Clinical outcomes and perioperative morbidity and mortality following segmental resections of the colon for Crohn's colitis.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease of a multifactorial pathogenesis. Recently numerous genetic variants linked to an aggressive phenotype were identified, leading to a progress in therapeutic options, resulting in a decreased necessity for surgery. Nevertheless, surgery is often inevitable. The aim of the study was to evaluate possible risk factors for postoperative complications and disease recurrence specifically after colonic resections for CD. PATIENTS AND METHODS: A total of 241 patients who underwent colonic and ileocaecal resections for CD at our instiution between 2008 and 2018 were included. All data was extracted from clinical charts. RESULTS: Major complications occurred in 23.8% of all patients. Patients after colonic resections showed a significantly higher rate of major postoperative complications compared to patients after ICR (p = < 0.0001). The most common complications after colonic resections were postoperative bleeding (22.2%), the need for revision surgery (27.4%) and ICU (17.2%) or hospital readmission (15%). As risk factors for the latter, we identified time interval between admission and surgery (p = 0.015) and the duration of the surgery (p = 0.001). Isolated distal resections had a higher risk for revision surgery and a secondary stoma (p = 0.019). Within the total study population, previous bowel resections (p = 0.037) were identified as independent risk factors for major perioperative complications. CONCLUSION: The results indicate that both a complex surgical site and a complex surgical procedure lead to a higher perioperative morbidity in colonic resections for Crohn's colitis.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Predictors of outcome for treatment of enterovaginal fistula : Therapeutical strategies for treatment.

BACKGROUND: Enterovaginal fistulas represent a serious complication of various diseases and therapeutic procedures, often associated with complicated clinical courses and massive impairment of quality of life. As underlying conditions and procedures are multifarious, therapeutic approaches are challenging and have to be tailored individually. As the therapeutic management is complex and individualized, multiple surgical interventions might be necessary. METHODS: The aim of this study was to identify possible predictors for outcome in the treatment enterovaginal fistula patients. The study was realized as a retrospective analysis. Ninety-two patients treated with enterovaginal fistulas between 2004 and 2016 were analyzed. Patient characteristics, therapeutic data, and endoscopic findings were stratified according to etiology, closure rate and time, as well as recurrence of fistula. Main outcome measure was the overall rate of fistula closure. RESULTS: Overall therapeutic success rate was 67.4%. Postoperatively derived fistulas were most frequent (40.2%), mainly after rectal surgery (59.5%). Postoperative and non-IBD-inflammation associated fistulas had better outcome than IBD-, radiotherapy-, and tumor-related fistulas (p = 0.001). Successful fistula closure was observed more frequently after radical surgical interventions, best results observed after transabdominal surgery (p < 0.001). Fistula recurrence was also less frequently observed after radical surgical therapies (p = 0.029). A temporary stoma was associated with higher incidence of fistula closure (p = 0.013) and lower incidence of fistula recurrence (p = 0.042) in the postoperative subgroup, as well as shortened therapy period in all groups (p = 0.031). CONCLUSION: Enterovaginal fistulas are a result of various etiologies, and treatment should be adjusted accordingly. A very sustainable, rapid, and persistent therapeutic success can be expected after radical surgical approaches with temporary diverting stoma. This is especially true for postoperatively derived fistulas.

Smoking as a risk factor for colorectal neoplasms in young individuals? A systematic meta-analysis.

