Exposure of Colon-Derived Epithelial Monolayers to Fecal Luminal Factors from Patients with Colon Cancer and Ulcerative Colitis Results in Distinct Gene Expression Patterns.

Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients (n = 6), UC patients with active disease (n = 6), and healthy subjects (HS) (n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions.

Complications of colonoscopy surveillance of patients with Lynch syndrome - 33 years of follow up.

BACKGROUND AND STUDY AIMS: Lynch syndrome (LS) is a hereditary autosomal dominant condition, with an increased lifetime risk of developing malignancies including colorectal cancer (CRC). Current guidelines differ in recommended colonoscopy-surveillance intervals from 1 to 2 years. Although colonoscopy is considered a safe procedure, there are risks of severe adverse events (SAEs), such as perforation and bleeding, as well as adverse events (AEs), such as abdominal discomfort and post-colonoscopy gastrointestinal infections. Colonoscopy-related bleeding and perforation rates have been reported 0.17% and 0.11%, respectively. However, there are insufficient data regarding complications of colonoscopy-surveillance for LS patients. This study aims to investigate the risk of AEs among LS patients during colonoscopy in the Stockholm region. PATIENTS AND METHODS: This retrospective cohort study includes 351 LS patients undergoing endoscopic surveillance at the Karolinska University Hospital, August 1989 - April 2021. Data from endoscopic surveillance colonoscopies were extracted from patients' medical records. RESULTS: Of 1873 endoscopies in 351 LS patients, 12 complications (AEs) were documented within 30 days (0.64%) and with a total of 3 bleedings (SAEs, 0.16%). No perforations were identified. CONCLUSION: Colonoscopy surveillance for LS patients shows a comparatively low risk of AEs per-examination. Colonoscopy complications per-patient, including both SAEs and AEs, show a significantly higher risk. Colonoscopy complications only including SAEs, show a comparatively low risk. Understanding the lifetime risk of surveillance-related colonoscopy complications is important when designing targeted surveillance programmes.

Quality of endoscopic surveillance of Lynch syndrome patients in a Swedish cohort.

Background and study aims Risk factors for colorectal cancer (CRC) in Lynch syndrome (LS) include sex, age, smoking, high body mass index (BMI), surveillance interval length, and risk genotype. The Boston Bowel Preparation Scale (BBPS) produces a standardized bowel cleanliness rating. A low BBPS score might be a risk factor for missed early lesions. The aim of this study was to investigate the correlation between BBPS score and adenoma detection (with known risk factors for CRC) and surveillance interval with CRC detection in LS patients. Methods A retrospective cohort study including 366 LS patients with 1,887 colonoscopies under surveillance in Stockholm, Sweden from 1989 to 2021 was conducted. Associations were tested using linear and logistic regression. Results We found no association between BBPS score and number of adenomas detected. A low BBPS score was found to be associated with older age (regression coefficient (coeff) -0.015; 95% confidence interval [CI] -0.026 to -0.004; P = 0.007) and obesity (coeff = -0.48; 95% CI: -0.89 to -0.062; P = 0.024). A higher number of detected adenomas was associated with older age (coeff = 0.008; 95% CI 0.004 to 0.012; P < 0.001), male sex (coeff = 0.097; 95% CI 0.008 to 0.19; P = 0.033) and CRC (coeff = 0.28; 95% CI 0.061 to 0.50; P = 0.012). Surveillance interval length was not significant in CRC detection. Conclusions Bowel cleanliness was not associated with adenoma detection and was less likely achieved in patients who were older and had higher BMI. Adenoma detection was associated with older age and male sex. The results indicate the need for better adherence to guidelines and attention to older age groups, men, and patients with obesity.

Symptom Distress Before and After Heart Transplantation - A Longitudinal 5-Year Follow-Up.

