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An estimated 25% of patients with colorectal cancer (CRC) present with distant metastases at the time of diagnosis, the most common site being the liver. Controversy exists regarding the safety of a simultaneous versus staged approach to resections in these patients, but reports have shown that minimally invasive surgery (MIS) approaches can mitigate morbidity. This is the first study utilizing a large national database to investigate colorectal and hepatic procedure-specific risks in robotic simultaneous resections for CRC and colorectal liver metastases (CRLM). Utilizing the ACS-NSQIP targeted colectomy, proctectomy, and hepatectomy files, 1,550 patients were identified who underwent simultaneous resections of CRC and CRLM from 2016–2020. Of these patients, 311 (20%) underwent resections by an MIS approach, defined as an either laparoscopic (n = 241, 78%) or robotic (n = 70, 23%). Patients who underwent robotic resections had lower rates of ileus compared to those who had an open surgery. The robotic group had similar rates of 30-day anastomotic leak, bile leak, hepatic failure, and post operative invasive hepatic procedures compared to both the open and laparoscopic groups. The rate of conversion to open was significantly lower for robotic compared to laparoscopic group (9% vs. 22%, p = 0.012). This report is the largest study to date of robotic simultaneous CRC and CRLM resections reported in the literature and supports the safety and potential benefits of this approach.

Background: Anal cancer incidence is increasing in the US. Though formally established national anal cancer screening guidelines are nonexistent, many providers advocate screening to avoid late disease presentation. This study assesses the knowledge, attitudes, and practices of anal cancer screening among providers to identify the degree of variation and barriers to screening. Methods: Healthcare providers from two academic medical centers and a statewide community primary care group were surveyed using a questionnaire adapted from the National Survey of Primary Care Physicians’ Recommendations and Practice for Cancer Screening. Descriptive statistics were performed to explore providers’ responses and Fisher’s exact test to explore variation. Results: 86 providers completed the questionnaire (response rate 24.2%): 81.4% physicians, 18.6% advanced practitioners. 48.2% of respondents perform anal cancer screening. 5.8% correctly identified all high-risk patient factors. “HIV+ patient” was identified most frequently as high-risk (93.5%), “organ transplant recipient” (42.9%) least frequently. Anal pap test was the most recommended first-line screening test (76.6%) followed by digital anorectal exam (19.2%), HPV test (8.5%), and high-resolution anoscopy (HRA) (6.4%). Clinical evidence (72.3%) and national guidelines (70.2%) were most influential in guiding providers’ screening recommendations. Lack of qualified screening providers (34.1%), lack of patient follow-up after positive test results (22.7%), and patient non-compliance to initial screening (15.9%) were identified as “usual” barriers. Conclusions: Anal cancer screening attitudes and practices vary among providers. Development of national practice guidelines that define a multidisciplinary team approach from primary care anal cancer screening to specialist referral for HRA may reduce screening variability.

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.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose and has dismal survival rates. Molecular imaging techniques such as positron emission tomography (PET) could fulfill an unmet need and enable an early diagnosis of PDAC to potentially improve survival. EphA2, a member of Erythropoietin-producing hepatocellular (Eph) receptors, plays a pivotal role in the tumorigenesis and development of an immune suppressive microenvironment in PDAC. We therefore developed a peptide-based PET imaging agent for EphA2, [68Ga]AJ201, and evaluated its pharmacokinetics and potential to non-invasively quantify variable EphA2 expression in PDAC. Methods: A Gallium-68 labeled EphA2 binding peptide, [68Ga]AJ201, was synthesized in high radiochemical yields and purity. Surface plasmon resonance (SPR) analysis was carried out to measure binding affinity. EphA2 expression was assessed in PDAC cell lines and tissues in CCLE and TCGA. EphA2 expression in seven PDAC cell lines (Panc1, AsPC1 BxPC3, CFPAC1, Hs766T, Panc1005, and SU8686) was validated by RT-qPCR and flow cytometry. Those cell lines were then used for in vitro binding assays and the corresponding xenografts in NSG mice for PET imaging and ex vivo biodistribution studies (n=4-5/tumor). Specificity of [68Ga]AJ201 was confirmed by co-injection of a blocking dose of non-radioactive AJ201 (1 mg/kg). Results: SPR analysis showed that AJ201 binds EphA2 with a high affinity (KD) of 0.2 nM. TCGA analysis revealed higher expression of EphA2 in PDAC vs healthy tissues. Flow cytometry analysis revealed high and variable EphA2 expression in all the PDAC cell lines tested with Panc1 exhibiting the highest levels. In vitro binding assays showed high and variable [68Ga]AJ201 uptake in all the PDAC cell lines and low uptake in the presence of 1µM non-radioactive AJ201 and in EphA2 negative Jurkat cells. Pharmacokinetics of [68Ga]AJ201 in mice with Panc1 tumors showed high contrast images of EphA2 expression at 60 minutes with a tumor/muscle ratio of 25.9±6.7. That high tumor uptake was significantly reduced in mice receiving blocking dose confirming the specificity of the radiotracer. Also, [68Ga]AJ201 PET quantified variable EphA2 expression in all the seven PDAC xenografts tested, with highest uptake observed in Panc1 tumor, followed by SU8686, and lowest in CFPAC1. Ex vivo biodistribution studies corroborated PET imaging findings. Conclusion: [68Ga]AJ201 is a EphA2 specific high affinity peptide-based PET imaging agent that provides high contrast PET images of PDAC by 60 minutes. [68Ga]AJ201 PET has the potential to non-invasively detect PDAC in patients. Citation Format: Kuldeep Gupta, Ajay Kumar Sharma, Akhilesh Mishra, Sophia Y. Chen, Gabi Lofland, Todd M. Armstrong, Lei Zhang, Elizabeth M. Jaffee, Sridhar Nimmagadda. Imaging pancreatic ductal adenocarcinoma using an EphA2 receptor tyrosine kinase binding 68Ga-labeled peptide radiotracer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2481.

