Ligand release from silicon phthalocyanine dyes triggered by X-ray irradiation.

Ligand release from silicon phthalocyanine (SiPc) dyes triggered by near-infrared (NIR) light is a key photochemical reaction involving caged compounds based on SiPc. Although NIR light is relatively permeable compared with visible light, this light can be attenuated by tissue absorption and scattering; therefore, using light to induce photochemical reactions deep inside the body is difficult. Herein, because X-rays are highly permeable and can produce radicals through the radiolysis of water, we investigated whether the axial ligands of SiPcs can be cleaved using X-ray irradiation. SiPcs with different axial ligands (alkoxy, siloxy, oxycarbonyl, and phenoxy groups) were irradiated with X-rays under hypoxic conditions. We found that the axial ligands were cleaved via reactions with hydrated electrons (e-aq), not OH radicals, generated from water in response to X-ray irradiation, and SiPc with alkoxy groups exhibited the highest cleavage efficiency. A quantitative investigation revealed that X-ray-induced axial ligand cleavage proceeds via a radical chain reaction. The reaction is expected to be applicable to the molecular design of X-ray-activatable functional molecules in the future.

Efficient Colonoscopic Identification of Colonic Bleeding Diverticulum Using Intradiverticular Water Injection with a Nontraumatic Tube.

OBJECTIVES: The colonoscopic identification of stigmata of recent hemorrhage (SRH) in patients with colonic diverticular bleeding (CDB) is difficult. Factors that influence the identification of SRH in the diagnosis of CDB were investigated. METHODS: This was a retrospective study of 487 early colonoscopy patients with acute lower gastrointestinal bleeding who were diagnosed with CDB. Comorbidities, medications, bowel preparation, use of a transparent cap, use of a water-jet scope, colonoscopy by an expert colonoscopist, and use of a nontraumatic (NT) tube were assessed. A multivariate analysis was used to estimate the odds ratio and 95% confidence interval. RESULTS: Of the 487 colonoscopy patients diagnosed with CDB, 191 (39%) were definitively identified with SRH. The use of a transparent cap, a water-jet scope, an expert colonoscopist, and an NT tube were independent predictive factors for SRH on univariate analysis. A multivariable logistic regression model showed that colonoscopy by an expert colonoscopist and the use of an NT tube were predictive factors for SRH. CONCLUSIONS: Intradiverticular water injection with an NT tube by an expert colonoscopist is useful in identifying CDB, and may help achieve effective endoscopic hemostasis.

A novel mask to prevent aerosolized droplet dispersion in endoscopic procedures during the coronavirus disease pandemic.

ABSTRACT: Endoscopic procedures increase the risk of transmission of severe acute respiratory syndrome coronavirus 2 to medical staff, because aerosols are generated during upper gastrointestinal endoscopy. There have been several reported studies on devices for infection prevention; however, few reports have validated them. Therefore, we developed a novel mask to prevent the diffusion of aerosol droplets from patients undergoing endoscopy.We compared microdroplet dispersion during coughing episodes when using the novel mask with microdroplet dispersion when using the conventional mouthpiece alone.The mean number of microdroplets was significantly smaller in the group that used the novel mask (57.9 ±â€Š122.91 vs 933.6 ±â€Š119.80 droplets; P = .01).The novel mask may aid in reducing the degree of exposure of medical personnel to microdroplets and the risk of subsequent infection.

Risk Factors for Late Rebleeding of Colonic Diverticular Bleeding in Elderly Individuals.

