Time Kills: Impact of Socioeconomic Deprivation on Timely Access to Guideline-Concordant Treatment in Foregut Cancer.

BACKGROUND: Receipt of guideline-concordant treatment (GCT) is associated with improved prognosis in foregut cancers. Studies show that patients living in areas of high neighborhood deprivation have worse healthcare outcomes; however, its effect on GCT in foregut cancers has not been evaluated. We studied the impact of the area deprivation index (ADI) as a barrier to GCT. STUDY DESIGN: A single-institution retrospective review of 498 foregut cancer patients (gastric, pancreatic, and hepatobiliary adenocarcinoma) from 2018 to 2022 was performed. GCT was defined based on National Comprehensive Cancer Network guidelines. ADI, a validated measure of neighborhood disadvantage was divided into terciles (low, medium, and high) with high ADI indicating the most disadvantage. RESULTS: Of 498 patients, 328 (66%) received GCT: 66%, 72%, and 59% in pancreatic, gastric, and hepatobiliary cancers, respectively. Median (interquartile range) time from symptoms to workup was 6 (3 to 13) weeks, from diagnosis to oncology appointment was 4 (1 to 10) weeks, and from oncology appointment to treatment was 4 (2 to 10) weeks. Forty-six percent were diagnosed in the emergency department. On multivariable analyses, age 75 years or older (odds ratio [OR] 0.39 [95% CI 0.18 to 0.87]), Black race (OR 0.52 [95% CI 0.31 to 0.86]), high ADI (OR 0.25 (95% CI 0.14 to 0.48]), 6 weeks or more from symptoms to workup (OR 0.44 [95% CI 0.27 to 0.73]), 4 weeks or more from diagnosis to oncology appointment (OR 0.76 [95% CI 0.46 to 0.93]), and 4 weeks or more from oncology appointment to treatment (OR 0.63 [95% CI 0.36 to 0.98]) were independently associated with nonreceipt of GCT. CONCLUSIONS: Residence in an area of high deprivation predicts nonreceipt of GCT. This is due to multiple individual- and system-level barriers. Identifying these barriers and developing effective interventions, including community outreach and collaboration, leveraging telehealth, and increasing oncologic expertise in underserved areas, may improve access to GCT.

Association between Rural Residence and Processes of Care in Pancreatic Cancer Treatment.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is an aggressive malignancy associated with poor outcomes. Surgical resection and receipt of multimodal therapy have been shown to improve outcomes in patients with potentially resectable PDAC; however treatment and outcome disparities persist on many fronts. The aim of this study was to analyze the relationship between rural residence and receipt of quality cancer care in patients diagnosed with non-metastatic PDAC. METHODS: Using the National Cancer Database, patients with non-metastatic pancreatic cancer were identified from 2006-2016. Patients were classified as living in metropolitan, urban, or rural areas. Multivariable logistic regression was used to identify predictors of cancer treatment and survival. RESULTS: A total of 41,786 patients were identified: 81.6% metropolitan, 16.2% urban, and 2.2% rural. Rural residing patients were less likely to receive curative-intent surgery (p = 0.037) and multimodal therapy (p < 0.001) compared to their metropolitan and urban counterparts. On logistic regression analysis, rural residence was independently associated with decreased surgical resection [OR 0.82; CI 95% 0.69-0.99; p = 0.039] and multimodal therapy [OR 0.70; CI 95% 0.38-0.97; p = 0.047]. Rural residence independently predicted decreased overall survival [OR 1.64; CI 95% 1.45-1.93; p < 0.001] for all patients that were analyzed. In the cohort of patients who underwent surgical resection, rural residence did not independently predict overall survival [OR 0.97; CI 95% 0.85-1.11; p = 0.652]. CONCLUSIONS: Rural residence impacts receipt of optimal cancer care in patients with non-metastatic PDAC but does not predict overall survival in patients who receive curative-intent treatment.

Palliative Therapies in Metastatic Pancreatic Cancer: Does Medicaid Expansion Make a Difference?

