Teleducation: medical education in the pandemic and beyond.

Medical education in the pandemic has been challenging owing to various physical and technological constraints in the current education landscape. This has resulted in reduced patient contact and opportunities for clinical exposure. In utilizing various platforms to supplement teaching, we adopted the use of Telegram, a cloud-based messaging application as an education aid for 3 cohorts of medical students in 1 medical school in Singapore. Herein, we share our experience with Telegram as a novel platform to augment medical education and to supplement clinical training amidst the various constraints. We believe that the circumstances have allowed us to find a method that may serve as an effective adjunct in education. Qualitative feedback has been positive and generally in line with our goals. We believe that further work could involve utilizing other features of the application, or by developing specialized applications to serve the same purpose. More needs to be done to consider applicability in different cultural and socioeconomic contexts.

Patterns in Cancer Incidence Among People Younger Than 50 Years in the US, 2010 to 2019.

Importance: Emerging data suggest that the incidence of early-onset cancers, defined as cancers diagnosed in people younger than 50 years, is increasing, but updated data are limited. Objective: To characterize the patterns in the incidence of early-onset cancers in the US from 2010 to 2019 and provide granular data on the cancers with the fastest-growing incidence rates. Design, Setting, and Participants: This population-based cohort study analyzed data from 17 National Cancer Institute Surveillance, Epidemiology, and End Results registries from January 1, 2010, to December 31, 2019. Age-standardized incidence rates per 100 000 people were extracted for early-onset cancers, with rates age adjusted to the US standard population. A total of 562 145 patients with early-onset cancer between 2010 and 2019 were identified and included. Data were analyzed from October 16, 2022, to May 23, 2023. Main Outcomes and Measures: Primary outcomes were incidence rates and descriptive epidemiological data for people younger than 50 years with cancer. The annual percentage change (APC) of the age-standardized incidence rate was estimated using the Joinpoint regression program. Results: Among 562 145 patients (324 138 [57.7%] aged 40-49 years; 351 120 [62.5%] female) with early-onset cancer, 4565 (0.8%) were American Indian or Alaska Native, 54 876 (9.8%) were Asian or Pacific Islander, 61 048 (10.9%) were Black, 118 099 (21.0%) were Hispanic, 314 610 (56.0%) were White, and 8947 (1.6%) were of unknown race and/or ethnicity. From 2010 to 2019, the age-standardized incidence rate of early-onset cancers increased overall (APC, 0.28%; 95% CI, 0.09%-0.47%; P = .01) and in female individuals (APC, 0.67%; 95% CI, 0.39%-0.94%; P = .001) but decreased in male individuals (APC, -0.37%; 95% CI, -0.51% to -0.22%; P < .001). In contrast, the age-standardized incidence rate of cancers in individuals aged 50 years and older decreased over the study period (APC, -0.87%; 95% CI, -1.06% to -0.67%; P < .001). In 2019, the highest number of incident cases of early-onset cancer were in the breast (n = 12 649). From 2010 to 2019, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancer groups (APC, 2.16%; 95% CI, 1.66%-2.67%; P < .001). Among gastrointestinal cancers, those with the fastest-growing incidence rates were in the appendix (APC, 15.61%; 95% CI, 9.21%-22.38%; P < .001), intrahepatic bile duct (APC, 8.12%; 95% CI, 4.94%-11.39%; P < .001), and pancreas (APC, 2.53%; 95% CI, 1.69%-3.38%; P < .001). Conclusions and Relevance: In this cohort study, the incidence rates of early-onset cancer increased from 2010 to 2019. Although breast cancer had the highest number of incident cases, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancers. These data may be useful for the development of surveillance strategies and funding priorities.

Preoperative Quality of Life and Mental Health Can Predict Postoperative Outcomes and Quality of Life after Colorectal Cancer Surgery.

Background and Objectives: It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R2: 0.546, F: 1.961, p = 0.023) and 30-day readmission (R2: 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Antibiotics vs observational therapy in acute uncomplicated diverticulitis, a systemic review and meta-analysis.

