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Yuri Iwata,1 Yumiko Iwata,2 Hiroshi Iida,1 Masahiko Inamori,1 Shin Maeda3 1Department of Medical Education, Yokohama City University, Yokohama, Japan; 2Department of English Language, Communication and Cultures, University of the Sacred Heart, Tokyo, Japan; 3Department of Gastroenterology, Yokohama City University, Yokohama, JapanCorrespondence: Yuri Iwata, Department of Medical Education, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan, Tel +81-45-787-2626, Fax +81-45-787-2620, Email yuri.sagamed@gmail.comAim: To report on the effects of a smartphone application, among the medical staff and medical students, for learning English as a foreign language.Methods: We conducted an exploratory quasi-experimental study among eight medical staff and 10 medical students in Japan. The participants used an application called ABC Talking (created by ABC Talking Laboratories Inc, currently unavailable due to application renewal), loaded onto their smartphones, to talk with native English speakers from overseas. The participants used the application for five minutes twice a day over five consecutive days as per their convenience. The study collected quantitative and qualitative data using assessments on the participants’ listening and speaking skills and questionnaire. The assessment scores of the first five sessions were compared to those of the last five. Average self-assessment scores and teacher assessment scores were compared using a t-test. A paired t-test was performed on quantitative data of the questionnaire, and content analysis was performed on qualitative data.Results: More than 80% of the calls were made from home and 70% occurred between 9PM and 1AM. The participants’ self-assessment scores on their listening and speaking skills increased significantly from the first five sessions to the last five sessions (14.8– 26.1%). However, there was no significant change in the assessments by the teachers (− 4.5– 2.1%). The self-assessment scores of those with low English proficiency were lower than the teachers’ assessment scores. Improvement of communicative self-confidence and communicative competence, two factors that affect willingness to communicate, were seen from the questionnaire.Conclusion: Using smartphone applications allows on-demand English training, which may be especially useful to medical staff and students who have unpredictable work schedules. Teachers should be aware that learners tend to assess themselves lower than their actual ability so that they can give appropriate feedback to the learners.Keywords: limited English proficiency, communication, medical training, professional competence, language barrier

Toinvestigate liver carcinogenesis and other causes of death by collecting clinical data, including the Fib-4 index, from patients with successfully eradicated hepatitis C virus (HCV) by direct-acting antivirals (DAA) treatment.Patients ( n = 690), who achieved a sustained virologic response (SVR) between 2014 and 2021, were identified and followed up for approximately 6.8 years; 71 incident hepatocellular carcinoma (HCC) cases were identified. The Fib-4 index was calculated at DAA-treatment initiation and HCV eradication, and its relationship with carcinogenesis and prognosis was analyzed.The Fib-4 index was initially calculated and divided into three groups: Fib-41.45, 1.45 ≤ Fib-43.25, and 3.25 ≤ Fib-4 to develop HCC over time. On analysis, no carcinogenic cases were observed at Fib-41.45. In patients with a Fib-4 index ≥3.25, the initial HCC carcinogenic rate was higher than that in patients with Fib-4=1.45-3.25, and a significant difference was obtained between the two groups [ P = 0.0057 (1.45 vs.3.25); P = 0.0004 (1.45-3.25 vs.3.25)]. Regarding all 18 death and Fib-4 at treatment initiation, a significant difference was observed after stratification into two groups [Fib-43.25 and 3.25 ≤ Fib-4; P = 0.0136 (3.25 vs. ≥3.25)]. Significant differences were obtained in another analysis of 13 deaths, not due to HCC.The high Fib-4 index calculated at baseline and SVR12 significantly correlated not only with liver carcinogenesis but also with all mortality rates, including those due to causes other than liver cancer. Our findings suggest that improving liver fibrosis by eradicating HCV improves prognosis related to all etiologies.

Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD.This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed.In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mmDuodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

Diversion colitis and ulcerative colitis (UC) can be caused by different mechanisms; however, several case reports have described the development of typical UC following diversion colitis. A 63-year-old man underwent Hartmann's operation following a diagnosis of perforation of a sigmoid colon diverticulum and peritonitis. Stoma closure was performed 4 months later, and the portion of the sigmoid colon with the diverticulum was unintentionally left as a blind end. Following stoma closure, hematochezia worsened, and he was diagnosed as having developed diversion colitis only in the blind sigmoid colon. Intermittent use of topical mesalazine enemas controlled the bowel symptoms; however, 4 years after the stoma closure, bloody stools were observed again. Colonoscopy revealed coarse and friable granular mucosa with adherent mucopurulent exudate in the rectum, and mucosal erythematous edema with adherent mucopurulent exudate in the blind sigmoid colon. The histological findings indicated basal plasmacytosis, and goblet cell depletion and cryptitis in the lamina propria, which is characteristic of UC. To the best of our knowledge, this is the fourth description of a patient who developed UC following diversion colitis. Local inflammation may have triggered the development of UC through hematogenous or lymphogenous circulation of lymphocytes or autoantibodies.

Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC.We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes.We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p 0.99).ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Background Immune checkpoint inhibitors (ICIs) are effective for advanced hepatocellular carcinoma (HCC). However, there are few reports on the correlation between the clinical efficacy of ICIs and the development of immune-related adverse events (irAEs) in patients with HCC. The aim of this study was to investigate the association between irAE development and survival in patients with HCC treated with atezolizumab plus bevacizumab. Patients and Methods We enrolled 150 patients with advanced HCC treated with atezolizumab plus bevacizumab between October 2020 and October 2021 at 5 territorial institutions. We compared the efficacy of atezolizumab plus bevacizumab between patients who experienced irAEs (irAE group) and those who did not (non-irAE group). Results Thirty-two patients (21.3%) developed irAEs of any grade. Grade 3/4 irAEs were observed in 9 patients (6.0%). The median progression-free survivals (PFS) in the irAE and non-irAE groups were 273 and 189 days, respectively (P = .055). The median overall survivals (OS) in the irAE and non-irAE groups were not reached and 458 days, respectively (P = .036). Grade 1/2 irAEs significantly prolonged PFS (P = .014) and OS (P = .003). Grade 1/2 irAEs were significantly associated with PFS (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.166-0.691; P = .003) and OS (HR, 0.086; 95% CI, 0.012-0.641; P = .017) on multivariate analysis. Conclusion The development of irAEs was associated with increased survival in a real-world population of patients with advanced HCC treated with atezolizumab plus bevacizumab. Grade 1/2 irAEs were strongly correlated with PFS and OS.

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Background: Aberrant crypt foci (ACF) are considered to be useful as surrogate biomarker for colorectal cancer (CRC), but the biological significance of ACF remains controversial. We attempted to investigate the relationship between the presence of ACF and human colorectal carcinogenesis using a relatively large sample size.Methods: We carried out high-magnification chromoscopic colonoscopy to identify ACFs in 861 subjects undergoing a diagnostic endoscopy at the Yokohama City University Hospital. The present study compared the prevalence and number of ACFs in three subject groups (normal subjects, adenoma cases, and CRC cases). The correlations between the demographic and behavioral characteristics of the subjects and the prevalence of ACFs were also assessed.Results: The prevalence of ACF was 64%, 88%, and 95%, and the mean number of ACF was 3.6, 6.2, and 10.1, in normal subjects, adenoma cases, and CRC cases, respectively. When differences in the prevalence and number of ACFs among age- and sex-stratified subject groups were examined, significant stepwise increments from normal subjects to adenoma cases to CRC cases were apparent (P < 0.001). Moreover, an age- and sex-adjusted multiple logistic regression analysis revealed that smoking and alcohol habits had a synergistic effect, increasing the prevalence of ACFs as well as the risk of CRC (P < 0.001).Conclusions: These results suggested that ACF may serve as a reliable surrogate biomarker for human colorectal carcinogenesis.Impact: The use of ACF as an endpoint may enable the size, duration, and cost of CRC chemoprevention studies to be reduced. Cancer Epidemiol Biomarkers Prev; 20(9); 1918–24. ©2011 AACR.

