Resection depth for small colorectal polyps comparing cold snare polypectomy, hot snare polypectomy and underwater endoscopic mucosal resection.

Background and study aims Small colorectal polyps are removed by various methods, including cold snare polypectomy (CSP), hot snare polypectomy (HSP), and underwater endoscopic mucosal resection (UEMR), but the indications for using these methods are unclear. We retrospectively assessed the efficacy of CSP, HSP, and UEMR for small polyps, focusing on the depth of the resected specimens. Patients and methods Outpatients with non-pedunculated small polyps (endoscopically diagnosed as 6 to 9 mm), resected by two endoscopists between July 2019 and September 2020, were enrolled. We histologically evaluated the specimens resected via CSP, HSP, and UEMR. The main outcome was the containment rate of the muscularis mucosa (MM) and submucosa (SM) tissues. Results Forty polyps resected via CSP (n = 14), HSP (n = 12), or UEMR (n = 14) were enrolled after excluding 13 polyps with resection depths that were difficult to determine. The rates of specimens containing MM and SM tissue differed significantly (57 % and 29 % for CSP, 92 % and 83 % for HSP, and 100 % and 100 % for UEMR, respectively ( P  = 0.005 for MM and P  < 0.001 for SM tissue). Multiple logistic regression analysis showed UEMR was an independent factor relating to the containment of SM tissue. The thickness of SM tissue by CSP, HSP, and UEMR were 52 µm, 623 µm, and 1119 µm, respectively ( P  < 0.001). The thickness by CSP was significantly less than those by HSP and UEMR ( P  < 0.001, Bonferroni correction). Conclusions UEMR could be the best method to contain SM tissue without injection. Further studies are needed to evaluate the indication of UEMR for small polyps.

A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection.

A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC.

Strategy for Removing an Impacted Enterolith using Double-Balloon Enteroscopy in Crohn's Disease.

An enterolith in Crohn's disease is an uncommon but serious condition because it can cause intestinal obstruction. Endoscopic treatment to remove the enterolith is attempted first, but is sometimes difficult owing to poor accessibility of the endoscope. In such cases, surgical treatment is inevitable. We successfully overcame poor accessibility and removed an enterolith using double-balloon enteroscopy. We describe our method below and suggest several helpful techniques. LEARNING POINTS: Patients with Crohn's disease sometimes have a history of intestinal stricture, which can cause intestinal obstruction by enterolith-related impaction.Endoscopic treatment is the first choice to remove an enterolith, but is sometimes difficult.We successfully removed an enterolith using double-balloon enteroscopy and employing several helpful techniques.

Traumatic cervical vertebral artery dissection: A case with cerebral infarct due to newly formed thrombus in the cerebral arteries.

We report a 50-year-old man who developed fatal brainstem infarction five days after traumatic cervical vertebral artery dissection (CVAD). Autopsy revealed multiple fresh infarcts in the territory of the vertebrobasilar system. No thrombus was found in the infarct lesions. The cervical vertebral artery (CVA) showed severe atherosclerotic stenosis extending to the proximal half of the left side, similar stenosis at the origin on the right side, fresh thrombotic occlusion extending to the proximal half of the right side, and multiple dissections in the distal foraminal segments on both sides. In the distal half of the basilar artery (BA) and the origin of the right posterior cerebral artery (PCA), the lumen was extensively filled with fresh thrombus. Although an intricate mixture of white and red thrombi filled the lumen at the origin of the right PCA, the white thrombus gradually appeared at the periphery whereas the red thrombus occupied the central and more proximal part of the BA. We confirm that cerebral infarction associated with CVAD is due not only to emboli originating from the dislodged thrombus at sites of arterial dissection, as reported previously, but also to newly formed thrombus in the cerebral arteries caused by impaired blood flow, as was seen in the present case.

Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics.

BACKGROUND AND AIM: Although previous studies compared the efficacy of infliximab (IFX) versus adalimumab (ADA) as the first-line biologics for Crohn's disease (CD), the difference in long-term prognosis based on which biologic was used first has scarcely been reported. In particular, the clinical courses after loss of response (LOR) of the first-line biologics are largely unknown. METHODS: A multicenter, retrospective study was performed. Disease courses of biologic-naïve CD patients who were started on IFX or ADA treatment were evaluated, even after LOR of the initial biologics. RESULTS: In total, 263 CD patients were eligible for analysis, 183 were treated with IFX first, and 80 were treated with ADA first. The median observation period was 64.2 months. The cumulative steroid-free remission rates and surgery-free rates did not differ significantly between the patients treated with IFX first and those treated with ADA first (log-rank test P = 0.42 and P = 0.74, respectively). In addition, no significant difference was observed in the rate of occurrence of events associated with ineffectiveness (modification of anti-tumor necrosis factor treatment including intensification, switch, discontinuation, or surgery) between the patient groups (log-rank test P = 0.62). The patients treated with IFX first were likely to discontinue the agent due to adverse events, whereas those treated with ADA first were likely to discontinue due to treatment failure or LOR. CONCLUSIONS: No significant difference was observed in the long-term prognosis between biologic-naïve patients with CD who were started treatment with IFX first and ADA first.

