Human RORγt(+)CD34(+) cells are lineage-specified progenitors of group 3 RORγt(+) innate lymphoid cells.

Group 3 innate lymphoid cells (ILC3s) are defined by the expression of the transcription factor RORγt, which is selectively required for their development. The lineage-specified progenitors of ILC3s and their site of development after birth remain undefined. Here we identified a population of human CD34(+) hematopoietic progenitor cells (HPCs) that express RORγt and share a distinct transcriptional signature with ILC3s. RORγt(+)CD34(+) HPCs were located in tonsils and intestinal lamina propria (LP) and selectively differentiated toward ILC3s. In contrast, RORγt(-)CD34(+) HPCs could differentiate to become either ILC3s or natural killer (NK) cells, with differentiation toward ILC3 lineage determined by stem cell factor (SCF) and aryl hydrocarbon receptor (AhR) signaling. Thus, we demonstrate that in humans RORγt(+)CD34(+) cells are lineage-specified progenitors of IL-22(+) ILC3s and propose that tonsils and intestinal LP, which are enriched both in committed precursors and mature ILC3s, might represent preferential sites of ILC3 lineage differentiation.

RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.

RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

Inflammation of the rectal remnant endangers the outcome of ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: Inflammation of the rectal remnant may affect the postoperative outcome of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We aimed to determine the extent of inflammation in the anastomotic area during IPAA and to investigate the impact of proctitis on postoperative complications and long-term outcomes. METHODS: Three hundred thirty-four UC patients with primary IPAA were included in this retrospective case-control study. The histopathologic degree of inflammation in the anastomotic area was graded into three stages of no proctitis ("NOP"), mild to medium proctitis ("MIP"), and severe proctitis ("SEP"). Preoperative risk factors, 30-day morbidity, and follow-up data were assessed. Kaplan-Meier analysis was performed in the event of pouch failure. RESULTS: The prevalence of proctitis was high (MIP 40.4%, and SEP 42.8%). During follow-up, the incidence of complications was highest among SEP: resulting in re-intervention (n = 40; 28.2%, p = 0.017), pouchitis (n = 36; 25.2%, p < 0.01), and pouch failure (n = 32; 22.4%, p = 0.032). The time interval to pouch failure was 5.0 (4.0-6.9) years among NOP, and 1.2 (0.5-2.3) years in SEP (p = 0.036). ASA 3, pouchitis, and pouch fistula were independent risk factors for pouch failure. CONCLUSION: Proctitis at the time of IPAA is common. A high degree of inflammation is associated with poor long-term outcomes, an effect that declines over time. In addition, a higher degree of proctitis leads to earlier pouch failure.

Timing of surgery in ulcerative colitis in the biologic therapy era-the patient's perspective.

BACKGROUND: There is no general consensus regarding the ideal timing of surgery in patients with refractory ulcerative colitis (UC). Decision-making and timing of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is influenced by treating physicians and patients themselves. The aim of this study was to determine whether or not patients would have preferred the operation to be performed earlier, at the same time, or at a later point of time and to determine the reasons for their preference. METHODS: Clinical data of 193 patients with UC who have undergone IPAA were documented in a prospective database at our institution between 2004 and 2015. From this database, 190 patients were identified and a standardized custom-made questionnaire was mailed for follow-up survey. Patients who did not respond were called by telephone and encouraged to complete the questionnaire. RESULTS: One hundred nine questionnaires were eligible for analysis (57.4%). Average time between diagnosis and surgery was 11.2 ± 10.8 years (mean ± SD). Indications for surgery were refractory disease (70.6%), colitis-associated colorectal cancer (11.0%), high-grade dysplasia or stenosis (11.9%), and septic complications of UC (6.4%); 39 of 77 patients (50.6%) with refractory UC reported to have preferred their operation to be carried out earlier as it was actually performed (16.8 ± 11.9 months). Refractory course of the disease was identified as a predictor for a retrospectively desired earlier surgical approach (p = 0.014). CONCLUSION: A substantial proportion of patients felt that they should have undergone surgery earlier than actually performed. It appears that timing of the decision to undergo surgery is suboptimal. This situation may be improved by earlier surgical consultation in the course of the disease.