INTRODUCTION: Symptom distress after heart transplantation (HTx) is a significant problem causing uncertainty, low self-efficacy, and psychological distress. Few studies have addressed self-reported symptoms. The aim was to explore self-reported symptom distress from time on the waiting list to 5 years after HTx and its association with self-reported psychological well-being, chronic pain, and fatigue in order to identify possible predictors of psychological or transplant specific well-being. METHODS: This multicenter, longitudinal cohort study includes 48 heart recipients (HTRs), 12 women, and 36 men, with a median age of 57 years followed from pretransplant to 5 years post-transplant. Symptom distress was explored by means of four instruments measuring psychological general wellbeing, transplant specific wellbeing, pain, and fatigue. RESULTS: Transplant specific well-being for the whole improved in a stepwise manner during the first 5 years compared to pretransplant. Heart transplant recipients with poor psychological wellbeing were significantly more burdened by symptom distress, in particular sleep problems and fatigue, for up to 5 years after HTx, and their transplant-specific well-being never improved compared to baseline. The prevalence of pain varied from 40% to 60% and explained a significant proportion of the variance in transplant-specific well-being, while psychological general well-being was mainly predicted by overall symptom distress. CONCLUSION: The presence of distressing symptoms explains a significant proportion of poor psychological wellbeing both among HTRs reporting chronic pain and those without pain.

Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial.

BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. RESULTS: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. CONCLUSIONS: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02078804.

Self-reported symptom occurrence and distress, and psychological well-being after liver transplantation - a descriptive cross-sectional study of Danish recipients.

Introduction: Symptom distress and impaired psychological well-being after liver transplantation may lead to limitations in everyday activities and lowered health-related quality of life. The aim of this nationwide, descriptive, and cross-sectional study was to explore self-reported symptom occurrence and distress, among Danish liver transplant recipients, and their association with self-reported psychological well-being as well as demographic, and clinical characteristics. Methods: Liver transplant recipients transplanted from 1990 to 2022 were included. All recipients were asked to complete the Organ Transplant Symptom and Wellbeing instruments consisting of two instruments measuring self-reported symptom occurrence and distress, respectively, as well as self-reported psychological well-being by the Psychological General well-being instrument. Results: Of 511 invited recipients 238 responded: 116 women and 122 men with a median post-transplant follow-up of 7.5 years (IQR 3.6-14.2 years). The most common single symptoms reported were decreased libido (18%), diarrhea (10%), and headache (8%). Sleep problems were the most common transplant-specific domain. 41% of the recipients reported poor psychological well-being, especially those who had undergone transplantation within the last 5 years, women, and younger recipients. Discussion: In the interest of equity, the fact that women reported a higher level of symptom distress than men requires attention. Research on symptom management support is warranted with interventions focusing on how to alleviate symptom distress, which might increase long-term survival, which has not improved in recent decades.

Impact of organised colorectal cancer screening on age-specific population incidences: evidence from a quasi-experimental study in Sweden.

Colorectal cancer (CRC) incurs a significant disease burden globally. Organised CRC screening programmes have been widely implemented for early detection and prevention. To understand the public health impact of these programmes, quantitative evidence of changes in overall and age-specific population incidences is fundamental. We aimed to provide such evidence by exploiting a time lag in the implementation of organised screening in Sweden: two out of 21 regions (these two regions comprise nearly 20% of the total Swedish population) have offered organised screening since 2008; the other regions have offered CRC screening since 2021. Using registry data on diagnosed CRC cases and socio-demographics for all regions in Sweden over the period 1970-2019, Bayesian structural time series modelling and difference-in-differences were applied to analyse the impact of screening on age-specific population incidences over time (CRC cases per 100.000 persons/year). After inviting birth-year cohorts aged 60-69 years for stool-based testing, the incidence rate in the 70-74-year age group decreased significantly over time, with an average reduction of - 44·40 (95% CI - 58·15 to - 31·31) from 2011 to 2019 in the intervention regions. In the overall population aged 60-74 years, there was a net incidence decrease of - 7·99 (95% CI - 13·85 to - 2·39) since the initiation of organised screening in the intervention regions (2008-2019). Organised CRC screening for 60-69-year-olds generated a change in age-specific incidence patterns with a long-lasting incidence decrease in the 70-74-year-old population, implying reductions in the excess mortality and burden of the disease.

The role of endoscopist adenoma detection rate in in sex differences in colonoscopy findings: cross-sectional analysis of the SCREESCO randomized controlled trial.

