Indikation, Operationsverfahren und Lebensqualität

Die restaurative Proktokolektomie mit Ileumpouchanlage gilt als Goldstandard in der operativen Therapie der Colitis ulcerosa. Das Verfahren wurde 1978 durch Parks und Nicholls erstbeschrieben und hat seitdem eine kontinuierliche Weiterentwicklung erfahren. Es wird heutzutage überwiegend mehrzeitig und minimalinvasiv durchgeführt. Dennoch entstehen, insbesondere im Hinblick auf die stetige Weiterentwicklung der medikamentösen Therapiemaßnahmen, immer wieder neue Herausforderungen an die Umsetzung und weitere Optimierung der chirurgischen Maßnahmen. Eine Heilung der Erkrankung ist zum aktuellen Zeitpunkt noch immer lediglich der Chirurgie zuzuschreiben. Da die immunsuppressive Therapie jedoch im Vordergrund der Behandlung von Colitis ulcerosa PatientInnen steht, muss deren Einfluss auf die Entscheidung zu einem operativen Vorgehen untersucht werden. Steht die Indikation zur Operation fest, muss noch zwischen zwei- oder dreizeitigem Verfahren entschieden werden. Hierbei sollte neben dem Allgemein- und Ernährungszustand der PatientInnen, die präoperative Immunsuppression beachtet werden. Es konnte gezeigt werden, dass das dreizeitige Vorgehen bei ausgeprägter präoperativer Immunsuppression über einen längeren Zeitabschnitt deutliche Vorzüge hinsichtlich einer kürzeren Liegedauer, einer kürzeren Intensivzeit und der geringeren Rate an Majorkomplikationen im Hinblick auf die Indexoperation Pouchanlage aufweist und daher bei PatientInnen mit Colitis Ulcerosa und einer hohen Rate an Immunsuppression als Verfahren der Wahl gewählt werden sollte. Diese Aspekte finden in den nationalen und internationalen Leitlinien bereits Anwendung. Ferner wurde im Rahmen der zunehmend an Bedeutung gewinnenden Minimalisierung des Zugangsweges von Operationstechniken deren Effekte auf die restaurative Proktokolektomie untersucht. Sowohl die komplette bergeinzisionslose als auch die klassische laparoskopische Proktokolektomie stellten in der vorliegenden Arbeit sichere Operationstechniken für PatientInnen mit chronisch entzündlichen Darmerkrankungen dar und sollten daher durchgeführt werden, wenn entsprechende Expertise vorhanden ist. Neben besseren kosmetischen Ergebnissen scheint sich durch eine weitere Minimierung des Zugangstraumas ein potenzieller Vorteil hinsichtlich reduzierter Wundinfektionen, insbesondere bei den häufig immunsupprimierten PatientInnen, zu ergeben. In einem weiteren Untersuchungsansatz sollte die Lebensqualität der PatientInnen nach einem mehrzeitigen Operationsverfahren, was einen zusätzlichen Krankenhausaufenthalt und eine weitere Operation beinhaltet, untersucht werden. Es konnte gezeigt werden, dass die restaurative Proktokolektomie zu einer verbesserten Lebensqualität, die sogar mit der Normalbevölkerung vergleichbar ist, führt. Die Lebensqualität wird dabei weder kurz- noch langfristig durch die Wahl für ein zwei- oder dreizeitiges Verfahren beeinflusst. Die Indikation für ein mehrzeitiges Verfahren sollte daher an die Schwere der Grunderkrankung, den Ernährungszustand der PatientInnen und dem Ausmaß der Immunsuppression zum Zeitpunkt der Operation angepasst werden. Sie sollte nicht von der Angst vor Komplikationen oder einer reduzierten Lebensqualität durch eine zusätzliche Operation beim mehrzeitigen Verfahren beeinflusst werden. Ferner sollte der optimale Zeitpunkt zur Operation untersucht werden. Oft kommt es zu einer Verzögerung einer nötigen Operation, entweder aus Sorge der PatientInnen vor eventuellen Komplikationen oder aufgrund zurückhaltender Überweisung der PatientInnen in einer chirurgischen Klinik. Der Operationszeitpunkt ist somit sehr variabel und abhängig vom Rat der betreuenden ÄrztInnen und der Präferenzen der PatientInnen. Ein Drittel der PatientInnen in der vorliegenden Untersuchung fand, dass ihre Operation früher hätte durchgeführt werden sollen. Bei einer therapierefraktären Erkrankung ist die Beratung zu einer frühen elektiven Operation patientInnenzentriert und in Übereinstimmung mit der Entscheidung der PatientInnen. Frühe interdisziplinäre Diskussionen durch ein auf chronisch entzündliche Darmerkrankungen spezialisiertes Team können Komplikationen reduzieren, Therapiekosten und Nebenwirkungen der immunsuppressiven Medikamente reduzieren. Trotz der über die Jahrzehnte gesammelten umfangreichen Erfahrung in der operativen Behandlung der Colitis ulcerosa gibt es immer wieder Fälle, in denen die Ileumpouchanlage frustran verläuft. In der vorliegenden Arbeit konnten mehrere unabhängige Risikofaktoren für eine frustrane IPAA identifiziert werden. Eine Verkürzung der Mesenterialwurzel bildet den technischen Hauptgrund für eine fehlgeschlagene IPAA ab. Die Optimierung der präoperativen Bedingungen, wie eine Reduktion des Übergewichts, Entzündung und immunsuppressive Medikation, kann dazu beitragen, die Rate der PatientInnen mit erfolgreicher ileoanaler Pouchkonstruktion zu erhöhen