PURPOSE: Antibiotics have long been recommended as a form of conservative therapy in patients with acute uncomplicated diverticulitis despite no supporting evidence. This meta-analysis aims to assess the difference in outcomes between observational therapy and antibiotics regime in patients with acute uncomplicated diverticulitis. METHODS: Medline and Embase electronic databases were reviewed. A comparative meta-analysis in odds ratios (ORs) or mean difference (MD) was conducted using a random effects model for dichotomous and continuous outcomes, respectively. Randomized controlled trials comparing outcomes in patients with acute uncomplicated diverticulitis on observational therapy compared to antibiotics regime were selected. Outcomes of interest included all-cause mortality, complications, emergency surgery rates, length of stay, and recurrence. RESULTS: A total of 7 articles looking at 5 different randomized controlled trials were included. A total of 2959 patients with acute uncomplicated diverticulitis comprising of 1485 patients on antibiotics therapy and 1474 patients on observational therapy were included in the comparison. We found that there was no statistically significant difference in all-cause mortality (OR = 0.98; 95% CI 0.53;1.81; p = 0.68), complications (OR = 1.04; 95% CI 0.36;3.02; p = 0.51), emergency surgery (OR = 1.24; 95% CI 0.70;2.19, p = 0.92), length of stay (M.D: -0.14, 95% CI -0.50;0.23, p < 0.001), and recurrent diverticulitis (OR 1.01; 95% CI 0.83;1.22, p < 0.91) between the two arms. CONCLUSION: This systemic review and meta-analysis found that there is no statistically significant difference in outcomes between patients with acute uncomplicated diverticulitis who were put on observational therapy compared to the antibiotics regime. This suggests that observational therapy is an equally safe and effective therapy as compared to antibiotics therapy.

Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities.

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities.

A randomized trial comparing cadaveric dissection and examination of prosections as applied surgical anatomy teaching pedagogies.

Anatomy is an important component in the vertical integration of basic science and clinical practice. Two common pedagogies are cadaveric dissection and examination of prosected specimens. Comparative studies mostly evaluate their immediate effectiveness. A randomized controlled trial design was employed to compare both the immediate and long-term effectiveness of dissection and prosection. Eighty third-year medical students undergoing their surgical rotation from the Yong Loo Lin School of Medicine were randomized into two groups: dissection and prosection. Each participated in a one-day hands-on course following a similar outline that demonstrated surgical anatomy in the context of its clinical relevance. A pre-course test was conducted to establish baseline knowledge. A post-course test was conducted immediately after and at a one-year interval to evaluate learner outcome and knowledge retention. A post-course survey was conducted to assess participant perception. Thirty-nine and thirty-eight participants for the dissection and prosection groups, respectively, were included for analysis. There was no significant difference between mean pre-course test scores between the dissection and prosection groups [12.6 (3.47) vs. 12.7 (3.16), P > 0.05]. Both the mean immediate [27.9 (4.30) vs. 24.9 (4.25), P < 0.05] and 1 year [23.9 (4.15) vs. 19.9 (4.05), P < 0.05] post-course test scores were significantly higher in the dissection group. However, when adjusted for course duration [dissection group took longer than prosection group (mean 411 vs. 265 min)], these findings were negated. There is no conclusive evidence of either pedagogy being superior in teaching surgical anatomy. Based on learner surveys, dissection provides a greater learner experience.

Open versus laparoscopic Hartmann's procedure: a systematic review and meta-analysis.

PURPOSE: Hartmann's procedure is traditionally performed in emergency situations where single-step procedures with immediate anastomosis may be unsafe. However, it can be associated with significant morbidity and low colostomy reversal rate. Whilst randomised controlled trials and a Cochrane review have reported strong evidence of laparoscopic over open colectomies, no such reviews have been performed for Hartmann's procedure. Hence, this paper aims to summarise the existing evidence to determine the efficacy of laparoscopic Hartmann's procedure over its open counterpart. METHODS: Embase, Medline and Cochrane databases were searched from inception to 15 November 2020 for keywords relating to 'laparoscopy' and 'Hartmann' using strict inclusion and exclusion criteria. Odds ratio was estimated for dichotomous outcomes and weighted mean difference was estimated for continuous outcomes. RESULTS: From the 836 articles yielded from the search strategy, 12 articles were selected for meta-analysis. Pooled analysis revealed that laparoscopic Hartmann's procedure (LHP) allows for a shorter length of stay, and a lower risk of overall surgical site infections and superficial surgical site infections. There was no significant difference in other outcomes. Single-arm analysis of LHP also showed an unprecedented high colostomy reversal rate of over 80%. CONCLUSION: In clinically suitable patients, laparoscopic Hartmann's procedure has benefits over open Hartmann's procedure. Despite the selection bias of single-arm studies, LHP has reported a high stoma reversal rate of over 80%. Future well-controlled studies should be done to affirm the findings.

