Takashi Kizu

Efficacy of an Endo-Knife With a Water-Jet Function (Flushknife) for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms

OBJECTIVES:Endoscopic submucosal dissection (ESD) is currently not a common treatment for colorectal neoplasms because it is time consuming and technically difficult. Flushknife—an electrosurgical endo-knife with a water-jet function—is expected to reduce the difficulty of colorectal ESD. The objective of this study was to investigate the efficacy of a water-jet function for colorectal ESD.METHODS:This study was a prospective randomized controlled trial, which was conducted at a cancer referral center. A total of 49 patients, with a total of 51 superficial colorectal neoplasms (median tumor size of 30 mm), were enrolled and randomly assigned to undergo ESD using either the Flexknife (electrosurgical endo-knife without a water-jet function) or the Flushknife. Tumors were resected by ESD using each endo-knife. The procedures were conducted by two endoscopists. Operation time was defined as the main outcome measure.RESULTS:En bloc resection was achieved in 23 out of 26 (88%) lesions in the Flexknife group and in 24 out of 24 (100%) lesions in the Flushknife group. The mean operation time (95% confidence interval) was 87.3 (71.3–103.4) min in the Flexknife group and 61.0 (49.3–72.7) min in the Flushknife group (P=0.02). The Flushknife reduced the number of endoscopic device changes (P=0.001), the number of submucosal injections (P=0.001), and the mean amount of injected hyaluronate sodium (P=0.001) compared with the Flexknife. No severe adverse events were observed in either group.CONCLUSIONS:Without increasing adverse events, the endo-knife with a water-jet function efficiently reduced the operation time of colorectal ESD in patients with large superficial colorectal neoplasms. (University hospital Medical Information Network Clinical Trials Registry number UMIN000001302)

Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high-cholesterol diet.

Recent studies indicate an accelerated progression of nonalcoholic steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an important risk factor for NASH progression, is often observed after menopause. This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen replenishment, OVX mice fed with HFHC diet were treated with implanted hormone release pellets (containing 17β-estradiol or placebo vehicle) for 6 wk. OVX mice on the HFHC diet showed enhanced liver injury with increased liver macrophage infiltration and elevated serum cholesterol levels compared with SO-HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In addition, hepatic inflammatory gene expressions, including monocytes chemokine (C-C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice. Estrogen treatment improved serum cholesterol levels, liver injury, macrophage infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2 expression in THP1 monocytes. Our study demonstrated that estrogen deficiency accelerated NASH progression in OVX mice fed HFHC diet and that this effect was improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would be a potential risk factor for NASH progression.

Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial

BACKGROUND Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN A 2 × 2 factorial designed, prospective, randomized, controlled trial. SETTING This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS A total of 561 patients. INTERVENTIONS Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH--colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93-1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS Open trial performed in single cancer referral center. CONCLUSION AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH.

Inflammatory pseudotumor of the liver and spleen diagnosed by percutaneous needle biopsy

An inflammatory pseudotumor (IPT) is a relatively rare lesion characterized by chronic infiltration of inflammatory cells and areas of fibrosis. IPTs are difficult to diagnose because of the absence of specific symptoms or of characteristic hematological or radiological findings. In this study, a case of a woman aged over 70 years was reported, who presented with a general malaise lasting more than two months. A computed tomography scan demonstrated a diffusely spread lesion of the liver with a portal vein occlusion and a splenic lesion surrounded by a soft density layer. Since the percutaneous liver biopsy showed findings that suggested an IPT, although the radiological findings did not exclude the possibility of a malignancy, we performed a percutaneous spleen biopsy to enable a more definitive diagnosis. The microscopic findings from the spleen specimen lead us to a diagnosis of IPT involving the liver and spleen. Subsequent steroid pulse therapy was effective, and rapid resolution of the disease was observed.

Scraping cytology with a guidewire for pancreatic-ductal strictures.

