What Is Lynch Syndrome?

This JAMA Patient Page describes Lynch syndrome, its risk factors and diagnosis, and its association with colorectal cancer and other specific cancers.

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis.

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. Data Sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. Study Selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. Data Extraction and Synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). Conclusions and Relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer.

BACKGROUND: Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. METHODS: We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. RESULTS: Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend < .001), respectively, with stronger associations for younger ages (Pinteraction < .001) and rectal cancer (Pheterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month). CONCLUSIONS: Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.

Cultivating Anti-Racism Allies in Academic Medicine.

Racial microaggressions, racially based remarks, or actions that negatively impact marginalized physicians of color (Black, Latino/a/x, and American Indian/Alaskan Natives) often go unaddressed. This article provides four strategies for how individuals and institutions can engage in anti-racism allyship: (1) be an upstander during microaggressions, (2) be a sponsor and advocate for physicians of color, (3) acknowledge academic titles and accomplishments, and (4) challenge the idea of a "standard fit" for academic faculty and research. Skills in academic allyship should be taught to all physicians throughout the educational continuum to mitigate feelings of isolation that racialized minority physicians frequently experience.

Supporting Breastfeeding Physicians Across the Educational and Professional Continuum: A Call to Action.

The benefits of breastmilk and lactation are well established for both infants and women. National organizations recommend exclusively breastfeeding for the first 6 months of life and continued breastfeeding for the first 1-2 years of life. For physicians, childbearing years often coincide with key periods of training and their early career. Physician mothers have high rates of initiating breastfeeding but low success in maintaining breastfeeding. Breastfeeding discontinuation among physicians is a well-described, multifactorial issue that has persisted for decades. Reasons for discontinuation include inadequate access to pumping rooms, insufficient workplace and coworker support, and constrained schedules. Pumping is viewed as a burden to teammates and superiors, and physicians are often required to make up time spent pumping. Vague or absent policies to support breastfeeding by accreditation organizations and institutions create workplace conflict and impose additional stress on breastfeeding physicians, who devote significant time, energy, and mental reserves navigating clinical responsibilities, workplace relationships, and licensing requirements to pump. The authors propose several recommendations to improve the environment, support, and resources for breastfeeding physicians with a focus on what individuals, institutions, and professional organizations can do. Creating lactation policies that allow breastfeeding physicians equitable participation in the workplace is a matter of reproductive justice. Improving the collective awareness and support for breastfeeding trainees and physicians is a critical step in recruiting, retaining, and supporting women in medicine.

Risk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers.

Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006-2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (<20%), intermediate (20%-49%), and high (≥50%). We also examined the associations by age of cancer diagnosis (earlier onset [<60] vs. ≥60). A total of 273 incident liver cancer and 4789 non-liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41-fold risk of liver cancer (RR = 2.41, 95% CI: 1.73-3.35) and 23% increased risk of non-liver GI cancers (RR = 1.23, 95% CI: 1.14-1.32) (all ptrend < 0.001). Stronger associations were observed for men and individuals who were obese (all pinteraction < 0.05). NAFLD-associated elevated risk was stronger for earlier-onset cancers. For each 25% increase in NAFLD risk, the RRs for earlier-onset cancers were 1.32 (95% CI: 1.05-1.66) for esophageal cancer, 1.35 (95% CI: 1.06-1.72) for gastric cancer, 1.34 (95% CI: 1.09-1.65) for pancreatic cancer, and 1.10 (95% CI: 1.01-1.20) for colorectal cancer. Conclusion: NAFLD risk was associated with an increased risk of liver and most GI cancers, especially those of earlier onset.

Evaluation and Management Strategies for GI Involvement with Amyloidosis.

Amyloidosis is a heterogeneous disease that can cause a wide array of nonspecific symptoms when the gastrointestinal (GI) tract is involved, including weight loss, early satiety, change in bowel habits with diarrhea, constipation, or alternating bowel pattern. Endoscopy with biopsy for Congo red staining establishes the diagnosis and fibril subtyping helps to guide targeted treatment options. Light chain amyloidosis is the most frequent subtype found throughout the GI tract. Transthyretin amyloidosis is most likely to be found on rectal biopsy. Management of the symptoms of GI tract involvement with amyloidosis relate to addressing the underlying symptom complex that is produced and generally abstracted from the management of severe forms of functional GI disorders. Attention to improving symptom management and nutrition status can improve quality of life in these patients.

Prolonged Cecal Insertion Time Is Not Associated with Decreased Adenoma Detection When a Longer Withdrawal Time Is Achieved.

