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Background: Pervasive symptoms from chronic pancreatitis despite noninvasive management is an indication for surgical intervention. Frey and Whipple procedures are appropriate options for proximal pancreas disease; however, data are limited on symptomatic outcomes., Methods: We conducted a retrospective analysis of patients who underwent surgical intervention for chronic pancreatitis of the proximal pancreas from 2005 to 2019. Preoperative patient characteristics and postoperative outcomes were evaluated., Results: One hundred forty patients underwent surgical intervention for chronic pancreatitis, 91 Whipple and 49 Frey procedures. Mean age was 53 years (SD 12), and mean BMI 24 (SD 5.6). At post-operative follow-up, 74 ​% were asymptomatic, and 84 ​% at average follow-up of 2 years. Groove pancreatitis, lack of post-operative delayed gastric emptying, and decreased length of stay were predictive of symptom resolution., Conclusions: Whipple and Frey procedures are appropriate surgical options for chronic pancreatitis affecting the proximal pancreas. Both lead to sustained symptom resolution for most patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work is not under consideration for publication elsewhere and has been approved for submission and publication by all authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: CPT coding allows addition of a 2-digit modifier code to denote particularly difficult procedures necessitating additional reimbursement, called the modifier 22. The use of modifier 22 in relation to pancreatic surgery and outcomes, specifically pancreaticoduodenectomy (PD), has not been explored., Study Design: All PDs performed from 2010 to 2019 at a quaternary healthcare system were analyzed for differences in preoperative characteristics, outcomes, and cost based on the use of modifier 22. Adjusted logistic regression analysis was used to identify factors predictive of modifier 22 use., Results: A total of 1,284 patients underwent PD between 2010 and 2019; 1,173 with complete data were included, of which 320 (27.3%) were coded with modifier 22. Patients coded with modifier 22 demonstrated a significantly longer duration of surgery (365.9 ± 168.4 vs 227 ± 97.1; p < 0.001). They also incurred significantly higher cost of index admission ($37,446 ± 34,187 vs $28,279 ± 27,980; p = 0.002). An adjusted multivariable analysis (specifically adjusted for surgeon variation) revealed duration of surgery (p < 0.001), neoadjuvant chemotherapy (p = 0.039), class II obesity (p = 0.019), and chronic pancreatitis (p = 0.005) to be predictive of modifier 22 use., Conclusions: Despite the subjective nature of this CPT modifier, modifier 22 is an appropriate marker of intraoperative difficulty. Preoperative and intraoperative characteristics that lead to its addition may be used to further delineate difficult PDs., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy., Competing Interests: Intellectual property related to the use of peptide antagonists to vasoactive intestinal polypeptides to treat cancer is the subject of US patent applications, which are licensed to Cambium Oncology, LLC. EW is a co-founder and has equity in Cambium Oncology. Duvelisb was a commercial product of Verastem Oncology now a product of Secura Bio. EW was on the Verastem Scientific Advisory Board. PS holds shares in Metaclipse Therapeutics Corporation, a company that is planning to use GPI-anchored molecules to develop a membrane-based TMV cancer vaccine in the future. A conflict-of-interest management plan has been reviewed and approved by Emory University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Passang, Ravindranathan, Bommireddy, Jajja, Yang, Selvaraj, Paulos and Waller.)

Background: Improved post-operative outcomes have been demonstrated in gastrointestinal procedures where a narcotic sparing strategy has been utilized. Data for pancreaticoduodenectomy (PD) patients is limited. This study reviews an institutional database for outcomes based on initial analgesic strategy., Methods: 1004 consecutive patients who underwent PD at Emory University between 2010 and 2017, were included in the analysis. Patients were divided into groups based on primary analgesic strategy employed: epidural alone (EPI), patient controlled opiate analgesia (PCA), dual (dual-PCA/EPI) and other (non-PCA/EPI). Postoperative outcomes for each group were analyzed utilizing univariate and multivariate linear regression., Results: 448 (44.6%) patients were treated with EPI, 300 (29.9%) were given a PCA, 78 (7.8%) had dual-PCA/EPI and 178 (17.7%) had non-PCA/EPI analgesia. On univariate analysis, increased BMI (p = 0.030), PCA use (p < 0.001), venous thromboembolism (VTE) (p < 0.001), post-operative pancreatic fistula (POPF) (p < 0.001) and Ileus/delayed gastric emptying (DGE) (p < 0.001) were all correlated with increased LOS. On multivariate linear regression, VTE (b-coefficient 9.07, p = 0.004) POPF (8.846, p = 