Pan-cancer pervasive upregulation of 3' UTR splicing drives tumourigenesis.

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations. Here we systematically map the pan-cancer landscape of 3' UTR splicing and present this in SpUR ( http://www.cbrc.kaust.edu.sa/spur/home/ ). 3' UTR splicing is widespread, upregulated in cancers, correlated with poor prognosis and more prevalent in oncogenes. We show that antisense oligonucleotide-mediated inhibition of 3' UTR splicing efficiently reduces oncogene expression and impedes tumour progression. Notably, CTNNB1 3' UTR splicing is the most consistently dysregulated event across cancers. We validate its upregulation in hepatocellular carcinoma and colon adenocarcinoma, and show that the spliced 3' UTR variant is the predominant contributor to its oncogenic functions. Overall, our study highlights the importance of 3' UTR splicing in cancer and may launch new avenues for RNA-based anti-cancer therapeutics.

A systematic review and meta-analysis on the effectiveness of web-based psychosocial interventions among patients with colorectal cancer.

AIMS: To synthesize the effectiveness of web-based psychosocial interventions on self-efficacy, anxiety, depression, quality of life (QoL), non-specific psychological and cancer-specific distress among patients with colorectal cancer (CRC). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Six databases (PubMed, PsycINFO, Embase, Scopus, CINAHL and CNKI) were searched from inception to December 2021. REVIEW METHODS: Experimental/quasi-experimental studies involving patients with CRC for the improvement of aforementioned outcomes were included. Two reviewers screened and extracted the data, and assessed studies' methodological quality using risk of bias tools. Meta-analyses and narrative syntheses were performed. RESULTS: Nineteen studies consisting of 1386 participants were identified. Cognitive-behavioural therapy delivered online was the most common trialled web-based psychosocial intervention. Meta-analyses revealed no positive effect for self-efficacy (standardized mean difference 0.93, 95% CI: 0.52 to 1.35, p < .01) and minimal benefit for QoL (mean difference [MD] 2.83, 95% CI: -0.31 to 5.98, p = .08) but significant positive effects for anxiety (MD -2.23, 95% CI: -3.31 to -1.14, p < .01) and depression (MD -2.84, 95% CI: -4.09 to -1.59, p < .01) among CRC survivors in the intervention group as compared with the control group. Narrative synthesis suggested possible benefits in reducing distress. CONCLUSION: Web-based psychosocial interventions are promising alternatives to conventional delivery methods in reducing patients' anxiety, depression and distress. However, evidence on self-efficacy and QoL remains inconsistent. More adequately powered, well-designed trials with targeted and theory-based interventions are required to ascertain findings. IMPACT: By highlighting the potential of web-based psychosocial interventions in reducing anxiety and depression among CRC survivors, this review has put forth beneficial information supporting the use and acceptance of web-based care delivery in light of COVID-19 restrictions and nationwide lockdowns. Meanwhile, the paucity of empirical support reflects the necessity of more extensive research to test and improve other health outcomes. PROSPERO registration number: CRD42021261396.

Comparison of short-term outcomes between single-incision plus one-port laparoscopic surgery and conventional laparoscopic surgery for distal gastric cancer: a randomized controlled trial.