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Supplementary Figures S1-S7 from Constitutive NF-κB Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth

Purpose: Nuclear factor κB (NF-κB) is an important transcription factor in various biological processes. Constitutive NF-κB activation has been noted in many tumors, including colorectal cancers. However, the precise role of this activation in colorectal cancer is unclear.Experimental Design: Constitutive NF-κB activation was evaluated in colorectal cancer tissues and cell lines. To inhibit NF-κB activation, we established cancer cells with stable knockdown of IκB kinase γ (NF-κB essential modulator), which is the regulatory subunit of the IκB kinase complex, by RNA interference. Cell growth and apoptosis were evaluated in wild-type cells (WT) and knocked-down cells (KD). Microarray and protein array analysis were also done. To determine involvement of angiogenesis, human umbilical vein endothelial cells were used. By s.c. transplantation of the cells into nude mice, tumor sizes, vascularity, and chemodrug sensitivity were analyzed.Results: Constitutive NF-κB activation was observed in 40% of colorectal cancer tissues and 67% of cell lines. Cell proliferation was not different between WT and KD in vitro, whereas apoptosis mediated by tumor necrosis factor-α and 5-fluorouracil were increased in KD. Several angiogenic chemokines were decreased in KD. Human umbilical vein endothelial cells incubated in WT supernatant showed more branch points than in KD, suggesting that constitutive NF-κB activation was involved in angiogenesis. Subcutaneous tumor expansion was suppressed to 23% in KD, and vessels were also decreased. By 5-fluoruracil treatment, tumor expansion was suppressed to a greater extent in KD (to 6%) than in WT (to 50%).Conclusion: NF-κB inhibition may represent a potent treatment modality in colorectal cancer, especially in cases with constitutive NF-κB activation.

Supplementary Figure 1 from c-Jun NH2-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

c-Jun NH2-terminal kinase (JNK) links several cellular processes, including proliferation and survival, and is believed to be involved in carcinogenesis. However, the role of JNK in gastric tumorigenesis is unknown. Immunohistochemical analysis reveals that JNK is frequently activated in human gastric cancer tissue. We investigated whether JNK1, a major JNK isozyme, is involved in chemically induced gastric cancer development. Mice lacking JNK1 exhibited a marked decrease in gastric carcinogenesis induced by N-methyl-N-nitrosourea, relative to their wild-type counterparts. Impaired tumor development correlated with decreased tumor initiation, which is associated with the production of reactive oxygen species. We also found that lower levels of tumorigenesis were correlated with the decreased expression of cyclin D and CDK as well as decreased cell proliferation. Taken together, JNK seems to be involved in both tumor initiation and promotion and may be an attractive target for the prevention of gastric carcinogenesis. [Cancer Res 2008;68(13):5031–9]

Supplementary Figure 2 from c-Jun NH2-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

Background Gastric tube cancer (GTC), whose usual histology is adenocarcinoma, occurs frequently as a result of improved survival after esophagectomy. Whether endoscopic resection (ER) for GTC is safe and suitable and guidelines for treatment and follow-up remains unclear. Methods Patients with GTC who underwent ER at Kanagawa Cancer Center Hospital between 1997 and 2020 were studied retrospectively to evaluate clinical characteristics and short- and long-term outcomes. Results Twenty-two consecutive patients with 43 lesions were treated in 42 sessions of ER. Lesions were discovered at a median of 9.0 (0–21.8) years after esophageal surgery. Nine (40.9%) patients had multiple lesions at the time of the initial ER session. However, six (54.5%) of the 11 co-existing lesions were overlooked. The location of the middle third was an estimated risk factor for overlooking (p = 0.028). In endoscopic submucosal dissection (ESD) cases, the en bloc dissection rate was as high as 97.1%, and the rates of bleeding, perforation, and aspiration pneumonitis were 17.6%, 0%, and 2.9%, respectively. The bleeding rate was relatively higher than that in usual gastric ESD. Twelve patients (54.5%) experienced synchronous and/or metachronous multiple GTCs during their life span. Thirteen (61.9%) patients died during the median follow-up period of 5.9 (0.7–15.5) years. One patient (7.7%) died of GTC recurrence, 15.4 years after the initial non-curative ER date; 3 (23.1%) patients died of esophageal cancer recurrence, and 3 (23.1%) died of other organ malignancies. The 5-year overall survival rate was 85.0%, and the 5-year disease-specific survival rate was 100%. Conclusions ER is feasible for GTCs. However, the rate of bleeding was high in ESD cases. Life-long endoscopic screening of metachronous lesions is desirable. Care should be taken not to overlook lesions in the middle third of the gastric tube. Early detection of esophageal cancer recurrence and other organ malignancies may improve prognosis.

