Changing epidemiology of colorectal cancer - birth cohort effects and emerging risk factors.

Incidence and mortality of colorectal cancer (CRC) are increasing worldwide, suggesting broad changes in the epidemiology of CRC. In this Review, we discuss the changes that are becoming evident, including trends in CRC incidence and mortality by age and birth cohort, and consider the contributions of early-life exposures and emerging risk factors to these changes. Importantly, incidence of CRC has increased among people born since the early 1950s in nearly all regions of the world. These so-called birth cohort effects imply the involvement of factors that influence the earliest stages of carcinogenesis and have effects across the life course. Accumulating evidence supports the idea that early-life exposures are important risk factors for CRC, including exposures during fetal development, childhood, adolescence and young adulthood. Environmental chemicals could also have a role because the introduction of many in the 1950s and 1960s coincides with increasing incidence of CRC among people born during those years. To reverse the expected increases in the global burden of CRC, participation in average-risk screening programmes needs to be increased by scaling up and implementing evidence-based screening strategies, and emerging risk factors responsible for these increases need to be identified.

Effect of Behavioral Interventions on the Uptake of Colonoscopy for Colorectal Cancer Screening: A Systematic Review and Meta-Analysis.

INTRODUCTION: Screening decreases colorectal cancer incidence and mortality, but uptake in the United States remains suboptimal. Prior studies have investigated the effect of various interventions on overall colorectal cancer screening and stool-based testing, but the effect on colonoscopy-the predominant screening test in the United States-has not been fully examined. We performed a systematic review and meta-analysis to assess the effect of behavioral interventions on screening colonoscopy uptake. METHODS: We searched PubMed, Embase, and Cochrane databases through January 2022 for controlled trials that assessed the effect of behavioral interventions on screening colonoscopy uptake. All titles, abstracts, and articles were screened by at least 2 independent reviewers. Odds ratios were extracted from the original article or calculated from the raw data. The primary outcome was the relative increase in screening colonoscopy completion with any behavioral intervention. We performed random-effects meta-analysis, with subgroup analysis by type of intervention. RESULTS: A total of 25 studies with 30 behavioral interventions were analyzed. The most common interventions were patient navigation (n = 11) and multicomponent interventions (n = 6). Overall, behavioral interventions increased colonoscopy completion by 54% compared with controls (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.26-1.88). Patient navigation (OR 1.78, 95% CI 1.35-2.34) and multicomponent interventions (OR 1.84, 95% CI 1.17-2.89) had the strongest effect on colonoscopy completion among interventions examined in multiple studies. Significant heterogeneity was observed both overall and by intervention type. There was no evidence of publication bias. DISCUSSION: Behavioral interventions increase screening colonoscopy completion and should be adopted in clinical practice. In particular, patient navigation and multicomponent interventions are the best-studied and most effective interventions.

Survival of Middle Eastern and North African Individuals Diagnosed with Colorectal Cancer: A Population-Based Study in California.

BACKGROUND: Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer-specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California. METHODS: We identified adults (ages 18-79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer-specific survival and used Cox proportional hazards regression models to examine the association of race/ethnicity and survival, adjusting for clinical and socio demographic factors. RESULTS: Of 110,192 persons diagnosed with colorectal cancer, five-year colorectal cancer-specific survival was lowest in Black (61.0%) and highest in MENA (73.2%) individuals. Asian (72.2%) individuals had higher survival than White (70.0%) and Hispanic (68.2%) individuals. In adjusted analysis, MENA [adjusted HR (aHR), 0.82; 95% confidence interval (CI), 0.76-0.89], Asian (aHR, 0.86; 95% CI, 0.83-0.90), and Hispanic (aHR, 0.94; 95% CI, 0.91-0.97) race/ethnicity were associated with higher, and Black (aHR, 1.13; 95% CI, 1.09-1.18) race/ethnicity was associated with lower survival compared with non-Hispanic White race/ethnicity. CONCLUSIONS: To our knowledge, this is the first study to report colorectal cancer survival in MENA individuals in the United States. We observed higher survival of MENA individuals compared with other racial/ethnic groups, adjusting for sociodemographic and clinical factors. IMPACT: Future studies are needed to identify factors contributing to cancer outcomes in this unique population.

In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring.

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. RESULTS: Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. CONCLUSION: Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood.

Risk of Hepatocellular Carcinoma in Patients With Indeterminate (LI-RADS 3) Liver Observations.

Early hepatocellular cancer (HCC) detection is associated with curative treatment and improved survival.1 The American Association for the Study of Liver Diseases recommends semiannual ultrasound and α-fetoprotein (AFP) in patients with cirrhosis, and those with abnormal results should undergo diagnostic multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) was devised to standardize reporting of liver observations in at-risk individuals, ranging from LR-1 ("definitely benign") to LR-5 ("definitely HCC''), with indeterminate observations classified as LR-3 ("intermediate probability of malignancy").3 A study among 999 cirrhosis patients found that indeterminate liver observations are common, being reported on diagnostic CT or MRI in 98 (38.3%) of 256 patients with abnormal ultrasound results.4 Prior studies have reported a wide range in HCC risk, from 4% to 31%, for LR-3 observations, so there is insufficient evidence to recommend a standardized strategy for monitoring LR-3 observations.5,6.

Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival.

BACKGROUND: Young adults diagnosed with colorectal cancer (CRC) comprise a growing, yet understudied, patient population. We estimated 5-year relative survival of early-onset CRC and examined disparities in survival by race-ethnicity in a population-based sample. METHODS: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries to identify patients diagnosed with early-onset CRC (20-49 years of age) between January 1, 1992, and December 31, 2013. For each racial-ethnic group, we estimated 5-year relative survival, overall and by sex, tumor site, and stage at diagnosis. To illustrate temporal trends, we compared 5-year relative survival in 1992-2002 vs 2003-2013. We also used Cox proportional hazards regression models to examine the association of race-ethnicity and all-cause mortality, adjusting for age at diagnosis, sex, county type (urban vs rural), county-level median household income, tumor site, and stage at diagnosis. RESULTS: We identified 33,777 patients diagnosed with early-onset CRC (58.5% White, 14.0% Black, 13.0% Asian, 14.5% Hispanic). Five-year relative survival ranged from 57.6% (Black patients) to 69.1% (White patients). Relative survival improved from 1992-2002 to 2003-2013 for White patients only; there was no improvement for Black, Asian, or Hispanic patients. This pattern was similar by sex, tumor site, and stage at diagnosis. In adjusted analysis, Black (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 1.36-1.49), Asian (aHR, 1.06; 95% CI, 1.01-1.12), and Hispanic (aHR, 1.16; 95% CI, 1.10-1.21) race-ethnicity were associated with all-cause mortality. CONCLUSION: Our study adds to the well-documented disparities in CRC in older adults by demonstrating persistent racial-ethnic disparities in relative survival and all-cause mortality in patients with early-onset CRC.

Video Consent for Upper Endoscopy and Colonoscopy Improves Patient Comprehension in a Safety-net, Multi-lingual Population.

The challenges of consenting for procedures are well documented and are compounded when patients have limited English proficiency (LEP). Standardized video consent has been studied, but research in gastroenterology is limited. We created educational videos in English and Spanish covering the elements of traditional consent for colonoscopy and upper endoscopy. All participants underwent traditional verbal consent and a subset viewed the language and procedure specific video. Participants from a multilingual, safety-net hospital patient population were then given a questionnaire to assess their comprehension and satisfaction. Participants who watched the video had higher comprehension scores than those who received traditional verbal consent alone. This difference persisted when data was stratified by language and procedure, and when controlled for educational level and prior procedure. Video consent improves comprehension and satisfaction for endoscopy and may mitigate some of the challenges encountered when consenting patients with LEP.

Recurrent pericardial effusion and tamponade after epicardial pacemaker lead placement: a case report.

Background: Epicardial pacemaker placement is often necessary in pacemaker-dependent patients with ongoing device pocket infection or lack of venous access. Pericardial effusion and tamponade are rare but serious complications of this procedure. Case summary: A 38-year-old woman presented with nausea, diaphoresis, and hypotension 7 days after epicardial lead placement. Echocardiography revealed a large pericardial effusion with signs of tamponade. Despite initial improvement after pericardiocentesis, she continued to develop symptomatic pericardial effusions. The patient ultimately underwent pleuro-pericardial window surgery, which resulted in sustained resolution of effusion recurrence. Discussion: Cases of recurrent pericardial effusion and tamponade following epicardial lead placement have been reported in the literature, although they are rare. While extensive partial pericardiectomy or total pericardiectomy was required to achieve adequate control of fluid accumulation in prior case reports, our patient was successfully managed with a pleuro-pericardial window.

Colorectal Cancer in Younger Adults.

Contrary to decreasing incidence rate of colorectal cancer (CRC) in older adults, incidence rates have nearly doubled in younger adults (age <50 years) in the United States since the early 1990s. A similar increase has been observed across the globe. Despite overall population trends in aging, about 15% of CRCs will be diagnosed in younger adults by 2030. The mechanisms and factors contributing to early-onset CRC (EOCRC) remain puzzling, especially because most young adults diagnosed with CRC have no known risk factors or predisposing conditions, such as family history of CRC or polyps or a hereditary syndrome (eg, Lynch syndrome, polyposis). In this up-to-date review, we discuss the current knowledge of EOCRC, including epidemiology, risk factors, clinical and molecular features, treatment and survival, and recognition and screening strategies.

Novel case of diabetic myonecrosis in a teenage patient with type 2 diabetes mellitus.