BACKGROUND: Fewer adenomas are detected at colonoscopy in women compared to men and failure to detect adenomas and sessile serrated polyps is associated with an increased risk of post-colonoscopy colorectal cancer. The aim of this study was to investigate whether this was in part due to the greater difficulty of conducting colonoscopy in women, with the difference being more apparent in colonoscopies conducted by less skilled endoscopists. MATERIAL AND METHODS: Cross-sectional exploratory analysis of data on 16,551 individuals undergoing a primary colonoscopy (PCOL group) or colonoscopy after positive faecal immunochemical test (FIT group) within the randomized controlled trial SCREESCO. Endoscopist adenoma detection rate (ADR; low or high) was determined based on each endoscopist's colonoscopies performed in SCREESCO. In each study group, the relationship between the sex difference in colonoscopy outcome and endoscopist ADR was assessed using multiplicative interaction tests. RESULTS: Endoscopists performed equally many colonoscopies in men and women (median 52% men). There were no signs of effect modification of the risk ratio of any finding (men vs women) by endoscopist ADR in the PCOL group (p = 0.33) or the FIT group (p = 0.30). The proportion of incomplete index colonoscopies was lower in men than in women in both groups and there was no effect modification by endoscopist ADR in either the PCOL group (p = 0.41) or the FIT group (p = 0.96). CONCLUSIONS: This study provides no evidence that endoscopist skill measured by ADR underlies the sex difference in adenoma detection at colonoscopy. This study has trial number NCT02078804 and is registered with ClinicalTrials.gov.

Operating Theater Nurses' Main Concerns During Organ Procurement Procedures: A Grounded Theory Study.

The purpose of this study was to explore the experiences of perioperative nurses in Sweden (ie, operating theater nurses) associated with caring for a donor patient during organ procurement procedures. We sought to determine the nurses' main concerns and how they dealt with them. Using constructivist grounded theory methodology, our participant sample included 10 nurses, one of whom self-identified as male. The average age of the participants was 51.8 years (range = 38 to 63 years). After interviewing the participants and coding their responses, we developed the core category of optimum organ procurement. The generated grounded theory comprises four main categories: brace oneself, facilitate, procurement, and completion. Commitment is the force that binds the perioperative nurse to a course of action. This theory may help guide a team-based approach to prepare nurses to care for donor patients with dignity and respect during procurement procedures.

Recovering from physical trauma in late life, a struggle to recapture autonomy: A grounded theory study.

AIM: The study aimed to explore the experiences of care and recovery among older patients treated for physical trauma. DESIGN: A qualitative study with a constructivist grounded theory design. METHODS: Fifteen in-depth interviews with older adults recovering from physical trauma were conducted and analysed between 2019 and 2023, in accordance with grounded theory methodology. RESULTS: The findings show that for older patients who suffered physical trauma, the core category was the strive to recapture autonomy. This was achieved by means of Adaptation, Reflection and Interactions, which constitute the three main categories. Recovery involves facing and navigating various new life challenges, such as increased dependency on others, managing difficult symptoms and adapting in various ways to everyday life. The recovery process was influenced by fear, hope and the attitude towards new challenges. CONCLUSION: Older adults being cared for after a traumatic event have a difficult path to recovery ahead of them. Dealing with increased unwanted dependency on others was a main concern for the participants. Undertreated symptoms can lead to undesired isolation, delayed recovery and further increase unwanted dependency. On the other hand, hope, which was defined as having a positive approach to life and longing for the future, was a strong accelerating factor in the recovery process. IMPACT: As a result of this study, we have established that older patients experience the initial period after trauma as difficult and that support in the initial phase can be helpful when returning home. As healthcare services are under increasing pressure because of an ageing population, this study contributes by addressing an understudied population and clarifying their concerns. REPORTING METHOD: Reporting adheres to the COREQ (COnsolidated criteria for REporting Qualitative research) Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Making the BEST decision-the BESTa project development, implementation and evaluation of a digital Decision Aid in Swedish cancer screening programmes- a description of a research project.

BACKGROUND: Sweden has a long tradition of organized national population-based screening programmes. Participation rates differ between programmes and regions, being relatively high in some groups, but lower in others. To ensure an equity perspective on screening, it is desirable that individuals make an informed decision based on knowledge rather than ignorance, misconceptions, or fear. Decision Aids (DAs) are set to deliver information about different healthcare options and help individuals to visualize the values associated with each available option. DAs are not intended to guide individuals to choose one option over another. The advantage of an individual Decision Aid (iDA) is that individuals gain knowledge about cancer and screening by accessing one webpage with the possibility to communicate with health professionals and thereafter make their decision regarding participation. The objective is therefore to develop, implement and evaluate a digital iDA for individuals invited to cancer screening in Sweden. METHODS: This study encompasses a process-, implementation-, and outcome evaluation. Multiple methods will be applied including focus group discussions, individual interviews and the usage of the think aloud technique and self-reported questionnaire data. The project is based on The International Patient Decision Aid Standards (IPDAS) framework and the proposed model development process for DAs. Individuals aged 23-74, including women (the cervical-, breast- and CRC screening module) and men (the CRC screening module), will be included in the developmental process. Efforts will be made to recruit participants with self-reported physical and mental limitations, individuals without a permanent residence and ethnic minorities. DISCUSSION: To the best of our knowledge, the present study is the first attempt aimed at developing an iDA for use in the Swedish context. The iDA is intended to facilitate shared decision making about participation in screening. Furthermore, the iDA is expected to increase knowledge and raise awareness about cancer and cancer screening. PATIENT OR PUBLIC CONTRIBUTION: Lay people are involved throughout the whole development and implementation process of the digital DA. TRIAL REGISTRATION: NCT05512260.

