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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Faecal calprotectin and lactoferrin as markers for monitoring disease activity and predicting clinical recurrence in patients with Crohn's disease after ileocolonic resection: A prospective pilot study.

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. METHODS: Twenty patients who remained in remission during 6-12 months after ileocolonic resection for CD were included. All patients underwent ileocolonoscopy for assessing endoscopic activity (Rutgeerts score) in the neo-terminal ileum. A stool sample was collected for measurement of calprotectin and lactoferrin. All patients were then followed up for 12 months, and clinical recurrence was defined as a CDAI >150 with an increase of ≥70 points. RESULTS: The mean time between surgery and the endoscopic examination at entry was 7.2 months. The endoscopic scores were i0 or i1 in 10 patients, i2 in six patients, i3 in three patients, and i4 in one patient. Both calprotectin and lactoferrin positively correlated with the endoscopic scores (p = 0.0001 and p = 0.038, respectively). Six patients developed clinical recurrence during the 12-month follow-up. Both calprotectin and lactoferrin levels were significantly higher in patients with clinical recurrence than those in remission (p = 0.0007 and p = 0.025, respectively). A cutoff value of 170 µg/g for calprotectin had a sensitivity of 83% and a specificity of 93% to predict a risk of clinical recurrence, while a cutoff value of 140 µg/g for lactoferrin had a sensitivity of 67% and a specificity of 71%. CONCLUSIONS: Both calprotectin and lactoferrin levels correlate well with endoscopic activity after ileocolonic resection for CD. Calprotectin and lactoferrin could be clinically relevant biomarkers for predicting postoperative recurrence. Further well-designed large trials should strengthen the findings of the present investigation.

Long-term clinical impact of early introduction of granulocyte and monocyte adsorptive apheresis in new onset, moderately active, extensive ulcerative colitis.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Daily granulocyte and monocyte adsorptive apheresis in patients with active ulcerative colitis: a prospective safety and feasibility study.

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

High-dose mesalazine treatment for ulcerative colitis patients who relapse under low-dose maintenance therapy.

BACKGROUND: Mesalazine is often used to maintain remission in patients with ulcerative colitis. AIM: To investigate if increasing the dose of mesalazine is safe and effective for patients with ulcerative colitis who relapse under low-dose maintenance therapy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Mucosal healing in patients with ulcerative colitis during a course of selective leukocytapheresis therapy: a prospective cohort study.

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.

Enteral nutrition for the maintenance of remission in Crohn's disease: a systematic review.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prospective clinical trial: enteral nutrition during maintenance infliximab in Crohn's disease.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn's disease: a prospective pilot study.

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