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A comprehensive framework for early-onset colorectal cancer research
Sporadic colorectal cancer has traditionally been viewed as a malignancy of older individuals. However, as the global prevalence of the disease diagnosed in younger individuals (<50 years) is expected to increase within the next decade, greater recognition is now being given to early-onset colorectal cancer. The cause of the predicted rise in prevalence is largely unknown and probably multifactorial. In this Series paper, we discuss the potential underlying causes of early-onset colorectal cancer, the role of energy balance, biological and genomic mechanisms (including microbiome aspects), and the treatment of early-onset colorectal cancer. We have specifically considered the psychosocial challenges of being diagnosed with colorectal cancer at younger age and the potential financial toxicity that might ensue. This Series paper brings a comprehensive review based on the existing data in the hopes of optimising the overall outcomes for patients with early-onset colorectal cancer.
Journal Article
Sidedness of Colorectal Cancer Impacts Risk of Second Primary Gastrointestinal Malignancy
Introduction
A history of colorectal cancer (CRC) increases the risk of subsequent gastrointestinal (GI) cancer. Cancers of the right colon, left colon, and rectum differ according to molecular profiles, responses to treatment, and outcomes.
Objective
The purpose of this study was to determine if CRC location is associated with differential risk for secondary primary GI malignancy.
Methods
A retrospective cohort of adults with CRC was compiled using the Surveillance, Epidemiology, and End Results database (1973–2015). Standardized incidence ratios (SIRs) for second primary GI malignancies were compared based on location of the index CRC (right colon, left colon, or rectum).
Results
The cohort included 281,413 adults with CRC (30.3% right, 35.3% left, 34.3% rectum). With a median 4.9-year follow-up, 12,064 (4.3%) patients developed a second primary GI malignancy (64% CRC, 36% non-CRC). Those with CRC at any location had higher than expected incidences of small intestine, bile duct, and other CRCs, and lower incidences of liver and gallbladder cancer. The SIR for small intestinal cancer was higher after right colon cancer than after left colon or rectal cancer. The esophageal cancer SIR was higher after left colon cancer. Pancreas cancer was higher than expected for right colon cancer, but lower for left colon and rectal cancer.
Conclusion
The location of CRC leads to differences in the incidence and location of second primary GI malignancies and may be related to similarities in the associated carcinogenesis and molecular pathways or response to treatment. CRC location not only impacts treatment response and outcomes, but should also be considered during subsequent surveillance.
Journal Article
Primary Tumor Resection Offers Survival Benefit in Patients with Metastatic Midgut Neuroendocrine Tumors
BackgroundApproximately 35% of patients with midgut neuroendocrine tumors (MNET) present with distant metastases. Although successful resection of these metastatic foci improves overall survival (OS), the role of primary tumor resection (PTR) in patients with unresectable metastatic disease is unclear. The aim of this study is to evaluate prevalence and survival impact of PTR in patients with unresectable metastatic MNET.Patients and MethodsA retrospective cohort study of patients with metastatic MNET was performed using the National Cancer Database (2004–2014). Demographic and clinicopathologic variables were compared between patients who did and did not undergo PTR. Survival analysis was performed using Kaplan–Meier and log-rank tests. Multivariable regression analysis was used to assess factors associated with PTR and all-cause mortality.ResultsThe cohort included 4076 patients; 2520 (61.8%) underwent PTR. Patients more likely to undergo PTR were younger and diagnosed earlier, underwent treatment at a nonacademic facility, lived on the West Coast or in the Central USA, and presented with smaller lower-grade small bowel primary tumors. Median OS was improved for patients who underwent PTR compared with those who did not (71 vs. 29 months, p < 0.001). On multivariable analysis, younger age, Black race, higher income, later year of diagnosis, treatment at an academic facility, private insurance, fewer comorbidities, small bowel primary, lower grade, and PTR (hazard ratio 0.63, 95% confidence interval 0.51–0.78, p < 0.001) were associated with lower mortality.ConclusionsPTR was associated with improved OS. Further study is needed to understand how clinicians select patients for PTR.
Journal Article
Impact of Insurance Status on Oncologic and Perioperative Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy
BackgroundA growing body of research has shown that underinsured patients are at increased risk of worse health outcomes compared with insured patients. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is largely performed at highly specialized cancer centers and may pose challenges for the underinsured. This study investigates surgical outcomes following CRS-HIPEC for insured and underinsured patients with peritoneal carcinomatosis.MethodsWe performed a retrospective cohort study of 125 patients undergoing CRS-HIPEC between 2013 and 2019. Patients were categorized into two groups. The insured group was comprised of patients with private insurance at the time of CRS-HIPEC or who obtained it during the follow-up period. The underinsured group consisted of patients with Medicaid, or self-pay. Perioperative and oncologic outcomes were compared between the two groups.ResultsA total of 102 (82.3%) patients were insured, and 22 (17.7%) patients were underinsured. There were no significant differences in age, medical morbidities, primary tumor characteristics, peritoneal carcinomatosis index, or completion of cytoreduction score between the two groups. The median overall survival (OS) for insured patients was 64.8 months and was 52.9 months for underinsured patients (p = 0.01). Additionally, insured patients had a significantly longer follow-up time. Underinsurance status also was associated with increased hospital and intensive care unit length of stay, and higher rate of Clavien–Dindo classification III–IV complications.ConclusionsIn this retrospective study conducted at a large, urban, specialized cancer center, private insurance status was associated with increased overall survival and longer follow-up period. Furthermore, underinsurance status was associated with increased perioperative morbidity.
