J. Frederik M. Slors

Increased expression of DC-SIGN+IL-12+IL-18+ and CD83+IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn's disease.

Dentritic cells (DC) as antigen‐presenting cells are most likely responsible for regulation of abnormal T cell activation in Crohns disease (CD), a chronic inflammatory bowel disease. Wehave analyzed the expression of activation and maturation markers on DC in the colon mucosa from patients with CD compared with normal colon, using immunohistochemical techniques. We found two distinct populations of DC present in CD patients: a DC‐specific ICAM‐3 grabbing non‐integrin (DC‐SIGN)+ population that was present scattered throughout the mucosa, and a CD83+ population that was present in aggregated lymphoid nodules and as single cells in the lamina propria. In normal colon the number of DC‐SIGN+ DC was lower and CD83+ DC were detected only in very few solitary lymphoid nodules. Co‐expression of activation markers and cytokine synthesis was analyzed with three‐color confocal laser scanning microscopy analysis. CD80 expression was enhanced on the majority of DC‐SIGN+ DC in CD patients, whereas only a proportion of the CD83+ DC co‐expressed CD80 in CD as well as in normal tissue. Surprisingly, IL‐12 and IL‐18were only detected in DC‐SIGN+ DC and not in CD83+ DC. A similar pattern of cytokine production was observed in normal colon albeit to a much lesser extent. The characteristics ofthese in‐situ‐differentiated DC markedly differ from the in‐vitro‐generated DC that simultaneously express DC‐SIGN, CD83 and cytokines.

Long-term functional outcome and risk factors for recurrence after surgical treatment for low and high perianal fistulas of cryptoglandular origin

PurposeThis study assessed long-term functional outcome and explored risk factors for fistula recurrence in patients surgically treated for cryptoglandular fistulas.MethodsThree hundred ten consecutive patients were surgically treated for perianal fistulas. After exclusion of patients with inflammatory bowel disease or HIV, 179 patients remained. Patients were divided into two groups: those who received fistulotomy for low perianal fistulas and those who received rectal advancement flap for high perianal fistulas. Time to fistula recurrence was the main outcome and Cox proportional hazard models were used to assess the importance of various risk factors. Functional outcome was assessed using the Vaizey and colorectal functional outcome (COREFO) questionnaires.ResultsThe median follow-up duration was 76xa0months (range, 7–134). The 3-year recurrence rate for low perianal fistulas treated by fistulotomy (nu2009=u2009109) was 7 percent (95 percent confidence interval, 1–13 percent). In high transsphincteric fistulas treated by rectal advancement flap (nu2009=u200970), the recurrence rate was 21 percent (95 percent confidence interval, 9–33 percent). In both groups, soiling was reported at 40 percent. None of the seven potential risk factors examined were statistically significant.ConclusionsFistula recurrence rate after fistulotomy was low. No clear risk factors were found. Overall functional outcome in terms of continence was good. However, a substantial amount of patients reported soiling.

Anal Fistula Plug for Closure of Difficult Anorectal Fistula: A Prospective Study

PurposeComplex high and recurrent fistulas remain a surgical challenge. Simple division, i.e., fistulotomy, will likely result in fecal incontinence. Various surgical treatment options for these fistulas have shown disappointing results. Recently a biologic anal fistula plug was developed to treat these high transsphincteric fistulas. To assess the results of the anal fistula plug in patients with complex high perianal fistulas, a prospective, two-center, clinical study was undertaken.MethodsBetween April 2006 and October 2006, a consecutive series of patients with difficult therapy-resistant high fistulas were enrolled. During surgery, the internal fistula tract opening was identified. A conical shaped collagen plug was pulled through the fistula tract. Any remaining portion of the plug that was not implanted in the tract was removed. The plug was fixed at the internal opening with a deep 3/0 polydioxanone suture.ResultsSeventeen patients with a median age of 45 (range, 27–75) years were included. Of these patients, 71 percent (12/17) were male. At a median length of follow-up of 7 (range, 3–9) months, 7 of 17 fistulas had healed (41 percent). In ten patients, the fistula recurred.ConclusionsIn these small series of 17 patients with difficult high perianal fistulas, a success rate of 41 percent is noted. Larger series, preferably in trial setting, must be performed to establish the efficacy of the anal fistula plug in perianal fistula.