BACKGROUND AND AIMS: Early-onset colorectal neoplasms (EoCRN) include both benign and malign colorectal tumors, which occur before the age of 50. The incidence of EoCRN is rising worldwide. Tobacco smoking has previously been proven to be related to the development of various tumor types. However, its relationship with EoCRN is not clearly defined. Hence, we carried out a systematic review and a meta-analysis to evaluate the relationship between smoking status and the risk of EoCRN. METHODS: A systematic search of PubMed, EMBASE, and Web of Science up to September 7, 2022, was performed for studies that evaluated the association of smoking status with EoCRN. The quality of the case-control study was evaluated with the Newcastle‒Ottawa Scale. The quality of the cross-sectional studies was evaluated with the American Health Care Research and Quality checklist. Fixed-effects models were used to pool odds ratios (ORs) to evaluate the relationship between the risk of developing EoCRN and smoking status. The meta-analyses were performed with Review Manager version 5.4, and funnel plots and publication bias tests were produced by STATA software. RESULTS: A total of six studies were included in this meta-analysis. After pooling the results of these six studies, we found that current smokers carry a relatively high risk of developing EoCRN (OR, 1.33; 95% confidence interval [CI], 1.17-1.52) compared to never-smokers. Ex-smokers were not at a significantly increased risk for developing EoCRN (OR, 1.00; 95% CI, 0.86-1.18). DISCUSSION: Smoking behavior is significantly associated with an increased risk for developing EoCRN and might be one of the reasons for the increasing incidence. Ex-smokers who quit are not at significant risk of developing EoCRN.

Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases.

The development of animal models reflecting the pathologies of ulcerative colitis (UC) and Crohn's disease (CD) remains a major challenge. The NOD/SCID/IL2rγnull (NSG) mouse strain, which is immune-compromised, tolerates the engraftment of human peripheral blood mononuclear cells (PBMC) derived from patients with UC (NSG-UC) or CD (NSG-CD). This offers the opportunity to examine the impact of individual immunological background on the development of pathophysiological manifestations. When challenged with ethanol, NSG-UC mice exhibited a strong pro-inflammatory response, including the development of edemas, influx of human T cells, B cells and monocytes into the mucosa and submucosa, and elevated expression of the inflammatory markers CRP and CCL-7. Fibrotic alterations were characterized by an influx of fibroblasts and a thickening of the muscularis mucosae. In contrast, the development of pathological manifestations in NSG-CD mice developed without challenge and was signified by extensive collagen deposition between the muscularis propria and muscularis mucosae, as observed in the areas of strictures in CD patients. Vimentin-expressing fibroblasts supplanting colonic crypts and elevated expression of HGF and TGFß corroborated the remodeling phenotype. In summary, the NSG-UC and NSG-CD models partially reflect these human diseases and are powerful tools to examine the mechanism underlying the inflammatory processes in UC and CD.

The Role of Microbiota in Liver Transplantation and Liver Transplantation-Related Biliary Complications.

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.

Survival Outcomes and Clinicopathological Features in Inflammatory Bowel Disease-associated Colorectal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of our study was to conduct a systematic review and meta-analysis comparing the survival outcomes of IBD-associated and non-IBD-associated CRC. SUMMARY OF BACKGROUND DATA: Investigations comparing the prognosis in CRC patients with and without IBD have yielded conflicting results. METHODS: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library were searched for studies evaluating the prognostic outcomes between CRC patients with IBD and those without IBD. Estimates of survival-related outcomes and clinicopathological features in IBD-CRC and non-IBD CRC were pooled through random-effects or fix-effects models. The study is registered with PROSPERO, CRD42021261513. RESULTS: Of 12,768 records identified, twenty-five studies with 8034 IBD-CRC and 810,526 non-IBD CRC patients were included in the analysis. IBD-CRC patients have a significant worse overall survival (OS) with the hazard ratio (HR) of 1.33 [95% confidence interval (CI): 1.20-1.47] than those without IBD. Pooled estimates of cancer-specific survival demonstrated that IBD-CRC patients had a poorer cancer-specific survival than those without IBD with fixed-effect model (HR, 2.17; 95% CI: 1.68-2.78; P < 0.0001). Moreover, ulcerative colitis-associated CRC patients have favorable OS than Crohn's disease-associated CRC (HR 0.79,95% CI: 0.72-0.87). Compared to non-IBD-CRC, patients with IBD-associated CRC are characterized by an increased rate of poor differentiation (OR 2.02, 95% CI: 1.57-2.61), mucinous or signet ring cell carcinoma (OR 2.43, 95% CI: 1.34-4.42), synchronous tumors (OR 3.18, 95% CI: 2.26-4.47), right-sided CRC (OR 1.62, 95%CI: 1.05-2.05), male patients (OR 1.10, 95% CI: 1.05-1.16), and a reduced rate of R0 resections (OR 0.60, 95% CI: 0.44-0.82). CONCLUSIONS: IBD-CRC patients have a significant worse OS than patients with non-IBD CRC, which may be attributed to more aggressive histological characteristics and a lower rate of R0 resections at the primary tumor site. Optimized therapeutic standards and tailored follow-up strategies might improve the prognosis of IBD-CRC patients.

