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329 result(s) for "Hawkins, Alexander T."
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Impact of Postoperative Complications on Oncologic Outcomes After Rectal Cancer Surgery: An Analysis of the US Rectal Cancer Consortium
BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not well studied.MethodsThe United States Rectal Cancer Consortium (2007–2017) was reviewed for primary rectal adenocarcinoma patients who underwent R0/R1 resection. Ninety-day POCs were categorized as major or minor and were grouped into infectious, cardiopulmonary, thromboembolic, renal, or intestinal dysmotility. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsAmong 1136 patients, the POC rate was 46% (n = 527), with 63% classified as minor and 32% classified as major. Of all POCs, infectious complications comprised 20%, cardiopulmonary 3%, thromboembolic 5%, renal 9%, and intestinal dysmotility 19%. Compared with minor or no POCs, major POCs were associated with both worse RFS and worse OS (both p < 0.01). Compared with no POCs, a single POC was associated with worse RFS (p < 0.01), while multiple POCs were associated with worse OS (p = 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (p < 0.01), while cardiopulmonary and thromboembolic POCs were associated with worse OS (both p < 0.01). Renal POCs were associated with both worse RFS (p < 0.001) and worse OS (p = 0.01). After accounting for pathologic stage, neoadjuvant therapy, and final margin status, Multivariable analysis (MVA) demonstrated worse outcomes with cardiopulmonary, thromboembolic, and renal POCs for OS (cardiopulmonary: hazard ratio [HR] 3.6, p = 0.01; thromboembolic: HR 19.4, p < 0.01; renal: HR 2.4, p = 0.01), and renal and infectious POCs for RFS (infectious: HR 2.1, p < 0.01; renal: HR 3.2, p < 0.01).ConclusionsMajor complications after proctectomy for cancer are associated with decreased RFS and OS. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.
Novel polygenic risk score associates with diverticulitis in a multi-institutional, ancestrally diverse cohort
Diverticulitis is a common and morbid colorectal disease that recurs after an initial attack in up to 30% of patients. Elective surgery to remove the affected portion of the colon is an effective intervention to prevent disease recurrence, but appropriate patient selection is challenging given the limited ability to predict which patients are likely to recur, or the severity with which they may do so. Genetics influence diverticulitis and can be used for risk stratification, but this has only been studied in European ancestry populations. Using state-of-the-art techniques, we created a polygenic risk score that associates with diverticulitis prevalence and severity and is externally validated on meta-analysis in a diverse patient population across three different biobanks. This work represents the first published diverticulitis polygenic score to demonstrate utility in associating specifically with diverticulitis in non-European populations, and may provide the basis for clinical implementation in elective surgical decision-making.
Preoperative Chemotherapy and Survival for Large Anorectal Gastrointestinal Stromal Tumors: A National Analysis of 333 Cases
Purpose Anorectal gastrointestinal stromal tumors (GISTs) are exceedingly rare, and management remains controversial in regard to local resection (LR) and preoperative chemotherapy. Methods The National Cancer Data Base was queried from 1998 to 2012 for cases of GIST resection in the rectum or anus. Patient demographics, type of surgery (LR vs. radical excision [RE]), short-term outcomes, and overall survival (OS) were analyzed. Preoperative chemotherapy was recorded following the US FDA approval of imatinib in 2002. Results Overall, 333 patients with resection of anorectal GISTs were included. Mean age at presentation was 62.3 years (range 22–90), and median tumor size was 4.0 cm (interquartile range 2.2–7.0). Five-year OS for all patients was 77.6%. In a multivariable survival analysis, only age and tumor size >5 cm (hazard ratio 2.48, 95% confidence interval 1.50–4.01; p  = 0.004) were associated with increased mortality. One hundred and sixty-three (49.0%) patients underwent LR, compared with 158 (47.4%) who underwent RE. For tumors smaller than 5 cm, no difference in 5-year survival by surgical approach was observed (LR 82.3% vs. RE 82.6%; p  = 0.71). Fifty-nine patients (17.7%) received preoperative chemotherapy; for patients undergoing RE with tumors >5 cm, there was decreased mortality in the group who received preoperative chemotherapy (5-year OS with chemotherapy 79.2% vs. no chemotherapy 51.2%; p  = 0.03). Conclusions Size is the most important determinant in survival following resection. Local excision is common, with resection split between LR and RE. For smaller tumors, LR may be adequate therapy. Preoperative chemotherapy may result in improved survival for large tumors treated with radical resection, but the data are imperfect.