0.001), Ileus/DGE (4.464, p = 0.004) and PCA use (1.75, p = 0.003) were associated with significantly increased LOS., Conclusion: A primary narcotic sparing strategy is associated with a significantly reduced LOS and lower rates of Ileus/DGE. Mean opiate usage was significantly lower in the EPI and non-EPI/PCA groups., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Morbidity after pancreaticoduodenectomy (PD) has been reported to be about 30-53%. These complications can double hospital costs. We sought to explore the financial implications of complications after PD in a large institutional database., Methods: A retrospective analysis of patients undergoing PD from 2010-2017 was performed. Costs for index hospitalization were divided into categories: operating room, postoperative ward, radiology and interventional radiology. Complications were categorized according to the Clavien-Dindo classification. Univariable and mutivariable analysis were performed., Results: Median cost of index admission for 997 patients who underwent PD was $23,704 (range $10,988-$528,531). Patients with major complications incurred significantly greater median costs compared to those without ($40,005 vs $21,306, p < 0.001). Patients with postoperative pancreatic fistula (POPF) grade A, B and C had progressively increasing costs ($32,164, $50,264 and $102,013, p < 0.001). On multivariable analysis ileus/delayed gastric emptying, respiratory failure, clinically significant POPF, thromboembolic complications, reoperation, duration of surgery >240 minutes and male sex were associated with significantly increased costs., Conclusion: Complications after PD significantly increase hospital costs. This study identifies the major contributors towards increased cost post-PD. Initiatives that focus on prevention of complications could reduce associated costs and ease financial burden on patients and healthcare organizations., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: For patients with periampullary adenocarcinoma (PAC), pancreatoduodenectomy (PD) provides the best survival. Surgery on a subset of patients is aborted during PD. We analyzed these patients., Methods: Patients who underwent laparotomy for planned PD for PAC were identified (2006-2019). From operative notes, we identified the subset with intraoperative decision to abort. Patient, treatment, and outcome data were analyzed. The subset with pancreatic ductal adenocarcinoma (PDAC) was analyzed for survival., Results: Only 6.7% (n = 55/819) of cases were aborted. Majority 78% (n = 43) had pathologically-confirmed diagnoses at time of surgery, and 18.2% (n = 10) received preoperative chemotherapy. Reasons for aborted PD included: distant metastases (65.5%, n = 36) and local invasion (34.5%, n = 19). Of patients with metastatic disease, 75% (n = 27) had liver metastases. Eighty-nine percent (n = 49) of patients underwent at least one palliative bypass procedure and 81.8% (n = 45) had both gastric and biliary bypass. Patients with computed tomography (CT) scans before surgery more commonly had missed metastatic disease (79.2% CT compared to 54.8% magnetic resonance imaging [MRI], χ 2  = 3.54, p = 0.059). In PDAC, 61.4% (n = 27/44) were aborted for metastatic disease and 38.7% (n = 17/44) for local invasion. Median overall survival for all PDAC patients after aborted PD was 334 days., Conclusion: Majority of pancreatoduodenectomies for periampullary adenocarcinoma are done to completion. Liver metastases is the most common reason for aborting. Preoperative MRI may help identify hepatic metastases., (© 2022 Wiley Periodicals LLC.)

Objective: To determine the trend of resistance to antimicrobials in Streptococcus pneumoniae infections, and the impact of new Clinical and Laboratory Standards Institute guidelines on 1211 among meningeal isolates., Methods: The descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory in Karachi, and comprised Streptococcus pneumoniae isolation and antimicrobial susceptibility data over a period of 24 years, from 1993 to 2016, which was compared in terms of pre-2008 and post-2008 data, which was analysed using SPSS 19., Results: Of the 7415 non-duplicate isolates identified, 4700(63.4%) were from male patients and 2,715(36.6%) were from female patients. The overall mean age of the patients was 38±27 years. Penicillin resistance in non-meningeal isolates during the two periods was not significantly different (p>0.05), but a significant rise in penicillin resistance in meningeal isolates was observed in the second period (p<0.05). High resistance rates were observed for co-trimoxazole, tetracycline and erythromycin, and an increased trend of multi-drug resistant strains was also noted from 1999 {n=35/317(11%)} to 2016 {n=110/314 (36%)}., Conclusions: The emergence of multi-drug resistant strains was evident. The spike in penicillin-resistant Streptococcus pneumoniae in meningeal isolates may have been due to the revised guidelines by the Clinical and Laboratory Standards Institute.