OBJECTIVES: This study aimed to examine the clinical characteristics of colonic diverticular bleeding (CDB) in elderly individuals. METHODS: This retrospective case-control study was conducted at a single tertiary center. A total of 519 patients (356 men and 163 women; mean age of 73.1 ± 12.5 years) with CDB and hospitalized between January 2004 and May 2019 were analyzed. The subjects were divided into two groups: the elderly (274 individuals aged ≥75 years; mean age, 82.1 ± 5.3 years) and non-elderly (245 individuals aged <75 years; mean age, 63.0 ± 10.3 years) groups. Primary outcomes were early and late rebleeding rates, and secondary outcomes were the risk factors for late rebleeding in elderly individuals. Rebleeding occurring within 30 days of hospitalization was defined as early rebleeding, whereas rebleeding occurring after 31 days was defined as late rebleeding. RESULTS: The early rebleeding rates were 30.6% and 33.1% (p = 0.557) in the elderly and non-elderly groups, respectively. The late rebleeding rates were 42.3% and 30.6% (p = 0.005) in the elderly and non-elderly groups, respectively. The 3-year recurrence-free survival was 63.6% in the elderly group and 75.6% in the non-elderly group (log-rank test: p < 0.001). Multivariate analysis revealed the use of non-steroidal anti-inflammatory drugs (NSAIDs) [odds ratio (OR), 3.55], chronic kidney disease (OR, 2.89), and presence of bilateral diverticula (OR, 1.83) as the independent risk factors for late rebleeding in elderly individuals. CONCLUSIONS: Elderly individuals with CDB require careful follow-up even after discharge. Furthermore, it is important to consider discontinuing NSAIDs to prevent rebleeding.

Risk factors of interventional radiology/surgery for colonic diverticular bleeding.

BACKGROUND AND AIM: Colonic diverticular bleeding (CDB) stops spontaneously, but sometimes, excessive bleeding does not allow hemostasis and requires interventional radiology (IR)/surgery. We examined risk factors in patients who required IR/surgery for CDB and late recurrent bleeding rate after IR/surgery. METHODS: This retrospective case-control study was conducted at a tertiary center. We included 608 patients who required hospitalization for CDB. Patients were investigated for risk factors using logistic regression analysis. We also investigated early and late recurrent bleeding rates following IR/surgery. RESULTS: In 261 patients (42.9%), the bleeding source was identified, and endoscopic hemostasis was performed; 23 (3.8%) required IR/surgery. In multivariate analysis, shock state with a blood pressure of ≤90 mmHg (P < 0.001; odds ratio [OR], 20.1; 95% confidence interval [CI], 5.08-79.5), positive extravasation on contrast-enhanced computed tomography (P < 0.001; OR 9.5, 95% CI 2.85-31.4), two or more early recurrent bleeding episodes (P = 0.002; OR 7.4, 95% CI 2.14-25.4), and right colon as the source of bleeding (P = 0.023; OR 4.1, 95% CI 1.25-14.0) were independent risk factors requiring IR/surgery. Early recurrent bleeding was observed in 0% and 28.0% patients (P < 0.001) in the IR/surgery and no IR/surgery groups, respectively, whereas late recurrent bleeding rate was observed in 43.4% and 30.7% patients (P = 0.203) in the IR/surgery and no IR/surgery groups, respectively. Four patients who required surgery experienced late recurrent bleeding at a site different from the initial CDB. CONCLUSIONS: Although IR/surgery is an effective hemostatic treatment wherein endoscopic treatment is unsuccessful, late recurrent bleeding cannot be prevented.

Tip-in endoscopic mucosal resection for large colorectal sessile polyps.

