Efficacy of eye movement desensitization and reprocessing therapy for fear of cancer recurrence among cancer survivors: a randomized single-case experimental design.

Background: Fear of cancer recurrence (FCR) is one of the greatest problems with which cancer survivors have to deal. High levels of FCR are characterized by intrusive thoughts about cancer-related events and re-experiencing these events, avoidance of reminders of cancer, and hypervigilance, similar to post-traumatic stress disorder (PTSD). Eye movement desensitization and reprocessing (EMDR) therapy focuses on these images and memories. It is effective in reducing PTSD and may be effective in reducing high levels of FCR.Objective: The aim of the present study is to investigate the effectiveness of EMDR for severe FCR in breast and colorectal cancer survivors.Method: A multiple-baseline single-case experimental design (n = 8) was used. Daily repeated measurements for FCR were taken during the baseline phase and treatment phase, post-treatment, and at the 3 month follow-up. Participants answered the Cancer Worry Scale (CWS) and the Fear of Cancer Recurrence Inventory, Dutch version (FCRI-NL) five times, i.e. at the start and at the end of each phase (baseline, treatment, post-treatment, and follow-up). The study was prospectively registered at clinicaltrials.gov (NL8223).Results: Visual analysis and effect size calculation by Tau-U were executed for the daily questionnaire on FCR. The weighted average Tau-U score was .63 (p < .01) for baseline versus post-treatment, indicating large change, and .53 (p < .01) between baseline and follow-up, indicating moderate change. The scores on the CWS and FCRI-NL-SF decreased significantly from baseline to follow-up.Conclusion: The results seem promising for EMDR therapy as a potentially effective treatment for FCR. Further research is recommended.

Patients who experience high fear of cancer recurrence (FCR) often have intrusive memories and images about (future) cancer-related events.Eye movement desensitization and reprocessing (EMDR) therapy can focus on these intrusions.EMDR therapy is found to be a promising therapy for patients experiencing high FCR.

Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial.

BACKGROUND: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. METHODS: We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a "Time Out consultation" (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. RESULTS: We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (- 14.2 (95%CI -27.0;-1.3)), availability (- 15,9 (- 29.1;-2.6)) and information provision (- 15.2 (- 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). CONCLUSIONS: In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. TRIAL REGISTRATION: GRIP is retrospectively (21/06/2016) registered in the 'Netherlands Trial Register' (NTR5909).

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

Time intervals between semen production, initiation of analysis, and IUI significantly influence clinical pregnancies and live births.

PURPOSE: Does IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates? METHOD: Retrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation. RESULTS: There was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome. Only female and male ages were significantly associated with the pregnancy outcome. There was a significant difference in the odds on clinical pregnancies and live births when analysis was ≤ 21 min initiated, and < 107 min between sample production and IUI, adjusted for male and female age. CONCLUSIONS: Adjusting for the couple's age, we could show that time intervals between semen production and analysis and IUI when kept low significantly influenced clinical pregnancies and live births.

Survival of the fittest: how the rice microbial community forces Sarocladium oryzae into pathogenicity.

The fungus Sarocladium oryzae (Sawada) causes rice sheath rot and produces the phytotoxins cerulenin and helvolic acid. Both toxins show antimicrobial activity but only helvolic acid production in the rice sheath correlates with virulence. Sarocladium oryzae isolates that differ in their toxin production were used to study their interaction with the rice culturable bacterial endophyte community. The diversity and community structure was defined in the edge of sheath rot lesions, followed by a null model-based co-occurrence analysis to discover pairwise interactions. Non-random pairs were co-cultured to study the nature of the interactions and the role of the toxins herein. Compared to healthy sheaths, endophyte diversity strongly increased when infected with the least virulent S. oryzae isolates producing low amounts of toxins. Virulent S. oryzae isolates did not affect diversity but caused strong shifts in species composition. The endophyte community of healthy rice plants was dominated by B. cereus. This bacterium was enriched in lesions produced by low-virulent S. oryzae isolates and caused hyphal lysis. Contrarily, helvolic acid producers eliminated this bacterium from the sheath endosphere. We conclude that S. oryzae needs to produce antibiotics to defend itself against antagonistic rice endophytes to successfully colonize and infect the rice sheath.

