[Investigation the contents of employment consultation and support in a cancer center hospital].

OBJECTIVES: This study aimed to analyze and categorize the actual situation of employment consultation and support according to consultation times or employment status at the Consultation Support Center of the National Cancer Center Hospital of Japan. METHODS: We retrospectively analyzed the patient backgrounds, consultation contents, and the number of employment consultation cases conducted at the Consultation Support Center of the National Cancer Center Hospital during a 6-month period from May to December 2018. RESULTS: During the study period, 117 patients (male: female = 46:71) visited the Consultation Support Center. The median age of patients was 48 years old. The most common primary cancer site was the breast in 28 patients followed by the lung in 16 patients, and then gynecologic cancer in 10 patients. The most common cancer treatment was chemotherapy in 53 patients (45.3%), and 12 patients (10.2%) were recurrent patients. Fifty-two patients were in regular employment, 24 were unemployed, 17 were of unknown employment status, 16 were in non-regular employment, and 8 were classified/categorized as other. In terms of working status, 40 were on leave, 35 were working, 15 were seeking work, 8 were unemployed, and 19 were categorized as other. The median number of consultations was 1 (1,11). The content of consultations was the social security system in 44 cases (37.6%) job seeking in 24 cases (20.5%), how to inform the workplace in 14 cases (12%), and workplace environment adjustment in 13 cases (11.1%). CONCLUSIONS: We conducted a survey on the actual status of employment consultation in a cancer center hospital. The majority of consultations were completed in one session. In terms of the content of consultations, there was a high need for consultations on the social security system and job seeking. Further study is needed on the characteristics of employment consultations according to employment status and other attributes.

Factors contributing to the systemic clearance of infliximab with long-term administration in Japanese patients with Crohn's disease: Analysis using population pharmacokinetics
.

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory gastrointestinal disease with repeated cycles of exacerbation and remission. Infliximab (IFX), a chimeric anti-TNF-α monoclonal antibody, has been widely used for the treatment of CD. However, no study in Japanese CD patients receiving continuous IFX for more than 1 year has been reported. To avoid therapeutic failure during long-term administration in Japanese CD patients, we evaluated the variable factors of IFX pharmacokinetics and the optimal trough IFX concentration at 8 weeks after administration. MATERIALS AND METHODS: Population pharmacokinetic (PPK) analysis was performed using the nonlinear mixed-effect model based on the IFX serum concentration in 832 samples from 121 patients. A one-compartment model was used to examine interindividual variability in the systemic clearance (CL) of intravenously administered IFX. RESULTS: PPK estimates (estimated value, RSE%) were total clearance (CL: 0.018 L/h, 9.1) and volumes of distribution (Vd: 7.35 L, 12.0). Interindividual variability for CL and Vd of 0.11 and 0.16, respectively, was found. Body weight, antibody to IFX (ATI), and albumin level were factors affecting the IFX CL. IFX CL was greater in the ATI-positive than in the ATI-negative group. CL was also greater in nonremission patients. There was a significant association between the predicted serum IFX trough concentration at 8 weeks and therapeutic response with long-term continuous administration (p < 0.05), with a higher concentration at 8 weeks seen in the remission group. CONCLUSION: Using these variables including body weight, ATI, and albumin level, the IFX dose could be calculated for individual CD patients to achieve the optimal therapeutic range.

Long-term effect of NUDT15 R139C on hematologic indices in inflammatory bowel disease patients treated with thiopurine.

BACKGROUND AND AIM: A missense variant of the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene (R139C) predisposes Asian patients with inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study evaluates the long-term effect of NUDT15 R139C heterozygosity on hematological parameters during thiopurine administration. METHODS: We enrolled 83 Japanese IBD patients who were on anti-tumor necrosis factor-α agents and had used thiopurine. NUDT15 R139C was genotyped by polymerase chain reaction. We retrospectively reviewed patient clinical charts to collect data on white blood cell (WBC) count, mean corpuscular volume (MCV), hemoglobin, and platelet count during the 24 months following thiopurine initiation. RESULTS: The included patients had either Crohn's disease (54; 65.1%) or ulcerative colitis (29; 34.9%). Genotyping of NUDT15 R139C identified 62 patients (74.7%) of genotype C/C and 21 (25.3%) of genotype C/T. The median dose of thiopurine was lower in the C/T group than in the C/C group after starting thiopurine. At 6 months, the mean WBC count of the C/T group became significantly lower than that of the C/C group (P = 0.008) and remained lower through the 24 months. The C/T group developed grade 2-4 leukopenia by 6 months, which persisted through 12-24 months. The mean MCV in the C/T group became higher than that of the C/C group after 3 months. CONCLUSIONS: NUDT15 R139C heterozygosity affected the WBC count and MCV for 24 months after thiopurine administration. Our results indicate that careful monitoring of leukopenia and dose adjustment are necessary throughout treatment in IBD patients heterozygous for the NUDT15 R139C.