Background: Optimal diagnostic and surgical approaches for patients with bile duct injuries (BDI) remain debated. This study reviews results from a standardized approach to management of high-grade BDIs at a North American center., Design: Patients undergoing surgical repair for BDIs over a 15-year period were included. Post-operative outcomes and biliary patency rates were calculated using imaging, laboratory values, and patient interviews., Results: A total of 107 consecutive patients underwent repair for BDIs. Bismuth grade I/II injuries were identified in 46 patients (41%), grade III/IV in 41 (38%), grade V in 11 patients (10%), and 9 (10%) were unclassified. BDI anatomy was commonly identified using magnetic resonance imaging (MRI) (75%). Concomitant arterial injuries were identified in 30 (28 with formal angiography). Fifteen had early repairs (within 4 days) and remainder interval repairs (median: 65 days). Hepp-Couinaud repair was method of choice (83%). Estimated primary biliary patency was 100% at 30 days and 87% at 5 years., Conclusion: With appropriate referral to a specialist, surgical reconstruction of BDIs can have excellent outcomes, even with accompanying arterial injuries. Based on our experience, MR as first imaging modality and supplemental angiography served as the optimal diagnostic strategy. Delayed repair, using Hepp-Couinaud technique, with selective liver resection results in high long-term patency rates., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: Minimally invasive approaches to major liver resection have been limited by presumed difficulty of the operation. While some concerns arise from mastering the techniques, factors such as tumor size and liver parenchymal features have anecdotally been described as surrogates for operative difficulty. These factors have not been systematically studied for minimally invasive right hepatectomy (MIRH)., Methods: Seventy-five patients who underwent MIRH during 2007-2016 by the senior author were evaluated; these were compared to control group of open right hepatectomy. Demographics, operative, and post-operative variables were collected. Operative times and estimated blood loss, two objective parameters of operative difficulty were correlated to volume of hepatic resection, parenchymal transection diameter and liver parenchymal features using regression analysis., Results: Thirty-eight (50.6%) resections were performed for malignant indications. Average tumor size was 5.7 cm (±3.6), mean operative time was 196 min (±74), and mean EBL was 220 mL (±170). Average transection diameter was 10.1 cm (±1.7). There was no correlation between operative difficulty with parenchymal transection diameter or presence of steatosis. Blood loss was higher with increased right hepatic lobe volume and body mass index., Conclusions: This analysis of a very defined anatomical resection suggests that the often quoted radiographic and pathologic features indicative of a challenging procedure were not significant in determining operative difficulty.

Background: The use of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has increased in recent years. Limited data exists on the impact of NAC on biliary microbiome., Methods: Patients who underwent pancreaticoduodenectomy (PD) for PDAC between 2014 and 2017 were reviewed. Patients were stratified into two groups based on their NAC status for comparison., Results: Of 168 patients included, 63 (37.5%) received NAC. Patients who received NAC exhibited significantly increased growth of Gram-negative anaerobic bacteria (p = 0.043). Patients in the non-NAC group were more likely to grow pathogens resistant to ampicillin-sulbactam (47% vs 21%, p = 0.007), cefazolin (49% vs 28%, p = 0.040), cefoxitin (42% vs 11%, p = 0.009) and cefuroxime (26% vs 4%, p = 0.019). NAC status did not impact infectious postoperative outcomes, including SSIs., Conclusion: Patients who did not receive NAC were more likely to grow pathogens resistant to cephalosporins. Perioperative antibiotic prophylaxis should be tailored to cover Gram-negative organisms and enterococci., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Existing research suggests patients with blood group O are less likely to develop pancreatic ductal adenocarcinoma (PDAC) compared to those with non-O blood groups, and that survival from PDAC may be affected by ABO blood type. This study assessed survival outcomes in PDAC patients who underwent pancreatoduodenectomy (PD) in one health system., Methods: From 2010 to 2017, demographic, operative, chemotherapy and survival data for patients undergoing PD at Emory Healthcare were reviewed. Patients with blood type AB were excluded due to small sample size. The relationship between ABO blood group and survival was analyzed using Kaplan-Meier survival curves and multivariate cox proportional regression analysis., Results: Of 449 PDAC patients assessed, 204 (45.4%), 60 (13.4%) and 185 (41.2%) were blood groups A, B and O, respectively. Patients were well matched in clinicopathologic characteristics. Median survival did not differ by blood group (p = 0.82), and this relationship remained insignificant on cox regression analysis (p = 0.15). On multivariate analysis, lymph node positivity (p < 0.001) and increasing age (p = 0.001) were associated with reduced survival., Conclusion: In contrast to recent reports, this larger study found that blood group did not impact overall survival among patients