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Background and Aims : EUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. Methods : A post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years of surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. Results : A reference diagnosis was available in 93 subjects (mean cyst size=36.4±15.7 mm; surgical histopathology, n=67 and diagnostic molecular markers in cyst fluid, n=26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically downstaged from mucinous to non-mucinous not warranting surgery (total cost savings= $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4,757.40 /patient) for this cohort. Conclusions : EUS-nCLE is potentially cost-beneficial in the management of PCLs (≥ 3 cm) by preventing at least one unnecessary pancreatic surgery for every ten subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

PURPOSE While not always sufficient, surgery is a critical component of contemporary multidisciplinary cancer care and is generally necessary for the curative-intent treatment of most solid organ cancers. Patients who undergo aborted cancer surgery may experience many of the same surgical symptoms, need for recovery, and risk of complications as patients who undergo successful curative-intent surgery while simultaneously experiencing the psychosocial distress of a terminal change in their prognosis as well as the side effects of cancer left in situ. METHODS A systematic review of the PubMed, Medline, CINAHL, and PsychInfo databases was performed of literature pertaining to the quality of life, experiences, care needs, coping strategies, and/or preferences of patients following aborted cancer surgery. RESULTS Among 12,060 initially identified articles, none met the final inclusion criteria. Given this evidence gap, this commentary summarizes the lack of relevant literature on patient-centered outcomes following aborted cancer surgery and highlights opportunities for future patient-centered research. CONCLUSION There is a significant lack of patient-centered research pertaining to outcomes of aborted cancer surgery. Future research should focus on characterizing patients' experiences, care needs, and preferences following aborted cancer surgery which might inform patient-centered interventions that can lead to improved quality and quantity of life.

Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.

“Textbook oncologic outcome” (TOO) is a composite quality measure representing the “ideal” outcome for patients undergoing cancer surgery. This study sought to assess the validity of TOO as a metric to evaluate hospital quality. Patients who underwent curative-intent resection of gastric, pancreatic, colon, rectal, lung, esophageal, bladder, or ovarian cancer were identified in the National Cancer Database (2006–2017). Cancer site-specific TOO was defined as adequate lymph node yield, R0 resection, non-length-of-stay outlier, no hospital readmission, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the adjusted TOO rate for each hospital stratified by cancer site. The association between hospital adjusted TOO rates and 5-year overall survival was assessed using mixed-effects Cox proportional hazards analyses. Among 852,988 cancer resections, the TOO rate varied across cancer sites as follows: stomach (31.8%), pancreas (25%), colon (66.9%), rectum (33.6%), lung (35.1%), esophagus (31.2%), bladder (43%), and ovary (44.7%). After characterization of adjusted hospital TOO rates into quintiles, an incremental improvement in overall survival was observed, with higher adjusted TOO rates. Similarly, with the adjusted hospital TOO rate treated as a continuous variable, there was a significant 4% to 12% improvement in overall survival for every 10% increase in the adjusted hospital TOO rate for gastric (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.85–0.91), pancreatic (HR, 0.90; 95% CI, 0.88–0.93), colon (0.93; 95% CI, 0.91–0.94), rectal (HR, 0.90; 95% CI, 0.87–0.93), lung (HR, 0.96; 95% CI, 0.95–0.97), esophageal (HR, 0.93; 95% CI, 0.90–0.95), bladder (HR, 0.94; 95% CI, 0.91–0.97), and ovarian (HR, 0.96; 95% CI, 0.94–0.98) cancer. A direct association exists between adjusted hospital TOO rates and survival after high-risk cancer procedures. As a valid hospital metric, TOO can be used to compare the overall quality of cancer care across hospitals.

Purpose To evaluate the association of retinal nonperfusion and diabetic retinopathy (DR) severity with location of vascular caliber measurement using ultrawide field (UWF) imaging. Design Retrospective image review. Participants Adults with diabetes mellitus. Methods All images from subjects with same-day UWF fluorescein angiography (FA) and color imaging were evaluated. Predominantly peripheral lesions (PPL) and DR severity were graded from UWF color images. Nonperfusion was quantified using UWF-FA in defined retinal regions [posterior pole (PP), mid-periphery (MP), far-periphery (FP)]. Retinal vessel calibers were measured at an optic disc centered inner and outer zone. Main Outcome Measures Nonperfusion index (NPI) in the PP, MP and FP. Mean arteriole and venule diameter in the inner and outer zones. Results Two hundred eighty-five eyes of 193 patients (24.9% mild nonproliferative DR [NPDR], 22.8% moderate NPDR, 37.5% severe NPDR and 14.7% proliferative DR [PDR]) were reviewed. No significant associations between inner zone arteriolar diameter and retinal NPI overall or in any retinal region. In the outer zone, eyes with thinnest arteriolar calibers (quartile 1) were associated with a 1.7- to 2.4-fold nonperfusion increase across all retinal regions compared to the remaining eyes (P = 0.002 [PP] to 0.048 [FP]). In the outer zone, the percentage of eyes in the thinnest quartile of retinal arteriolar diameter increased with worsening DR severity (mild NPDR: 10% vs PDR: 31%, P = 0.007). This association was not observed when measured within the inner zone (P = 0.129). All venular caliber associations were not statistically significant when corrected for potentially confounding factors. Thinner outer zone retinal arteriolar caliber (quartile 1) was more common in eyes with PPL compared to eyes without PPL (34.1% vs 20.8%, P = 0.017) as were thicker outer venular calibers (quartile 4) (33% vs 21.3%, P = 0.036). Presence of PPL was associated with thinner outer zone arteriolar caliber (109.7 ± 26.5μm vs 123.0 ± 29.5μm, P = 0.001). Conclusions The association of vascular caliber with nonperfusion and DR severity differs based upon the retinal location at which vascular caliber is measured. Peripheral arterial narrowing is associated with increasing nonperfusion, worsening DR severity and presence of PPL. In contrast, inner zone retinal arteriolar caliber is not associated with these findings.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Neutrophil-to-lymphocyte ratio has been correlated with clinical outcomes in many cancers. We investigated whether the delta-NLR (ΔNLR) following radiation therapy (RT) could predict achieving surgical resection and the overall survival (OS) of patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC), and whether the splenic radiation dose impacted ΔNLR.101 patients with biopsy-proven BRPC or LAPC who received induction chemotherapy followed by RT were retrospectively enrolled. Following contouring of spleens, dose-volume histograms (DVHs) for splenic dosimetric parameters were calculated. Pre- and post-RT complete blood counts (CBC) within two weeks were recorded. Delta (Δ) values were calculated by subtracting the post-RT value from the pre-RT value. Cox regression survival analysis for pre and postradiation CBC values and OS was performed. Receiver operating curves (ROC) were generated and optimal cutoff points for highest sensitivity and specificity were identified. Kaplan-Meier curves for OS were generated.On univariate Cox regression analysis, the only significant CBC value associated with OS was ΔNLR (HR 1.06, CI 1.03-1.09, p 0.001). On multivariate analysis, ΔNLR, age, and completed resection all significantly predicted for worse OS (p 0.05). ΔNLR significantly predicted achieving surgical resection (p = 0.04) and the optimal cutoff point for ΔNLR was 2.5. Patients with ΔNLR 2.5 had significantly longer OS (log rank p = 0.046). Spleen radiation dose parameters were all significantly higher in patients with a ΔNLR ≥ 2.5. Optimal radiation cutoff points to predict a ΔNLR ≥ 2.5 were splenic Dmean of 308 cGy and V5 of 10.3%.Among patients with BRPC or LAPC who have received induction chemotherapy, elevated ΔNLR after RT significantly predicts worse OS and decreased odds of achieving resection. Furthermore, ΔNLR is correlated with higher splenic doses, suggesting the spleen may be an important organ at risk.

