Faecal calprotectin level for assessing endoscopic activity and predicting future clinical course in patients with moderately active ulcerative colitis undergoing granulomonocytapheresis: a prospective cohort study.

BACKGROUND: Calprotectin is a stable neutrophil protein, which can be measured in faecal samples. The faecal level of calprotectin increases during disease activity in ulcerative colitis (UC). Nonetheless, the relevance of faecal calprotectin (FC) measurement during granulomonocytapheresis (GMA) for UC has not yet been fully evaluated. This prospective study was to investigate the value of FC for assessing disease activity and predicting clinical course in UC patients undergoing GMA therapy. METHODS: One hundred and eighty-four patients with moderately active UC with endoscopic activity (Mayo endoscopic subscore [MES] = 2 or 3) received Adacolumn GMA therapy (10 apheresis sessions over consecutive 5 weeks). Patients who achieved clinical remission were subsequently given maintenance medications for 12 months. FC levels were measured at entry and after treatment. RESULTS: After GMA, 80 of the 184 patients (43%) achieved clinical remission, and 51 (28%) achieved mucosal healing (MH; MES = 0 or 1). The median FC level significantly decreased in patients who achieved MH (P = 0.02), but not in those without MH. Thirty-four patients (43%) relapsed during the 12-month follow-up. The median FC level at the end of GMA therapy was significantly higher in patients who subsequently relapsed than in those who maintained remission (149.5 vs 45.5 µg/g, P < 0.001). A cut off value of 114 µg/g had a sensitivity of 76% and a specificity of 85% to predict future relapse. CONCLUSIONS: Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy.

PURPOSE: This prospective study was to evaluate the significance of fecal calprotectin and lactoferrin for the prediction of ulcerative colitis (UC) relapse. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effects of preoperative leukocytapheresis on inflammatory cytokines following surgery for ulcerative colitis: a prospective randomized study.

Targeted extracorporeal granulocyte and monocyte apheresis (GMA) has produced clinical efficacy together with down modulation of specific inflammatory cytokines in patients with ulcerative colitis (UC). This study was to investigate if preoperative GMA produces immunological effect on dysregulated immune activity after restorative proctocolectomy (RPC) in patients with UC. Forty patients requiring RPC were included. Twenty randomly selected patients received five GMA sessions with the Adacolumn over two consecutive weeks before RPC (GMA group). RPC was performed within 2 weeks following the last GMA session. The other 20 patients did not receive GMA before RPC (non-GMA group). Blood samples were obtained immediately before surgery, at 1 h after surgery, and on postoperative Days 1, 3, and 7 from all patients. Abdominal exudate was obtained from the drainage tube at 1 h after surgery, and on postoperative Days 1, 3, and 7. Concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in plasma and peritoneal fluid from a drainage tube were measured by enzyme linked immunosorbent assay. Between the two groups, patients were matched with respect to age, sex, UC duration, severity, extent and the dose of prednisolone at surgery. IL-1ß, IL-6, and TNF-α levels in plasma and peritoneal fluid were not significantly different between the two groups during the entire study period. Based on the assays of IL-1ß, IL-6, and TNF-α levels in the plasma and the peritoneal fluid, this study did not find any effect on these inflammatory cytokines by preoperative GMA in patients with UC who underwent RPC.

Enteral nutrition to suppress postoperative Crohn's disease recurrence: a five-year prospective cohort study.

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. METHODS: 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. RESULTS: 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). CONCLUSION: The outcomes of this study suggest that EN therapy reduces the incidence of postoperative CD recurrence.

Leucine-Rich Alpha-2 Glycoprotein Is a Reliable Serum Biomarker for Evaluating Clinical and Endoscopic Disease Activity in Inflammatory Bowel Disease.