Auxin, Abscisic Acid and Jasmonate Are the Central Players in Rice Sheath Rot Caused by Sarocladium oryzae and Pseudomonas fuscovaginae.

Sheath rot is an emerging rice disease that causes severe yield losses worldwide. The main causal agents are the toxin producers Sarocladium oryzae and Pseudomonas fuscovaginae. The fungus S. oryzae produces helvolic acid and cerulenin and the bacterium P. fuscovaginae produces cyclic lipopeptides. Helvolic acid and the lipopeptide, fuscopeptin, inhibit membrane-bound H+-ATPase pumps in the rice plant. To manage rice sheath rot, a better understanding of the host response and virulence strategies of the pathogens is required. This study investigated the interaction of the sheath rot pathogens with their host and the role of their toxins herein. Japonica rice was inoculated with high- and low-helvolic acid-producing S. oryzae isolates or with P. fuscovaginae wild type and fuscopeptin mutant strains. During infection, cerulenin, helvolic acid and the phytohormones abscisic acid, jasmonate, auxin and salicylic acid were quantified in the sheath. In addition, disease severity and grain yield parameters were assessed. Rice plants responded to high-toxin-producing S. oryzae and P. fuscovaginae strains with an increase in abscisic acid, jasmonate and auxin levels. We conclude that, for both pathogens, toxins play a core role during sheath rot infection. S. oryzae and P. fuscovaginae interact with their host in a similar way. This may explain why both sheath rot pathogens cause very similar symptoms despite their different nature.

Multicentre study of surgical referral and outcomes of patients with benign colorectal lesions.

Background: A multicentre cohort study was performed to analyse the motivations for surgical referral of patients with benign colorectal lesions, and to evaluate the endoscopic and pathological characteristics of these lesions as well as short-term surgical outcomes. Methods: Patients who underwent surgery for a benign colorectal lesion in 15 Dutch hospitals between January 2014 and December 2017 were selected from the pathology registry. Lesions were defined as complex when at least one of the following features was present: size at least 40 mm, difficult location according to the endoscopist, previous failed attempt at resection, or non-lifting sign. Results: A total of 358 patients were included (322 colonic and 36 rectal lesions). The main reasons for surgical referral of lesions in the colon and rectum were large size (33·5 and 47 per cent respectively) and suspicion of invasive growth (31·1 and 58 per cent). Benign lesions could be categorized as complex in 80·6 per cent for colonic and 80 per cent for rectal locations. Surgery consisted of local excision in 5·9 and 64 per cent of colonic and rectal lesions respectively, and complicated postoperative course rates were noted in 11·2 and 3 per cent. In the majority of patients, no attempt was made to resect the lesion endoscopically (77·0 per cent of colonic and 83 per cent of rectal lesions). Conclusion: The vast majority of the benign lesions referred for surgical resection could be classified as complex. Considering the substantial morbidity of surgery for benign colonic lesions, reassessment for endoscopic resection by another advanced endoscopy centre seems to be underused and should be encouraged.

Antecedentes: Se realizó un estudio de cohorte multicéntrico para analizar los motivos de la derivación quirúrgica de pacientes con lesiones colorrectales benignas y evaluar las características endoscópicas y patológicas de estas lesiones, así como los resultados quirúrgicos a corto plazo. Métodos: A partir de un registro anatomopatológico, se seleccionaron los pacientes que se sometieron a cirugía por una lesión colorrectal benigna en 15 hospitales holandeses entre enero de 2014 y diciembre de 2017. Se definió como lesión compleja aquella que presentaba, al menos, una de las siguientes características: tamaño > 40 mm, ubicación difícil según el endoscopista, fracaso previo de la resección o signo de no­elevación. Resultados: Se incluyeron 358 pacientes (322 lesiones de colon y 36 rectales). Las principales razones para la derivación quirúrgica de las lesiones de colon y recto fueron el gran tamaño (34% y 47%) y la sospecha de crecimiento invasivo (31% y 58%). Las lesiones benignas se consideraron complejas en el 81% de los casos del colon y en el 80% del recto. La cirugía consistió en una exéresis local en el 6% y el 64% y se observó una tasa de complicaciones postoperatorias del 11% y el 3% de las lesiones de colon y recto, respectivamente. En la mayoría de los casos, no se intentó la resección endoscópica de la lesión (77% en colon y 83% en recto). Conclusión: La gran mayoría de las lesiones benignas derivadas para la resección quirúrgica podrían clasificarse como complejas. Considerando la notable morbilidad de la cirugía de las lesiones benignas de colon, debería contemplarse y fomentarse la reevaluación de la resección endoscópica en un centro de endoscopia avanzada.

