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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: 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 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: 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: 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.

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.

Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis.

Aim. Little is known about the usefulness of narrow band imaging (NBI) for surveillance of patients after chemoradiotherapy for esophageal neoplasia. Its usefulness in detecting esophageal squamous cell carcinoma (SCC) or high-grade intraepithelial neoplasia (HGIN) in these patients was retrospectively compared to Lugol chromoendoscopy. Patients and Methods. We assessed the diagnostic ability of NBI with magnification based on the biopsy specimens obtained from iodine-unstained lesions. Seventy-two iodine-unstained lesions were biopsied and consecutively enrolled for this study. The lesions were divided into NBI positive and NBI negative. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of NBI with magnification and PPV of Lugol chromoendoscopy was calculated using histological assessment as a gold standard. Results. Forty-six endoscopic examinations using NBI with magnification followed by Lugol chromoendoscopy were performed to 28 patients. The prevalence of SCC and HGIN was 21.4%. Sensitivity, specificity, PPV, NPV, and accuracy of NBI were 100.0%, 98.5%, 85.7%, 100%, and 98.6%, respectively. On the contrary, PPV of Lugol chromoendoscopy were 8.3%. Compared to Lugol chromoendoscopy, NBI with magnification showed equal sensitivity and significantly higher PPV (P < 0.0001). Conclusion. NBI with magnification would be able to pick up esophageal neoplasia more efficiently than Lugol chromoendoscopy in patients after chemoradiotherapy.

Background: Gastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce., Methods: To elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H₂-receptor antagonist (H₂RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Student's t-test or Pearson's correlation coefficient, and were further analyzed with multiple linear regression modelling., Results: Average FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H₂RA users. Among the total population, positively correlated factors and standardized coefficients (β) for FSSG scores are inadequate sleep (β = 0.158), digestive drug users (β = 0.0972 for PPI, β = 0.0903 for H₂RA, and β = 0.104 for others), increased body weight in adulthood (β = 0.081), dinner just before bedtime (β = 0.061), the habit of midnight snack (β = 0.055), lower body mass index (β = 0.054), NSAID users (β = 0.051), female gender (β = 0.048), lack of breakfast (β = 0.045), lack of physical exercise (β = 0.035), younger age (β = 0.033), antihyperglycemic agents non-users (β = 0.026), the habit of quick eating (β = 0.025), alcohol drinking (β = 0.025), history of gastrectomy (β = 0.024), history of cardiovascular disease (β = 0.020), and smoking (β = 0.018). Positively correlated factors for PPI users are female gender (β = 0.198), inadequate sleep (β = 0.150), lack of breakfast (β = 0.146), antihypertensive agent non-users (β = 0.134), and dinner just before bedtime (β = 0.129), whereas those for H₂RA users are inadequate sleep (β = 0.248), habit of midnight snack (β = 0.160), anticoagulants non-users (β = 0.106), and antihypertensive agents non-users (β = 0.095)., Conclusions: Among many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H₂RA in Japan cannot fully relieve GERD symptoms.

Susabinori (Porphyra yezoensis), a red alga, is cultured and processed into a sheet-style dried food, nori, in Japan. But significant amounts of cultured susabinori, which has a low protein content is discarded because of its low quality. The protein content of nori has been reported to be correlated inversely with the carbohydrate content. In this study, we examined the relationship between the protein content and the fermentation of nori by means of bfidobacteria. nori with a low protein content (25% on dry base) was strongly fermented by bifidobacteria, whereas nori with a high protein content (41% on dry base) was not. nori with a low protein content contained large amounts of glycerol galactoside (GG, floridoside: 2-O-glycerol-alpha-D-galactoside, isofloridoside: 1-O-glycerol-alpha-D-galactoside), more than 10% w/w in the dried condition, and GG was the main substrate for fermentation by bifidobacteria. GG was not digested by digestive enzymes, and was not absorbed in the small intestine. These results suggest that GG can be used as a substrate for fermentation by bifidobacteria, and possibility of GG as a prebiotic.