Frailty and functional dependence are important factors in assessing preoperative risk. No studies to date have compared frailty with functional dependence as a predictor of surgical outcomes. We sought to compare the impact of frailty and functional dependence on early outcomes after gastrointestinal surgery.Patients who underwent gastrointestinal surgery were identified using the American College of Surgeons National Surgical Quality Improvement Program database (2012-2015). Propensity score matching analysis was used to separately match dependent and independent patients, and patients with modified frailty index3 and modified frailty index ≥3 on baseline characteristics. Multivariable logistic regression analysis was used. Postoperative outcomes were compared.Of 765,082 patients, 1.71% were dependent and 1.49% had a modified frailty index score ≥3. Similar outcomes were observed in matched cohorts for those who were dependent and patients with a modified frailty index score ≥3: readmission (15.61% dependent and 15.75% modified frailty index ≥3), overall morbidity (37.91% and 34.81%), serious morbidity (19.06% and 17.06%), mortality (6.73% and 5.43%), and reoperation (7.01% and 6.48%). Dependent and modified frailty index ≥3 patients had similar odds of outcomes on adjusted multivariable logistic analysis and shared 3 of the top 5 indicators for readmission: complication of surgical procedure (11.46% dependent and 11.23% mFI ≥3), intestinal obstruction (10.70% and 7.65%), and organ space surgical site infection (7.93% and 8.65%). Comparable outcomes and reasons for readmission were also obtained for dependent patients and colectomy patients with a modified frailty index score ≥3.Frailty and functional dependence are comparable in predicting postoperative outcomes after gastrointestinal surgery. Functional dependence should be considered an acceptable and practical alternative for preoperative risk stratification in a clinical setting.

Background Our objective was to determine the association between indicators of surgical quality – incidence of major complications and failure-to-rescue – and hospital market concentration in light of differences in costs of care. Methods Patients undergoing coronary artery bypass graft (CABG), colon resection, pancreatic resection, or liver resection in the 2008–2011 Nationwide Inpatient Sample were identified. The effect of hospital market concentration on major complications, failure-to-rescue, and inpatient costs was estimated at the lowest and highest mortality hospitals using multivariable regression techniques. Results A weighted total of 527,459 patients were identified. Higher market concentration was associated with between 4% and 6% increased odds of failure-to-rescue across all four procedures. Across procedures, more concentrated markets had decreased inpatient costs (average marginal effect ranging from -$3064 (95% CI: -$5812 - -$316) for CABG to -$4876 (-$7773 - -$1980) for liver resection. Conclusion In less competitive (more concentrated) hospital markets, higher overall risk of failure-to-rescue after complications was accompanied by lower inpatient costs, on average. These data suggest that market controls may be leveraged to influence surgical quality and costs.

