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Abstract: Aim: The aim of this study is to evaluate the safety and efficacy of hepatic artery infusion (HAI) of 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinoma after radiological placement of infusion catheters. Methods: Forty-two patients with liver metastases from colorectal carcinoma received radiological placement of infusion catheters using the distal fixation method. They received continuous HAI of 5FU 1000–1500mg for 5h weekly or biweekly. Tumor status was assessed by chest-abdominal computed tomography (CT) scan after every 10 infusions. Hepatic perfusion was checked by CT arteriography via the infusion port after every 10 infusions. Results: Radiological placements of catheters were performed successfully in all cases. Each patient received an average of 36 treatments (range: 10–98). Catheter failure was found in 3 patients (7.1%). Nine incidents of grade 1 toxicity were observed in 8 patients (19.0%). There was a complete response in 6 patients, partial remission in 18, stable disease in 9, and progression of disease in 9 (response rate: 57.1%). Overall median survival time was 29.1months. Using Cox''s proportional hazard model, lymph node metastases in primary colorectal carcinoma and pre-treatment serum CEA affected overall survival (P =0.011, P =0.005). Conclusions: HAI after radiological placement of infusion catheters is a safe and effective treatment particularly for patients with no lymph node metastasis in primary carcinoma or with a low pre-treatment serum CEA level. [Copyright &y& Elsevier]

SUMMARY:The sensory basis of the behavior of cuttlefish towards basket traps explains in part the mechanism of capture by the gear. Previous studies have shown that the reaction of cuttlefish Sepia esculenta to basket traps is mediated mainly by vision. In this study, visual factors that attract cuttlefish to basket traps were examined in the laboratory. The reaction of cuttlefish was divided into three processes of recognition, approach, and entry; the frequency and the duration of each process indicated the strength of the reaction. Cuttlefish were most attracted to a basket trap that contrasted most strongly with the background. When the dismantled components of the basket trap were presented as visual targets to cuttlefish, all the components were approached by the cuttlefish, which remained in the internal space. Cuttlefish have a habit of occupying the internal space of a structure and this habit seems to be the main motivation for entry into a trap. Another experiment was carried out to examine the social attraction between individuals inside and outside a trap. Social interference between males and females seems to be part of the mechanism of capture of cuttlefish by basket traps. [ABSTRACT FROM AUTHOR]

The receptor-type protein tyrosine kinases in murine pancreatic islets were screened to identify possible growth/differentiation factors in pancreatic beta-cells. The analysis revealed that insulin receptor-related receptor (IRR) is highly expressed in the islets as well as in several highly differentiated beta-cell lines derived from transgenic mice. Islets predominantly contain IRR as uncleaved proreceptors compared with IRR as processed forms in the beta-cell lines, suggesting that the activity of IRR is regulated on the level of processing proteases in vivo. To examine the IRR signaling pathway, a chimeric receptor consisting of the extracellular domain of insulin receptor and the intracellular domain of IRR was expressed in Chinese hamster ovary cells. The hybrid receptor is functional because insulin is capable of tyrosine-phosphorylating the catalytic domain in these cells. It also stimulates the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2, indicating that both proteins serve as substrates of IRR-protein tyrosine kinase in intact cells. The phenotype of the IRS-2 knockout mouse recently reported suggests that an IRS-2-mediated signaling pathway controls the compensatory increase in pancreatic beta-cell mass in insulin-resistant states. From our findings of the specific expression of IRR and its ability of signaling to IRS-2, we speculate that this receptor might play a role in the regulation of beta-cell mass. [ABSTRACT FROM AUTHOR]

