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.

Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer.

OBJECTIVE: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. DESIGN: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs. RESULTS: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09). CONCLUSIONS: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

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.

EUS-guided drainage of peripancreatic fluid collections with lumen-apposing metal stents and plastic double-pigtail stents: comparison of efficacy and adverse event rates.

BACKGROUND AND AIMS: Transmural drainage with double-pigtail plastic stents (DPPSs) was the mainstay of endoscopic therapy for symptomatic peripancreatic fluid collections (PPFCs) until the introduction of lumen-apposing covered self-expanding metal stents (LAMSs). Currently, there are limited data regarding the efficacy and adverse event rate of LAMSs compared with DPPSs. METHODS: A retrospective analysis of EUS-guided PPFC drainage at a single tertiary care center between 2008 and 2015 was performed. Patients were classified based on drainage method: DPPSs and LAMSs. Adverse event rates, unplanned endoscopic procedures/necrosectomies, and PPFC resolution within 6 months were recorded. Significant bleeding was defined as necessitating transfusion or requiring endoscopic treatment/radiographic embolization. Subsequent endoscopic procedures were defined as unplanned procedures; stent removals were excluded. RESULTS: A total of 103 patients met inclusion criteria (84 DPPSs, 19 LAMSs). PPFCs were classified as walled-off necrosis (WON) in 23 (14 DPPSs, 9 LAMSs). There were significantly more bleeding episodes in the LAMS group (4 [19%]: 2 splenic artery pseudo-aneurysms, 1 collateral vessel bleed, 1 intracavitary variceal bleed; P = .0003) than in the DPPS group (1 (1%]: stent erosion into the gastric wall). One perforation occurred in the DPPS group. Unplanned repeat endoscopy was more frequent in the LAMS group (10% vs 26%, P = .07). Among retreated LAMS patients in with WON, 5 (56%) had obstruction by necrotic debris. In patients for whom follow-up was available, 67 of 70 (96%) with DPPSs and 16 of 17 (94%) with LAMSs had resolution of PPFCs within 6 months (P = .78). CONCLUSIONS: DPPSs and LAMSs are effective methods for treatment of PPFCs. In our cohort, use of LAMSs was associated with significantly higher rates of procedure-related bleeding and greater need for repeat endoscopic intervention.

Evaluating screening colonoscopy quality in an uninsured urban population following patient navigation.

Patient navigation (PN) increases screening colonoscopy completion in minority and uninsured populations. However, colonoscopy quality is under-reported in the setting of PN and quality indicators have often failed to meet benchmark standards. This study investigated screening colonoscopy quality indicators after year-one of a PN initiative targeting the medically uninsured. This was a retrospective analysis of 296 outpatient screening colonoscopies. Patients were 45 to 75 years of age with no history of bowel cancer, inflammatory bowel disease, or colorectal surgery. The screening colonoscopy quality indicators: adenoma detection rate (ADR), cecal intubation rate (CIR), and bowel preparation quality were compared in 89 uninsured Federally Qualified Health Center (FQHC) patients who received PN and 207 University Hospital patients who received usual care. The FQHC PN and University Hospital cohorts were similar in female sex (69% vs. 70%; p = 0.861) and African American race (61% vs. 61%; p = 0.920). The FQHC PN cohort was younger (57 years vs. 60 years; p < 0.001). There was no difference in ADR (33% vs. 32%; p = 0.971) or CIR (96% vs. 95%; p = 0.900) comparing the FQHC PN and University Hospital cohorts. The FQHC PN patients had a greater likelihood of an optimal bowel preparation on multivariate logistic regression (odds ratio 4.17; 95% confidence interval 1.07 to 16.20). Uninsured FQHC patients who received PN were observed to have intra-procedure quality indicators that exceeded bench-mark standards for high-quality screening colonoscopy and were equivalent to those observed in an insured University Hospital patient population.

Knowledge of Polyp History and Recommended Follow-Up Among a Predominately African American Patient Population and the Impact of Patient Navigation.

