[Show abstract][Hide abstract] ABSTRACT: This prospective study was conducted to evaluate the significance of consecutive monitoring of fecal calprotectin and lactoferrin for the early diagnosis and prediction of pouchitis after restorative proctocolectomy for ulcerative colitis (UC).
Sixty patients who had ileostomy closure following total proctocolectomy and ileal pouch-anal anastomosis for UC were included. Stool samples were collected for the measurement of calprotectin and lactoferrin every 2 months up to 12 months after the ileostomy closure. When patients had symptoms suggestive of pouchitis, endoscopic examination was immediately undertaken. All asymptomatic patients underwent endoscopy at 12 months. Pouchitis was defined as a pouchitis disease activity index score of ≥7.
During the 12 months, 10 patients (17%) developed pouchitis. In patients with pouchitis, fecal calprotectin and lactoferrin levels were elevated already 2 months before the diagnosis of pouchitis. In contrast, these fecal biomarkers remained at low levels, and they did not change significantly in patients without pouchitis. A cutoff value of 56 μg/g for calprotectin had a sensitivity of 100% and a specificity of 84% to predict pouchitis, whereas a cutoff value of 50 μg/g for lactoferrin had a sensitivity of 90% and a specificity of 86%. At the time of endoscopy, the median calprotectin and lactoferrin levels were significantly higher in patients with pouchitis than those without pouchitis.
Elevated fecal calprotectin and lactoferrin levels appeared to be significant predictors of pouchitis after restorative proctocolectomy for UC. Consecutive monitoring of these fecal biomarkers is useful for the early diagnosis of pouchitis.Am J Gastroenterol advance online publication, 28 April 2015; doi:10.1038/ajg.2015.129.
Full-text · Article · Apr 2015 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: This prospective study was to evaluate the significance of fecal calprotectin and lactoferrin for the prediction of ulcerative colitis (UC) relapse.
Eighty UC patients in remission for ≥3 months on mesalamine as maintenance therapy were included. At entry, stool samples were collected for the measurement of calprotectin and lactoferrin. All patients were followed up for the following 12 months. To identify predictive factors for relapse, time-dependent analyses using the Kaplan-Meier graphs and Cox's proportional hazard model were applied.
During the 12 months, 21 patients relapsed. Mean calprotectin and lactoferrin levels were significantly higher in patients with relapse than those in remission (calprotectin-173.7 vs 135.5 μg/g, P = 0.02; lactoferrin-165.1 vs 130.7 μg/g, P = 0.03). A cutoff value of 170 μg/g for calprotectin had a sensitivity of 76 % and a specificity of 76 % to predict relapse, while a cutoff value of 140 μg/g for lactoferrin had a sensitivity of 67 % and a specificity of 68 %. In a multivariate analysis, calprotectin (≥170 μg/g) was a predictor of relapse (hazard ratio, 7.23; P = 0.002). None of the following parameters were significantly associated with relapse: age, gender, duration of UC, number of UC episode, severity of the previous episode, extent of UC, extraintestinal manifestation, and lactoferrin level.
Fecal calprotectin showed a higher sensitivity and specificity than fecal lactoferrin for predicting UC relapse. Fecal calprotectin level appeared to be a significant predictor of relapse in patients with quiescent UC on mesalamine as maintenance therapy.
Full-text · Article · Dec 2013 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Background: Several studies have reported that faecal calprotectin and lactoferrin showed a close correlation with endoscopic inflammation in patients with inflammatory bowel disease. However, the clinical significance of faecal calprotectin or lactoferrin in postoperative Crohn’s disease (CD) is not fully evaluated. This prospective study was to investigate the relationship between endoscopic activity, and faecal calprotectin and lactoferrin, and assess the predictive value of these markers for future recurrence.
Full-text · Article · Oct 2013 · United European Gastroenterology Journal
[Show abstract][Hide abstract] ABSTRACT: Background:
Early endoscopic lesions following resection for Crohn's disease (CD) are often observed. Currently, the relationship between this endoscopic observation and subsequent occurrence of CD lesions or recurrence is not understood well, but should be valuable in the context of predicting CD course. This prospective study was to investigate the impact of early endoscopic lesions on future clinical recurrence rates following ileocolonic resection for CD.
