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The objective of the current study was to summarize current research on burnout among surgical trainees and surgeons during the COVID-19 pandemic.PubMed, SCOPUS, Embase, and Psych INFO were systematically searched for studies that evaluated burnout during the COVID-19 pandemic among surgical trainees and surgeons.A total of 29 articles met inclusion criteria, most of which originated from the United States (n = 18, 62.1%). Rates of burnout ranged from 6.0% to 86.0%. Personal factors responsible for burnout were fear of contracting/transmitting COVID-19 (8 studies, 27.6%), female gender (8, 27.6%), and younger age (5, 17.2%). Professional factors contributing to burnout included increased COVID-19 patient clinical load (6, 20.7%), limited work experience (6, 20.7%), reduction in operative cases (5, 17.2%) and redeployment to COVID-19 wards (4, 13.8%). The COVID-19 pandemic negatively impacted surgical education due to reduced number of operative cases (11, 37.9%), decreased hands-on experience (4, 13.8%), and not being able to complete case requirements (3, 10.34%). The shift of didactics to virtual formats (3, 10.3%), increased use of telemedicine (2, 6.9%), and improved camaraderie among residents (1, 3.4%) were viewed as positive consequences.COVID-19 related burnout was reported in as many as 1 in 2 surgical trainees and attending surgeons. Intrinsic- (i.e., gender, age), family- (i.e., family/being married/having children or being single/not having children), as well as work-related extrinsic- (i.e., work-force deployment, risk of infection/spread, changes in educational format) factors were strongly associated with risk of burnout. These factors should be considered when designing interventions to ameliorate burnout among surgical trainees and surgeons.

Post-traumatic epilepsy (PTE) and behavioral comorbidities frequently develop after traumatic brain injury (TBI). Aberrant neurogenesis of dentate granule cells (DGCs) after TBI may contribute to the synaptic reorganization that occurs in PTE, but how neurogenesis at different times relative to the injury contributes to feedback inhibition and recurrent excitation in the dentate gyrus is unknown. Thus, we examined whether DGCs born at different postnatal ages differentially participate in feedback inhibition and recurrent excitation in the dentate gyrus using the controlled cortical impact (CCI) model of TBI. Both sexes of transgenic mice expressing channelrhodopsin2 (ChR2) in postnatally born DGCs were used for optogenetic activation of three DGC cohorts: postnatally early born DGCs, or those born just before or after CCI. We performed whole-cell patch-clamp recordings from ChR2-negative, mature DGCs and parvalbumin-expressing basket cells (PVBCs) in hippocampal slices to determine whether optogenetic activation of postnatally born DGCs increases feedback inhibition and/or recurrent excitation in mice 8-10 weeks after CCI and whether PVBCs are targets of ChR2-positive DGCs. In the dentate gyrus ipsilateral to CCI, activation of ChR2-expressing DGCs born before CCI produced increased feedback inhibition in ChR2-negative DGCs and increased excitation in PVBCs compared with those from sham controls. This upregulated feedback inhibition was less prominent in DGCs born early in life or after CCI. Surprisingly, ChR2-positive DGC activation rarely evoked recurrent excitation in mature DGCs from any cohort. These results support that DGC birth date-related increased feedback inhibition in of DGCs may contribute to altered excitability after TBI. SIGNIFICANCE STATEMENT Dentate granule cells (DGCs) control excitability of the dentate gyrus through synaptic interactions with inhibitory GABAergic interneurons. Persistent changes in DGC synaptic connectivity develop after traumatic brain injury, contributing to hyperexcitability in post-traumatic epilepsy (PTE). However, the impact of DGC neurogenesis on synaptic reorganization, especially on inhibitory circuits, after brain injury is not adequately described. Here, upregulation of feedback inhibition in mature DGCs from male and female mice was associated with increased excitation of parvalbumin-expressing basket cells by postnatally born DGCs, providing novel insights into underlying mechanisms of altered excitability after brain injury. A better understanding of these inhibitory circuit changes can help formulate hypotheses for development of novel, evidence-based treatments for post-traumatic epilepsy by targeting birth date-specific subsets of DGCs.