Chemokine receptor CXCR3 expression in inflammatory bowel disease

CD4+ T lymphocytes in the lamina propria (LP) of the gut play a central role in the immune response in inflammatory bowel disease (IBD). CXCR3 is a chemokine receptor expressed on activated T lymphocytes, and a key component for the recruitment of T helper (Th1) effector cells to the site of inflammation. To determine if CXCR3 is involved in localization of T cells to the gut in IBD patients, we investigated the expression of CXCR3 on CD4+ T lymphocytes in the LP and in the submucosa of resection specimens from 51 IBD patients and 15 control patients. Positive cells were microscopically scored using a semiquantitative analysis on a five-point scale. We found that CD4+ T cells, CXCR3+ cells, and CD4+CXCR3+ T cells in the LP were slightly increased in both IBD groups compared with control non-IBD specimens. In addition, CD4+ and CXCR3+ cells in the submucosa were significant increased in the CD group compared with the control group. CD4+ and CXCR3+ expression was not statistically different between CD and UC. Flow cytometry was used to analyze the percentage of CXCR3+ cells within the CD4+ T-cell population isolated from biopsy specimens and peripheral blood from IBD patients and control patients. There was no difference in the percentage of CD4+CXCR3+ cells between the different groups in the gut as well as in the circulation. These results suggest that CD4+CXCR3+ T cells migrate to the normal and inflamed intestinal mucosa, indicating a role in maintaining normal gut homeostasis. The selective expression of CXCR3+ cells in the submucosa of CD patients might also indicate that these cells play a role in inflammation.

Development and validation of a colorectal functional outcome questionnaire

BackgroundAfter colorectal surgery, patients often experience impaired functional outcome. Faecal incontinence grading systems and self-assessment questionnaires are frequently used to assess these complaints. The available faecal incontinence grading systems have been validated, but have a limited focus, while more comprehensive questionnaires, which have been developed, have not been validated.AimsTo investigate the reliability and validity of a newly developed, colorectal functional outcome (COREFO) questionnaire and of Dutch translations of the Hallböök questionnaire and an adapted version of the Vaizey questionnaire.Patient/methodsTwo hundred fifty-seven patients with and without impaired functional outcome after (colorectal) surgery received a booklet containing the three questionnaires in random order by mail. One hundred seventy-nine (70%) completed them, and 160 patients (90%) completed a retest within, on average, 18 days.Results/findingsReliability and validity were adequate for the COREFO and Hallböök questionnaire, with slight differences in the psychometric analyses in favour of the COREFO questionnaire. Significantly more patients found the COREFO questionnaire to reflect their problems best. The reliability of the Vaizey questionnaire was not sufficient.Interpretation/conclusionsThe newly developed COREFO questionnaire and the previously unvalidated Hallböök questionnaire are both suitable instruments to evaluate functional outcome after colorectal surgery. The psychometric analyses showed a slight difference in favour of the COREFO questionnaire and significantly more patients preferred the COREFO questionnaire to the other questionnaires. Therefore, we prefer to use the COREFO questionnaire in future research.

Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulas; is there any advantage?