Endoscopic Vacuum Therapy for Left-Sided Colorectal Anastomotic Leak Without Fecal Diversion.

BACKGROUND: Endoscopic vacuum therapy for the treatment of rectal anastomotic leak has been shown to be effective and safe. The majority of patients are treated after fecal diversion to avoid further septic complications. OBJECTIVE: To report the effectiveness of endoscopic vacuum therapy for rectal anastomotic leak without diversion compared to secondary stoma creation. DESIGN: Retrospective cohort analysis. SETTINGS: University hospital, single-center. PATIENTS: Patients undergoing sigmoid or rectal resection without fecal diversion during primary surgery who were treated with endoscopic vacuum therapy for clinically relevant anastomotic leak. MAIN OUTCOME MEASURES: Treatment success (sepsis control, granulation and closure of the leak cavity, and no subsequent interventional or surgical procedure required); treatment duration; complications associated with endoscopic vacuum therapy; outpatient treatment; and restoration of intestinal continuity in diverted patients. RESULTS: Fifty-seven patients were included. In 20 patients (35%), endoscopic vacuum therapy was initiated without secondary diversion since the leak was extraperitoneal, and the sponge could be placed into the leak cavity with an adequate seal toward the lumen. In 18 patients (90%), this approach was successful. None of these patients required subsequent diversion in the further course of their disease. In two patients, secondary diversion was necessary due to treatment failure. Balloon dilatation for luminal stenosis was required in two patients. When comparing patient and treatment characteristics of patients with and without a stoma, including treatment success and duration, no significant differences were found. Restoration of intestinal continuity was achieved in 69% of diverted patients. LIMITATIONS: Unrandomized, retrospective study design; confounding factors of treatment assignment; low patient numbers and short follow-up of diverted patients; and low statistical power. CONCLUSION: In this single-institution study, endoscopic vacuum therapy for rectal anastomotic leak was successful in 90% of patients without diversion with regard to sepsis control, granulation of the leak cavity, avoidance of surgery, and long-term stoma-free survival. See Video Abstract at http://links.lww.com/DCR/B737.TERAPIA ENDOSCÓPICA POR ASPIRACIÓN AL VACÍO EN CASOS DE FUGA ANASTOMÓTICA RECTO-CÓLICA IZQUIERDA SIN OSTOMÍA DE PROTECCIÓNANTECEDENTES:Se ha demostrado que la terapia endoscópica por aspiración al vacío en casos de fuga anastomótica recto-cólica izquierda en el tratamiento de la fuga anastomótica rectal es eficaz y segura. La mayoría de los casos beneficiaron del tratamiento después de la confeción de un ostomía de protección para evitar más complicaciones sépticas.OBJETIVO:Demostrar la efectividad de la terapia endoscópica por aspiración al vacío en casos de fuga anastomótica recto-cólica izquierda sin ostomía de protección comparada con los casos que tuvieron la creación de una ostomía secundaria.DISEÑO:Análisis de cohortes de tipo retrospectivo.AJUSTE:Hospital universitario, unicéntrico.PACIENTES:Aquellos pacientes sometidos a una resección sigmoidea o rectal sin ostomía de protección durante una cirugía primaria, y que fueron tratados con terapia endoscópica por aspiración al vacío en caso de fuga anastomótica clínicamente relevante.PRINCIPALES MEDIDAS DE RESULTADO:Tratamiento exitoso (control de la sepsis, granulación y cierre de la cavidad de la fuga, sin requerir procedimiento quirúrgico o intervención ulteterior); duración del tratamiento; complicaciones asociadas con la terapia endoscópica por aspiración al vacío; tratamiento ambulatorio; restablecimiento de la continuidad intestinal en los pacientes portadores de ostomía.RESULTADOS:Se incluyeron 57 pacientes. En 20 pacientes (35%), se inició la terapia endoscópica por aspiración al vacío sin derivación secundaria, ya que la fuga era extraperitoneal y la esponja podía colocarse en la cavidad de la fuga con un sellado adecuado hacia el lumen. En 18 pacientes (90%), este enfoque fue exitoso. Ninguno de estos pacientes requirió una derivación posterior durante la evolución de la enfermedad. En dos pacientes, fue necesaria una derivación secundaria debido al fracaso del tratamiento. Se requirió dilatación con balón por estenosis luminal en dos pacientes. Al comparar las características de los pacientes y del tratamiento con y sin ostomía, incluido el éxito y la duración del tratamiento, no se encontraron diferencias significativas. El restablecimiento de la continuidad intestinal se logró en el 69% de los pacientes derivados.LIMITACIONES:Diseño de estudio retrospectivo no aleatorio; factores de confusión en la asignación del tratamiento; escaso número de pacientes y seguimiento a corto plazo de los pacientes ostomizados; bajo poder estadístico.CONCLUSIÓN:En este estudio de una sola institución, la terapia al vacío por vía endoscópica en casos de fuga anastomótica rectal fue exitosa en el 90% de los pacientes sin derivación con respecto al control de la sepsis, granulación de la cavidad de la fuga, como se evitó la cirugía y la sobrevida sin ostomía a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B737. (Traducción-Dr. Xavier Delgadillo).