undergoing PD for PDAC., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The amount of IV fluids sufficient to prevent post-operative acute kidney injury (AKI) during pancreaticoduodenectomy (PD) is unknown. We assessed the restrictive IOIVF use in PD on the rate of post-operative AKI, delayed gastric emptying and ileus, and pancreatic fistulas (POPF)., Methods: Patients who underwent PD between 2012 and 2017 were reviewed. Univariate and multivariate analyses looked for association between pre- and intra-operative factors on AKI, ileus and POPF., Results: Of 395 included patients, 97, 172, and 126 patients received less than 1000 mL (ultra-restrictive), 1000 mL to less than 2000 mL (restrictive), and 2000 mL and greater (nonrestrictive) normalized total IOIVF respectively. Of these 23 (24.2%), 34(20.4%), and 21(17.4%) developed AKI respectively, most of them mild. There was no difference in odds of developing AKI, ileus, or pancreatic fistula among fluid groups. While there was no difference in Clavien-Dindo III-IV complications, the incidence of Clavien-Dindo type I-II complications was lower in the restricted fluid groups., Discussion: Restricted fluids did not lead to higher AKI rates but were associated with fewer low-grade complications., Competing Interests: Declaration of competing interest We, all the authors listed above, attest that we have no conflicts of interests to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Limited literature is available on the postoperative development of impaired glucose tolerance (IGT) and new-onset diabetes mellitus (NODM) following Distal Pancreatectomy (DP). We aimed to study the post-surgical clinical evolution of IGT/DM and its association with preoperative glycemic profiles of patients undergoing DP., Methods: Pre- and postoperative glycemic laboratories were measured in patients undergoing DP by the senior author from 2007-2017. Multivariate risk factor analysis was performed to determine risk factors for new-onset IGT/DM after DP. Kaplan-Meier curves were constructed for development of NODM postoperatively., Results: Of 216 included patients, n = 63, n = 68 and n = 85 were preoperatively diagnosed with no-diabetes (No-DM), pre-diabetes (Pre-DM), and diabetes (DM), respectively. At 2-year follow-up, n = 37, n = 80 and n = 99 were classified as No-DM, Pre-DM or DM, respectively. Pre-diabetics had a higher risk of developing postoperative dysglycemia (RR 2.230, 95% CI 1.732-2.870, p = 0.001). Preoperative OGTT>130, HbA1c >6.0, and chronic pancreatitis were risk factors for postoperative DM., Conclusion: 40% of patients undergoing DP were unaware of their dysglycemic status (pre-DM or DM) pre-operatively. At 2-year follow-up, 36% non-diabetic and 57% pre-diabetic patients had developed NODM. Appropriate pre-operative diabetic assessment is warranted for all patients undergoing pancreatic resections., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Bile cultures (BC) have routinely been used to guide empiric antibiotic therapy for developing postoperative infections. The ability of BCs to predict sensitivity and resistance patterns (SRP) of site of infection cultures (SOIC) remains controversial. The aim was to assess the concordance of pathogens and SRPs between paired BC/SOICs., Methods: Medical records of consecutive patients undergoing pancreaticoduodenectomy were reviewed between 2014 and 2018. BC/SOIC pathogens and SRPs were compared on a patient-by-patient basis and concordance (K) was assessed., Results: Common patient characteristics of 522 included patients were 65-years-old, Caucasian (75.5%), male (54.2%), malignant indication (79.3%), and preoperative biliary stent (59.0%). Overall, 275 (89.6%) BCs matured identifiable isolates with 152 (55.2%) demonstrating polymicrobial growth. Ninety-two (17.6%) SOICs were obtained: 48 and 44 occurred in patients with and without intraoperative BCs. Stents were associated with bacteriobilia (85.7%, K = 0.947, p < 0.001; OR 22.727, p < 0.001), but not postoperative infections (15.2%; K = 0.302, p < 0.001; OR 1.428, p = 0.122). Forty-eight patients demonstrated paired BC/SOICs to evaluate. Pathogenic concordance of this group was 31.1% (K = 0.605, p < 0.001) while SRP concordance of matched pathogens was 46.7% (K = 0.167, p = 0.008)., Conclusion: Bile cultures demonstrate poor concordance with the susceptibility/resistance patterns of postoperative infections following pancreaticoduodenectomy and may lead to inappropriate antibiotic therapies., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Postoperative emergency department (ED) visits represent fragmented care, are costly, and often evolve into readmission. Readmission rates after pancreatoduodenectomy (PD) are defined, while ED visits following PD are not. We examined the pattern of 30-day post-discharge ED visits for PD patients., Methods: A quaternary institutional database analysis of adult patients who underwent PD between 2010-2017 was reviewed for ED utilization within 30 days from discharge., Results: Of the 1,004 patients who underwent PD, 12% (N = 117) patients sought care in the ED within 30 days from postoperative discharge. The median time to ED presentation was 5 days post-discharge (IQR 3-9). Half of ED visits occurred during nights and weekends (N = 59, 50%). Of ED-utilizing patients, 64% (N = 76) were admitted to the hospital and 29% (N = 34) were discharged from the ED. ED visits were associated with a