Background There has been increased interest in understanding how social determinants of health (SDH) may affect care both in the medical and surgical setting. We sought to define the impact of various aspects of social vulnerability on the ability of patients to achieve a “textbook outcome” (TO) following hepatopancreatic surgery. Methods Medicare beneficiaries who underwent hepatopancreatic resection between 2013 and 2017 were identified using the Medicare database. Social vulnerability was defined using the Centers for Disease Control Social Vulnerability Index (SVI), which is comprised of four subthemes: socioeconomic (SE), household composition and disability (HCD), minority status and language (MSL), and housing type and transportation (HTT). TO was defined as the composite endpoint: absence of 90-day mortality or readmission, absence of an extended length of stay (LOS), and no complications during the index admission. Cluster analysis was used to identify vulnerability cohorts, and multivariable logistic regression was utilized to assess the impact of these SVI subthemes on the likelihood to achieve a textbook outcome. Results Among 37,707 Medicare beneficiaries, 64.9% (n = 24,462) of patients underwent pancreatic resection while 35.1% (n = 13,245) underwent hepatic resection. Median patient age was 72 years (IQR: 68–77), just over one-half were male (51.9%; n = 19,558), and the median CCI was 3 (IQR: 2–8). Cluster analysis revealed five distinct SVI profiles with wide variability in the distribution of SVI subthemes, ranging from 15 (profile 1 IQR: 7–26) to 83 (profile 5 IQR: 66–93). The five profiles were grouped into 3 categories based on median composite SVI: “low vulnerability” (profile 1), “average vulnerability” (profiles 2 and 3), or “high vulnerability” (profiles 4 and 5). The rate of TO ranged from 44.6% in profile 5 (n = 4022) to 49.2% in profile 1 (n = 4836). Multivariable analyses comparing patients categorized into the two average SVI profiles revealed that despite having similar composite SVI scores, the risk of adverse postoperative outcomes was not similar. Specifically, patients from profile 5 had lower odds of achieving a TO (OR 0.89, 95%CI: 0.83–0.95) and higher odds of 90-day mortality (OR 1.29, 95%CI: 1.15–1.44) versus patients in profile 4. Conclusion Distinct profiles of SVI subtheme characteristics were independently associated with postoperative outcomes among Medicare beneficiaries undergoing HP surgery, even among patients with similar overall composite SVI scores. Supplementary Information The online version contains supplementary material available at 10.1007/s11605-022-05245-9.

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.

Estimating early exposure of drugs used for the treatment of emergent conditions is challenging because blood sampling to measure concentrations is difficult. The objective of this work was to evaluate predictive performance of two early concentrations and prior pharmacokinetic (PK) information for estimating early exposure. The performance of a modeling approach was compared with a noncompartmental analysis (NCA). A simulation study was performed using literature‐based models for phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA). These models were used to simulate rich concentration‐time profiles from 0 to 2 h. Profiles without residual unexplained variability (RUV) were used to obtain the true partial area under the curve (pAUC) until 2 h after the start of drug infusion. From the profiles with the RUV, two concentrations per patient were randomly selected. These concentrations were analyzed under a population model to obtain individual population PK (PopPK) pAUCs. The NCA pAUCs were calculated using a linear trapezoidal rule. Percent prediction errors (PPEs) for the PopPK pAUCs and NCA pAUCs were calculated. A PPE within ±20% of the true value was considered a success and the number of successes was obtained for 100 simulated datasets. For PHT, LEV, and VPA, respectively, the median value of the success statistics obtained using the PopPK approach of 81%, 92%, and 88% were significantly higher than the 72%, 80%, and 67% using the NCA approach (p

We sought to determine the impact of payer-mix on post-operative outcomes among Medicare beneficiaries following hepatopancreatic surgery.Medicare beneficiaries who underwent hepatopancreatic surgery were identified. Hospital quality markers were obtained from the Hospital General Information dataset. Hospitals were dichotomized (low/average vs. high) based on Medicare patient days versus all patient days irrespective of payer type.High Medicare patient-mix hospitals were more likely to be ranked higher than the national average relative to safety of care (29.4% vs. 38.1%) and timeliness of care (15.4% vs. 26.3%) versus low burden Medicare hospitals (both p 0.001). However, Medicare beneficiaries who had hepatopancreatic surgery at a high Medicare patient-mix hospital were at higher risk of a complication (OR = 1.13, 95%CI 1.04-1.22), and death within 30-days (OR = 1.37, 95%CI 1.23-1.53) following surgery.While hospitals caring for higher numbers of Medicare beneficiaries generally performed better on CMS quality indicators, these rankings did not equate to improved post-operative outcomes.