An area of contention among colorectal surgeons is when it is safe to discharge patients who have undergone closure of diverting ostomies. This study aimed to review the trends in outpatient stoma closure (OSC), to assess the safety of this practice, and to identify appropriate surgical candidates for the outpatient procedure.Patients were queried from the ACS National Surgical Quality Improvement Program database (2005-2016). Main outcomes included Clavien-Dindo (C-D) III-V class surgical complications, and readmission. Outpatient stay was defined as a hospital stay of less than or equal to 1 day. Multivariable logistic regression analysis was used to identify risk factors for C-D III-V complications and readmission.Of 24,393 patients, 668 (2.74%) underwent an OSC. OSC has increased over the last decade (3.16% 2005-2006, 4.14% 2016, p 0.001). Outpatients had significantly lower ASA class and fewer comorbidities than inpatients. Outpatient complication rate was significantly lower than the inpatient rate (2.99% vs. 7.25%, p 0.001). Readmissions were comparable (8.92% outpatient vs. 9.77% inpatient, p = 0.54). ASA 2, smoking, COPD, dyspnea, steroid use, bleeding disorder, and partial/total dependency were associated with increased risk of complications and readmission. Patients without any risk factors had lower complication (4.75%) and readmission rates (8.09%) compared to those with ≥ 2 risk factors (11.50% complication and 13.07% readmission rate, p 0.001).There is an increasing trend in the percentage of stoma closures being performed as outpatient procedures. Appropriate selection of patients preoperatively who are suitable candidates for OSC can be helpful in managing patient expectations and hospital resources.

Timing of surgical intervention for acute ulcerative colitis has not been fully examined during the modern immunotherapy era. Although early surgical intervention is recommended, historical consensus for "early" ranges widely. The purpose of this study was to evaluate outcomes according to timing of urgent surgery for acute ulcerative colitis.All non-elective total colectomies in ulcerative colitis patients were identified in the National Inpatient Sample from 2002 to 2014. Procedures, comorbidities, diagnoses, and in-hospital outcomes were collected using International Classification of Disease, 9th Revision codes. An operation was defined as early if within 24 hours of admission. Results were compared between the early versus delayed surgery groups.We found 69,936 patients that were admitted with ulcerative colitis, and 2650 patients that underwent non-elective total colectomy (3.8%). Early intervention was performed in 20.4% of patients who went to surgery. More early operations were performed laparoscopically (28.1% versus 23.3%, p = 0.021) and on more comorbid patients (Charlson Index, p = 0.008). Median total hospitalization costs were $20,948 with an early operation versus $33,666 with a delayed operation (p 0.001). Delayed operation was an independent risk for a complication (OR = 1.46, p = 0.001). Increased hospitalization costs in the delayed surgery group were statistically significantly higher with a reported complication (OR = 3.00, p 0.001) and lengths of stay (OR = 1.26, p 0.001).Delayed operations for acute ulcerative colitis are associated with increased postoperative complications, increased lengths of stay, and increased hospital costs. Further prospective studies could demonstrate that this association leads to improved outcomes with immediate surgical intervention for medically refractory ulcerative colitis.

Guidelines for transfusion focus on nadir levels of hemoglobin. Hemoglobin triggers may not be helpful, however, in defining appropriate intraoperative use of packed red blood cells. We sought to define the use of intraoperative packed red blood cells relative to quantitative physiologic factors at the time of operation.Prospective intraoperative data on patients undergoing a major gastrointestinal operation between 2010 and 2014 were analyzed. Risk of intraoperative transfusion was assessed with multivariable extended Cox models using baseline clinical covariates and time-varying intraoperative covariates.Among 2,316 patients, the mean preoperative hemoglobin was 12.6 g/dL (standard deviation = 2.0 g/dL), while the median estimated blood loss was 200 mL (interquartile range: 100-55 mL). Overall, 357 (15.4%) patients received a transfusion intraoperatively. A greater hazard of transfusion was associated with a greater American Society of Anesthesiologists class (ref: American Society of Anesthesiologists class I-II; American Society of Anesthesiologists class III-IV; hazard ratio = 1.44, 95% confidence interval, 1.18-1.77, P .001), and a lesser preoperative hemoglobin level (per 1 g/dL increase; hazard ratio = 0.70, 95% confidence interval, 0.65-0.74, P .001). In addition, an increase in heart rate of 10 beats/min above the cumulative average at any measurement was associated with up to a 30% increased probability of transfusion (hazard ratio = 1.30, 95% confidence interval, 1.15-1.47, P .001); similarly, an increase in mean arterial pressure of 10 mm Hg was associated with an 8% decreased likelihood of transfusion (hazard ratio = 0.92, 95% confidence interval, 87-0.99, P = .017). In contrast, nadir hemoglobin was not associated with the risk of receiving a transfusion (hazard ratio = 1.10, 95% confidence interval, 0.97-1.23, P = .129). Among patients who received an intraoperative transfusion, 9.2% (n = 33) never had a hemoglobin nadir below 10 g/dL, nor an average mean arterial pressure less than 65 mm Hg or a heart rate greater than 100 beats/min around the time of transfusion.Among the intraoperative factors, heart rate, and mean arterial pressure were strongly associated with the likelihood of receiving a transfusion, despite the observation that 9.2% of patients never had a physiologic indicator for transfusion or a nadir hemoglobin below 10 g/dL, suggesting a subset of patients could benefit from a decrease in intraoperative rate of transfusion.

