To determine the effect of biological mesh closure on perineal wound healing after extralevator abdominoperineal resection (eAPR).
Perineal wound complications frequently occur after eAPR with ...preoperative radiotherapy for rectal cancer. Cohort studies have suggested that biological mesh closure of the pelvic floor improves perineal wound healing.
Patients were randomly assigned to primary closure (standard arm) or biological mesh closure (intervention arm). A non-cross-linked porcine acellular dermal mesh was sutured to the pelvic floor remnants in the intervention arm, followed by a layered closure of the ischioanal and subcutaneous fat and skin similar to the control intervention. The outcome of the randomization was concealed from the patient and perineal wound assessor. The primary endpoint was the rate of uncomplicated perineal wound healing defined as a Southampton wound score of less than 2 at 30 days postoperatively. Patients were followed for 1 year.
In total, 104 patients were randomly assigned to primary closure (n = 54; 1 dropouts) and biological mesh closure (n = 50; 2 dropouts). Uncomplicated perineal wound healing rate at 30 days was 66% (33/50; 3 not evaluable) after primary closure, which did not significantly differ from 63% (30/48) after biological mesh closure relative risk 1.056; 95% confidence interval (CI) 0.7854-1.4197; P = 0.7177). Freedom from perineal hernia at 1 year was 73% (95% CI 60.93-85.07) versus 87% (95% CI 77.49-96.51), respectively (P = 0.0316).
Perineal wound healing after eAPR with preoperative radiotherapy for rectal cancer was not improved when using a biological mesh. A significantly lower 1-year perineal hernia rate after biological mesh closure is a promising secondary finding that needs longer follow-up to determine its clinical relevance.
To determine long-term outcomes of a randomized trial (BIOPEX) comparing biological mesh and primary perineal closure in rectal cancer patients after extralevator abdominoperineal resection and ...preoperative radiotherapy, with a primary focus on symptomatic perineal hernia.
BIOPEX is the only randomized trial in this field, which was negative on its primary endpoint (30-day wound healing).
This was a posthoc secondary analysis of patients randomized in the BIOPEX trial to either biological mesh closure (n = 50; 2 dropouts) or primary perineal closure (n = 54; 1 dropout). Patients were followed for 5 years. Actuarial 5-year probabilities were determined by the Kaplan-Meier statistic.
Actuarial 5-year symptomatic perineal hernia rates were 7% (95% CI, 0-30) after biological mesh closure versus 30% (95% CI, 10-49) after primary closure (P = 0.006). One patient (2%) in the biomesh group underwent elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P = 0.062). Reoperations for small bowel obstruction were necessary in 1/48 patients (2%) and 5/53 patients (9%), respectively (P = 0.208). No significant differences were found for chronic perineal wound problems, locoregional recurrence, overall survival, and main domains of quality of life and functional outcome.
Symptomatic perineal hernia rate at 5-year follow-up after abdominoperineal resection for rectal cancer was significantly lower after biological mesh closure. Biological mesh closure did not improve quality of life or functional outcomes.
Background
Endoscopic self‐expanding metal stent (SEMS) placement as a bridge to surgery is an option for acute malignant colonic obstruction. There is ongoing debate regarding the superiority and ...oncological safety of SEMS placement compared with emergency surgery. This retrospective study aimed to compare outcomes of these treatment approaches.
Methods
Patients were identified from cohorts treated between 2005 and 2012 in two teaching hospitals, of which one used emergency surgery only in patients with large bowel obstruction, whereas the other attempted SEMS placement. Only patients treated with curative intent were included.
Results
The study included 59 patients in whom SEMS placement was attempted and 51 who underwent surgery alone. The successful primary anastomosis rate was higher in the SEMS group than in the surgery‐alone group among patients with left‐sided obstruction (30 of 43 versus 10 of 34 respectively; P = 0·001), whereas stoma formation was less common (11 of 43 versus 23 of 34; P < 0·001). Such differences were not apparent in patients with right‐sided obstruction. Secondary stoma rates were comparable between treatment approaches (left‐sided: 11 of 43 versus 13 of 34, P = 0·322; right‐sided: 1 of 16 versus 1 of 17, P = 1·000). There were no significant differences in morbidity, mortality, recurrence or survival.