Impact of staged surgery on quality of life in refractory ulcerative colitis.

INTRODUCTION: Coloproctomucosectomy (CPM) with ileopouchanal anastomosis (IPAA), as the procedure of choice for surgical management of ulcerative colitis (UC), is commonly performed either as a 2- or 3-staged procedure. For patients with considerable immunosuppression, reduced nutritional or general health status, and as part of emergency treatment, a 3-staged (3S) procedure is recommended by guidelines to minimize perioperative complication rates compared to 2-staged (2S) procedure. However, the necessity of additional hospitalization and surgery is suspect to affect quality of life (QoL). In this prospective, observational study, we evaluate the long-term QoL after 2- and 3-staged interventions of CPM with IPAA for patients with UC. PATIENTS AND METHODS: Between 1997 and 2011, a total of 233 patients underwent CPM and had a 2- or 3-staged procedure. In 108 patients, surgical procedure was completed, and evaluation of QoL was performed by specific questionnaires (IBDQ, FIQoL, SF-12, CCS) up to 20 years after ileostomy closure. Data were collected within the framework of a prospective study. RESULTS: Observing a total of 84 patients (2S: n = 59; 3S: n = 25), QoL measured by IBDQ was higher after CPM, compared to preoperative (2S: 15 â†’ 31; 3S: 17 â†’ 28; p < 0.01), with no differences between 2S or 3S procedures (p > 0.05). Specific QoL assessment concerning incontinence and stool frequency (CCS, FIQoL) did not differ either (CCS: 2S:3S = 12:15; p > 0.05). General health-related QoL, determined by SF-12 score, did not differ between 2S or 3S procedures. CONCLUSION: The indication for a 2-staged or 3-staged procedure should be adjusted to the severity of the underlying disease, nutritional status of the patient, and the extent of immunosuppression at the time of surgery. It should not be affected by the fear of complications or a reduced quality of life by additional surgery in 3-staged versus 2-staged procedures.

Surgical Management of Iatrogenic Perforation of the Gastrointestinal Tract: 15 Years of Experience in a Single Center.

BACKGROUND: Gastrointestinal (GI) tract perforation during endoscopy is a rare but severe complication. The aim of this study was to determine predictors of morbidity and mortality after iatrogenic endoscopic perforation. MATERIALS AND METHODS: All cases with iatrogenic endoscopic perforation receiving surgery at a tertiary referral center in a 15-year period (2000-2015) were retrospectively analyzed. Demographics, type of endoscopy, site of perforation, operative procedure, morbidity and mortality were analyzed. Multiple logistic regression was used to identify parameters predicting survival. RESULTS: A total of 106.492 endoscopies were performed, and 82 (0.08%) patients were diagnosed with GI perforation. Most perforations (63.4%) occurred in the lower GI tract, compared to 36.6% in the upper GI tract. In 21 cases (25%), perforation was noticed during endoscopy, whereas 61 perforations (75%) were diagnosed during the further clinical course. Operative care was applied within 24 h in 61%. Surgery of perforations was almost completely performed maintaining the intestinal continuity (68%), whereas diversion was performed in 32%. Mortality was associated with age above 70 (OR 4.89, p = 0.027), ASA class > 3 (OR 4.08, p = 0.018), delayed surgery later than 24 h after perforation (OR 5.9, p = 0.015), peritonitis/mediastinitis intraoperatively (OR 4.68, p = 0.031) and severe postoperative complications with a Clavien-Dindo grade ≥III (OR 5.12, p = 0.023). CONCLUSION: The prevalence of iatrogenic endoscopic perforation is low, although it is associated with a serious impact on morbidity and mortality. Delayed management worsens prognosis. To achieve successful management of endoscopic perforations, early diagnosis is essential in cases of deviation from the normal post-interventional course, especially in elderly.

CT-based measurement of the inner pelvic volume.