Readmission has received attention as a potential healthcare quality metric. No studies have investigated the relationship between readmission and survival in patients undergoing rectal cancer surgery. The aims of this study were to identify factors associated with 30-day readmission after rectal cancer surgery and to determine the impact of readmission on overall survival (OS). Patients who underwent surgical treatment for rectal/rectosigmoid adenocarcinoma stages I–IV were identified using the National Cancer Database (2004–2014). Multivariable logistic regression was used to identify factors for readmission. 2:1 nearest neighbor caliper matching without replacement was used to ensure similarity of patients being compared. Survival analyses were performed using Kaplan–Meier method along with log-rank test and Cox proportional hazards model. Of 110,167 patients, 7045 (6.39%) were readmitted. Factors associated with readmission included higher Charlson comorbidity score, non-private or no insurance, procedure type, hospitals in the Northeast, South, and Midwest regions, and prolonged length of stay. Within the matched cohort (13,756 non-readmitted and 6878 readmitted), readmitted patients had worse 5- and 10-year OS regardless of cancer stage (p

Immunotherapy advances for the treatment of cutaneous melanoma question its efficacy in treating anorectal mucosal melanoma (ARMM). We aimed to identify the prevalence, current management, and overall survival (OS) for ARMM. Review of patients with ARMM from 2004 to 2015 National Cancer Database. Factors associated with immunotherapy were identified using multivariable logistic regression. The primary outcome was 2- and 5-year OS. Subgroup analysis by treatment type was performed. A total of 1331 patients were identified with a significant increase in prevalence (2004: 6.99%, 2015: 10.53%). ARMM patients were older, white, on Medicare, and from the South. The most common treatment was surgery (48.77%), followed by surgery + radiation (11.75%), surgery + immunotherapy (8.68%), and surgery + chemotherapy (8.68%). 16.93% of patients received immunotherapy, with utilization increasing (7.24%: 2004, 21.27%: 2015, p

Background Although uncoordinated postdischarge care has been associated with poor clinical outcomes, the effect of discharge to a low healthcare resource area (LHRA) on readmission remains undetermined. We sought to assess how the quality of discharge area health resources impact readmission following major surgery. Methods This cross-sectional study was performed by linking Maryland state data for 2012-2015 to the Agency for Healthcare Research and Quality Area Health-Resource File. Patients undergoing one of 11 common surgical procedures were identified. Multivariable logistic regression was performed to assess the effect of discharge area health resource quality on readmission. Results A total of 76,747 patients were identified of which 9.4% were discharged to a high healthcare resource area (HHRA), whereas 81.9% of patients were discharged to an LHRA. Perioperative morbidity and length of stay were comparable between HHRA versus LHRA patients (both P > 0.05). Among all patients, 30-d and 90-d readmission was 6.5% and 12.4%, respectively. On multivariable analysis, discharge to LHRA was independently associated with a 19% (odds ratio = 1.19; 95% CI, 1.01-1.41; P = 0.043) and 18% (odds ratio = 1.18; 95% CI, 1.04-1.33; P = 0.010) greater odds of 30-d and 90-day readmission, respectively. Conclusions Patients discharged to an area characterized by LHRA were more likely to be readmitted at 30 d and 90 d following index discharge.