The effect of community-level factors on surgical outcomes has not been well examined. We sought to characterize differences in "textbook outcomes" (TO) relative to social vulnerability among Medicare beneficiaries who underwent operations for cancer.Individuals who underwent operations for lung, esophageal, colon, or rectal cancer between 2013 and 2017 were identified using the Medicare database, which was merged with the CDC's Social Vulnerability Index (SVI). TO was defined as surgical episodes with the absence of complications, extended length of stay, readmission, and mortality. The association of SVI and TO was assessed using mixed-effects logistic regression.Among 203,800 patients (colon, n = 113,929; lung, n = 70,642; rectal, n = 14,849; and esophageal, n = 4,380), median age was 75 years (interquartile range 70 to 80 years) and the overwhelming majority of patients was White (n = 184,989 [90.8%]). The overall incidence of TO was 56.1% (n = 114,393). The incidence of complications (low SVI: 21.5% vs high SVI: 24.0%) and 90-day mortality (low SVI: 7.0% vs high SVI: 8.4%) were higher among patients from highly vulnerable neighborhoods (both, p0.05). In turn, there were lower odds of achieving TO among high-vs low-SVI patients (odds ratio 0.83; 95% CI, 0.78 to 0.87). Although high-SVI White patients had 10% lower odds (95% CI, 0.87 to 0.93) of achieving TO, high-SVI non-White patients were at 22% lower odds (95% CI, 0.71 to 0.85) of postoperative TO. Compared with low-SVI White patients, high-SVI minority patients had 47% increased odds of an extended length of stay, 40% increased odds of a complication, and 23% increased odds of 90-day mortality (all, p0.05).Only roughly one-half of Medicare beneficiaries achieved the composite optimal TO quality metric. Social vulnerability was associated with lower attainment of TO and an increased risk of adverse postoperative surgical outcomes after several common oncologic procedures. The effect of high SVI was most pronounced among minority patients.

The utilization of cancer-directed treatment for patients with all stages of pancreatic cancer in the USA is unknown. This study sought to examine national practice patterns and identify patient, hospital, regional, and other factors associated with disparities in the use of guideline-concordant cancer-directed therapy. Patients diagnosed with PDAC between 2004 and 2015 were queried from the National Cancer Data Base. Standard of care cancer-directed treatment was defined as surgical resection plus chemotherapy or chemoradiation for patients with stage 1 and 2 disease, chemotherapy for patients with metastatic disease (stage 4), and chemotherapy with or without surgery or chemoradiation for patients with locally advanced stage 3 disease. A total of 336,629 patients with stage 1 (n = 38,443, 11.4%), stage 2 (n = 93,923, 27.9%), stage 3 (n = 37,492, 11.1%), or stage 4 metastatic (n = 166,771, 49.5%) disease were identified. Adherence with stage-specific standard of care treatment occurred in only 45.3% (n = 152,560) of patients among the entire cohort and varied by stage of disease (stage 1: 14.6% vs. stage 2: 39.9% vs. stage 3: 67.6%, vs. stage 4: 50.9%). Older age (OR 0.95, 95%CI 0.94–0.95; p < 0.001), female sex (OR 0.94, 95%CI 0.943–0.97; p < 0.001), African Americans (OR 0.89, 95%CI 0.87–0.91; P < 0.001), and increasing comorbidity burden (Charlson-Deyo score ≥3: OR 0.52, 95%CI 0.50–0.55; P < 0.001) were associated with a lower likelihood of receiving stage-specific standard of care treatment. Conversely, treatment at a high-volume center (quartile 4: OR: 1.13, 95%CI 1.10–1.16; P < 0.001) and higher education level (OR 1.32, 95%CI 1.28–1.36; p < 0.001) was associated with higher likelihood of receiving stage-specific standard of care treatment. Patients who received standard of care treatment had a 47% lower risk of death compared with patients who did not receive standard of care treatment (HR 0.53, 95%CI 0.52–0.53; P < 0.001). Pancreatic adenocarcinoma is a complex disease requiring a multi-disciplinary approach for optimal outcomes. Receipt of stage-specific standard of care treatment for PDAC is associated with improved long-term oncological outcomes, but is only achieved in less than half of patients. Further studies are needed to evaluate interventions to address these treatment disparities for patients with PDAC.