Background Surgery in the lesser pelvis is associated with a high complication rate as surgeons are spatially limited by solid anatomic structures and soft tissue borders. So far, only two-dimensional (2D) parameters have been used for risk stratification. Purpose To precisely measure the inner pelvic volume a computed tomography (CT)-based three-dimensional (3D) approach was established and compared to approximations by 2D parameter combinations. Material and Methods Thin-layered multi-slice CT datasets were used retrospectively for slice by slice depiction of the inner pelvic surface. The inner pelvic volume was then automatically compounded. Combinations of two to four 2D dimensions determined in 3D volume rendered reconstructions were correlated with the inner pelvic volume. Pearson's correlation coefficient and Chi square test were used for statistical calculations. Significance level was set at P < 0.05. Results In total 142 patients (91 men, 51 women) aged 64.8 ± 10.6 years at surgery were included in the study. Mean calculated pelvic volume was 1031.13 ± 180.06 cm3 (men, 996.57 ± 172.43 cm3; women, 1093.34 ± 178.39 cm3). Best approximations were obtained by combination of the 2D measurements transverse inlet and pelvic height for men (r = 0.799, P < 0.05) as well as transverse inlet, obstetric conjugate, interspinous distance and pelvic depth for women (r = 0.855, P < 0.05). Conclusion We describe a precise and reproducible CT-based method for pelvic volumetry. A less time consuming but still reliable approximation can be achieved by combination of two to four 2D dimensions.

Dendritic cells from human mesenteric lymph nodes in inflammatory and non-inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDC) in mesenteric lymph nodes (MLN) may be important regulators of both inflammatory and non-inflammatory mucosal immune responses but human studies are rare. Here we compare pDC from human MLN and peripheral blood (PB) by phenotype and function. MLN from patients with or without inflammatory bowel disease (IBD) undergoing colon surgery and PB from patients with IBD and from controls were used to isolate mononuclear cells. The pDC were analysed by flow cytometry for the expression of CD40, CD80, CD83, CD86, CCR6, CCR7, CX3CR1, CD103 and HLA-DR. Purified pDC from MLN and PB were stimulated with staphylococcus enterotoxin B (SEB), CpG-A, interleukin-3 (IL-3), SEB + IL-3, CpG-A + IL-3 or left unstimulated, and cultured alone or with purified allogeneic CD4(+) CD45RA(+) HLA-DR- T cells. Subsequently, concentrations of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, interferon-α (IFN-α), IFN-γ and tumour necrosis factor-α (TNF-α) in culture supernatants were determined by multiplex bead array. The PB pDC from IBD patients exhibited an activated and matured phenotype whereas MLN pDC and control PB pDC were less activated. CpG-A and CpG-A + IL-3-stimulated MLN pDC secreted less IL-6 and TNF-α compared with PB pDC from controls. Compared with co-cultures of naive CD4 T cells with PB pDC, co-cultures with MLN pDC contained more IL-2, IL-10 and IFN-γ when stimulated with SEB and SEB + IL-3, and less IFN-α when stimulated with CpG-A. MLN pDC differ phenotypically from PB pDC and their pattern of cytokine secretion and may contribute to specific outcomes of mucosal immune reactions.

Endo-ß-N-acetylglucosaminidase H de-N-glycosylation in a domestic microwave oven: application to biomarker discovery.

Sample preparation is the rate-limiting step in glycan analysis workflows. Among all of the steps, enzymatic digestions, which are usually performed overnight, are the most time-consuming. In the current study, we report an economical and fast preparation of N-glycans from serum, including microwave-assisted enzymatic digestion in the absence of denaturing chemicals and solvents during the release. To this end, we used a household microwave oven to accelerate both pronase and endo-ß-N-acetylglucosaminidase H (Endo H) digestions. Purification was then performed using self-made SP20SS and carbon tips. We were able to prepare samples in 55 min instead of 21 h. Finally, the method was applied in the context of oncological biomarker discovery exemplarily to ovarian and colon cancer. We observed a significant downregulation of sialylated hybrid structures in ovarian cancer samples using capillary electrophoresis-laser-induced fluorescence (CE-LIF). Furthermore, sepsis, a systemic inflammatory response syndrome, was also included in the study to understand whether the changes observed in ovarian cancer patients were due to the cancer itself or to the inflammation that usually accompanies its development. Because sialylated hybrid structures were upregulated in sepsis samples, the downregulation of these structures in ovarian cancer is specific to the cancer itself and, therefore, could be used as a biomarker.