Background All-cause readmission rates in patients undergoing ileostomy formation are as high as 20% to 30%. Dehydration is a leading cause. No predictive model for dehydration readmission has been described. Objective The purpose of this study was to develop and validate the Dehydration Readmission After Ileostomy Prediction scoring system to predict the risk of readmission for dehydration after ileostomy formation. Design Patients who underwent ileostomy formation were identified using the American College of Surgeons National Surgical Quality Improvement Program data set (2012-2015). Predictors for dehydration were identified using multivariable logistic regression analysis and translated into a point scoring system based on corresponding β-coefficients using 2012-2014 data (derivation). Model discrimination was assessed with receiver operating characteristic curves using 2015 data (validation). Settings This study used the American College of Surgeons National Surgical Quality Improvement Program. Patients A total of 8064 (derivation) and 3467 patients (validation) were included from the American College of Surgeons National Surgical Quality Improvement Program. Main outcome measures Dehydration readmission within 30 days of operation was measured. Results A total of 8064 patients were in the derivation sample, with 2.9% (20.1% overall) readmitted for dehydration. Twenty-five variables were queried, and 7 predictors were identified with points assigned: ASA class III (4 points), female sex (5 points), IPAA (4 points), age ≥65 years (5 points), shortened length of stay (5 points), ASA class I to II with IBD (7 points), and hypertension (9 points). A 39-point, 5-tier risk category scoring system was developed. The model performed well in derivation (area under curve = 0.71) and validation samples (area under curve = 0.74) and passed the Hosmer-Lemeshow goodness-of-fit test. Limitations Limitations of this study pertained to those of the American College of Surgeons National Surgical Quality Improvement Program, including a lack of generalizability, lack of ileostomy-specific variables, and inability to capture multiple readmission International Classification of Diseases, 9/10 edition, codes. Conclusions The Dehydration Readmission After Ileostomy Prediction score is a validated scoring system that identifies patients at risk for dehydration readmission after ileostomy formation. It is a specific approach to optimize patient factors, implement interventions, and prevent readmissions. See Video Abstract at http://links.lww.com/DCR/A746.

Enhanced recovery pathways have been shown to improve clinical outcomes after surgery. Concerns exist about the feasibility of implementing enhanced recovery pathways in frail patients, who are at a greater risk for adverse postoperative outcomes. This study evaluated compliance and outcomes after enhanced recovery pathway implementation in high-risk, abdominal surgery patients.Patients entered into the American College of Surgeons National Surgical Quality Improvement Program database who underwent abdominal surgery after enhanced recovery pathway implementation at two Johns Hopkins Medical Institutions were included. Risk was assessed using the American College of Surgeons National Surgical Quality Improvement Program validated, modified 5-item frailty index. Primary outcomes included compliance with 14 enhanced recovery pathway standards and postoperative length of stay, major complications (Clavien-Dindo score II-IV), and 30-day readmission.This study included 646 patients who participated in our enhanced recovery pathway program and 65 patients with modified 5-item frailty index ≥ 2 before enhanced recovery pathway implementation. Overall, 325 patients (50.3%) were high compliers (75% compliance) with enhanced recovery pathway standards, with similar proportions of patients with a modified 5-item frailty index ≥ 2 or2 achieving high compliance (51.6% vs 50.2%, P = .89, respectively). Examining causality for "low compliers" among patients with a high frailty score (modified 5-item frailty index ≥2) demonstrated significant less use of goal-directed therapy when compared with "high compliers" (43% vs 75%, P = .01). Low compliers were also less likely than high compliers to experience mobilization the day of surgery (43% vs 78%, P = .01), postoperative day 1 (43% vs 88%, P.01), and postoperative day 2 (60% vs 100%, P.01). In addition, low compliers were less likely than high compliers to have their diet advanced to solids on postoperative day 1 (17% vs 59%, P.01) and have their Foley catheter removed on postoperative day 1 (45% vs 97%, P.01). Comparing our pre-enhanced recovery pathway patients with our enhanced recovery pathway cohort with a high frailty score, enhanced recovery pathway patients had a significantly shorter length of stay (4.5 vs 6 days, P = .04). However, adjusted analysis demonstrated that high compliance, and not just the enhanced recovery pathway intervention among patients with a high frailty score, was independently associated with a decrease in length of stay (odds ratio 0.72, 95% confidence interval 0.63-0.82, P.01) and a significant reduction in major complications (odds ratio 0.30, 95% confidence interval 0.14-0.65, P.01.This study demonstrates that frail patients comply well with a robust enhanced recovery pathway protocol and subsequently experience improved outcomes. Targeted interventions that seek to maximize compliance with specific enhanced recovery pathway standards may further improve outcomes in this population.

