Takuya Inoue

Delayed perforation: A hazardous complication of endoscopic resection for non-ampullary duodenal neoplasm

Perforation is a major complication of endoscopic resection for gastrointestinal neoplasms. However, little is known about delayed perforation after endoscopic resection for non‐ampullary duodenal neoplasm. The aim of the present study was to investigate the clinical features of delayed perforation after endoscopic resection for non‐ampullary duodenal neoplasm.

Clinical features of post-polypectomy bleeding associated with heparin bridge therapy

u2002Heparin is given to patients undergoing colonoscopic polypectomy at high risk for thromboembolism. Little is known, however, about how heparin bridge therapy (HB) affects post‐polypectomy bleeding (PPB). The present study aimed to identify the clinical features of PPB associated with HB.

Integrated diagnostic strategy for the invasion depth of early gastric cancer by conventional endoscopy and EUS

BACKGROUNDnAlthough conventional endoscopy (CE) and EUS are considered useful for predicting the invasion depth (T-staging) in early gastric cancer (EGC), no effective diagnostic strategy has been established.nnnOBJECTIVEnTo produce simple CE criteria and to elucidate an efficient diagnostic method by combining CE and EUS for accurate T-staging.nnnDESIGNnSingle-center retrospective analysis.nnnSETTINGnAcademic university hospital.nnnPATIENTSnConsecutive patients with EGC from April 2007 to March 2012 who underwent CE and EUS before treatment.nnnINTERVENTIONSnRecorded endoscopic images were independently reviewed by 3 observers. The CE criteria for massive invasion were defined, and their utility and the additional value of EUS were assessed.nnnMAIN OUTCOME MEASUREMENTSnThe accuracy of CE based on the criteria and the accuracy of EUS.nnnRESULTSnTwo hundred thirty patients were enrolled: 195 with mucosal cancer or cancer in the submucosa less than 500 μm from the muscularis mucosae and 35 with invasive cancers. Multivariate analysis of the CE findings by 1 observer revealed that an irregular surface and a submucosal tumor-like marginal elevation were significantly associated with massive invasion. The simple CE criteria, consisting of those 2 features, had an overall accuracy of 73% to 82% and no significant differences in the diagnostic yield compared with EUS in all observers. CE accurately revealed mucosal cancer, and EUS efficiently salvaged the lesions that were over-diagnosed by CE. With our strategy, which involved the CE criteria and the optimal use of EUS, the comprehensive accuracy exceeded 85% in each observer.nnnLIMITATIONSnRetrospective, single-center study.nnnCONCLUSIONSnWe demonstrated a practical strategy for T-staging in EGC using simple CE criteria and EUS.

Autofluorescence imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia: A phase II study

Background and Aim:u2002 Few prospective studies examining the efficacy of autofluorescence imaging (AFI) screening for esophageal cancer have been reported. This study aimed to investigate the diagnostic value of AFI endoscopy for the screening of squamous mucosal high‐grade neoplasia of the esophagus, performed by experienced and less‐experienced endoscopists.

cDNA cloning of rat LRP, a receptor like protein tyrosine phosphatase, and evidence for its gene regulation in cultured rat niesangial cells

Protein tyrosine phosphatases (PTPases) are a family of enzymes that play a crucial role in the regulation of signal transduction mediated by reversible protein tyrosine phosphorylation. To understand the significance of PTPases in physiological and pathophysiological processes in the kidney, we isolated three cDNA segments encoding PTPases (LAR, LRP and a novel PTPase) from rat kidney by polymerase chain reaction (PCR). Using PCR product as a probe, we isolated a full-length cDNA of rat LRP. LRP cDNA encoded a single membrane spanning protein consisted of 796 amino acids, with two tandemly located intracellular PTPase domains. By Northern analysis, a ubiquitous pattern of LRP gene expression in rat tissues was demonstrated. In cultured rat mesangial cells, LRP mRNA was detected and the mRNA level was suppressed by either interleukin-1 or interleukin-6 treatment.

Evaluation of Endoscopic Ultrasound Image Quality Is Necessary in Endosonographic Assessment of Early Gastric Cancer Invasion Depth