Post-colonoscopy rectal cancer in Swedish patients with Crohn's disease 2001-2015: a population-based case review study.

OBJECTIVE: Post-colonoscopy colorectal cancer (PCCRC) is a key quality indicator of colonoscopy, and PCCRC rates are high in the IBD population. Rectal cancer, an important risk factor for PCCRC among patients with Crohn's disease (CD), has not previously been examined. METHODS: Swedish adult patients with CD who underwent a colonoscopy within 36 months before a rectal cancer diagnosis between 2001 and 2015 were identified through the National Patient and Cancer registers. Their medical records were reviewed and a root-cause analysis and a sub-categorization according to the World Endoscopic Organization (WEO) were performed. RESULTS: Of 24 patients with CD and PCCRC in the rectum, 79% were men and the median age was 50 (IQR 45-59) years. The median disease duration was 21.5 (IQR 19-30) years. The cancer was located in the distal 5 cm of the rectum in 63% of the cases. Retroversion in the rectum was reported in only one case. The most common plausible explanation for PCCRC was 'possible missed lesion, prior examination adequate' (63%); when adding retroversion in the rectum, instead 77% of examinations were considered negative but deemed as inadequate. The most common PCCRC sub-category was non-interval type C (54%) and B (37%). Among those with type C, 38% should have been included in surveillance according to present guidelines. CONCLUSION: Better adherence to surveillance guidelines and more meticulous follow-up is warranted. The importance of performing rectal palpation and retroversion in the rectum is underscored and we suggest that this is included in the WEO algorithm.

Causes of nephrotic syndrome in Sweden: The relevance of clinical presentation and demographics.

Background: Many pathological processes can disrupt the integrity of the glomerular capillary wall and cause a massive leakage of protein, resulting in nephrotic syndrome (NS). Clinical parameters such as age, sex, renal function, presence of diabetes, and how NS is defined influence the spectrum of underlying diseases. In this study, we examine how these parameters interact. Methods: Age, sex, hematuria, proteinuria, plasma creatinine plasma albumin levels, and final diagnosis were retrieved for all adult patients with NS as an indication for biopsy and/or massive albuminuria in conjunction with low plasma albumin from the biopsy module of the Swedish Renal Registry (SRR) between 2014 and 2019. A basic calculator was developed to demonstrate the importance of clinical presentation in relation to the likelihood of having a specific diagnosis. Results: A total of 913 unique patients were included in the study. Diabetic nephropathy (DN) and membranous nephropathy (MN) (both found in 17% of patients) were the most common diagnoses. With a stringent definition of NS, MN and minimal change nephropathy (MCN) increased in proportion. Among the cohort as a whole, MCN was the most frequent diagnosis in women and those < 50 years of age (found in 21% and 17%, respectively). In the case of patients aged between 50 and 70 years, those with chronic kidney disease stage 4, and those with negative dipstick tests for hematuria, the most common underlying disease was DN (in 23%, 30%, and 21% of cases, respectively). Among those with high-grade hematuria (dipstick grade 3 or 4), membranoproliferative glomerulonephritis was the most common diagnosis (14%), closely followed by IgA nephropathy (13%). Focal segmental glomerulosclerosis (9.7%) was less common than in many comparable studies. Conclusion: Clinical parameters have a profound impact on the likelihood of different diagnoses in adult patients with NS. Differences in clinical practice and study inclusion criteria may be more important than genetic background and environmental factors when explaining differences between studies in different parts of the world.

Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy-a Nationwide Population-based Study in Sweden.

BACKGROUND AND AIMS: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study. METHODS: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation. RESULTS: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation. CONCLUSIONS: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.