BACKGROUND Strictures of the pancreatic duct may be caused by a variety of underlying pathologic conditions that imaging examinations often fail to define. Conventional procedures for acquisition of a specimen for cytology during ERCP have been limited in their ability to discriminate pancreatic-ductal strictures. OBJECTIVE Our aim was to discriminate pancreatic-ductal strictures by a new technique of sampling material for cytodiagnosis: scraping cytology with a guidewire. DESIGN A retrospective study. SETTING A single cancer center. PATIENTS AND METHODS Eighty-six patients with pancreatic-ductal strictures composed of 71 malignant and 15 benign diseases were evaluated. Malignant diseases included 70 pancreatic carcinomas and 1 endocrine tumor; benign diseases included the following: 7 chronic pancreatitis, 3 autoimmune pancreatitis, 3 idiopathic pancreatic-ductal strictures, and 2 pancreatic cysts. During ERCP, pancreatic juice was collected with a cannula in the main duct just below the stricture after scraping it with a 0.025-inch hydrophilic guidewire. Cytodiagnosis of the specimen was performed by the Papanicolaou method. MAIN OUTCOME MEASUREMENTS Diagnostic sensitivities and specificities of scraping cytology with a guidewire for pancreatic carcinoma. RESULTS Scraping cytology with a guidewire yielded 93% sensitivity, 100% specificity, 100% positive predictive value, 75% negative predictive value, and 94% accuracy. Sensitivities for pancreatic carcinoma in the head, body, and tail of the pancreas were 91%, 100%, and 91%, respectively. Sensitivities for pancreatic carcinoma with a tumor of <20 mm, 21 to 40 mm, 41 to 60 mm, and >61 mm were 95%, 92%, 100%, and 100%, respectively. Pancreatitis subsequent to the procedure occurred in 4 patients (5%), all of whom were cured by conservative treatment. CONCLUSIONS Benign or malignant pancreatic-ductal strictures were accurately discriminated by scraping cytology with a guidewire during ERCP. The technique yielded high diagnostic sensitivities in pancreatic carcinoma, regardless of the location or size of the tumor.

Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice.

Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibrotic livers, and was increased in bile duct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis.

Analysis of the color patterns of early gastric cancer using an autofluorescence imaging video endoscopy system

BackgroundUsing a novel autofluorescence imaging video endoscopy system (AFI), tumors in the esophagus and the colon appeared purple in a green background, but the color patterns of early gastric cancer (EGC) were found to vary. Factors associated with these patterns remain unknown. The aims of the present study were to classify the color patterns of EGCs and to investigate the correlation between the patterns and clinicopathological features.MethodsA total of 107 EGCs that had been evaluated by AFI endoscopy, prior to endoscopic or surgical resection, were included. The color patterns of EGCs in AFI images and the association between tumor color and clinicopathological factors were evaluated. These factors included tumor morphology, location, size, background color, histological type, depth of invasion, lymphatic or vessel permeation, and ulceration.ResultsThe color patterns of EGCs were classified into the following four groups: purple tumors in a green background (52%); green tumors with a purple margin in a green background (21%); green tumors in a purple background (17%); and purple tumors in a purple background (10%). Univariate analysis showed that macroscopic type, histological type, ulceration, and background AFI color were significantly associated with tumor color, whereas multivariate analysis revealed that macroscopic type was the only independent contributor to tumor color.ConclusionThe present study has enabled a clearer understanding of the significance of tumor color in relation to the AFI imaging of EGCs. Recognition of the color patterns in AFI images should help in the diagnosis of EGCs.

Protective role of adiponectin against ethanol-induced gastric injury in mice

Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E(2) (PGE(2)) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE(2) and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE(2) expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE(2) expression.

Secreted frizzled-related protein 5 (Sfrp5) decreases hepatic stellate cell activation and liver fibrosis

Obesity‐related adipocytokine dysregulation is known to accelerate liver fibrosis progression. Recently, a natural Wnt5a inhibitor, secreted frizzled‐related protein 5 (Sfrp5), was identified as a novel adipocytokine that has reduced expression in obese adipose tissue in both rodents and human. In addition, hepatic gene expression of Wnt5a and its receptor frizzled 2 (Fz2) is elevated during fibrosis progression. Therefore, Sfrp5 could have biological significance in liver fibrosis.

Adiponectin negatively correlates with alcoholic and non‐alcoholic liver dysfunction: Health check‐up study of Japanese men

Aim:  Central obesity, insulin resistance and alcohol consumption are thought to be major risk factors for fatty liver formation. Adiponectin (APN) prevents fatty liver formation, and its serum levels are lower in subjects with central obesity and/or insulin resistance. The aim of this study was to explore the association among serum APN levels, central obesity, insulin resistance and liver dysfunction with or without fatty liver classified by alcohol consumption in healthy subjects.