[Utility of abdominal ultrasonography in the management of ulcerative colitis:proposal of a new scoring system].

In the management of ulcerative colitis (UC), colonoscopy (CS) is considered essential for diagnosis;however, its invasiveness poses a challenge. Conversely, recent advancements in ultrasound diagnostic devices have improved imaging quality for the digestive tract, rendering them valuable in UC management. Therefore, this study aimed to elucidate the correlation between abdominal ultrasonography (AUS) and CS in assessing UC activity. The indices adopted for UC evaluation using AUS were as follows:1) bowel wall stratification, 2) bowel wall thickness, 3) bowel wall flow at power Doppler, 4) presence of increased brightness of inflammatory fat, and 5) presence of mesenteric lymph node swelling greater than 5mm. Subsequently, we developed a new AUS index for UC, termed the UCUS score, which comprises the aforementioned five indices. Finally, we compared the UCUS score with representative endoscopic indices, the Mayo endoscopic sub-score, and the Ulcerative Colitis Endoscopic Index of Severity. The results demonstrated that our proposed UCUS score better reflected disease activity than individual items assessed separately. ROC curve analysis revealed a UCUS score cutoff of 3 points. Therefore, a UCUS score of ≥3 points indicates the need for further examination with CS. Conversely, a score below 3 points suggests low disease activity, and in situations when evaluating treatment effectiveness, AUS could potentially substitute for CS. We believe that the UCUS score is an important source of information to understand the patient's condition and to motivate the patient to undergo endoscopy.

Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice.

BACKGROUND: Although evidence for the short- to medium-term efficacy of adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited number of reports on the long-term efficacy of adalimumab. This study was to understand baseline demographic features, which potentially could be risk factors for relapse or colectomy following induction of remission by adalimumab in UC patients. Additionally, factors affecting long-term outcomes were to be identified. METHODS: Twenty-one patients with UC who had been treated with adalimumab were reviewed retrospectively. Comparative analyses were undertaken by factoring steroid withdrawal versus non-withdrawal, long-term remission versus relapse following remission, and requiring surgical intervention for UC versus surgery-free. RESULTS: Adalimumab treatment was associated with steroid tapering in steroid-dependent cases in the long term. Of the 14 patients in whom clinical remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was 43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for surgery included intolerance to salicylates (p = 0.005) and past treatment with tacrolimus (p = 0.023). CONCLUSIONS: Adalimumab treatment was associated with long-term efficacy in patients with mild UC - patients achieved a high cumulative nonoperative survival rate over a long period of time, beyond 6 years.

Comparison of Targeted vs Random Biopsies for Surveillance of Ulcerative Colitis-Associated Colorectal Cancer.

BACKGROUND & AIMS: A random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC. METHODS: We performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups. RESULTS: The mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679-2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation. CONCLUSIONS: In a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Real life results in using 5-ASA for maintaining mild to moderate UC patients in Japan, a multi-center study, OPTIMUM Study.

BACKGROUND: Efficacy of maintenance therapy in ulcerative colitis (UC) in the remission stage has been reported to depend on release profile or dosing regimen of oral 5-aminosalicylic acid (5-ASA) products used. Aim of this study is to investigate real life results in using oral 5-ASA products for maintaining mild to moderate UC patients in Japan. METHODS: Adult UC outpatients treated with oral 5-ASA products were enrolled from 379 sites in Japan between July 2012 and July 2013, and followed for 52 weeks. Remission maintenance rate was evaluated by products and dosages. Factors affecting recurrence were also examined. RESULTS: A total of 5695 UC patients were registered. Among the 4677 patients in whom remission maintenance was observed, remission maintenance rate at week 52 was 80.2%. As for disease duration and dosage, Pentasa® 4000 mg/day in 2 divided doses was administered to 480 (21.0%) patients in remission and 341 (46.6%) patients in active stage, and Asacol® 3600 mg/day in 3 divided doses was administered to 696 (46.4%) patients in remission and 473 (67.3%) patients in active stage. The remission maintenance rate at week 52 by dosage and frequency did not significantly differ between Pentasa® Tablets at 4000 mg/day in 2 divided doses (76.5%) and Asacol® Tablets at 3600 mg/day in 3 divided doses (76.1%, P = 0.7868). Factors affecting the risk of relapse in UC were identified. Significantly persistent remission maintenance was noted in patients in whom duration of remission maintenance until enrollment was 12 to <24 months or ≥24 months relative to the reference category of <3 months (12 to <24 months: HR 0.600 [0.486-0.740], p < 0.0001]; ≥24 months: HR 0.352 [0.289-0.431], p < 0.0001). CONCLUSIONS: Efficacy of real life results in using oral 5-ASA products for maintaining mild to moderate UC patients was favorable. Maintaining remission for 12 months or longer after induction therapy was shown to reduce recurrence risk thereafter. TRIAL REGISTRATION: UMIN 000008563 (the date of registration: July 30, 2012), ClinicalTrials.gov NCT01654783 (the date of registration: July 30, 2012).