We evaluated whether endoscopic ultrasonography (EUS) image quality affects the accuracy of diagnosing the vertical invasion depth of early gastric cancer (EGC). A total of 75 lesions in 75 patients suspected of having EGC were enrolled. All patients underwent EUS examination. Findings of EUS were compared with histopathologic results. We evaluated the effect of the following clinicopathologic factors: location, diameter, surface pattern, concomitant ulceration, histology type, and EUS image quality score. EUS image quality was scored based on detection repeatability, appropriate probe placement, and clarity of the five gastric wall layers including the lesion. Sixty-three lesions (84%) were pathologically mucosal and 12 lesions (16%) were submucosal cancer. Overall accuracy was 82.7%. Significantly more lesions in the upper and middle portions of the stomach were incorrectly diagnosed than in the lower portion (P = 0.0019). Lesion diameter was significantly larger among incorrectly diagnosed lesions (P = 0.0257). Low-quality images were significantly more often associated with incorrectly diagnosed lesions than with correctly diagnosed lesions (P = 0.0001). Multivariate analysis revealed that EUS image quality was associated with EUS staging accuracy (odds ratio, 21.8; 95% confidence interval, 4.5–137.6). Low-quality EUS images led to an incorrect diagnosis of invasion depth of EGC, independent of tumor location or size.

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies, whether as follow-up or total incisional biopsy for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen, are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment. Based on the histological findings of the biopsy specimen, it is difficult to differentiate between reactive or regenerative changes, inflammation and neoplastic changes, intraepithelial and invasive tumors. Therefore, gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up. Recent advances in endoscopic modalities and treatment devices, such as image-enhanced endoscopy and high-frequency generators, may make endoscopic treatment, such as endoscopic submucosal dissection (ESD), a therapeutic option for gastric intraepithelial neoplasia, including low-grade neoplasms. Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.

A Case of Polycystic Kidney Disease with Nephrotic Syndrome

Nephrotic syndrome developed in a patient with autosomal-dominant polycystic kidney disease. Renal biopsy revealed minor glomerular abnormalities. This type of nephrotic syndrome complication in an autosomal-dominant polycystic kidney disease has only rarely been reported.

5-FU resistance abrogates the amplified cytotoxic effects induced by inhibiting checkpoint kinase 1 in p53-mutated colon cancer cells

The emergence of chemoresistance is a major limitation of current cancer therapies, and checkpoint kinasexa0(Chk1)xa01 positively correlates with resistance to chemo‑xa0or radio‑therapy. Cancer cells lacking p53 pathways are completely dependent on the S and G2/M checkpoints via Chk1; therefore, Chk1 inhibition enhances the cytotoxicity of DNA‑damaging agents only in p53‑deficient cells. However, little is known about the synergistic effect of Chk1 inhibition with 5‑FU, the most frequently used antimetabolite, in chemoresistant colorectal cells. In this study, we found that 5‑FU induced S‑phase arrest only in p53‑deficient colorectal cancer cells. 5‑FU treatment induced DNA damage and activation of ataxia telangiectasia mutatedxa0(ATM) and Chk1, leading to S‑phase arrest, and Chk1 inhibition using SB218078 reduced S‑phase arrest and increased apoptosis in the presence of 5‑FU. In contrast, in p53‑deficient, 5‑FU‑resistantxa0(5FUR) colon cancer cells that we developed, 5‑FU enhanced DNA damage but did not induce Chk1/ATM activation or cell cycle arrest. SB218078 in combination with 5‑FU did not induce apoptosis. These results indicate that 5‑FU‑resistance abrogated the anticancer effect amplified by Chk1 inhibition, even in p53‑deficient cancer cells.

p53 functional deficiency in human colon cancer cells promotes fibroblast-mediated angiogenesis and tumor growth

Cancer-associated fibroblasts (CAFs) create a microenvironment that contributes to tumor growth; however, the mechanism by which fibroblasts are phenotypically altered to CAFs remains unclear. Loss or mutation of the tumor suppressor p53 plays a crucial role in cancer progression. Herein, we analyzed how the p53 status of cancer cells affects fibroblasts by investigating the in vivo and in vitro effects of loss of p53 function in cancer cells on phenotypic changes in fibroblasts and subsequent tumor progression in human colon cancer cell lines containing wild-type p53 and in cells with a p53 functional deficiency. The growth of p53-deficient tumors was significantly enhanced in the presence of fibroblasts compared with that of p53-wild-type tumors or p53-deficient tumors without fibroblasts. p53-deficient cancer cells produced reactive oxygen species, which activated fibroblasts to mediate angiogenesis by secreting vascular endothelial growth factor (VEGF) both in vivo and in vitro Activated fibroblasts significantly contributed to tumor progression. Deletion of fibroblast-derived VEGF or treatment with N-acetylcysteine suppressed the growth of p53-deficient xenograft tumors. The growth effect of blocking VEGF secreted from cancer cells was equivalent regardless of p53 functional status. Human colon cancer tissues also showed a significant positive correlation between p53 cancer cell staining activated fibroblasts and microvessel density. These results reveal that fibroblasts were altered by exposure to p53-deficient epithelial cancer cells and contributed to tumor progression by promoting neovascularization. Thus, p53 acts as a modulator of the tumor microenvironment.