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

The role of neoadjuvant therapy (NT) for ampullary carcinoma (AC) has not been clearly established.Patients who underwent pancreatoduodenectomy for AC between 2004 and 2016 were identified in the National Cancer Database. Overall survival (OS) was compared between those who received NT before resection and those who underwent surgery first (SF). Propensity score matching (PSM) was performed using age, pathologic T and N stage, and tumor differentiation.Among 8688 patients with AC, 175 (2.0%) received NT before surgery. While patients who received NT were younger (p = .022) and more likely to have nodal metastasis (43.3% vs. 35.1%, p .001), there was no difference in OS on univariate (43 vs. 33 months; hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.88-1.37, p = .401) or multivariate (HR: 1.09, 95% CI: 0.88-1.36, p = .416) analysis between groups. After PSM, there remained no difference in OS between NT or SF groups on univariate (37 vs. 32 months; HR: 1.20, 95% CI: 0.87-1.64, p = .350) or multivariate (HR: 0.99, 95% CI: 0.71-1.38, p = .943) analysis.NT followed by surgery was not associated with improved survival outcomes compared with SF among patients with localized AC. While NT is an acceptable alternative for patients with advanced disease, SF should remain the standard of care.

The objective of this study was to analyze whether primary tumor resection (PTR) among patients with stage IV gastrointestinal neuroendocrine tumor (GI-NET) and unresected metastases was associated with improved outcomes. Patients diagnosed with stage IV GI-NETs were identified in the linked SEER-Medicare database from 2004 to 2015. Overall survival (OS) of patients who did versus did not undergo PTR was examined using bivariate and multivariable cox regression analysis as well as propensity score matching (PSM). Among 2219 patients with metastatic GI-NETs, 632 (28.5%) underwent PTR, whereas 1587 (71.5%) did not. The majority of individuals had a NET in the pancreas (n = 969, 43.6%); the most common site of metastatic disease was the liver (n = 1064, 47.9%). Patients with stage IV small intestinal NETs most frequently underwent PTR (62.6%) followed by individuals with colon NETs (56.5%). After adjusting for all competing factors, PTR remained independently associated with improved OS (HR = 0.65, 95% CI: 0.56–0.76). Following PSM (n = 236 per group), patients who underwent PTR had improved OS (median OS: 1.3 years vs 0.8 years, p = 0.016). While PTR of NETs originating from stomach, small intestine, colon, and pancreas was associated with improved OS, PTR of rectal NET did not yield a survival benefit. Primary GI-NET resection was associated with a survival benefit among individuals presenting with metastatic GI-NET with unresected metastases. Resection of primary GI-NET among patients with stage IV disease and unresected metastases should only be performed in selected cases following multi-disciplinary evaluation.

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients.Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD.The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P 0.001).Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). The US HIPEC collaborative database (2000–2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. A total of 174 patients were identified. Median PCI was 16 (3–39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59–4.74; MOR-2+ : HR 0.77, 95% CI 0.22–2.69). MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms arising from pancreatic islet cells that remain relatively rare but are increasing in incidence worldwide. While significant advances have been made in recent years with regard to systemic therapies for patients with advanced disease, surgical resection remains the standard of care for most patients with localized tumors. Although formal pancreatectomy with regional lymphadenectomy is the standard approach for most PNETs, pancreas-preserving approaches without formal lymphadenectomy are acceptable for smaller tumors at low risk for lymph node metastases. Furthermore, observation of small, asymptomatic, low-grade PNETs is a safe, initial strategy and is generally recommended for tumors

Geographic variations in access to care exist in the USA. We sought to characterize county-level disparities relative to access to surgery among patients with early-stage hepatopancreatic (HP) cancer. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked database from 2004 to 2015 to identify patients undergoing surgery for early-stage HP cancer . County-level information was acquired from the Area Health Resources Files (AHRF). Multivariable logistic regression analysis was performed to assess factors associated with utilization of HP surgery on the county level. Among 13,639 patients who met inclusion criteria, 66.9% (n = 9125) were diagnosed with pancreatic cancer and 33.1% (n = 4514) of patients had liver cancer. Among patients diagnosed with early-stage liver and pancreas malignancy, two-thirds (n = 8878, 65%) underwent surgery. Marked county-level variation in the utilization of surgery was noted among patients with early-stage HP cancer ranging from 57.1% to more than 83.3% depending on which county a patient resided. After controlling for patient and tumor-related characteristics, counties with the highest quartile of patients living below the poverty level had 35% lower odds of receiving surgery for early stage HP cancer compared patients who lived in a county with the lowest proportion of patients below the poverty line (OR 0.65, 95% CI 0.55–0.77). In addition, patients residing in counties with the highest surgeon-to-population ratio (OR 2.01, 95% CI 1.52–2.65), as well as the highest hospital bed-to-population ratio (OR 1.29, 95% CI 1.07–1.54), were more likely to undergo surgical treatment for an early-stage HP malignancy. Area-level variations among patients undergoing surgery for early-stage HP cancer were mainly due to differences in structural measures and county-level factors. Policies targeting high-poverty counties and improvement in structural measures may reduce variations in utilization of surgery among patients diagnosed with early-stage HP cancer.