DNA fragmentation in concert with the simultaneous assessment of cell viability in a subfertile population: establishing thresholds of normality both before and after density gradient centrifugation.

PURPOSE: TUNEL assay is the most common, direct test for sperm chromatin integrity assessment. But, lack of standardized protocols makes interlaboratory comparisons impossible. Consequently, clinical thresholds to predict the chance of a clinical pregnancy also vary with the technique adopted. This prospective study was undertaken to assess the incidence of sperm DNA fragmentation in a subfertile population and to establish threshold values of normality as compared to a fertile cohort, both before and after density gradient centrifugation in the total and vital fractions. METHOD: Men presenting at a university hospital setup for infertility treatment. DNA damage via TUNEL assay was validated on fresh semen samples, as conventional semen parameters, to reduce variability of results. RESULTS: Total DNA fragmentation in the neat semen was significantly higher in the subfertile group, but the vital fraction was not significantly different between the two cohorts. After gradient centrifugation, DNA fragmentation increased significantly in the total fraction of the subfertile group but decreased significantly in the vital fraction. In the fertile cohort, there was a non-significant increase in total fragmentation and in the vital fraction the trend was unclear. CONCLUSIONS: Estimating total and vital sperm DNA fragmentation, after density gradient centrifugation, increased both the sensitivity and the specificity, thereby lowering the number of false negatives and false positives encountered. These findings provide opportunities to investigate the significance of the total and the vital fractions after different assisted reproductive technologies.

National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.

Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer. Methods: This was a population-based cohort study of patients treated surgically for pT1-3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit. Postoperative complications (overall, surgical, severe complications and mortality) were compared using multivariable logistic regression. A risk stratification table was developed based on factors independently associated with severe complications (reintervention and/or mortality) after elective surgery. Results: Of 39 813 patients, 5170 had pT1 colorectal cancer. No statistically significant differences were observed between patients with pT1 and pT2-3 disease in the rate of severe complications (8·3 versus 9·5 per cent respectively; odds ratio (OR) 0·89, 95 per cent c.i. 0·80 to 1·01, P = 0·061), surgical complications (12·6 versus 13·5 per cent; OR 0·93, 0·84 to 1·02, P = 0·119) or mortality (1·7 versus 2·5 per cent; OR 0·94, 0·74 to 1·19, P = 0·604). Male sex, higher ASA grade, previous abdominal surgery, open approach and type of procedure were associated with a higher severe complication rate in patients with pT1 colorectal cancer. Conclusion: Elective bowel resection was associated with similar morbidity and mortality rates in patients with pT1 and those with pT2-3 colorectal carcinoma.

Introduction of a colorectal cancer screening programme: results from a single-centre study.

AIM: In 2014, a national colorectal cancer (CRC) screening programme was launched in the Netherlands. It is difficult to assess for the individual patients with CRC whether the oncological benefits of surgery will outweigh the morbidity of the procedure, especially in early lesions. This study compares patient and tumour characteristics between screen-detected and nonscreen-detected patients. Also, we present an overview of treatment options and clinical dilemmas when treating patients with early-stage colorectal disease. METHOD: Between January 2014 and December 2016, all patients with nonmalignant polyps or CRC who were referred to the Department of Surgery of the Leiden University Medical Centre in the Netherlands were included. Baseline characteristics, type of treatment and short-term outcomes of patients with screen-detected and nonscreen-detected colorectal tumours were compared. RESULTS: A total of 426 patients were included, of whom 240 (56.3%) were identified by screening. Nonscreen-detected patients more often had comorbidity (P = 0.03), the primary tumour was more often located in the rectum (P = 0.001) and there was a higher rate of metastatic disease (P < 0.001). Of 354 surgically treated patients, postoperative adverse events did not significantly differ between the two groups (P = 0.38). Of 46 patients with T1 CRC in the endoscopic resection specimen, 23 underwent surgical resection of whom only 30.4% had residual invasive disease at colectomy. CONCLUSION: Despite differences in comorbidity, stage and surgical outcome of patients with screen-detected tumours compared to nonscreen-detected tumours were not significantly different. Considering its limited oncological benefits as well as the rate of adverse events, surgery for nonmalignant polyps and T1 CRC should be considered carefully.