It is not NOD2 - genetic and clinical risk factors for postoperative complications following ileocolic resection in Crohn's disease.

PURPOSE: To evaluate the role of the nucleotide oligomerization domain 2 (NOD2) mutation status and other risk factors for the incidence of postoperative complications after ileocolic resection for Crohn's disease (CD). METHODS: Data of 138 patients consecutively undergoing ileocolic resection for CD at a tertiary academic referral center were retrospectively analyzed including single nucleotide polymorphism (SNP) data of the NOD2 gene. Uni- and multivariate regression analysis was performed to identify factors associated with increased risk of severe postoperative complications. RESULTS: From 114 patients (83%), the NOD2 mutation status was available. Of these, 60 (53%) had a NOD2 wildtype, whereas eleven (10%) were homozygous for the high risk p.Leu1007fsX1008 (rs2066847) variant. Major postoperative complications occurred in 28 patients (20%). Twenty-seven of these (96%) were intraabdominal septic complications such as anastomotic leakage or abscess. Male gender (P = 0.029; OR 3.052, the duration of CD (time [months] from initial diagnosis of CD to surgery; P = 0.001; OR 1.009), previous abdominal surgery for CD (P = 0.017; OR 3.49), and the presence of enteric fistulas (P = 0.023; OR 3.21) were identified as independent risk factors for major postoperative complications. Homozygosity for the NOD2 high-risk variant p.Leu1007fsX1008 did not show increased postoperative morbidity in the short and long-term outcome. CONCLUSIONS: We could detect independent risk factors for major postoperative complications after ileocolic resection for Crohn's disease. However, patients with the high-risk variant p.Leu1007fsX1008 of the NOD2 gene did not show increased postoperative morbidity.

Endoscopic vacuum therapy for the treatment of colorectal leaks - a systematic review and meta-analysis.

BACKGROUND: During the last two decades, vacuum-assisted wound therapy has been successfully transferred to an endoscopic treatment approach of various upper and lower gastrointestinal leaks called endoscopic vacuum therapy (EVT). As mostly small case series are published in this field, the aim of our systematic review and meta-analysis was to evaluate the efficacy and safety of EVT in the treatment of colorectal leaks. METHODS: A systematic search of MEDLINE/PubMed and Cochrane databases was performed using search terms related to EVT and colorectal defects (anastomotic leakage, rectal stump insufficiency) according to the PRISMA guidelines. Randomized controlled trials (RCTs), observational studies, and case series published by December 2020 were eligible for inclusion. A meta-analysis was conducted on the success of EVT, stoma reversal rate after EVT as well as procedure-related complications. Statistical interferences were based on pooled estimates from random effects models using DerSimonian-Laird estimator. RESULTS: Only data from observational studies and case series were available. Twenty-four studies reporting on 690 patients with colorectal defects undergoing EVT were included. The mean rate of success was 81.4% (95% CI: 74.0%-87.1%). The proportion of diverted patients was 76.4% (95% CI: 64.9%-85.0%). The mean rate of ostomy reversal across the studies was 66.7% (95% CI: 58.0%-74.4%). Sixty-four patients were reported with EVT-associated complications, the weighted mean complication rate across the studies was 12.1% (95% CI: 9.7%-15.2%). CONCLUSIONS: Current medical evidence on EVT in patients with colorectal leaks lacks high quality data from RCTs. Based on the data available, EVT can be seen as a feasible treatment option with manageable risks for selected patients with colorectal leaks.

