Genetic Testing Utilization: Discrepancies Between Somatic and Germline Results in Patients With Cancer Reviewed at the UW Health Precision Medicine Molecular Tumor Board.

PURPOSE: Somatic and germline testing are increasingly used to estimate risks for patients with cancer. Although both germline testing and somatic testing can identify genetic variants that could change a patient's care and eligible treatments, the aims of these tests and their technologies are fundamentally different and cannot be used interchangeably. This study examines the timing and results of somatic and germline genetic testing for patients with cancer at UW Health. METHODS: Eight hundred and seventy-seven participants underwent somatic genetic testing, which was reviewed by the Precision Medicine Molecular Tumor Board (PMMTB). Patients were diagnosed with cancers, including breast, colorectal, endometrial, pancreatic, or ovarian cancer, and met National Comprehensive Cancer Network criteria for germline genetic testing. Germline testing details were collected by medical record review. RESULTS: The results of this study found that only 310 patients (35%) had germline evaluation before PMMTB review. The percent of germline pathogenic/likely pathogenic variants identified in actionable genes was 28%. Most germline variants were identified in the BRCA1 (26%) and BRCA2 (28%) genes. In total, 65% (54/83) of germline variants were detected with both germline testing and somatic testing; however, 35% (29/83) of germline variants were not identified on somatic results. These results demonstrate the importance of combination germline and somatic testing. CONCLUSION: This study highlights the differences in genetic testing types and demonstrates that conducting germline testing at earlier stages of diagnoses is necessary to identify potentially actionable and treatment-specific variants in patients with cancer.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease.

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

Transarticular Versus Retroarticular Drilling of Stable Osteochondritis Dissecans of the Knee: A Prospective Multicenter Randomized Controlled Trial by the ROCK Group.

BACKGROUND: When stable osteochondritis dissecans (OCD) lesions of the femoral condyle in a skeletally immature patient fail to heal with nonoperative methods, the standard of care treatment is condylar OCD drilling. Two primary OCD drilling techniques have been described, but no prospective studies have compared their relative effectiveness. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the healing and function after transarticular drilling (TAD) with that after retroarticular drilling (RAD). It was hypothesized that there would be no difference in rate or time to healing, rate or time to return to sports, patient-reported outcomes (PROs), or secondary OCD-related surgery. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Skeletally immature patients with magnetic resonance imaging-confirmed stable OCD lesions of the medial femoral condyle who did not demonstrate substantial healing after a minimum of 3 months of nonoperative treatment were prospectively enrolled by 1 of 17 surgeon-investigators at 1 of 14 centers. Patients were randomized to the TAD or RAD group. Tourniquet time, fluoroscopy time, and complications were compared between the treatment groups. Postoperatively, serial radiographs were obtained every 6 weeks to assess healing, and PROs were obtained at 6 months, 12 months, and 24 months. RESULTS: A total of 91 patients were included, consisting of 51 patients in the TAD and 40 patients in the RAD group, who were similar in age, sex distribution, and 2-year PRO response rate. Tourniquet time and fluoroscopy time were significantly shorter with TAD (mean, 38.1 minutes and 0.85 minutes, respectively) than RAD (mean, 48.2 minutes and 1.34 minutes respectively) (P = .02; P = .004). In the RAD group, chondral injury from K-wire passage into the intra-articular space was reported in 9 of 40 (22%) patients, but no associated postoperative clinical sequelae were identified in these patients. No significant differences between groups were detected in follow-up Pediatric-International Knee Documentation Committee, Lysholm, Marx Activity Scale, or Knee injury and Osteoarthritis Outcome Score Quality of Life scores. Healing parameters were superior at 6 months and 12 months in the TAD group, compared with the RAD group, and secondary OCD surgery occurred in 4% of patients who underwent TAD and 10% of patients who underwent RAD (P = .40). Patients in the TAD group returned to sports earlier than those in the RAD group (P = .049). CONCLUSION: TAD showed shorter operative time and fluoroscopy time and superior healing parameters at 6 and 12 months, but no differences were seen in 24-month healing parameters or PROs at all follow-up time points, when compared with RAD. REGISTRATION: NCT01754298 (ClinicalTrials.gov identifier).