BACKGROUND: Leucine-rich alpha-2 glycoprotein (LRG) is a novel serum biomarker for inflammation in inflammatory bowel disease (IBD). This prospective study aimed to compare the value of LRG with C-reactive protein (CRP) and fecal calprotectin for evaluating clinical and endoscopic disease activity in patients with IBD. METHODS: At entry, clinical and endoscopic disease activity was assessed in 267 patients with IBD (ulcerative colitis [UC] 203; Crohn's disease [CD] 64), and the levels of LRG, CRP and fecal calprotectin were measured. The accuracy of the biomarkers for the detection of clinical and endoscopic disease activity was determined by the area under the receiver operating characteristic curve. RESULTS: Leucine-rich alpha-2 glycoprotein showed a significant relationship with the clinical and endoscopic severity in both UC and CD (both diseases, P < .0001). In the clinical assessment of UC, the accuracy of LRG was significantly higher than that of CRP (0.73 vs 0.63; P < .001). In the endoscopic assessment of UC, the accuracy of LRG was significantly higher than that of CRP (P = .01), but it was significantly lower than that of fecal calprotectin (P = .009; LRG, 0.80; CRP, 0.72; fecal calprotectin, 0.91). In the clinical and endoscopic assessment of CD, the accuracy was not significantly different between the biomarkers (clinical activity: LRG, 0.71; CRP, 0.64; fecal calprotectin, 0.66; in endoscopic activity: LRG, 0.79; CRP, 0.78; fecal calprotectin, 0.81). CONCLUSIONS: Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to CRP for the assessment of UC.

Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to C-reactive protein for the assessment of ulcerative colitis.

Peritoneal cytokines as early markers of peritonitis following surgery for colorectal carcinoma: a prospective study.

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)-1ß, 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-1ßP=0.32, IL-6 P=0.45, TNF-αP=0.85; day 2, IL-1ßP=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-1ßP=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-1ßP=0.049, IL-6 P=0.03, TNF-αP=0.01, while significantly decreased in patients who did not: IL-1ßP<0.0001, IL-6 P<0.0001, TNF-αP<0.0001. The outcomes of this investigation showed that the rise in peritoneal IL-1ß, IL-6 and TNF-α levels may be an additional early diagnostic predictor of intraabdominal complications following colorectal surgery.

Coronary Microvascular Dysfunction Restored After Surgery in Inflammatory Bowel Disease: A Prospective Observational Study.

Background We aimed to investigate the presence and severity of coronary microvascular dysfunction (CMD) in inflammatory bowel disease (IBD) including Crohn disease and ulcerative colitis and to elucidate the influence of surgical resection of the diseased intestines on CMD by assessing coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography. Methods and Results Thirty-seven patients with IBD (aged 44±15 years; 22 patients with Crohn disease and 15 patients with ulcerative colitis) and 30 controls (aged 46±12 years) were enrolled. For CFVR measurement, coronary flow velocity was recorded at rest and during hyperemia by ADP infusion using transthoracic Doppler echocardiography, and CFVR <2.5 defined CMD. CFVR measurement was repeated before and within 1 year after surgery. CFVR was similarly and significantly lower in patients with Crohn disease and those with ulcerative colitis than controls (Crohn disease: 2.92±1.03 [P<0.05 versus controls], ulcerative colitis: 2.99±0.65 [P<0.05 versus controls], and controls: 3.84±0.75). Multiple linear regression analysis showed that the presence of IBD and baseline hs-CRP (high-sensitivity C-reactive protein) were independently associated with low CFVR among all study participants (ß=-0.403 [P=0.001] and -0.237 [P=0.037], respectively). Hyperemic coronary flow velocity significantly improved after surgery only in patients with IBD who had CMD. CFVR significantly improved in patients with IBD who had both CMD and non-CMD, and the extent of CFVR improvements were greater in patients with CMD than non-CMD. Multiple linear regression analysis showed that the reduction of hs-CRP was independently associated with improvement of hyperemic coronary flow velocity and CFVR among all patients with IBD (ß=-0.481 [P=0.003] and ß=-0.334 [P=0.043], respectively). Conclusions IBD is associated with CMD, which improved after surgical resection of diseased intestines.