The molecular pathogenesis of diabetes remains poorly understood because of the genetic complexity of the disease. One possibly effective approach to elucidate the pathogenesis is to study an animal model with a similar phenotype. The TSOD (Tsumura, Suzuki, Obese Diabetes) mouse, a newly developed animal model, exhibits both diabetes and obesity with marked hyperinsulinemia and hypertrophy of the pancreatic islets and might represent a common form of obese type 2 diabetes in humans. Phenotypic characterization revealed that the TSOD mouse had both insulin resistance and impaired glucose-stimulated insulin secretion. A comprehensive genetic dissection of diabetes and obesity has been performed using F1 and F2 progeny between the TSOD and control BALB/cA strains. A genome-wide screen for loci linked to glucose homeostasis and body weight allowed us to map three quantitative trait loci (QTLs) involved in this disorder. The major genetic determinant of blood glucose levels was identified on chromosome 11. Furthermore, two independent QTLs involved in controlling body weight were found on chromosomes 1 and 2. The QTL on chromosome 2 also affected insulin levels significantly. Each QTL has distinct effects on different traits and a different mode of inheritance. Our study indicates that hyperglycemia and obesity are clearly controlled by distinct combinations of genetic loci in this mouse model and provides insights into the genetic basis of common forms of human type 2 diabetes with obesity. [ABSTRACT FROM AUTHOR]

We report the case of an 84-year-old male patient who was transferred to our hospital because of impaired consciousness and high fever, and died about 10 weeks after his fourth "coronavirus disease 2019" (COVID-19) vaccination. Autopsy revealed acute ischemic change with microhemorrhage and perivascular T-cell infiltration in the thalamus, pons, and cerebellum, which were considered to be related to neurological symptoms. There were dilatation of the right ventricle, accumulation of pleural effusion, and ascites, suggesting right heart failure. Although the patient had a negative COVID-19 polymerase chain reaction test, immunohistochemical analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens (spike and nucleocapsid proteins) was performed to identify the cause of death. Surprisingly, only SARS-CoV-2 spike protein was detected in the thalamus, pons, and pituitary and adrenal glands. The presence of SARS-CoV-2 spike protein might have been due to vaccination rather than viral infection, because no SARS-CoV-2 nucleocapsid protein was detected. The spike protein in the central nervous system might have been related to the acute ischemic change, and that in the pituitary and adrenal glands may have been associated with right heart failure, possibly through dysfunction of the renin-angiotensin-aldosterone system., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Guanfacine is an alpha-2 adrenergic agonist that decreases norepinephrine release and sympathetic outflow. With the increased use of guanfacine for attention-deficit hyperactivity disorder (ADHD), reports of guanfacine poisoning have also risen., Case Presentation: A 15-year-old male (height: 170 cm, weight: 48 kg), who was taking 2 mg/day of guanfacine for ADHD, was brought to our emergency department after ingesting 40 tablets of guanfacine due to poor exam results. He presented with impaired consciousness and sinus bradycardia on an electrocardiogram (ECG), leading to diagnosis of guanfacine poisoning. Gastric lavage (5 L) was performed, and activated charcoal was administered. Although his consciousness gradually recovered, he developed ST-segment elevation on the ECG. Despite the absence of chest pain and elevated myocardial enzymes, coronary artery stenosis was not observed on coronary artery computed tomography. As his blood guanfacine level decreased, his ECG returned to normal., Conclusions: This case highlights the need for careful monitoring of guanfacine poisoning patients due to the potential for various cardiovascular events., (© 2024. The Author(s).)

Environmental DNA (eDNA) is an increasingly popular tool in biological and ecological studies. As a biproduct of its increasing use, large number of eDNA samples are being collected and stored, that potentially contain information of many non-target species. One potential use for these eDNA samples is a surveillance and early detection of pathogens and parasites that are otherwise difficult to detect. Echinococcus multilocularis is such a parasite with serious zoonotic concern, and whose range has been expanding. If eDNA samples from various studies can be repurposed in detecting the parasite, it can significantly reduce the costs and efforts in surveillance and early detection of the parasite. We designed and tested a new set of primer-probe for detecting E. multilocularis mitochondrial DNA in environmental medium. Using this primer-probe set, we conducted real-time PCR on repurposed eDNA samples collected from three streams flowing through an area of Japan endemic to the parasite. We detected the DNA of E. multilocularis in one of the 128 samples (0.78%). The discovery suggests that while detecting E. multilocularis using eDNA samples is possible, the rate of detection appear to be very low. However, given the naturally low prevalence of the parasite among wild hosts in endemic areas, the repurposed eDNAs may still be a valid option for surveillance in newly introduced areas with the reduced cost and efforts. Further work is needed to assess and improve the effectiveness of using eDNA for detection of E. multilocularis ., Competing Interests: The authors declare there are no competing interests., (©2023 Mori et al.)