Little is reported about postdischarge complications after bariatric surgery. We sought to identify the rates of postdischarge complications, associated risk factors, and their influence on early hospital readmission.Using the database of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) (2005-2013), we identified patients ≥18 years of age who underwent a bariatric operation with a primary diagnosis of morbid/severe obesity and a body mass index ≥35. The incidence of postdischarge complication was the primary outcome, and hospital readmission was the secondary outcome. The association between postdischarge complications and various patient factors was explored by the use of multivariable logistic regression.A total of 113,898 patients were identified with an overall postdischarge complication rate of 3.2% within 30 days of operation. The rates decreased from 2005 to 2006 (4.6%) to 2013 (3.0%) (P.001). On average, postdischarge complications occurred 10 days postoperatively, with wound infection (49.4%), reoperation (30.7%), urinary tract infection (16.9%), shock/sepsis (12.4%), and organ space surgical-site infection (11.0%) being the most common. Patients undergoing open gastric bypass had the greatest postdischarge complication rate of 8.5%. Of those patients experiencing postdischarge complications, 51.6% were readmitted. The overall readmission rate was 4.9%. The factors associated most strongly with increased odds of postdischarge complications were body mass index ≥ 50, use of steroids, procedure type, predischarge complication, prolonged duration of stay, and prolonged operative time.Postdischarge complications after bariatric surgery represent a substantial source of patient morbidity and hospital readmissions. The majority of postdischarge complications are infection-related, including surgical-site infections and catheter-associated urinary tract infections. Adopting and implementing standardized pre- and postoperative strategies to decrease perioperative infection may help to decrease the rate of postdischarge complications and associated readmissions and enhance overall quality of care.

In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have recently been identified as rare cause of multiple colorectal adenomas and carcinomas, a condition termed polymerase proofreading-associated polyposis (PPAP). The aim of the present study was to evaluate the clinical relevance and phenotypic spectrum of polymerase germline mutations. Therefore, targeted sequencing of the polymerase genes POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3 and POLE4 was performed in 266 unrelated patients with polyposis or fulfilled Amsterdam criteria. The POLE mutation c.1270C>G;p.Leu424Val was detected in four unrelated patients. The mutation was present in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. The colorectal phenotype in 14 affected individuals ranged from typical adenomatous polyposis to a HNPCC phenotype, with high intrafamilial variability. Multiple colorectal carcinomas and duodenal adenomas were common, and one case of duodenal carcinoma was reported. Additionally, various extraintestinal lesions were evident. Nine further putative pathogenic variants were identified. The most promising was c.1306C>T;p.Pro436Ser in POLE. In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes.

Increasing hospital market concentration (with concomitantly decreasing hospital market competition) may be associated with rising hospital prices. Hospital markup - the relative increase in price over costs - has been associated with greater hospital market concentration.Patients undergoing a cardiothoracic or gastrointestinal procedure in the 2008-2011 Nationwide Inpatient Sample (NIS) were identified and linked to Hospital Market Structure Files. The association between market concentration, hospital markup and hospital for-profit status was assessed using mixed-effects log-linear models.A weighted total of 1,181,936 patients were identified. In highly concentrated markets, private for-profit status was associated with an 80.8% higher markup compared to public/private not-for-profit status (95%CI: +69.5% - +96.9%; p 0.001). However, private for-profit status in highly concentrated markets was associated with only a 62.9% higher markup compared to public/private not-for-profit status in unconcentrated markets (95%CI: +45.4% - +81.1%; p 0.001).Hospital for-profit status modified the association between hospitals' market concentration and markup. Government and private not-for-profit hospitals employed lower markups in more concentrated markets, whereas private for-profit hospitals employed higher markups in more concentrated markets.

Although previous studies have examined frailty as a potential predictor of adverse surgical outcomes, little is reported on its application. We sought to assess the impact of the 5-item modified frailty index (mFI) on morbidity in patients undergoing combined colorectal and liver resections. Adult patients who underwent combined colorectal and liver resections were identified using the ACS-NSQIP database (2005–2015). The 5-item mFI consists of history of chronic obstructive pulmonary disease, congestive heart failure, hypertension, diabetes, and partial/total dependence. Patients were stratified into three groups: mFI 0, 1, or ≥ 2. The impact of the mFI on primary outcomes (30-day overall and serious morbidity) was assessed using multivariable logistic regression. Subgroup analyses by age and hepatectomy type was also performed. A total of 1928 patients were identified: 55.1% with mFI = 0, 33.2% with mFI = 1, and 11.7% with mFI ≥ 2. 75.9% of patients underwent wedge resection/segmentectomy (84.6% colon, 15.4% rectum), and 24.1% underwent hemihepatectomy (88.8% colon, 11.2% rectum). On unadjusted analysis, patients with mFI ≥ 2 had significantly greater rates of overall and serious morbidity, regardless of age and hepatectomy type. These findings were consistent with the multivariable analysis, where patients with mFI ≥ 2 had increased odds of overall morbidity (OR 1.41, 95% CI 1.02–1.96, p = 0.037) and were more than twice likely to experience serious morbidity (OR 2.12, 95% CI 1.47–3.04, p