Impact of Preoperative Nutritional Status on the Incidence Rate of Surgical Complications in Patients With Inflammatory Bowel Disease With Vs Without Preoperative Biologic Therapy: A Case-Control Study.

OBJECTIVES: A case-control study was undertaken to assess the impact of preoperative nutrition on surgical outcomes in patients with inflammatory bowel disease with vs without preoperative biologic therapy. METHODS: Seventy patients who had received biologic therapy within 8 weeks before undergoing resection for active ulcerative colitis (n = 34) or Crohn's disease (n = 36) were included (BIO group). The control group comprised 70 patients without exposure to biologics, selected based on 5 matching criteria: inflammatory bowel disease subtype (ulcerative colitis/Crohn's disease), age (≤ or >40 years), disease severity (moderate/severe), surgical approach (open/laparoscopic), and main surgical procedure. Poor nutrition was defined as the presence of at least one of the following criteria: weight loss >10%-15% within 6 months, body mass index <18.5 kg/m, Subjective Global Assessment Grade C, or serum albumin <30 g/L. RESULTS: The proportion of patients with preoperative poor nutrition was 43% in the BIO and 33% in the control groups (P = 0.22). The incidence of postoperative infectious complications (anastomotic leak, intra-abdominal abscess, enterocutaneous fistula, or wound infection) was 16% in the BIO and 14% in the control groups (P = 0.81). In the BIO group, poor nutrition significantly increased the risk of infectious complications (27% vs 8% without poor nutrition, P = 0.03). In addition, in the control group, the incidence of infectious complications was higher in patients with poor nutrition, but not significantly (22% vs 11%, P = 0.21). DISCUSSION: Poor nutrition increases the risk of infectious complications after surgery. The detrimental effects of poor nutrition on postsurgical infection may be enhanced in patients who have received biologic therapy preoperatively.

Mucosal inflammation in the terminal ileum of ulcerative colitis patients: endoscopic findings and cytokine profiles.

BACKGROUND: Currently, published reports of mucosal inflammation in the terminal ileum of ulcerative colitis (UC) before colectomy are scarce. AIM: To investigate inflammation in the terminal ileum of UC patients by endoscopic examinations and measurement of mucosal cytokine profiles. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoscopic score vs. fecal biomarkers for predicting relapse in patients with ulcerative colitis after clinical remission and mucosal healing.

Objectives: Achieving endoscopic remission or decreasing the level of fecal biomarkers as an ideal therapeutic goal in ulcerative colitis has not been determined. This prospective study was to compare the clinical relevance of endoscopic score with fecal biomarkers for predicting relapse after clinical remission and mucosal healing (MH). Methods: One hundred and sixty-four patients who achieved clinical remission and MH (Mayo endoscopic subscore (MES) 0 or 1) were included. At entry, fecal samples were collected for the measurement of calprotectin, lactoferrin, and hemoglobin. Thereafter patients received masalamine maintenance therapy, and were followed for 12 months. Results: During the 12-month study, 46 patients (28%) relapsed. The relapse rate was not significantly higher in 27/80 patients (34%) with MES 1 than in 19/84 patients (23%) with MES 0 (P = 0.16). The median fecal calprotectin, lactoferrin, and hemoglobin were significantly higher in patients with relapse than those in remission (calprotectin, 182 vs. 94 µg/g; lactoferrin, 185.5 vs. 111 µg/g; hemoglobin, 168 vs. 104 ng/mL; all P < 0.0001). A cutoff value of 115 µg/g calprotectin had 83% sensitivity and 81% specificity to predict relapse, whereas lactoferrin, 145 µg/g had 70% sensitivity and 79% specificity, and hemoglobin, 135 ng/mL showed 74% sensitivity and 73% specificity. The accuracy was significantly lower for hemoglobin as compared with calprotectin and lactoferrin. Conclusions: Fecal calprotectin, lactoferrin, and to a lesser degree fecal hemoglobin appeared to be objective biomarkers for predicting future relapse after achieving clinical remission and MH. The predictive value of these biomarkers was higher than with MES.