Background and Aims: A hybrid technique may be a reasonable compromise to make endoscopic mucosal resection (EMR) more reliable for lesions ≥ 20 mm and a good way of approaching to endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy and safety of a novel hybrid EMR technique, triple-anchoring EMR (T-EMR) for colorectal lesions 20-30 mm.Methods: Fifteen patients have been prospectively enrolled to T-EMR from December 2019 to April 2020 in two Endoscopy Units: Policlinico A. Gemelli, Rome, and University Hospital of Udine, Italy. Patients eligible for the study were ≥18 years old with superficial colorectal lesions 20-30 mm, morphologically liable to endoscopic treatment based on chromoendoscopy. The primary endpoint was assessment of the “en bloc” and the free resection margins (R0) rates. The secondary endpoints were resected specimen size, procedure time, complication rate, and recurrence rate at 6 months.Results: Among the 15 patients enrolled, 12 were males (80%), mean age 68.73±11.04 years. The mean size of the lesions was 24.93±2.89 mm. Mean procedure time was 22.13±4.31 min. T-EMR was performed en bloc in 14/15 patients (93.3%) with R0 in 13/15 patients (86.7%). No major intra-/peri-procedural or delayed complications occurred. At histological analysis, 13/15 lesions (86.7%) were adenomas, while 2 were early colorectal cancer. At a 6-month follow-up colonoscopy, only one patient (6.7%) had a recurrence of adenoma.Conclusions: T-EMR seems to be an effective and safe option to treat colorectal lesions between 20 and 30 mm, with a short procedure time and low costs.

In this study, we investigated the impact of simple measurement of psoas muscle index (PMI) on the tolerability of sorafenib treatment of switch from sorafenib to regorafenib.This retrospective study enrolled 109 patients with Child-Pugh A hepatocellular carcinoma (HCC) treated with sorafenib. Pretreatment PMI was calculated by measuring and multiplying the greatest anterior/posterior and transverse diameters of the psoas muscles on axial computed tomography images at the L3 vertebral level, and normalizing the sum of bilateral psoas muscle areas by the square of the height in meters. We, then, statistically analyzed the association between PMI and adverse events (AEs) to treatment, tolerability of sorafenib, time to treatment failure (TTF), and prognosis in patients stratified according to PMI.Patients were divided into high PMI (n = 41) and low PMI (n = 68) groups based on the cutoff PMI values (men: 7.04 cm2/m2; women: 4.40 cm2/m2) determined by receiver operating characteristic curve analysis to determine sorafenib tolerability. Frequencies of all types of severe AEs were higher in the low PMI group (50.0%) than in the high PMI group (29.3%; P = 0.045). The high PMI group (51.2%) had greater tolerance to sorafenib than the low PMI group (25.0%; P = 0.007). Moreover, in multivariable analysis, PMI was associated with sorafenib tolerability (odds ratio 0.26; P = 0.008) and was a prognostic factor affecting TTF (hazard ratio 1.77; P = 0.021).PMI might be a predictive marker of tolerance to treatment and TTF in HCC patients receiving sorafenib treatment.