Conclusion
Endoscopic SEMS placement increased the primary anastomosis rate in patients with left‐sided large bowel obstruction.
Fewer stomas in left‐sided tumours
•Physical activity does not necessarily have effects on children’s brain activation.•Different types of physical activity do not differentially affect brain activation.•Large individual differences ...exist in intervention effects on brain activation.•A combination of aerobic and cognitively-engaging activity might be most effective.
Different types of physical activity are thought to differentially affect children’s brain activation, via physiological mechanisms, or by activating similar brain areas during physical and cognitive tasks. Despite many behavioral studies relying on these mechanisms, they have been rarely studied. This study looks at both mechanisms simultaneously, by examining effects of two physical activity interventions (aerobic vs. cognitively-engaging) on children’s brain activation. Functional Magnetic Resonance Imaging (fMRI) data of 62 children (48.4% boys, mean age 9.2 years) was analyzed. Children’s visuospatial working memory related brain activity patterns were tested using a Spatial Span Task before and after the 14-week interventions consisting of four physical education lessons per week. The control group followed their regular program of two lessons per week. Analyses of activation patterns in SPM 12.0 revealed no activation changes between pretest and posttest (p > .05), and no differences between the three conditions in pretest–posttest changes in brain activation (p > .05). Large inter-individual differences were found, suggesting that not every child benefited from the interventions in the same way. To get more insight into the assumed mechanisms, further research is needed to understand whether, when, for whom, and how physical activity results in changed brain activation patterns.
Aim
Laparoscopic peritoneal lavage has increasingly been investigated as a promising alternative to sigmoidectomy for perforated diverticulitis with purulent peritonitis. Most studies only reported ...outcomes up to 12 months. Therefore, the objective of this study was to evaluate long‐term outcomes of patients treated with laparoscopic lavage.
Methods
Between 2008 and 2010, 38 patients treated with laparoscopic lavage for perforated diverticulitis in 10 Dutch teaching hospitals were included. Long‐term follow‐up data on patient outcomes, e.g. diverticulitis recurrence, reoperations and readmissions, were collected retrospectively. The characteristics of patients with recurrent diverticulitis or complications requiring surgery or leading to death, categorized as ‘overall complicated outcome’, were compared with patients who developed no complications or complications not requiring surgery.
Results
The median follow‐up was 46 months (interquartile range 7–77), during which 17 episodes of recurrent diverticulitis (seven complicated) in 12 patients (32%) occurred. Twelve patients (32%) required additional surgery with a total of 29 procedures. Fifteen patients (39%) had a total of 50 readmissions. Of initially successfully treated patients (n = 31), 12 (31%) had recurrent diverticulitis or other complications. At 90 days, 32 (84%) patients were alive without undergoing a sigmoidectomy. However, seven (22%) of these patients eventually had a sigmoidectomy after 90 days. Diverticulitis‐related events occurred up to 6 years after the index procedure.
Conclusion
Long‐term diverticulitis recurrence, re‐intervention and readmission rates after laparoscopic lavage were high. A complicated outcome was also seen in patients who had initially been treated successfully with laparoscopic lavage with relevant events occurring up to 6 years after initial surgery.
In early rectal cancer, organ sparing treatment strategies such as local excision have gained popularity. The necessity of radical surgery is based on the histopathological evaluation of the local ...excision specimen. This study aimed to describe diagnostic variability between pathologists, and its impact on treatment allocation in patients with locally excised early rectal cancer.
Patients with locally excised pT1-2 rectal cancer were included in this prospective cohort study. Both quantitative measures and histopathological risk factors (i.e. poor differentiation, deep submucosal invasion, and lymphatic- or venous invasion) were evaluated. Interobserver variability was reported by both percentages and Fleiss’ Kappa- (ĸ) or intra-class correlation coefficients.