Well-differentiated neuroendocrine tumors (NETs) are globally increasing in prevalence and the liver is the most common site of metastasis. Neuroendocrine liver metastases (NELM) are heterogeneous in clinical presentation and prognosis. Fortunately, recent advances in diagnostic techniques and therapeutic strategies have improved the multidisciplinary management of this challenging condition. When feasible, surgical resection of NELM offers the best long-term outcomes. General indications for hepatic resection include performance status acceptable for major liver surgery, grade 1 or 2 tumors, absence of extrahepatic disease, adequate size and function of future liver remnant, and feasibility of resecting >90% of metastases. Adjunct therapies including concomitant liver ablation are generally safe when used appropriately and may expand the number of patients eligible for surgery. Among patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. For patients who are not surgical candidates, liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization can provide locoregional control and improve symptoms of carcinoid syndrome. Multiple systemic therapy options also exist for patients with advanced or progressive disease. Ongoing research efforts are needed to identify novel biomarkers that will define the optimal indications for and sequencing of treatments to be delivered in a personalized fashion.

BACKGROUND The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data. METHODS All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed. RESULTS Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size

The current study aimed to define the relationship between patient satisfaction, hospital-level factors, and clinical outcomes among patients undergoing major surgery for cancer. The Medicare Inpatient Standard Analytic Files were used to identify patients undergoing lung, esophageal, colorectal, hepatic, or pancreatic surgery between 2016 and 2017, and Hospital Consumer Assessment of Healthcare Providers and Systems survey data were used to assess performance in terms of patient satisfaction. Among 60,446 patients, half were female (n = 31,244, 52%) with a median age of 73 years (interquartile range [IQR] 69–78 years). Patients who underwent surgery for esophageal resection (odds ratio [OR] 2.44; 95% confidence interval [CI] 1.10–5.40) and were Caucasian (OR 2.43; 95% CI 2.11–2.81) had optimal patient satisfaction. Hospital level factors such as urban location (OR 3.69; 95% CI 3.16–4.29), 200 + beds (OR 3.58; 95% CI 3.09–4.13), greater inpatient surgical volume (OR 3.03; 95% CI 2.82–3.25), higher nurse-to-bed ratio (OR 4.57; 95% CI 4.25–4.92), non-profit hospital status (OR 1.14; 95% CI 1.01–1.29), and non-teaching hospital status (OR 1.52; 95% CI 1.39–1.65) were related to optimal patient satisfaction. In adjusted analysis, patients undergoing surgery at hospitals reporting poor or average patient satisfaction had 22% higher odds of 90-day mortality than patients undergoing surgery at optimal-satisfaction hospitals (OR 1.22; 95% CI 1.09–1.36). In addition, hospitals with the highest patient satisfaction scores also had the highest proportion of surgical cases that achieved the composite textbook outcome (TO) quality metric (OR 1.12; 95% CI 1.05–1.20). Higher patient satisfaction was strongly associated with hospital structural measures such as bed number, urban location, nurse-to-bed ratio, and “optimal” TO after cancer surgery. These data highlight how high quality of care can directly lead to improved patient satisfaction among surgical patients with cancer.

Assessing composite measures of quality such as textbook outcome may be superior to focusing on individual parameters when evaluating hospital performance. The aim of the current study was to assess the impact of teaching hospital status on the occurrence of a textbook outcome after hepatopancreatic surgery.The Medicare Inpatient Standard Analytic Files were used to identify patients undergoing hepatopancreatic surgery from 2013 to 2015 for a malignant indication. Stratified and multivariable regression analyses were performed to determine the relationship between teaching hospital status, hospital surgical volume and textbook outcome.Among 8,035 Medicare patients (hepatectomy; 41.8%, pancreatectomy; 58.2%), 6,196 (77.1%) patients underwent surgery at a major teaching hospital, whereas 1,839 (22.9%) patients underwent surgery at a minor teaching hospital. Patients undergoing surgery for pancreatic cancer at a major teaching hospital had a greater likelihood of achieving a textbook outcome compared with patients treated at a minor teaching hospital (minor teaching hospital: 456, 40% versus major teaching hospital: 1,606, 45.4%; P = .002). The likelihood of textbook outcome was also greater among patients undergoing hepatopancreatic surgery at high-volume centers (pancreas, low volume: 875, 40.5% versus high volume: 1,187, 47.1% P.001; liver, low volume: 608, 41.8% versus high volume: 886, 46.6%; P = .005). When examining only major teaching hospitals, patients undergoing a pancreatectomy at a high-volume center had 29% greater odds of achieving a textbook outcome (odds ratio 1.29, 95% confidence interval 1.12-1.49). In contrast, among patients undergoing pancreatic resection at high-volume centers, the odds of achieving a textbook outcome was comparable among major versus minor teaching hospital (odds ratio 1.17, 95% confidence interval 0.89-1.53).The odds of achieving a textbook outcome after pancreatic and hepatic surgery was greater at major versus minor teaching hospitals; however, this effect was largely mediated by hepatopancreatic procedural volume. Patients and payers should focus on regionalization of pancreatic and liver resection to high-volume centers in an effort to optimize the chances of achieving a textbook outcome.