Backgrounds and aimIn recent decades, fibrin glue has appeared as an alternative treatment for high perianal fistulas. Early results seemed promising, with high success rates being reported. However, with increasing follow-up, the enthusiasm was tempered because of disappointing results. The aim of this retrospective study was to assess the additional value of fibrin glue in combination with transanal advancement flap, compared to advancement flap alone, for the treatment of high transsphincteric fistulas of cryptoglandular origin.Materials and methodsBetween January 1995 and January 2006, 127 patients were operated for high perianal fistulas with an advancement flap. After exclusion of patients with inflammatory bowel disease or HIV, 80 patients remained. A consecutive series of 26 patients had an advancement flap combined with obliteration of the fistula tract with fibrin glue. Patients were matched for prior fistula surgery, and the advancement was performed identically in all patients. In the fibrin glue group, glue was installed retrogradely in the fistula tract after the advancement was completed and the fistula tract had been curetted.ResultsMinimal follow-up after surgery was 13 months [median of 67 months (range, 13–127)]. The overall recurrence rate was 26% (n = 21). Recurrence rates for advancement flap alone vs the combination with glue were 13% vs 56% (p = 0.014) in the group without previous fistula surgery and 23% vs 41% (p = 0.216) in the group with previous fistula surgery.ConclusionObliterating the fistula tract with fibrin glue was associated with worse outcome after rectal advancement flap for high perianal fistulas.

Feasibility of early closure of loop ileostomies: a pilot study.

PurposeA loop ileostomy is constructed to protect a distal anastomosis, and closure is usually performed not earlier than after two to three months. Earlier closure might reduce stoma-related morbidity, improve quality of life, and still effectively protect the distal anastomosis. This pilot study was designed to investigate the feasibility of early closure of loop ileostomies, i.e., during the same hospital admission as the initial operation. METHODS: Twenty-seven consecutive patients with a protective loop ileostomy were included. If patient’s recovery was uneventful, water-soluble contrast enema examination was performed, preferably after seven to eight days. If no radiologie signs of leakage were detected, the ileostomy was closed during the same hospital admission. RESULTS: Twenty-seven patients (8 females; mean age, 60 years) were analyzed. Eighteen patients had early ileostomy closure on average 11 (range, 7-21) days after the initial procedure. In nine patients the procedure was postponed because of leakage of the anastomosis (n = 3), delayed recovery (n = 1), small bowel obstruction (n = 1), gastroparesis (n = 1), logistic reasons (n = 2), or irradical cancer resection followed by radiotherapy (n = 1). There was no mortality and four mild complications occurred after early closure: superficial wound infection (n = 2), intravenous-catheter sepsis (n = 1), small bowel obstruction (n = 1). CONCLUSION: Closure of a loop ileostomy early after the initial operation was feasible in 18 of 27 patients and was associated with low morbidity and no mortality.

The Anal Fistula Plug versus the mucosal advancement flap for the treatment of Anorectal Fistula (PLUG trial)

BackgroundLow transsphincteric fistulas less than 1/3 of the sphincter complex are easy to treat by fistulotomy with a high success rate. High transsphincteric fistulas remain a surgical challenge. Various surgical procedures are available, but recurrence rates of these techniques are disappointingly high. The mucosal flap advancement is considered the gold standard for the treatment of high perianal fistula of cryptoglandular origin by most colorectal surgeons. In the literature a recurrence rate between 0 and 63% is reported for the mucosal flap advancement. Recently Armstrong and colleagues reported on a new biologic anal fistula plug, a bioabsorbable xenograft made of lyophilized porcine intestinal submucosa. Their prospective series of 15 patients with high perianal fistula treated with the anal fistula plug showed promising results.The anal fistula plug trial is designed to compare the anal fistula plug with the mucosal flap advancement in the treatment of high perianal fistula in terms of success rate, continence, postoperative pain, and quality of life.Methods/designThe PLUG trial is a randomized controlled multicenter trial. Sixty patients with high perianal fistulas of cryptoglandular origin will be randomized to either the fistula plug or the mucosal advancement flap. Study parameters will be anorectal fistula closure-rate, continence, post-operative pain, and quality of life. Patients will be followed-up at two weeks, four weeks, and 16 weeks. At the final follow-up closure rate is determined by clinical examination by a surgeon blinded for the intervention.DiscussionBefore broadly implementing the anal fistula plug results of randomized trials using the plug should be awaited. This randomized controlled trial comparing the anal fistula plug and the mucosal advancement flap should provide evidence regarding the effectiveness of the anal fistula plug in the treatment of high perianal fistulas.Trial registrationISRCTN: 97376902

Total laparoscopic restorative proctocolectomy: are there advantages compared with the open and hand-assisted approaches?