Policies, Practices, and Attitudes Related to Parental Leave for Practicing Pediatric Orthopaedic Surgeons.

BACKGROUND: Parental leave impacts family engagement, bonding, stress, and happiness. Because parental leave benefits are important to all surgeons regardless of sex, understanding parental leave practices in pediatric orthopaedic surgery is critical to promote equity within the profession and supporting balance in work and family life. The aim of this study was to survey pediatric orthopaedic surgeons about their knowledge of parental leave policies, attitudes towards parental leave, and their individual experiences taking leave. METHODS: A 34-question anonymous survey was distributed to the Pediatric Orthopaedic Society of North America membership. Eligible respondents were attending pediatric orthopaedic surgeons practicing in the United States or Canada. The survey gathered information about employer parental leave policies, perceptions about and experiences with parental leave while practicing as a surgeon, and demographic information about respondents. RESULTS: A total of 77 responses were completed and used for analysis. Most respondents were men (59.7%), <50 years old (67.5%), married (90.9%), and in urban communities (75.3%). A large majority were practicing in the United States (97.4%). Most respondents were unfamiliar with employer parental leave policies (maternity: 53.3%; paternity: 67.5%; and adoption: 85.7%). Those familiar with policies reported that employers offered 7 to 12 weeks for maternity leave (45.7%) and <1 week for paternity leave (50%) and adoption leave (45.5%). Most respondents believed 7 to 12 weeks should be offered for maternity leave (66.2%), 1 to 6 weeks for paternity leave (54.6%), and 7 to 12 weeks for adoption leave (46.8%). Many respondents reported taking 1 to 6 weeks of parental leave as a surgeon (53.3%) and that their colleagues were supportive of their parental leave (40.3%). CONCLUSIONS: Most pediatric orthopaedic surgeons were unfamiliar with parental leave benefits provided by employers. Respondents who were familiar with these policies believed that more parental leave should be provided, especially for men who may feel social pressure to take less time for leave. Although respondents reported that their work environments were supportive, this study identified opportunities for improvement to support surgeons who wish to balance parental experiences with work responsibilities. LEVEL OF EVIDENCE: Level V.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

Yield of upper gastrointestinal screening in colonic adenomatous polyposis of unknown etiology: a multicenter study.

Background and study aims The majority of patients with 10 or more cumulative colorectal adenomas have uninformative genetic testing and meet criteria for colonic adenomatous polyposis of unknown etiology (CPUE). The yield of upper gastrointestinal screening in patients with CPUE after multi-gene panel testing is unknown and our objective was to characterize this. Patient and methods A multicenter, retrospective analysis of screening upper endoscopies in adults with CPUE after multi-gene panel testing was performed. Those with a history of gastroduodenal neoplasia prior to CPUE diagnosis were excluded. Demographic and clinical variables were collected and compared. Results One hundred and twenty-eight patients with CPUE were included from five participating centers. Nine (7.0 %) had gastroduodenal neoplasia on initial screening upper endoscopy. Those with over 100 colorectal adenomas had a significantly higher rate of gastroduodenal neoplasia than those with 20-99 or 10-19 colorectal adenomas (44.4 % vs 4.1 % vs 4.4 %, P  = 0.002). Similar results were seen when the analysis was restricted to only duodenal or ampullary adenomas. The only malignancy was a gastric cancer in a patient with 20 to 99 colorectal adenomas. When comparing patients with gastroduodenal neoplasia to those without, the only significantly different characteristic was the cumulative number of colorectal adenomas. Conclusions We found a 7 % rate of gastroduodenal neoplasia in patients with CPUE after multi-gene panel testing. Although patients with ≥ 100 colorectal adenomas had a significantly higher risk, over 4 % of patients with 10 to 99 colorectal adenomas had gastroduodenal neoplasia. Given this, we recommend a screening upper endoscopy at the time of a colonoscopy after CPUE diagnosis.

Detection of High-Risk Sessile Serrated Lesions: Multitarget Stool DNA Versus CT Colonography.