Nintedanib in Japanese patients with idiopathic pulmonary fibrosis: A subgroup analysis of the INPULSIS® randomized trials.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia. Nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo in patients with IPF in two replicate trials (INPULSIS®). We examined the efficacy and safety of nintedanib in Japanese patients. METHODS: We conducted pre-specified subgroup analyses of the annual rate of decline in FVC, time to first acute exacerbation (AE), change from baseline in St George's Respiratory Questionnaire (SGRQ) total score and safety using pooled data from the INPULSIS® trials for Japanese patients. RESULTS: In the overall population, 76 of 638 and 50 of 423 patients in the nintedanib and placebo groups, respectively, were Japanese. Results in Japanese patients were consistent with those in the overall population. In Japanese patients, the adjusted annual rate of decline in FVC was -135.9 mL/year in the nintedanib group and -267.7 mL/year in the placebo group (difference (95% CI): 131.9 (50.7, 213.1) mL/year); the hazard ratio for the time to first AE was 0.25 (0.06, 1.02); and the adjusted mean change from baseline in SGRQ total score at week 52 was 5.81 in the nintedanib group and 9.68 in the placebo group (difference: -3.87 (-8.51, 0.76)). Diarrhoea and liver-related adverse events were the most common events in the nintedanib group, but were reversible following dose reduction, drug interruption or symptomatic therapy. CONCLUSION: The present results indicate that the efficacy and safety of nintedanib in Japanese patients are comparable with those in the overall population.

Subgroup analysis of Asian patients in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: In the two-replicate randomized Phase III INPULSIS® trials in patients with idiopathic pulmonary fibrosis (IPF), nintedanib 150 mg bd significantly reduced the annual rate of decline in forced vital capacity (FVC) compared with placebo. The key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in St George's Respiratory Questionnaire total score, both over 52 weeks. Here, we assessed the effect of nintedanib in Asian patients. METHODS: Pre-specified subgroup analyses of the effect of nintedanib on the primary and key secondary endpoints in Asian versus White patients were undertaken based on pooled data from the two INPULSIS® trials. Safety data were analyzed descriptively. RESULTS: Of the treated patients, 322 were Asian (nintedanib n = 194; placebo n = 128) and 608 were White (nintedanib n = 360; placebo n = 248). In Asian patients, the nintedanib versus placebo difference in the adjusted annual rate of decline in FVC was 94.1 mL/year (95% CI: 33.7, 154.6). The treatment effect of nintedanib on the annual rate of decline in FVC in Asian and White patients was similar (treatment-by-subgroup interaction P = 0.72) and consistent with the overall population. No significant treatment-by-subgroup interaction was observed for the key secondary endpoints between Asian and White patients. In Asian patients, the most common adverse event in the nintedanib group was diarrhoea (56.2% of patients vs 15.6% for placebo). CONCLUSION: In pre-specified subgroup analyses of Asian versus White patients with IPF in the INPULSIS® trials, race did not influence the effect of nintedanib on disease progression.

Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone.

Enteral nutrition improves health-related quality of life in Crohn's disease patients with long disease duration.

BACKGROUND/AIMS: Although enteral nutrition therapy has been highlighted as maintenance therapy for Crohn's disease, few reports have investigated the impact of enteral nutrition on the health-related quality of life of Crohn's disease patients. METHODOLOGY: We cross-sectionally evaluated the effect of multiple clinical factors including enteral nutrition on the health-related quality of life of Crohn's disease patients focusing on patient disease duration using the Inflammatory Bowel Disease Questionnaire. RESULTS: Of all 126 patients examined, 95 patients were receiving enteral nutrition. Multiple linear regression analysis using 18 clinical parameters revealed that disease activity was a dominant factor that affected the health-related quality of life of Crohn's disease patients, and that enteral nutrition was also an independent factor that improved the Inflammatory Bowel Disease Questionnaire total score, bowel symptoms, and systemic symptoms for patients with a disease duration of 10 years or more (P = 0.0090, 0.0033, and 0.016, respectively). CONCLUSIONS: Enteral nutrition improved the health-related quality of life of Crohn's disease patients with long-term disease duration. Thus, enteral nutrition should be recommended as one of the options for maintenance therapy for Crohn's disease.

