Gundi Heuschen

Risk factors for ileoanal J pouch-related septic complications in ulcerative colitis and familial adenomatous polyposis

ObjectiveTo analyze the association between pre- and perioperative factors and pouch-related septic complications (PRSC) in ulcerative colitis (UC) and in familial adenomatous polyposis (FAP) after ileal pouch–anal anastomosis (IPAA). Summary Background DataFor patients with UC and FAP, IPAA is the surgical therapy of choice, but in some patients the outcome is compromised by PRSC. MethodsA total of 706 consecutive patients (494 UC, 212 FAP) were assessed in a study aimed at identifying subgroups of patients who were at high risk for PRSC. The rate of PRSC was analyzed as a time-dependent function (Kaplan-Meier estimation). Patients with UC and FAP were stratified separately according to associated factors (age, sex, surgeon’s experience, temporary ileostomy, colectomy before IPAA, anastomotic tension, and several factors specific for UC). ResultsIn all, 131 (19.2%) patients had PRSC (23.4% UC, 9.4% FAP). In patients with UC, the estimated 1-year PRSC rate was 15.6% and the estimated 3-year PRSC rate was 24.2%. In patients with FAP, the estimated 1-year and 3-year PRSC rates were 9.2%. The difference between the estimated rates of PRSC was significant (P < .001). In the univariate analysis, patients with UC younger than 50 years, with severe proctitis, with preoperative hemoglobin levels less than 10 g/L, or receiving corticoid medication had a significantly higher risk for PRSC (P = .039, P = .037, P = .047, P = .003, respectively). Multivariate analysis showed that patients with UC receiving a systemic prednisolone-equivalent corticoid medication of more than 40 mg/day had a significantly greater risk of developing pouch-related complications than patients with UC receiving 1 to 40 mg/day and patients with UC who were not receiving corticoid medication (RR: 3.78, 2.25, 1, respectively, P < .001). Patients with FAP proved to have a significantly higher risk for PRSC in the univariate and multivariate analyses if anastomotic tension had occurred (RR 3.60, P = .0086). ConclusionsPouch-related septic complications occur as late complications and should therefore be considered in regular, specific long-term follow-up examinations. The authors identified significant risk factors for PRSC specific to patients with UC and FAP; these must be considered for each individual surgical strategy.

One- or two-stage procedure for restorative proctocolectomy: Rationale for a surgical strategy in ulcerative colitis

ObjectiveTo analyze the results of different strategies for restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) in ulcerative colitis. Summary Background DataNo commonly accepted criteria exist for choosing between the one-stage or the two-stage procedure (with or without temporary diverting ileostomy) for IPAA. The authors analyzed the outcome of patients principally suitable for either of the two alternative surgical strategies. MethodsA matched-pair control study was performed, comparing surgical details and the early and late outcome of the one-stage (study group, n = 57) versus the two-stage procedure (control group, n = 114), for IPAA. ResultsNo differences were found between the study group and the control group regarding the matching criteria gender, median age at IPAA, systemic corticoid medication, or activity of colitis. Comparing the patients who underwent a one-stage procedure with those who underwent a two-stage procedure, the proportion of patients without complications was significantly higher (P = .0042) and the frequency of late complications was significantly lower (P = .0022) in patients who underwent the one-stage procedure. The percentage of patients with anastomotic strictures was significantly higher in the control group than in the study group (P = .0022). No significant difference was found between the two groups regarding early complications, pouch-related septic complications, pouchitis, median duration of surgery for IPAA, median blood loss, need for transfusion, or median hospital stay. ConclusionsIn patients with ulcerative colitis in whom there is a choice between a one-stage procedure or a two-stage procedure with a defunctioning ileostomy, the one-stage procedure is clearly superior. This finding is of great clinical relevance both for the subjective interests of the patient and from an economic point of view.