BACKGROUND. The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Sessile serrated lesions (SSLs) that are large (≥ 10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of noninvasive screening tests for detection of high-risk SSLs is unclear. OBJECTIVE. The aim of this study was to compare noninvasive screening detection of high-risk SSLs between the multitarget stool DNA (mt-sDNA) test and CT colonography (CTC). METHODS. This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age, 60.0 years) who underwent CRC screening at a single center by mt-sDNA from 2014 to 2019 (n = 3987) or by CTC from 2009 to 2019 (n = 3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. RESULTS. The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p = .23) and 6.5% (260/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA versus 14.4% (66/457; p < .001) and 25.9% (63/243; p < .001) for CTC at the 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; p < .001) and 1.6% (63/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. CONCLUSION. CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. CLINICAL IMPACT. The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.

Descriptive Epidemiology From the Research in Osteochondritis Dissecans of the Knee (ROCK) Prospective Cohort.

BACKGROUND: Osteochondritis dissecans (OCD) occurs most commonly in the knees of young individuals. This condition is known to cause pain and discomfort in the knee and can lead to disability and early knee osteoarthritis. The cause is not well understood, and treatment plans are not well delineated. The Research in Osteochondritis Dissecans of the Knee (ROCK) group established a multicenter, prospective cohort to better understand this disease. PURPOSE: To provide a baseline report of the ROCK multicenter prospective cohort and present a descriptive analysis of baseline data for patient characteristics, lesion characteristics, and clinical findings of the first 1000 cases enrolled into the prospective cohort. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients were recruited from centers throughout the United States. Baseline data were obtained for patient characteristics, sports participation, patient-reported measures of functional capabilities and limitations, physical examination, diagnostic imaging results, and initial treatment plan. Descriptive statistics were completed for all outcomes of interest. RESULTS: As of November 2020, a total of 27 orthopaedic surgeons from 17 institutions had enrolled 1004 knees with OCD, representing 903 patients (68.9% males; median age, 13.1 years; range, 6.3-25.4 years), into the prospective cohort. Lesions were located on the medial femoral condyle (66.2%), lateral femoral condyle (18.1%), trochlea (9.5%), patella (6.0%), and tibial plateau (0.2%). Most cases involved multisport athletes (68.1%), with the most common primary sport being basketball for males (27.3% of cases) and soccer for females (27.6% of cases). The median Pediatric International Knee Documentation Committee (Pedi-IKCD) score was 59.9 (IQR, 45.6-73.9), and the median Pediatric Functional Activity Brief Scale (Pedi-FABS) score was 21.0 (IQR, 5.0-28.0). Initial treatments were surgical intervention (55.4%) and activity restriction (44.0%). When surgery was performed, surgeons deemed the lesion to be stable at intraoperative assessment in 48.1% of cases. CONCLUSION: The multicenter ROCK group has been able to enroll the largest knee OCD cohort to date. This information is being used to further understand the pathology of OCD, including its cause, associated comorbidities, and initial presentation and symptoms. The cohort having been established is now being followed longitudinally to better define and elucidate the best treatment algorithms based on these presenting signs and symptoms.

#SpeakUpOrtho: Narratives of Women in Orthopaedic Surgery-Invited Manuscript.

Microaggressions, bullying, harassment, sexual harassment, and discrimination continue to be experienced by orthopaedic physicians in the workplace. Oftentimes, these behaviors go unreported because of fear of retaliation, and many perpetrators are not held accountable. This article provides examples of stories anonymously submitted to #SpeakUpOrtho on the topics of microaggressions, bullying/harassment, sexual harassment, discrimination, and retaliation by orthopaedic surgery residents, fellows, and attending surgeons. Commentary by experts in the field is also included to provide ways to manage and prevent the perpetuation of these behaviors.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Colorectal Cancer Screening After Changes in US Preventive Services Task Force Guidelines With Increased Screening Options.