[Fluorophothometric determination of aldehyde by utilizing condensation reaction with resorcinol].

A simple and sensitive fluorophotometric method for the determination of aldehyde was established by utilizing condensation reaction with resorcinol. In the determination of vanillin that is one of aldehydes, the calibration curve exhibited linearity over the vanillin concentration range of 3.0-7600 ng ml(-1) at an emission wavelength of 507 nm with an excitation of 410 nm and with the relative standard deviations (n=5) of 2.5%, 2.0% for 7.6 ng ml(-1), 760 ng ml(-1) of vanillin, respectively. This method was successfully applied in the assay of vanillin in cold medicine.

Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration.

BACKGROUND AND AIM: The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. METHODS: The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. RESULTS: Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. CONCLUSION: Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients.

Fluorophotometric determination of hydrogen peroxide and other reactive oxygen species with fluorescein hydrazide (FH) and its crystal structure.

Methods for the fluorophotometric determination of hydrogen peroxide (H(2)O(2)) and other reactive oxygen species (ROS) were proposed by using the fluorescence reaction between H(2)O(2) or other ROS and fluorescein hydrazide (FH). In the determination of H(2)O(2), the calibration curve exhibited linearity over the H(2)O(2) concentration range of 2.1-460 ng ml(-1) at an emission wavelength of 527 nm with an excitation of 460 nm and with the relative standard deviations (n=6) of 4.06%, 1.78%, and 2.21% for 3.1 ng ml(-1), 30.8 ng ml(-1), and for 308 ng ml(-1) of H(2)O(2), respectively. The detection limit for H(2)O(2) was 0.7 ng ml(-1) due to three blank determinations (rho=3). The calibration curves for ROS-related compounds were also constructed under the optimum conditions. This method was successfully applied in the assay of H(2)O(2) in human urine. In addition, we performed the characterization of FH, and interesting information was obtained with regard to the relationship between the chemical structure and fluorescence.

Risk factors for high-grade dysplasia or carcinoma in colorectal adenoma cases treated with endoscopic polypectomy.

OBJECTIVE: Our aim is to establish the risk factors for carrying high-grade dysplasia or carcinoma by analyzing endoscopically treated adenoma cases. METHODS: Patients who underwent endoscopic polypectomy at our hospitals between January 2003 and August 2004 were analyzed. RESULTS: A total of 889 patients (mean age: 63+/-11 years), and 1486 adenomas resected from these patients, were included in the analysis. Seventy-five adenomas (5%) from 72 patients (8%) were found to have high-grade dysplasia or carcinoma. Among patient factors, female sex [odds ratio (OR) 2.25, 95% confidence intervals (CI)=1.34-3.76], presence of multiple adenomas (OR=2.15, 95% CI=1.15-4.00), older age (OR=1.02, 95% CI=1.00-1.04), and rectal bleeding as the indication for colonoscopy (OR=2.57, 95% CI=1.34-4.92) were identified as the significant risk factors for carrying high-grade dysplasia or carcinoma using the multivariate analysis. In addition, a size of > or = 10 mm (OR=10.83, 95% CI=5.86-20.0), flat appearance (OR=3.91, 95% CI=2.20-6.95), and location on the left side of the colon (OR=1.80, 95% CI=1.03-3.13) were identified as tumor risk factors. CONCLUSION: Distinct factors were proved to be associated with high-grade dysplasia or carcinoma. These results are useful to select lesions that require immediate treatment. Moreover, female sex as a risk factor raises an interesting problem regarding the progression from adenoma to carcinoma.

Endoscopic mucosal resection of primary anorectal malignant melanoma: a case report.

Anorectal melanoma is a rare malignant tumor with a poor prognosis. However, several studies have reported cases of long-term survival. In this report, we present a patient with anorectal melanoma who has survived for 9 years after endoscopic mucosal resection. An 85-year-old man was referred to our hospital for further examination and treatment of an anal tumor 2 cm in size. Endoscopic ultrasonography revealed that the depth of tumor invasion was confined to the submucosal layer. Endoscopic mucosal resection was performed, and the tumor was diagnosed as a malignant melanoma. The patient was followed without any additional treatment, which was per his wishes. Although melanoma recurred 4 times thereafter, endoscopic mucosal resection was performed for each recurrent lesion. Thus, he has been alive for 9 years since the first endoscopic mucosal resection without distant metastases. If the depth of tumor invasion is shallow, endoscopic mucosal resection is a useful option among other therapeutic modalities.

Endoscopic stent placement for treatment of secondary bilateral occlusion of the Monro foramina following endoscopic third ventriculostomy in a patient with aqueductal stenosis. Case report.