Pancreatic cancer has higher concentrations of angiotensin II compared with other cancers. This study sought to assess the effect of angiotensin II receptor blockers (ARBs) on survival of patients undergoing resection using a large, nationally representative dataset. Patients undergoing pancreatic cancer resection were identified in the Truven Health MarketScan database. Multivariable Cox proportional hazards regression was used to assess the effect of ARB use on overall survival. A total of 4299 patients were identified, among whom 479 (11.1%) filled a prescription for an ARB. Mean patient age was 54.5 years (SD = 8.6 years); 2187 (51.1%) were female. Exactly 49.4% (n = 2125) of patients had a Charlson comorbidity index >2 at the time of surgery (n = 2125, 49.4%) and 59.6% (n = 2563) underwent a pancreaticoduodenectomy. Kaplan–Meier estimates of survival at 1, 2, and 4 years were 62.8% (95% CI: 61.3–64.2%), 38.2% (95% CI: 36.6–39.8%), and 19.0% (95% CI: 17.1–21.0%), respectively. On multivariable analysis, ARB use was associated with a 24% decreased risk of death over the 5-year period in which patients were under observation (HR = 0.76, 95% CI: 0.67–0.87, p

OBJECTIVE: The aim of this study is to assess the financial burden associated with treatment options for resectable pancreatic cancer. BACKGROUND: As the volume of cancer care increases in the United States, there is growing interest among both clinicians and policy-makers to reduce its financial impact on the healthcare system. However, costs relative to the survival benefit for differing treatment modalities used in practice have not been described. METHODS: Patients undergoing resection for pancreatic cancer were identified in the Truven Health MarketScan database. Associations between chemoradiation therapies and survival were performed using parameterized multivariable accelerated failure time models. Median payments over time were calculated for surgery, chemoradiation, and subsequent hospitalizations. RESULTS: A total of 2408 patients were included. Median survival among all patients was 21.1 months [95% confidence interval (CI): 19.8–22.5 months], whereas median follow-up time was 25.1 months (95% CI: 23.5–26.5 months). After controlling for comorbidity, receipt of neoadjuvant therapy, and nodal involvement, a longer survival was associated with undergoing combination gemcitabine and nab-paclitaxel [time ratio (TR) = 1.26, 95% CI: 1.02–1.57, P = 0.035) or capecitabine and radiation (TR = 1.25, 95% CI: 1.04–1.51, P = 0.018). However, median cumulative paymentsvfor gemcitabine with nab-paclitaxel were highest overall [median $74,051, interquartile range (IQR): $38,929–$133,603). CONCLUSIONS: Total payments for an episode of care relative to improvement in survival vary significantly by treatment modality. These data can be used to inform management decisions about pursuing further care for pancreatic cancer. Future investigations should seek to refine estimates of the cost-effectiveness of different treatments.

Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4–67.3 %] vs. 69.2 % [95 % CI 64.2–73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67–0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.

AIM: To identify rates of post-discharge complications (PDC), associated risk factors, and their influence on early hospital outcomes after esophagectomy. METHODS: We used the 2005-2013 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify patients ≥ 18 years of age who underwent an esophagectomy. These procedures were categorized into four operative approaches: transhiatal, Ivor-Lewis, 3-holes, and non-gastric conduit. We selected patient data based on clinical relevance to patients undergoing esophagectomy and compared demographic and clinical characteristics. The primary outcome was PDC, and secondary outcomes were hospital readmission and reoperation. The patients were then divided in 3 groups: no complication (Group 1), only pre-discharge complication (Group 2), and PDC patients (Group 3). A modified Poisson regression analysis was used to identify risk factors associated with developing post-discharge complication, and risk ratios were estimated. RESULTS: 4483 total patients were identified, with 8.9% developing PDC within 30-d after esophagectomy. Patients who experienced complications post-discharge had a median initial hospital length of stay (LOS) of 9 d; however, PDC occurred on average 14 d following surgery. Patients with PDC had greater rates of wound infection (41.0% vs 19.3%, P < 0.001), venous thromboembolism (16.3% vs 8.9%, P < 0.001), and organ space surgical site infection (17.1% vs 11.0%, P = 0.001) than patients with pre-discharge complication. The readmission rate in our entire population was 12.8%. PDC patients were overwhelmingly more likely to have a reoperation (39.5% vs 22.4%, P < 0.001) and readmission (66.9% vs 6.6%, P < 0.001). BMI 25-29.9 and BMI ≥ 30 were associated with increased risk of PDC compared to normal BMI (18.5-25). CONCLUSION: PDC after esophagectomy account for significant number of reoperations and readmissions. Efforts should be directed towards optimizing patient’s health pre-discharge, with possible prevention programs at discharge.