Impacts of long-term enteral nutrition on clinical and endoscopic disease activities and mucosal cytokines during remission in patients with Crohn's disease: a prospective study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pouchitis and pre-pouch ileitis developed after restorative proctocolectomy for ulcerative colitis: a case report.

We report a case of pouchitis and pre-pouch ileitis, and inflammation in the neo-terminal ileum proximal to the pouch, developed after restorative proctocolectomy for ulcerative colitis. A 35-year old female presented with fever and abdominal pain five weeks after ileostomy closure following proctocolectomy. Computed tomography showed collection of feces in the pouch and proximal ileum. A drainage tube was placed in the pouch perianally, and purulent feces were discharged. With antibiotic treatment, her symptoms disappeared, but two weeks later, she repeatedly developed fever and abdominal pain along with anal bleeding. Pouchscopy showed mucosal inflammation in both the pouch and the pre-pouch ileum. The mucosal cytokine production was elevated in the pouch and pre-pouch ileum. With antibiotic and corticosteroid therapy, her symptoms were improved along with improvement of endoscopic inflammation and decrease of mucosal cytokine production. The fecal stasis with bacterial overgrowth is the major pathogenesis of pouchitis and pre-pouch ileitis in our case.

Faecal biomarkers for screening small bowel inflammation in patients with Crohn's disease: a prospective study.

BACKGROUND: The value of faecal biomarkers for screening small bowel inflammation in patients with Crohn's disease (CD) remains to be elucidated. This prospective study was to evaluate the utility of faecal biomarkers for detecting small intestinal inflammation. METHODS: A total of 122 consecutive patients with a diagnosis of CD in the small intestine were screened for eligibility. Computed tomography enterography (CTE) was undertaken to evaluate small bowel inflammation followed by colonoscopy to confirm no large bowel involvement. Seventy eligible patients with inflammation confined to the small intestine were included. Faecal samples were collected for assaying calprotectin, lactoferrin and haemoglobin. For assessing the degree of small bowel inflammation, a semi-quantitative scoring system (CTE0, normal; CTE1, mild; CTE2, moderate; CTE3, severe) was applied. RESULTS: The median calprotectin, lactoferrin and haemoglobin levels were significantly higher in patients with small bowel inflammation, CTE scores 1-3 (n = 42) versus 0 (n = 28): calprotectin, 330 versus 40 ng/ml, p < 0.0001; lactoferrin, 14 versus 3 ng/ml, p < 0.0001; haemoglobin, 29.5 versus 6.5 ng/ml, p = 0.005. There was a strong positive relationship between the faecal biomarkers and CTE score: calprotectin, p < 0.0001; lactoferrin, p < 0.0001; haemoglobin, p = 0.0004. A cutoff value of 140 ng/ml for calprotectin had a sensitivity of 69% and a specificity of 82% with an area under the receiver operating characteristic curve (AUC) of 0.82 to detect small bowel inflammation (CTE scores 1-3), while lactoferrin 6 ng/ml had a sensitivity of 69% and a specificity of 79% with an AUC of 0.83, and haemoglobin 9 ng/ml showed a sensitivity of 71% and a specificity of 39% with an AUC of 0.70. CONCLUSIONS: Faecal calprotectin, lactoferrin, and to a lesser degree haemoglobin are relevant biomarkers for screening small bowel inflammation in CD patients without large bowel involvement. Further well-designed large-scale studies in this clinical setting should strengthen our findings.

Impact of selective leukocytapheresis on mucosal inflammation and ulcerative colitis: cytokine profiles and endoscopic findings.