BACKGROUND AND AIMS: Colorectal screening (CRS) rates in minority and uninsured populations have increased through patient navigation (PN) interventions. However, patient knowledge of colonoscopy results and follow-up recommendations has not been described in an African American (AA) population or following PN. Our objectives were to determine patient knowledge of colonoscopy results and follow-up recommendations within an AA patient population and to compare post-colonoscopy knowledge among patients who received either PN or usual care. METHODS: This is a prospective observational study of patients who completed a screening colonoscopy in 2014. A semi-structured telephone survey was completed by 96 participants (69 % AA, 78 % female, and mean age 63 years). The survey assessed patient recall of polyp results and follow-up recommendations. Responses were compared with the medical record. RESULTS: Of 96 patients surveyed (response rate, 68 %), 83 % accurately reported if polyps were detected and 66 % accurately reported their recommended follow-up. The identification of adenomatous polyps on colonoscopy was a predictor of accurate recall of colonoscopy results and follow-up recommendations. Uninsured patients who completed PN (18 of 96) were more likely to accurately report polyp results (100 vs. 80 %; P = 0.036), but the rates of accurate follow-up recall were not statistically significant (44 vs. 71 %; P = 0.053) when compared to usual care patients. CONCLUSIONS: In an AA population, post-colonoscopy polyp recall rates were similar to those described in white populations. Uninsured patients who completed PN were more likely than insured usual care patients to accurately report the presence of polyps on colonoscopy.

Establishing Medical Students' Cultural and Linguistic Competence for the Care of Spanish-Speaking Limited English Proficient Patients.

Limited English proficient (LEP) patients are at risk of disparities in health and health care quality. These disparities can be mitigated by providing care in a language they understand. Undergraduate medical education provides an opportunity to stress that language barriers negatively impact the quality and safety of health care for LEP patients and to teach students how to overcome them. Because the preponderance of LEP patients in the USA is Spanish speaking, the majority of US medical schools have established medical Spanish coursework for interested students. However, 70 % of medical schools note significant obstacles to delivering this curriculum. The most commonly cited obstacles include a lack of time to deliver it, heterogeneous student skill levels, and insufficient faculty support. We also note that educators need to make sure not to propagate disparities and medical errors for LEP patients. We provide recommendations for establishing medical students' linguistic and cultural competence for the care Spanish-speaking limited English proficiency patients, with the caution that this instruction must be coupled with education as to when to call on an interpreter if participants are not fluent in Spanish at the end of the course.

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.

Medical Students' Experiences and Perspectives on Interpreting for LEP Patients at Two US Medical Schools.

THEORY: Language concordance between patient and provider has been shown to improve health outcomes for Limited English Proficiency (LEP) patients. However, health care teams often use available ad hoc interpreters without knowing whether their language skills are adequate. Little is known about the role of medical students working as ad hoc interpreters. HYPOTHESIS: Bilingual medical students are engaged as interpreters in the care of LEP patients and may serve as a potential resource for health care teams caring for LEP patients. METHOD: We conducted a multi-institutional online survey of graduating medical students at the University of Illinois and the University of Chicago in 2011 and 2012, containing both qualitative and quantitative questions regarding their experiences as interpreters for LEP patients. RESULTS: Half (216/430) of contacted students completed the survey; 40 % (87/216) of responding students reported being bilingual. Of these students, the vast majority, 84 % (73/87), had been asked to interpret for patients in the clinical setting. Only 12 % (10/87) of students reported having felt uncomfortable interpreting for patients "often" or "very often." Over half (53 %, 46/87) described incidents during which they felt uncomfortable interpreting. Seventeen (17/46, 37 %) students described those incidents as high-stakes clinical settings. CONCLUSIONS: Medical schools and health care institutions should establish guidelines for students who identify as fluent in another language and are interested in interpreting for LEP patients in clinical settings, to protect both students and patients when language poses a barrier to quality care.