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.

Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates.To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS.This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021.Cytoreductive surgery.Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC).Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes.In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses particularly in young children. The Established Status Epilepticus Treatment Trial (ESETT), a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients ≥ 2 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomized to FOS, LEV or VPA infused over 10 minutes. A sparse blood sampling approach was used, with up to two samples collected per patient within two hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV and VPA and plasma protein binding of PHT and VPA. Twenty-seven children with median (interquartile range) age of 4 (2.5, 6.5) years were enrolled. The total plasma concentrations ranged from 69-151.3 μg/mL for LEV, 11.3-26.7 μg/mL for PHT and 126-223 μg/mL for VPA. Free fraction ranged from 4-19% for PHT and 17-51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure-response relationships in this emergent condition. This article is protected by copyright. All rights reserved.

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.

Background Many hospitals have implemented visitor restriction policies in response to the COVID-19 pandemic. Since caregivers serve an important role in postoperative recovery, the purpose of this study was to evaluate the impact of visitor restrictions on the postoperative experience of COVID-negative patients undergoing surgery. Methods Patients who underwent surgery immediately prior to or following the implementation of a visitor restriction policy were enrolled. Patients were surveyed on their inpatient experience and preparedness for discharge using items adapted from validated questionnaires. Results Among 128 eligible patients, 117 agreed to participate (91.4% response rate): 58 (49.6%) in the Visitor Cohort and 59 (50.4%) in the No-Visitor Cohort. Mean age was 57.5 years (SD 13.9) and 66 (56.4%) were female. Among all patients, 47.8% underwent oncologic surgery, 31.6% transplant, and 20.5% general/other. Patients in the No-Visitor Cohort were less likely to report complete satisfaction with the hospital experience (80.7% vs 66.0%, p=0.044), timely receipt of medications (84.5% vs 69.0%, p=0.048) and assistance getting out of bed (70.7% vs 51.7%, p=0.036). No-Visitor Cohort patients were less likely to feel that their discharge preferences were adequately considered (79.3% vs 54.2%, p=0.004). Qualitative analysis of patient responses highlighted the consistent psychosocial support provided by visitors following surgery (84.5%) and patients in the No-Visitor Cohort reported social isolation due to lack of psychosocial support (50.8%). Conclusion The implementation of hospital visitor restriction policies may adversely impact the postoperative experience of COVID-negative patients undergoing surgery. These findings highlight the urgent need for novel patient-centered strategies to improve the postoperative experience of patients during ongoing or future disruptions to routine hospital practice., Highlights TOC Statement- 20201117 This observational cohort study found that COVID-19-related hospital visitor restriction policies adversely impacted the post-operative experience of patients in several unique domains. The importance of this report reveals the need for strategies to improve the postoperative experience of patients during ongoing visitor restrictions associated with the COVID-19 pandemic.

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.

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

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 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. Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS. Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000–2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS. Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7–20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16–3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08–5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS. Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.

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.

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.

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.

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.

Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection. While adjuvant chemotherapy improves survival, a significant proportion of patients are unable to initiate or complete all intended therapy following pancreatectomy due to postoperative complications or poor performance status. The administration of chemotherapy prior to surgical resection is an alternative strategy that ensures its early and near universal delivery as well as improves margin-negative resection rates and potentially improves long-term survival outcomes. Neoadjuvant therapy is increasingly being recommended to patients with pancreatic ductal adenocarcinoma, however, patient-centered research on its use is lacking. In this review, we highlight opportunities to focus research efforts in the domains of patient preferences, patient-reported outcomes, patient experience, and survivorship. Novel research in these areas may identify relevant barriers and facilitators to the use of neoadjuvant therapy thereby increasing its utilization, improve shared-decision making for patients and providers, and optimize the experience of those undergoing neoadjuvant therapy.

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.