Background: Several clinical guidelines recommend monitoring blood lactate levels and central venous oxygen saturation for hemodynamic management of patients with sepsis. We hypothesized that carbon dioxide production (VCO 2 ) and oxygen extraction (VO 2 ) evaluated using indirect calorimetry (IC) might provide additional information to understand the dynamic metabolic changes in sepsis., Methods: Adult patients with sepsis who required mechanical ventilation in the intensive care unit (ICU) of our hospital between September 2019 and March 2020 were prospectively enrolled. Sepsis was diagnosed according to Sepsis-3. Continuous measurement of VCO 2 and VO 2 using IC for 2 h was conducted within 24 h after tracheal intubation, and the changes in VCO 2 and VO 2 over 2 h were calculated as the slopes by linear regression analysis. Furthermore, temporal lactate changes were evaluated. The primary outcome was 28-day survival., Results: Thirty-four patients with sepsis were enrolled, 26 of whom survived 76%. Significant differences in the slope of VCO 2 (- 1.412 vs. - 0.446) (p = 0.012) and VO 2 (- 2.098 vs. - 0.851) (p = 0.023) changes were observed between non-survivors and survivors. Of note, all eight non-survivors and 17 of the 26 survivors showed negative slopes of VCO 2 and VO 2 changes. For these patients, 17 survivors had a median lactate of - 2.4% changes per hour (%/h), whereas non-survivors had a median lactate of 2.6%/hr (p = 0.023)., Conclusions: The non-survivors in this study showed temporal decreases in both VCO 2 and VO 2 along with lactate elevation. Monitoring the temporal changes in VCO 2 and VO 2 along with blood lactate levels may be useful in predicting the prognosis of sepsis., (© 2021. The Author(s).)

The frequencies of autonomous bystander-initiated cardiopulmonary resuscitation (CPR) and public access defibrillation have not yet been clarified. We aimed to evaluate the frequency of autonomous actions by citizens not having a duty to act.This retrospective observational study included patients who suffered an out-of-hospital cardiac arrest (OHCA) in Tokyo between January 1, 2013 and December 31, 2017. The Delphi method with a panel of 11 experts classified the locations of OHCA resuscitations into 3 categories as follows; autonomous, non autonomous, and undetermined. The locations determined as autonomous were further divided into 2 groups; home and other locations. Bystander-initiated CPR and application of an automated external defibrillator (AED) pad were evaluated in 43,460 patients with OHCA.Group A (non autonomous), group B (autonomous, not home), and group C (home), consisted of 7,352, 3,193, and 32,915 patients, respectively. Compared with group A, group B and group C had significantly lower rates of bystander-initiated CPR (group A, B, C; 68.3% versus 38.6% versus 23.9%) and AED pad application (groups A, B, C; 26.8% versus 15.1% versus 0.6%). In addition, multivariate analysis demonstrated that an autonomous location of resuscitation was independently associated with the frequencies of bystander-initiated CPR and AED pad application, even after adjusting for age, sex, and witness status.Autonomous actions by citizens were unacceptably infrequent. Therefore, the education and training of citizens is necessary to further enhance autonomous CPR.