Healing of rectal advancement flaps for anal fistulas in patients with and without Crohn’s disease: a retrospective cohort analysis

Background: Surgical closure of anal fistulas with rectal advancement flaps is an established standard method, but it has a high degree of healing failure in some cases. The aim of this study was to identify risk factors for anal fistula healing failure after advancement flap placement between patients with cryptoglandular fistulas and patients with Crohn's disease (CD). Methods: From January 2010 to October 2020, 155 rectal advancement flaps (CD patients = 55, non-CD patients = 100) were performed. Patients were entered into a prospective database, and healing rates were retrospectively analysed. Results: The median follow-up period was 189 days (95% CI: 109-269). The overall complication rate was 5.8%. The total healing rate for all rectal advancement flaps was 56%. CD patients were younger (33 vs. 43 years, p < 0.001), more often female (76% vs. 30%, p < 0.001), were administered more immunosuppressant medication (65% vs. 5%, p < 0.001), and had more rectovaginal fistulas (29% vs. 8%, p = 0.001) and more protective stomas (49% vs. 2%, p < 0.001) than patients without CD. However, no difference in healing rate was noted between patients with or without CD (47% vs. 60%, p = 0.088). Conclusions: Patients with anal fistulas with and without Crohn's disease exhibit the same healing rate. Although patients with CD display different patient-specific characteristics, no independent factors for the occurrence of anal fistula healing failure could be determined. Trial registration Not applicable due to the retrospective study design

Sacral nerve stimulation in patients with ileal pouch-anal anastomosis

Purpose: Functional results after proctocolectomy and ileal pouch-anal anastomosis (IPAA) are generally good. However, some patients suffer from high stool frequency or fecal incontinence. Sacral nerve stimulation (SNS) may represent a therapeutic alternative in these patients, but little is known about indication and results. The aim of this study was to evaluate incontinence after IPAA and demonstrate SNS feasibility in these patients. Methods: This retrospective study includes patients who received a SNS between 1993 and 2020 for increased stool frequency or fecal incontinence after proctocolectomy with IPAA for ulcerative colitis. Proctocolectomy was performed in a two- or three-step approach with ileostomy closure as the last step. Demographic, follow-up data and functional results were obtained from the hospital database. Results: SNS was performed in 23 patients. Median follow-up time after SNS was 6.5 years (min. 4.2-max. 8.8). Two patients were lost to follow-up. The median time from ileostomy closure to SNS implantation was 6 years (min. 0.5-max. 14.5). Continence after SNS improved in 16 patients (69%) with a median St. Marks score for anal incontinence of 19 (min. 4-max. 22) before SNS compared to 4 (0-10) after SNS placement (p = 0.012). In seven patients, SNS therapy was not successful. Conclusion: SNS implantation improves symptoms in over two-thirds of patients suffering from high stool frequency or fecal incontinence after proctocolectomy with IPAA. Awareness of the beneficial effects of SNS should be increased in physicians involved in the management of these patients