Forty patients who had maintained clinical remission, CD activity index (CDAI) <150 with mesalazine during 6 months after ileocolonic resection for CD were included. At 6 months after surgery, ileocolonoscopy was performed, and the endoscopic activity score at the proximal site of the anastomosis was determined according to Rutgeerts. All patients were regularly monitored for 5 years, and clinical recurrence was defined as CDAI ≥ 150. Corticosteroids, immunosuppressants, or biological agents were not given unless there was clinical recurrence.
At 6 months after surgery, the endoscopic scores were i0 or i1 in 27 patients, i2 in seven patients, i3 in four patients, and i4 in two patients. During the following 5 years, the clinical recurrence occurred in three (11%) patients with endoscopic score of i0 or i1, four (57%) patients with i2 score, three (75%) patients with i3 score, and two (100%) patients with i4 score, showing a significant positive correlation (p = 0.001) between the endoscopic severity of the proximal site of the anastomosis at 6 months after surgery and the clinical recurrence rate during the following 5 years.
The assessment of endoscopic lesions at the proximal site of the anastomosis appeared to be valuable for predicting subsequent clinical recurrence after ileocolonic resection for CD. Further studies in larger cohorts of patients are warranted to strengthen our findings.
Full-text · Article · Aug 2013 · United European Gastroenterology Journal
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim of this study was to investigate the long-term effect of enteral nutrition (EN) as a maintenance therapy in Crohn's disease (CD) patients following surgery.
This study was an extension of our previous study to prolong the duration of intervention and follow-up from 1 to 5 years. Forty consecutive patients who underwent resection for ileal or ileocolic CD were included. Following surgery, 20 patients received continuous elemental diet infusion during the nighttime plus a low-fat diet during the daytime (EN group). Another 20 patients received neither nutritional therapy nor food restriction (control group). All patients were followed for 5 years after operation. No patient received corticosteroid, immunosuppressants, or infliximab except patients who developed recurrence. The end point of this study was recurrence requiring biologic therapy or reoperation. Recurrence rates were analyzed on an intention-to-treat basis.
In the EN group, four patients could not continue tube intubation for elemental diet intake. Two patients (10 %) in the EN group and nine patients (45 %) in the control group developed recurrence requiring infliximab therapy (P = 0.03). The cumulative recurrence incidence rate requiring infliximab was significantly lower in the EN group vs the control group (P = 0.02). One patient (5 %) in the EN group and five patients (25 %) in the control group required reoperation for recurrence (P = 0.18). The cumulative incidence of reoperation was lower in the EN group vs the control group, the difference not being significant (P = 0.08).
The outcomes of this study suggest that EN therapy reduces the incidence of postoperative CD recurrence.
Full-text · Article · Sep 2012 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: The efficacy of granulocyte and monocyte adsorptive apheresis (GMA) for patients with a first episode of ulcerative colitis (UC) has been scarcely reported. This study was to see if the introduction of GMA at an early stage reduces corticosteroid administration and steroid dependency in the long term clinical course of UC.
Forty consecutive patients with moderately active symptoms as the first attack of UC were included. Twenty patients were treated with GMA, with or without corticosteroids (GMA group), and the other 20 were given corticosteroids without GMA (steroid group). All patients were monitored for 5 years. Relapses were treated in the same manner as the first attack in both groups. The total dose of steroid administered and the appearance of steroid-dependency were to be compared between the two groups.
All patients in both groups achieved clinical remission after the first attack. The mean number of relapses per patient was 2.8 in the GMA group and 2.9 in the steroid group (P=0.86). During this study, 5 patients in the GMA group did not require corticosteroids. The mean dose of steroid administered during the 5 years was 2141 mg in the GMA group vs 5443 mg in the steroid group (P=0.002). One patient in the GMA group and 7 in the steroid group were steroid-dependent at the end of the study (P=0.048).