BACKGROUND: The aim of this study was to evaluate the impact of medicaid expansion (ME) on receipt of palliative therapies in metastatic pancreatic cancer patients. PATIENTS AND METHODS: A difference-in-differences (DID) approach was used to analyze patients with metastatic pancreatic cancer identified from the National Cancer Database diagnosed during two time periods: pre-expansion (2010-2012) and post-expansion (2014-2016). Patients diagnosed while residing in ME states were compared with those in non-ME states. Multivariable logistic regression was used to identify predictors of receipt of palliative therapies. RESULTS: Of 87,738 patients overall, 7483(18.1%) received palliative therapies in the pre-expansion, while 10,211(21.5%) received palliative therapies in the post-expansion period. In the pre-expansion period, treatment at a high-volume facility (HVF) (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18) and non-west geographic location were predictive of increased palliative therapies. In the post-expansion period, treatment at an HVF (OR 1.09, 95% CI 1.02-1.16), geographic location, and living in an ME state at the time of diagnosis (OR 1.14, 95% CI 1.06-1.22) were predictive of increased palliative therapies. Older age, highest quartile median income (zip-code based), and treatment at a nonacademic facility were independently associated with decreased palliative therapies in both periods. DID analysis demonstrated that patients with metastatic pancreatic cancer living in ME states had increased receipt of palliative therapies relative to those in non-ME states (DID = 2.68, p < 0.001). CONCLUSIONS: The overall utilization of palliative therapies in metastatic pancreatic cancer is low. Multiple sociodemographic disparities exist in the receipt of palliative therapies. ME is associated with increased receipt of palliative therapies in patients with metastatic pancreatic cancer.

Fragmentation of Care in Pancreatic Cancer: Effects on Receipt of Care and Survival.

BACKGROUND: The impact of fragmentation of care (FC), i.e., receipt of care at > 1 institution, on treatment of pancreatic cancer is unknown. The purpose of this study was to determine factors associated with FC in curative-intent treatment of pancreatic cancer (PDAC) patients and evaluate how FC affects survival outcomes. METHODS: Using the National Cancer Database (NCDB), data on stage I-III PDAC patients diagnosed 2006-2016 were extracted. Multiple logistic regression analyses were performed to identify factors predictive of FC and survival. RESULTS: Of the 20,013 patients identified, 24.1% had FC. Factors predictive of FC were stage-III tumors (odds ratio [OR] 1.36; p = 0.014), higher median-income [third quartile (OR 1.38; p = 0.006) and highest-quartile (OR 1.50; p = 0.003)], care at high-volume facility (OR 1.47; p < 0.001), and receipt of multi-modal therapy (OR 1.69; p < 0.001). In contrast, age > 80 years (OR 0.82; p = 0.018), Black (OR 0.85; p = 0.013) or Asian race (OR 0.76; p = 0.033), Charlson comorbidity-index 2 (OR 0.85; p = 0.033), treatment at non-academic facility (OR 0.87; p = 0.041), and non-private insurance were negatively predictive of FC. FC independently predicted decreased 30-day [OR 0.57; p < 0.001] and 90-day mortality [OR 0.61; p < 0.001] and improved overall survival [hazard ratio 0.91; p < 0.001]. DISCUSSION: Sociodemographic factors are significantly associated with FC in curative-intent treatment of PDAC patients. FC was found to predict improved 30-day, 90-day, and overall survival outcomes.

Disparities in Access to Oncologic Care in Pancreatic Cancer: A Systematic Review.

BACKGROUND: Pancreatic cancer care is complex, and multiple disparities in receipt of therapies have been documented. The authors aimed to conduct a systematic review of the literature to critically assess and summarize disparities in access to oncologic therapies for pancreatic cancer. METHODS: A search of PubMed, Scopus, Web of Science, and Cochrane databases were performed for studies reporting disparities in access to oncologic care for pancreatic cancer. Primary research articles published in the United States from 2000 to 2020 were included. Data were independently extracted, and risk of bias was assessed using the modified Newcastle-Ottawa scale. RESULTS: The inclusion criteria were met by 47 studies. All the studies used retrospective data, with 70 % involving national database studies, 41 assessing the impact of race/ethnicity, 22 assessing the impact of socioeconomic status, 18 assessing the impact of insurance status, 23 assessing the impact of gender, 26 assessing the impact of age, and 3 assessing the impact of location on the delivery of cancer-directed therapies. Race, socioeconomic status, insurance status, gender, and age- based disparities in receipt of surgical resection, treatment at high-volume facilities and multimodal therapy for resectable pancreatic cancer, receipt of systemic chemotherapy for metastatic cancer, and receipt of expected standard-of-care treatment are reported. CONCLUSION: Significant sociodemographic disparities in access to equitable oncologic care exist along the continuum of pancreatic cancer care. Multiple patient, provider, and systemic factors contribute to these disparities. The ongoing study of these disparities is important to elucidate processes that may be targeted to improve access to equitable oncologic care for patients with pancreatic cancer.