Late-onset visceral varicella-zoster virus infection presented as acute liver failure after allogeneic hematopoietic stem cell transplantation.

Although much less common than localized zoster, initial presentation of varicella-zoster virus (VZV) as visceral infection can occur especially after allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of post-transplant visceral VZV infection presenting as fatal acute liver failure. It developed 4 years after allogeneic HSCT when a long-term prophylactic anti-VZV agent administration was discontinued. VZV should be listed as a causative pathogen of acute liver failure even years after allogeneic HSCT. Indication for, and duration of anti-VZV prophylaxis should be further investigated.

Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells.

Background & Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS). Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease. Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non-cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis. Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.

Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn's disease.

Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.

Fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient with ulcerative colitis.

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application.

Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the bloodstream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application. The aim of this study is to evaluate the disposition, nasal absorption, and therapeutic potential of OXT after nasal administration. The pharmacokinetics of OXT after intravenous bolus injection to rats followed a two-compartment model, with a rapid initial half-life of 3 min. The nasal bioavailability of OXT was approximately 2%. The brain concentration of OXT after nasal application was much higher than that after intravenous application, despite much lower concentrations in the plasma. More than 95% of OXT in the brain was directly transported from the nasal cavity. The in vivo stress-relief effect by OXT was observed only after intranasal administration. These results indicate that pharmacologically active OXT was effectively delivered to the brain after intranasal administration. In conclusion, the nasal cavity is a promising route for the efficient delivery of OXT to the brain.

Wearing Compression Tights on the Thigh during Prolonged Running Attenuated Exercise-Induced Increase in Muscle Damage Marker in Blood.

Purpose: To examine the effects of wearing a lower-body compression garment with different body coverage areas during prolonged running on exercise performance and muscle damage. Methods: Thirty male subjects were randomly assigned to one of three groups: (1) wearing a compression tights with 15 mmHg to thigh [n = 10, CT group], (2) wearing a compression socks with 15 mmHg to calf [n = 10, CS group], and (3) wearing a lower-body garment with < 5 mmHg to thigh and calf [n = 10, CON group]. The exercise consisted of 120 min of uphill running at 55% of [Formula: see text]O2max. Heart rate (HR), rate of perceived exertion (RPE), and running economy (evaluated by VO2) were monitored during exercise every 10 min. Changes in maximum voluntary contraction (MVC) of knee extension and plantar flexion, height of counter movement jump (CMJ) and drop jump (DJ), and scores of subjective feelings of muscle soreness and fatigue were evaluated before exercise, and 60 and 180 min after exercise. Blood samples were collected to determine blood glucose, lactate, serum free fatty acid, myoglobin (Mb), high-sensitivity C-reactive protein, and plasma interleukin-6 concentrations before exercise (after 20 min of rest), at 60 min of exercise, immediately after exercise, and 60 and 180 min after exercise. Results: Changes in HR, RPE, and running economy during exercise did not differ significantly among the three groups. MVC of knee extension and plantar flexion, and DJ decreased significantly following exercise, with no difference among groups. The serum Mb concentration increased significantly with exercise in all groups, whereas the area under the curve for Mb concentration during 180 min post-exercise was significantly lower in the CT group (13,833 ± 1,397 pg/mL 180 min) than in the CON group (24,343 ± 3,370 pg/mL 180 min, P = 0.03). Conclusion: Wearing compression garment on the thigh significantly attenuated the increase in serum Mb concentration after exercise, suggesting that exercise-induced muscle damage was attenuated.

Wearing lower-body compression garment with medium pressure impaired exercise-induced performance decrement during prolonged running.