Clavien-Dindo Classification of 0 in 10.2% (N = 13) of patients, I-II in 62.4% (N = 73), and III-V in 26.5% (N = 31)., Discussion: Post-discharge ED utilization is a novel quality metric and represents a potential target population for reducing hospital readmissions. Over two-thirds (72%) of ED visits were associated with low acuity complications, and promoting institutional strategies addressing postoperative ED visits may improve patient care and efficient utilization of healthcare resources., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Literature is varied regarding risk factors associated with diabetes development after major pancreatic resection. The aim was to develop and validate a scoring index that preoperatively predicts the development of diabetes after pancreaticoduodenectomy and distal pancreatectomy., Study Design: In this prospective study, perioperative fasting and postprandial (OGTT, oral glucose tolerance test) plasma glucose, glycated hemoglobin A1c (HbA1c), insulin, and c-peptide were measured in select consecutive patients undergoing pancreaticoduodenectomy and distal pancreatectomy by the senior author, from 2007 to 2018. American Diabetes Association definitions were used for glycemic classifications. Statistical analyses included multivariate generalized estimated equation for factor identification and variable weighting; area under the receiver operating curve (ROC) c-statistic for predictive ability, and survival analysis risk score grouping., Results: Of 1,083 included patients with preoperative normoglycemia (253; 23.4%), prediabetes (362; 33.4%), and diabetes (468; 43.2%), the overall postoperative incidence of each diabetic class at 120 months was 152 (14.0%), 466 (43.0%), and 465 (42.9%), respectively. The development and validation groups included 1,023 and 60 patients, respectively. Five factors were identified predicting diabetes development, with a total possible score of 8. The C-statistics for development and validation groups were 0.727 (CI 0.696 to 0.759, p < 0.001) and 0.823 (CI 0.718 to 0.928, p < 0.001), respectively. At a cut point of 3 (sensitivity 0.691, specificity 0.644) the Post-pancreatectomy Diabetes Index (PDI) independently predicted diabetes in development (odds ratio [OR] 4.298, relative risk [RR] 2.486, CI 1.238 to 5.704, p < 0.001) and validation (OR 6.970, RR 2.768, CI 2.182 to 22.261, p < 0.001) groups. The PDI similarly predicted pre-diabetes in development (OR 1.961, RR 1.325, CI 1.202 to 2.564, p < 0.001) and validation (OR 4.255, RR 1.798, CI 1.247 to 14.492, p = 0.021) groups., Conclusions: The Post-pancreatectomy Diabetes Index predicts the development of diabetes and pre-diabetes in patients undergoing major pancreatectomy using routine endocrine laboratories and pre-surgical clinical data., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative pancreatic fistula (POPF) is a potentially debilitating complication following pancreatoduodenectomy (PD). There are limited data correlating pancreatic parenchymal histopathologic features specifically fat and fibrosis content with development of POPF after PD., Methods: Patients who underwent PD (January 2010-May 2015) with archived pathologic slides were included. Each pancreatic neck transection margin was histologically graded for fat and fibrosis, scored from 0 to 4, and grader was blinded to clinical outcomes. Main pancreatic duct diameter and duct wall thickness were microscopically measured. Patients were dichotomized into high and low categories with respect to pancreatic fat and fibrosis and primary outcome of POPF., Results: Of 301 patients, 24 developed POPF (8.0%). One hundred ten patients (36.5%) had low fat (score <2), and 149 (49.5%) had low fibrosis (score <2), and average duct diameter was 3.9 ± 1.3 mm. Patients with low fibrosis had a higher rate of POPF (12.8% versus 3.3%, P = 0.005). Low fibrosis (odds ratio [OR] 4.29, 95% confidence interval [CI] 1.56-11.7, P = 0.005), nonpancreatic adenocarcinoma pathology (OR 3.25, 95% CI 1.25-8.43, P = 0.02), and increased body mass index (BMI) (OR 1.11, 95% CI 1.03-1.12, P = 0.007) were associated with POPF development on univariate analysis. Low fibrosis and increased BMI remained independently associated on multivariate analysis. High fat content was frequently concurrently identified in specimens with high fibrosis (67.8%). Surgeon-described gland consistency did not correlate with histopathologic findings (Spearman's rank correlation coefficients of -0.144 and 0.304, respectively) or to incidence of POPF. No patient who underwent preoperative chemotherapy developed POPF (n = 30, 10%)., Conclusions: Low pancreatic neck fibrosis content and increased patient BMI are associated with increased rates of POPF following PD, while pancreatic fat content does not appear to influence this outcome. Pancreatic neck fat and fibrosis often coexist in the same specimen. The association between preoperative chemotherapy and low POPF rates needs further examination. Frozen section analysis of pancreatic neck margin for fibrosis content may be more accurate than surgeon assessment in identifying patients at risk for POPF. These assessments can potentially guide therapeutic interventions, including selective prophylactic drain placement and use of postoperative somatostatin analog therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Incisional ventral hernias(IVH) are a common complication following open abdominal surgery. The aim of this study was to uncover the hidden costs of IVH following right-sided hepatectomy., Methods: Outcomes and hospital billing data for patients undergoing open(ORH) and laparoscopic right-sided hepatectomies(LRH) were reviewed from 2008 to 2018., Results: Of 327 patients undergoing right-sided hepatectomies, 231 patients were included into two groups: ORH(n = 118) and LRH(n = 113). Median follow-up-times and time-to-hernia were 24.9-months(0.3-128.4 months) and 40.5-months(0.4-81.4 months), respectively. The incidence of hernias at 1, 3, 5, and 10 years was 6/231(2.6%), 13/231(5.6%), 15(6.5%), and 17/231(7.4%); ORH = 14, LRH = 3, p = 0.003), respectively. In terms of IVH repair(IVHR), total operative costs ($10,719.27vs.