INTRODUCTION: In 2016, the US Preventive Services Task Force (USPSTF) added multitarget stool DNA and computed tomography colonography (CTC) as accepted colorectal cancer screening modalities to the already recommended tests: fecal immunochemical test (FIT), sigmoidoscopy, and colonoscopy. The aim of our study was to determine trends in screening after the USPSTF update, with the effect of additional tests on the use of existing colorectal cancer screening modalities and overall screening rates. METHODS: We prospectively compared monthly colorectal cancer overall screening rates and the mean total numbers of patients screened by multitarget stool DNA, colonoscopy, sigmoidoscopy, CTC, and FIT 6 months prior to the new USPSTF guidelines until 30 months after. RESULTS: At completion of the study, 72,202 patients were eligible for screening. The overall rate of eligible patients screened for colorectal cancer did not change (80.9% vs 81.3%; P = 0.287). There was a significant increase in the percent of patients screened with multitarget stool DNA (1.6% to 15.6%; P = .001) and a significant decrease in the percent of patients screened using CTC (3.8 % to 1.5%; P = .004), FIT (9.3% to 4.9%; P = .003), and sigmoidoscopy (2.4% to 1.5%, P = .024). There was a nonsignificant decrease in the percent use of screening colonoscopy, from 82.9 % to 76.5% (P = .313). CONCLUSION: While the overall colorectal cancer screening rate did not increase after the USPSTF update with additional recommended screening tests, practice patterns did change with a shift in the type of screening test used.

Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant.

Juvenile polyposis syndrome (JPS) is a clinically diagnosed hamartomatous polyposis syndrome that increases the risk of gastrointestinal cancer. Approximately 40%-50% of JPS is caused by a germline disease-causing variant (DCV) in the SMAD4 or BMPR1A genes. The aim of this study was to characterize the phenotype of DCV-negative JPS and compare it with DCV-positive JPS. Herein, we analyzed a cohort of 145 individuals with JPS from nine institutions, including both pediatric and adult centers. Data analyzed included age at diagnosis, family history, cancer history, need for colectomy/gastrectomy, and polyp number and location. Compared with DCV-positive JPS, DCV-negative JPS was associated with younger age at diagnosis (P < 0.001), lower likelihood of having a family history of JPS (P < 0.001), and a lower risk of colectomy (P = 0.032). None of the DCV-negative individuals had gastric or duodenal polyps, and polyp burden decreased after the first decade compared with DCV-positive JPS. Subgroup analysis between SMAD4 and BMPR1A carriers showed that SMAD4 carriers were more likely to have a family history of JPS and required gastrectomy. Taken together, these data provide the largest phenotypic characterization of individuals with DCV-negative JPS to date, showing that this group has distinct differences compared with JPS due to a SMAD4 or BMPR1A variant. Better understanding of phenotype and cancer risk associated with JPS both with and without a DCV may ultimately allow for individualized management of polyposis and cancer risk.Prevention Relevance: Juvenile Polyposis Syndrome (JPS) is a gastrointestinal cancer predisposition syndrome requiring lifelong surveillance, however there is limited data comparing individuals with and without a germline disease-causing variant in SMAD4 or BMPR1A Herein we show that individuals with JPS without an underlying disease-causing variant have distinct phenotypic differences including lack of upper gastrointestinal polyps and lower rates of a family history of JPS, suggesting that a different approach to management may be appropriate in this population.

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 2.2020.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening describe various colorectal screening modalities as well as recommended screening schedules for patients at average or increased risk of developing sporadic CRC. They are intended to aid physicians with clinical decision-making regarding CRC screening for patients without defined genetic syndromes. These NCCN Guidelines Insights focus on select recent updates to the NCCN Guidelines, including a section on primary and secondary CRC prevention, and provide context for the panel's recommendations regarding the age to initiate screening in average risk individuals and follow-up for low-risk adenomas.

Demographics and Epidemiology of Discoid Menisci of the Knee: Analysis of a Large Regional Insurance Database.