Risk factors for upper and lower type prolonged postoperative ileus following surgery for Crohn’s disease

Purpose: Prolonged postoperative ileus (PPOI) is common after bowel resections, especially in Crohn's disease (CD). The pathophysiology of PPOI is not fully understood. PPOI could affect only the upper or lower gastrointestinal (GI) tract. The aim of this study was to assess risk factors for diverse types of PPOI, particularly to differentiate PPOI of upper and lower GI tract. Methods: A retrospective analysis of 163 patients with CD undergoing ileocecal resection from 2015 to 2020 in a single center was performed. PPOI of the upper GI tract was predefined as the presence of vomiting or use of nasogastric tube longer than the third postoperative day. Lower PPOI was predefined as the absence of defecation for more than three days. Independent risk factors were identified by multivariable logistic regression analysis. Results: Overall incidence of PPOI was 42.7%. PPOI of the upper GI tract was observed in 30.7% and lower PPOI in 20.9% of patients. Independent risk factors for upper PPOI included older age, surgery by a resident surgeon, hand-sewn anastomosis, prolonged opioid analgesia, and reoperation, while for lower PPOI included BMI <= 25 kg/m(2), preoperative anemia, and absence of ileostomy. Conclusion: This study identified different risk factors for upper and lower PPOI after ileocecal resection in patients with CD. A differentiated upper/lower type approach should be considered in future research and clinical practice. High-risk patients for each type of PPOI should be closely monitored, and modifiable risk factors, such as preoperative anemia and opioids, should be avoided if possible

Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn’s disease

PURPOSE: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn’s disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. METHODS: A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. RESULTS: A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0–82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn’s recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840–1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. CONCLUSION: Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn’s disease undergoing ileocecal resection

The impact of surgical site infection—a cost analysis

Purpose: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. Methods: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 euro; 19.703 USD (IQR 21.638 euro; 25.552 USD) vs. median 11.235 euro; 13.276 USD (IQR 11.564 euro; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 euro; 7.870 USD with SSI vs. median 5.040 euro; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 euro; 9.924 USD with SSI vs. median 4.690 euro; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 euro; 14.237 USD vs. median 12.793 euro; 15.107 USD in the polyhexanide group (p = 0.52). Conclusion: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide

Growth factor-induced stabilization of the chondrogenic potential of human articular chondrocytes in vitro