Cytokine/chemokine messenger-RNA expression profiles in ulcerative colitis and Crohn's disease

Abstract Abstract. To define mediator profiles in inflamed and noninflamed areas in inflammatory bowel disease (IBD) we analyzed the expression of 35 messenger-RNAs (mRNAs) encoding cytokines, chemokines, and some related molecules in transmural gut tissues (n=138) from patients with ulcerative colitis (UC), Crohns disease (CD), and inflammatory and normal controls by real-time quantitative reverse transcription polymerase chain reaction. Using sample collectives with a comparable degree of inflammation, most parameters investigated showed similarly increased mRNA expression levels in both active UC and CD. This included proinflammatory cytokines, but also interferon (IFN) γ and several IFN-γ inducible chemokines. Only macrophage inflammatory protein (MIP)-2α mRNA was expressed at higher levels in inflamed UC vs. CD. IH revealed that MIP-2α protein was produced mainly by intestinal epithelial cells. Importantly, in histologically noninflamed/inactive IBD samples mRNAs for several mediators were significantly enhanced, accompanied by elevated levels of migration-inhibition factor related protein (MRP) 14 transcripts. CD14 positive macrophages were found especially in noninflamed/inactive UC, many of which coexpressed the RFD-7 antigen. Our results indicate a substantial overlap in cytokine/chemokine mRNA expression in UC and CD. Elevated mediator expression is evident in noninflamed/inactive areas in both diseases. Local recruitment of MRP-14 positive leukocytes might contribute to this phenomenon. In inactive UC a phenotypically altered population of macrophages expressing CD14 might play an additional role.

Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy.

Restorative proctocolectomy and ileal pouch–anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. As a long-term complication of this procedure, chronic pouchitis impairs the outcome in a number of patients. Aneuploidia and dysplasia have been observed after long-lasting inflammation of ileal mucosa. The question arises whether chronic inflammation of ileal mucosa predisposes to malignant transformation similar to the situation in the chronically inflamed colon. Cancer of the ileal mucosa has been reported in patients with Brookes ileostomy and in patients with Kock pouch but not as yet in those with an ileoanal pouch. We report a patient with carcinoma in an ileoanal pouch originating from terminal ileal mucosa who had been suffering from pancolitis with long-term backwash ileitis before, and from chronic pouchitis after, restorative proctocolectomy. This case demonstrates the importance of regular follow-up with pouchoscopy and random biopsies in all patients with long-standing inflammation of the ileal mucosa.

Long-term follow-up after ileoanal pouch procedure

PURPOSE: Inflammation of the ileoanal pouch (pouchitis) is one of the main complications after restorative proctocolectomy, yet its cause remains poorly understood. A standardized definition and diagnostic procedures in pouchitis are lacking. METHOD: We analyzed all cases of pouchitis occurring in a group of 308 patients (210 with ulcerative colitis, 98 with familial adenomatous polyposis) who took part in a prospective long-term follow-up program. The severity of pouchitis was measured using a pouchitis activity score (Heidelberg Pouchitis Activity Score). An algorithm for the classification and management of pouchitis was established which enables the clinician: 1) to determine theseverity of pouchitis, 2) to differentiate betweenprimary pouchitis and pouchitis caused by surgical complications (secondary pouchitis), and 3) to evaluate the course (acute vs. chronic (>3 months)). RESULTS: The median duration of follow-up was 48 (range, 13–119) months. At least one episode of pouchitis was diagnosed in 29 percent of patients with ulcerative colitis and in 2 percent of familial adenomatous polyposis patients. Secondary pouchitis occurred in 6 percent of ulcerative colitis patients and was cured by surgical treatment in 13 (87 percent) of 15 cases. Primary pouchitis was diagnosed in 23 percent of ulcerative colitis patients, including 6 percent of all ulcerative colitis patients with chronic primary pouchitis. The latter showed poor response to medical treatment. In one case multifocal high-grade dysplasia occurred. Histologic examination of the excised pouch identified a carcinoma originating from the ileal mucosa. CONCLUSIONS: Ulcerative colitis patients after restorative proctocolectomy face a high risk of developing pouchitis. The algorithm used in this study was highly efficient in identifying patients with a secondary pouchitis who require surgical treatment and patients with chronic primary pouchitis. For the latter, long-term surveillance seems mandatory because of the risk of malignant transformation of the pouch mucosa.

diagnosing Pouchitis : comparative Validation of Two Scoring Systems in Routine Follow-up

AbstractPURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of “ pouchitis” or “no pouchitis” concurrently made by a physician and a surgeon. RESULTS: The median score of examinations in which the clinicians’ diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14–21) and 8 (interquartile range, 5–10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5–8) and 2.5 (interquartile range, 1–4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score ≥ 5) would result in an 88 percent sensitivity and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies.