PurposeA randomized, controlled trial comparing hand-assisted laparoscopic restorative proctocolectomy with open surgery did not show an advantage for the laparoscopic approach. The trial was criticized because hand-assisted laparoscopic restorative proctocolectomy was not considered a true laparoscopic proctocolectomy. The objective of the present study was to assess whether total laparoscopic restorative proctocolectomy has advantages over hand-assisted laparoscopic restorative proctocolectomy with respect to early recovery.MethodsThirty-five patients underwent total laparoscopic restorative proctocolectomy and were compared to 60 patients from a previously conducted randomized, controlled trial comparing hand-assisted laparoscopic restorative proctocolectomy and open restorative proctocolectomy. End points included operating time, conversion rate, reoperation rate, hospital stay, morbidity, quality of life, and costs. The Medical Outcomes Study Short Form 36 and the Gastrointestinal Quality of Life Index were used to evaluate general and bowel-related quality of life.ResultsGroups were comparable for patient characteristics, such as sex, body mass index, preoperative disease duration, and age. There were neither conversions nor intraoperative complications. Median operating time was longer in the total laparoscopic compared with the hand-assisted laparoscopic group (298 vs. 214 minutes; Pu2009<u20090.001). Morbidity and reoperation rates in the total laparoscopic, hand-assisted laparoscopic, and open groups were comparable (29 vs. 20 vs. 23 percent and 17 vs.10 vs. 13 percent, respectively). Median hospital-stay was 9xa0days in the total laparoscopic group compared with 10xa0days in the hand-assisted laparoscopic group and 11xa0days in the open group (Pu2009=u2009not significant). There were no differences in quality of life and total costs.ConclusionsThere were no significant short-term benefits for total laparoscopic compared with hand-assisted laparoscopic restorative proctocolectomy with respect to early morbidity, operating time, quality of life, costs, and hospital stay.

The Role of Endoluminal Imaging in Clinical Outcome of Overlapping Anterior Anal Sphincter Repair in Patients with Fecal Incontinence

OBJECTIVEnAnterior sphincter repair has become the operation of choice in patients with fecal incontinence who have defects of the external anal sphincter (EAS), but not all patients benefit from surgery. The aim of this study was to investigate whether endoluminal imaging can identify determinants that play a role in the outcome of sphincter repair.nnnSUBJECTS AND METHODSnThirty fecal incontinent patients with an EAS defect were included. The severity of incontinence was evaluated pre- and postoperatively using the Vaizey incontinence score. Patients underwent endoanal MRI and endoanal sonography before and after sphincter repair. We evaluated the association between preoperatively assessed EAS measurements with outcome and postoperatively depicted residual defects, atrophy, tissue at overlap, and sphincter overlap with clinical outcome.nnnRESULTSnAfter surgery, the mean Vaizey score in 30 patients (97% females; mean age, 50 years) had improved from 18 to 13 (p < 0.001). MRI showed that baseline measurement of preserved EAS thickness correlated with a better outcome (r = 0.42; p = 0.03). Clinical outcome did not differ between patients with and those without a persistent EAS defect (p = 0.54) or EAS atrophy (p = 0.26) depicted on MRI. Patients with a visible overlap and less than 20% fat tissue had a better outcome than patients with nonvisible, fatty overlap (decrease in Vaizey score, 7 vs 2 points, respectively; p = 0.04). Sonography showed that patients with a persistent EAS defect had a worse outcome than those without an EAS defect (17 vs 10 points, respectively; p = 0.003).nnnCONCLUSIONnEndoanal MRI was useful in determining EAS thickness and structure, and endoanal sonography was effective in depicting residual EAS defects.