Hepatic cysts usually do not cause symptoms and may be detected incidentally on abdominal imaging. However, a giant hepatic cyst can rarely compress the inferior vena cava, right lung, and spine, leading to edema of lower extremities and scoliosis., Competing Interests: None declared., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.

Background: Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported., Case Presentation: An 18-year-old Japanese woman who had taken an overdose of prescription colchicine (15 mg; 0.2 mg/kg) was brought to our emergency out-patient department. Although her colchicine intake was below 0.8 mg/kg (considered the lethal dose), she reached a critical state and underwent three phases characterizing colchicine poisoning (gastrointestinal symptoms, multiple organ failure, and recovery). Her condition was critical, with a Sequential Organ Failure Assessment score of a maximum of 14., Conclusions: Patients might reach a critical stage after colchicine ingestion at a non-lethal dose. Thus, it might be necessary to review which dose of colchicine should be considered lethal.

Background/aims: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated., Methods: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs)., Results: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p < 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002)., Conclusion: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients., (© 2018 S. Karger AG, Basel.)

Background and Study Aims: Image-enhanced endoscopy (IEE) plays an important role in early detection and detailed examination of early gastric cancer (EGC). The current study aimed to clarify the efficacy of IEE using advanced diagnostic endoscopy for EGC detection without magnification., Patients and Methods: We performed endoscopic examinations without magnification in patients referred to our hospital with a diagnosis of upper gastrointestinal tumor detected through routine screening endoscopy. In this study, we used three IEE technologies: narrow-band imaging; blue laser imaging; and i-scan optical enhancement. The detection rates for EGC between IEE and white-light imaging (WLI) were compared., Results: Between July 2013 and June 2014, 156 patients were enrolled. Among upper gastrointestinal tumors, we analyzed endoscopic examination results of 119 lesions that were histologically diagnosed as EGC in 109 patients. The EGC detection rate in the IEE plus WLI groups was 77.3 %. Although the EGC detection rate in the IEE group was higher than that in the WLI group (80.0 % vs. 70.3 %), there was no significant difference between these two modalities. An important detection factor using IEE was tumor circumference, where the rate of detection in the anterior wall and lesser curvature was significantly higher than that in the posterior wall and greater curvature ( P  = 0.046). An important detection factor using WLI was color variation, where the rate of occurrence of a reddened or pale tumor was significantly higher than that of normal colored tumors ( P  = 0.030)., Conclusions: The detection rate of EGC without magnification was similar between the IEE group and the WLI group. Important detection factors differed between IEE and WLI; therefore, the IEE and WLI modalities have different characteristics regarding EGC detection. Consequently, we propose to use both IEE and WLI in the evaluation of EGC.

Background and Study Aims: Endosurgical devices with injection function have been reported to decrease endoscopic submucosal dissection (ESD) operation times for experts, but the efficacy of these devices for inexperienced endoscopists is unclear. The aim of this study was to evaluate the feasibility of ESD using a novel ESD knife (DN-D2718B)., Patients and Methods: This is a single-center prospective pilot clinical feasibility study. Patients diagnosed with superficial gastrointestinal neoplasms were enrolled. A pre-specified group of ESD trainees with ESD experience on a porcine gastric model and fewer than 30 cases of ESD in their selected fields performed ESD under expert supervision, using the DN-D2718B. En bloc resection rates, R0 resection rates, procedure times, and incidence of intra-operational/post-operational adverse events were assessed., Results: Between June 2015 and January 2016, 13 esophageal, 27 gastric, and 14 colorectal ESD cases were performed per-protocol with mean resection speeds of 10.2, 12.0, and 15.5 mm 2 /min, respectively. There were no intra-operational complications., Conclusion: ESD with this novel knife is feasible even when performed by non-experts.