BACKGROUND: A discoid meniscus is a morphological variant of normal knee joint meniscus shape and ultrastructure that can lead to traumatic tearing of this tissue and early joint osteoarthritis. PURPOSE/HYPOTHESIS: The purpose of this study was to determine the prevalence of discoid menisci in a large, ethnically diverse regional cohort and to evaluate possible risk factors. The hypothesis was that there would be no difference in the epidemiological distribution of discoid menisci based on ethnicity or sex. STUDY DESIGN: Descriptive epidemiology study. METHODS: The study population was from a regional, integrated health care system cohort from Kaiser Permanente of Southern California that, as of 2016, included more than 4.5 million patients. Patient demographics included age, sex, and ethnicity within this cohort. Potential risk factors analyzed included age, sex, ethnicity, and body mass index (BMI). Unique characteristics of a discoid meniscus were analyzed, including a symptomatic versus asymptomatic meniscus, location of meniscal tear and type of meniscus, and frequency of meniscal surgical treatment. RESULTS: A total of 223 patients with a confirmed discoid meniscus were identified, yielding an overall prevalence rate of 4.88 per 100,000 patients. Those identifying as Black had the lowest prevalence (2.68/100,000), while Hispanic ethnicity had the highest (6.01/100,000). However, there was no significant difference with regard to ethnicity (P = .283), nor any significant difference between sexes. BMI did not significantly influence the rate of discoid menisci (P = .504). A majority (77.5%) of patients were symptomatic, while 22.5% of patients with discoid menisci were asymptomatic and discovered incidentally. Symptomatic discoid menisci were more likely to be operated on compared with asymptomatic discoid menisci (71% vs 14%, respectively; P = .001; odds ratio, 14.8 [95% CI, 5.8-37.2]). Horizontal and bucket-handle tears were the more common tear types. Of the discoid menisci in this cohort, 55.6% underwent surgery, with 95.2% undergoing reported saucerization. CONCLUSION: In this very diverse population-based cohort of patients, there did not seem to be a significant predilection of discoid menisci with regard to ethnicity. Neither sex nor BMI significantly influenced the rate of discoid menisci. More than three-quarters of those with a diagnosed discoid meniscus were symptomatic. Of the tears that occurred with discoid menisci, horizontal and bucket-handle tears made up the largest proportion.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis.

BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown. METHODS: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease. RESULTS: A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups. CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening.

BackgroundMultitarget stool DNA (mt-sDNA) screening has increased rapidly since simultaneous approval by the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services in 2014, whereas CT colonography screening remains underused and is not covered by Centers for Medicare and Medicaid Services.PurposeTo report postapproval clinical experience with mt-sDNA screening for colorectal cancer (CRC) and compare results with CT colonography screening at the same center.Materials and MethodsIn this retrospective cohort study, asymptomatic adults underwent clinical mt-sDNA screening during a 5-year interval (2014-2019). Electronic medical records were searched to verify test results and document subsequent optical colonoscopy and histopathologic findings. A similar analysis was performed for CT colonography screening during a 15-year interval (2004-2019), with consideration of thresholds for positivity of both 6-mm and 10-mm polyp sizes. χ2 or two-sample t tests were used for group comparisons.ResultsA total of 3987 asymptomatic adult patients (mean age, 64 years ± 9 [standard deviation]; 2567 women) underwent mt-sDNA screening and 9656 patients (mean age, 57 years ± 8; 5200 women) underwent CT colonography. Test-positive rates for mt-sDNA and for 6-mm- and 10-mm-threshold CT colonography were 15.2%, 16.4%, and 6.7%, respectively. Optical colonoscopy follow-up rates for positive results of mt-sDNA and 6-mm- and 10-mm-threshold CT colonography were 13.1%, 12.3%, and 5.9%, respectively. Positive predictive values (PPVs) for any neoplasm 6 mm or greater, advanced neoplasia, and CRC for mt-sDNA were 54.2%, 22.7%, and 1.9% respectively; for 6-mm-threshold CT colonography, PPVs were 76.8%, 44.3%, and 2.7%; for 10-mm-threshold CT colonography, PPVs were 84.5%, 75.2%, and 5.2%, respectively (P < .001 for mt-sDNA vs CT colonography for all except 6-mm CRC at CT colonography). For mt-sDNA versus 6-mm-threshold CT colonography, overall detection rates for advanced neoplasia were 2.7% and 5.0%, respectively (P < .001); corresponding detection rates for CRC were 0.23% and 0.31%, respectively (P = .43).ConclusionThe detection rates of advanced neoplasia at CT colonography screening were greater than those of multitarget stool DNA. Detection rates were similar for colorectal cancer.© RSNA, 2020See also the editorial by Yee in this issue.