Sperm DNA fragmentation in the total and vital fractions before and after density gradient centrifugation: Significance in male fertility diagnosis.

BACKGROUND: Sperm DNA fragmentation measured by different techniques make comparisons impossible due to lack of standardization. Induction of DNA damage after sperm preparation in the entire fraction has been observed on independent occasions but findings are not consistent. METHODS: Men presenting at a University hospital setup for infertility treatment. DNA damage via TUNEL assay was validated on fresh semen samples, as conventional semen parameters, to reduce variability of results. RESULTS: Sperm motility in neat semen inversely correlated with sperm DNA fragmentation in the total fraction, but, total count, leukocytes and immature germ cells significantly affected the vital fraction. Sperm DNA fragmentation was observed both in normal and subnormal semen samples, but was significantly different in the total fraction of astheno-, asthenoterato- and oligoteratozoospermic men. After density gradient centrifugation, sperm DNA fragmentation increased significantly in the total but decreased in the vital fraction. Advancing male age significantly influenced damage in the total but not in the vital population. CONCLUSIONS: These findings provide opportunities to investigate the significance of the total and the vital fractions both in natural conception and after different assisted reproductive technologies.

Validating semen processing for an intrauterine program should take into consideration the inputs, actions and the outputs of the process.

To validate semen preparation via density gradient centrifugation, we took into account the input via the semen sample, the action generated by technical and equipment characteristics and the output measured by the level of performance. Longer periods of abstinence reduced % yield, but increased viscosity and incomplete samples collected had no effect. Under controlled technical and equipment characteristics, precision and reproducibility were validated for density gradient. Additionally, as a good laboratory practice, internal and external quality control measures were implemented to guarantee the level of performance. Inseminating motile sperm count is an important predictive parameter for IUI success. In our group of patients, a yield of an absolute lower limit of 2 million motile spermatozoa was sufficient to contemplate IUI. Pregnancy rate of 13.8% where >2 million rapid progressive spermatozoa were inseminated was significantly higher than the pregnancies (4.4%) obtained with <2 million rapid progressive spermatozoa. This percentage was even higher than the national data registered for IUI (12.2%). To make IUI an attractive first-line treatment, standardization and proper validation of semen preparation procedure are mandatory.

Meckel's enterolith : a rare cause of mechanical small bowel subobstruction.

Meckel's diverticulum is the most common congenital gastrointestinal malformation and may present with bleeding, obstruction and diverticulitis. Symptomatic Meckel's diverticulum is associated with age <50 years, male gender, diverticular length > 2 cm and ectopic mucosa. Formation of enteroliths is a rare complication of Meckel's diverticulum and the majority of stones will remain in the diverticulum. Factors promoting enterolith formation through precipitation of calcium in the small intestinal alkaline environment include stasis as well as diverticular anatomy and histology. Mechanical obstruction due to liberation of enteroliths is even more rare and other mechanisms include intussusception, adhesions, volvulus and neoplasms. Visualization of enteroliths on plain abdominal films is challenging because not all stones are radiopaque. Surgical diverticulectomy or segmental bowel resection with anastomosis is preferred in case of complications. We present a case of mechanical small bowel sub-obstruction resulting from an expelled Meckel's enterolith.

Colorectal cancer screening: Systematic review of screen-related morbidity and mortality.