Adsorptive Depletion of Myeloid Lineage Leucocytes as Remission Induction Therapy in Patients with Ulcerative Colitis after Failure of First-Line Medications: Results from a Three-Year Real World, Clinical Practice.

BACKGROUND/AIMS: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. METHODS: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. RESULTS: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. CONCLUSION: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.

Enteral nutrition for maintaining remission in patients with quiescent Crohn's disease: current status and future perspectives.

PURPOSE: The value of enteral nutrition (EN) as maintenance therapy in patients with quiescent Crohn's disease (CD) has not been fully evaluated. The purpose of this study was to review the efficacy of EN for the maintenance of remission in patients with quiescent CD. METHODS: Seven prospective cohort studies evaluating the efficacy of EN for the maintenance of remission in quiescent CD were included. Three of the seven studies were randomized-controlled trials (RCTs). In all studies, patients used EN as a supplement or as a nocturnal tube feeding in addition to their normal food. RESULTS: One study compared the efficacy of elemental diet and polymeric diet. Elemental and polymeric diets were equally effective for the maintenance of clinical remission and for allowing tapering and cessation of steroid therapy. The other six studies compared the outcomes between patients treated with and without EN. The maintained clinical remission rate at 1 year was significantly higher in patients treated with EN in four of the six studies. Quantitative pooling of the studies was not feasible due to a small number of RCTs and a narrative account of the study characteristics. CONCLUSIONS: Our review suggests that EN is useful for the maintenance of remission in patients with quiescent CD. However, there are several limitations in the reviewed studies. There are few RCTs. Further, the sample size is small, and the duration of intervention and follow-up is short. Large and well-designed RCTs should be conducted to rigorously evaluate the efficacy of EN for maintaining remission.

An Increased Serum N-Terminal Telopeptide of Type I Collagen, a Biochemical Marker of Increased Bone Resorption, Is Associated with Infliximab Therapy in Patients with Crohn's Disease.

BACKGROUND: Osteopenia and osteoporosis are considered to be extra-intestinal manifestations of inflammatory bowel disease (IBD). Anti-tumor necrosis factor (TNF)-α biologics have been introduced as novel medications for an active IBD. However, it is still not well documented whether anti-TNF-α affects the frequency of bone loss or abnormality of bone mineral markers among patients with IBD. AIMS: This study was to investigate the biochemical basis of low bone mineral density (BMD) and increased turnover in IBD during infliximab (IFX) therapy. METHODS: Forty patients with Crohn's disease (CD), 80 patients with ulcerative colitis (UC), and 65 age- and gender-matched controls were included. BMD was measured with dual-energy X-ray absorptiometry, and vitamins K and D were measured as serum undercarboxylated osteocalcin (ucOC) and 1,25-(OH)2D, respectively. Bone formation and resorption were based on measuring bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), respectively. RESULTS: Significantly lower BMD was found in patients with UC and CD as compared to controls (P < 0.05). BAP, 1,25-(OH)2D, ucOC, and NTx were significantly higher in CD patients, but not in UC patients as compared to controls (P < 0.05). Further, serum NTx level was significantly higher in CD patients who were receiving IFX as compared to CD patients who were not receiving IFX (P < 0.01). CONCLUSIONS: A lower BMD and higher bone metabolism markers were found in CD patients as compared to controls or UC patients. A significant increased serum level of NTx, a biochemical marker of increased bone resorption, was observed in CD patients during IFX therapy.

An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/µL to 6950/µL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

[Coexistence of lymphoid follicular proctitis and ulcerative colitis].

We describe a rare case of ulcerative colitis (UC) with lymphoid follicular proctitis (LFP) extending discontinuously from the rectum to the ascending colon. The patient was a 42-year-old female presenting with a positive fecal occult blood test. Colonoscopy revealed erosions and disappearance of vascular patterns in the ascending colon and lower rectum, together with circumferential, uniform, granular lesions in the lower rectum. Histological examinations of the rectal biopsy specimens revealed lymphoid follicles, hyperplasia, and infiltration of chronic inflammatory cells. We suspected rectal and segmental UC with LFP. Initially, the patient was managed conservatively because of the lack of symptoms; however, on developing mucoid stools and haematochezia, mesalazine administration was started. Her symptoms and endoscopic findings resolved completely. LFP is closely associated with UC. Therefore, while diagnosing and managing LFP, it is necessary to ascertain or rule out potential complications.