoscope (AOE) for ERCP in patients with a retained major duodenal papilla after GI reconstruction. Methods This was a retrospective study involving 40 patients (50 procedures) with a retained papilla after GI reconstruction who underwent ERCP using AOE. Reconstruction consisted of Billroth II gastrectomy (BII) in 25 patients (30 procedures) and Roux-en-Y anastomosis (RY) in 15 patients (20 procedures). In RY cases, the long single-balloon enteroscope (LSBE) was exchanged with AOE after reaching the papilla. Results The overall rate of reaching the papilla using AOE was 90.0 % (45/50) [BII; 86.7 % (26/30), RY; 95.0 % (19/20)]. The overall rate of biliary cannulation was 97.8 % (44/45) [BII; 100 % (26/26), RY; 94.7 % (18/19)], and the rate of biliary cannulation for intact papilla was 96.6 % (28/29) [BII; 100 % (14/14), RY; 93.3 % (14/15)]. Treatment success rate in cases of successful biliary cannulation was 97.7 % (43/44) [BII; 100 % (26/26), RY; 94.4 % (17/18)]. The rate of adverse events was 6.0 % (3/50) [BII; 3.3 % (1/30), RY; 10.0 % (2/20)], with mild pancreatitis occurring in 3 cases. Conclusions High biliary cannulation and treatment rates can be achieved during ERCP using AOE in altered GI anatomy cases with a retained papilla, as long as the papilla can be reached. In RY cases, exchanging AOE with LSBE is useful after reaching the papilla.

OBJECTIVE We evaluated the diagnostic performance of computed tomography (CT) as an initial radiologic test for assessing the optimal timing of colonoscopy in patients with acute lower gastrointestinal bleeding (LGIB) and investigated the effectiveness of contrast-enhanced (CE) CT for detecting colonic diverticular bleeding. METHODS This was a retrospective study of 1,604 consecutive patients who visited or were referred to St. Marianna University Hospital due to acute LGIB and underwent colonoscopy within three months after presentation between September 2004 and December 2012. The clinicopathological data of the subjects were obtained from their medical records. RESULTS Among the 1,604 patients presenting with LGIB, 879 (55%) underwent a CT scan. Elective colonoscopy was considered in cases in which typical colonic wall thickening was observed on CT, suggesting colonic inflammation or malignancy (239 patients; 27%). The diagnoses in the elective cases included ischemic colitis (38%), infectious colitis (8%), inflammatory bowel disease (8%) and malignancy (5%). Urgent colonoscopy was performed after the CT examination in 640 cases (73%). The most common presumptive CT diagnosis was diverticulum (402/640; 63%). Of the 638 patients who underwent CE-CT, diverticula were observed in 346 cases, including 104 cases of extravasation indicating ongoing diverticular bleeding. Among these 104 patients, the site of bleeding was identified in 71 subjects (68%) during colonoscopy. The rate of detection of the bleeding source on colonoscopy was significantly higher in the patients with extravasation on CE-CT than in those without extravasation on CE-CT (68% vs. 20%, respectively; p<0.001). CONCLUSION Urgent CT is useful for determining the optimal timing of colonoscopy in cases of acute LGIB. CE-CT may be used to depict the presence and location of active hemorrhage and provides useful information for subsequent colonoscopy, especially in patients with diverticular bleeding.

Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.

症例は27歳，男性。心窩部痛を主訴に近医受診。上部消化管内視鏡にて食道胃接合部に粘膜不整を認め，生検にてGroup 4であり悪性疾患が疑われ当院へ紹介受診となった。当院での上部消化管内視鏡では，NBI拡大観察にて血管蛇行や癒合を伴う異型血管を認め，short segment Barrett’s esophagus（SSBE）より発生したBarrett腺癌が疑われ，診断的治療目的に内視鏡的粘膜下層剥離術を施行した。病理組織学的診断にてBarrett腺癌と診断され，粘膜下層浸潤，脈管侵襲を認めたため追加外科的切除となった。本邦では全食道癌の90％以上が扁平上皮癌であり腺癌は比較的稀である。しかしH. pylori感染率低下，食生活欧米化によるGERD増加に伴い，近年Barrett腺癌の増加が懸念されている。一方，若年者におけるBarrett腺癌の報告は本邦，欧米含め散見されるのみである。今回我々は若年者に発生したBarrett腺癌を経験したので文献的考察を含め報告する。

Giardia lamblia is one cause of prolonged diarrhea in overseas travelers. Demonstration of trophozoites in stool is the traditional method of diagnosis. Here we present a case of giardiasis diagnosed by lavage fluid collected during colonoscopy (CS) .A 60-year-old woman presented at our hospital with prolonged watery diarrhea since travel in Southeast Asia. She had been treated empirically due to negative results from EGD, CS and stool culture. A second CS was performed one year and nine months after the first CS, because the diarrhea persisted. Trophozoites of Giardia lamblia were detected microscopically in lavage fluid sediment collected during this CS. Oral administration of metronidazole (750 mg/day) for one week dramatically improved the patient’s symptoms. This case suggests that CS lavage fluid assessment is a useful method to detect Giardia lamblia in patients with chronic diarrhea.

Purpose: Although minimal invasive treatment is accepted for gastric cancer, we still do not have any appropriate risk markers to detect residual neoplasia and recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of neoplasia. Our goal is to find some candidate genes as a treatment marker using genome wide DNA methylation analysis for early gastric cancer (EGC). Methods: We studied MCA Microarray analysis using 12 gastric washes (each before and after treatment in same patients). One of them is BARHL2. We examined the DNA methylation status of BARHL2 in a validation set consisting of 128 washes samples at EGC. We next identified functional studies about BARHL2 gene.Figure: [129] MCA microarray.Results: BARHL2 showed significantly differential methylation between before and after treatment in EGC patient (p<0.0001). Moreover, treating GCa cells that lacked BARHL2 expression with DAC, restored the gene's expression. Introduction of exogenous BARHL2 into silenced cells suppressed colony formation. Conclusion: Our data suggest that silencing of BARHL2 occurs frequently in EGC and may play a key role in development and progression of the disease.

In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) microarray analysis, we developed a new output value. The signal log ratio reflected the global methylation levels, but had only moderate linear correlation (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying the signal log ratio using a coefficient obtained from the probability value that took account of signals in neighbouring probes, its linearity was markedly improved (r = 0.94). The new output value, Me value, reflected the global methylation level, had a strong correlation also with the fraction of methylated CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of 71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis of gastric cancer cell lines using the Me value showed that methylation of CGIs in promoters and gene bodies was associated with low and high, respectively, gene expression. The degree of demethylation of promoter CGIs after 5-aza-2'-deoxycytidine treatment had no association with that of induction of gene expression. The Me value was considered to be useful for analysis of intermediate methylation levels of CGIs.