$4,441.30,p < 0.001) and overall care costs ($20,541.09vs.$7,149.21,p = 0.044) were significantly greater for patients undergoing ORH. Patients whom underwent ORHs had longer hospital stays and more complications following IVHR. Risk analysis identified ORH(RR-10.860), male gender(RR-3.558), BMI ≥30 kg/m 2 (RR-5.157), and previous abdominal surgery(RR-6.870) as predictors for hernia development (p < 0.030)., Conclusion: Evaluation of pre-operative hernia risk factors and utilization of a laparoscopic approach to right-sided hepatectomy reduces incisional ventral hernia incidence and cost when repair is needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Autonomy is of foremost concern in the current era of surgical residency, and it is especially important to trainees when considering their surgical education. Factors impacting trainee independence include the restriction of clinical work hours and the development of advanced minimally invasive techniques such as robotics, which requires separate technical education outside of conventional surgical education. Moreover, when residents are left to learn fundamental exposures via their clinical experience alone, they run the risk of not being exposed to some fundamental skills based on case volume and type. The Department of Surgery at Emory University developed a cadaver-based simulation curriculum to standardize exposure to fundamental operative skills and enhance proficiency outside the operating room, with the larger aim of improving resident autonomy., Methods: Residents were assigned to small groups led by a chief resident with an even distribution of postgraduate year (PGY) levels. Each group participated in core surgical exposures and fundamental maneuvers on a cadaver over a 6-hour session. Residents were tested on skills according to their PGY level about 1 month after the course. Testing included recitation of the skill in an oral boards format, highlighting major steps, followed by performance of the skill. All steps were video-recorded with no resident identifiers. These were reviewed by 2 independent, blinded faculty examiners who assigned proficiency grades to each resident video., Results: Three hundred and thirty-three individual procedure evaluations were done over the 5-year period. Senior residents (PGY3-5) had 86% pass rate while junior residents (PGY1-2) had 70% pass rate. Overall, 21% of residents failed to achieve competence in their assigned skills. Junior residents were less likely to achieve competence compared to senior residents. Faculty graders had improved congruence in grading as the course progressed through the 5 years. The most recent 2 years had >80% congruence in faculty grading compared to less than 50% congruence in the first 2 years. 81% of attendings agreed this course positively influenced the granting of autonomy in the operating room., Conclusions: A cadaveric skills course focused on fundamental maneuvers with objective confirmation of achieving competency is a viable adjunct to clinical operative experience. Video-recorded evaluation, of these fundamental skills improved both resident and attending confidence in trainee operative skill., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Etiologies, levels, and associated factors of psychological distress in cancer patients facing surgery are poorly defined. We conducted a prospective comparative study of perioperative anxiety and depression in patients undergoing abdominal surgery for either malignant or benign disease., Methods: With Institutional Review Board approval, patients consenting for surgery at our institution were enrolled. Surveys were completed at a preoperative visit and within 2 weeks of a postoperative appointment. Participants listed their top three sources of anxiety, and completed the Patient Health Questionnaire-9 and the General Anxiety Disorder-7., Results: A total of 79 patients completed the preoperative assessment and 44 (58.7%) finished the postoperative survey. Forty-one were male (51.9%), 12 (15.2%) had a psychiatric comorbidity (PSYHx), and 47 (59.5%) had cancer. Perioperative anxiety and depression did not differ by malignancy status. Patients were most concerned about surgery (22.5%) preoperatively and finances (27.9%) postoperatively. PSYHx, frailty, insurance status, and opioid use were all associated with perioperative psychological distress., Conclusions: Cancer patients did not have significantly higher levels of perioperative psychological distress compared with benign controls. Socioeconomic worries are prevalent throughout the perioperative period, and efforts to alleviate distress should focus on providing adequate counseling., (© 2019 Wiley Periodicals, Inc.)