We sought to characterize surgeon perceptions of patient attachment-related behaviors relative to patient-centered approaches during treatment decision-making within the clinical encounter. An online survey including clinical vignettes was sent to board-certified surgeons to assess their approach to patient-centered treatment decision-making. Within these vignettes, patient behaviors associated with attachment styles (secure vs 3 insecure subtypes: avoidant, anxious, and fearful) were fixed and patient factors (age, race, occupation, and gender) were randomized. Analysis included repeated measures mixed-effects linear regression. Among the 208 respondents, the majority were male (65.4%) and White/Caucasian (84.5%) with an average age of 51.6 years (SD = 9.9). Most surgeons had been in practice for more than 10 years (66.8%) and treated adult patients (77.4%). Surgical specializations included breast (27.2%), HPB (35.0%), and broad-based/general (21.8%). Patient race, age, and gender did not impact surgeons’ patient-centered approach to treatment decision-making (all ps > 0.05). However, when the “patient” had a white collar occupation and were securely attached, surgeons reported a greater likeliness to spend equal time presenting all treatment options (p = 0.02 and p < 0.001, respectively) and believe the patient wanted an active role in decision-making (p = 0.01 and p < 0.001, respectively). Surgeons reported being least likely to agree with a patient’s treatment decision (p < 0.001) and an increased likelihood of being directive (p = 0.002) when patients exhibited behaviors associated with avoidant attachment. Attachment-related behaviors were associated with differences in surgeon approaches to patient-centered decision-making. Attachment styles may offer a framework for providers to understand patient behaviors and needs, thereby providing insight on how to tailor their approach and provide optimal patient-centered care.

Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of neoplasms that vary in their clinical presentation, behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of neuroendocrine liver metastases (NELM) is thought to afford the best long-term outcomes when feasible. Initial preoperative workup should include surveillance for carcinoid syndrome, screening for evidence of liver insufficiency, and performance of imaging specific to neuroendocrine tumors such as a somatostatin receptor positron emission tomography scan. Standard surgical principles apply to hepatic surgery for NELM, namely prioritizing low central venous pressure anesthesia, minimizing blood loss, knowledge of liver anatomy, generous use of intraoperative ultrasound, as well as safe parenchymal transection techniques and practices to avoid bile leakage. Knowledge of established prognostic factors may assist with patient selection, which is important for optimizing short- and long-term outcomes of hepatic resection. Adjunct therapies such as concomitant liver ablation are used frequently and are generally safe when used appropriately. For patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. Primary tumor resection in the setting of unresectable metastatic disease is more controversial, however generally recommended if morbidity is acceptable. For patients who are not surgical candidates, due to either patient performance status or burden of liver disease, several liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization are available to assist with locoregional control, extend progression-free survival (PFS), and improve symptoms of carcinoid syndrome. Multiple systemic therapy options exist for patients with metastatic PNET which are often prioritized for those patients with advanced or progressive disease. A systematic approach in a multi-disciplinary setting is likely to result in the best long-term outcomes for patients with pancreatic NELM. Ongoing research is needed to determine the optimal patient selection for hepatic surgery as well as the ideal treatment sequencing for those patients with NELM.

We conducted an institutional study to compare the clinical and pathological efficacy between the neoadjuvant therapy (NAT)‐modified FOLFIRINOX (mFOLF) vs nanoparticle albumin–bound paclitaxel plus gemcitabine (nab‐P/G) for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients who completed resection. The study retrospectively enrolled patients with pathologically confirmed BRPC or LAPC from 2010 to 2018 at our institution. The survival rates were determined by the Kaplan‐Meier method and log‐rank test was used to test differences. Cox's proportional hazard model was used to assess survival with respect to covariates. Seventy‐two patients who completed at least two cycles of neoadjuvant chemotherapy and surgical resection were included, with 52 (72.2%) patients receiving mFOLF and 20 (27.8%) receiving nab‐P/G. Patients treated with mFOLF had statistically higher rates of RECIST 1.1 partial or complete response (16/52 vs 1/20, P = .028). Additionally, mFOLF patients had greater pathological tumor size reduction, fewer positive lymph nodes, and higher treatment response grade compared to the nab‐P/G patients (all P, Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with poor survival rates. For borderline resectable or unresectable disease, intensive multi‐drug chemotherapy regimens with either modified FOLFIRINOX (mFOLF) or nab‐paclitaxel plus gemcitabine are preferred. We retrospectively compared these two chemotherapy regimens in patients who completed resection and found the mFOLF group had better overall clinical and pathological response rates. Randomized clinical trials are needed, and this study provides valuable information in the interim.

Background The objective of the current study was to define and compare rates of textbook outcomes (TO) among patients undergoing colorectal, lung, esophagus, liver, and pancreatic surgery for cancer at U.S. News & World Report (USNWR) ranked hospitals. Methods Medicare Inpatient Standard Analytic Files 2013-2015 were utilized to examine the relationship of TO and USNWR hospital ratings following surgery for colorectal, lung, esophageal, pancreatic, and liver cancer. TO was defined as no postoperative surgical complications, no prolonged length of hospital stay, no readmission within 90 days after discharge, and no postoperative mortality within 90 days after surgery. Results Among the 35,352 Medicare patients included in the cohort, 16,820 (47.6%) underwent surgery at honor roll hospitals, whereas 18 532 (52.4%) underwent surgery at non-honor roll hospitals. The overall proportion of patients who achieved TO was 50.1%. In examining the clinical outcomes of patients who underwent surgery, there was no difference in the odds of achieving TO at honor roll vs non-honor roll hospitals (colorectal: odds ratio [OR], 0.87; 95% confidence interval [CI], 0.69-1.10; lung: OR, 1.07; 95% CI, 0.87-1.32; esophagus: OR, 1.44; 95% CI, 0.72-2.89; liver: OR, 1.27; 95% CI, 0.87-1.84; pancreas: OR, 1.04; 95% CI, 0.67-1.62). Conclusion and relevance Patients undergoing surgery for lung, esophageal, liver, pancreatic, and colorectal cancer had comparable rates of TO at honor roll vs non-honor roll hospitals. No linear association was observed between hospital position in the rank and postoperative outcomes such as TO indicating that patients should not overly focus on the exact position within USNWR ranked hospitals. These data highlight to patients and physicians that up to one-half of patients undergoing surgery for cancer should anticipate at least one adverse outcome.