A total of 126 patients were included. Ninety-four percent of the original histopathological reports contained all required parameters. In 73 of the 126 (57.9%) patients, at least one discordant parameter was observed, which regarded histopathological risk factors for lymph node metastases in 36 patients (28.6%). Interobserver agreement among different variables varied between 74% and 95% or ĸ 0.530–0.962. The assessment of lymphovascular invasion showed discordances in 26% (ĸ = 0.530, 95% CI 0.375–0.684) of the cases. In fourteen (11%) patients, discordances led to a change in treatment strategy.
This study demonstrated that there is substantial interobserver variability between pathologists, especially in the assessment of lymphovascular invasion. Pathologists play a key role in treatment allocation after local excision of early rectal cancer, therefore interobserver variability needs to be reduced to decrease the number of patients that are over- or undertreated.
Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy ...and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure.
In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs.
The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia.
NCT01927497 (Clinicaltrial.gov).
Background
Anastomotic leakage is a potential major complication after colorectal surgery. The C‐seal was developed to help reduce the clinical leakage rate. It is an intraluminal sheath that is ...stapled proximal to a colorectal anastomosis, covering it intraluminally and thus preventing intestinal leakage in case of anastomotic dehiscence. The C‐seal trial was initiated to evaluate the efficacy of the C‐seal in reducing anastomotic leakage in stapled colorectal anastomoses.
Methods
This RCT was performed in 41 hospitals in the Netherlands, Germany, France, Hungary and Spain. Patients undergoing elective surgery with a stapled colorectal anastomosis less than 15 cm from the anal verge were eligible. Included patients were randomized to the C‐seal and control groups, stratified for centre, anastomotic height and intention to create a defunctioning stoma. Primary outcome was anastomotic leakage requiring invasive treatment.
Results
Between December 2011 and December 2013, 402 patients were included in the trial, 202 in the C‐seal group and 200 in the control group. Anastomotic leakage was diagnosed in 31 patients (7·7 per cent), with a 10·4 per cent leak rate in the C‐seal group and 5·0 per cent in the control group (P = 0·060). Male sex showed a trend towards a higher leak rate (P = 0·055). Construction of a defunctioning stoma led to a lower leakage rate, although this was not significant (P = 0·095).
Conclusion
C‐seal application in stapled colorectal anastomoses does not reduce anastomotic leakage. Registration number: NTR3080 (http://www.trialregister.nl/trialreg/index.asp).
Not effective
Aerobic fitness and fundamental motor skills have both been related to children’s academic achievement. Results of studies that have simultaneously related aerobic fitness and fundamental motor ...skills to academic achievement have provided inconsistent results, and the exact relations with achievement in distinct academic domains remain unknown. The current study examined unique relations between aerobic fitness, fundamental motor skills, and achievement in reading, mathematics and spelling.
In total, 891 students (mean age = 9.17 years, SD = 0.66) from 22 primary schools participated. Two multilevel structural equation models were constructed, with relations between aerobic fitness (20m-shuttle run test), fundamental motor skills (tested with items of the Körperkoordinationstest für Kinder and Bruininks-Oseretsky Test for Motor Proficiency) and: (1) overall academic achievement, or; (2) achievement in the domains of reading, mathematics, and spelling (assessed with standardized academic achievement tests).
Fundamental motor skills were more strongly related to overall academic achievement than aerobic fitness, but the exact relations differed by academic domain. Aerobic fitness predicted spelling achievement, whereas motor skills predicted reading achievement, and both were predictive of mathematics achievement.
Although more research is needed to disentangle the exact way in which aerobic fitness, motor skills, and academic achievement are linked, the results suggest that children’s academic achievement benefits most from engagement in various physical activities which target both aerobic fitness and gross motor skills. These findings emphasize the importance of providing children with opportunities to engage in a wide variety of sports and activities.
•Motor skills are a stronger predictor of academic achievement than aerobic fitness.•Motor skills predict achievement in mathematics and spelling, but not reading.•Aerobic fitness predicts achievement in mathematics and reading, but not spelling.
Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and ...single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case-control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P=0.038; odds ratio (OR) AT=1.10, 95% CI 0.95-1.29; OR TT=1.21, 95% confidence interval (CI) 1.01-1.47) and NPY (rs16139; P=0.034; OR C allele=0.73, 95% CI 0.55-0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13-1.63; P=0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P=0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors.
PDF