OBJECTIVE: To investigate the effect of wearing a lower body compression garment (CG) exerting different pressure levels during prolonged running on exercise-induced muscle damage and the inflammatory response. METHODS: Eight male participants completed three exercise trials in a random order. The exercise consisted of 120 min of uphill running at 60% of VO2max. The exercise trials included 1) wearing a lower-body CG with 30 mmHg pressure [HIGH]; 2) wearing a lower-body CG with 15 mmHg pressure [MED]; and 3) wearing a lower-body garment with < 5 mmHg pressure [CON]. Heart rate (HR), and rate of perceived exertion for respiration and legs were monitored continuously during exercise. Time-course change in jump height was evaluated before and immediately after exercise. Blood samples were collected to determine blood glucose, lactate, serum creatine kinase, myoglobin, free fatty acids, glycerol, cortisol, and plasma interleukin-6 (IL-6) concentrations before exercise, 60 min of the 120 min exercise period, immediately after exercise, and 60 min after exercise. RESULTS: Jump height was significantly higher immediately after the exercise in the MED trial compared with that in the HIGH trial (P = 0.04). Mean HR during the 120 min exercise was significantly lower in the MED trial (162 ± 4 bpm) than that in the CON trial (170 ± 4 bpm, P = 0.01). Plasma IL-6 concentrations increased significantly with exercise in all trials, but the area under the curve during exercise was significantly lower in the MED trial (397 ± 58 pg/ml·120 min) compared with that in the CON trial (670 ± 86 pg/ml·120 min, P = 0.04). CONCLUSION: Wearing a lower body CG exerting medium pressure (approximately 15 mmHg) significantly attenuated decrease in jump performance than that with wearing a lower body CG exerting high pressure (approximately 30 mmHg). Furthermore, exercise-induced increases in HR and the inflammatory response were significantly smaller with CG exerted 15mmHg than that with garment exerted < 5 mmHg.

Limited Identification of Dual-time-point Positron Emission Tomography/Computed Tomography in Advanced Colorectal Neoplasms.

Objective We investigated whether dual-time-point 18-Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) could improve the positive predictive value for detecting advanced colorectal neoplasms (cancer, adenoma ≥10 mm or adenoma with high-grade dysplasia). Methods We retrospectively searched for consecutive patients with a known primary cancer, who had a colonic 18FDG uptake incidentally found by PET/CT, followed by colonoscopy between January 2013 and August 2014. The clinical characteristics including the maximum standardized uptake value (SUVmax) were compared between advanced colorectal neoplasms and non-advanced lesions. Results Forty-eight patients had 51 foci with an incidental focal colorectal uptake of 18FDG. Among these 51 foci, 28 foci were judged as being advanced neoplasms, whereas 23 foci identified as non-advanced lesions. Four cases were missed by PET/CT: two laterally spreading tumors (LSTs) with intramucosal cancer and two severe adenomas (<10 mm). The positive predictive value for the detection of advanced neoplasms was 55%. The per-spot performance of PET/CT showed that SUVmax was significantly higher in advanced neoplasms than in non-advanced lesions for the early-phase (10.1±4.9 vs. 6.5±3.2, p=0.029) and the delayed-phase (12.0±6.0 vs. 7.4±4.0, p=0.022). However, more importantly, there was a significant overlap of the SUVmax and no significant difference was found in the retention index (19.2±20.1 vs. 16.6±29.4, p=0.767). Conclusion Dual-time-point PET/CT was found to have limited impact for identifying advanced colorectal neoplasms in spite of its high sensitivity and it might therefore not be able to identify either LSTs or small advanced neoplasms.

Endocytoscopy can be used to assess histological healing in ulcerative colitis.

Background and study aim Endocytoscopy (ECS) is used in the in vivo microscopic inspection of microstructural mucosal features and enables endoscopists to assess the histological severity of ulcerative colitis (UC). The aim of this study was to assess histological healing in UC patients by using ECS. Patients and methods A total of 64 patients in clinical and endoscopic remission who underwent ECS were selected. The correlation between the ECS score and Geboes score at the rectum was evaluated in patients with a Mayo endoscopic score (MES) of 0. The diagnostic accuracy of the ECS score for histological remission (Geboes score ≤ 2) was also assessed. Results The ECS score ranged from 0 to 5 in patients with endoscopic remission on conventional white-light images (MES of 0). The agreement between histological remission regarding the ECS score and the Geboes score had a κ value of 0.72, and the ECS score showed high accuracy for histological remission, with a sensitivity of 0.77, a specificity of 0.97, and a diagnostic accuracy of 0.86. Conclusion ECS can be used to assess histological healing in patients with UC without the need for biopsy specimens.

Evaluation of the severity of ulcerative colitis using endoscopic dual red imaging targeting deep vessels.