Im Rahmen der modernen gelenktherapeutischen Forschung, steht seit einigen Jahren eine neue viel versprechende Methode, die autologe Chondrozyten Transplantation (ACT), zur Verfügung. Aus einem gesunden Knorpelareal werden Proben entnommen, die Chondrozyten isoliert und in vitro vermehrt. Ist eine ausreichende Zellzahl vorhanden, werden die Chondrozyten in den bestehenden Knorpeldefekt transplantiert und mit einem Periostlappen gedeckt. Die ACT weist jedoch einige Beschränkungen und Probleme auf. Die Anwendung bleibt derzeit auf kleinere, oberflächliche Knorpeldefekte beschränkt. Außerdem kommt es zur Dedifferenzierung der Chondrozyten während der Proliferationsphase in der Monolayer-Kultur (ML) in vitro. Diese dedifferenzierten Zellen sind nicht fähig, den Knorpeldefekt suffizient und lang anhaltend zu füllen. Ziel dieser Arbeit war es daher, nach Möglichkeiten zur Gewinnung von vitalem Knorpelmaterial zu suchen, um das Verfahren der ACT zu verbessern. Von Wachstumsfaktoren ist bekannt, dass sie anabole Wirkungen auf das Wachstum, die Differenzierung und das Überleben der Chondrozyten aufweisen. Aus diesem Grund wurden die Effekte von IGF-I und TGF-b1 auf das chondrogene Potential und somit auf das Redifferenzierungsverhalten der Chondrozyten in vitro untersucht. Die Wachstumsfaktoren wurden einzeln oder in Kombination miteinander verwendet. Zusätzlich zu den Untersuchungen in ML wurde der Einfluss von IGF-I und TGF-b1 auf das Redifferenzierungspotential der Zellen in einem 3D Kultursystem untersucht. Die Ergebnisse mit IGF-I und TGF-b1 in dieser Arbeit konnten auf morphologischer Ebene zeigen, dass beide Wachstumsfaktoren in der Lage waren den chondrogenen Phänotyp der Zellen aufrechtzuerhalten. Die Synthese wichtiger knorpelspezifischer Proteine, wie Kollagen Typ II, Proteoglykane und chondrogener Transkriptionsfaktor Sox9 konnte durch die Behandlung mit IGF-I oder/und TGF-b1 stimuliert werden. Zusätzlich ergaben sich additive Effekte auf die Expression der oben genannten Proteine. Um das Redifferenzierungsverhalten der Zellen aus der ML Kultur in 3D zu untersuchen, wurden die Zellen aus der ML Kultur in Massenkultur überführt und hier für weitere sieben Tage kultiviert. Hier zeigte sich, dass IL-1b-stimulierte Zellen nicht fähig waren zu redifferenzieren. Im Gegensatz dazu führte die Behandlung mit Wachstumsfaktoren zur Redifferenzierung der Chondrozyten in Massenkultur sowohl morphologisch als auch auf Proteinebene. Das höchste Redifferenzierungspotential wiesen Chondrozyten nach der kombinierten Behandlung mit beiden Wachstumsfaktoren auf. Zusammenfassend lässt sich sagen, dass Wachstumsfaktoren (vor allem in Kombination) die Zytokin-induzierten Effekte hemmen und die Chondrozyten in die Lage versetzen in 3D zu redifferenzieren. Auf diesem Weg sind sie fähig die Differenzierung der Chondrozyten zu stabilisieren. Durch die Aufrechterhaltung des chondrogenen Potentials besteht demnach die Möglichkeit, vitale Chondrozyten für die ACT zu gewinnen und somit die Therapie von Knorpelverletzungen zu verbessern.Concerning cartilage defect repair the autologous chondrocyte transplantation (ACT) plays a central role. Therfore samples are taken from a healthy part of the joint, cells are isolated and expanded in monolayer culture in vitro. When a sufficient number of chondrocytes is obtained, cells are transferred into the cartilage defect and covered with a periostal flap. Although results obtained until now are quite encouraging, the main limitation for successful ACT is often the poor integration of the newly formed cartilage tissue. This is mainly due to the expansion phase in monolayer culture where chondrocytes gradually lose their specific phenotype, dedifferentiate into fibroblast-like cells and thus lose their chondrogenic potential. These dedifferentiating processes lead to chondrocytes that are incapable of initiating cartilage defect repair, resulting in fibrous cartilage tissue. For this reason, new and improved in vitro strategies need to be investigated. Growth factors are known to exert anabolic effects on chondrocytes in vivo and in vitro by influencing chondrocyte proliferation, differentiation, growth and survival. In this work we wanted to examine the influence of IGF-I and TGF-b1 on restoring the chondrogenic potential of IL-1b-treated dedifferentiated chondrocytes from monolayer culture. Growth factors were used separately or in combination. To further investigate the redifferention potential of the cells in 3D culture, cells were transferred in high-density culture and cultured for further seven days. Our results demonstrated, that growth factors were able to restore the chondrogenic phenotype. Furthermore, the synthesis of chondrocyte specific proteins like collagen type II or proteoglycanes and the chondrogenic transcription factor Sox9 was stimulated by IGF-I and TGF-b1. Additive effects on the above mentioned proteins could be observed. To investigate the redifferentiation potential of chondrocytes from monolayer culture, cells were transferred into high-density culture. IL-1b-treated chondrocytes from monolayer were inable to redifferentiate in 3D. In contrast, growth factor treatment resulted in redifferentiation on morphological as well as on protein level. The highest redifferentiation potential was obtained after combined treatment with both growth factors. In conclusion, growth factors (especially combined treatment) are able to inhibit the cytokine-induced effects on chondrocytes. Treatment with growth factors results in stimulation of redifferentiation in 3D culture and therefore stabilisation of the differentiated phenotype. By restoring the chondrogenic potential it is possible to improve the results of ACT