BACKGROUND: Tip-in endoscopic mucosal resection (EMR) is a modified EMR technique using which en bloc resection of large colorectal sessile polyps can be performed; however, its usefulness for colorectal sessile polyps of > 20 mm has not been reported. This study examined treatment outcomes of tip-in and conventional EMR for large colorectal sessile polyps of ≥ 20 mm. METHODS: This was a retrospective case-control study conducted at a single tertiary center in Japan. Subjects included those with large colorectal sessile polyps of ≥ 20 mm, excluding pedunculated-type polyps, who underwent endoscopic resection between January 2010 and January 2019. The primary outcome was endoscopic treatment outcomes when using tip-in and conventional EMR, and the secondary outcome was the local recurrence rate after endoscopic treatment. RESULTS: Forty-three colorectal lesions were treated using tip-in EMR and 83 using conventional EMR. Tip-in EMR had a significantly higher en bloc resection rate (90.7% vs. 69.8.%), and significantly shorter treatment duration (6.64 ± 0.64 min vs. 10.47 ± 0.81 min) than conventional EMR. However, for lesions > 30 mm, en bloc resection rate was 50.0% and 52.6% for tip-in and conventional EMR, respectively, indicating no significant difference. Perforation rates with tip-in and conventional EMR were 4.6% and 3.6%, respectively, indicating no significant difference. Local recurrence was examined in 80 cases who were followed up for > 6 months after endoscopic resection; recurrence rate was 0% and 7.0% in tip-in and conventional EMR cases, respectively, without significance difference. CONCLUSIONS: Tip-in EMR showed high en-block resection rate, particularly in polyps of < 30 mm, and no residual tumor was found. This technique is a potential endoscopic treatment alternative for large colorectal sessile polyps of ≥ 20 mm.

Predicting a rapid response to adalimumab treatment and favorable short-term outcomes through the high platelet count in patients with ulcerative colitis: A multicenter retrospective cohort study.

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 10/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.

Non-tuberculous Mycobacterial Pseudo-outbreak of an Intestinal Culture Specimen Caused by a Water Tap in an Endoscopy Unit.

Objective Gastrointestinal lesions of non-tuberculous mycobacteria (NTM) are regarded as opportunistic infections. A large number of positive specimens of NTM were identified in an intestinal fluid culture in the endoscopy unit and it was considered to be a pseudo-outbreak. Methods We reviewed the hospital, laboratory, and colonoscopy records of 263 consecutive patients whose intestinal fluids were analyzed for a mycobacterial culture by colonoscopy at St. Marianna University Hospital, between January 2009 and December 2018. The endoscopy reprocessing procedures were reviewed and samples of water used in the endoscopy unit were cultured. Results An intestinal fluid culture of 154 (58.6%) patients tested positive for NTM (M. intracellulare; 125 cases, M. gordonae; 14 cases, M. avium; 4 cases, M. abscessus; 3 cases, and 8 other cases). In 182 cases (69.2%), an intestinal mucosal culture was performed simultaneously with a fluid culture and tested positive for NTM in 2 cases. Next, we examined the endoscopy unit for any possible environmental contamination. NTM were detected in the tap water used to prepare the antifoaming solution in the endoscopy unit. The water faucets in the endoscopy unit were considered to be the source of the contamination of NTMs. Conclusion We observed that a large number of cases tested positive due to contaminated water that had been used in an endoscopy unit, thus leading to a pseudo-outbreak of NTM.

Intra-abdominal bleeding as a rare complication after colonic endoscopic mucosal resection in a patient taking direct oral anticoagulants.

We describe the case of an 84-year old female who was taking rivaroxaban 30 mg/day and had a medical history of atrial fibrillation. She underwent endoscopic mucosal resection of a 5-mm adenoma located in the hepatic flexure of the transverse colon. Following the procedure, she developed gradually intensifying abdominal pain, with the appearance of small amount of blood in the feces. For that reason, she visited our facility on the 5th day post-endoscopic mucosal resection. At the time of the visit, contrast-enhanced abdominal computed tomography revealed no extravasation or free air; however, bloody ascites was confirmed in the peritoneal cavity. Thus, the patient was diagnosed with post-endoscopic mucosal resection intra-abdominal hemorrhage and hospitalized the same day. After admission, rivaroxaban was discontinued and patient condition monitored. Because subsequent abdominal computed tomography revealed no distinct increase in bloody ascites, no interventional radiological or surgical procedure was performed, and the patient was discharged after providing only conservative treatment. While hemorrhage and perforation are the main complications after colonic endoscopic mucosal resection, so far, there have been a few reports on the occurrence of intra-abdominal hemorrhage following endoscopic mucosal resection. Emergency treatment is sometimes required in patients with intra-abdominal hemorrhage. It is important to keep in mind that this complication, although very rare, may occur, particularly in patients taking anticoagulants.