Background The focus of the current Medicare payment reform is to increase value – i.e. improve health care quality while lowering costs. This study sought to define cost variation and surgical quality among hospitals within small geographic areas typical of work commute patterns. Methods Medicare Provider Analysis and Review (MEDPAR) Inpatient Files was used to identify patients undergoing elective liver and pancreatic surgery between 2013 and 2015. Hospitals were assigned to combined statistical areas (CSAs) based on zip codes. Average price-standardized Medicare payments were used to identify highest- and lowest-cost hospitals within CSAs, and clinical outcomes were compared. Results The study included 12,016 patients. Medicare payments for index hospitalization were 45% ($12,580), 42% ($16,831), 44% ($12,901) and 50% ($18,605) higher for the highest-vs. lowest-cost hospitals for non-complex pancreatic procedures, complex pancreatic procedures, non-complex liver procedures, and complex liver procedures, respectively. Surgical quality was worse at highest-vs. lowest-cost hospitals, demonstrated by higher rates of complications, prolonged LOS and 90-day mortality. Conclusion There was a significant variation in surgical cost for each procedure between CSAs, and within CSAs. Highest-cost hospitals demonstrated worse quality metrics than the lowest-cost hospitals. Local referrals to low-cost hospitals represent an opportunity for increasing value of surgical care.

Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood.Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula).Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p 0.01), higher complication rate (90% vs 59%; p 0.01), higher reoperation rate (41% vs 9%; p 0.01), more 30-day readmissions (59% vs 22%; p 0.01), greater 30-day mortality (9% vs 1%; p 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p 0.01).Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

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.

Background Despite recent enthusiasm for the use of laparoscopic liver resection, data evaluating costs associated with laparoscopic liver resections are lacking. We sought to examine the use of laparoscopic liver surgery, and investigate variations in cost among hospitals performing these procedures. Methods A nationally representative sample of 12,560 patients who underwent a liver resection in 2012 was identified. Multivariable analyses were performed to compare outcomes associated with liver resection. Results Among the 12,560 patients who underwent liver resection, 685 (5.4%) underwent a laparoscopic liver resection. The proportion of liver resections performed laparoscopically varied among hospitals ranging from 4.6% to 20.0%; the median volume of laparoscopic liver resections was 10 operations/year. Although laparoscopic surgery was associated with lower postoperative morbidity (aOR = 0.60, 95%CI: 0.36–0.99) and shorter lengths of stay [(LOS) aIRR = 0.83, 95%CI: 0.70–0.97], it was not associated with inpatient mortality (p = 0.971) or hospital costs (p = 0.863). Costs associated with laparoscopic liver resection varied ranging from $5,907 (95%CI: $5,140-$6,674) to $67,178 (95%CI: $66,271-$68,083). The observed variations between hospitals were due to differences in morbidity (coefficient: $20,415, 95%CI: $16,000-$24,830) and LOS (coefficient: $24,690, 95%CI: $21,688-$27,692). Conclusions Although laparoscopic liver resection was associated with improved short-term perioperative clinical outcomes, utilization of laparoscopic liver resection remains low.

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.

Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC.The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed.Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA.While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

Background We sought to characterize epidural analgesia (EA) use among Medicare patients undergoing hepatopancreatic (HP) procedures, identify factors associated with EA use and asses perioperative outcomes. Methods Patients undergoing HP surgery were identified using the Inpatient Standard Analytic Files. Logistic regression was utilized to identify factors associated with EA receipt, and assess associations of EA with in-hospital outcomes and Medicare expenditures. Results Among 20,562 patients included in the study, 6.7% (n =1362) had EA. There was no difference in the odds of complications (OR 1.05, 95% CI 0.93–1.19) or blood transfusions (OR 0.90, 95% CI 0.79–1.03) with EA versus conventional analgesia (CA). The odds of prolonged LOS (OR 1.16, 95% CI 1.03–1.30) were higher with EA; the odds of in-hospital mortality were higher with conventional analgesia (OR 1.90, 95% CI 1.28–2.83). Medicare payments for liver surgery were comparable among EA ($19,500) versus conventional analgesia ($19,300, p = 0.85) and slightly higher for EA ($23,600) versus conventional analgesia ($22,000, p Conclusion EA utilization among Medicare patients undergoing HP was low. While EA was not associated with morbidity, it resulted in an average additional one day LOS and slightly higher expenditures in pancreatic surgery.