Anabolic actions of IGF-I and TGF-B1 on Interleukin-1B-treated human articular chondrocytes: Evaluation in two and three dimensional cultures

Pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-a (TNF-a) play a key role in the pathogenesis of Osteoarthritis (OA). The aim of this study was to investigate the potential anti-inflammatory properties of the growth factors IGF-I and/or TGF-ß1 on IL-1ß signalling pathways and their effect on the chondrogenic potential of dedifferentiated human articular chondrocytes in vitro. Serum-starved human articular chondrocytes were treated with IL-1ß to induce dedifferentiation and further treated with IGF-I and/or TGF-ß1 at various concentrations. The effects of growth factors were evaluated both in monolayer and high-density cultures. Incubation with the cytokine IL-1ß resulted in rapid dedifferentiation of the cells; they lost their chondrocytelike phenotype while down-regulating the expression of collagen type II, integrin, extracellular regulated kinase (Erk 1/2) and the chondrogenic transcription factor Sox9. Co-treatment with IGF-I and/or TGF-ß1 stimulated the cells to redifferentiate, increasing the expression of the above-mentioned cartilage-specific proteins. These events correlated with down-regulation of cyclooxygenase-2 (COX-2) and matrix metalloproteinase- 13 (MMP-13). Furthermore, in high-density cultures, we observed evidence for new cartilage formation after co-treatment with these growth factors. We further detected that all examined proteins were more strongly expressed during combination treatment. These results indicate that IGF-I and TGF-ß1 exert additive anabolic effects on chondrocytes and may stabilize the chondrogenic potential. The additive action of these growth factors on chondrocytes may find practical applications in the fields of OA and cartilage tissue engineering

Sacral nerve stimulation in patients with ileal pouch-anal anastomosis

Purpose!#!Functional results after proctocolectomy and ileal pouch-anal anastomosis (IPAA) are generally good. However, some patients suffer from high stool frequency or fecal incontinence. Sacral nerve stimulation (SNS) may represent a therapeutic alternative in these patients, but little is known about indication and results. The aim of this study was to evaluate incontinence after IPAA and demonstrate SNS feasibility in these patients.!##!Methods!#!This retrospective study includes patients who received a SNS between 1993 and 2020 for increased stool frequency or fecal incontinence after proctocolectomy with IPAA for ulcerative colitis. Proctocolectomy was performed in a two- or three-step approach with ileostomy closure as the last step. Demographic, follow-up data and functional results were obtained from the hospital database.!##!Results!#!SNS was performed in 23 patients. Median follow-up time after SNS was 6.5 years (min. 4.2-max. 8.8). Two patients were lost to follow-up. The median time from ileostomy closure to SNS implantation was 6 years (min. 0.5-max. 14.5). Continence after SNS improved in 16 patients (69%) with a median St. Marks score for anal incontinence of 19 (min. 4-max. 22) before SNS compared to 4 (0-10) after SNS placement (p = 0.012). In seven patients, SNS therapy was not successful.!##!Conclusion!#!SNS implantation improves symptoms in over two-thirds of patients suffering from high stool frequency or fecal incontinence after proctocolectomy with IPAA. Awareness of the beneficial effects of SNS should be increased in physicians involved in the management of these patients