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Post-Colonoscopy Colorectal Cancer in Fecal Immunochemical Test-Positive Individuals: Prevalence, Predictors, and Root-Cause Analysis in a Nationwide Cohort

Wilson, Natalie; Bilal, Mohammad; Westanmo, Anders; Karna, Rahul; Gravely, Amy; Shaukat, Aasma
OBJECTIVES/OBJECTIVE:Post-colonoscopy colorectal cancer (PCCRC) represents an important real-world colonoscopy quality indicator. Using a national database, we evaluated predictors of PCCRC in fecal immunochemical test (FIT)-positive individuals, determined the PCCRC 3-year rate (PCCRC-3y), and performed a root cause analysis (RCA). METHODS:This retrospective cohort study evaluated FIT-positive patients who underwent colonoscopy from January 2015 to July 2022. Data was collected from the Veterans Affairs (VA) national database. PCCRC was defined as CRC detected ≥6 months after colonoscopy. CRC was identified using SNOMED codes and the VA Cancer Registry. The World Endoscopy Organization methodology was used to perform the RCA and calculate the PCCRC-3y rate. RESULTS:We identified 132 PCCRCs among 52,167 FIT-positive individuals. The PCCRC-3y rate was 6.4% (95% CI, 5.0-7.7%). PCCRC locations were proximal colon (43.2%), distal colon (34.8%), and rectum (22%). Root causes were likely new CRC (17.4%), missed lesions with adequate (31.2%) or inadequate (9.8%) examination, incomplete polyp resection (22%), and detected but unresected lesions (19.7%). 16.7% of patients with PCCRC had poor bowel preparation on index colonoscopy. The cecal intubation rate was 88.6% and rectal retroflexion rate was 84.5%. In 14.4% of cases, recommended surveillance intervals did not adhere to established guidelines. Independent predictors of PCCRC were ages 70-79 (HR 7.86; 95% CI, 1.08-57.39), age ≥80 (HR 10.18; 95% CI, 1.06-97.98), tubulovillous adenoma (HR 3.98; 95% CI, 2.52-6.29), and adenoma with high-grade dysplasia (HR 10.15; 95% CI, 5.91-17.42). CONCLUSIONS:Among FIT-positive individuals, the PCCRC-3y rate was 6.4%, with missed lesions and incomplete resection as key contributors. These findings provide useful information on quality metrics in FIT-based CRC screening programs.
PMID: 40622402
ISSN: 1572-0241
CID: 5890422

How I Approach It: Stool Testing for Colon Cancer: Growing options

Shaukat, Aasma; Crockett, Seth
PMID: 40600971
ISSN: 1572-0241
CID: 5888002

Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer

Shaukat, Aasma; Burke, Carol A; Chan, Andrew T; Grady, William M; Gupta, Samir; Katona, Bryson W; Ladabaum, Uri; Liang, Peter S; Liu, Julia J; Putcha, Girish; Robertson, Douglas J; Schoen, Robert E; Meng, Zhen; Piscitello, Andrew; Sun, Chung-Kai; Xu, Chuanbo; Lin, C Jimmy; Lee, Lilian C; Baldo, Lance; Levin, Theodore R; ,
IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.
PMID: 40455622
ISSN: 1538-3598
CID: 5862132

Sarcopenia Is a Risk Factor for Postoperative Complications Among Older Adults With Inflammatory Bowel Disease

Minawala, Ria; Kim, Michelle; Delau, Olivia; Ghiasian, Ghoncheh; McKenney, Anna Sophia; Da Luz Moreira, Andre; Chodosh, Joshua; McAdams-DeMarco, Mara; Segev, Dorry L; Adhikari, Samrachana; Dodson, John; Shaukat, Aasma; Dane, Bari; Faye, Adam S
BACKGROUND:Sarcopenia has been associated with adverse postoperative outcomes in older age cohorts, but has not been assessed in older adults with inflammatory bowel disease (IBD). Further, current assessments of sarcopenia among all aged individuals with IBD have used various measures of muscle mass as well as cutoffs to define its presence, leading to heterogeneous findings. METHODS:In this single-institution, multihospital retrospective study, we identified all patients aged 60 years and older with IBD who underwent disease-related intestinal resection between 2012 and 2022. Skeletal Muscle Index (SMI) and Total Psoas Index (TPI) were measured at the superior L3 endplate on preoperative computed tomography scans and compared through receiver operating characteristic curve. We then performed multivariable logistic regression to assess risk factors associated with an adverse 30-day postoperative outcome. Our primary outcome included a 30-day composite of postoperative mortality and complications, including infection, bleeding, cardiac event, cerebrovascular accident, acute kidney injury, venous thromboembolism, reoperation, all-cause rehospitalization, and need for intensive care unit-level care. RESULTS:A total of 120 individuals were included. Overall, 52% were female, 40% had ulcerative colitis, 60% had Crohn's disease, and median age at time of surgery was 70 years (interquartile range: 65-75). Forty percent of older adults had an adverse 30-day postoperative outcome, including infection (23%), readmission (17%), acute kidney injury (13%), bleeding (13%), intensive care unit admission (10%), cardiac event (8%), venous thromboembolism (7%), reoperation (6%), mortality (5%), and cerebrovascular accident (2%). When evaluating the predictive performance of SMI vs TPI for an adverse 30-day postoperative event, SMI had a significantly higher area under the curve of 0.66 (95% CI, 0.56-0.76) as compared to 0.58 (95% CI, 0.48-0.69) for TPI (P = .02). On multivariable logistic regression, prior IBD-related surgery (adjusted odds ratio [adjOR] 6.46, 95% CI, 1.85-22.51) and preoperative sepsis (adjOR 5.74, 95% CI, 1.36-24.17) significantly increased the odds of adverse postoperative outcomes, whereas increasing SMI was associated with a decreased risk of an adverse postoperative outcome (adjOR 0.88, 95% CI, 0.82-0.94). CONCLUSIONS:Sarcopenia, as measured by SMI, is associated with an increased risk of postoperative complications among older adults with IBD. Measurement of SMI from preoperative imaging can help risk stratify older adults with IBD undergoing intestinal resection.
PMID: 39177976
ISSN: 1536-4844
CID: 5681162