BACKGROUND: Implementation of mass colorectal cancer screening, using faecal occult blood test or colonoscopy, is recommended by the European Union in order to increase cancer-specific survival by diagnosing disease in an earlier stage. Post-colonoscopy complications have been addressed by previous systematic reviews, but morbidity of colorectal cancer screening on multiple levels has never been evaluated before. AIM: To evaluate potential harm as a result of mass colorectal cancer screening in terms of complications after colonoscopy, morbidity and mortality following surgery, psychological distress and inappropriate use of the screening test. METHODS: A systematic review of all literature on morbidity and mortality attributed to colorectal cancer screening, using faecal occult blood test or colonoscopy, from each databases' inception to August 2016 was performed. A meta-analysis was conducted to examine the pooled incidence of major complications of colonoscopy (major bleedings and perforations). RESULTS: Sixty studies were included. Five out of seven included prospective studies on psychological morbidity reported an association between participation in a colorectal screening program and psychological distress. Serious morbidity from colonoscopy in asymptomatic patients included major bleedings (0.8/1000 procedures, 95% CI 0.18-1.63) and perforations (0.07/1000 procedures, 95% CI 0.006-0.17). CONCLUSIONS: Participation in a colorectal cancer screening program is associated with psychological distress and can cause serious adverse events. Nevertheless, the short duration of psychological impact as well as the low colonoscopy complication rate seems reassuring. Because of limited literature on harms other than perforation and bleeding, future research on this topic is greatly needed to contribute to future screening recommendations.

A novel approach for BCR-ABL1 standardization to improve International Scale estimation.

INTRODUCTION: Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results. METHODS: To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA) data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results. RESULTS AND CONCLUSION: We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the proposed method is a valuable alternative.

The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter.

Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (P<0.05) most likely explained by an association of methylation state of the 5' flanking CpG island and expansion size in blood (P<0.0001) and brain (P<0.05). In several informative C9orf72 parent-child transmissions, we identified earlier onset ages, increasing expansion sizes and/or increasing methylation states (P=0.0034) of the 5' CpG island, reminiscent of disease anticipation. Also, intermediate repeats (7-24 units) showed a slightly higher methylation degree (P<0.0001) and a decrease of C9orf72 promoter activity (P<0.0001) compared with normal short repeats (2-6 units). Decrease of transcriptional activity was even more prominent in the presence of small deletions flanking G4C2 (P<0.0001). Here we showed that increased methylation of CpGs in the C9orf72 promoter may explain how an increasing G4C2 size lead to loss-of-function without excluding repeat length-dependent toxic gain-of-function. These data provide insights into disease mechanisms and have important implications for diagnostic counseling and potential therapeutic approaches.

Indirect genetic effects for survival in domestic chickens (Gallus gallus) are magnified in crossbred genotypes and show a parent-of-origin effect.

Through social interactions, individuals can affect one another's phenotype. The heritable effect of an individual on the phenotype of a conspecific is known as an indirect genetic effect (IGE). Although IGEs can have a substantial impact on heritable variation and response to selection, little is known about the genetic architecture of traits affected by IGEs. We studied IGEs for survival in domestic chickens (Gallus gallus), using data on two purebred lines and their reciprocal cross. Birds were kept in groups of four. Feather pecking and cannibalism caused mortality, as beaks were kept intact. Survival time was shorter in crossbreds than in purebreds, indicating outbreeding depression and the presence of nonadditive genetic effects. IGEs contributed the majority of heritable variation in crossbreds (87 and 72%) and around half of heritable variation in purebreds (65 and 44%). There was no evidence of dominance variance, neither direct nor indirect. Absence of dominance variance in combination with considerable outbreeding depression suggests that survival is affected by many loci. Direct-indirect genetic correlations were moderately to highly negative in crossbreds (-0.37 ± 0.17 and -0.83 ± 0.10), but low and not significantly different from zero in purebreds (0.20 ± 0.21 and -0.28 ± 0.18). Consequently, unlike purebreds, crossbreds would fail to respond positively to mass selection. The direct genetic correlation between both crosses was high (0.95 ± 0.23), whereas the indirect genetic correlation was moderate (0.41 ± 0.26). Thus, for IGEs, it mattered which parental line provided the sire and which provided the dam. This indirect parent-of-origin effect appeared to be paternally transmitted and is probably Z chromosome linked.