BACKGROUND Endoscopic resection, especially endoscopic submucosal dissection (ESD), is increasingly performed in elderly patients with early gastric cancer, and lesions beyond the expanded indications are also resected endoscopically in some patients. It is essential to assess whether gastric ESD is safe and suitable for elderly patients and investigate what type of lesions carry an increased risk of ESD-related complications. AIM To assess the efficacy and feasibility of gastric ESD for elderly patients, and define high-risk lesions and prognostic indicators. METHODS Among a total of 1169 sessions of gastric ESD performed in Kanagawa Cancer Center Hospital from 2006 to 2014, 179 sessions (15.3%) were performed in patients aged ≥ 80 years, and 172 of these sessions were done in patients with a final diagnosis of gastric cancer. These patients were studied retrospectively to evaluate short-term outcomes and survival. The short-term outcomes included the rates of en bloc resection and curative resection, complications, and procedure-related mortality. Curability was assessed according to the Japanese Gastric Cancer Treatment Guidelines 2010. Fisher’s exact test was used to statistically analyze risk factors. Clinical characteristics of each group were compared using Fisher’s exact test and Mann-Whitney U test. Survival rates at each time point were based on Kaplan-Meier estimation. Overall survival rates were compared between patients with gastric cancer in each group with use of the log-rank test. To identify prognostic factors that jointly predict the hazard of death while controlling for model overfitting, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model including factors curative/ noncurative, age, gender, body mass index, prognostic nutritional index, Charlson comorbidity index (CCI), Glasgow prognostic score, neutrophil-to-lymphocyte ratio, and antithrombotic agent use. We selected the LASSO Cox regression model that resulted in minimal prediction error in 10-fold cross-validation. P < 0.05 was considered statistically significant. RESULTS The en bloc dissection rate was 97.1%, indicating that a high quality of treatment was achieved even in elderly patients. As for complications, the rates of bleeding, perforation and aspiration pneumonitis were 3.4%, 1.1% and 0.6%, respectively. These complication rates indicated that ESD was not associated with a particularly higher risk in elderly patients than in nonelderly patients. A dissection incision > 40 mm, lesions associated with depressions, and lesions with ulcers were risk factors for post-ESD bleeding, and location of the lesion in the upper third of the stomach was a risk factor for perforation in elderly patients (P < 0.05). Location of the lesion in the lower third of the stomach tended to be associated with a higher risk of bleeding. The overall survival (OS) did not differ significantly between curative and noncurative ESD (P = 0.69). In patients without additional surgery, OS rate was significantly lower in patients with a high CCI (≥ 2) than in those with a low CCI (≤ 1) (P < 0.001). CONCLUSION Gastric ESD is feasible even in patients aged ≥ 80 years. Observation without additional surgery after noncurative ESD is reasonable, especially in elderly patients with CCI ≥ 2.

Background Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma. Methods We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m2), levo-leucovorin calcium (200 mg/m2) and 5-FU (2400 mg/m2) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated. Results At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1–4.8) and 1.3 months (95% CI, 1.0–1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3–4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010–4.107; p = 0.047) and 2.471 (95% CI, 1.063–5.745; p = 0.036), respectively. Conclusion FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels.

Background In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). Methods We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to Results During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to 3 months CFREM group compared with those in the other groups, but this difference was not significant. Conclusions A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.

Vonoprazan (VPZ), a new potassium-competitive acid blocker, has been approved and used for Helicobacter pylori eradication in Japan. To date, many studies, as well as several systematic reviews and meta-analyses (MAs), have compared VPZ-based 7-day triple therapy with proton pump inhibitor (PPI)-based therapy. An MA of randomized controlled trials (RCTs) comparing first-line VPZ- with PPI-based triple therapy, the latter featuring amoxicillin (AMPC) and clarithromycin (CAM), found that approximately 30% of patients hosted CAM-resistant H. pylori; however, the reliability was poor because of high heterogeneity and a risk of selection bias. VPZ-based triple therapy is superior to PPI-based triple therapy for patients with CAM-resistant H. pylori, but not for those with CAM-susceptible H. pylori. An MA of non-RCTs found that second-line VPZ-based triple therapies were slightly (~2.6%) better than PPI-based triple therapies (with AMPC and metronidazole). However, the reliability of that MA was also low because of selection bias, confounding variables and a risk of publication bias; in addition, it is difficult to generalize the results because of a lack of data on antibiotic resistance. VPZ-based triple therapy (involving AMPC and sitafloxacin) was more effective than PPI-based triple therapy in a third-line setting, but a confirmatory RCT is needed. Non-RCT studies indicated that VPZ-based triple therapy involving CAM and metronidazole may be promising. Any further RCTs must explore the antibiotic-resistance status when evaluating the possible superiority of a potassium-competitive acid blocker.

For an esophageal submucosal mass suspicious of granular cell tumor (GCT) based on gross appearance and endoscopic ultrasound findings, a sufficient number of biopsy specimens is required for a definite diagnosis using immunohistochemical examination. When the specimen obtained by forceps biopsy is insufficient, endoscopic ultrasound-fine needle aspiration (EUS-FNA) is believed to be an useful alternative. However, it may be difficult to obtain an adequate amount of tumor material using EUS-FNA. Mucosal incision-assisted biopsy (MIAB) is a simple method that can collect larger amounts of specimens. This procedure is helpful for physicians who encounter the problem of obtaining an adequate amount of biopsy material from esophageal tumors suspicious for GCT. We present a case of esophageal GCT that was successfully diagnosed through MIAB.

Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD.An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia.The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

The difficulty of life scale (DLS) instrument is used to measure specific life problems in patients with ulcerative colitis (UC). Importantly, health care providers should consider the characteristics of the country in which they support patients with UC. This cross-cultural comparison study investigated DLS among patients with UC in Japan and the United Kingdom (UK). Outpatients attending one hospital in London and one in Osaka were included. We collected patient information using the DLS questionnaire, which comprises 18 items in three domains. Mean differences between Japan and the UK were compared for the total score and each domain of the DLS. Variables with P.05 in univariate analysis were entered into a multiple regression model. We included 142 patients from Japan and 100 patients from the UK in the analysis. Univariate results showed that UK patients had more difficulties than Japanese patients in all three domains. Multivariate results showed that only "decline of vitality or vigor" showed significantly lower difficulty scores in Japanese patients. Having four or more bowel movements per day, visible bleeding, and being a homemaker or unemployed were significantly associated with greater difficulty according to the DLS total score. The level of daily life difficulties assessed using the DLS was greater among patients in the UK than among Japanese patients. This comparative study between patients with UC in Japan and the UK demonstrated certain country-related features for domain 3, "decline of vitality or vigor," of the DLS. The reasons why UK patients felt greater decline in vitality or vigor may be that these patients may have symptoms other than bowel symptoms; also, Japanese patients are more hesitant to express discomfort. The findings of this study might lead to a better understanding of culturally sensitive perceptions of daily life difficulties in UC.

Sarcopenia often affects patients with various types of cancer, and has been reported to affect patient prognosis and therapeutic effects. However, to the best of our knowledge, there are no reports on the relationship between gemcitabine plus nab-paclitaxel combination therapy (GnP) and sarcopenia in patients with unresectable pancreatic cancer. The present study analyzed the relationship between overall survival (OS), progression-free survival (PFS), response rate, disease control rate, adverse events (AEs) and sarcopenia in patients with pancreatic cancer treated with GnP. A total of 121 consecutive patients with advanced pancreatic cancer who received GnP as first-line chemotherapy between January 2015 and December 2017 were retrospectively analyzed. GnP consisted of 1,000 mg/m

Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Endoscopic ultrasonography has become a routine procedure in clinical practice and is widely accepted as a safe procedure. Previous studies have reported that severe bleeding rarely occurs even when performing fine-needle aspiration biopsy. Severe hemorrhage following non-interventional endoscopic ultrasonography has never been reported. We herein report a case of hemorrhagic shock due to hemoperitoneum caused by a ruptured right gastroepiploic artery consequent to a diagnostic endoscopic ultrasonography. The patient was administered two antithrombotic agents. An extensive diagnostic workup contributed to the correct diagnosis, which led to a successful treatment by transcatheter arterial embolization. Endoscopists should be aware of this rare, but potentially fatal, adverse event of endoscopic ultrasonography.

Backgrounds : Endoscopic full-thickness resection (EFTR) without laparoscopic assistance—pure EFTR—is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been applied outside of China due to concerns about pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing regarding its procedure. This study aimed to evaluate the efficacy and safety of endoscopic resection with one port placement (EROPP) for gastric GISTs. Methods This retrospective study included 14 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2021. One camera port was inserted in the umbilicus before starting the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layer around the lesion by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect with an over-the-scope-clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. Results All procedures were completed successfully without conversion to laparoscopic surgery. The median size of resected tumors was 23 mm (range, 10–35 mm) and the median procedure time was 37 min (range, 22–95 min). The rates of en bloc and curative resection were 100% and 86%, respectively. In two cases, another port was added to aspirate leaking fluid or to check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful and no adverse events were reported Conclusions EROPP is a safe and minimally invasive treatment for gastric GISTs and seems to be suitable as a pure EFTR procedure.