Decision Aid for Colectomy in Recurrent Diverticulitis: Development and Usability Study
Diverticular disease is a common gastrointestinal diagnosis with over 2.7 million clinic visits yearly. National guidelines from the American Society of Colon and Rectal Surgeons state that \"the decision to recommend elective sigmoid colectomy after recovery from uncomplicated acute diverticulitis should be individualized.\" However, tools to individualize this decision are lacking. This study aimed to develop an online educational decision aid (DA) to facilitate effective surgeon and patient communication about treatment options for recurrent left-sided diverticulitis. We used a modified design sprint methodology to create a prototype DA. We engaged a multidisciplinary team and adapted elements from the Ottawa Personal Decision Guide. We then iteratively refined the prototype by conducting a mixed methods assessment of content and usability testing, involving cognitive interviews with patients and surgeons. The findings informed the refinement of the DA. Further testing included an in-clinic feasibility review. Over a 4-day in-person rapid design sprint, including patients, surgeons, and health communication experts, we developed a prototype of a diverticulitis DA, comprising an interactive website and handout with 3 discrete sections. The first section contains education about diverticulitis and treatment options. The second section clarifies the potential risks and benefits of both clinical treatment options (medical management vs colectomy). The third section invites patients to participate in a value clarification exercise. After navigating the DA, the patient prints a synopsis that they bring to their clinic appointment, which serves as a guide for shared decision-making. Design sprint methodology, emphasizing stakeholder co-design and complemented by extensive user testing, is an effective and efficient strategy to create a DA for patients living with recurrent diverticulitis facing critical treatment decisions.
A randomized trial of a specialist palliative care intervention for patients undergoing surgery for cancer: rationale and design of the Surgery for Cancer with Option of Palliative Care Expert (SCOPE) Trial
Background In medical oncology settings, early specialist palliative care interventions have demonstrated improvements in patient quality of life and survival compared with usual oncologic care. However, the effect of early specialist palliative care interventions in surgical oncology settings is not well studied. Methods The Surgery for Cancer with Option for Palliative Care Expert (SCOPE) Trial is a single-center, prospective, single-blind, randomized controlled trial of a specialist palliative care intervention for cancer patients undergoing non-palliative surgery. It will enroll 236 patients scheduled for major abdominal operations for malignancy, who will be randomized 1:1 at enrollment to receive usual care (control arm) or specialist palliative care consultation (intervention arm). Intervention arm patients will receive consultations from a palliative care specialist (physician or nurse practitioner) preoperatively and postoperatively. The primary outcome is physical and functional wellbeing at 90 days postoperatively. Secondary outcomes are quality of life at 90 days postoperatively, posttraumatic stress disorder symptoms at 180 days postoperatively, days alive at home without an emergency room visit in the first 90 postoperative days, and overall survival at 1 year postoperatively. Participants will be followed for 3 years after surgery for exploratory analyses of their ongoing quality of life, healthcare utilization, and mortality. Discussion SCOPE is an ongoing randomized controlled trial evaluating specialist palliative care interventions for cancer patients undergoing non-palliative oncologic surgery. Findings from the study will inform ways to identify and improve care of surgical patients who will likely benefit from specialist palliative care services. Trial registration ClinicalTrials.gov Identifier: NCT03436290 First Registered: 16 February 2018 Enrollment Began: 1 March 2018 Last Update: 20 December 2018
Multiancestry transferability of a polygenic risk score for diverticulitis