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn's disease.

BACKGROUND: Small bowel stricture is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD. METHODS: Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available. RESULTS: A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation. CONCLUSIONS: In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.

Delayed perforation after endoscopic band ligation for colonic diverticular hemorrhage.

A 77-year-old woman presented with the chief complaint of large amounts of hematochezia. Contrast-enhanced computed tomography (CT) revealed extravasation of contrast medium from the diverticula in the sigmoid colon; therefore, upon diagnosis of sigmoid colonic diverticular hemorrhage, she was immediately admitted to our hospital. Emergency colonoscopy revealed active bleeding from the diverticula in the sigmoid colon; hemostasis was achieved with endoscopic band ligation (EBL). However, 4 days later, she suddenly developed severe abdominal pain while defecation, prompting the requirement for obtaining a CT scan, which revealed intraabdominal free air, and delayed perforation after EBL was diagnosed. Emergency surgery was immediately performed; the perforation site was closed with sutures. EBL is useful in achieving hemostasis for colonic diverticular hemorrhage; however, it carries the risk of serious complications, such as delayed perforation, which require surgery. Although EBL is useful to achieve hemostasis for diverticular hemorrhage in the colon, it is preferable to carefully judge its indication owing to the risk of serious complications.

Daclatasvir and asunaprevir improves health-related quality of life in Japanese patients infected with hepatitis C virus.

AIMS: Interferon-free direct-acting antiviral agent (DAA) regimens for chronic hepatitis C virus (HCV) patients have improved their health-related quality of life (HRQOL). Currently, there are no published data assessing the impact of DAAs regimens without sofosbuvir on HRQOL. The aim of this study was to investigate the improvement of HRQOL in Japanese HCV patients treated with a protease inhibitor and a nonstructural protein 5A inhibitor. METHODS AND RESULTS: A total of 123 Japanese genotype 1b HCV patients receiving daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks were enrolled. HRQOL was assessed using the Japanese version of the Chronic Liver Disease Questionnaire (CLDQ) at baseline; weeks 4, 12, and 24; and post-24 weeks. Changes in CLDQ scores were calculated by subtracting the CLDQ score at each time point from the baseline value. Improvement in the mean change of the Japanese version of the CLDQ score became statistically significant as early as week 4 after the initiation of treatment (+9.3%; P < 0.0001) and was sustained during and after DCV/ASV treatment. The changes of CLDQ at posttreatment week 24 in patients with sustained virological responses (SVR) were significantly higher than those in patients without SVR (0.4% and -4.1%, respectively; P < 0.05). CONCLUSIONS: This study of DCV/ASV treatment for Japanese HCV patients in a clinical setting demonstrated that HRQOL can improve as early as at the initiation of treatment and can continue during and after treatment, regardless of the classes of DAAs regimens and race. Moreover, SVR are needed to continue HRQOL improvement.

Endoscopic small-capacity forceps increase the pathological diagnosis of gastric indefinite neoplasia.

BACKGROUND/AIMS: A definitive biopsy-based diagnosis of gastric cancer is sometimes difficult, and some cases are pathologically diagnosed as gastric indefinite neoplasia (GIN). The most appropriate forceps size for gastric biopsy has yet to be determined. In this study, we investigated the relation between the forceps size and the frequency of GIN diagnosis. MATERIALS AND METHODS: The records of patients from two historical groups were reviewed. The first group comprised patients evaluated during the period when standard biopsy forceps (StF) were used (April 2010-March 2011), and the second group comprised patients evaluated during the period when small biopsy forceps (SmF) were used (April 2011-March 2013). Patients in whom GIN lesions were diagnosed with biopsy were identified, and pertinent data were compared between the two groups of patients. RESULTS: Among the 8,420 patients who underwent esophagogastroduodenoscopy (EGD) during the first period, 2,584 (30.7%) underwent gastric biopsy with StF. Among the 15,968 patients who underwent EGD during the second period, 4,204 (26.3%) underwent gastric biopsy with SmF. GIN was diagnosed in a significantly greater number of patients in the SmF group than in the StF group (52 [1.25%] vs. 19 [0.73%]; p=0.048). The mean minor-axis lengths of the biopsy samples were 1.50±0.50 mm and 1.38±0.40 mm in the StF group and the SmF group, respectively, with the SmF group samples tending to be shorter (p=0.088). CONCLUSION: Because the SmF use may increase the rate of GIN diagnosis, the use of SmF with a standard-caliber endoscope should be avoided.