BACKGROUND: This prospective study assessed the impact of selective leukocytapheresis (SLA) on mucosal inflammation in patients with active ulcerative colitis (UC) by endoscopic investigations and measurement of mucosal cytokine profiles. MATERIALS AND METHODS: Twenty-eight patients with moderately active UC received 5 SLA sessions with the Adacolumn over 5 consecutive weeks. The Adacolumn leukocytapheresis carriers selectively adsorb granulocytes, monocytes/macrophages, and smaller subsets of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Before and after treatment, mucosal biopsies were obtained from multiple sites in the large bowel. As control, colonic biopsies from 20 patients without bowel inflammation were examined. Mucosal cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: At entry, the mucosal concentrations of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were significantly higher compared with the control group, whereas IL-1ra/IL-1beta ratio was significantly lower. Clinical remission was achieved in 19 (68%) patients. In patients with clinical remission but not in those without remission, the mucosal tissue concentrations of IL-1beta, IL-1ra, IL-6, IL-8, and TNF-alpha significantly decreased, whereas the IL-1ra/IL-1beta ratio significantly increased. Furthermore, endoscopic remission of mucosal inflammation was observed in 14 (50%) patients, which was associated with a decline in mucosal IL-1beta, IL-1ra, IL-6, IL-8, and TNF-alpha and an increase in IL-1ra/IL-1beta ratio. CONCLUSIONS: Depleting granulocytes and monocytes/macrophages by SLA should mitigate cytokine profiles in the intestinal mucosa and correct an imbalance between pro- and anti-inflammatory cytokines in active UC.

Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis.

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs 145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.

Acute duodenal Crohn's disease successfully managed with low-speed elemental diet infusion via nasogastric tube: a case report.

Duodenal Crohn's disease is rare, and patients without obstruction are treated medically. We herein report one case whose duodenal Crohn's disease was successfully managed with low-speed elemental diet infusion through a nasogastric tube. A 28-year-old female developed acute duodenal Crohn's disease. Upper GI radiologic and endoscopic examinations showed a stricture in the duodenal bulb. Using the duodenal biopsy specimens, mucosal cytokine levels were measured; interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha levels were remarkably elevated. For initial 2 wk, powdered mesalazine was orally given but it was not effective. For the next 2 wk, she was treated with low-speed elemental diet therapy using a commercially available Elental(TM), which was infused continuously through a nasogastric tube using an infusion pump. The tip of the nasogastric tube was placed at an immediate oral side of the pylorus. The infusion speed was 10 mL/h (usual speed, 100 mL/h). After the 2-wk treatment, her symptoms were very much improved, and endoscopically, the duodenal stricture and inflammation improved. The duodenal mucosal cytokine levels remarkably decreased compared with those before the treatment. Although our experience was limited, low-speed elemental diet infusion through a nasogastric tube may be a useful treatment for acute duodenal Crohn's disease.

Serial monitoring of faecal calprotectin for the assessment of endoscopic recurrence in asymptomatic patients after ileocolonic resection for Crohn's disease: a long-term prospective study.

BACKGROUND: It is recommended that ileocolonoscopy is performed within 1 year after resection for Crohn's disease (CD). Nevertheless, optimal monitoring strategies for recurrence after the ileocolonoscopy remain to be elucidated. This prospective study was to evaluate the value of serial monitoring of faecal calprotectin (FC) after ileocolonoscopy for the assessment of endoscopic recurrence in asymptomatic patients. METHODS: Patients in clinical remission who had no endoscopic recurrence at ileocolonoscopy 6-12 months after ileocolonic resection were studied. FC levels were measured every 2 months up to 24 months after the ileocolonoscopy. When the FC level was elevated (⩾140 µg/g), a second ileocolonoscopy was immediately undertaken. In contrast, patients who maintained low FC levels (<140 µg/g) during the 24-month follow up underwent a second ileocolonoscopy at the end of the study. Endoscopic recurrence was defined as a Rutgeerts score ⩾i2. RESULTS: A total of 30 patients were studied. In eight patients, the FC level was raised during the 24-month follow up. Six of the eight patients (75%) had endoscopic recurrence. Of 22 patients who maintained low FC levels, 20 (91%) had no endoscopic recurrence, whereas two showed endoscopic recurrence at the end of the follow up. The incidence of endoscopic recurrence was significantly higher in patients with elevation of FC levels versus those with maintained low FC levels (75% versus 9%). A cut-off value of 140 µg/g for FC had a sensitivity of 75%, a specificity of 91%, a positive predictive value of 75%, a negative predictive value of 91% and a diagnostic accuracy of 87% to detect endoscopic recurrence. CONCLUSIONS: Consecutive monitoring of FC is useful for the assessment of endoscopic recurrence after the initial ileocolonoscopy. Increased FC levels indicate a need for repeat ileocolonoscopy, while sustained low FC levels predict a low risk of endoscopic recurrence. In patients maintaining low FC levels, unnecessary invasive endoscopic examinations can be avoided.