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.

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.

Many children recovering from anesthesia experience pain that is severe enough to warrant intravenous (IV) opioid treatment within moments of admission to the postanesthesia care unit (PACU). Postoperative pain has several negative consequences; therefore, preventing significant PACU pain in children is both a major clinical goal and a moral/ethical imperative. This requires identifying patient-level and perioperative factors that may be used to predict PACU IV opioid requirement. This should allow for the development of personalized care protocols to prevent clinically significant PACU pain in children. Our objective was to develop prediction models enabling practitioners to identify children at risk for PACU IV opioid requirement after various painful ambulatory surgical procedures.After Institutional Review Board approval, clinical, demographic, and anthropometric data were prospectively collected on 1256 children 4-17 years of age scheduled for painful ambulatory surgery (defined as intraoperative administration of analgesia or local anesthetic infiltration). Three multivariable logistic regression models to determine possible predictors of PACU IV opioid requirement were constructed based on (1) preoperative history; (2) history + intraoperative variables; and (3) history + intraoperative variables + PACU variables. Candidate predictors were chosen from readily obtainable parameters routinely collected during the surgical visit. Predictive performance of each model was assessed by calculating the area under the respective receiver operating characteristic curves.Overall, 29.5% of patients required a PACU IV opioid, while total PACU analgesia requirement (oral or IV) was 41.1%. Independent predictors using history alone were female sex, decreasing age, surgical history, and non-Caucasian ethnicity (model area under the receiver operating characteristic curve [AUROC], 0.59 [95% confidence interval {CI}, 0.55-0.63]). Adding a few intraoperative variables improved the discriminant ability of the model (AUROC for the history + intraoperative variables model, 0.71 [95% CI, 0.67-0.74]). Addition of first-documented PACU pain score produced a substantially improved model (AUROC, 0.85 [95% CI, 0.82-0.87]).Postoperative pain requiring PACU IV opioid in children may be determined using a small set of easily obtainable perioperative variables. Our models require validation in other settings to determine their clinical usefulness.

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.

BACKGROUND: Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance. METHODS: A single institutional, cross-sectional analysis of the preferences of adult cancer survivors regarding the means (secure digital communication versus phone call or office visit) to receive surveillance test results was undertaken. RESULTS: Among 257 respondents, the average age was 59.1 years (SD 13.5) and 61.8% were female. Common malignancies included melanoma/sarcoma (29.5%), thyroid (25.7%), breast (22.8%), and gastrointestinal (22.0%) cancer. Although patients expressed a relative preference to receive normal surveillance results via MyChart or secure e-mail, the majority preferred abnormal imaging (87.2%) or blood results (85.9%) to be communicated by in-office appointments or phone calls irrespective of age or cancer type. Patients with a college degree or higher were more likely to prefer electronic means of communication of abnormal blood results compared with a telephone call or in-person visit (odds ratio 2.18, 95% confidence interval: 1.01−4.73, P < .05). In contrast, patients >65 years were more likely to express a preference for telephone or in-person communication of normal imaging results (odds ratio: 2.03, 95% CI: 1.16−3.56, P < .05) versus patients ≤65 years. Preference also varied according to malignancy type. CONCLUSION: Although many cancer patients preferred to receive “normal” surveillance results electronically, the majority preferred receiving abnormal results via direct conversation with their provider. Shifting routine communication of normal surveillance results to technology-based applications may improve patient satisfaction and decrease health care system costs.