Oral antibiotic bowel decontamination in open and laparoscopic sigmoid resections for diverticular disease.

PURPOSE: There is an ongoing debate on whether or not to use oral antibiotic bowel decontamination in colorectal surgery, despite the numerous different regimens in terms of antibiotic substances and duration of application. As we routinely use oral antibiotic bowel decontamination (selective decontamination of the digestive tract (SDD) regimen and SDD regimen plus vancomycin since 2016) in surgery for diverticular disease, our aim was to retrospectively analyze the perioperative outcome in two independent centers. METHODS: Data from two centers with a routine use of oral antibiotic bowel decontamination for up to 20 years of experience were analyzed for the perioperative outcome of 384 patients undergoing surgery for diverticular disease. RESULTS: Overall morbidity was 12.8%, overall mortality was 0.3%, the overall rate of anastomotic leakage (AL) was 1.0%, and surgical site infections (SSIs) were 5.5% and 7.8% of all infectious complications including urinary tract infections and pneumonia. No serious adverse events were related to use of oral antibiotic bowel decontamination. Most of the patients (93.8%) completed the perioperative regimen. Additional use of vancomycin to the SDD regimen did not show a further reduction of infectious complications, including SSI and AL. CONCLUSION: Oral antibiotic decontamination appears to be safe and effective with low rates of AL and infectious complications in surgery for diverticular disease.

Endoscopic vacuum therapy for in- and outpatient treatment of colorectal defects.

BACKGROUND: Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment. METHODS: Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (n = 281). RESULTS: The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (P = 0.037) and recent surgical revision after primary surgery (P = 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (P = 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (P = 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%. CONCLUSIONS: In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment.

Endoscopic vacuum therapy for treatment of rectal stump leakage.

BACKGROUND: Symptomatic rectal stump leakage (RSL) is a serious complication after discontinuity resection and requires immediate surgical, interventional, or endoscopic therapy. Re-operations are associated with high morbidity and mortality in these mostly very ill patients. Endoscopic vacuum therapy (EVT) has been established for management of anastomotic leakage; however, its effectiveness for RSL treatment has not been analyzed in detail yet. METHODS: A retrospective analysis of patients treated with EVT for RSL between 2001 and 2018 analyzing factors predicting therapy success and duration was carried out. RESULTS: Fifty-six patients with RSL at a median age of 66 years were included. Of these, 18 patients (32%) had been referred for EVT from external departments or institutions. RSL was associated with a relevant clinical deterioration in all patients, and 55 patients (98%) had been classified as ASA 3 and 4, preoperatively. In 9 patients (16%), additional surgical revision was necessary with initiation of EVT. In 47 patients (84%), EVT was successful and local control of the inflammatory focus was achieved. The median duration of therapy was 20 days. Two patients (4%) suffered from minor EVT-associated bleeding that was endoscopically controlled. Preoperative radiation of the pelvis was significantly associated with EVT failure (P = 0.035), whereas patient age represented a predictive factor for therapy length (P = 0.039). In 12 patients (21%), restoration of intestinal continuity was achieved in the further course. CONCLUSIONS: We present the first specific series on EVT for RSL. EVT for RSL was shown to be an effective and safe minimal-invasive treatment option, avoiding surgical revision in the majority of patients.

Experimental postoperative ileus: is Th2 immune response involved?