ObjectivePolygenic risk scores (PRS) for diverticular disease must be evaluated in diverse cohorts. We sought to explore shared genetic predisposition across the phenome and to assess risk stratification in individuals genetically similar to European, African and Admixed-American reference samples.MethodsA 44-variant PRS was applied to the All of Us Research Program. Phenome-wide association studies (PheWAS) identified conditions linked with heightened genetic susceptibility to diverticular disease. To evaluate the PRS in risk stratification, logistic regression models for symptomatic and for severe diverticulitis were compared with base models with covariates of age, sex, body mass index, smoking and principal components. Performance was assessed using area under the receiver operating characteristic curves (AUROC) and Nagelkerke’s R2.ResultsThe cohort comprised 181 719 individuals for PheWAS and 50 037 for risk modelling. PheWAS identified associations with diverticular disease, connective tissue disease and hernias. Across ancestry groups, one SD PRS increase was consistently associated with greater odds of severe (range of ORs (95% CI) 1.60 (1.27 to 2.02) to 1.86 (1.42 to 2.42)) and of symptomatic diverticulitis ((95% CI) 1.27 (1.10 to 1.46) to 1.66 (1.55 to 1.79)) relative to controls. European models achieved the highest AUROC and Nagelkerke’s R2 (AUROC (95% CI) 0.78 (0.75 to 0.81); R2 0.25). The PRS provided a maximum R2 increase of 0.034 and modest AUROC improvement.ConclusionAssociations between a diverticular disease PRS and severe presentations persisted in diverse cohorts when controlling for known risk factors. Relative improvements in model performance were observed, but absolute change magnitudes were modest.
Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients
Background The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. Methods We identified 6708 young adults aged 18–45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan–Meier estimation, log rank test, and multivariate Cox proportional hazards model. Results Sixty‐three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31–0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43–0.49, p < 0.001 and HR 0.64, 95% CI: 0.55–0.76, p < 0.001, respectively). Conclusion This is the largest observational study to evaluate survival outcomes in young‐onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site. The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) vs palliative therapy in this patient population. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.
270 Development of a Predictive Nomogram for Circumferential Resection Margin in Rectal Cancer Surgery
OBJECTIVES/GOALS: A negative circumferential resection margin (CRM) after surgical resection of rectal cancer decreases local recurrence and increases overall survival. While MRI is used to predict this risk, there is no predictive model that incorporates clinical factors to predict the risk of CRM positivity. METHODS/STUDY POPULATION: Utilizing the National Cancer Database from 2010-2014, we performed a retrospective study evaluating factors predictive for positive CRM after surgical resection of rectal cancer. The primary outcome was positive CRM (tumor≤1 mm from the surgical margin). Our population included patients with clinical stage I-III rectal cancer who underwent total mesorectal excision. For the primary outcome, multivariable logistic models were used to estimate the probability of a positive CRM. Model performance was evaluated by using the area under the receiver operating characteristic curve (AUC). Model calibration was assessed by examining the calibration plot. Bootstrapping method (300-iteration) was used to internally validate and estimate optimism-adjusted measures of discrimination and overall model fit. RESULTS/ANTICIPATED RESULTS: There were 28,790 patients included. 2,245 (7.8%) had positive CRM. Older age, race, larger tumor size, higher tumor grade, mucinous and signet tumor histology, APR, open operative approach, facility location, higher T stage, lymphovascular invasion, lack of neoadjuvant chemotherapy/radiation, and perineural invasion were all significantly associated with positive CRM (p DISCUSSION/SIGNIFICANCE: An objective model that predicts positive CRM and associated poor clinical outcomes is possible to be used in conjunction with MRI. Positive CRM is associated with specific patient demographics, tumor characteristics, and operative approach. These factors can be used to predict CRM positivity in the preoperative period and plan accordingly.
Abdominoperineal Resection for Rectal Cancer in the Twenty-First Century: Indications, Techniques, and Outcomes
Background Management of low rectal cancer continues to be a challenge, and decision making regarding the need for an abdominoperineal resection (APR) in patients with low-lying tumors is complicated. Furthermore, choices need to be made regarding need for modification of the surgical approach based on tumor anatomy and patient goals. Discussion In this article, we address patient selection, preoperative planning, and intraoperative technique required to perform the three types of abdominoperineal resections for rectal cancer: extrasphincteric, extralevator, and intersphincteric. Attention is paid not only to traditional oncologic outcomes such as recurrence and survival but also to patient-reported outcomes and quality of life.