Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan.

BACKGROUND: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. METHODS: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. RESULTS: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. CONCLUSION: Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.

Development of multi-class computer-aided diagnostic systems using the NICE/JNET classifications for colorectal lesions.

BACKGROUND AND AIM: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification. METHODS: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate. RESULTS: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively. CONCLUSIONS: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions.

Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium.

Baculovirus (BV), an enveloped insect virus with a circular dsDNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. In this study, we show that BV administration in BALB/c mice not only provides complete protection against a subsequent Plasmodium berghei sporozoite infection for up to 7 d after the injection but also eliminates existing liver-stage parasites completely. The elimination of sporozoites by BV was superior to that by primaquine, and this effect occurred in a TLR9-independent manner. At 6 h after BV administration, IFN-α and IFN-γ were robustly produced in the serum, and RNA transcripts of IFN-stimulated genes were markedly upregulated in the liver compared with control mice. The in vivo passive transfer of serum after BV administration effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite-killing mechanism is downstream of the type I IFN signaling pathway. These findings provide evidence that BV-induced, fast-acting innate immunity completely kills liver-stage parasites and, thus, may lead to new malaria drug and vaccine strategies.

Down-selecting circumsporozoite protein-based malaria vaccine: A comparison of malaria sporozoite challenge model.

Plasmodium falciparum circumsporozoite protein (PfCSP) is the main target antigen in development of pre-erythrocytic malaria vaccines. To evaluate PfCSP vaccines in animal models, challenge by intravenous sporozoite injection is preferentially used. However, in clinical trials, vaccinated human volunteers are exposed to the bites of malaria-infected mosquitoes. In this study, we down-selected Escherichia coli-produced full-length PfCSP (PfCSP-F) and its three truncated PfCSPs based on their abilities to elicit immune response and protection in mice against two challenge models. We showed that immunization with three doses of PfCSP-F elicited high anti-PfCSP antibody titres and 100% protection against the bites of infected mosquitoes. Meanwhile, three-dose truncated PfCSP induced 60%-70% protection after immunization with each truncated PfCSP. Heterologous prime-boost immunization regimen with adenovirus-PfCSP-F and R32LR greatly induced complete protection against intravenous sporozoite injection. Our results suggest that Abs to both anti-repeat and anti-nonrepeat regions induced by PfCSP-F are required to confer complete protection against challenge by the bites of infected mosquitoes, whereas anti-repeat Abs play an important role in protection against intravenous sporozoite injection. Our findings provide a potential clinical application that PfCSP-F vaccine induces potent Abs capable of neutralizing sporozoites in the dermis inoculated by infected mosquitoes and subsequently sporozoites in the blood circulation.

DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice.

BACKGROUND: Previous studies have shown that the baculovirus-vectored vaccine based on the "baculovirus dual expression system (BDES)" is an effective vaccine delivery platform for malaria. However, a point of weakness remaining for use of this vaccine platform in vivo concerns viral inactivation by serum complement. In an effort to achieve complement resistance, the gene encoding the human decay-accelerating factor (hDAF) was incorporated into the BDES malaria vaccine expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). RESULTS: The newly-developed BDES vaccine, designated BDES-sPfCSP2-Spider, effectively displayed hDAF and PfCSP on the surface of the viral envelope, resulting in complement resistance both in vitro and in vivo. Importantly, upon intramuscular inoculation into mice, the BDES-sPfCSP2-Spider vaccine had a higher protective efficacy (60%) than that of the control vaccine BDES-sPfCSP2-Spier (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. CONCLUSION: DAF-shielded BDES-vaccines offer great potential for development as a new malaria vaccine platform against the sporozoite challenge.

Magnifying Blue Laser Imaging versus Magnifying Narrow-Band Imaging for the Diagnosis of Early Gastric Cancer: A Prospective, Multicenter, Comparative Study.