Rationale: Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. Methods: The intestinal transit test was performed using carbon gum arabic. Electron microscopy was employed to assess tissue morphology and the presence of immune cells. Cytokines, IgE and ROS were measured. Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. Transcriptional factors were analyzed by Western blot. Results: POI is associated with an increase in both Th2 cytokines and Th2 cells. We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response. Conclusion: Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.

Comparison Between Endoscopic Vacuum Therapy and Conventional Treatment for Leakage After Rectal Resection.

BACKGROUND: Anastomotic leakage after rectal resection represents a severe complication for the patient and requires an early and appropriate management. Endoscopic vacuum therapy (EVT) has become the treatment of choice for anastomotic leakage after rectal resection in several institutions in Germany, and commercially available systems are currently distributed in approximately 30 countries worldwide. However, there is no evidence that EVT is superior to any other treatment for anastomotic leakage after rectal resection. METHODS: Twenty-one patients treated with EVT for anastomotic leakage after rectal resection were retrospectively compared to a historical cohort of 41 patients that received conventional treatment. Primary endpoints were death, treatment success and long-term preservation of intestinal continuity. Secondary endpoints were length of hospital stay and duration of treatment. RESULTS: There was no difference in mortality (p = 0.624). The intention-to-treat analysis showed a significantly higher success rate of EVT compared to conventional treatment (95.2% vs. 65.9%, p = 0.011). EVT was associated with preservation of intestinal continuity in a significant higher percentage of patients than patients undergoing conventional treatment (86.7% vs. 37.5%, p = 0.001). Conventional treatment tended to a shorter length of hospital stay (31.1 vs. 42.2 days, p = 0.066) but with no difference in overall duration of treatment. Time until closing of a diverting stoma did not differ between groups (10.2 months in the EVT group vs. 9.4 months in the conventional treatment group, p = 0.721). CONCLUSION: According to this retrospective study, conventional therapy and EVT are both options for the treatment of anastomotic leakage after rectal resection. EVT might be more effective in terms of definite healing and preservation of intestinal continuity.

[Risk Factors for Mental Health Problems in Children with Cerebral Palsy and Spina Bifida]. / Risikofaktoren für psychische Auffälligkeiten von Kindern und Jugendlichen mit Infantiler Zerebralparese und Spina bifida.

BACKGROUND: Children with cerebral palsy (CP) and spina bifida (SB) are at an increased risk for mental health problems. Aim of this study was to correlate disease specific and psychosocial risk factors with characteristic mental health problems. PATIENTS: 271 children with CP and 84 with SB aged 3-17 years were included in a cross sectional study of 15 centers. METHODS: Parents answered the Strengths and Difficulties Questionnaire (SDQ) for mental health problems, rated social participation of their children and gave data to their own educational and professional level. IQ and motor impairment were tested or rated by the caring pediatricians. RESULTS: Abnormal Total-Difficulties Scores were found in CP (30,2%) and SB (18,1%) as compared to the norm (10,0%). Increased prevalences persisted after controlling for IQ as covariate. In both groups, moderate correlations between externalizing problems and levels of cognitive and motor impairment were found. Emotional problems correlated with participation irrespective of level of impairment. Weak correlations were found with age and gender in both groups. After controlling for IQ as covariate mental health problems showed no systematic difference between both groups. DISCUSSION: Mental health problems in children and youth with CP and SB are frequent. They correlated with various risk factors (IQ, motor impairment, age, gender, participation). Early recognition, participation and psychotherapeutic facilities should be strengthened.

[Risk Factors for Early Surgery and Surgical Complications in Crohn's Disease]. / Risikofaktoren für einen frühen OP-Zeitpunkt und chirurgische Komplikationen bei Morbus Crohn.