BACKGROUND: The association between withdrawal time and adenoma detection has been established; however, the effect of cecal insertion time on adenoma detection remains unclear. AIM: To determine the association between cecal insertion time and adenoma detection. METHODS: This study completed a retrospective analysis of data collected in 4 prospective randomized-controlled trials related to screening and surveillance colonoscopy at a single tertiary care from 2010 to 2016. The primary outcome was cecal insertion time and its association with mean number of adenomas per patient and adenoma detection rate (ADR). RESULTS: 1303 patients met inclusion criteria (average age 59.7 ± 8.7 years; 759 females (58.3%), and 763 Caucasians (58.6%). Mean cecal insertion time was significantly longer in patients who were female (p < 0.001), received moderate sedation (p = 0.001), had fellow involvement (p < 0.001), older (p = 0.002), and lower Boston bowel preparation scale (p < 0.001). Withdrawal time was found to increase as mean cecal insertion time increased (p < 0.001). The mean cecal insertion time was not different in patients with or without adenomas (p = 0.94). Cecal insertion time did not correlate with the mean number of adenomas or advanced adenomas per patient (p > 0.05), which was also true on Poisson regression analysis. Adenomas and advanced adenomas per patient were found to decrease when cecal insertion to withdrawal time ratios were greater than 1 (p < 0.001). CONCLUSIONS: Prolonged cecal insertion time was not associated with a decrease in ADR, mean number of adenomas or advanced adenomas per patient. When withdrawal times were longer than cecal insertion times, the number of adenomas and advanced adenomas detected per patient was significantly improved.

SEALS: an Innovative Pipeline Program Targeting Obstacles to Diversity in the Physician Workforce.

OBJECTIVE: Medical schools may find implementing pipeline programs for minority pre-medical students prohibitive due to a number of factors including the lack of well-described programs in the literature, the limited evidence for program development, and institutional financial barriers. Our goals were to (1) design a pipeline program based on educational theory; (2) deliver the program in a low cost, sustainable manner; and (3) evaluate intermediate outcomes of the program. METHODS: SEALS is a 6-week program based on an asset bundles model designed to promote: (1) socialization and professionalism, (2) education in science learning tools, (3) acquisition of finance literacy, (4) the leveraging of mentorship and networks, and (5) social expectations and resilience, among minority pre-medical students. This is a prospective mixed methods study. Students completed survey instruments pre-program, post-program, and 6 months post-program, establishing intermediate outcome measures. RESULTS: Thirteen students matriculated to SEALS. The SEALS cohort rated themselves as improved or significantly improved when asked to rate their familiarity with MCAT components (p < 0.01), ability to ask for a letter of recommendation (p = 0.04), and importance of interview skills (p = 0.04) compared with before the program. Over 90 % of students referenced the health disparities lecture series as an inspiration to advocate for minority health. Six-month surveys suggested that SEALS students acquired and applied four of the five assets at their college campuses. CONCLUSIONS: This low-cost, high-quality, program can be undertaken by medical schools interested in promoting a diverse workforce that may ultimately begin to address and reduce health care disparities.

First year medical student attitudes about advocacy in medicine across multiple fields of discipline: analysis of reflective essays.

BACKGROUND: Advocacy is often described as a pillar of the medical profession. However, the impact of advocacy training on medical students' identity as advocates in the medical profession is not well-described. AIM/SETTING/PARTICIPANTS: We sought to introduce an advocacy curriculum to a mandatory Health Care Disparities (HCD) course for 88 first year medical students. PROGRAM DESCRIPTION: The 2013 HCD added advocacy curriculum that included: guest lecturers' perspectives on their advocacy experience; reflective essay assignments assessing self-identify as an advocate; advocacy-specific lectures and large group discussions; and participation in small group community projects. EVALUATION: A mixed methods approached was used to evaluate 88 first year medical students' advocacy themed reflective essays, independently coded by three investigators, and Likert-response questions were compared to published benchmarked items. The IRB exempted this study. Analysis of student essays revealed that students were better able to identify as an advocate in medicine. The survey also revealed that 86% post-course vs. 73% precourse agreed/strongly agreed with the statement: "I consider myself an advocate" (p=0.006). DISCUSSION: Exposing all medical students to advocacy within medicine may help shape and define their perceived professional role. Future work will explore adding advocacy and leadership skill training to the HCD course.

A New-Onset Rash in the Setting of Rifaximin Treatment for Hepatic Encephalopathy.

We present one of the first cases in the literature to describe an association between Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and rifaximin treatment in a patient with a recent diagnosis of alcoholic hepatitis, stage 2 hepatic encephalopathy, and no known existing allergies. Although SJS/TEN may be a rare reaction with rifaximin, it should be an important clinical consideration.