BACKGROUND/AIMS: The diagnostic efficacy of magnifying blue laser imaging (M-BLI) and M-BLI in bright mode (M-BLI-bright) in the identification of early gastric cancer (EGC) was evaluated for comparison to that of magnifying narrow-band imaging (M-NBI). METHODS: This prospective, multicenter study evaluated 114 gastric lesions examined using M-BLI, M-BLI-bright, and M-NBI between May 2012 and November 2012; 104 EGCs were evaluated by each modality. The vessel plus surface classification system was used to evaluate the demarcation line (DL), microvascular pattern (MVP), and microsurface pattern (MSP). RESULTS: M-BLI, M-BLI-bright, and M-NBI revealed a DL for 96.1, 98.1, and 98.1% and irregular MVP for 95.1, 95.1, and 96.2% of lesions, respectively, with no significant difference. Irregular MSP was observed by M-BLI, M-BLI-bright, and M-NBI in 97.1, 90.4, and 78.8% of lesions, respectively, with significant differences (p < 0.001). The proportion of moderately differentiated adenocarcinoma with irregular MSP on M-BLI and absent MSP on M-NBI was significantly higher than that with irregular MSP on M-BLI and M-NBI (35.0 and 9.9%, respectively; p = 0.002). CONCLUSION: M-BLI and M-BLI-bright provided excellent visualization of microstructures and microvessels similar to M-NBI. Irregular MSP in a moderately differentiated adenocarcinoma might be frequently visualized using M-BLI and M-BLI-bright compared with using M-NBI.

Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes.

BACKGROUND: Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity. METHODS: BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated. RESULTS: We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus. CONCLUSIONS: BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright © 2016 John Wiley & Sons, Ltd.

Computer-aided diagnosis of colorectal polyp histology by using a real-time image recognition system and narrow-band imaging magnifying colonoscopy.

BACKGROUND AND AIMS: It is necessary to establish cost-effective examinations and treatments for diminutive colorectal tumors that consider the treatment risk and surveillance interval after treatment. The Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) committee of the American Society for Gastrointestinal Endoscopy published a statement recommending the establishment of endoscopic techniques that practice the resect and discard strategy. The aims of this study were to evaluate whether our newly developed real-time image recognition system can predict histologic diagnoses of colorectal lesions depicted on narrow-band imaging and to satisfy some problems with the PIVI recommendations. METHODS: We enrolled 41 patients who had undergone endoscopic resection of 118 colorectal lesions (45 nonneoplastic lesions and 73 neoplastic lesions). We compared the results of real-time image recognition system analysis with that of narrow-band imaging diagnosis and evaluated the correlation between image analysis and the pathological results. RESULTS: Concordance between the endoscopic diagnosis and diagnosis by a real-time image recognition system with a support vector machine output value was 97.5% (115/118). Accuracy between the histologic findings of diminutive colorectal lesions (polyps) and diagnosis by a real-time image recognition system with a support vector machine output value was 93.2% (sensitivity, 93.0%; specificity, 93.3%; positive predictive value (PPV), 93.0%; and negative predictive value, 93.3%). CONCLUSIONS: Although further investigation is necessary to establish our computer-aided diagnosis system, this real-time image recognition system may satisfy the PIVI recommendations and be useful for predicting the histology of colorectal tumors.

Development of a Plasmodium berghei transgenic parasite expressing the full-length Plasmodium vivax circumsporozoite VK247 protein for testing vaccine efficacy in a murine model.

BACKGROUND: The approach of using transgenic rodent malaria parasites to assess the immune system's response to antigenic targets from a human malaria parasite has been shown to be useful for preclinical evaluation of new vaccine formulations. The transgenic Plasmodium berghei parasite line [PvCSP(VK210)/Pb] generated previously expresses the full-length circumsporozoite protein (CSP) VK210 from Plasmodium vivax. The transgenic parasite expresses one of the two most common alleles of CSP, defined by nine amino acids at the central repeat region of this protein. In the present study, a transgenic P. berghei parasite line [PvCSP(VK247)/Pb] expressing the full-length PvCSP(VK247), which is the alternative common allele, was generated and characterized. METHODS: The P. berghei expressing full-length PvCSP(VK247) was generated and examined its applicability to CSP-based vaccine research by examining its biological characteristics in mosquitoes and mice. RESULTS: Similar to PvCSP(VK210)/Pb, PvCSP(VK247)/Pb developed normally in mosquitoes and produced infectious sporozoites equipped to generate patent infections in mice. Invasion of HepG2 cells by PvCSP(VK247)/Pb sporozoites was inhibited by an anti-PvCSP(VK247) repeat monoclonal antibody (mAb), but not by an anti-PvCSP(VK210) repeat mAb. CONCLUSIONS: These two transgenic parasites thus far can be used to evaluate the potential efficacy of PvCSP-based vaccine candidates encompassing the two major genetic variants in preclinical trials.

The crystal structure of the active domain of Anopheles anti-platelet protein, a powerful anti-coagulant, in complex with an antibody.