Repeatability of anorectal manometry in healthy volunteers and patients.

BACKGROUND: Anorectal manometry is used extensively in the assessment of patients with disorders of the pelvic floor. The present study investigated the repeatability of anorectal manometry in healthy volunteers and patients. PATIENTS AND METHODS: A total of 30 healthy volunteers (15 men and 15 women) and 10 patients with fecal incontinence (4 men and 6 women) underwent perfusion manometry and volumetry. Intraindividual variability was evaluated using the intraindividual correlation coefficient (ICC). Interindividual variability was expressed as the standard deviation from the calculated mean values. RESULTS: We found a high intraindividual correlation for the squeezing pressure (ICC 0.75-0.95), vector volume (ICC 0.88-0.97), and rectal perception (ICC 0.82-0.98). The anal resting pressure showed moderate repeatability (ICC 0.60-0.72). However, with regard to sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex, a wide range of variability was found. In the female volunteers, the squeezing pressure and vector volume were lower than in those in the male volunteers. The anal pressure, vector volume, thresholds for urgency, and the maximum tolerable volume were lower in the incontinent patients than in the healthy volunteers. CONCLUSIONS: The squeezing pressure, vector volume, and rectal perception allow a reliable analysis of anal sphincter function. Sphincter asymmetry, rectal compliance, and the rectoanal inhibitory reflex were of limited diagnostic value.

Educational and training aspects of new surgical techniques: experience with the endoscopic­laparoscopic interdisciplinary training entity (ELITE) model in training for a natural orifice translumenal endoscopic surgery (NOTES) approach to appendectomy.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is a new surgical concept that requires training before it is introduced into clinical practice. The endoscopic­laparoscopic interdisciplinary training entity (ELITE) is a training model for NOTES interventions. The latest research has concentrated on new materials for organs with realistic optical and haptic characteristics and the possibility of high-frequency dissection. This study aimed to assess both the ELITE model in a surgical training course and the construct validity of a newly developed NOTES appendectomy scenario. METHODS: The 70 attendees of the 2010 Practical Course for Visceral Surgery (Warnemuende, Germany) took part in the study and performed a NOTES appendectomy via a transsigmoidal access. The primary end point was the total time required for the appendectomy, including retrieval of the appendix. Subjective evaluation of the model was performed using a questionnaire. Subgroups were analyzed according to laparoscopic and endoscopic experience. RESULTS: The participants with endoscopic or laparoscopic experience completed the task significantly faster than the inexperienced participants (p = 0.009 and 0.019, respectively). Endoscopic experience was the strongest influencing factor, whereas laparoscopic experience had limited impact on the participants with previous endoscopic experience. As shown by the findings, 87.3% of the participants stated that the ELITE model was suitable for the NOTES training scenario, and 88.7% found the newly developed model anatomically realistic. CONCLUSIONS: This study was able to establish face and construct validity for the ELITE model with a large group of surgeons. The ELITE model seems to be well suited for the training of NOTES as a new surgical technique in an established gastrointestinal surgery skills course.

Risk factors for failure of ileal pouch-anal anastomosis in patients with refractory ulcerative colitis.

BACKGROUND: Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. METHODS: In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. RESULTS: The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P < .001), and had extraintestinal manifestations more frequently (65.4% vs 26.3%, P < .001). Further risk factors for failed ileal pouch-anal anastomosis were hypertension and Cushing's syndrome. CONCLUSION: Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

Rectal anatomy after rectopexy: cinedefecography versus MR-defecography.