Systemic and local cytokine production in quiescent ulcerative colitis and its relationship to future relapse: a prospective pilot study.

BACKGROUND: The main aim of this prospective study was to examine whether systemic (plasma) and local (mucosal) cytokine production is a predictor of future relapse in patients with quiescent ulcerative colitis (UC). The impact of other clinical and laboratory parameters on relapse was also studied. METHODS: Fifty consecutive patients with quiescent UC were included. At enrollment, blood and mucosal (rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrollment. Plasma and mucosal cytokine levels were measured by enzyme-linked immunosorbent assay. To identify independent significant predictive factors for relapse, time-dependent analyses using the Kaplan-Meier method and the Cox proportional hazard model were performed. RESULTS: Thirty-four patients remained in remission, and 16 patients relapsed during the 1-year follow-up. Higher interleukin (IL)-8 levels in the rectal mucosa were significantly associated with relapse. In contrast, IL-1beta, IL-6, and tumor necrosis factor-alpha levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokines (IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha) did not correlate with relapse. Among clinical factors, age and number of prior relapses were significantly associated with relapse. In multivariate analysis, a higher rectal mucosal IL-8 level (> or = 160 pg/mg of tissue; hazard ratio, 4.7), younger age (<30 yr; hazard ratio, 7.3), and a greater number of prior relapses (> or = 5; hazard ratio, 4.3) were independent significant risk factors for future relapse. CONCLUSIONS: Rectal mucosal IL-8 measurement might be an additional objective diagnostic tool that can predict relapse in patients with quiescent UC.

Impact of elemental diet on mucosal inflammation in patients with active Crohn's disease: cytokine production and endoscopic and histological findings.

BACKGROUND: The aim of this study was to examine the impact of elemental diet on mucosal inflammation in Crohn's disease (CD), mainly by cytokine measurements. METHODS: Twenty-eight consecutive patients with active CD were treated with an elemental diet (Elental) for 4 weeks. The mucosal biopsies were obtained from the terminal ileum and large bowel before and after treatment. As a control group, mucosal biopsies were obtained from 20 patients without inflammation. Mucosal cytokine concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: After treatment, clinical remission was achieved in 20 patients (71%). Endoscopic healing and improvement rates were 44% and 76% in the terminal ileum and 39% and 78% in the large bowel, respectively. Histologic healing and improvement rates were 19% and 54% in the terminal ileum and 20% and 55% in the large bowel, respectively. Before treatment, the mucosal concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, and tumor necrosis factor-alpha in the ileum and large bowel were significantly higher than in controls. These cytokine concentrations decreased to the levels of control after treatment. IL-1ra/IL-1beta ratio in the ileum and large bowel was significantly lower than in controls before treatment. The ratio increased to the level of controls after treatment. The endoscopic and histologic healing of the mucosal inflammation was associated with a decline of the mucosal cytokines and an increase of the IL-1ra/IL-1beta ratio. CONCLUSIONS: The elemental diet (Elental) reduced mucosal cytokine production and corrected an imbalance between proinflammatory and anti-inflammatory cytokines in CD.

The impact of early endoscopic lesions on the clinical course of patients following ileocolonic resection for Crohn's disease: A 5-year prospective cohort study.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.