By analyzing possible factors contributing to imaging misevaluation of arterial phase (AP) vascularity, we aimed to provide a more proper way to detect AP hypervascularity of hepatocellular carcinomas (HCCs) using the noninvasive imaging modalities magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS). We retrospectively recruited 164 pathologically confirmed HCC lesions from 128 patients. Using CEUS with Sonazoid (SCEUS) and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid MRI (EOB-MRI), AP vascularity of the lesions was evaluated and inconsistencies in interpretation were examined. Indicators of margin, echogenicity, and halo and mosaic signs of lesions on grayscale US; depth of lesions on SCEUS; and tumoral homogeneity, signal contrast ratio of lesions to the surrounding area on precontrast and AP images on EOB-MRI, and histological grade were investigated. When precontrast images were used to adjust the AP enhancement ratio, the proportion of inconsistent interpretations of AP vascularity declined from 26.2% (43/164; 29 non-hypervascularity instances using EOB-MRI and 14 using SCEUS) to 16.5% (27/164; 7 using EOB-MRI and 20 using SCEUS). Greater lesion depth (P = 0.017), ill-defined tumoral margin (P = 0.028), absence of halo sign (P = 0.034), and histologically early HCC (P = 0.007) on SCEUS, and small size (P = 0.012) and heterogeneity (P = 0.013) of lesions and slight enhancement (low AP enhancement ratio) (P = 0.018 and 0.009 before and after adjustment) on EOB-MRI, may relate to undetectable hypervascularity. SCEUS and EOB-MRI may show discrepancies in evaluating AP vascularity in the case of deep, ill-defined, heterogeneous, slightly enhanced lesions, and histologically early HCCs. We recommend adjusting AP with precontrast images in EOB-MRI, and combining both modalities to detect hypervascularity.

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

BACKGROUND The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIM To investigate the reduction of HCC development due to ETV therapy by meta-analysis. METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019). RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log10IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log10IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment. CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

Superficial nonampullary duodenal epithelial tumors (SNADETs) have become frequently detected and referred for endoscopic resection (ER). However, optimal treatment methods and long-term outcomes after ER of SNADETs have not been fully elucidated. We aimed to clarify them by analyzing our large cohort of patients with SNADETs.We enrolled 190 consecutive tumors from 189 patients undergoing ER between January 2004 and September 2019. Cases were stratified into endoscopic submucosal dissection (ESD), conventional endoscopic mucosal resection, (CEMR) and underwater endoscopic mucosal resection (UEMR). Baseline characteristics and short-term outcomes were compared between the groups. Long-term outcomes were also investigated with a median follow-up of 36 months.ESD significantly exceeded CEMR (96.4% vs. 52.9%;While tumors ≤10 mm seem to be good indications for endoscopic mucosal resection, ESD should be considered for larger tumors to better achieve complete resection. Patients with submucosal invasive carcinomas have a great risk of cancer death. Therefore, a close follow-up and an additional treatment are desirable.

The Morisky Medication Adherence Scale is a clinically relevant tool used to evaluate medication adherence. In the current study, the validity and reliability of a Japanese version of the Morisky Medication Adherence Scale and factors related to low adherence were investigated in patients with ulcerative colitis. The original English version was translated into Japanese and then 3 institutions in Japan administered that Japanese version to 428 patients taking medication. Factor validity, internal consistency, and correlations between the Morisky Medication Adherence Scale and adherence were calculated on the basis of patients' own reports of skipped medication, and known group validity between clinically different groups was assessed. Logistic regression was used to assess relationships between low adherence and other factors. The Morisky Medication Adherence Scale identified 184 of 428 patients (43.0%) who exhibited low adherence. Confirmed factor analysis indicated one-dimensionality of the scale. Cronbach's α was 0.74. The Morisky Medication Adherence Scale score was significantly correlated with self-reported missed medication. Patients who were on concomitant induction therapy exhibited significantly better Morisky Medication Adherence Scale scores than those who were not. Patients with low adherence reported difficulty taking medicine, having proctitis, and ulcerative colitis duration of less than 5 years, and were of younger age. The Japanese Morisky Medication Adherence Scale yielded clinically relevant measures of adherence in patients with ulcerative colitis and may promote further international comparative studies.

Hepatocellular carcinoma (HCC) has the third-highest incidence in cancers and has become one of the leading threats to cancer death. With the research on the etiological reasons for cirrhosis and HCC, early diagnosis has been placed great hope to form a favorable prognosis. Non-invasive medical imaging, including the associated contrast media (CM)-based enhancement scan, is taking charge of early diagnosis as mainstream. Meanwhile, it is notable that various CM with different advantages are playing an important role in the different imaging modalities, or even combined modalities. For both physicians and radiologists, it is necessary to know more about the proper imaging approach, along with the characteristic CM, for HCC diagnosis and treatment. Therefore, a summarized navigating map of CM commonly used in the clinic, along with ongoing work of agent research and potential seeded agents in the future, could be a needed practicable aid for HCC diagnosis and prognosis.