Background: The technical safety and efficacy of single-incision plus one-port laparoscopic surgery (SILS+1) for distal gastric cancer remain unclear. This study was performed to compare the short-term outcomes of patients with distal gastric cancer undergoing SILS+1 versus conventional laparoscopic surgery (CLS). Methods: This randomized controlled trial involved patients with clinical stage cT1b-3N0-2M0 distal gastric cancer. The patients were randomized to the CLS group or SILS+1 group. The surgical and pathologic outcomes, postoperative mortality, and pain intensity were compared between the two groups. Results: From January 2019 to April 2021, 117 patients were enrolled and assigned to either the CLS group (n=59) or SILS+1 group (n=58). The clinical characteristics, including blood loss, tumor diameter, pathologic stage, number of lymph nodes harvested, and postoperative recovery, were similar between the two groups (P>0.05). There were no statistically significant differences in the overall postoperative complication rates between the CLS group and SILS+1 group (10.2% vs. 6.9%, respectively; P=0.743). The Clavien-Dindo classification was also comparable (P=0.435). However, the operating time was significantly longer in the CLS group than SILS+1 group (207.0±41.2 vs. 185.1±40.7 min, respectively; P=0.005), and the total incision length was significantly shorter in the SILS+1 group than CLS group (6.1±0.6 vs. 7.6±0.7 cm, respectively; P=0.000). Moreover, on the third day after surgery, the visual analog scale (VAS) score was significantly higher in the CLS group than SILS+1 group (1.6±0.6 vs. 0.6±0.7, respectively; P=0.000). Conclusions: The results of this study suggest that SILS+1 for distal gastric cancer performed by an experienced surgeon might be a feasible and safe technique with better cosmetic results and less pain in strictly selected patients. Trial Registration: This trial was registered at www.chictr.org.cn (ChiCTR2100051491).

Perioperative experiences and needs of patients who undergo colorectal cancer surgery and their family caregivers: a qualitative study.

PURPOSE: Colorectal cancer (CRC) surgeries are major, complex, and often associated with debilitating symptoms or significant deconditioning that may impair patients' quality of life. Little is known about how patients and family caregivers cope and their unmet needs during this daunting perioperative phase. This study aimed to explore the experiences and needs of CRC patients who undergo surgery and their family caregivers. METHODS: An exploratory qualitative design was adopted. A total of 27 participants comprising fifteen outpatients who had undergone colorectal cancer surgery and twelve family caregivers were recruited through purposive sampling from a public tertiary hospital in Singapore between December 2019 and November 2020. Individual, audio-recorded, semi-structured interviews were conducted, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Four themes emerged: initial reactions to the diagnosis, impact of the illness and surgery, personal coping, and external support. The lack of apparent assessments on the psychological well-being of patients was found despite several participants exhibiting early signs of distress. Access to psychological support provided by healthcare professionals or peers was selective, and knowledge deficit was prevalent, especially in the preoperative stage. CONCLUSION: Psychological priming and strengthening are important for CRC patients' and their caregivers' adaptive coping throughout the treatment continuum. Technology-based, dyadic psychoeducation should be offered preoperatively to ease CRC patients' acceptance of their diagnosis and adjustment to life after surgery while at the same time reduce the burden of family carers.

Personal motivation, self-regulation barriers and strategies for weight loss in people with overweight and obesity: a thematic framework analysis.

OBJECTIVE: To explore motivations, self-regulation barriers and strategies in a multi-ethnic Southeast Asian population with overweight and obesity. DESIGN: Qualitative design using semi-structured face-to-face and videoconferencing interviews. Data were analysed using thematic framework analysis and constant comparison method. SETTING: Specialist weight management clinic. PARTICIPANTS: Twenty-two participants were purposively sampled from 13 April to 30 April 2021. Median age and BMI of the participants were 37·5 (interquartile range (IQR) = 13·3) and 39·2 kg/m2 (IQR = 6·1), respectively. And 31·8 % were men, majority had a high intention to adopt healthy eating behaviours (median = 6·5; IQR = 4·8-6·3) and 59 % of the participants had a medium level of self-regulation. RESULTS: Six themes and fifteen subthemes were derived. Participants were motivated to lose weight by the sense of responsibility as the family's pillar of support and to feel 'normal' again. We coupled self-regulation barriers with corresponding strategies to come up with four broad themes: habitual overconsumption - mindful self-discipline; proximity and convenience of food available - mental tenacity; momentary lack of motivation and sense of control - motivational boosters; and overeating triggers - removing triggers. We highlighted six unique overeating triggers namely: trigger activities (e.g. using social media); eating with family, friends and colleagues; provision of food by someone; emotions (e.g. feeling bored at home, sad and stressed); physiological condition (e.g. premenstrual syndrome); and the time of the day. CONCLUSIONS: Future weight management interventions should consider encompassing participant-led weight loss planning, motivation boosters and self-regulation skills to cope with momentary overeating triggers.

Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis.

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we identify LARP1 as one of the most upregulated RBPs in colorectal cancer (CRC) and demonstrate its oncogenic properties. We perform LARP1:RNA interactome profiling and unveil a previously unexplored role for LARP1 in targeting the 3'UTR of oncogenes in CRC. Notably, we identify the proto-oncogenic transcription factor MYC as a key LARP1-regulated target. Our data show that LARP1 positively modulates MYC expression by associating with its 3'UTR. In addition, antisense oligonucleotide-mediated blocking of the interaction between LARP1 and the MYC 3'UTR reduces MYC expression and in vitro CRC growth. Furthermore, a systematic analysis of LARP1:protein interactions reveals IGF2BP3 and YBX1 as LARP1-interacting proteins that also regulate MYC expression and CRC development. Finally, we demonstrate that MYC reciprocally modulates LARP1 expression by targeting its enhancer. In summary, our data reveal a critical, previously uncharacterized role of LARP1 in promoting CRC tumorigenesis, validate its direct regulation of the proto-oncogene MYC and delineate a model of the positive feedback loop between MYC and LARP1 that promotes CRC growth and development.

Side-to-side versus end-to-side ileocolic anastomosis in right-sided colectomies: A cohort control study.

Aims: The three main types of anastomotic configurations following colorectal resection are Side-to-Side Anastomosis (S-S), End-to-Side Anastomosis (E-S) and End-to-End Anastomosis (E-E). This study aims to present results from a local cohort supplemented by a systematic review with meta-analysis of existing literature to compare the post-operative outcomes between E-S and S-S. Methods: A cohort study of patients who underwent right colectomy with E-S or S-S anastomosis, was conducted at the National University Hospital Singapore. Electronic databases Embase and Medline were systematically searched from inception to 21 August 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Studies were included if they compared post-operative outcomes between E-S and S-S. Results: In the cohort study, 40 underwent E-S and 154 underwent S-S. Both post-operative ileus (12.5% vs. 29.2%, P = 0.041) and length of hospital stay (9.35 days vs. 14.04 days, P = 0.024) favoured E-S, but anastomotic bleed favoured S-S (15.0% vs. 3.2%, P = 0.004). Five studies were included in the meta-analysis with 860 E-S and 1126 S-S patients. Similarly, post-operative ileus (odds ratio [OR] =0.302; 95% confidence interval [CI]: 0.122-0.747; P = 0.010) and length of hospital stay (mean differences = ‒1.54 days; CI: ‒3.00 to ‒0.076 days; P = 0.039) favoured E-S. Additional sensitivity analysis including only stapled anastomosis showed a lower rate of anastomotic leak in E-S patients (OR = 0.185; 95% CI: 0.054-0.627; P = 0.007). Conclusions: This is the first systematic review to show that the E-S technique produces superior post-operative outcomes after right colectomy compared to S-S. However, the choice of anastomosis was largely surgeon dependent, but surgeon factors were not reported.

Is underwater endoscopic mucosal resection of colon polyps superior to conventional techniques? A network analysis of endoscopic mucosal resection and submucosal dissection.