Nontumoral bilateral occlusion of the Monro foramina is a rare clinical condition. Treatment includes shunt placement, endoscopic procedures, or both. The authors describe the case of a 22-year-old woman who had previously undergone placement of a ventriculoperitoneal shunt via a right frontal approach for management of triventricular dilation due to aqueductal stenosis. Six years postoperatively she presented with right-sided slit-ventricle syndrome and stenosis of the right Monro foramen, which was treated with an endoscopic third ventriculostomy and fenestration of the septum pellucidum. Two years later she presented with bilateral lateral ventricular dilation. Inspection of the right lateral ventricle with a fiberscope revealed occlusion of the septum pellucidum fenestration; on observation, the right Monro foramen was covered by thick, tough granulation tissue and the left was occluded by thin membranous tissue. Repeated fenestration of the septum pellucidum and left Monro foraminoplasty were therefore performed by perforating this thin tissue. A stent was then introduced into the third ventricle via the right lateral ventricle, the fenestration in the septum pellucidum, and the left Monro foramen. The authors note that fiberscopes are in general more maneuverable than rigid endoscopes and conclude that they are particularly useful for the treatment of this type of hydrocephalus.

Spectrophotometric determination of oxalate ion with N,N'-diethyl-N,N'-[[4,4'-dihydroxy-1,1'-binaphthalene]-3,3'-diyl]bisbenzamide and copper(II).

A simple and rapid spectrophotometric method for the determination of oxalate ion was established by the fading of a colored complex between N,N'-diethyl-N,N'-[[4,4'-dihydroxy-1,1'-binaphthalene]-3,3'-diyl]bisbenzamide and copper(II). Beer's law was obeyed in the concentration range of 0.1 - 2.0 microg cm(-3) for oxalate ion, with an effective molar absorptivity at 533 nm and the relative standard deviation being 8.0 x 10(3) dm(3) mol(-1) cm(-1) and 1.0% (n = 5), respectively. This proposed method has excellent reproducibility, and was applied to recovery tests of oxalate ion in tap water and human urine; the results were satisfactory. This is suggested that the method is based on the reaction of copper(II) to copper(I) with oxalate ion.

Change of clinical characteristics of ulcerative colitis in Japan: analysis of 844 hospital-based patients from 1981 to 2000.

BACKGROUND: Although the number of ulcerative colitis patients has increased rapidly in Japan, few reports have been published regarding their clinical aspects. We investigated the clinical characteristics and chronological change of ulcerative colitis in Japanese patients. METHODS: Patients diagnosed with ulcerative colitis during the period from 1981 to 2000 were registered and their clinical profiles were analyzed. The chronological changes in clinical aspects, such as onset age, sex distribution, severity, extent of disease, clinical course, and corticosteroid use, were also determined. RESULTS: A total of 844 patients were registered, composed of 431 men and 413 women, with a median onset age of 34 years. The proportion of mild colitis and proctitis was significantly larger in patients with an onset at over 60 years of age, relative to those with an onset at less than 30 years (P<0.016). The proportion of ulcerative colitis patients with old age onset (P=0.09), male sex (P<0.01), mild colitis (P<0.01), proctitis (P<0.01), one-attack-only type (P<0.01), and not-treated-with-corticosteroid (P<0.01) demonstrated a chronological increase from 1981 to 2000. CONCLUSIONS: The distinctive clinical features and chronological change were seen in Japanese ulcerative colitis patients in recent years. Our data can help understand clinical aspects of ulcerative colitis patients in Asia, where the incidence of ulcerative colitis is still increasing.

Risk factors and indications for first surgery in Crohn's disease patients.

BACKGROUND/AIMS: Despite appropriate medical treatment, a large part of CD patients undergo surgery. In this study, we aimed to identify the risk factors and indications for first surgery in CD patients. METHODOLOGY: The clinical records of 289 consecutive Japanese CD patients treated at 23 hospitals between January 1981 and August 2003 were reviewed. Clinical factors, including gender, age at onset, year at onset, and disease extent were examined, in order to identify the risk factors for first surgery. In addition, indications for first surgery were investigated, and stratified by these risk factors. RESULTS: A total of 113 (39%) patients underwent surgery at least once. Female gender (RR, 1.62; 95% CI, 1.09-2.41), and disease affecting the ileum (RR, 2.06; 95% CI, 1.20-3.53) were identified as the independent risk factors for surgery. In addition, female CD patients were more likely to undergo first surgery due to the indication of perforation than male patients (25% vs. 6%, p=0.006). Recent clinical and demographic changes of Japanese CD patients, such as increases in female and aged patients, did not affect the surgical risk factors and indications. CONCLUSIONS: Female CD patients should be consulted with special attention to the high risk of surgery due to perforation.