Background: With current emphasis on improving cost-quality relationship in medicine, it is imperative to evaluate cost-value relationships for surgical procedures. Previously the authors demonstrated comparable clinical outcomes for minimally invasive right hepatectomy (MIRH) and open right hepatectomy (ORH). MIRH had significantly higher intraoperative cost, though overall costs were similar., Methods: MIRH was decoded into its component critical steps using value stream mapping, analyzing each associated cost. MIRH technique was prospectively modified, targeting high cost steps and outcomes were re-examined. Records were reviewed for elective MIRH before (pre-MIRH n = 50), after (post MIRH n = 25) intervention and ORH (n = 98), between January 1, 2008 and November 30, 2016., Results: Average overall cost was significantly lower for post-standardization MIRH (post-MIRH $21 768, pre-MIRH $28 066, ORH $33 020; p < 0.001). Average intraoperative blood loss was reduced with MIRH (167, 292 and 509 mL p < 0.001). Operative times were shorter (147, 190 and 229 min p < 0.001) and LOS was reduced for MIRH (3, 4, 7 days p < 0.002)., Conclusions: Using a common quality improvement tool, the authors established a model for cost effective clinical care. These tools allow surgeons to overcome personal or traditional biases such as stapler choices, but most importantly eliminate non-value added interventions for patients., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Talimogene laherparepvec (TVEC) is an FDA-approved oncolytic herpes virus used to treat unresectable stage IIIB to IV metastatic melanoma via intralesional injection. This study aims to characterize the efficacy TVEC in patients with unresectable stage IIIB to IV melanoma., Methods: We performed a multi-institutional, IRB-approved review of all patients who received TVEC at 3 centers from October 2015 to October 2018. Clinicopathologic characteristics, TVEC treatment data, and outcomes were assessed., Results: One hundred and twenty-one patients received TVEC, of which 80 patients had available treatment response data with at least 3-month follow-up. Anatomic sites treated were 19 (24%) head and neck, 9 (11%) upper extremity, 12 (15%) torso, and 40 (50%) lower extremity. Thirty-four (42.5%) patients did not receive therapy before TVEC. Side effects were mild and self-limited, most commonly flu-like symptoms seen in 22 (28%) patients. Median follow-up was 9 months (range 3 to 28 months), with complete local response in 31 (39%) and partial response in 14 (18%) patients. Of complete responders, 29 (37%) had no evidence of disease at last follow-up and received a median of 6 (range 2 to 12) cycles of therapy., Conclusions: Talimogene laherparepvec is a well-tolerated, durable treatment option for patients with unresectable locoregional melanoma, particularly in stage IIIB/C disease. Additionally, we found that TVEC can be administered safely across anatomic sites that are otherwise not amenable to other local therapies., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Limited literature is available on the development of impaired glucose tolerance and diabetes mellitus after pancreaticoduodenectomy. The primary aim was to define the diabetic phenotype and correlate preoperative glycemic laboratory results to new-onset diabetes after pancreaticoduodenectomy., Study Design: In this prospective study, perioperative fasting and postprandial (oral glucose tolerance test) plasma glucose, glycated hemoglobin, insulin, and c-peptide were measured in consecutive patients undergoing pancreaticoduodenectomy by the senior author from 2006 to 2017. American Diabetes Association definitions were used for glycemic classifications. Multivariate risk factor analysis was performed., Results: Of 774 identified patients, 371 diabetics were excluded and 403 patients were included: 167 and 236 were preoperatively classified as nondiabetic and prediabetic, respectively. The incidence rates of diabetes at 120 months post pancreaticoduodenectomy were 9.0% (nondiabetics), 22.0% (prediabetics), and 16.6% (overall). Patients in whom diabetes developed demonstrated a 3-fold larger difference between oral glucose tolerance test and fasting glucose (Δ), and 2-fold larger Δinsulin and Δc-peptide values. Tiered multivariate analysis identified glycated hemoglobin >5.4% with a relative risk (RR) of 2.944 (p = 0.047) as an independent predictor of impaired glucose tolerance and diabetes mellitus. Analysis of patients stratified by preoperative classification identified fasting glucose >95 mg/dL (nondiabetics, RR 1.925; p = 0.002), and glycated hemoglobin ≥5.4% (prediabetics, RR 3.125; p = 0.040) as independent risk factors for diabetes. Compared with nondiabetics, prediabetics classified by any laboratory results demonstrated an RR of 2.471 (p = 0.001) for diabetes developing postoperatively. There was no association between primary pathology, advancing age, or BMI and increased risk of diabetes development., Conclusions: Diabetes will develop after pancreaticoduodenectomy in approximately 16.6% of patients. A preoperative glycated hemoglobin >5.4% independently predicts new-onset diabetes. Pre- and postoperative endocrine analysis remains paramount for proper patient risk stratification., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive approaches for major hepatectomy