Blood clotting is a vitally important process that must be carefully regulated to prevent blood loss on one hand and thrombosis on the other. Severe injury and hemophilia may be treated with pro-coagulants, whereas risk of obstructive clotting or embolism may be reduced with anti-coagulants. Anti-coagulants are an extremely important class of drug, one of the most widely used types of medication, but there remains a pressing need for novel treatments, however, as present drugs such as warfarin have significant drawbacks. Nature provides a number of examples of anti-coagulant proteins produced by blood-sucking animals, which may provide templates for the development of new small molecules with similar physiological effects. We have, therefore, studied an Anopheles anti-platelet protein from a malaria vector mosquito and report its crystal structure in complex with an antibody. Overall the protein is extremely sensitive to proteolysis, but the crystal structure reveals a stable domain built from two helices and a turn, which corresponds to the functional region. The antibody raised against Anopheles anti-platelet protein prevents it from binding collagen. Our work, therefore, opens new avenues to the development of both novel small molecule anti-clotting agents and anti-malarials.

A computer system to be used with laser-based endoscopy for quantitative diagnosis of early gastric cancer.

GOALS: To evaluate the usefulness of a newly devised computer system for use with laser-based endoscopy in differentiating between early gastric cancer, reddened lesions, and surrounding tissue. BACKGROUND: Narrow-band imaging based on laser light illumination has come into recent use. We devised a support vector machine (SVM)-based analysis system to be used with the newly devised endoscopy system to quantitatively identify gastric cancer on images obtained by magnifying endoscopy with blue-laser imaging (BLI). We evaluated the usefulness of the computer system in combination with the new endoscopy system. STUDY: We evaluated the system as applied to 100 consecutive early gastric cancers in 95 patients examined by BLI magnification at Hiroshima University Hospital. We produced a set of images from the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened lesions; and surrounding tissues, and we attempted to identify gastric cancer, reddened lesions, and surrounding tissue quantitatively. RESULTS: The average SVM output value was 0.846 ± 0.220 for cancerous lesions, 0.381 ± 0.349 for reddened lesions, and 0.219 ± 0.277 for surrounding tissue, with the SVM output value for cancerous lesions being significantly greater than that for reddened lesions or surrounding tissue. The average SVM output value for differentiated-type cancer was 0.840 ± 0.207 and for undifferentiated-type cancer was 0.865 ± 0.259. CONCLUSIONS: Although further development is needed, we conclude that our computer-based analysis system used with BLI will identify gastric cancers quantitatively.

Evaluation of dual-wavelength excitation autofluorescence imaging of colorectal tumours with a high-sensitivity CMOS imager: a cross-sectional study.

BACKGROUND: It is important to devise efficient and easy methods of detecting colorectal tumours to reduce mortality from colorectal cancer. Dual-wavelength excitation autofluorescence intensity can be used to visualize colorectal tumours. Therefore, we evaluated dual-wavelength excitation autofluorescence images of colorectal tumours obtained with a newly developed, high-sensitivity complementary metal-oxide-semiconductor (CMOS) imager. METHODS: A total 107 colorectal tumours (44 adenomas, 43 adenocarcinomas with intramucosal invasion, and 20 sessile serrated adenoma/polyps [SSA/Ps]) in 98 patients who underwent endoscopic tumour resection were included. The specimens were irradiated with excitation light at 365 nm and 405 nm, and autofluorescence images measured with a 475 ± 25-nm band pass filter were obtained using a new, high-sensitivity CMOS imager. Ratio images (F365ex/F405ex) were created to evaluate the lesion brightness compared with that of normal mucosa, and specimens were categorized into a no signal or high signal group. RESULTS: Adenomas and adenocarcinomas were depicted in 87 ratio images, with 86.2% (n = 75) in the High signal group. SSA/P was depicted in 20 ratio images, with 70.0% (n = 14) in the High signal group. CONCLUSIONS: Dual-wavelength excitation autofluorescence images of colorectal tumours can be acquired using our high-sensitivity CMOS imager, and are useful in detecting colorectal tumours.

