Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

Construction of an Explanatory Model for Quality of Life in Outpatients with Ulcerative Colitis.

Introduction: To date, no studies have reported explanatory models of health-related quality of life (HRQoL) in patients with ulcerative colitis. Therefore, this study aimed to examine HRQoL and its related factors in outpatients with ulcerative colitis to construct an explanatory model. Methods: We conducted a cross-sectional survey at a clinic in Japan. The HRQoL was evaluated using the 32-item Inflammatory Bowel Disease Questionnaire. We extracted explanatory variables of HRQoL from demographic, physical, psychological, and social factors reported in previous studies and created a predictive explanatory model. The relationship between explanatory variables and the questionnaire total score was examined using Spearman's rank correlation coefficient, the Mann-Whitney test, or the Kruskal-Wallis test. We conducted multiple regression and path analyses to examine the effect of explanatory variables on the total score. Results: We included 203 patients. Variables that were associated with the total score were the partial Mayo score (r = -0.451), treatment side effects (p = 0.004), the Hospital Anxiety and Depression Scale-Anxiety score (r = -0.678), the Hospital Anxiety and Depression Scale-Depression score (r = -0.528), and the availability of an advisor during difficult times (p = 0.001). The model included the partial Mayo score, treatment side effects, the Hospital Anxiety and Depression Scale-Anxiety score, and the availability of an advisor during difficult times as explanatory variables of the total score that showed the best goodness-of-fit (adjusted R2 = 0.597). The anxiety score exerted the greatest negative effect on the questionnaire total score (ß = -0.586), followed by the partial Mayo score (ß = -0.373), treatment side effects (ß = 0.121), and availability of an advisor during difficult times (ß = -0.101). Conclusion: Psychological symptoms exerted the strongest direct effect on HRQoL in outpatients with ulcerative colitis and mediated the relationship between social support and HRQoL. Nurses should listen carefully to the concerns and anxieties of patients to ensure that a social support system is provided by leveraging multidisciplinary collaborations.

Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Upadacitinib Induction and Maintenance Therapy Improves Abdominal Pain, Bowel Urgency, and Fatigue in Patients With Ulcerative Colitis: A Post Hoc Analysis of Phase 3 Data.

BACKGROUND: This post hoc analysis of a large, phase 3 program evaluated the effects of upadacitinib on fatigue, bowel urgency, and abdominal pain in patients with moderately to severely active ulcerative colitis. METHODS: Induction data were pooled from 2 identical studies, the U-ACHIEVE induction and U-ACCOMPLISH studies. Patients in these studies received upadacitinib 45 mg once daily or placebo as induction treatment. Responders to induction treatment were rerandomized in the U-ACHIEVE maintenance study to upadacitinib 15 mg once daily, upadacitinib 30 mg, or placebo. The percentage of patients reporting no abdominal pain and no bowel urgency daily via an electronic diary and a meaningful within-person change (≥5 points) in the Functional Assessment of Chronic Illness Therapy-Fatigue score were evaluated. RESULTS: The results demonstrated a statistically significantly greater percentage of patients reporting no abdominal pain and absence of bowel urgency observed from week 2 (P < .001), with upadacitinib induction treatment and clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue score observed at week 8 (P < .001), when compared with placebo. The maintenance study showed that significant and meaningful improvements in abdominal pain, bowel urgency, and Functional Assessment of Chronic Illness Therapy-Fatigue score achieved during induction were sustained through 52 weeks of maintenance treatment in upadacitinib- vs placebo-treated patients. CONCLUSIONS: The findings of this study support the additional benefit of upadacitinib in treating moderately to severely active ulcerative colitis by demonstrating a statistically significant impact on clinically meaningful symptoms of fatigue, bowel urgency, and abdominal pain.(U-ACHIEVE induction and maintenance studies; NCT02819635; U-ACCOMPLISH induction study; NCT03653026).

A significantly higher percentage of patients with moderately to severely active ulcerative colitis reported no abdominal pain, no bowel urgency, and a meaningful change in fatigue following 8-week upadacitinib induction treatment and 52-week maintenance treatment compared with placebo.

Approach to the Seamless Management of Inflammatory Bowel Disease, Considering Special Situations, Shared Decision-Making, and Disease Burden.

