Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas

Most genome-wide association studies (GWAS) were analyzed using single marker tests in combination with stringent correction procedures for multiple testing. Thus, a substantial proportion of associated single nucleotide polymorphisms (SNPs) remained undetected and may account for missing heritability in complex traits. Model selection procedures present a powerful alternative to identify associated SNPs in high-dimensional settings. In this GWAS including 1060 colorectal cancer cases, 689 cases of advanced colorectal adenomas and 4367 controls we pursued a dual approach to investigate genome-wide associations with disease risk applying both, single marker analysis and model selection based on the modified Bayesian information criterion, mBIC2, implemented in the software package MOSGWA. For different case-control comparisons, we report models including between 1-14 candidate SNPs. A genome-wide significant association of rs17659990 (P=5.43x10(-9), DOCK3, chromosome 3p21.2) with colorectal cancer risk was observed. Furthermore, 56 SNPs known to influence susceptibility to colorectal cancer and advanced adenoma were tested in a hypothesis-driven approach and several of them were found to be relevant in our Austrian cohort. After correction for multiple testing (alpha=8.9x10(-4)), the most significant associations were observed for SNPs rs10505477 (P=6.08x10(-4)) and rs6983267 (P=7.35x10(-4)) of CASC8, rs3802842 (P=8.98x10(-5), COLCA1,2), and rs12953717 (P=4.64x10(-4), SMAD7). All previously unreported SNPs demand replication in additional samples. Reanalysis of existing GWAS datasets using model selection as tool to detect SNPs associated with a complex trait may present a promising resource to identify further genetic risk variants not only for colorectal cancer

Petiole hyponasty: an ethylene-driven, adaptive response to changes in the environment

Hyponastic (upwardly bending) growth by leaves is a response of numerous plant species to adverse environmental conditions. This review summarises current knowledge on hyponasty with a particular focus on the role of ethylene in regulating this phenomenon and its possible adaptive significance

Minimal-invasive approach for penetrating Crohns disease is not associated with increased complications

Background Laparoscopic surgery for penetrating Crohns disease (CD) still remains highly conflicting due to a lack of sufficient data. Therefore, the following large study was designed to compare postoperative outcomes after minimal-invasive resections for penetrating and non-penetrating CD. Methods Consecutive patients, who underwent laparoscopic intestinal resection for symptomatic CD at a tertiary academic referral center, were included. Patients were divided according to perioperative findings in penetrating and non-penetrating type of disease. All clinical data were obtained from an institutional database and analyzed retrospectively. Results Of 234 patients enrolled, 101 patients [females: n = 54 (53.5 %)] were operated on for non-penetrating CD and 133 patients [females: n = 50 (37.6 %)] for penetrating CD. Fistulas (p < 0.001), inflammatory mass (p < 0.001) and abscess formation (p < 0.001) were observed more frequently in the perforating group. Ileocolic resections were performed predominantly in both groups [perforating CD: n = 110 (82.7 %), non-perforating CD: n = 82 (81.2 %)], with more complex resections (>1 intestinal resection) found in perforating CD (p < 0.001). Conversion rates did not differ significantly. Notably, 30-day postoperative morbidity was comparable for both groups [perforating CD: n = 20 (15 %), non-perforating CD: n = 19 (18.8 %), p = 0.44]. Postoperative complication rates graded according to the ClavienDindo classification showed no difference too (p = 0.49). Conclusion Laparoscopic surgery can be conducted safely in selected patients with penetrating CD without increasing the risk of postoperative complications. This finding needs to be implemented in future guidelines.(VLID)348927

Visceral fat area measured with computed tomography does not predict postoperative course in Crohn´s disease patients.