Successful endoscopic fragmentation of large hardened fecaloma using jumbo forceps.

We present a rare case of fecaloma, 7 cm in size, in the setting of systemic scleroderma. A colonoscopy revealed a giant brown fecaloma occupying the lumen of the colon and a colonic ulcer that was caused by the fecaloma. The surface of the fecaloma was hard, large and slippery, and fragmentation was not possible despite the use of various devices, including standard biopsy forceps, an injection needle, and a snare. However, jumbo forceps were able to shave the surface of the fecaloma and break it successfully by repeated biting for 6 h over 2 d. The ability of the jumbo forceps to collect large mucosal samples was also appropriate for achieving fragmentation of the giant fecaloma.

A case of Takayasu's arteritis detected in a patient with Crohn's disease following infliximab treatment.

A 19-year-old male with diarrhea, abdominal pain, fever, and elevated C-reactive protein (CRP) levels was admitted to our hospital. Endoscopic examination and small intestinal contrast radiography revealed multiple longitudinal ulcers in the large intestine and ileum. A specimen biopsied from one of these ulcers revealed non-caseating epithelioid cell granuloma. He also had a draining anal fistula. Plain chest computed tomography (CT) and abdominal contrast-enhanced CT did not reveal any vascular abnormality. A diagnosis of Crohn's disease was made, and infliximab was administered. Following infliximab administration, the diarrhea and abdominal pain disappeared, longitudinal ulcers in the large intestine healed (as evidenced by endoscopic examination), and his anal lesion improved. However, fever and elevated CRP levels persisted. With the concomitant use of prednisolone, the fever and elevation of CRP levels eventually improved, and the patient was discharged. Both, however, recurred as the patient was weaned off prednisolone treatment; consequently, he was re-hospitalized. Contrast-enhanced CT upon re-admission revealed stenoses of the right renal artery, left common carotid artery, and left subclavian artery. In addition to Crohn's disease, the patient was diagnosed with co-existing Takayasu's arteritis.

Hemostasis Achieved Endoscopically for Diverticular Bleeding from the Horizontal Portion of the Duodenum.

Diverticulum of the horizontal portion of the duodenum is a rare cause of upper gastrointestinal (GI) bleeding. Since it is difficult to access the horizontal portion of the duodenum by standard upper GI endoscopy, only a very few cases of endoscopic hemostasis have been reported. Herein, we report a case of diverticular bleeding from the horizontal portion of the duodenum for which hemostasis was achieved using a small-caliber colonoscope, which has an insertion part designed with a passive-bending function/high-force transmission and a transparent tip hood.

Treatment and prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy.

Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors (PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.

An updated review of gastric cancer in the next-generation sequencing era: insights from bench to bedside and vice versa.

Gastric cancer (GC) is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs. Recent studies using next-generation sequencing (NGS) have revealed a number of potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4, a member of the cadherin gene family. Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in 47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC. Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery, such as DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs and microRNAs. Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings. The anti-human epidermal growth receptor 2 (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In addition, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2, is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after first-line chemotherapy. Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets, as well as useful biomarkers. In this review, we will summarize the recent advances in the understanding of the molecular pathogenesis of GC, focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.