Background & Aims: Clinical significance of molecules involving innate immunity in treatment response remains unclear. The aim is to elucidate the mechanisms underlying resistance to antiviral therapy and predictive usefulness of gene quantification in chronic hepatitis C (CH-C)., Methods: We conducted a human study in 74 CH-C patients treated with pegylated interferon alpha-2b and ribavirin and 5 nonviral control patients. Expression of viral sensors, adaptor molecule, related ubiquitin E3-ligase, and modulators were quantified., Results: Hepatic RIG-I, MDA5, LGP2, ISG15, and USP18 in CH-C patients were up-regulated at 2- to 8-fold compared with nonhepatitis C virus patients with a relatively constitutive Cardif. Hepatic RIG-I, MDA5, and LGP2 were significantly up-regulated in nonvirologic responders (NVR) compared with transient (TR) or sustained virologic responders (SVR). Cardif and RNF125 were negatively correlated with RIG-I and significantly suppressed in NVR. Differences among clinical responses in RIG-I/Cardif and RIG-I/RNF125 ratios were conspicuous (NVR/TR/SVR = 1.3:0.6:0.4 and 2.3:1.3:0.8, respectively). Like viral sensors, ISG15 and USP18 were significantly up-regulated in NVR (4-fold and 2.3-fold, respectively). Multivariate and receiver operator characteristic analyses revealed higher RIG-I/Cardif ratio, ISG15, and USP18 predicted NVR. Lower Cardif in NVR was confirmed by its protein level in Western blot. Also, transcriptional responses in peripheral blood mononuclear cells to the therapy were rapid and strong except for Cardif in not only a positive (RIG-I, ISG15, and USP18) but also in a negative regulatory manner (RNF125)., Conclusions: NVR may have adopted a different equilibrium in their innate immune response. High RIG-I/Cardif and RIG-I/RNF125 ratios and ISG15 and USP18 are useful in identifying NVR.

Aim: To predict the therapeutic efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinomas, 5FU-related gene expressions were examined in primary colorectal carcinomas., Patients and Methods: Thirty-eight patients with liver metastases from colorectal carcinoma received HAI of 5FU. The expressions of the mRNAs for thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and oroteta phophoribosyl transferase (OPRT) in primary colorectal carcinomas were measured by RT-PCR., Results: The response rate was 52.6% (20/38). The overall median survival time was 29.1 months. DPD and TP expression was significantly higher in the progressive disease (PD) group than in the complete response (CR) or partial response (PR) group (p = 0.032, p = 0.014), respectively. The levels of DPD and TP mRNAs showed a significant correlation (r = 0.76, p = 0.0001)., Conclusion: The expression of DPD and TP mRNAs in primary colorectal carcinomas was significantly predictive of the therapeutic response to 5FU HAI.

Background: The characteristics of stage II gastric cancer according to the Japanese Classification of Gastric Cancer (JCGC) were examined and the high-risk factors predicting poor prognosis were detected., Patients and Methods: In total, 107 patients, who underwent clinically curative gastrectomy with D2 lymphadenectomy for stage II gastric cancer, were included. Survival curves of the depth of invasion, lymph node metastasis, the ratio of involved: resected lymph nodes and chemotherapy treatment were compared., Results: The survival curves were related to tumor invasion depth and lymph node metastasis. The ratio of involved resected lymph nodes was a good prognostic indicator compared to the classification of regional lymph node metastasis (N classification). Survival rates with adjuvant chemotherapy were slightly higher than without adjuvant chemotherapy, but the difference was not significant., Conclusion: pT2pN1 (stage II) gastric cancers according to the JCGC, especially pSSpN1 cases, included stage IIIB and IV gastric cancers according to the International Union Against Cancer / American Joint Committee on Cancer (UICC/AJCC); therefore, the prognosis of these might be poor. With pSSpN1 cases, according to the JCGC, anticancer chemotherapy equivalent to that required for stage III gastric cancer cases is necessary.