BACKGROUND: Conventional defecography can reveal abnormalities in patients with evacuatory disorders. With fast dynamic MR imaging systems, MR-defecography has become possible, which does not expose patients to ionizing radiation. The purpose of this study was to assess the correlation of both methods after rectopexy. MATERIALS AND METHODS: Twenty-one consecutive patients underwent abdominal sigmoidectomy and rectopexy due to evacuatory disorders. Postoperatively, all patients were investigated by cineradiographic defecography. Fourteen patients underwent MR-defecography additionally. The results were screened for anorectal angle and pelvic floor position (rest, squeezing, and evacuation). The findings were depicted in Box plot analysis and compared with the Friedman-test. Descent of pelvic organs was also assessed. RESULTS: In MR-defecography, anorectal angle at rest was smaller than in conventional defecography, but there was no difference during squeezing and defecation. Concerning pelvic floor position, during squeezing, MR-defecography illustrated a lower perineum and a broader range of pelvic settings, but no difference at rest and during evacuation. In four patients, MR-defecography visualized a descent of the bladder. However, in four patients with complete evacuation in cineradiography and with no clinical complaints about incomplete evacuation, MR imaging showed deficient evacuation. Overall continence of patients was significantly improved through surgery, but there was no change in sphincter pressure, radial asymmetry, or sphincter length. CONCLUSIONS: In general, with respect to anorectal angle and perineal motility, both methods revealed consistent results. The concomitant depiction of structures in MR-defecography is helpful in the assessment of descent of pelvic organs and permits visualization of enteroceles. However, in 30% of patients, MR-defecography wrongly showed incomplete evacuation.

Molecular profiles and clinical outcome of stage UICC II colon cancer patients.

PURPOSE: Published multigene classifiers suggesting outcome prediction for patients with stage UICC II colon cancer have not been translated into a clinical application so far. Therefore, we aimed at validating own and published gene expression signatures employing methods which enable their reconstruction in routine diagnostic specimens. METHODS: Immunohistochemistry was applied to 68 stage UICC II colon cancers to determine the protein expression of previously published prognostic classifier genes (CDH17, LAT, CA2, EMR3, and TNFRSF11A). RNA from macrodissected tumor samples from 53 of these 68 patients was profiled on Affymetrix GeneChips (HG-U133 Plus 2.0). Prognostic signatures were generated by "nearest shrunken centroids" with cross-validation. Previously published gene signatures were applied to our data set using "global tests" and leave-one-out cross-validation RESULTS: Correlation of protein expression with clinical outcome failed to separate patients with disease-free follow-up (group DF) and relapse (group R). Although gene expression profiling allowed the identification of differentially expressed genes ("DF" vs. "R"), a stable classification/prognosis signature was not discernable. Furthermore, the application of previously published gene signatures to our data was unable to predict clinical outcome (prediction rate 75.5% and 64.2%; n.s.). T-stage was the only independent prognostic factor for relapse with established clinical and pathological parameters including microsatellite status (multivariate analysis). CONCLUSIONS: Our protein and gene expression analyses do not support application of molecular classifiers for prediction of clinical outcome in current routine diagnostic as a basis for patient-orientated therapy in stage UICC II colon cancer. Further studies are needed to develop prognosis signatures applicable in patient care.

Long-term outcome after conservative and surgical treatment of acute sigmoid diverticulitis.

PURPOSE: This study was designed to compare the long-term outcome of patients treated with conservative versus surgical treatment for acute sigmoid diverticulitis (SD). PATIENTS AND METHODS: Consecutive admissions of all patients with acute SD were prospectively recruited from January 2004 to June 2007. In June 2008, all patients were contacted using a standardized questionnaire. Outcomes were compared based on initial therapy (conservative vs. surgical). Furthermore, multiple logistic regression was used to identify risk factors for recurrence of SD. RESULTS: A total of 210 patients were included in the study. One hundred fifty-three patients were reached for follow-up: 70 (45.8%) presented with their first episode, and 83 (54.2%) had a prior history of SD. The median follow-up was 32 months (range 12-52). Thirteen (32.5%) of 40 conservatively treated patients and four (3.5%) of 113 surgically treated patients had a recurrence of SD (p < 0.001) during follow-up. One patient (2.5%) required emergency surgery after conservative treatment due to free perforation (p = 0.567). Treatment groups did not differ in age, gender, and inflammatory parameters, but conservatively treated patients had a significantly higher comorbidity (>2 disorders; p = 0.038) and less frequently a severe SD (p = 0.022) at the index admission. Recurrent episode of SD, covered perforated SD, and conservative treatment were identified as risk factors for recurrence of SD on multiple logistic regression. CONCLUSIONS: Surgical treatment of acute SD is more effective in preventing an eventual relapse of SD than conservative treatment, particularly in patients with recurrent and severe diverticulitis. The necessity for an emergency operation during follow-up is low and did not differ between the two treatment groups. The initial clinical presentation of SD is not a strong predictor of recurrence.