Surgical Resection of Colorectal Liver Metastases: Attitudes and Practice Patterns in the Deep South.

BACKGROUND: Metastatic disease is the leading cause of mortality in colorectal cancer. Resection of colorectal liver metastases, when possible, is associated with improved long-term survival and the possibility of cure. However, nationwide studies suggest that liver resection is under-utilized in the treatment of colorectal liver metastases. This study was undertaken to understand attitudes and practice patterns among medical oncologists in the Deep South. METHODS: A survey of medical oncologists in the states of Alabama, Mississippi, and the Florida panhandle was performed. Respondents were queried regarding perceptions of resectability and attitudes towards surgical referral. RESULTS: We received 63 responses (32% response rate). Fifty percent of respondents reported no liver surgeons in their practice area. Commonly perceived contraindications to liver resection included extrahepatic metastatic disease (72%), presence of > 4 metastases (72%), bilobar metastases (61%), and metastases > 5 cm (46%). Bilobar metastatic disease was perceived as a contraindication more frequently by non-academic medical oncologists (70% vs. 33%, p = 0.03). CONCLUSIONS: Wide variations exist in perceptions of resectability and referral patterns for colorectal liver metastases among surveyed medical oncologists. There is a need for wider dissemination of resectability criteria and more liver surgeon involvement in the management of patients with colorectal liver metastases.

Association of Medicaid Expansion with Pancreatic Cancer Treatment and Outcomes: Evidence from the National Cancer Database.

BACKGROUND: Socioeconomic- and demographic-based disparities exist in the treatment of pancreatic adenocarcinoma (PDAC). Medicaid expansion (ME) may have an impact on these disparities. Analyses of patients with PDAC from the National Cancer Database (NCDB) were performed to examine the impact of ME on access to treatment and outcomes. METHODS: Patients with non-metastatic PDAC diagnosed between 2006 and 2016 were identified. Multiple logistic regression analyses were performed to evaluate factors associated with curative-intent surgical resection, multimodal therapy, treatment at a high-volume facility (HVF), and survival. RESULTS: The study identified 41,876 patients who met the criteria. Medicaid expansion was independently associated with curative-intent resection (odds ratio [OR] 1.54; 95 % confidence interval [CI] 1.43-1.67; p < 0.001). In a multivariable analysis, ME was independently associated with multimodal therapy (OR 1.60; 95 % CI 1.44-1.76; p < 0.001) and treatment at an HVF (OR 1.57; 95 % CI 1.42-1.74; p < 0.001). Medicaid expansion was independently associated with improved 30-day mortality (OR 0.49; 95 % CI 0.34-0.79) and 90-day mortality (OR 0.48 95 % CI 0.35-0.59). Cox regression analysis demonstrated that after adjustment for other variables, ME status was associated with improved overall survival (hazard ratio [HR], 0.82; 95 % CI 0.73-0.90; p < 0.001). CONCLUSIONS: Medicaid expansion is associated with increased use of care processes that improve outcomes in PDAC, operative outcomes, and overall survival. The study data suggest that ME has helped to improve disparities in PDAC in ME states.

Radiation and Its Impact on Local Recurrence in Extremity and Trunk Well-Differentiated Liposarcomas.