The role of visceral fat measured by computer tomography is yet not well defined in patients with Crohn's disease. Therefore, the present study was designed to assess the impact of visceral fat area on postoperative short-term outcome and surgical characteristics. We analyzed 95 patients, who underwent intestinal resection for symptomatic Crohn's disease at an academic tertiary referral center between 2003 and 2008. Visceral fat area was measured on preoperative computed tomography scans. Postoperative morbidity was graded according to the Clavien-Dindo classification. Visceral fat area was correlated with baseline characteristics, disease phenotype and 30-day morbidity. Body mass index and age were significantly associated with a higher visceral fat area (p = 0.001). Overall 19 (20.0%) postoperative complications were observed, of whom 7 (7.4%) patients required surgical re-intervention. No significant difference was found with regard to visceral fat area between patients with an uneventful and eventful postoperative course (no complications: median visceral fat area 52.0 cm2 SD 59.7, complications: 41.3 cm2 SD 42.8; p = 0.465). In contrast to current literature, we cannot support the role of visceral fat area for predicting postoperative course in Crohn's disease. In addition, no correlation of the visceral fat area and disease behavior was detected

The modified Glasgow prognostic score in Crohns diseasedoes it predict short-term outcome?

Background The modified Glasgow prognostic score (mGPS) has recently gained increased attention as a prognostic marker for malignant disease survival and postoperative short-term complications. Due to lacking data, the present study was conducted to correlate the mGPS with the postoperative course in patients following surgery for Crohns disease. Methods We enrolled 341 patients who underwent intestinal resection for symptomatic Crohns disease at a tertiary referral centre between 2000 and 2014. All relevant data were obtained from the institutional database and individual chart review. Thirty-day morbidity was defined according to the ClavienDindo classification. Results A total of 79 (23.17%) postoperative complications were identified (grade I and II: n = 54, 15.84%; grade III and IV: n = 23, 6.74%; grade V: n = 2, 0.59%). The mGPS did not show any correlation with an eventful postoperative course following surgery (no complication: median mGPS: 1, range 02; complications: median mGPS: 1, range 02; p = 0.8521). In addition, the occurrence of an anastomotic leakage was not associated with a higher mGPS (p = 0.8592). Patients with an acute indication for surgery (n = 29, 11.44%) had higher median mGPS (median: 2, range 02) in contrast to patients who were operated on electively (median: 1, range 02; p = 0.0003). No other correlation between surgical characteristics and mGPS was detected. Conclusions In the present study, we could clearly demonstrate that an acute indication for surgery in symptomatic Crohns disease is associated with higher mGPS scores. However, the mGPS did not correlate with postoperative complications. Further studies are required to define the prognostic value of mGPS in Crohns disease patients.(VLID)359159

Recurrent abscess after primary successful endo-sponge treatment of anastomotic leakage following rectal surgery

AIM: To assess long-term efficacy of initially successful endo-sponge assisted therapy

Delta albumin is a better prognostic marker for complications following laparoscopic intestinal resection for Crohn's disease than albumin alone - A retrospective cohort study.

PURPOSE:Little is known about the perioperative dynamic of albumin and its effect on surgical outcome in Crohn's disease. Thus, we aimed to assess postoperative changes of albumin levels and their potentially predictive role for complications after laparoscopic intestinal resections. METHODS:We identified 182 patients who underwent laparoscopic intestinal resection for symptomatic Crohn´s disease between 2000 and 2014 for this retrospective cohort study. Pre- and postoperative serum albumin levels (within 4 days) were recorded retrospectively and proportional postoperative reduction (delta (Δ) albumin) was calculated. Complications were defined according to the Clavien-Dindo classification. Univariate and multivariate analysis describing an eventful postoperative course were conducted. RESULTS:Complications were found in 22.5% (n = 41), 6% (n = 11) developed major complications defined as Clavien Dindo III-V and 16.5% (n = 30) had minor complications (Clavien Dindo I-II). The median Δ albumin was 22.75% (range: -18.46-47.14%). Delta albumin was found to be significantly higher in patients who developed complications after surgery (p = 0.03). Notably, neither preoperative (p = 0.28) nor postoperative albumin levels (p = 0.41) taken as absolute numerical values correlated with an eventful course following intestinal resection. In the multivariate analysis, based on a cut-off of 24.27%, Δ albumin remained an independent factor for surgical complications (p = 0.04, OR 2.232) next to conversion rate (p<0.001, OR 5.577) and the presence of an inflammatory mass (p = 0.003, OR 0.280). CONCLUSION:Δ albumin is a better prognostic marker for an eventful postoperative course after laparoscopic surgery in patients with Crohn's disease in comparison to albumin alone