Endoscopic submucosal dissection (ESD) has become widely accepted as a standard method of treatment for superficial gastrointestinal neoplasms because it enables en block resection even for large lesions or fibrotic lesions with minimal invasiveness, and decreases the local recurrence rate. Moreover, specimens resected in an en block fashion enable accurate histological assessment. Taking these factors into consideration, ESD seems to be more advantageous than conventional endoscopic mucosal resection (EMR), but the associated risks of perioperative adverse events are higher than in EMR. Bleeding after ESD is the most frequent among these adverse events. Although post-ESD bleeding can be controlled by endoscopic hemostasis in most cases, it may lead to serious conditions including hemorrhagic shock. Even with preventive methods including administration of acid secretion inhibitors and preventive hemostasis, post-ESD bleeding cannot be completely prevented. In addition high-risk cases for post-ESD bleeding, which include cases with the use of antithrombotic agents or which require large resection, are increasing. Although there have been many reports about associated risk factors and methods of preventing post-ESD bleeding, many issues remain unsolved. Therefore, in this review, we have overviewed risk factors and methods of preventing post-ESD bleeding from previous studies. Endoscopists should have sufficient knowledge of these risk factors and preventive methods when performing ESD.

Background: Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is the standard gastric cancer screening method in Japan. Atrophic gastritis and enlarged gastric folds are considered the two major features of Helicobacter pylori-induced chronic gastritis, but the clinical meaning of evaluating them by UGI-XR has not been elucidated., Methods: We analyzed healthy UGI-XR examinees without a history of gastrectomy, previous Helicobacter pylori eradication and usage of gastric acid suppressants., Results and Conclusions: Of the 6433 subjects, 1936 (30.1 %) had atrophic gastritis and 1253 (19.5 %) had enlarged gastric folds. During the 3-year prospective observational follow-up, gastric cancer developed in seven subjects, six of whom (85.7 %) had atrophic gastritis with H. pylori infection and five of whom (71.4 %) had enlarged gastric folds with H. pylori infection. The Kaplan-Meier method with log-rank testing revealed that both UGI-XR-based atrophic gastritis (p = 0.0011) and enlarged gastric folds (p = 0.0003) are significant predictors for future gastric cancer incidence.

Background and Study Aims: Although magnifying endoscopy with narrow-band imaging (ME-NBI) is reported to be useful for delineating the horizontal extent of early gastric cancers (EGCs), there are few reports which have objectively demonstrated the superiority of ME-NBI over chromoendoscopy with indigo carmine for this purpose. We conducted an exploratory comparison of the diagnostic accuracy of both modalities for the delineation of EGCs using prospectively collected data, and clarified the clinicopathological features related to inaccurate evaluation of the horizontal extent of EGCs., Patients and Methods: EGCs were assigned to the oral narrow-band imaging (O-NBI) group or the oral chromoendoscopy (O-CE) group before endoscopic submucosal dissection (ESD). The oral border was observed according to assignment, and the anal border with the other modality. The horizontal extent of the tumor was evaluated by each modality and a marking dot was placed on the visible delineation line. After ESD, the marking dots were identified pathologically and defined as "accurate evaluation" if they were located within 1 mm of the pathological tumor border. We compared the rate of accurate evaluation of ME-NBI and chromoendoscopy, and analyzed the clinicopathological features related to inaccurate evaluation., Results: A total of 113 marking dots evaluated by ME-NBI and 116 evaluated by chromoendoscopy were analyzed. The rate of accurate evaluation by ME-NBI was significantly higher than that by chromoendoscopy (89.4 % vs 75.9 %, P = 0.0071). The EGCs with flat borders and large EGCs were significantly related to inaccurate evaluation using ME-NBI. There were no significant factors related to inaccurate evaluation with chromoendoscopy., Conclusions: The accurate evaluation rate of the horizontal extent of EGCs by ME-NBI is significantly higher than that by chromoendoscopy., Study Registration: UMIN000007641.