Background and study aims Colonoscopies can predict long-term prognoses in patients with ulcerative colitis (UC). Recently, a new imaging technology has been developed that uses 3 types of illumination with center wavelengths of 540 nm, 600 nm, and 630 nm. The use of both the 600-nm and 630-nm lights (Dual red imaging; DRI) is critical for identifying blood vessels in deeper tissue. The aim of this study was to evaluate the usefulness of DRI for assessing the severity of inflammation in patients with UC. Patients and methods A total of 43 UC patients were retrospectively enrolled to evaluate the endoscopic severity of 112 colon segments, and Mayo endoscopic scores, DRI scores and the severity of inflammation on a visual analogue scale (VAS) were compared. The Mayo endoscopic scores, DRI scores, and histologic scores were evaluated, and the interobserver agreement on DRI scores among 5 investigators was also assessed. The usefulness of DRI scores for predicting prognoses was also assessed in patients with clinical remission. Results The DRI scores were closely correlated with the VAS for the severity of colonic inflammation (r = 0.96) and the histologic scores (r = 0.72 - 0.8). The DRI scores had a higher rate of interobserver agreement (κ values = 0.63 - 0.88) than the Mayo endoscopic scores (κ values = 0.44 - 0.59). Inter-observer agreement between 4 non-experts was also excellent (mean κ value = 0.76, range 0.63 - 0.82). The expected time until recurrence was significantly longer in patients with lower DRI scores (P < 0.01). Conclusion DRI can be used in patients with mild to moderate endoscopic severity because it targets the deep vascular pattern. The prognosis of UC can be predicted by assessing deep vessels using DRI.

Single fecal microbiota transplantation failed to change intestinal microbiota and had limited effectiveness against ulcerative colitis in Japanese patients.

BACKGROUND/AIMS: Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan. METHODS: We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814). RESULTS: Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels. CONCLUSIONS: The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.

Impact of Scoliosis on Laparoscopic Nissen Fundoplication.

AIM: Scoliosis, which is often associated with neurological impairment in children, sometimes makes it difficult to perform laparoscopic procedures. This study assessed the impact of scoliosis on performing laparoscopic Nissen fundoplication. METHODS: Medical records and radiographic examinations of patients who underwent laparoscopic Nissen fundoplication at a single institution from 2006 to 2015 were reviewed retrospectively. Patients' data on age at surgery, height, weight, duration of pneumoperitoneum, and amount of bleeding were collected. The Cobb angle was measured using X-rays, and the direction (right or left) of the scoliotic curve was recorded. The chest compression ratio was calculated using computed tomography axial images. RESULTS: Eighty-five patients were included and analyzed in this study, of which 89% were neurologically impaired. Median age, height, and weight were 120 months, 110 cm, and 17 kg, respectively. A positive correlation between age and the Cobb angle (ρ = 0.64) and a negative correlation between age and the chest compression ratio (ρ = -0.56) were observed. The right-curved scoliotic group showed significantly more bleeding than the nonscoliotic (<10°) group (P = .01; nonscoliotic, 0 mL; right curved, 7.5 mL; left curved, 0 mL). The severe scoliotic group (≥45°) showed more bleeding than the nonscoliotic group (P = .02). Neither the direction of the scoliotic curve nor scoliotic severity showed a significant difference in the duration of pneumoperitoneum. CONCLUSIONS: The older the patient, the more severe their scoliosis and chest compression were. Right-curved or severe scoliosis could be risk factors for intraoperative bleeding in laparoscopic Nissen fundoplication.

Minimally invasive surgery for diaphragmatic diseases in neonates and infants.

Owing to recent advances in minimally invasive surgery (MIS), laparoscopic and thoracoscopic surgery have been gradually introduced for use in neonates and infants. This review focuses on two popular MIS procedures for diaphragmatic diseases in neonates and infants: congenital diaphragmatic hernia (CHD) repair and plication for diaphragmatic eventration. While several advantages of MIS are proposed for CDH repair in neonates, there are also some concerns, namely intraoperative hypercapnia and acidosis and a higher recurrence rate than open techniques. Thus, neonates with severe CDH, along with an unstable circulatory and respiratory status, may be unsuitable for MIS repair, and the use of selection criteria is, therefore, important in these patients. It is generally believed that a learning curve is associated with the higher recurrence rate. Contrary to CDH repair, no major disadvantages associated with the use of MIS for diaphragmatic eventration have been reported in the literature, other than technical difficulty. Thus, if technically feasible, all pediatric patients with diaphragmatic eventration requiring surgical treatment are potential candidates for MIS. Due to a shortage of studies on this procedure, the potential advantages of MIS compared to open techniques for diaphragmatic eventration, such as early recovery and more rapid extubation, need to be confirmed by further studies.

The Ulcerative Colitis Endoscopic Index of Severity is Useful to Predict Medium- to Long-Term Prognosis in Ulcerative Colitis Patients with Clinical Remission.