PRA- UND POSTOPERATIVE LEBENSQUALITAT VON PATIENTEN MIT COLITIS ULCEROSA UND FAMILIARER ADENOMATOSER POLYPOSIS BEI ILEOANALER POUCHOPERATION

Summary. After ileal pouch-anal anastomosis in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP), in addition to postoperative morbidity and functional outcome quality of life is a relevant factor for assessment of the operations success. Between 1982 and 1997 restorative proctocolectomy was performed in 602 patients (UC: n = 424; FAP: n = 178) at the Department of Surgery, University of Heidelberg. The assessment of pre- and postoperative quality of life was done through a prospective study (before restorative proctocolectomy, before and 1 year after closure of ileostomy). This study (UC: n = 27; FAP: n = 7) revealed a poor preoperative quality of life in patients with ulcerative colitis. Proctocolectomy is the decisive factor for the improvement of quality of life in the surgical treatment in UC. Quality of life could not be further significantly improved by ileostomy closure. Before proctocolectomy, FAP patients showed a quality of life, activity and function similar to that of healthy controls. In FAP patients proctocolectomy led to a significant loss of quality of life. This loss could only partly be regained by ileostomy closure. Quality of life and activity comparable to that of healthy controls can be achieved in UC patients by restorative proctocolectomy.Zusammenfassung. Die Lebensqualität stellt nach ileoanaler Pouchoperation bei Patienten mit Colitis ulcerosa (CU) und familiärer adenomatöser Polyposis (FAP), neben postoperativer Morbidität und funktionellen Parametern, eine relevante Größe zur Beurteilung des Operationserfolges dar. In den Jahren 1982 bis 1997 wurden an der Chirurgischen Universitätsklinik Heidelberg 602 Patienten (CU: n = 424; FAP: n = 178) mit einer Proktocolektomie und kontinenzerhaltenden ileoanalen Pouchanlage versorgt. Bei 27 CU- und 7 FAP-Patienten führten wir eine prospektive Verlaufsbe-obachtung zur prä- und postoperativen Lebensqualität – vor restaurativer Proktocolektomie, vor Ileostomarückverlagerung, ein Jahr nach Ileostomarückverlagerung – durch. CU-Patienten zeigten präoperativ eine sehr schlechte Lebensqualität. Der entscheidende therapeutische Schritt war die Proktocolektomie. Durch die Rückverlagerung der protektiven Ileostomie konnte die Lebensqualität nicht mehr signifikant gesteigert werden. FAP-Patienten besaßen vor Proktocolektomie eine gute Lebensqualität, Aktivität und Funktion, entsprechend der einer gesunden Kontrollgruppe. Durch die Proktocolektomie zeigten sie deutliche Verluste. Diese wurden durch Ileostomarückverlagerung teilweise wieder ausgeglichen. Wichtigstes Ergebnis ist, daß bei CU- und FAP-Patienten durch die restaurative Proktocolektomie eine gute Lebensqualität und Aktivität, vergleichbar einer gesunden Kontrollgruppe, erreicht werden kann.

Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients

Background and aimsThe pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis.Materials and methodsClinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score.ResultsIn the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group.ConclusionDifferential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Der ileoanale Pouch als Rectumersatz