BACKGROUND: While the number of inflammatory bowel disease (IBD) patients has been steadily increasing, a lot of effective treatments have become available, including biological drugs. However, there still exists no effective treatment universally for all types of IBD patients. We have continuously discussed "Total Care" for IBD patients in the 3 consecutive annual meetings of the Japanese Gastroenterological Association from the 14th meeting to the 16th meeting in 2018-2020. SUMMARY: In the 14th meeting, we summarized cross-sectional issues under the title "From Total Care to Microbiota" as for their subthemes. In the 15th meeting, under the title of "Consensus and Pitfalls in Special Situations," we discussed the thiopurine treatment for the patients in their childhood or pregnancy and lactation period as well as the cytapheresis treatment for elderly patients. In the 16th meeting, under the title "Future Issues in Special Situations: Including Disease Burden," we discussed about the issues in childhood-onset IBD, including transitional care and the new option of combination of treatments in their adulthood and their disease burdens. Key Messages: "Total Care" for IBD patients should be considered from a broad perspective with shared decision-making. It is imperative to involve medical staff members for careful handling of a wide range of disease burdens.

Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab.

BACKGROUND AND AIMS: In inflammatory bowel disease [IBD] patients, antibody-to-infliximab [ATI] generation is responsible for loss of response [LOR] and infusion reaction [IR] to infliximab. An immuno-therapeutic approach is considered an option to overcome LOR. Granulocyte/monocyte adsorptive apheresis [GMA] using an Adacolumn has been shown to have clinical efficacy together with immunomodulatory effects in IBD patients. METHODS: We developed an ATI-CAI assay utilizing a C1q immobilized plate and applied it to measure ATI in patients who were receiving infliximab, including 56 with sustained response, 76 with LOR and six with IR. Furthermore, 14 patients with LOR and two with paradoxical skin reactions who received infliximab + GMA combination therapy were analysed. RESULTS: Fourteen patients with LOR, seven with Crohn's disease and seven with ulcerative colitis, showed significantly improved clinical indices [p = 0.0009], and decreased ATI [p = 0.0171] and interleukin-6 [p = 0.0537] levels at week 8 following initiation of infliximab + GMA therapy. Nine patients who received combination therapy achieved remission, which was maintained to week 24 with infliximab alone. Additionally, cutaneous lesions in two patients with IR were improved. ATI-CAI assay efficiency was not influenced by infliximab concentration during the test. Pre- and post-infliximab infusion ATI levels were not different. Patients with ATI greater than the 0.153 µg/mL cut-off value were likely to experience LOR [odds ratio 3.0]. CONCLUSIONS: Patients who received infliximab + GMA therapy appeared to regain clinical response to infliximab by a decrease in ATI level. Furthermore, the concentration of infliximab in the test did not influence ATI measurement, but was associated with clinical response.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. METHODS: We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. RESULTS: The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. CONCLUSIONS: GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

Clinical importance of cold polypectomy during the insertion phase in the left side of the colon and rectum: a multicenter randomized controlled trial (PRESECT study).

BACKGROUND AND AIMS: Colorectal polyps are often detected during the insertion phase of colonoscopy but are commonly removed during the withdrawal phase. We aimed to investigate the clinical advantages of instant removal of colorectal polyps during the insertion phase to determine the appropriate strategy for polyps detected on insertion. METHODS: This prospective, multicenter, randomized trial targeted patients with at least 1 left-sided polyp <10 mm in size detected unintentionally on endoscope insertion from April 2018 to March 2019. Patients were allocated to the following 2 groups: study group, consisting of patients who had polyp removal instantly on insertion, and control group, comprising patients who had the endoscope inserted to the cecum first and polyps removed subsequently on withdrawal. Carbon dioxide gas insufflation and cold polypectomy were applied to minimize the influences of polypectomy on endoscope insertion. Twenty advanced endoscopists from 7 community-based institutions participated in this trial. RESULTS: Of 1451 patients enrolled, 220 patients were eligible for full assessment. Mean total procedure time was significantly shorter in the study group (18.9 vs 22.3 minutes, P < .001). Mean pure cecal intubation time and number of polyps per patient were similar between the 2 groups. In the control group, among 107 polyps found during insertion, 48 (45.8%) required reinspection and 7 (6.5%) were completely missed, with an average reinspection time of approximately 3 minutes. CONCLUSIONS: Polypectomy during the insertion phase in the colon and rectum significantly shortens the total procedure time and eliminates all missed polyps without experiencing any disadvantages.

Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study.

BACKGROUND: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS: This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS: A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS: The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam.

