Publications by authors named "Ajaratu Keshinro"

6 Publications

  • Page 1 of 1

Advances in the treatment of locally advanced rectal cancer.

Ann Gastroenterol Surg 2021 Jan 30;5(1):32-38. Epub 2020 Aug 30.

Department of Surgery Memorial Sloan Kettering Cancer Center New York NY USA.

Locally advanced rectal cancer requires multidisciplinary care. In the United States, most patients are treated with neoadjuvant chemoradiation delivered over 25-28 days, total mesorectal excision, and 4 months of adjuvant chemotherapy. While effective, this trimodal approach is arduous. Alternative approaches have emerged to streamline treatment without sacrificing oncologic outcomes. These approaches include preoperative chemotherapy with selective use of radiation, short-course radiotherapy delivered over 5 days, and total neoadjuvant therapy with attempted nonoperative organ-preserving management (watch and wait). Ongoing trials are assessing the efficacies of these approaches in combination with various risk stratification strategies.
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January 2021

Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer.

J Clin Oncol 2021 Mar 13;39(8):911-919. Epub 2021 Jan 13.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer.

Methods: Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis.

Results: The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal.

Conclusion: This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.
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March 2021

Quantitative assessment of tumor-infiltrating lymphocytes in mismatch repair proficient colon cancer.

Oncoimmunology 2020 11 11;9(1):1841948. Epub 2020 Nov 11.

Departments of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Tumor infiltrating lymphocytes (TIL), which represent host adaptive response to the tumor, were first identified at scanning magnification to select areas with the highest counts on hematoxylin and eosin slides, quantitated per high-power field (HPF), and analyzed for association with recurrence-free survival (RFS) in 848 patients. Highest TIL in a single HPF was analyzed as a continuous and categorical variable, and optimal cutoff analysis was performed to predict RFS. Highest TIL count in a single HPF ranged from 0 to 45, and the optimal cutoff for TIL high vs TIL low was determined to be ≥ 3 vs < 3 with a concordance probability estimate of 0.74. In the entire cohort, 5-year RFS was 90.2% (95% CI = 83.7-94.2) in TIL high compared to 78.9% (95% CI = 74.1-82.9) in TIL low (log rank < .0001). TIL remained significant in the mismatch repair-proficient (pMMR) cohort where 5-year RFS was 94.6% (95% CI = 88.3-97.5) in TIL high compared to 77.9% (95% CI = 69.2-84.4) in TIL low ( = .008). On multivariable analysis, TIL and AJCC Stage were independently associated with RFS in the pMMR cohort. Qualitatively in the pMMR cohort, RFS in Stage II TIL high patients was similar to that in Stage I patients and RFS in Stage III TIL high was similar to that in Stage II TIL low patients. Assessment of TIL in a single HPF using standard H&E slides provides important prognostic information independent of MMR status and AJCC stage.
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November 2020

Underrepresented Minorities in Surgical Residencies: Where are They? A Call to Action to Increase the Pipeline.

Ann Surg 2020 09;272(3):512-520

Department of Surgery, New York University School of Medicine, New York, New York.

Objective: To describe and evaluate trends of general surgery residency applicants, matriculants, and graduates over the last 13 years.

Summary Of Background Data: The application and matriculation rates of URMs to medical school has remained unchanged over the last three decades with Blacks and Hispanics representing 7.1% and 6.3% of matriculants, respectively. With each succession along the surgical career pathway, from medical school to residency to a faculty position, the percentage of URMs decreases.

Methods: The Electronic Residency Application Service to General Surgery Residency and the Graduate Medical Education Survey of residents completing general surgery residency were retrospectively analyzed (2005-2018). Data were stratified by race, descriptive statistics were performed, and time series were charted.

Results: From 2005 to 2018, there were 71,687 Electronic Residency Application Service applicants to general surgery residencies, 26,237 first year matriculants, and 24,893 general surgery residency graduates. Whites followed by Asians represented the highest percentage of applicants (n = 31,197, 43.5% and n = 16,602, 23%), matriculants (n = 16,395, 62.5% and n = 4768, 18.2%), and graduates (n = 15,239, 61% and n = 4804, 19%). For URMs, the applicants (n = 8603, 12%, P < 0.00001), matriculants (n = 2420, 9.2%, P = 0.0158), and graduates (n = 2508, 10%, P = 0.906) remained significantly low and unchanged, respectively, whereas the attrition was significantly higher (3.6%, P = 0.049) when compared to Whites (2.6%) and Asians (2.9%).