Background and study aims Evidence from recent trials comparing conventional endoscopic mucosal resection (EMR) to underwater EMR (UEMR) have matured. However, studies comparing UEMR to endoscopic submucosal dissection (ESD) are lacking. Hence, we sought to conduct a comprehensive network meta-analysis to compare the efficacy of UEMR, ESD, and EMR. Methods Embase and Medline databases were searched from inception to December 2020 for articles comparing UEMR with EMR and ESD. Outcomes of interest included rates of en bloc and complete polyp resection, risk of perforation and bleeding, and local recurrence. A network meta-analysis comparing all three approaches was conducted. In addition, a conventional comparative meta-analysis comparing UEMR to EMR was performed. Analysis was stratified according to polyp sizes (< 10 mm, ≥ 10 mm, and ≥ 20 mm). Results Twenty-two articles were included in this study. For polyps ≥ 10 mm, UEMR was inferior to ESD in achieving en bloc resection ( P  = 0.02). However, UEMR had shorter operating time for polyps ≥ 10 mm ( P  < 0.001), and ≥20 mm ( P  = 0.019) with reduced perforation risk for polyps ≥ 10 mm ( P  = 0.05) compared to ESD. In addition, en bloc resection rates were similar between UEMR and EMR, although UEMR had reduced recurrence for polyps ≥ 10 mm ( P  = 0.013) and ≥ 20 mm ( P  = 0.014). UEMR also had shorter mean operating than EMR for polyps ≥ 10 mm ( P  < 0.001) and ≥ 20 mm ( P  < 0.001). Risk of bleeding and perforation with UEMR and EMR were similar for polyp of all sizes. Conclusions UEMR has demonstrated technical and oncological outcomes comparable to ESD and EMR, along with a desirable safety profile. UEMR appears to be a safe and effective alternative to conventional methods for resection of polyps ≥ 10 mm.

MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers.

3'UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers. MYC overexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of the MYC 3'UTR in cancer, and identify miR-138 as a potent regulator of the heterogenous MYC transcript population.

Colorectal cancer patients advocating screening to their siblings: a randomized behavioral intervention.

BACKGROUND AND AIMS: Siblings of colorectal cancer (CRC) patients are at increased risk of developing CRC, but screening rates remain low. Through a randomized behavioral intervention, this study aimed to determine whether patients can advocate screening to their siblings using a tailored educational package. METHODS: CRC survivors were recruited and randomized into relaying either tailored materials (intervention group) or existing national screening guidelines (control group) to their siblings. Siblings could respond to the study team if they were interested in learning about CRC screening. Study outcomes were patient advocacy rates (number of patients who had successfully contacted at least 1 eligible sibling) between groups and the proportion of eligible siblings who responded. RESULTS: Between May 2017 and March 2021, 219 CRC patients were randomized to the intervention (n = 110) and control (n = 109) groups. Patient advocacy rates were high and did not differ significantly between groups. However, only 14.3% of eligible siblings (n = 85) responded to the study team. Siblings of patients from the intervention group were more likely to respond (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-3.0; P < .05). Moreover, after controlling for potential confounders, siblings aged ≥60 years were significantly less likely to respond (adjusted odds ratio, .3; 95% confidence interval, .1-.7; P < .01). CONCLUSIONS: CRC patients are willing advocates of screening, and siblings contacted by patients from the intervention group were also more likely to reach out to the study team. However, overall sibling response rates were low despite advocacy, suggesting that patient-led advocacy should at best be used as an adjunct to other, multipronged CRC screening promotion modalities.

Elective surgical versus conservative management of complicated diverticulitis: A systematic review and meta-analysis.

OBJECTIVES: There is no consensus on the optimal treatment for patients with complicated diverticulitis. In this systematic review and meta-analysis we aimed to determine the indications for elective surgery in complicated diverticulitis by comparing conservative treatment with elective surgery. METHODS: A meta-analysis of recurrence, morbidity and stoma rates was performed using a random effects model. Patient-reported quality of life (QoL) and cost-effectiveness outcomes were synthesized qualitatively. RESULTS: Eleven randomized controlled trials and non-randomized studies with a total of 7415 patients were included. In statistical terms, the recurrence of diverticulitis was significantly higher in the conservatively treated group than in the elective surgery group (odds ratio [OR] 0.24, 95% confidence interval [CI] 0.12-0.51). The stoma rate (OR 2.34, 95% CI 1.88-2.92) and the morbidity rate (OR 4.29, 95% CI 2.24-8.23) were significantly higher in the elective surgery group than in the conservatively treated group. There was some evidence for a significant increase in QoL and long-term cost-effectiveness in the elective surgery group than in the conservatively treated group. CONCLUSIONS: Indications for elective surgery should not include the prevention of emergency colostomy or complications. Elective surgical resection may be considered in patients with complicated diverticulitis with the goal of improving their QoL and long-term cost-effectiveness.