Diabetic myonecrosis is a rare complication of diabetes that is typically described in patients with long-standing, uncontrolled diabetes. We report a case in which diabetic myonecrosis presents as an early complication of diabetes. To our knowledge, this is the first report of diabetic myonecrosis observed in an adolescent patient with type 2 diabetes. A 16-year-old girl presented with acute-onset, bilateral lower extremity pain and tenderness concerning for bilateral gastrocnemius myonecrosis in the setting of poorly controlled type 2 diabetes for at least 4-5 years. Investigations revealed elevated creatine kinase levels and MRI suggestive of myonecrosis. A left gastrocnemius muscle biopsy had histological findings consistent with active myofibre necrosis and multifocal perivascular lymphocytic infiltration consistent with diabetic myonecrosis. The patient's symptoms improved after 11 days of treatment with intravenous fluids, non-steroidal anti-inflammatory drugs, glycaemic control and physical therapy.

Maternal obesity, pregnancy weight gain, and birth weight and risk of colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring. DESIGN: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2019 by linkage with the California Cancer Registry. We used Cox proportional hazards models to estimate adjusted HR (aHR); we examined effect measure modification using single-referent models to estimate the relative excess risk due to interaction (RERI). RESULTS: 68 offspring were diagnosed with CRC over 738 048 person-years of follow-up, and half (48.5%) were diagnosed younger than age 50 years. Maternal obesity (≥30 kg/m2) increased the risk of CRC in offspring (aHR 2.51, 95% CI 1.05 to 6.02). Total weight gain modified the association of rate of early weight gain (RERI -4.37, 95% CI -9.49 to 0.76), suggesting discordant growth from early to late pregnancy increases risk. There was an elevated association with birth weight (≥4000 g: aHR 1.95, 95% CI 0.8 to 4.38). CONCLUSION: Our results suggest that in utero events are important risk factors for CRC and may contribute to increasing incidence rates in younger adults.

Colorectal Cancer Screening and Yield in a Mailed Outreach Program in a Safety-Net Healthcare System.

BACKGROUND: Screening with fecal immunochemical testing (FIT) reduces colorectal cancer mortality; however, screening remains low in underserved populations. Mailed outreach, including an invitation letter, FIT, and test instructions, is an evidence-based strategy to improve screening. AIMS: To examine screening completion and yield in a mailed outreach program in a safety-net healthcare system. METHODS: We identified and mailed outreach invitations to patients due for screening in a large safety-net system between September 1, 2018, and August 31, 2019. We examined: (1) screening completion, the proportion of patients completing FIT or screening colonoscopy within 6 months of the mailed invitation; and (2) timely diagnostic colonoscopy, the proportion of patients completing colonoscopy within 6 months of positive FIT. RESULTS: We mailed 14,879 invitations to 13,190 patients. Nearly half (n = 6098, 46.2%) of patients completed screening: 4,896 (80.3%) completed FIT through mailed outreach; 1,114 (18.3%) FIT through usual care; and 88 (1.4%) screening colonoscopy through usual care. Of patients with a positive FIT (n = 289), 50.5% completed diagnostic colonoscopy within 6 months, 10.7% within 6-12 months, and 4.8% after 12 months. A total of 8 cancers and 83 advanced adenomas were detected in the 191 patients completing diagnostic colonoscopy. CONCLUSION: After implementing and scaling up mailed outreach in a safety-net system, about half of patients completed screening, and the majority did so through mailed outreach. However, many patients failed to complete diagnostic colonoscopy after positive FIT. Results highlight the importance of adapting mailed outreach programs to local contexts and constraints of healthcare systems, in order to support efforts to improve CRC screening in underserved populations.

Comparative Evaluation of Conventional Stool Testing and Multiplex Molecular Panel in Outpatients With Relapse of Inflammatory Bowel Disease.

BACKGROUND: Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compare the impact of PCR stool testing to conventional stool testing in outpatients presenting with relapse of IBD. METHODS: In a retrospective cohort study of outpatients with IBD presenting to NYU Langone Health with flare from September 2015 to April 2019, we compared patients who underwent stool testing with GI PCR to age-, sex-, and IBD-subtype-matched patients who underwent culture and ova and parasite exam (conventional testing). The primary outcome was IBD therapy escalation after testing. Secondary outcomes included rates of posttesting endoscopy, abdominal radiography, antibiotics, and IBD-related emergency department visits, hospitalizations, and abdominal surgeries. RESULTS: We identified 134 patients who underwent GI PCR matched to 134 patients who underwent conventional testing. Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01). We found that GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes. On multivariate analysis, testing with GI PCR was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; P = 0.02) for escalation of IBD therapies. CONCLUSIONS: Testing with GI PCR was associated with higher rates of pathogen detection and lower rates of IBD therapy escalation and endoscopy in the outpatient setting. These changes in management were not associated with a difference in IBD outcomes.

Utility of Unrefined Carbohydrates in Type 2 Diabetes. Comment on "Reversing Type 2 Diabetes: A Narrative Review of the Evidence, Nutrients, 2019, 11, 766".

Hallberg et al. provide a limited literature review on the reversal of type 2 diabetes mellitus (T2DM) [...].

A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy.

PURPOSE: Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort. METHODS: We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression. RESULTS: We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR = 2.57, P = 0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HR = 0.16, P < 0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent. CONCLUSION: Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.