BACKGROUND Composite outcomes may more accurately reflect patient and provider expectations around optimal care. We sought to determine the impact of achieving a so-called "textbook oncologic outcome" (TOO) among patients undergoing resection of pancreatic adenocarcinoma (PDAC). METHODS Patients undergoing pancreaticoduodenectomy (PD) for PDAC between 2006 and 2016 were identified in the National Cancer Database (NCDB). TOO was defined by: margin negative resection, compliant lymph node evaluation, no prolonged length-of-stay, no 30-day readmission/mortality, and receipt of adjuvant chemotherapy. Factors associated with TOO and overall survival (OS) were evaluated using multivariable logistic and Cox regression models, respectively. RESULTS Among 18 608 patients who underwent PD at 782 hospitals, many patients successfully achieved certain TOO factors such as R0 margin (77.9%) and no 30-day mortality (96.9%), while other TOO criteria such as receipt of adjuvant therapy (48.2%) were achieved less frequently. Overall, only 3124 (16.8%) patients achieved a TOO. Factors associated with lower odds of TOO included: older age, Black race, Medicaid insurance, Community facility, and low PD facility (

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan–Meier and Cox estimates were used to assess survival. In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE.Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37).In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.

Objectives The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established. Methods The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed. Results Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%. Conclusions Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.

Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction.Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations.A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P .001; colorectal: r = 0.729; P .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071).In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

The aim of the current study is to assess rates of textbook outcome (TO) among Medicare beneficiaries undergoing hepatopancreatic (HP) surgery for cancer at dedicated cancer centers (DCCs) and National Cancer Institute affiliated cancer centers (NCI-CCs) versus non-DCC non-NCI hospitals. Medicare Inpatient Standard Analytic Files were utilized to identify patients undergoing HP surgery between 2013 and 2017. TO was defined as no postoperative surgical complications, no 90-day mortality, no prolonged length of hospital stay, and no 90-day readmission after discharge. Among 21,234 Medicare patients, 8.2% patients underwent surgery at DCCs whereas 32.1% underwent surgery at NCI-CCs and 59.7% underwent an operation at neither DCCs nor NCI-CCs. Although DCCs more often cared for patients with severe comorbidities [Charlson score > 5: DCCs, 1195 (68.9%), NCI-CCs, 3687 (54.1%), others, 3970 (31.3%); p

Mitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease. Preliminary data have shown lower brain adenosine triphosphate (ATP) levels in Parkinson's disease versus age-matched healthy controls. Ursodeoxycholic acid (UDCA) may improve impaired mitochondrial function. Our objective was to evaluate UDCA tolerability, pharmacokinetics, and its effect on brain bioenergetics in individuals with Parkinson's disease. An open-label, prospective, multiple-ascending-dose study of oral UDCA in 5 individuals with Parkinson's disease was completed. A blood safety panel, plasma concentrations of UDCA and UDCA conjugates, and brain ATP levels were measured before and after therapy (week 1: 15 mg/kg/day; week 2: 30 mg/kg/day; and weeks 3-6: 50 mg/kg/day). UDCA and conjugates were measured using liquid chromatography-mass spectrometry. ATP levels and ATPase activity were measured using 7-Tesla 31 P magnetic resonance spectroscopy. Secondary measures included the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. UDCA was generally well tolerated. The most frequent adverse event was gastrointestinal discomfort, rated by subjects as mild to moderate. Noncompartmental pharmacokinetic analysis resulted in (mean ± standard deviation) a maximum concentration of 8749 ± 2840 ng/mL and half-life of 2.1 ± 0.71 hr. Magnetic resonance spectroscopy data were obtained in 3 individuals with Parkinson's disease and showed modest increases in ATP and decreases in ATPase activity. Changes in Unified Parkinson's Disease Rating Scale (parts I-IV) and Montreal Cognitive Assessment scores (mean ± standard deviation) were -4.6 ± 6.4 and 2 ± 1.7, respectively. This is the first report of UDCA use in individuals with Parkinson's disease. Its pharmacokinetics are variable, and at high doses it appears reasonably well tolerated. Our findings warrant additional studies of its effect on brain bioenergetics.

Background: Previous research has demonstrated that specific radiographic criteria, including the presence of calcifications and the enhancement pattern on computed tomography (CT) imaging, correlates with clinicopathologic features and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (NET). We sought to investigate whether these radiographic characteristics were prognostic among patients with neuroendocrine liver metastases (NELM) undergoing surgical resection. Methods: The preoperative contrast-enhanced CT scans of all patients who underwent resection of NELM at a single institution between 2000–2015 were retrospectively reviewed. The presence of calcifications was determined on non-contrast phase imaging. Enhancement on the arterial phase scan was categorized as hyperenhancing, hypoenhancing, or mixed. Relevant clinicopathologic characteristics as well as recurrence-free survival (RFS) and overall survival (OS) were compared between groups. Results: Among 82 patients who underwent resection of NELM, 57 had available data on calcifications while 51 had data available on arterial enhancement patterns. Among all patients, median age was 58 (IQR: 47–63) and the majority were female (N=48, 59.5%). The most common primary tumor locations were pancreas (N=25, 30.5%) and small bowel (N=27, 32.9%). The most commonly performed operations were right hepatectomy (N=29, 35.4%), bisegmentectomy (N=15, 18.3%), and segmentectomy (N=14, 17.1%). Median tumor number was 4 (IQR: 2–9), median Ki-67 was 5% (IQR: 2–10%), and median size of the largest liver metastasis was 4.5 (IQR: 2.8–7.7) cm. Twelve (21%) patients had tumor calcifications. Among patients with and without calcifications there were no differences in demographics, clinicopathologic characteristics, RFS (P=0.772) or OS (P=0.095). Arterial enhancement was hypoenhancing in 23 (45.1%), hyperenhancing in 10 (19.6%), and mixed in 18 (35.3%). Similarly, there were no differences between arterial enhancement groups in demographics, clinicopathologic characteristics, RFS (P=0.618) or OS (P=0.268). Conclusions: Radiographic characteristics on contrast-enhanced CT are not associated with the outcomes of patients undergoing resection of NELM. Future investigations should evaluate the prognostic impact of functional neuroendocrine imaging.