Conclusion: Significant disparities in the application, matriculation, graduation, and attrition rates for general surgery residency exists for URMs. A call to action is needed to re-examine and improve existing recommendations/paradigms to increase the number of URMs in the surgery training pipeline.
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September 2020

Discordant DNA mismatch repair protein status between synchronous or metachronous gastrointestinal carcinomas: frequency, patterns, and molecular etiologies.

Fam Cancer 2020 Oct 9. Epub 2020 Oct 9.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

The widespread use of tumor DNA mismatch repair (MMR) protein immunohistochemistry in gastrointestinal tract (GIT) carcinomas has unveiled cases where the MMR protein status differs between synchronous/metachronous tumors from the same patients. This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated molecular abnormalities. The 10 patients consisted of 3 patients with Lynch syndrome (LS), 1 with polymerase proofreading-associated polyposis (PAPP), 1 with familial adenomatous polyposis (FAP), and 5 deemed to have no cancer disposing hereditary syndromes. Their MMR discordances were associated with the following etiologies: (1) PMS2-LS manifesting PMS2-deficient cancer at an old age when a co-incidental sporadic MMR-proficient cancer also occurred; (2) microsatellite instability-driven secondary somatic MSH6-inactivation occurring in only one-and not all-PMS2-LS associated MMR-deficient carcinomas; (3) "compound LS" with germline mutations in two MMR genes manifesting different tumors with deficiencies in different MMR proteins; (4) PAPP or FAP syndrome-associated MMR-proficient cancer co-occurring metachronously with a somatic MMR-deficient cancer; and (5) non-syndromic patients with sporadic MMR-proficient cancers co-occurring synchronously/metachronously with sporadic MMR-deficient cancers. Our study thus suggests that inter-tumoral MMR discordance is not uncommon among patients with multiple primary GIT carcinomas (25.9% in patients with ≥ 2 CRCs), and may be associated with widely varied molecular etiologies. Awareness of these patterns is essential in ensuring the most effective strategies in both LS detection and treatment decision-making. When selecting patients for immunotherapy, MMR testing should be performed on the tumor or tumors that are being treated.
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October 2020

The Impact of Primary Care Providers on Patient Screening Mammography and Initial Presentation in an Underserved Clinical Setting.

Ann Surg Oncol 2017 Mar 20;24(3):692-697. Epub 2016 Oct 20.

Department of Surgery, NYU Langone Medical Center, Bellevue Hospital Medical Center, New York, NY, USA.

Introduction: Cancer screening is a key component of primary care, and access to regular screening mammography (SMG) is highly dependent on recommendation and referral by a primary care provider (PCP). Women with no health insurance or who are underinsured often lack access to a regular PCP and thus access to routine screening.

Methods: We retrospectively reviewed the charts of 173 surgical patients diagnosed between January 2012 and December 2013. The main outcome variables were PCP status, method of cancer detection, and breast cancer stage at diagnosis. Additional variables included race, age at diagnosis, family history of breast and ovarian cancer, and medical comorbidities.

Results: Patients with a PCP received more mammograms (SMG) compared with patients without a PCP (61 vs. 37 %; p = 0.003). The majority (73 %) of patients without a PCP presented symptomatically with a palpable mass versus 42 % of patients with a PCP. A significant difference was noted with regard to final pathologic stage of breast cancer between the two groups (p = 0.019), and Caucasian and African American patients were more likely to have locally advanced breast cancer.

Conclusions: Underserved patients with a PCP are more likely to present asymptomatically and at an earlier stage of breast cancer compared with patients without a PCP. Community engagement programs that build relationships with patients may help bring vulnerable patients into the healthcare system for routine screening. Moreover, PCP education regarding the subtleties of breast cancer screening guidelines and referral to a breast specialist is also critical in improving outcomes of underserved patients.
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March 2017