Background and Objectives: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an effective method for tissue diagnosis of gastrointestinal submucosal tumors (SMTs) that are difficult to diagnose by standard endoscopic biopsy. However, the learning curve, especially for gastrointestinal SMT, has not been sufficiently established. The aim of our study was to assess the skill acquisition and diagnostic accuracy of EUS-FNA for gastrointestinal SMT in trainee endoscopists in order to elucidate the optimal starting standards of EUS-FNA., Materials and Methods: We prospectively evaluated 51 EUS-FNA procedures for gastrointestinal SMT between May 2010 and March 2014. The procedure was performed by two trainee endoscopists and two expert endoscopists. We investigated the diagnostic yield of EUS-FNA and the factors associated with the accuracy between the trainee endoscopists and expert endoscopists., Results: The rate of adequate EUS-FNA materials for histological examination was 86.3%. Although infections occurred in two cases (3.9%), which were managed conservatively, no severe complications were identified. Comparing the trainee endoscopists with expert endoscopists, there was no significant difference in the rate of gaining adequate specimen (76.5% vs. 82.3%, P = 0.4626). However, the mean number of passes of the trainees tended to be more than that of the expert endoscopists (2.1 pass vs. 1.7 pass, P = 0.0511), and lesions located in the middle third of the stomach were the predictive factors for nondiagnostic tumors by the trainee endoscopists (P = 0.0075)., Conclusion: EUS-FNA for gastrointestinal SMT by trainee endoscopists can be safely performed under the supervision of EUS-FNA expert endoscopists.

Background: Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan., Methods: We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors., Results: Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that age (β = 0.217-0.674, OR = 1.24-1.96), male gender (β = 0.185, OR = 1.20), smoking (β = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (β = 0.153, OR = 1.17), HbA1c (β = 0.136, OR = 1.15), drinking (β = 0.109, OR = 1.11), and serum triglyceride (β = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not., Conclusions: The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.

Background and Study Aims: Suitable techniques for the prevention of stricture formation after esophageal endoscopic submucosal dissection (ESD) are still lacking. We investigated the efficacy of polyglycolic acid (PGA) sheets with fibrin glue to prevent post-ESD stricture., Patients and Methods: We conducted a pilot study on a total of eight consecutive patients who underwent esophageal ESD that left a mucosal defect of more than three-quarters of the esophageal circumference. PGA sheets were attached to the defect with fibrin glue immediately after the completion of ESD. The primary endpoint was the incidence of post-ESD stricture. The secondary endpoints were the number of sessions of endoscopic balloon dilation (EBD) required to resolve any stricture and the rate of complications., Results: There were no adverse events related to the use of PGA sheets and fibrin glue. Post-ESD stricture occurred in 37.5 % of the subjects and 0.8 ± 1.2 sessions of EBD were required., Conclusion: The use of PGA sheets and fibrin glue after esophageal ESD is a novel method that radically decreases the incidence of esophageal stricture and the number of EBD sessions subsequently required. University Hospital Medical Network Clinical Trial Registry (UMIN000011058)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The prevention of bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasms is still an important problem., Objective: To investigate the efficacy and safety of a shielding method that uses polyglycolic acid (PGA) sheets and fibrin glue to prevent post-ESD bleeding in high-risk patients., Design: A nonrandomized trial with historical control subjects., Setting: A single academic hospital in Japan., Patients: From July 2013 to February 2014, 45 ESD-induced ulcers in 41 patients with a high risk of bleeding were enrolled in a study group. Forty-one consecutive ESD-induced ulcers in 37 control subjects with a high risk of bleeding were treated in 2013 before the first enrollment., Interventions: We placed PGA sheets on the mucosal defect and fixed with fibrin glue in the study group., Main Outcome Measurements: The post-ESD bleeding rate., Results: The post-ESD bleeding occurred at a rate of 6.7% in the study group (3/45 lesions) and 22.0% in the historical control group (9/41 lesions). There was a significant difference in the post-ESD bleeding rate between the 2 groups (P = .041)., Limitations: A nonrandomized trial with historical control subjects; a single-center analysis; small sample size., Conclusions: The endoscopic tissue shielding method with PGA sheets and fibrin glue appears to be promising for the prevention of post-ESD bleeding. (, Clinical Trial Registration Number: UMIN000011058.)., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection., Methods: We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach., Results: Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H2-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects., Conclusions: The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.