BACKGROUND: The ulcerative colitis endoscopic index of severity [UCEIS] is a validated scoring system. Nevertheless, few studies have investigated its usefulness in clinical settings. In this study, we aimed to predict the clinical prognosis of patients with ulcerative colitis [UC] in clinical remission using the UCEIS. METHODS: A total of 285 UC patients who underwent a colonoscopy between April 2012 and March 2013 were enrolled. We reviewed clinical characteristics and endoscopic scores at the time of the colonoscopy and checked the clinical remission rate of the patients until September 2015. Clinical remission and recurrence were defined as a partial Mayo score of ≤1 and ≥3, respectively. RESULTS: UCEIS was strongly correlated with the Mayo endoscopic score [r=0.93], moderately correlated with clinical severity [r=0.64] and mildly correlated with C-reactive protein [r=0.34]. The recurrence rate increased gradually as it became more endoscopically severe [5.0% for UCEIS=0, 22.4% for UCEIS=1, 27.0% for UCEIS=2, 35.7% for UCEIS=3 and 75.0% for UCEIS=4-5] in patients with clinical remission. UCEIS and the concomitant use of thiopurine were independent factors predicting clinical recurrence. A multivariate analysis indicated that the absence of bleeding [p≤0.001] and the absence of mucosal damage [p<0.001] in a colonoscopy were independent factors for prolongation of clinical remission. CONCLUSION: The UCEIS is useful to predict the medium- to long-term outcomes of UC patients with clinical remission. The absence of bleeding or mucosal damage is important for maintaining clinical remission.

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

BACKGROUND/AIMS: Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. METHODS: The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. RESULTS: At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. CONCLUSION: This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted.

Ulcerative colitis endoscopic index of severity is associated with long-term prognosis in ulcerative colitis patients treated with infliximab.

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by periods of remission and episodes of relapse. Mucosal healing is an emerging therapeutic target in UC and various scoring systems have been used. The UC endoscopic index of severity (UCEIS) is the only validated endoscopic index at present, with minimum interobserver variation. Correlation of UCEIS scores after treatment and clinical outcomes of UC has not been examined. In the present study, we aimed to evaluate the usefulness of UCEIS after treatment with infliximab. METHODS: The medical records of 82 UC patients, treated with infliximab at Keio University Hospital between October 2010 and July 2013, were reviewed retrospectively. Endoscopic findings were evaluated based on the UCEIS. RESULTS: Mean pre-therapeutic UCEIS score was 5.1. Pre-therapeutic UCEIS scores were not associated with short-term outcomes. Forty-five patients underwent colonoscopy at 3-12 months after starting treatment; mean post-therapeutic UCEIS score was 2.4, with a score of 0-1 in 16 (35.6%) patients, 2-4 in 19 (42.2%) patients, and 5-8 in 10 (22.2%) patients. Importantly, a post-therapeutic UCEIS score of 0 or 1 after treatment was associated with a favorable long-term outcome. CONCLUSION: UCEIS score is a useful instrument for evaluating endoscopic improvement in UC patients treated with infliximab, and mucosal healing may be defined with a UCEIS score of 0 or 1.

Endoscopic Severity Predicts Long-Term Prognosis in Crohn's Disease Patients with Clinical Remission.

INTRODUCTION: Mucosal healing has emerged as a desirable treatment goal in clinical practice for patients with Crohn's disease (CD). The aim of this study was to assess the relationship between endoscopic activity and the long-term prognosis of CD using simple endoscopic score for Crohn's disease (SESCD) and Rutgeerts' score. METHODS: We conducted a cohort study in clinical practice at a single center. Among CD patients who underwent colonoscopy between July 2008 and June 2011 at our hospital, 131 patients with clinical remission were selected, and the patients were divided into 2 groups: a non-surgical group (n = 84) and a surgical group (n = 47). The primary endpoint of this study was to assess the associations between variables and clinical relapse after endoscopic procedures. The cut-off levels of SESCD or Rutgeerts' score for the prediction of relapse were also assessed in patients with clinical remission. RESULTS: In the non-surgical group, SESCD and C-reactive protein at baseline were significantly higher in patients who had clinical recurrence than in patients who maintained remission. A factor of SESCD ≤2 was independently associated with sustained remission, even in patients with clinical remission. In the surgical group, patients with Rutgeerts' scores ≤1 had significantly prolonged clinical remission compared to patients with Rutgeerts' scores ≥3. CONCLUSION: A cut-off value of SESCD ≤2 and a Rutgeerts' score ≤1 enabled the prediction of long-term prognosis. These cut-off values could be used in clinical trials of endoscopic remission from the point of view of the clinical outcomes of CD.