[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
Full-text · Article · Dec 2015 · BMC Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Refractory ulcerative colitis (UC) that does not respond to medical therapy often requires surgery even during pregnancy. Although surgical cases of UC during pregnancy were reported previously, the standard surgical strategy for both colitis and pregnancy was unclear. Herein, fetal and maternal safety as well as the strategy for this unusual surgical procedure during pregnancy in patients with UC are considered. A 28-year-old woman was diagnosed with left-sided moderate UC at 12 weeks of pregnancy; toxic megacolon was suspected, and surgery was required. Although the baby's gestational age was 23 weeks and 3 days, a cesarean section was performed before the colectomy. In a next case, a 28-year-old woman had a 2-year history of left-sided UC. Her colitis flared up at 11 weeks of pregnancy. Colectomy was performed because her colitis was unresponsive to conservative therapy, and the pregnancy was continued, with a transvaginal delivery at 36 weeks. In patients with UC, the need for surgery should be determined promptly based on disease severity, whether or not the patient is pregnant. The need for surgery should not be affected by pregnancy. The pregnancy should be continued for as long as possible when there are no fetal and maternal complications. Both cesarean section and colectomy should be performed independently if necessary.
Preview · Article · Mar 2015 · Case Reports in Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Background and aims
Leukocytapheresis is an extracorporeal therapy for ulcerative colitis. However, no large-scale study on leukocytapheresis has been reported. This large-scale, prospective, observational study aimed to evaluate the treatment outcomes of leukocytapheresis for active ulcerative colitis in clinical practice.
Patients with active ulcerative colitis treated with leukocytapheresis using a Cellsorba E column between May 2010 and December 2012 were enrolled from 116 medical facilities in Japan.
A total of 847 patients were enrolled, and 623 were available for efficacy analysis. Out of 847 patients, 80.3% of the patients had moderate to severe disease activity, and 67.6% were steroid refractory. As concomitant medications, 5-aminosalicylic acids, corticosteroids, and thiopurines were administered to 94.8%, 63.8%, and 32.8% of the patients, respectively. In addition, infliximab and tacrolimus were concomitantly used in 5.8% and 12.3%, respectively. Intensive leukocytapheresis (≥ 4 leukocytapheresis sessions within the first 2 weeks) was used in > 70% of the patients. Adverse events were seen in 10.3% (87/847), which were severe in only 5 patients (0.6%). Any concomitant medications did not increase the incidence of adverse events. Intensive leukocytapheresis was as safe as the conventional weekly procedure. The overall clinical remission rate was 68.9% (429/623), and the mucosal healing rate was 62.5% (145/232). Clinical remission was achieved more frequently and rapidly in the intensive group than in the weekly group.
This large-scale study indicates that leukocytapheresis, including intensive procedure, is a safe and effective therapeutic option for active ulcerative colitis.
Full-text · Article · Sep 2014 · Journal of Crohn s and Colitis
[Show abstract][Hide abstract] ABSTRACT: Background & aims
To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC.
Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used.
The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (rs = 0.7371, P < 0.0001) in the validation set.
Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.
No preview · Article · Sep 2014 · Journal of Crohn s and Colitis
[Show abstract][Hide abstract] ABSTRACT: Background aims
In patients with inflammatory bowel disease infected with hepatitis B virus (HBV), immunosuppressive therapy required to suppress active inflammatory bowel disease may promote HBV reactivation.
A 27-year-old corticosteroid-naive woman with Crohn's disease (CD) activity index of 249.8 complicated by HBV infection was offered Entecavir to control HBV reactivation during immunosuppressive therapy for CD. The patient refused Entecavir, fearing that it might adversely affect her pregnancy outcome. Instead, we applied intensive granulocyte/monocyte adsorptive apheresis (GMA) at two sessions per week to deplete inflammatory cytokine-producing leucocytes as an immunosuppressive therapy in this case.
GMA induced stable remission (CD activity index, I 105) and endoscopic improvement without HBV reactivation or safety concern. Furthermore, CD remission was paralleled by suppression of tumor necrosis factor and interleukin as measured in serum samples.
Immunosuppressive therapy required to treat an active CD potentially can promote HBV reactivation and worsen liver function. In this study involving a CD case complicated by chronic HBV infection, intensive GMA as a non-pharmacologic treatment intervention was associated with clinical remission and endoscopic improvement without HBV reactivation. Furthermore, GMA was well-tolerated and was without any safety concern. However, suppression of tumor necrosis and interleukin-6by GMA in this clinical setting is potentially very interesting.
[Show abstract][Hide abstract] ABSTRACT: To clarify the usefulness of postsurgical capsule endoscopy (CE) in the diagnosis of recurrent small bowel lesions of Crohn's disease (CD).
This prospective study included 19 patients who underwent ileocolectomy or partial ileal resection for CD. CE was performed 2-3 wk after surgery to check for the presence/absence and severity of lesions remaining in the small bowel, and for any recurrence at the anastomosed area. CE was repeated 6-8 mo after surgery and the findings were compared with those obtained shortly after surgery. The Lewis score (LS) was used to evaluate any inflammatory changes of the small bowel.
One patient was excluded from analysis because of insufficient endoscopy data at the initial CE. The total LS shortly after surgery was 428.3 on average (median, 174; range, 8-4264), and was ≥ 135 (active stage) in 78% (14 of 18) of the patients. When the remaining unresected small bowel was divided into 3 equal portions according to the transition time (proximal, middle, and distal tertiles), the mean LS was 286.6, 83.0, and 146.7, respectively, without any significant difference. Ulcerous lesions in the anastomosed area were observed in 83% of all patients. In 38% of the 13 patients who could undergo CE again after 6-8 mo, the total LS was higher by ≥ 100 than that recorded shortly after surgery, thus indicating a diagnosis of endoscopic progressive recurrence.
Our pilot study suggests that CE can be used to objectively evaluate the postoperative recurrence of small bowel lesions after surgery for CD.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess patients' acceptance of therapeutic leukocytapheresis known as cytapheresis (CAP) for the treatment of an active flare of inflammatory bowel disease (IBD). A questionnaire was sent to 155 IBD patients who had been treated with CAP for an active flare of IBD at the IBD center of Hyogo College of Medicine between January 2009 and July 2012. In the questionnaire, patients were asked to evaluate CAP including efficacy, safety, unfavorable features and their willingness to be retreated with CAP for a subsequent IBD flare-up. Seventy-eight percent (112 of 155 patients) including 86 with ulcerative colitis and 26 with Crohn's disease completed the questionnaire. The need for coming to hospital for CAP, needle pain during blood access, sparing time for CAP process were scored by 57%, 58%, and 58.9% of the patients, respectively as unfavorable. Patients highly favored the safety of CAP, the sum of very and relatively favorable was 89%, higher than for efficacy (68%). Seventy-two percent of patients favored retreatment with CAP. In binary logistic regression analysis, the levels of satisfaction for efficacy (P < 0.001), and inconvenience for CAP treatment time (P < 0.001) were highly significant factors for patients' willingness to be retreated. Bearing in mind that CAP is a non-pharmacologic treatment intervention, our analyses indicated that IBD patients favored high efficacy, as well as comfort of CAP or maintaining their normal social activity even during an active phase of the disease. Patient's acceptability for CAP appeared to be determined by the balance of these factors.
No preview · Article · Oct 2013 · Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
[Show abstract][Hide abstract] ABSTRACT: Background
Adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients’ demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC.
In a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger’s clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients’ demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied.
After 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032).
In this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.
Full-text · Article · Feb 2013 · BMC Gastroenterology