Patients with well-differentiated liposarcomas (WDLPS) of the extremity and trunk are treated primarily with surgical resection, with radiation used for a number of anecdotal reasons, including large size and positive margins. In this study, we evaluate the appropriate role for radiation in these tumors. A retrospective chart review of patients with extremity and trunk soft tissue liposarcomas referred to a free-standing cancer center from January 1995 to December 2011 was performed. One hundred eighty-three patients with extremity and trunk soft tissue WDLPS were identified: 61 per cent were female, median age was 60 years (range, 19-84 years) and 2 per cent had a focal area of dedifferentiation, margin status was positive in 57 per cent. Fourteen per cent of patients received radiation. Fifty patients developed recurrent disease; 28 per cent of these received radiation. Median time to recurrence was 18 years (range, 0.7-22 years). Of the 50 patients who recurred, 14 (28%) received radiation. Radiation was associated with decreased second recurrence when administered for recurrent disease (P = 0.03). On multivariable analysis, tumor size ≤ 10 cm (P = 0.014) and anatomically difficult area of resection (P = 0.008) were predictive of increased risk of recurrence. Older age (P = 0.02), dedifferentiated liposarcomas (P < 0.001), and difficult area of resection (P = 0.02) were associated with the administration of radiotherapy. Administration of radiation therapy was not associated with decreased time to recurrence in WDLPS overall; however, it should be considered in patients with recurrent disease.

Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?

BACKGROUND: Significant overtreatment of intraductal papillary mucinous neoplasms can be attributed to low specificity of the current International Consensus Guidelines as well as nonconformity with the guidelines. We compare the ability of the 2012 and revised 2017 intraductal papillary mucinous neoplasms International Consensus Guidelines to predict high-grade dysplasia/invasive cancer and to determine the preoperative variables that predict resection of benign or low-grade dysplasia in tertiary care centers. METHODS: Clinical, radiographic, and pathologic data for resected intraductal papillary mucinous neoplasms at 3 high-volume National Cancer Institute Cancer Centers were reviewed and the 2012 and 2017 consensus criteria were retrospectively applied. When International Consensus Guidelines were not met, clinical decision analysis was used to determine the primary indication for resection. Logistic regression identified variables associated with pathologic grade. RESULTS: Records for a total of 251 patients were reviewed, 129 of whom (52%) had low-grade dysplasia. The revised 2017 International Consensus Guidelines had high sensitivity (98.4%) and negative predicted value (96.1%), and all high-risk stigmata predicted high-grade dysplasia/invasive cancer; however, specificity remained low (14.8%). Nonconformity with International Consensus Guidelines was the most powerful predictor of low-grade dysplasia on final pathologic examination (9.5; 2.12-40.78). Independent predictors of low-grade dysplasia included age younger than 50 (2.46; 1.08-5.62), fine-needle aspiration without epithelial cells (2.6; 1.43-4.72), and normal duct diameter (3.07; 1.99-4.75). Diabetes developed in 30% of patients after resection. CONCLUSION: Management of intraductal papillary mucinous neoplasms remains clinically challenging. Low specificity of the International Consensus Guidelines and nonconformity with the guidelines continue to contribute to unnecessary pancreatic resections. Improved tools for disease classification as well as a better understanding of the natural history, biology, and rates of progression of intraductal papillary mucinous neoplasms are needed to avoid surgical overtreatment of low-grade intraductal papillary mucinous neoplasms.

Intraductal Papillary Mucinous Neoplasms of the Pancreas: Current Understanding and Future Directions for Stratification of Malignancy Risk.

The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.

Surgery for pancreatic cancer: critical radiologic findings for clinical decision making.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, with an estimated 53,670 new cases diagnosed and an estimated 43,090 deaths in 2017. This high mortality rate is in part due to the small percentage of patients diagnosed with local disease, as well as the biologically aggressive nature of the disease. While only 10-20% of patients will present with surgically resectable disease, this is the only possible curative therapy. Five-year survival of resected pancreatic cancer ranges from 12 to 27%. The National Comprehensive Cancer Network (NCCN) guidelines recommend specific guidelines for imaging modalities used in the diagnosis and staging of pancreatic adenocarcinoma. Indeed, high-quality imaging is not only necessary to accurately stage the disease, but is critical for the determination of key clinical decision branch points such as the determination of surgical resectability. Identification of the lesion within the pancreas, the degree of extra-pancreatic extension, and potential involvement of surrounding vascular structures with the tumor are all findings necessary to classify patients as having resectable, borderline resectable, or with unresectable primary tumors. This article reviews imaging modalities used to evaluate the pancreatic cancer patient from the surgeon's perspective, with particular emphasis on determination of resectability and preoperative planning, as well as imaging in the postoperative period.