Summary. The ileoanal pouch procedure (IAPP) was the most remarkable breakthrough in the surgical therapy of ulcerative colitis (UC) and familial adenomatous polyposis (FAP) in the last 20 years. The underlying disease is under control, the function preserved and the quality of life markedly improved. Alternative procedures (terminal ileostomy, ileorectal anastomosis) are only indicated in special cases. In the last 16 years we have operated on 662 patients (n = 493 UC; n = 169 FAP) with an ileoanal J-pouch, short rectal cuff, complete mucosectomy and hand-sewn anastomosis. Normally there is a good function for UC and FAP patients after IAPP. Surgical experience, technical modifications concerning the pouch design and the pouch-anal anastomosis, and a differentiated indication lead to a further improvement of these complex procedures with consecutive reduction of complications. Specific complications concerned mainly the pouch-anal anastomosis (fistulas, abscesses, consecutive stenosis) and inflammation of the pouch mucosa (pouchitis). A multivariate analysis showed, that increasing experience of the specialized center is a significant factor reducing inflammatory problems at the anastomosis. The cumulative incidence of pouchitis was 29 %. In general there is no problem in successful treatment. But patients with chronic pouchitis are a problematic group (6.2 %). Chronic pouchitis is difficult to treat. It is likely that there exists an inflammation dysplasia carcinoma sequence for the ileal pouch mucosa, analogous to the colorectum. Recently we diagnosed the first case of a real ileum pouch carcinoma with associated epithelial dysplasias following chronic pouchitis. Therefore patients with chronic pouchitis must be followed up by endoscopy and random biopsies in a surveillance program. Patients with UC and FAP can gain the life quality of healthy controls, if postoperative complications can be avoided or treated successfully. For the further development of the procedure and the individual long-term success a qualified follow-up and therapy of complications is essential. Both can be carried out only by a specialized center.Zusammenfassung. Durch die ileoanale Pouchoperation (IAP) gelang in den letzten beiden Dekaden der entscheidende Durchbruch in der chirurgischen Therapie der Colitis ulcerosa (CU) und der familiären adenomatösen Polyposis (FAP). Die Grunderkrankung ist beherrscht, die Funktion erhalten und die Lebensqualität deutlich verbessert. Alternative Verfahren (terminale Ileostomie, ileorectale Anastomose) sind nur noch Sonderindikationen vorbehalten. In den letzten 16 Jahren versorgten wir 662 Patienten (n = 492 CU; n = 169 FAP) mit einem gestapelten ileoanalen J-Pouch, kurzem Rectum-Cuff, kompletter Mucosektomie und handgenähter Anastomose. Durch die IAP läßt sich für Patienten mit CU und FAP in der Regel eine gute Funktion erreichen. Chirurgische Erfahrung, technische Modifikationen im Pouchdesign und im Bereich der Anastomose sowie eine differenzierte Indikationsstellung führten zu einer steten Optimierung dieses komplexen Operationsverfahrens mit konsekutiver Reduktion postoperativer Komplikationen. Spezifische Komplikationen betrafen in erster Linie die Anastomose (Fisteln, Abscesse, konsekutive Stenosen) und entzündliche Veränderungen der Reservoirmucosa (Pouchitis). In einer multivariaten Analyse konnte gezeigt werden, daß die zunehmende Erfahrung des Zentrums ein signifikanter Faktor zur Reduktion entzündlicher Anastomosenprobleme ist. Die kumulative Incidenz der Pouchitis betrug 29 %. Sie war in den meisten Fällen unproblematisch zu behandeln. Eine problematische Gruppe stellen jedoch Patienten mit einer chronischen Pouchitis dar (6,2 %). Die chronische Pouchitis ist kaum therapeutisch zu beeinflussen. Wahrscheinlich besteht für die Ileumpouchmucosa, analog zum Colorectum eine Entzündungs-Dysplasie-Carcinom-Sequenz. Patienten mit chronischer Pouchitis müssen deshalb lebenslang endoskopisch-bioptisch nachgesorgt werden. Sowohl für CU- als auch für FAP-Patienten kann nach IAP eine Lebensqualität erzielt werden, die einer gesunden Kontrollgruppe entspricht, wenn postoperative Komplikationen vermieden oder im weiteren Verlauf beherrscht werden. Essentiell für die Weiterentwicklung des Verfahrens und den individuellen Langzeiterfolg nach IAP ist deshalb eine qualifizierte Nachsorge und eine adäquate Therapie von Komplikationen. Beides kann nur von spezialisierten Zentren geleistet werden.

Surgical Treatment of Severe Inflammatory Bowel Diseases

Surgical treatment of severe inflammatory bowel diseases is required in failed medical treatment, in emergencies and for complications. Indications for surgery and operative techniques have changed significantly over the last few years. There is a clear tendency towards earlier and less invasive surgical interventions performed in specialized and experienced centers. Improved quality of life of patients with Crohn’s disease or ulcerative colitis after surgical therapy supports an earlier consideration of the surgical treatment option. A close cooperation with the involved gastroenterologist is mandatory in this context.