Risk factors and management of positive horizontal margin in early gastric cancer resected by en bloc endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), there is no consensus regarding the management of positive horizontal margin (HM) despite en bloc ESD. The aim of the current study was to identify the risk factors and optimal management of positive HM in EGCs resected by en bloc ESD. METHODS: A total of 890 consecutive patients with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June 2011. Clinicopathological data were retrieved retrospectively to assess the positive HM rate, local recurrence rate, risk factors for positive HM, and outcomes of treatment for local recurrent tumor. Positive HM was defined as a margin with direct tumor invasion (type A), the presence of cancerous cells on either end of 2-mm-thick cut sections (type B), or an unclear tumor margin resulting from crush or burn damage (type C). RESULTS: The positive HM rate was 2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local recurrent tumors were intramucosal carcinomas, and were resected curatively by re-ESD. Multivariate analysis with logistic regression showed tumor location in the upper third of the stomach and lesions not matching the absolute indication to be independent risk factors for positive HM. CONCLUSION: The risk factors for HM positivity in cases of EGC resected by en bloc ESD are tumor location in the upper third of the stomach and dissatisfaction of the absolute indication for curative ESD.

Major predictors of portal hypertensive enteropathy in patients with liver cirrhosis.

BACKGROUND AND AIM: Portal hypertensive enteropathy (PHE) is acknowledged as a source of bleeding, and predicting its presence has become more important. We assessed PHE using capsule endoscopy (CE) and investigated factors that may predict its presence, including portosystemic shunts (PSs). METHODS: We analyzed data from 134 consecutive patients with liver cirrhosis, from February 2009 to September 2013. All patients had undergone dynamic computed tomography and esophagogastroduodenoscopy before CE examination. The frequencies and types of PHE lesions, and the relationships between the presence of PHE and patients' clinical characteristics were evaluated. The distribution of the lesions was also determined. RESULTS: PHE was found in 91 (68%), erythema in 70 (52%), erosions in 25 (19%), angioectasia in 24 (18%), villous edema in 18 (13%), and varices in 10 (7%) patients. Most lesions were located in the jejunum. The clinical characteristics associated with the presence of PHE were a Child-Pugh grade of B or C (P = 0.0058), and the presence of PSs (P < 0.0001), ascites (P = 0.0017), portal thrombosis (P = 0.016), esophageal varices (P = 0.0017), and portal hypertensive gastropathy (P = 0.0029). The presence of PSs was an independent predictor of PHE (odds ratio [OR]: 3.15; 95% confidence interval [CI]: 1.27-7.95). Among the shunt types, left gastric vein (OR: 5.31; 95% CI: 1.97-17.0) and splenorenal shunts (OR: 4.26; 95% CI: 1.29-19.4) were independent predictors of PHE. CONCLUSION: PSs, especially left gastric vein and splenorenal shunts, appear to reliably predict the presence of PHE.

Reduction of conventional dendritic cells during Plasmodium infection is dependent on activation induced cell death by type I and II interferons.

Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in pathogenesis during the blood stage of malaria infection. The mechanisms underlying DC homeostasis during malaria infection are not well understood. In this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the spleens after lethal rodent malaria infection were examined, and were found to be significantly reduced. Concomitant with up-regulation of maturation-associated molecules, activation of caspase-3 was significantly increased, suggesting induction of cell death. Studies using neutralizing antibody and gene-deficient mice showed that type I and II interferons were critically involved in activation induced cell death of cDCs during malaria infection. These results demonstrate that DCs rapidly disappeared following IFN-mediated DC activation, and that homeostasis of DCs was significantly impaired during malaria infection.

Baculovirus-vectored multistage Plasmodium vivax vaccine induces both protective and transmission-blocking immunities against transgenic rodent malaria parasites.

A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen.

Clinical outcomes of endoscopic submucosal dissection for superficial Barrett's adenocarcinoma.