In patients with the first UC episode, GMA therapy at an early stage significantly reduces steroid administration and steroid-dependency in the long-term clinical course.
Full-text · Article · Jan 2012 · Journal of Crohn s and Colitis
[Show abstract][Hide abstract] ABSTRACT: This prospective study was to assess the safety and feasibility of daily granulocyte and monocyte adsorptive apheresis (GMA) therapy in patients with active ulcerative colitis (UC).
Thirty consecutive patients with moderately or severely active UC received daily GMA treatment (5 sessions over 5 consecutive days) with the Adacolumn. Adverse events (AE), patient tolerability, and clinical symptoms were monitored daily.
Sixteen patients (53%) experienced AE during at least one GMA session. The most frequent AE was mild headache followed by fatigue and fever. None of the AE was serious, and all patients completed the 5 consecutive GMA sessions. Clinical symptoms (stool frequency and/or rectal bleeding) were improved in 21 patients (70%) during the course of GMA therapy. Clinical remission defined as normal stool frequency and no rectal bleeding was achieved in 7 patients (23%) after 5 GMA sessions. Seven of 20 patients (35%) with moderately active disease achieved clinical remission, whereas none of the 10 patients with severely active disease achieved clinical remission. Total and differential leukocyte counts, platelet count, and hemoglobin level did not significantly change, but C-reactive protein level significantly decreased during the course of GMA therapy.
This is the first report on daily GMA in the treatment of patients with UC. Daily GMA was safe and well tolerated without serious AE. Furthermore, daily GMA was associated with rapid improvement of clinical symptoms in patients with moderately active UC. However, controlled trials are warranted to assess a definite efficacy for daily GMA therapy.
Full-text · Article · Jun 2011 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Mesalazine is often used to maintain remission in patients with ulcerative colitis.
To investigate if increasing the dose of mesalazine is safe and effective for patients with ulcerative colitis who relapse under low-dose maintenance therapy.
Ninety consecutive patients who relapsed during maintenance therapy with oral mesalazine at 1.5-2.25g/day were included. All patients had mildly or moderately active ulcerative colitis at entry, and were treated with oral mesalazine at 4.0g/day for the following 8 weeks. At entry and week 8, endoscopic examinations were carried out to assess the severity of endoscopic inflammation. The primary as well as the secondary endpoints were clinical and endoscopic improvements at week 8.
No patient experienced any serious side effect, and the treatment with 4.0g/day mesalazine over the 8 week period was well tolerated by all patients. Fifty-nine patients (66%) achieved clinical improvement in stool frequency and/or rectal bleeding including 40 (44%) with clinical remission (normal stool frequency and no rectal bleeding). Forty-three patients (48%) showed endoscopic improvement including 25 (28%) with endoscopic remission.
Increasing the dose of mesalazine up to 4.0g/day appeared to be safe and effective for patients who relapsed under low-dose, 1.5-2.25g/day maintenance therapy.
Full-text · Article · Dec 2010 · Digestive and Liver Disease
[Show abstract][Hide abstract] ABSTRACT: This study was to investigate if measurement of peritoneal cytokines is valuable for an early diagnosis of peritonitis following colorectal surgery. One hundred consecutive patients who were to undergo elective resection for carcinoma of the sigmoid colon or the rectum were investigated. Abdominal exudate was obtained from a drainage tube daily after surgery for measuring interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. The relationship between peritoneal cytokine levels during the first 3 days after surgery and the development of peritonitis was investigated. Eight patients developed postoperative peritonitis due to anastomotic leakage and pelvic abscess, which was diagnosed on postoperative days 5-8. Peritoneal cytokine levels on postoperative days 1 and 2 were not significantly different between the 8 patients who developed peritonitis and 92 patients who did not: day 1, IL-1βP=0.32, IL-6 P=0.45, TNF-αP=0.85; day 2, IL-1βP=0.26, IL-6 P=0.68, TNF-αP=0.22. In contrast, the cytokine levels on day 3 were significantly higher in patients who developed peritonitis as compared with patients who did not: IL-1βP=0.008, IL-6 P<0.0001, TNF-αP=0.0001. The cytokines significantly increased during the first 3 days in patients who developed peritonitis: IL-1βP=0.049, IL-6 P=0.03, TNF-αP=0.01, while significantly decreased in patients who did not: IL-1βP<0.0001, IL-6 P<0.0001, TNF-αP<0.0001. The outcomes of this investigation showed that the rise in peritoneal IL-1β, IL-6 and TNF-α levels may be an additional early diagnostic predictor of intraabdominal complications following colorectal surgery.