Oligosymptomatic vs. symptomatic incisional hernias--who benefits from open repair?

INTRODUCTION: Incisional hernias are one of the most often complications in abdominal surgery and therefore present a significant surgical and socioeconomic problem. To date, incisional hernias are always an indication for surgery, regardless of the patient's symptoms. However, it remains unclear to what extent the surgery actually results in symptomatic improvement and whether a relevant risk of incarceration exists. The purpose of this study was to investigate the motivation that led to incisional hernia repairs and whether patients benefit from surgery with regard to pain and subjective criteria. MATERIALS AND METHODS: This prospective study included patients who underwent open abdominal incisional hernia repair using mesh implantation. Data collection was done preoperatively and 6 months postoperatively. The intensity of pain was evaluated using the Numeric Analog Scale (NAS). Patients were divided according to their preoperative level of pain into oligosymptomatic (NAS 0-3) and symptomatic (NAS 4-10) groups, and the postoperative outcome of both groups was compared. RESULTS: Ninety patients were prospectively enrolled: 45 males (50.0%) and 45 females (50.0%); 43 patients (47.8%) were oligosymptomatic preoperatively, while 47 patients (52.2%) reported relevant pain. The most frequent motivation for surgery named by the oligosymptomatic patients was fear of incarceration (79.1%), while the symptomatic patients mostly mentioned pain (76.6%). At 6 months postoperatively, significantly more oligosymptomatic patients complained of relevant pain (p < 0.001). In the symptomatic patient group, there was a significant reduction in relevant pain (p < 0.001). At that time, the level of relevant pain was comparable in both groups (33.3% versus 35.6%). Seven of 87 patients (8.0%) experienced recurrence within 6 months. Three patients with acute incarceration were treated with emergency repair (3.2%). CONCLUSIONS: In patients with oligosymptomatic incisional hernias, fear of incarceration is the most frequent motivation for surgical treatment, even though the actual risk of incarceration seems to be rather low. If the incisional hernia causes relevant discomfort preoperatively, the surgery provides significant relief. In contrast, there is no improvement regarding pain in the oligosymptomatic patient group. This leads to the conclusion that, in the case of oligosymptomatic incisional hernias, the general indication for surgical revision should be viewed critically.

Exon array analysis using re-defined probe sets results in reliable identification of alternatively spliced genes in non-small cell lung cancer.

BACKGROUND: Treatment of non-small cell lung cancer with novel targeted therapies is a major unmet clinical need. Alternative splicing is a mechanism which generates diverse protein products and is of functional relevance in cancer. RESULTS: In this study, a genome-wide analysis of the alteration of splicing patterns between lung cancer and normal lung tissue was performed. We generated an exon array data set derived from matched pairs of lung cancer and normal lung tissue including both the adenocarcinoma and the squamous cell carcinoma subtypes. An enhanced workflow was developed to reliably detect differential splicing in an exon array data set. In total, 330 genes were found to be differentially spliced in non-small cell lung cancer compared to normal lung tissue. Microarray findings were validated with independent laboratory methods for CLSTN1, FN1, KIAA1217, MYO18A, NCOR2, NUMB, SLK, SYNE2, TPM1, (in total, 10 events) and ADD3, which was analysed in depth. We achieved a high validation rate of 69%. Evidence was found that the activity of FOX2, the splicing factor shown to cause cancer-specific splicing patterns in breast and ovarian cancer, is not altered at the transcript level in several cancer types including lung cancer. CONCLUSIONS: This study demonstrates how alternatively spliced genes can reliably be identified in a cancer data set. Our findings underline that key processes of cancer progression in NSCLC are affected by alternative splicing, which can be exploited in the search for novel targeted therapies.