Current Perspectives on Colorectal Cancer Screening and Surveillance in the Geriatric Population

Udaikumar, Jahnavi; Nimmagadda, Rithish; Ingawale, Sushrut; Lella, Vindhya Vasini; Vijayakumar, Keerthika; Faye, Adam S; Shaukat, Aasma
PURPOSE OF REVIEW/OBJECTIVE:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with 44% of deaths occurring in individuals aged 75 years and older. With 78 million adults over 65 years projected by 2035, optimizing CRC screening and surveillance is crucial. This review examines guidelines, risks, and personalized approaches. RECENT FINDINGS/RESULTS:CRC screening reduces incidence by 17-33% and mortality by 11-53%. Colonoscopy lowers mortality by 61% but has a 6.8% complication rate in those aged 75 years and older. The risk of gastrointestinal bleeding is 8.7 per 1,000 for polypectomy, and perforation occurs in 0.6 per 1,000. Frailty indices assess suitability, but surveillance guidelines lack clear discontinuation criteria. Screening should balance risk, complications, and health status. It may be cost-effective up to age 86 years in healthy individuals, but more research is needed to refine surveillance strategies and reduce overtreatment in older adults.
PMID: 40455318
ISSN: 1534-312x
CID: 5862092

AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary

Shaukat, Aasma; Ladabaum, Uri; Kanth, Priyanka; Lieberman, David
Description Colorectal cancer (CRC) is a leading cause of morbidity and cancer-related mortality in the US. Despite multiple screening options, adherence to CRC screening in the US remains suboptimal and there are racial, ethnic and geographic disparities in CRC screening rates and outcomes. Advances in diagnostic technology have allowed for development and validation of blood tests for CRC screening. In this clinical practice update, our aims were to review the current evidence on blood tests, and the potential implications for CRC screening. We leveraged published modelling studies to understand the optimal test performance characteristics, interval, and uptake that would be needed for blood tests to achieve comparable effectiveness to that of currently available stool tests and screening colonoscopy.
PMID: 40267995
ISSN: 1542-7714
CID: 5830332

Clin-STAR Corner: Practice-Changing Advances at the Interface of Gastroenterology & Geriatrics

Faye, Adam S; Kochar, Bharati; Shaukat, Aasma
With nearly 60 million Americans aged 65 and older, gastrointestinal (GI) conditions are a leading cause of healthcare utilization in this population. Despite this, older adults remain underrepresented in GI clinical trials and research, limiting evidence-based care. This review highlights three pivotal studies addressing this gap: (1) proton pump inhibitors, which are commonly used to treat gastroesophageal reflux disease, are not associated with the later development of dementia; (2) undertreatment of chronic inflammation among older adults with inflammatory bowel disease is associated with a higher rate of adverse events compared to treatment with anti-TNF therapy, a biologic agent; (3) the majority (85%) of surveillance colonoscopies among older adults with a life expectancy of ≥ 10 years did not yield colorectal cancer, advanced dysplasia, or ≥ 3 polyps.
PMID: 40202331
ISSN: 1532-5415
CID: 5823852

Severe Polypharmacy Increases Risk of Hospitalization Among Older Adults with IBD