Orthopaedic Systems Response to and Return from the COVID-19 Pandemic: Lessons for Future Crisis Management.

The coronavirus disease 2019 (COVID-19) pandemic has become the dominant health-care issue of this generation and has reached every corner of the health-care delivery spectrum. Our 3 orthopaedic departments enacted a response to the COVID-19 pandemic within our organizations. We discuss our health-care systems' response to the outbreak and offer discussion for the recovery of the orthopaedic service line within large health-care systems.

A Multi-Institutional Cohort of Therapy-Associated Polyposis in Childhood and Young Adulthood Cancer Survivors.

Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC: 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20-33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair-deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening.

Does the Proportion of Women in Orthopaedic Leadership Roles Reflect the Gender Composition of Specialty Societies?

BACKGROUND: Increasing the number of women in surgical subspecialties has been challenging, especially in orthopaedics, in which the percentage of women has remained relatively the same for the past several decades. Certain subspecialties, such as pediatric orthopaedics, have a greater proportion of women than other orthopaedic subspecialties do. Women in leadership roles in a specialty society (for example, on the board of directors) may serve as role models and help attract women to our specialty, leading to increased diversity. As the proportion of women in a specialty society increases, the leadership (board of directors) of the society might reflect the gender composition of that society's membership. It is not known whether gender diversity in orthopaedic societies is reflected in their leadership. QUESTION/PURPOSES: (1) Does the percentage of women members in a specialty society correlate with the percentage of women on its board of directors? (2) Does having a junior position on an orthopaedics subspecialty society's board of directors correlate with an increased percentage of women on its board of directors? METHODS: We queried the executive directors of each of the 23 societies of the Board of Specialty Societies of the American Academy of Orthopaedic Surgeons to obtain the number and percentage of women members in each society, the number of women on each society's board of directors, the criteria for becoming a board member, and the presence or absence of junior board members. All 23 societies responded. We supplemented the data by reviewing these societies' bylaws. Society bylaws were studied to determine if the presence of a junior board member affected the percentage of women on its board of directors. We correlated the percentage of women in each society with the percentage of women on that society's board of directors and compared this across the studied societies. RESULTS: We found a strong correlation between the percentage of women in a society and the percentage of women on the society's board of directors (r = .2333; p = .0495). The subspecialty society with the highest percentage of women (26%), the Pediatric Orthopaedic Society of North America, did not have the highest percentage of women on its board of directors (three of 20 members were women, 15%). The subspecialty society with the highest percentage of women on its board of directors, the Orthopaedic Research Society (seven of 16 members, 44%), did not have the highest percentage of women (25%). There was no correlation between presence of a junior board member and increased percentage of women in an orthopaedic society, nor was there a correlation between the presence of a junior board member and percentage of women on the board of directors in a society. CONCLUSIONS: There is a correlation between the number of women members in an orthopaedic specialty society and the number of women on its board of directors. The correlation is not explained by the presence of a junior member position, which may be inspiring to younger women. Although a correlation exists, we could not predictably match societies with the highest percentage of women members to those with the highest percentage of women on their boards of directors, and vice versa. This study reveals the current percentage of women in orthopaedic specialty societies and the percentage of women in leadership positions. This is the first step towards diversity of gender in orthopaedics. LEVEL OF EVIDENCE: Level III, prognostic study.

Chemoprevention of Colorectal Cancer.

Although colorectal cancer (CRC) screening has reduced the incidence of and mortality from CRC, chemoprevention strategies have the potential to further reduce CRC incidence and mortality. Chemoprevention agents might be used for average-risk as well as high-risk groups, and to prevent CRC recurrence after therapy. CRC chemoprevention agents that have been studied include aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, statins, agents that target metabolic pathways, and vitamins and minerals. We review the prospect of chemoprevention of CRC, results from preclinical and human studies, challenges, and future directions.