[Show abstract][Hide abstract] ABSTRACT: Background:During active ulcerative colitis (UC), vast numbers of granulocytes, monocytes/macrophages (GM) infiltrate the mucosal tissue and can potentially exacerbate inflammation and injury. Accordingly, we were interested to see if selective depletion of GM by adsorption (GMA) impacts mucosal healing (MH) in UC patients.Methods:In all, 124 patients with clinically and endoscopically active UC received 5 or 10 GMA sessions at one or two sessions/week. The endoscopic severity of mucosal inflammation at entry and 1 week after the last GMA session were scored as follows: 0 = normal mucosa and inactive disease; 1 = mild inflammation; 2 = moderate inflammation; 3 = severe inflammation. Likewise, a score 0 or 1 at post-GMA course was defined as MH.Results:At entry the endoscopic severity of the mucosal inflammation was 2 in 100 patients (81%) and 3 in 24 patients (19%). Following the course of GMA, 56 patients (45%) achieved clinical remission (normal stool frequency and no rectal bleeding). Thirty-four of these 56 responders achieved MH; 32 (94%) of the 34 patients with MH had an endoscopic score of 2 (moderate inflammation) at entry. The maintained clinical remission rate was significantly higher in the 34 patients who achieved MH as compared with 22 patients who achieved clinical remission without MH (P = 0.0005).Conclusions:MH is achieved more frequently in patients with moderate than with severe endoscopic severity at entry. Further, patients with MH have a reduced risk of future clinical relapse as compared with patients who achieve remission without MH. (Inflamm Bowel Dis 2010)
Full-text · Article · Nov 2010 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: The efficacy of infliximab for endoscopic recurrence after resection of Crohn's disease (CD) has not yet been reported. The aim of this prospective study was to investigate the impact of infliximab on early endoscopic lesions after resection for CD.
Twenty-six patients maintaining clinical remission (CD activity index [CDAI] score <150) with mesalamine (3 g/day) after resection showed endoscopic recurrence in the neoterminal ileum at 6 months postoperatively (=baseline). Over the following 6 months, 10 patients were treated with continuous mesalamine (3 g/day), 8 patients were treated with azathioprine therapy (50 mg/day), and the other 8 patients were treated with infliximab therapy (5 mg/kg, every 8 weeks). During ileocolonoscopy at baseline and 6 months later, mucosal biopsies were taken for cytokine assays.
During 6-month observation, no patients in the infliximab group, 3 (38%) in the azathioprine group, and 7 (70%) in the mesalamine group developed clinical recurrence (CDAI >or=150) (P = 0.01). At 6 months, endoscopic inflammation was improved in 75% of patients in the infliximab group, 38% in the azathioprine group, and 0% in the mesalamine group (P = 0.006). The mucosal interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha levels significantly decreased in the infliximab group, while they significantly increased in the mesalamine group, and they did not change significantly in the azathioprine group.
Infliximab therapy showed clear suppressive effects on clinical and endoscopic disease activity, and mucosal cytokine production in patients with early endoscopic lesions after resection. To confirm our conclusions, randomized controlled trials with a larger number of patients are necessary.
Full-text · Article · Oct 2009 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: Hitherto, the efficacy of enteral nutrition (EN) on clinical outcomes during biological maintenance therapy in Crohn's disease (CD) has not been investigated. This prospective study was to assess the efficacy of EN on the maintenance rate of clinical remission in patients with quiescent CD receiving infliximab as maintenance therapy.