Examining the continuum of resistance model in two population-based screening studies in Sweden.

In studies recruited on a voluntary basis, lack of representativity may impair the ability to generalize findings to the target population. Previous studies, primarily based on surveys, have suggested that generalizability may be improved by exploiting data on individuals who agreed to participate only after receiving one or several reminders, as such individuals may be more similar to non-participants than what early participants are. Assessing this idea in the context of screenings, we compared sociodemographic characteristics and health across early, late, and non-participants in two large population-based screening studies in Sweden: STROKESTOP II (screening for atrial fibrillation; 6,867 participants) and SCREESCO (screening for colorectal cancer; 39,363 participants). We also explored the opportunities to reproduce the distributions of characteristics in the full invited populations, either by assuming that the non-participants were similar to the late participants, or by applying a linear extrapolation model based on both early and late participants. Findings showed that early and late participants exhibited similar characteristics along most dimensions, including civil status, education, income, and health examination results. Both these types of participants in turn differed from the non-participants, with fewer married, lower educational attainments, and lower incomes. Compared to early participants, late participants were more likely to be born outside of Sweden and to have comorbidities, with non-participants similar or even more so. The two empirical models improved representativity in some cases, but not always. Overall, we found mixed support that data on late participation may be useful for improving representativeness of screening studies.

Characterization of the biochemical activity and tumor-promoting role of the dual protein methyltransferase METL-13/METTL13 in Caenorhabditis elegans.

The methyltransferase-like protein 13 (METTL13) methylates the eukaryotic elongation factor 1 alpha (eEF1A) on two locations: the N-terminal amino group and lysine 55. The absence of this methylation leads to reduced protein synthesis and cell proliferation in human cancer cells. Previous studies showed that METTL13 is dispensable in non-transformed cells, making it potentially interesting for cancer therapy. However, METTL13 has not been examined yet in whole animals. Here, we used the nematode Caenorhabditis elegans as a simple model to assess the functions of METTL13. Using methyltransferase assays and mass spectrometry, we show that the C. elegans METTL13 (METL-13) methylates eEF1A (EEF-1A) in the same way as the human protein. Crucially, the cancer-promoting role of METL-13 is also conserved and depends on the methylation of EEF-1A, like in human cells. At the same time, METL-13 appears dispensable for animal growth, development, and stress responses. This makes C. elegans a convenient whole-animal model for studying METL13-dependent carcinogenesis without the complications of interfering with essential wild-type functions.

Endoscopic surveillance of Lynch syndrome at a highly specialized center in Sweden: An observational study of interval colorectal cancer and individual risk factors.

Introduction: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC). In order to detect CRCs amongst LS patients, regular colonoscopies are recommended. However, an international agreement on an optimal surveillance interval has not yet been reached. In addition, few studies have investigated factors that could potentially increase the CRC risk amongst LS patients. Aims: The primary aim was to describe the frequency of CRCs detected during endoscopic surveillance and to estimate the interval from a clean colonoscopy to CRC detection amongst LS patients. The secondary aim was to investigate individual risk factors, including sex, LS genotype, smoking, aspirin use and body mass index (BMI), on CRC risk amongst patients that develop CRC before and during surveillance. Material and methods: Clinical data and colonoscopy findings from 366 LS patients' 1437 surveillance colonoscopies were collected from medical records and patient protocols. Logistic regression and Fisher's exact test were used to investigate associations between individual risk factors and CRC development. Mann-Whitney U test was used to compare the distribution of TNM stages of CRC detected before surveillance and after index. Results: CRC was detected in 80 patients before surveillance and in 28 patients during surveillance (10 at index and 18 after index). During the surveillance programme, CRC was detected within 24 months in 65% of the patients, and after 24 months within 35% of the patients. CRC was more common amongst men, previous and current smokers, and the odds of developing CRC also increased with an increasing BMI. CRCs were more often detected amongst MLH1 and MSH2 carriers during surveillance, compared to the other genotypes. Conclusions: We found that 35% of the CRC cases detected during surveillance were found after 24 months. MLH1 and MSH2 carriers were at higher risk of developing CRC during surveillance. Additionally, men, current or previous smokers, and patients with a higher BMI were at higher risk of developing CRC. Currently, LS patients are recommended a "one-size-fits-all" surveillance program. The results support the development of a risk-score whereby individual risk factors should be taken into consideration when deciding on an optimal surveillance interval.