BACKGROUND: In recent decades, developments in drug therapy have significantly postponed the need for surgery. Nevertheless, the majority of patients with Crohn's disease still require one or more surgical interventions during the course of their disease. An analysis of epidemiological data as well as the surgical results of our own patients should help to identify risk factors for early surgery, re-operations and perioperative complications. METHODS: A retrospective analysis including 120 consecutive patients with Crohn's disease and needing surgical intervention was carried out at the University Hospital of Rostock (UMR), Germany. Statistical analysis was performed using SPSS. RESULTS: A total of 284 operations were recorded in 120 patients, of which 207 were performed on the UMR. The mean age at first surgery was 38 years (range: 17 - 66); initial diagnosis of Crohn's was on average at the age of 30 (range: 9 - 62). Each patient was operated 2 - 3 times during the course of their disease (range 1 - 9). Patients older than 30 years had significantly shorter time interval to the first operation. The number of operations per patient was significantly influenced by the localisation and behaviour of the disease. Penetrative behavior was associated with more frequent operations and terminal ileum involvement (L1) with significantly less frequent operations. Risk factors for complication of at least grade III according to Clavien-Dindo included greater age at surgery and at first diagnosis, decreased albumin levels and increased CRP. Anastomotic leakages were also associated with these risk factors as well as preoperative intake of > 20 mg prednisolone equivalent per day or cumulative dosage of 280 mg over the last 14 days prior to surgery. Anastomosis configuration and microscopic involvement of the resection margins had no statistically significant influence on the development of anastomotic leakage. CONCLUSION: Diagnosis after the age of 30 was associated with a significantly earlier need for surgery in this analysis. Patients with terminal ileum involvement (L1) had a significantly lower surgical frequency than patients with colon or combined Crohn's disease. Age, albumin, CRP and a steroid medication > 20 mg per day were predictors for perioperative complications.

Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study.

PURPOSE: Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. METHODS: Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. RESULTS: N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. CONCLUSION: Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.

Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.

BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function and intestinal homeostasis and prevents endotoxemia by detoxifying lipopolysaccharides (LPSs). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significantly stronger decrease in IAP than other major abdominal surgery. STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD, as well as other major surgical procedures without duodenectomy. The samples were analyzed using enzyme histochemistry, the para -nitrophenyl phosphate method for IAP, and the limulus amebocyte lysate assay for LPS. RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p < 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p = 0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP-also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p = 0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p = 0.0062) and more prominent in pancreatic cancer (p = 0.0009). CONCLUSIONS: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.

Baseline Interleukin-6 as a Preoperative Biomarker for Liver Fibrosis.

Introduction: Liver (hepatic) fibrosis (LF) is characterized by impaired function and regenerative capacity of the liver and can lead to significantly increased morbidity and mortality in the context of surgical liver resection (LR). For this reason, it is crucial to identify the extent of LF preoperatively. Interleukin-6 (IL-6) is known to play a key role in the pathogenesis of LF, but its exact value as a preoperative marker is unknown. This study aimed to investigate the correlation between preoperatively determined IL-6 and the presence of LF. Methods: In this prospective study, IL-6 was determined in 134 consecutive patients undergoing LR. Patients with liver cirrhosis (LC) and patients with clinical or laboratory signs of inflammation were excluded. LF was graded by a blinded pathologist with regard to the degree of LF according to the Desmet classification (0-4). Baseline IL-6 and degree of LF were correlated. Results: A total of 134 patients were prospectively included prior to LR. For 104 patients, LF was graded and inflammatory parameters were available. Thirty-five of these patients showed LC (Desmet 4), and another 33 patients showed preoperatively elevated inflammatory markers. Two of the remaining patients were liver transplant patients. These patients were excluded from the final analysis. According to Desmet, the remaining 34 patients had LF grade 0 or 1 (none or minimal LF) in 26 cases and LF grade 2 or 3 (moderate-to-severe LF) in 8 cases. Correlation of LF with preoperatively determined IL-6 yielded significantly higher IL-6 levels in the group of patients with moderate-to-severe LF (Desmet 2 or 3) compared to the group with none or minimal LF (Desmet 0 or 1; p = 0.0495). Conclusion: In the context of LR, our results showed a correlation of preoperatively determined IL-6 with the extent of LF present. Higher serum baseline IL-6 concentrations were associated with a higher degree of LF, whereas no other blood parameter or score was that predictive for LF. Our results suggest that baseline IL-6 might serve as a valuable parameter to assess LF prior to LR. More patients need to be analyzed to further evaluate and confirm the predictive accuracy of IL-6 for LF.