Senior Surgical Resident Confidence in Performing Flexible Endoscopy: What Can We Do Differently?

INTRODUCTION: The American Board of Surgery endoscopy requirements for general surgery training are evolving. In 2006, the Residency Review Committee in Surgery increased the total number of endoscopy cases required before completion of general surgery residency training. This requirement is set to change further, given the new Flexible Endoscopic Curriculum that would be a requirement for applicants graduating surgical training during or after the 2017 to 2018 academic year. Given these changes, our goal was to evaluate the confidence of senior surgical residents performing flexible endoscopy. METHODS: A survey was developed and sent to general surgery residents nationally, querying them regarding demographics and program-specific characteristics; additionally they were asked to rate their confidence level in performing flexible upper endoscopy and colonoscopy on a Likert scale of 1 to 5. We then compared those residents who indicated confidence (Likert scale 4-5) to those who did not (Likert scale 1-3). For the purpose of this study, only senior (postgraduate year 4 and 5) general surgery residents were assessed. RESULTS: We received 1176 responses from senior surgical residents: 56% of these were postgraduate year 5 residents, 65% male, 68% from University Programs, and 56% from programs associated with a Veteran's Affairs Hospital; 33% were from programs in the Northeast, 29% in the South, 24% in the Midwest, and 14% in the West; 75% were going on to additional fellowship training after the completion of residency; 42% indicated that they would go into academic practice and 32% into private practice; 66.7% reported confidence performing upper endoscopy and 52.7% reported confidence performing colonoscopy. Male gender, overall operative volume, and graduating from a medium-sized program or program in the South were associated with increased confidence performing flexible endoscopy. CONCLUSIONS: A large percentage of senior residents do not report confidence in performing flexible endoscopy. Although increasing the number of cases required for graduation has likely helped improve the training of residents in endoscopy, additional improvements in training are required. The Flexible Endoscopic Curriculum helps standardize the curriculum and demonstrate that the graduating resident has the fundamental knowledge and skills required in the performance of endoscopy. Simulation training and dedicated endoscopic rotations during the course of residency training could help improve endoscopy training and proficiency for future graduating residents.

Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype.

UNLABELLED: Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1 have been described in APAs. OBJECTIVE: To characterize clinical-pathological features in APAs and unilateral adrenal hyperplasia, and correlate them with genotypes. DESIGN: Retrospective study. SUBJECTS AND MEASUREMENTS: Clinical and pathological characteristics of 90 APAs and seven diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing. RESULTS: Mutation frequencies were as follows: KCNJ5, 37·1%; CACNA1D, 10·3%; ATP1A1, 8·2%; ATP2B3, 3·1%; and CTNNB1, 2·1%. Previously unidentified mutations included I157K, F154C and two insertions (I150_G151insM and I144_E145insAI) in KCNJ5, all close to the selectivity filter, V426G_V427Q_A428_L433del in ATP2B3 and A39Efs*3 in CTNNB1. Mutations in KCNJ5 were associated with female and other mutations with male gender (P = 0·007). On computed tomography, KCNJ5-mutant tumours displayed significantly greater diameter (P = 0·023), calculated area (P = 0·002) and lower precontrast Hounsfield units (P = 0·0002) vs tumours with mutations in other genes. Accordingly, KCNJ5-mutant tumours were predominantly comprised of lipid-rich fasciculata-like clear cells, whereas other tumours were heterogeneous (P = 5 × 10(-6) vs non-KCNJ5 mutant and P = 0·0003 vs wild-type tumours, respectively). CACNA1D mutations were present in two samples with hyperplasia without adenoma. CONCLUSIONS: KCNJ5-mutant tumours appear to be associated with fasciculata-like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic KCNJ5 variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations.

Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.

Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca(2+) channel); both are expressed at very low levels in normal ß-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca(2+) signaling pathways involved in insulin secretion.