BACKGROUND: Budesonide foam is effective in inducing clinical remission in ulcerative colitis (UC) patients with active proctosigmoiditis. The aim of this study was to evaluate the duration of remission and predictors of relapse in UC patients who achieved clinical remission and mucosal healing by 6-week treatment with topical budesonide. METHODS: This is a retrospective, observational, multicenter study with a 2-year follow-up period. UC patients who were treated with budesonide foam in phase 2 or phase 3 clinical trials and achieved both clinical remission and mucosal healing were enrolled. RESULTS: Among 84 patients who met the eligibility criteria, 60 participated in the study. Eighteen of the 60 patients (30.0%; 95% confidence interval [CI]: 18.9-43.2) experienced no relapse (i.e., maintenance of remission) during the 2-year follow-up period. The median relapse-free survival time was 0.82 years (95% CI: 0.51-1.52). Of 37 patients with a Mayo endoscopic subscore of 0 after inducing remission with budesonide foam, 25 (67.6%) relapsed within 2 years. Patients with a disease duration of <1 year experienced a worse clinical outcome than patients with a disease duration of >5 years, and the hazard ratio was 2.38 (95% CI: 1.04-5.45). CONCLUSION: This is the first study to evaluate the short- to middle-term prognosis in UC patients who achieved mucosal healing with topical preparations. After inducing remission by budesonide foam, treatment for maintaining remissions and strict follow-up may be needed for patients with shorter disease duration.

Development of a C1q-immobilized (Cim) assay to measure total antibodies to infliximab and its clinical relevance in patients with inflammatory bowel disease.

OBJECTIVE: Determination of antibodies to infliximab (ATI) is desirable for the management of patients with inflammatory bowel disease (IBD) who receive infliximab. Conventional ligand-binding ATI-assays detect only free-form of ATI, potentially increasing the proportion of patients with undetectable ATI, but with adequate trough infliximab (TRI) level who experience loss of response (LOR) to infliximab. We investigated this assertion using a novel ATI-Cim assay. METHODS: An ATI-Cim assay was developed by utilizing a C1q-immobilized plate, detecting free-form and ATI-infliximab complexes. Plasma ATI in 137 consecutive IBD patients, 56 with sustained clinical response (SCR), 76 with LOR and 5 with infusion reactions was measured. RESULTS: ATI levels reached a plateau following addition of up to 25 µg/mL infliximab to different concentrations of free-form ATI. ATI concentration did not significantly change during infliximab infusion (P = 0.4316). ATI concentration > 0.153 µg/mL was associated with LOR (odds ratio 3.0: 95%, confidence interval 1.5 to 6.1, P = 0.0029). The number of patients with undetectable ATI was higher in SCR than in LOR, 53.6% vs 22.4% (P = 0.0004). Patients with SCR and LOR were divided into 4 subgroups by combined cut-off ATI and TRI values. (A) ATI > 0.153 µg/mL and TRI ≤ 2 µg/mL; (B) ATI > 0.153 µg/mL and TRI > 2 µg/mL; (C) ATI ≤ 0.153 µg/mL and TRI ≤ 2 µg/mL; (D) ATI ≤ 0.153 µg/mL and TRI > 2 µg/mL. The frequency of LOR showed a decreasing trend from subgroup A to D, 80.8%, 64.1%, 55.2% and 36.8%, respectively (P = 0.0003). CONCLUSIONS: The measured ATI level appeared to define the patients' response to infliximab. Combining ATI and trough infliximab levels should help to understand the mechanism of LOR and make therapeutic algorithms.

Correction to: Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study.

In Fig. 2(c) of this article, the length of the "95% CI difference bars" under the items labelled "Left-sided and Pancolitis" and "Left-sided" under the heading "Disease type" was corrected. The correct figure is shown in the following page.

Complete mucosal healing of distal lesions induced by twice-daily budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative colitis with distal active inflammation: double-blind, randomized study.

BACKGROUND: Budesonide foam is used for the topical treatment of distal ulcerative colitis. This phase III study was performed to confirm mucosal healing and other therapeutic effects of twice-daily budesonide 2-mg foam in patients with mild-to-moderate ulcerative colitis including left-sided colitis and pancolitis. METHODS: This was a multicenter, randomized, placebo-controlled, double-blind trial. A total of 126 patients with mild-to-moderate ulcerative colitis with active inflammation in the distal colon were randomized to two groups receiving twice-daily budesonide 2 mg/25 ml foam or placebo foam. The primary endpoint was the percentage of complete mucosal healing of distal lesions (endoscopic subscore of 0) at week 6. Some patients continued the treatment through week 12. Drug efficacy and safety were evaluated. RESULTS: The percentages of both complete mucosal healing of distal lesions and clinical remission were significantly improved in the budesonide as compared with the placebo group (p = 0.0003 and p = 0.0035). Subgroup analysis showed similar efficacy of budesonide foam for complete mucosal healing of distal lesions and clinical remission regardless of disease type. The clinical remission percentage tended to be higher in patients achieving complete mucosal healing of distal lesions than in other patients. There were no safety concerns with budesonide foam. CONCLUSIONS: This study confirmed for the first time complete mucosal healing with twice-daily budesonide 2-mg foam in mild-to-moderate ulcerative colitis with distal active inflammation. The results also indicated that complete mucosal healing of distal lesions by budesonide foam promotes clinical remission of ulcerative colitis. Clinical trial registration no.: Japic CTI-142704.