Association between activation of atypical NF-kappaB1 p105 signaling pathway and nuclear beta-catenin accumulation in colorectal carcinoma.

Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to beta-catenin signaling leads to the stabilization of beta-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of IkappaBalpha and activation of canonical nuclear factor-kappaB (NF-kappaB) pathway. Here, we show that the noncanonical NF-kappaB1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with beta-catenin-mediated increased expression of CRD-BP and beta-TrCP1. In the carcinoma tissues exhibiting high levels of nuclear beta-catenin the phospho-p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF-kappaB pathway. Knockdown of CRD-BP in colorectal cancer cell line SW620 resulted in significantly higher basal levels of both NF-kappaB inhibitory proteins, p105 and IkappaBalpha. Furthermore decreased NF-kappaB binding activity was observed in CRD-BP siRNA-transfected SW620 cells as compared with those transfected with control siRNA. Altogether, our findings suggest that activation of NF-kappaB1 p105 signaling in colorectal carcinoma might be attributed to beta-catenin-mediated induction of CRD-BP and beta-TrCP1.

Measurable learning effects after a 1-week skills course in digestive surgery.

AIM: The aim of this study was to assess the learning effects of a surgical skills course focussed on theoretical knowledge, anastomosis techniques and practical suturing skills in digestive surgery. METHODS: One hundred eight participants of a 1-week skills course, comprising practical exercises in conventional and laparascopic digestive surgery, were asked to complete questionnaires (self-evaluation and course evaluation) and a theoretical knowledge test prior to the beginning (tp1) and at the end of the course (tp2). Thirty-six randomly selected participants performed a handsewn anastomosis at tp1 and at tp2, whereby the respective performance of each participant was recorded on video film and awarded a comparative rating (points score). RESULTS: In regard to course expectations, 93.52% of the participants had expressed the objective to acquire knowledge in the field of standard surgical techniques, and 71.30% aimed to brush up their existing knowledge and skills. In this respect, participants' satisfaction at tp2 was recorded as high to very high. Confidence to carry out simple and more complex anastomosis was significantly increased (p < 0.001) at tp2. A significantly higher intestinal suture score (11.94 vs. 9.75) was attained at tp2 in a shorter time (176.22 vs. 277.11 s). The reduction in the time needed to complete the given task was accompanied by a corresponding improvement in the quality (p < 0.001). CONCLUSION: Surgical skill courses constitute an effective component of surgical training with a sustained impact and, therefore, should be integrated into a future curriculum.

Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn's disease--review of the literature.

BACKGROUND: Stricturing Crohn's disease is accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Strictureplasty (SP) and endoscopic balloon dilatation (EBD) have been developed to prevent, or at least delay, the requirement for resection. The goal of this study was to compare the outcome of these two procedures with regard to complications and disease recurrence. METHODS: We conducted a MEDLINE literature search to give a current overview about the safety and efficacy of EBD and SP. RESULTS: The initial search yielded 744 articles. Case reports, reviews and meta-analyses were excluded. Finally, 63 articles (SP, 40 articles; EBD, 23 articles) were used for the review. None of the studies compared the two methods directly. A total of 2,532 patients (SP, n = 1,958; EBD, n = 574) were included. The incidence of perioperative complications after SP was 11% and the incidence of major complications was 5%. The median surgical recurrence rate was 24% after a median follow-up of 46 months. The median technical success for EBD was 90%. Major complications occurred in 3% of the cases. According to an intention-to-treat protocol, the median surgical recurrence rate was 27.6%. Per-protocol analysis revealed a median surgical recurrence rate of 21.4% after a median follow-up of 21 months. CONCLUSION: Due to the lack of comparable data, there is currently no reliable information on whether one treatment option is superior to the other. Regarding the limited applicability of EBD in strictures of the small bowel, only a controlled trial would provide evidence as a basis for clinical decision making in CD strictures that are potentially treatable by EBD and SP.