Fifty-six patients who achieved clinical remission with infliximab induction therapy received infliximab as maintenance therapy (5 mg/kg, every 8 weeks). Thirty-two of the 56 patients received concomitant EN: elemental diet infusion during night-time and a low fat diet during daytime (EN group), while the remaining 24 patients received neither nutritional therapy nor food restriction (non-EN group). All patients were followed for 56 weeks; CD activity index (CDAI) was assessed and CDAI < 150 was defined as clinical remission.
During the 56-week observation, the mean CDAI was not significantly different between the 2 groups. Seven patients in the EN group ceased EN therapy because they maintained complete remission. On an intention-to-treat basis, 25 patients in the EN group (78%) and 16 patients in the non-EN group (67%) remained in clinical remission during the 56-week observation (P = 0.51).
The outcomes of this prospective study showed that concomitant EN during infliximab maintenance therapy does not significantly increase the maintenance rate of clinical remission in patients with CD.
Full-text · Article · Oct 2009 · Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: This review study was designed to evaluate the efficacy of enteral nutrition (EN) for the maintenance of remission in patients with Crohn's disease (CD) who achieved medically or surgically induced remission.
The Medline, Embase, Ovid, and Cochrane database search of literature was carried out to identify studies that reported the efficacy of EN for the maintenance of remission in CD. The main outcome measure was the occurrence of clinical or endoscopic relapse.
Ten studies were included: one randomized controlled trial, three prospective non-randomized trials, and six retrospective studies. Elemental, semielemental or polymeric diets were used as an oral supplement or a nocturnal tube feeding in addition to ordinary foods. Comparing outcomes between patients who received EN and those who did not, the clinical remission rate was significantly higher in those with EN in all seven studies. In two studies, EN showed suppressive effects on endoscopic disease activity. In all four studies investigating impacts of the quantity of enteral formula on clinical remission, higher amounts of enteral formula were associated with higher remission rates: > or =30 kcal/kg ideal body weight/day (vs. <30 kcal/kg ideal body weight/day), > or =1200 kcal/day (vs. <1200 kcal/day), and > or =1600 kcal/day (vs. <1600 kcal/day). Quantitative pooling of studies was not feasible because of the diversity of interventions and outcome measures among the studies.
Although the evidence level is not high, the available data suggest that EN may be useful for maintaining remission in patients with CD. Large randomized controlled trials are necessary to assess a definite efficacy of EN for the maintenance of remission.
Full-text · Article · Sep 2009 · European journal of gastroenterology & hepatology
[Show abstract][Hide abstract] ABSTRACT: Currently, published reports of mucosal inflammation in the terminal ileum of ulcerative colitis (UC) before colectomy are scarce.
To investigate inflammation in the terminal ileum of UC patients by endoscopic examinations and measurement of mucosal cytokine profiles.
Fifty consecutive patients with active UC were studied. At ileocolonoscopy, mucosal biopsies were taken from the terminal ileum. As control, mucosal biopsies from 20 patients without inflammation were examined.
Thirty-eight patients showed endoscopically normal terminal ileum, four showed backwash ileitis, and eight showed non-backwash ileitis (ileitis with normal caecum). Pancolitis was observed in all of four patients with backwash ileitis, in 4 of 8 (50%) with non-backwash ileitis, and in 4 of 38 (11%) without ileal inflammation (P=0.0002). Extraintestinal manifestations were observed in none of 4 patients with backwash ileitis, in 6 of 8 (75%) with non-backwash ileitis, and in 3 of 38 (8%) without ileal inflammation (P<0.0001). In patients with backwash ileitis and non-backwash ileitis, ileal interleukin [IL]-1beta, IL-6, IL-8 and tumour necrosis factor-alpha levels were significantly elevated compared with the control group. Only extraintestinal manifestation was associated with higher ileal cytokine levels, whereas age, sex, and duration, extent and severity of UC did not show any apparent association.