Journal Article
Undifferentiated Embryonal Sarcoma of the Liver in Children Versus Adults: A National Cancer Database Analysis
This study evaluates the clinicopathological characteristics and outcomes of children vs. adults with undifferentiated embryonal sarcoma of the liver (UESL). A retrospective analysis of 82 children (<18 years) and 41 adults (≥18 years) with UESL registered in the National Cancer Database between 2004–2015 was conducted. No between-group differences were observed regarding tumor size, metastasis, surgical treatment, margin status, and radiation. Children received chemotherapy more often than adults (92.7% vs. 65.9%; p < 0.001). Children demonstrated superior overall survival vs. adults (log-rank, p < 0.001) with 5-year rates of 84.4% vs. 48.2%, respectively. In multivariable Cox regression for all patients, adults demonstrated an increased risk of mortality compared to children (p < 0.001), while metastasis was associated with an increased (p = 0.02) and surgical treatment with a decreased (p = 0.001) risk of mortality. In multivariable Cox regression for surgically-treated patients, adulthood (p = 0.004) and margin-positive resection (p = 0.03) were independently associated with an increased risk of mortality. Multimodal treatment including complete surgical resection and chemotherapy results in long-term survival in most children with UESL. However, adults with UESL have poorer long-term survival that may reflect differences in disease biology and an opportunity to further refine currently available treatment schemas.
Journal Article
Radiographic Tumor–Vein Interface as a Predictor of Intraoperative, Pathologic, and Oncologic Outcomes in Resectable and Borderline Resectable Pancreatic Cancer
Background
Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric–portal vein (SMV-PV) resection and the presence of histologic vein invasion.
Methods
All patients who underwent pancreaticoduodenectomy from 2004 to 2011 at the authors’ institution were identified. Preoperative pancreatic protocol CT images were re-reviewed to characterize the extent of tumor–vein circumferential interface (TVI) as demonstrating no interface, ≤180° of vessel circumference, >180° of vessel circumference, or occlusion. Findings were correlated with the need for venous resection, histologic venous invasion, and survival.
Results
A total of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98 (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received neoadjuvant chemoradiation. The TVI classification system predicted with fair accuracy both the need for SMV-PV resection at the time of surgery and histologic invasion of the vein. In particular, 89.5 % of patients with TVI >180° or occlusion required SMV-PV resection. Of those, 82.4 % had documented histologic SMV-PV invasion. TVI ≤180° was associated with favorable overall survival compared to a greater circumferential interface.
Conclusions
A tomographic classification of the tumor–SMV-PV interface can predict the need for venous resection, pathologic venous involvement, and survival. To assist in treatment planning, a standardized assessment of this anatomic relationship should be routinely performed.
Journal Article
Racial/Ethnic Disparities in Mortality Related to Access to Care for Major Cancers in the United States
Importance: The reasons underlying racial/ethnic mortality disparities for cancer patients remain poorly understood, especially regarding the role of access to care. Participants: Over five million patients with a primary diagnosis of lung, breast, prostate, colon/rectum, pancreas, ovary, or liver cancer during 2004–2014, were identified from the National Cancer Database. Cox proportional hazards models were applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for total mortality associated with race/ethnicity, and access to care related factors (i.e., socioeconomic status [SES], insurance, treating facility, and residential type) for each cancer. Results: Racial/ethnic disparities in total mortality were observed across seven cancers. Compared with non-Hispanic (NH)-white patients, NH-black patients with breast (HR = 1.27, 95% CI: 1.26 to 1.29), ovarian (HR = 1.20, 95% CI: 1.17 to 1.23), prostate (HR = 1.31, 95% CI: 1.30 to 1.33), colorectal (HR = 1.11, 95% CI: 1.10 to 1.12) or pancreatic (HR = 1.03, 95% CI: 1.02 to 1.05) cancers had significantly elevated mortality, while Asians (13–31%) and Hispanics (13–19%) had lower mortality for all cancers. Racial/ethnic disparities were observed across all strata of access to care related factors and modified by those factors. NH-black and NH-white disparities were most evident among patients with high SES or those with private insurance, while Hispanic/Asian versus NH-white disparities were more evident among patients with low SES or those with no/poor insurance. Conclusions and Relevance: Racial/ethnic mortality disparities for major cancers exist across all patient groups with different access to care levels. The influence of SES or insurance on mortality disparity follows different patterns for racial/ethnic minorities versus NH-whites. Impact: Our study highlights the need for racial/ethnic-specific strategies to reduce the mortality disparities for major cancers.
Journal Article