An understanding of the overall routine intensive care unit utilization, and characterization of the factors associated with a routine intensive care unit stay, may help identify ways to decrease overutilization of this resource after pancreatic surgery.Patients undergoing major pancreatic resection were identified in the Truven Health Analytics (Ann Arbor, MI) MarketScan Commercial Claims and Encounters Database from 2010 to 2014. Routine postoperative intensive care unit admission was defined as an admission to the intensive care unit of 24 hours or less on postoperative day zero. The association between routine intensive care unit admission and postoperative outcomes, including extended length of stay, failure to rescue, and total inpatient costs were evaluated.Of 3,280 patients who underwent a major pancreatic resection, 1,715 patients (52.3%) had a routine intensive care unit admission, which trended down over time (2010, n = 349; 53.0% versus 2014, n = 299; 47.5%; P = .019). The incidence of failure to rescue among patients who were routinely admitted to the intensive care unit (3.7%) was comparable to those admitted to the floor (1.7%, P = .098). Patients who were routinely admitted to the intensive care unit after major pancreatic resection had a median length of stay of 10 days (IQR: 7-15 days) versus 8 days (IQR: 7-12 days) for patients who were not admitted to the ICU (P.001). Routine intensive care unit admission was not associated with higher overall payments (ratio of adjusted total payments: 1.02, 95% CI: 0.98-1.06, P = .297).Routine intensive care unit admission was associated with a longer length of stay but did not translate into lower failure to rescue among patients.

Recent studies on postoperative pancreatic fistula (POPF) prevention suggest that omission of perioperative drains is safe for negligible- or low-risk patients undergoing pancreatoduodenectomy (PD). However, this proposed pathway has not been validated in a nationwide cohort.The ACS-NSQIP-targeted pancreatectomy database from 2014 to 2016 was queried to identify patients who underwent PD. Using a previously validated modified Fistula Risk Score (mFRS), patients were stratified as negligible/low- or intermediate/high-risk. Multivariate regression models were used to analyze the effect of intraoperative drain placement on relevant perioperative outcomes in both high- and low-risk patients.Among 6,730 patients undergoing PD, 3,375 (50%) were high-risk; 3,355 (50%) were low-risk. Among high-risk patients, drain placement (n = 3,093, 92%) was associated with a higher rate of POPF (26% vs 16%, p = 0.0003), clinically relevant (CR) POPF (20% vs 12%, p = 0.0015), and extended hospital length of stay (LOS, 9 vs 7 days, p0.0001), but decreased serious morbidity (29% vs 35%, p = 0.0330). Similarly, drain placement in low-risk patients (n = 2,785, 83%) was associated with a higher rate of POPF (11% vs 6%, p = 0.0006) and extended LOS (8 vs 7 days, p0.0001), yet lower serious morbidity (18% vs 23%, p = 0.0037). On multivariate logistic regression, drain placement was associated with significantly increased odds of CR-POPF and a significantly reduced incidence of serious morbidity among both high-risk (odds ratio [OR] 0.72, 95% CI 0.55 to 0.94, p = 0.0155) and low-risk patients (OR 0.71, 95% CI 0.57 to 0.89, p = 0.0027).In this population-based cohort, the mFRS was unable to stratify patients relative to the need for selective drain placement during PD. For both high- and low-risk patients, perioperative drain placement was associated with increased rates of POPF, CR-POPF, and extended LOS, but decreased incidence of serious morbidity.

The aim of the current study was to identify the minimum number and the optimal range of lymph nodes (LNs) to be examined among patients with gallbladder cancer (GBC).Between January 1, 2004, and December 31, 2015, patients with a diagnosis of GBC were identified in the National Cancer Database. A machine-based learning approach was used to identify the minimum number and range of LNs to evaluate relative to long-term outcomes.Among 6531 patients with GBC, median number of LNs evaluated was 2 (IQR:1-5); only 21.1% (n = 1376) of patients had 6 or more LNs evaluated. The median number of metastatic LNs was 0 (IQR: 0-1). On multivariable analysis, evaluation of 4 LNs was associated with a higher hazard of death (referent 4-7 LNs: 4 LNs, HR = 1.27, 95% CI, 1.16-1.40; P 0.001), whereas, patients who had 4 to 7 LNs and 7 LNs evaluated had comparable long-term mortality risk (HR = 1.10, 95%CI, 0.98-1.24; P = 0.11). There was no difference in the proportion of patients who had at least one metastatic LN identified per T category based on total number of nodes resected (all P 0.05).The overwhelming majority of patients did not have the American Joint Committee on Cancer (AJCC) recommended 6 total LN count . A machine-based learning approach identified evaluation of 4 to 7 LNs as the LN number associated with optimal staging and survival. While obtaining 6 LNs may be challenging, evaluation of at least 4 LNs may be a more appropriate threshold as this cut-off value was associated with optimal patient outcomes and staging.