The discovery that patients with Gaucher Disease (GD), a rare lysosomal storage disorder, were developing symptoms similar to Parkinson's disease (PD) led to investigation of the relationship between the two seemingly unrelated pathologies. GD, an autosomal recessive disorder, is the result of a biallelic mutation in the gene GBA1, which encodes for the enzyme glucocerebrosidase (GCase). Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies. Although the exact mechanism by which GBA1 mutations promote PD is unknown, current understanding suggests that impaired GCase inhibits lysosomal activity and decreases the overall ability of the cell to degrade proteins, specifically the neuronal protein α-synuclein. Decreased elimination of α-synuclein can lead to its abnormal accumulation and aggregation, an important component of PD development. Further understanding of how decreased GCase activity increases risk for α-synuclein pathology can assist with the development of clinical biomarkers for early detection of synucleinopathies, as well as promote novel treatments tailored for people with a GBA1 mutation. Historically, α-synuclein has not been a reliable biomarker for PD. However, recent research on α-synuclein content within exosomes, which are small vesicles released by cells that carry specific cellular cargo, has yielded encouraging results. Moreover, decreased GCase activity has been shown to influence exosomal contents. Exosomes have emerged as a promising new avenue for the identification of novel biomarkers and therapeutic targets aimed at improving neuronal GCase function and limiting the development of synucleinopathies.

Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.

INTRODUCTION: Neoadjuvant therapy (NT) is increasingly used for localized pancreatic ductal adenocarcinoma (PDAC). The impact of care fragmentation during NT on the outcomes of patients with PDAC is unknown. METHODS: Adult patients with Stage I–III PDAC who received NT and patients who underwent surgery first followed by adjuvant therapy (AT) between 2004 and 2016 were queried from the National Cancer Database. Short- and long-term outcomes were compared between patients who received fragmented care (FC; care provided at >1 hospital) versus integrated care (IC; care at a single institution). RESULTS: Among 6522 patients who underwent NT before pancreatectomy, 3755 (57.6%) received FC and 2767 (42.4%) received IC. While patients who received FC had a longer time to initiation of treatment (33.2 vs. 29.7 days, p < 0.001), there was no difference in median overall survival (OS) (26.7 vs. 26.5 months, p = 0.6). Among patients who underwent upfront surgery followed by AT (n = 15 291), patients who received FC had a longer time from diagnosis to undergoing surgery but less time from surgery to AT and no difference in OS (24.0 vs. 24.0 months, p = 0.910). CONCLUSION: Although care fragmentation was associated with slightly longer times to initiate and complete treatment among patients with localized PDAC, long-term survival outcomes were similar.

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34, 95%CI 1.27–11.38, p = 0.017) and OS (HR = 2.89, 95%CI 1.10–4.76, p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39, 95%CI 1.03–5.54, p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71, 95%CI 1.14–6.48, p = 0.025), DR (HR = 1.93, 95%CI 1.10–3.38, p = 0.022), and OS (HR = 1.97, 95%CI 1.17–3.34, p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p &lt, 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

The novel coronavirus disease 2019 (COVID-19) pandemic presents unique challenges for surgical management of laryngotracheal stenosis. High viral concentrations in the upper aerodigestive tract, the ability of the virus to be transmitted by asymptomatic carriers and through aerosols, and the need for open airway access during laryngotracheal surgery create a high-risk situation for airway surgeons, anesthesiologists, and operating room personnel. While some surgical cases of laryngotracheal stenosis may be deferred, patients with significant airway obstruction or progressing symptoms often require urgent surgical intervention. We present best practices from our institutional experience for surgical management of laryngotracheal stenosis during this pandemic, including preoperative triage, intraoperative airway management, and personal protective measures.

The relationship of volume and travel distance to patient outcomes after resection of gallbladder cancer (GBC) remains poorly defined.The 2004-2015 National Cancer Database was used to identify GBC resection patients and examine the impact of travel distance, hospital volume and both on overall survival (OS) and quality of care indicators.Among 10,174 patients undergoing surgery for GBC, the majority of patients were Caucasian (N = 8,175, 80%) and had a Charlson-Deyo comorbidity score of 0 (N = 6,785, 67%). On unadjusted survival analysis increasing travel distance and hospital volume were associated with improved OS (both p0.001). After controlling for competing risk factors, the 4th quartile of hospital volume was associated with a decreased hazard of death (HR 0.831, 95% CI 0.751-0.920, p0.001). When both hospital volume and travel distance were included, the association with improved OS persisted only for hospital volume (4th quartile HR 0.835, 95% CI 0.753-0.925, p0.001), whereas there was no independent association of increasing travel distance with OS.Both increasing travel distance and hospital volume were associated with improved OS; however, adjusted models demonstrated that the impact of travel distance was mediated through hospital volume.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Recent studies on postoperative pancreatic fistula (POPF) prevention following pancreatoduodenectomy (PD) have proposed omission of perioperative drains for negligible/low-risk patients and early drain removal (≤POD3) for intermediate/high-risk patients with POD1 drain amylase levels of ≤5000 U/L, though this has not been validated using a nationwide cohort.The ACS-NSQIP targeted pancreatectomy database from 2014 to 2016 was queried to identify patients who underwent PD. Patients with POD1 drain amylase levels of ≤5000 U/L were initially stratified as negligible/low- or intermediate/high-risk based on a previously validated modified fistula risk score (mFRS). Differences in relevant postoperative outcomes were then compared among patients who underwent early (≤POD3) vs. late (≥POD4) drain removal.Among 1825 patients who underwent PD, 1540 (84%) had POD1 drain amylase of ≤5000 U/L: 719 (47%) high-risk and 821 (53%) low-risk. Among high-risk patients, early drain removal (n = 205, 29%) was associated with lower rates of POPF (3% vs. 18%, p 0.001), clinically relevant (CR)-POPF (2% vs. 15%, p 0.001), overall morbidity (27% vs. 47%, p 0.001), serious morbidity (15% vs. 24%, p = 0.007) and hospital length of stay (LOS, 7 vs. 8 days, p 0.001). Similarly, early drain removal in low-risk patients (n = 273, 33%) was associated with decreased rates of POPF (1% vs. 6%, p = 0.003), CR-POPF (1% vs. 5%, p = 0.014), overall morbidity (28% vs. 41%, p = 0.0003), serious morbidity (8% vs. 14%, p = 0.015) and LOS (6 vs. 8 days, p 0.001). On multivariate logistic regression analysis, early drain removal remained associated with significantly decreased odds of POPF, CR-POPF, overall and serious morbidity as well as LOS among both high- and low-risk patients (all p 0.05).Among patients with POD1 drain amylase ≤5000 U/L following PD, early drain removal (≤POD3) is associated with improved postoperative outcomes among both high- and low-risk patients. Early drain removal based on POD1 drain amylase is indicated regardless of mFRS.