Background: The aim of the present study was to evaluate the clinical utility of a new image-enhanced endoscopy (IEE) technology called optical enhancement imaging (OEI-1, -2, -3) by quantitatively evaluating diagnostic performance in superficial esophageal squamous cell carcinoma (SCC) in order to facilitate detection and characterization of gastrointestinal tumors., Patients and Methods: The study involved 10 esophageal SCC resected endoscopically at our hospital. Ex vivo observation of the boundary area between normal and SCC was done using each mode (white light image [WLI], OEI-1, OEI-2, and OEI-3) with and without magnification. The additional effect of OEI on WLI was evaluated by calculating the color difference (expressed as ΔE94 ) between SCC and normal epithelium, and that between the intraepithelial papillary capillary loop (IPCL) and inter-vascular background coloration (IVBC)., Results: Mean ΔE94 values between SCC and normal epithelium for WLI, OEI-1, OEI-2, and OEI-3 were 9.37 ± 4.64, 13.82 ± 4.46,13.26 ± 4.73, and 16.44 ± 4.83, respectively; the corresponding values between IPCL and IVBC were 17.57 ± 10.17, 29.32 ± 9.95, 25.41 ± 11.72, and 23.71 ± 11.58, respectively. Compared with WLI, all OEI exhibited significant additional effect on ΔE94 . Furthermore, we found significant additional effect of OEI-3 in observing SCC and normal epithelium, and of OEI-1 in observing IPCL and IVBC, compared with other OEI., Conclusion: These results suggest that OEI improves endoscopic detection and characterization of esophageal SCC compared with WLI. Moreover, the data indicate that OEI-3 is useful for detection and OEI-1 is useful for characterization of esophageal SCC., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Background: There have been very few reports assessing the relationship between various upper gastrointestinal (GI) symptoms or evaluating each individual upper GI symptom separately., Methods: Based on the answers to Frequency Scale for the Symptoms of GERD from a large-scale population of healthy adults in Japan, a hierarchical cluster analysis was performed to categorize the typical 12 upper GI symptoms. The associations between the 12 symptoms and 13 background factors were systematically analyzed among the 18,097 digestive drug-free subjects, 364 proton-pump inhibitor (PPI) users, and 528 histamine H₂-receptor antagonist (H₂RA) users., Results: The derived relationship between the 12 upper GI symptoms suggests the five symptom categories: heartburn (2), dyspepsia (4), acid regurgitation (3), pharyngo-upper esophageal discomfort (2), and fullness while eating (1). Among the digestive drug-free subjects, inadequate sleep, weight gain in adulthood, NSAID use, meals immediately prior to sleep, and frequent skipping of breakfast showed significant positive association with most upper GI symptoms. Compared to the digestive drug-free subjects, significantly associated factors for PPI and H₂RA users are respectively different in "4 of 5" and "5 of 5" symptoms in heartburn and acid regurgitation categories, "1 of 2" and "1 of 2" symptoms in pharyngo-upper esophageal discomfort category, and "0 of 5" and "3 of 5" symptoms in dyspepsia and fullness while eating categories. These differences between digestive drug-free subjects and gastric acid suppressant users seem to correlate with our experiences in clinical situations: heartburn and acid regurgitation category symptoms are effectively controlled with PPI and H₂RA whereas other category symptoms are not., Conclusions: The 12 upper GI symptoms can be classified into five categories, which are statistically associated with various background factors. The differences of associated factors between digestive drug-free subjects and digestive drug users may be useful in studying the drug effects upon diverse upper GI symptoms.