Comparison of efficacy of multimatrix mesalazine 4.8 g/day once-daily with other high-dose mesalazine in active ulcerative colitis: a randomized, double-blind study.

BACKGROUND/AIMS: This study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine. METHODS: In this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period. RESULTS: The change in the UC-DAI (mean±standard deviation) in the per-protocol set was -2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and -1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was -0.7 (two-sided 95% confidence interval, -1.3 to -0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups. CONCLUSIONS: Multimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.

Twice-daily Budesonide 2-mg Foam Induces Complete Mucosal Healing in Patients with Distal Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal healing is an important therapeutic goal for ulcerative colitis. Once-daily administration of budesonide 2-mg foam is widely used for inducing clinical remission. No study has assessed the usefulness of twice-daily budesonide 2mg foam on mucosal healing in ulcerative colitis patients. We explored the efficacy for mucosal healing of once- or twice-daily budesonide foam in distal ulcerative colitis patients. METHODS: This study was a multicentre, randomised, double-blind, placebo-controlled trial. In all, 165 patients with active, mild to moderate distal ulcerative colitis were randomised to three groups: once- or twice-daily budesonide 2mg/25ml foam, or placebo foam, for 6 weeks. Complete mucosal healing [endoscopic subscore = 0] and the safety profile were assessed at Week 6. Prespecified and post hoc analyses were used. RESULTS: The percentages of complete mucosal healing in the twice-daily budesonide foam group were 46.4% compared with 23.6% in the once-daily group [p = 0.0097], or 5.6% in the placebo group [p < 0.0001]. The percentages of clinical remission and the percentages of endoscopic subscore ≤ 1 in the twice-daily budesonide foam group were 48.2% and 76.8%, compared with 50.9% and 69.1% in the once-daily group [no difference], or 20.4% and 46.3% in the placebo group [p = 0.0029 and p = 0.0007], respectively. In the subgroup of patients with previous use of a 5-aminosalicylic acid suppository or enema, there was a greater percentage of complete mucosal healing in the twice-daily budesonide foam group [32.0%] compared with that in the once-daily [8.7%, p = 0.0774] or placebo groups [4.8%, p = 0.0763], though there was no significant difference. No serious adverse event occurred. CONCLUSIONS: A significantly greater percentage of patients receiving twice-daily administration of budesonide foam compared with once-daily administration/placebo achieved complete mucosal healing. This is the first study to evaluate the endoscopic efficacy of twice-daily administration of 6-week budesonide foam treatment for ulcerative colitis.

Metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer.

BACKGROUND: Colorectal metastasis of lobular carcinoma of the breast is a diagnostic challenge. It may macroscopically simulate primary colon cancer or inflammatory bowel disease. In some cases, the interval between the primary breast cancer and metastatic colorectal lesions is so long that the critical records for diagnosis including history might be lost or missed. CASE PRESENTATION: Reported herein is a case of metastatic lobular carcinoma of the breast masquerading as a primary rectal cancer developed in a 62-year-old Japanese woman. The case initially presented as a circumferential rectal lesion, and information on the patient's history of breast cancer was not noted. As the result of endoscopic biopsy, diagnosis of poorly differentiated rectal adenocarcinoma was made. The lesion was surgically resected after chemo-radiotherapy. Histopathological examination of the resected specimen with hematoxylin and eosin (HE) stain revealed a single-file arrangement of the tumor cells, reminiscent of lobular carcinoma of the breast. Immunohistochemical analysis revealed an immunophenotype consistent with lobular carcinoma of the breast. Because further review of the patient's history revealed an occurrence of 'poorly differentiated adenocarcinoma of the breast', which she had experienced 24 years earlier, the final diagnosis of the lesion was made as rectal metastasis from lobular breast carcinoma. CONCLUSIONS: Poorly differentiated adenocarcinoma of the colorectum is rarer than that of the stomach. Linitis plastica-type cancer of the colorectum is also rarer than that of the stomach. A lesson from the present case is that before we conclude a linitis plastica-type cancer of poorly differentiated type as a primary colorectal cancer, it is critical to exclude a possibility of metastatic colorectal cancer.

A large-scale nationwide multicenter prospective observational study of triple therapy using rabeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in Japan.

BACKGROUND: In recent years in Japan, the rate of clarithromycin (CAM) resistance in Helicobacter pylori has risen to around 30%, and the eradication rate with triple therapy [proton pump inhibitor + amoxicillin (AMPC) + CAM] has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice. METHODS: Patients with H. pylori-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days. RESULTS: The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of H. pylori treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies. CONCLUSION: In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe.

A multicenter study of the efficacy and safety of leukocytapheresis therapy without concomitant systemic steroid treatment in patients with active ulcerative colitis.

We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger's clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.