Formal gastrectomy is occasionally required to achieve complete cytoreduction for patients with peritoneal surface malignancies. In addition, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer is increasingly being explored. Nevertheless, data on the safety of gastrectomy at the time of CRS-HIPEC are limited.The American College of Surgeons-National Surgical Quality Improvement Program databases from 2005 to 2016 were used to identify patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative outcomes were compared between patients who underwent CRS-HIPEC with and without gastrectomy.Among 1168 patients who underwent CRS-HIPEC, 43 (4%) underwent partial (n = 20) or total (n = 23) gastrectomy. Patients who underwent gastrectomy at the time of CRS-HIPEC had a longer operative time (529.3 versus 457.6 min, P = 0.004), were more likely to need an intraoperative transfusion (32.6% versus 14.3%, P = 0.001), experienced a longer length of stay (19.0 versus 11.3 d, P 0.001), and had a significantly greater complication rate (60.5% versus 27.9%, P 0.001), whereas postoperative mortality was not statistically significantly different (4.7% versus 1.4%, P = 0.09). On multivariate logistic regression, gastrectomy (odds ratio [OR] 3.52, P 0.001) was the strongest predictor of postoperative morbidity, in addition to American Society of Anesthesiologists class 4 (OR 2.82, P = 0.001), malnutrition (OR 1.63, P = 0.01), liver resection (OR 1.88, P = 0.01), and colectomy (OR 2.04, P 0.001).Patients undergoing gastrectomy at the time of CRS-HIPEC experience a substantial postoperative complication rate (60%) and extended length of stay (mean 19 d). These findings highlight the need for cautious patient selection and preoperative counseling before performing concomitant gastrectomy and CRS-HIPEC.

Introduction: Neuroendocrine liver metastases (NELM) occur in roughly 60–90% of patients with neuroendocrine tumors during the disease course. Understanding the available treatment options ...

A retrospective study was performed to characterize trends in centralization of care and compliance with National Comprehensive Cancer Network (NCCN) guidelines for resected cholangiocarcinoma (CCA), and their impact on overall survival (OS).Using the National Cancer Database (NCDB) 2004-2015 we identified patients undergoing resection for CCA. Receiver Operating Characteristic (ROC) analyses identified time periods and hospital volume groups for comparison. Propensity score matching provided case-mix adjusted patient cohorts. Cox hazard analysis identified risk factors for OS.Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p0.001). Using ROC analyses, a hospital volume of 14 operations/year was the most sensitive and specific value associated with mortality. Surgery at high volume hospitals [HR] = 0.92, 95% CI: 0.88-0.97, p0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p0.001) were independently associated with improved OS.Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival.

Benzodiazepines, including diazepam (DZP), lorazepam (LZP), and midazolam (MDZ), are considered the initial drugs of choice for status epilepticus (SE) treatment. A number of trials have demonstrated their safety and efficacy; however, the failure rate ranges from 10‐55%.1,2 This may be attributable, in part, to sub‐optimal benzodiazepine dosing and timing of administration.\ud \ud The Neurocritical Care Society (NCS) and American Epilepsy Society (AES) have published evidence‐based guidelines for benzodiazepine use in SE that specify drugs, doses, and routes of administration.

Background The burden of health care spending in the United States is a major concern, as health care costs have exponentially increased during the last three decades. The objective of the current study was to investigate the degree of cost-concentration among Medicare patients undergoing liver and pancreatic surgery. Methods Medicare claims data from 2013 to 2015 were used to identify patients undergoing elective liver and pancreatic resections. Patients were divided into four groups: 1) non-complex pancreatic procedures; 2) complex pancreatic procedures; 3) non-complex liver procedures; and 4) complex liver procedures. Unadjusted price-standardized Medicare payments were calculated and payments were divided into quintiles. Patient-level factors associated with payments were analyzed by multivariable linear regression. Results A total of 17,125 patients were included in the study. Patients in the top quintile of spending accounted for over 40% of payments for all liver and pancreatic procedures. Patients with comorbidity scores ≥5, male sex, open surgical approach and a diagnosis of congestive heart failure were associated with higher costs. Conclusion Patients undergoing liver and pancreatic resections on the top 20% of payments were responsible for a disproportionate share of Medicare payments – over 40% of total expenditures. Overall hospital surgical volume was lower among the highest quintile of payments.

The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.