Full-thickness resection for gastric malignancy carries a risk of peritoneal dissemination due to opening of the gastric lumen. We evaluated the feasibility and safety a novel method of full-thickness resection without transmural communication, called nonexposed endoscopic wall-inversion surgery in ex vivo and in vivo porcine models. Six explanted porcine stomachs and 6 live pigs were used for this study. After marking and submucosal injection around 3 cm simulated lesions, the seromuscular layer was laparoscopically cut and sutured with the lesion inverted to the inside. Consecutively, a mucosubmucosal incision was made endoscopically. Three pigs used for the survival study were monitored for 7 days. All 12 lesions were successfully resected en bloc without perforation. The 3 pigs survived for 1 week without adverse events, and necropsy revealed neither leakage nor abscess formation related to the operation. We demonstrated nonexposed endoscopic wall-inversion surgery to be technically feasible and safe in both ex vivo and in vivo porcine studies.

Background: Certain tumor characteristics may pose challenges when endoscopically determining the horizontal extent of early gastric cancers (EGC). In the present study, clinicopathological features related to inaccurate endoscopic evaluation of horizontal extent of intestinal-type EGC were analyzed., Patients and Methods: We analyzed 431 lesions with intestinal-type EGC treated by endoscopic submucosal dissection (ESD) at our hospital. We focused on whether pretreatment demarcation was accurate by comparing positional relationships between marking dots and tumor edges in resected specimens, and factors related to inaccurate evaluation were analyzed. Gender, age, tumor size, location, circumference, depth, ulceration, macroscopic type, presence of a flat (0-IIb) component, predominant histological type, mixture of diffuse-type adenocarcinoma, mixed histology, and use of magnification endoscopy with narrow band imaging were analyzed. Reasons for inaccurate evaluation were also investigated by re-examining endoscopic images and prepared histological slides., Results: Rate of inaccurate evaluation of horizontal extent was 7.4% (32/431 lesions). Multivariate analysis revealed the following significant independent variables contributing to inaccurate endoscopic evaluation: presence of a flat component, large size, and predominant histological findings of moderately differentiated adenocarcinoma. Re-examination of prepared histological slides of inaccurately evaluated cases revealed a marginal flat spreading area in 28 of the 32 lesions (87.5%). In 14 of the 32 lesions (43.8%), tumor margins were composed of moderately differentiated adenocarcinoma., Conclusions: For lesions with a flat component, large lesions, and moderately differentiated adenocarcinoma, determination of the horizontal extent can be challenging in EGC indicated for ESD, even with the best available endoscopic tools., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

Background: Despite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of Helicobacter pylori infection and gastric atrophy., Methods: We analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20-87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and p-value., Results: Of the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), HP non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, HP infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic HP infection and successful HP eradication denotes significant difference (2.3% and 8.8%; p<0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; p = 0.064)., Conclusions: Significantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of Helicobacter pylori may have disadvantageous effects on RE but not on NERD.

A 53-year-old man was suspected of having an esophageal neoplasm. An endoscopic examination including Lugol chromoendoscopy suggested an esophageal squamous cell neoplasm limited to the lamina propria. A targeted biopsy showed atypical squamous cells, and an endoscopic submucosal dissection was performed 22 days after the previous endoscopy. Although a single 40 mm unstained area was observed by preoperative Lugol chromoendoscopy, intraoperative endoscopy revealed a 25 mm iodine-unstained area, with small unstained areas scattered on the oral side. We included the small unstained areas in the extent of the resection through assessment by preoperative endoscopy. Histopathologically, the tumor extent appeared to coincide with the preoperative assessment. Tumor cells were found in the basal-parabasal layers of the mucosa, in which small unstained areas were scattered, although the superficial layers exhibited well-differentiated cells containing glycogen in the cytoplasm. Although Lugol chromoendoscopy, which can induce chemical esophagitis, is widely used, re-epithelialization after mucosal damage by preoperative iodine staining may complicate the intraoperative demarcation of tumors.