The aim of this study was to assess whether adherence to National Comprehensive Cancer Network (NCCN) guidelines leads to differences in survival in patients diagnosed with locally advanced esophageal cancer. This is a retrospective cohort study of patients with stage II and III esophageal cancer included in the Cancer Registry at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital from 2008 to 2013. Seven quality indicators were identified using the 2014 NCCN guidelines, and individual and overall quality measure scores were calculated and used to define low and high quality of care groups. One hundred forty-one patients met inclusion criteria, and 88 patients (62.4 %) were identified as receiving high-quality care. Adherence to guidelines ranged from 63.1 to 100.0 %, with an overall compliance of 81.3 %. Risk factors for receiving low quality of care included advanced age, non-white race, lower education level, and unspecified primary site of tumor. A significantly better overall survival was observed in patients who received high-quality care (HR, 0.58; 95 %, 0.37–0.90, p = 0.015). Delivery of high-quality care is associated with improved survival in these patients. Efforts should be directed at minimizing disparities in treatment in regards to race and educational levels.

Trade-offs involved with market competition, overall costs to payers and consumers, and quality of care have not been well defined. Less competition within any given market may enable provider-driven increases in charges.To examine the association between regional hospital market concentration and hospital charges for hepatopancreaticobiliary surgical procedures.This study included all patients undergoing hepatic or pancreatic resection in the Nationwide Inpatient Sample from January 1, 2003, through December 31, 2011. Hospital market concentration was assessed using a variable-radius Herfindahl-Hirschman Index (HHI) in the 2003, 2006, and 2009 Hospital Market Structure files. Data were analyzed from November 19, 2016, through March 2, 2017.Hepatic or pancreatic resection.Multivariable mixed-effects log-linear models were constructed to determine the association between HHI and total costs and charges for hepatic or pancreatic resection.Weighted totals of 38 711 patients undergoing pancreatic resection (50.8% men and 49.2% women; median age, 65 years [interquartile range, 55-73 years]) and 52 284 patients undergoing hepatic resection (46.8% men and 53.2% women; median age, 59 years [interquartile range, 49-69 years]) were identified. Higher institutional volume was associated with lower cost of pancreatic resection (-5.4%; 95% CI, -10.0% to -0.5%; P = .03) and higher cost of hepatic resection (13.4%; 95% CI, 8.2% to 18.8%; P .001). For pancreatic resections, costs were 5.5% higher (95% CI, 0.1% to 11.1%; P = .047) in unconcentrated hospital markets relative to moderately concentrated markets, although overall charges were 8.3% lower (95% CI, -14.0% to -2.3%; P = .008) in highly concentrated markets. For hepatic resections, hospitals in highly concentrated markets had 8.4% lower costs (95% CI, -13.0% to -3.6%; P = .001) compared with those in unconcentrated markets and charges that were 13.4% lower (95% CI, -19.3% to -7.1%; P .001) compared with moderately concentrated markets and 10.5% lower (95% CI, -16.2% to -4.4%; P = .001) compared with unconcentrated markets.Higher market concentration was associated with lower overall charges and lower costs of pancreatic and hepatic surgery. For complex, highly specialized procedures, hospital market consolidation may represent the best value proposition: better quality of care with lower costs.

9575 Background: Distress is defined as an unpleasant emotional experience that may interfere with the ability to cope with cancer or its treatment. Distress screening is recommended during transitions including survivorship. We describe distress in cancer survivors before and after participation in a multidisciplinary survivorship clinic. Methods: All patients participating in the Yale Adult Survivorship Clinic were asked to complete the National Comprehensive Cancer Network Distress Thermometer (DT) immediately before and after a visit. Survivors ranked distress from 0 (none) to 10 (extreme) and indicated associated problems from a 39-item list. A score ≥ 4 was considered clinically significant. Survivors were seen by an MD/APRN, social worker, registered dietitian and physical therapist. Survivors received individual counseling on topics including survivorship care, diet and exercise, and coping. All were offered a follow-up visit approximately 8 weeks later. Distress screening was repeated at the foll...