BACKGROUND: Advances in diagnostic techniques have allowed early stage detection of superficial Barrett's adenocarcinoma (SBA) as well as resection by endoscopic submucosal dissection (ESD). Few reports exist, however, on the safety and efficacy of ESD for SBA. OBJECTIVE: To analyze outcomes of ESD for SBA in relation to clinicopathological features of the lesions. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Twenty-three patients (21 men, 2 women; mean age, 63 years) with 26 SBAs. INTERVENTION ESD MAIN OUTCOME MEASUREMENTS: We examined outcomes of ESD in relation to the clinicopathological features of SBAs. The main outcomes assessed were en bloc resection rate, operation time, adverse event rates, additional resection rate, and time between ESD and any recurrence. RESULTS: Twenty lesions (87%) derived from short-segment Barrett's esophagus, and 3 lesions (13%) derived from long-segment Barrett's esophagus. The majority of SBAs (54%) were located in the 0 to 3 o'clock circumferential quadrant. Median tumor size was 15 mm (range 5-60 mm). Macroscopic types were flat elevated (n = 13, 50%), depressed (n = 12, 46%), and protruded (n = 1, 4%). The SBAs appeared red (n = 23, 88%) or normally pale (n = 3, 12%). Under magnifying narrow-band imaging, all SBAs showed an irregular mucosal pattern and an irregular vascular pattern. The endoscopic en bloc resection rate was 100% (26/26), and the pathological en bloc resection rate was 85% (22/26). The median procedure time was 95 minutes (range, 30-210 minutes). Delayed bleeding occurred in 1 case, but there was no perforation. The SBAs were of the differentiated type (n = 25, 96%) or poorly differentiated type (n = 1, 4%). The tumor had invaded the superficial muscularis mucosa (n = 3, 12%), lamina propria mucosa (n = 5, 19%, deep muscularis mucosa (n = 9, 34%), SM1 (n = 3, 12%), and SM2 (n = 6, 23%). Additional surgical resection after ESD was performed in 9 cases, and there were no residual tumors, but 1 lymph node metastasis was found. There were no recurrent tumors; however, 1 metachronous adenocarcinoma was diagnosed 42 months after ESD. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: ESD appears to be a safe and effective treatment strategy for early stage SBA.

Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Although recent guidelines for endoscopic submucosal dissection (ESD) as treatment for early gastric cancer (EGC) recommend noninterruption of low-dose aspirin (LDA) perioperatively, this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before to ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. Our purpose in this study was to confirm the validity of noninterrupted use of LDA in patients undergoing ESD for EGC. METHODS: We studied 78 consecutive patients with 94 EGCs who were routinely taking LDA and were treated by ESD at Hiroshima University Hospital between April 2005 and June 2012. The patients were of two groups: those in whom LDA was interrupted perioperatively (53 patients with 66 EGCs) and those in whom LDA was continued perioperatively (25 patients with 28 EGCs). RESULTS: The complete resection rate was 92.4 % (61/66) in the LDA-interrupted group and 100 % (28/28) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after procedure were 10.6 % (7/66) and 4.8 % (3/66), respectively, in the LDA-interrupted group and 7.1 % (2/28) and 3.6 % (1/28) in the LDA-continued group. Two patients in the interrupted-LDA group suffered cerebrovascular infarction before ESD, and 2 patients in this group suffered acute myocardial infarction after ESD. CONCLUSIONS: Our data suggest that continued use of LDA does not increase the risk of bleeding during or after ESD for EGC and does decrease the risk of ischemic events.

Is small-bowel capsule endoscopy effective for diagnosis of esophagogastric lesions related to portal hypertension?

BACKGROUND AND AIM: Effectiveness of capsule endoscopy (CE) for screening the small bowel in patients with portal hypertension (PHT) has been reported. However, few reports discuss CE detection of specific esophagogastric lesions related to PHT. Thus, we assessed whether CE is useful for detecting such lesions. METHODS: One hundred nineteen consecutive patients with PHT comprised the study group. All had undergone esophagogastroduodenoscopy (EGD) prior to CE. The diagnostic yield of CE for esophageal varices (EVs), gastric varices (GVs), and portal hypertensive gastropathy (PHG) was evaluated. In addition, diagnostic yield in relation to form, location of the varices, grade, and extent of PHG was evaluated. RESULTS: EVs were found by EGD in 71 patients. The overall diagnostic yield of CE for EVs was 72% (51/71). The diagnostic yield was significantly greater for F2/F3 EVs than for F1 EVs (87% vs 61%, P = 0.03). The diagnostic yield was significantly greater for Lm/Ls EVs than for Li EVs (85% vs 55%, P = 0.01). The diagnostic yield was significantly greater for locus superior/locus medialis EVs than for locus inferior EVs (85% vs 55%, P = 0.01). GVs were found by EGD in 29 patients. Only one case was detected by CE. PHG was found by EGD in 35 patients. The diagnostic yield of CE for PHG was 69% (24/35). There was no difference in diagnostic yield between cases of severe and mild PHG (82% vs 63%, P = 0.44). Diagnostic yield of CE for PHG in the gastric body was significantly greater than that in the fundus (100% vs 48%, P = 0.0009). CONCLUSION: CE is reliable for diagnosis of F2/F3 and/or Lm/Ls EVs and of PHG in the gastric body.