In patients with backwash ileitis, elevated ileal cytokines might reflect a reaction to regurgitation of colonic content into the ileum, but in patients without backwash ileitis, alternative factors are expected to contribute to the aetiology of ileal inflammation. Patients with extraintestinal manifestations had elevated ileal cytokine levels.
No preview · Article · Apr 2008 · Digestive and Liver Disease
[Show abstract][Hide abstract] ABSTRACT: This study used meta-analytical techniques to compare the incidence of recurrence and the indication for reoperation in patients with Crohn's disease (CD) who underwent their first operation, due to perforating disease versus patients who underwent their first operation due to nonperforating disease.
Comparative studies published between 1988 and 2005 of perforating versus nonperforating CD were included. Using a random effects model, end points evaluated were recurrence of CD given as reoperation, and the indication for reoperation, i.e., perforating or nonperforating. Heterogeneity (HG) was assessed and a sensitivity analysis was performed to account for bias in patient selection.
Thirteen studies (12 nonrandomized retrospective, 1 nonrandomized prospective) reported on 3,044 patients, of which 1,337 (43.9%) had perforating indications (P group) and 1,707 (56.1%) had nonperforating indications (NP group) for surgery. The recurrence was found to be significantly higher in the P group compared to the NP group (HR 1.50, P= 0.002), with significant HG among studies (P < 0.001). The recurrence remained significantly higher in the P group compared with the NP group during sensitivity analysis of high-quality studies (HR 1.47, P= 0.005) and more recent studies (HR 1.51, P= 0.05), but still demonstrating significant HG (P= 0.08 and P < 0.001, respectively). At reoperation, concordance was found in the disease type of those patients re-presenting with perforating disease (OR 5.93, P < 0.001, without significant HG among studies P= 0.15) and those with nonperforating disease (OR 5.73, P < 0.001, with significant HG among studies P < 0.001). Concordance in disease type remained when considering only high-quality studies (P: OR 7.48, P < 0.001; NP: OR 7.48, P < 0.001) and more recent studies (P: OR 5.95, P < 0.001; NP: OR 5.95, P < 0.001), both not associated with HG among studies (P= 0.47 and P= 0.60, respectively).
The indication for reoperation in CD tends to be the same as the primary operation, i.e., perforating disease tends to re-present as perforating disease, and nonperforating as nonperforating. Also, perforating CD appears to be associated with a higher recurrence rate compared with nonperforating CD. However, because of significant HG among studies, further studies should be undertaken to confirm this finding.
Full-text · Article · Feb 2008 · The American Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Long-term enteral nutrition may maintain clinical and endoscopic remission in patients with Crohn's disease (CD). The aim of this prospective study was to investigate the impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal tissue cytokines in patients with quiescent CD.
Forty patients with CD who achieved clinical remission were included. Of these, 20 received continuous elemental diet (Elental) infusion during the nighttime and a low-fat diet during the daytime (EN group) and 20 received neither nutritional therapy nor food restriction (non-EN group). With these regimens, all 40 patients were monitored for 1 year. Further, ileocolonoscopy was performed at entry, at 6 and 12 months, and mucosal biopsies were taken for cytokine assays.
On an intention-to-treat basis, 5 patients (25%) in the EN group and 13 (65%) in the non-EN group had a clinical relapse during the 1-year observation (P = 0.03). The mean endoscopic inflammation (EI) scores were not significantly different between the groups at both entry and 6 months, but at 12 months EI scores were significantly higher in the non-EN group than in the EN group (P = 0.04). Additionally, the mucosal tissue interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha levels significantly increased with time in the non-EN group (entry versus 12 months, IL-1beta, P = 0.02; IL-6, P = 0.002; TNF-alpha, P = 0.001). In the EN group these cytokines did not show a significant increase.
Long-term enteral nutrition in patients with quiescent CD has a clear suppressive effect on clinical and endoscopic disease activities and the mucosal inflammatory cytokine levels.
Full-text · Article · Dec 2007 · Inflammatory Bowel Diseases