Drittel, Darren; Schreiber-Stainthorp, William; Delau, Olivia; Gurunathan, Sakteesh V; Chodosh, Joshua; Segev, Dorry L; McAdams-DeMarco, Mara; Katz, Seymour; Dodson, John; Shaukat, Aasma; Faye, Adam S
BACKGROUND:As the inflammatory bowel disease (IBD) patient population is aging, the prevalence of polypharmacy is rising. However, data exploring the prevalence, risk factors, and clinical outcomes associated with polypharmacy among older adults with IBD are limited. AIMS/OBJECTIVE:To determine (i) prevalence of polypharmacy (≥5 medications) and potentially inappropriate medication (PIM) utilization in older adults with IBD, (ii) changes in medications over time (iii) predictors of polypharmacy, and (iv) the impact of polypharmacy/PIMs on one-year hospitalization rates. METHODS:We conducted a retrospective single-center study of older adults with IBD from September 1st 2011 to December 31st 2022. Wilcoxon-signed rank and McNemar's tests were used to assess changes in polypharmacy between visits, with ordinal logistic regression and Cox proportional hazards models used to determine risk factors for polypharmacy and time to hospitalization, respectively. RESULTS:Among 512 older adults with IBD, 74.0% experienced polypharmacy at initial visit, with 42.6% receiving at least one PIM. Additionally, severe polypharmacy (≥10 medications) was present among 28.6% individuals at index visit and increased to 38.6% by last visit (p<0.01). Multivariable analysis revealed that age ≥70 years, BMI ≥30.0 kg/m2, prior IBD-related surgery, and the presence of comorbidities were associated with polypharmacy. Moreover, severe polypharmacy (adjHR 1.95, 95%CI 1.29-2.92), as well as PIM use (adjHR 2.16, 95%CI 1.37-3.43) among those with polypharmacy, were significantly associated with all-cause hospitalization within a year of index visit. DISCUSSION/CONCLUSIONS:Severe polypharmacy was initially present in more than 25% of older adults with IBD and increased to 34% within 4 years of index visit. Severe polypharmacy, as well as PIM utilization among those with polypharmacy, were also associated with an increased risk of hospitalization at one-year, highlighting the need for deprescribing efforts in this population.
PMID: 39162710
ISSN: 1572-0241
CID: 5680582

Fact or Myth? Black Patients Do Not Want to Participate in Clinical Trials

Mills, Krystal; Figueroa, Francisco; Knight, RaKetra; Ekpo, Emem; Lee, Lilian C; Baldo, Lance; Xu, Chuanbo; Wang, Siqi; Adelman, Robert M; Pemu, Priscilla; Levin, Theodore; Shaukat, Aasma; Liu, Julia J
OBJECTIVES/OBJECTIVE:To assess strategies for optimizing participation of underserved minorities in a blood-based early CRC detection test study (PREEMPT CRC; NCT04369053) at a hospital serving primarily Black patients. METHODS:Culturally sensitive, racially congruent research staff approached patients undergoing average-risk screening colonoscopy. Consent/study procedures were synchronized with clinical appointments. Enrolled and not-enrolled patient characteristics were compared. Recruitment was compared with other study sites. RESULTS:247/509 eligible participants enrolled; most identified as Black (88.7%). No baseline characteristics were associated with participation. Recruitment was high compared to other sites (11th centile). CONCLUSIONS:Recruitment barriers for Black individuals can be overcome when easy, culturally sensitive access is facilitated.
PMID: 39878425
ISSN: 2155-384x
CID: 5780892

Optimizing Bowel Preparation Quality for Colonoscopy: Consensus Recommendations by the US Multi-Society Task Force on Colorectal Cancer

Jacobson, Brian C; Anderson, Joseph C; Burke, Carol A; Dominitz, Jason A; Gross, Seth A; May, Folasade P; Patel, Swati G; Shaukat, Aasma; Robertson, Douglas J
This document is an update to the 2014 recommendations for optimizing the adequacy of bowel cleansing for colonoscopy from the US Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. The US Multi-Society Task Force developed consensus statements and key clinical concepts addressing important aspects of bowel preparation for colonoscopy. The majority of consensus statements focus on individuals at average risk for inadequate bowel preparation. However, statements addressing individuals at risk for inadequate bowel preparation quality are also provided. The quality of a bowel preparation is defined as adequate when standard screening or surveillance intervals can be assigned based on the findings of the colonoscopy. We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient. A same-day regimen is recommended as an acceptable alternative for individuals undergoing afternoon colonoscopy, but we suggest that a same-day regimen is an inferior alternative for individuals undergoing morning colonoscopy. We recommend limiting dietary restrictions to the day before a colonoscopy, relying on either clear liquids or low-fiber/low-residue diets for the early and midday meals. We suggest the adjunctive use of oral simethicone for bowel preparation before colonoscopy. Routine tracking of the rate of adequate bowel preparations at the level of individual endoscopists and at the level of the endoscopy unit is also recommended, with a target of >90% for both rates.
PMID: 40035345
ISSN: 1572-0241
CID: 5818562