have been marred by significant rates of conversion and associated morbidity. This study aimed to determine risk factors for conversion as well as postoperative morbidity in patients undergoing minimally invasive right-sided hepatectomy (MIRH)., Methods: Data for patients undergoing MIRH between 2008 and 2017 at Emory University were reviewed. Risk factors for conversion were determined using multivariate regression analysis. Outcomes of conversion patients were compared with those who underwent successful MIRH or elective open surgery., Results: Unplanned conversion occurred in 7 (6.25%) of 112 patients undergoing MIRH. Primary reason for conversion was difficult dissection secondary to inflammation and severe adhesions. No preoperative clinical factor was identified that predicted conversions. Converted cases had higher EBL and pRBC transfusion compared to non-converted cases however morbidity was similar to those undergoing primary open surgery., Conclusion: Difficult dissection and adhesions remained the only clinically applicable parameter leading to unplanned conversions. While these did offset benefits of a successful minimally invasive approach, it did not increase risk of postoperative complications compared with planned open surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: International Medical Graduates (IMGs) secured greater than 10% of all general surgery (GS) residency positions in the US during the past decade. The Match process remains competitive, with a significant number of IMGs performing dedicated research before residency application. The impact of such research remains largely unknown. We aimed to provide an objective analysis of the impact of dedicated research time on obtaining a categorical GS residency position., Design: Data for National Resident Matching Program Match results from 2008-2017 was compiled from annual Match lists of the Aga Khan University, Medical College (Karachi, Pakistan). Medical graduates provided this information voluntarily each year. Data was exported to Microsoft Excel and used for descriptive and statistical analysis using SPSS. Candidates were divided into quasi-experimental groups based on their preference for direct application (no-research group, n = 64) or research prior to Match (research group, n = 20)., Results: A total of 84 IMG applicants matched into GS residency positions in the US within the past decade. Amongst these, 18 matched directly into categorical positions while 66 applicants secured preliminary spots. A total of 37 (56%) preliminary candidates eventually secured categorical GS residency positions. Research group applicants had an overall 85% (n = 17) success rate of obtaining a categorical position, while no-research group had a 59% (n = 39) success rate (chi-square test, p = 0.04). Success rate was 69% (n = 38) for male applicants and 57% (n = 17) for female applicants. Median time to a categorical position was 4 years (2-6) for the research group and 3 years (1-6) for the no-research group., Conclusions: Our quasi-experimental study demonstrated a higher success rate for Aga Khan University, Medical College applicants with significant research background in the US, compared to those who did not. Better social integration, enhanced mentorship available during research, overcoming of cultural and linguistic barriers and a perception as better qualified candidate can be some factors contributing to higher success rates., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.

Background: This study was conducted primarily to determine the prevalence and incidence of intra-abdominal hypertension (IAH) in a mixed ICU (medical & surgical) population and, secondarily, to compare outcomes between patients with and without IAH., Methods: The prospective cohort study was conducted from April to July 2011 on adult patients admitted in ICU, on mechanical ventilation and with an indwelling urinary catheter. Intra-vesicular pressure was measured. Primary endpoint was IAH and it was defined as Intra-abdominal pressure>12 mm Hg on two consecutive readings 6 h apart., Results: Total 83 patients were enrolled in the study; 61% from medical services and 39% from surgical services. Mean age in years±SD was 47 ± 17.5 with male preponderance (66%). IAH was detected in 23/83 (28%) at the time of admission, while six out of remaining 60 patients (10%) developed the condition during their ICU stay; the incidence and prevalence was 10% and 35%, respectively. Secondary end points of the study comparing outcomes between patients with and without IAH, though different in the two groups, did not achieve statistical significance. In-hospital mortality 65.5% vs. 44.4% p-value 0.054. New onset renal failure 34.5% vs. 16.7% p-value 0.054%. Difficulty in weaning from mechanical ventilation 37.9% vs. 25.9% p-value 0.008., Conclusion: IAH is a poorly recognized clinical entity with potentially devastating impact on patient outcomes. Since majority of patients had IAH at the time of admission, all ICU patients especially on ventilator should have baseline intra-abdominal pressures measured at the time of admission and subjected to appropriate management to prevent them from developing abdominal compartment syndrome., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors., (Copyright © 2015, American Association for the Advancement of Science.)

Objective: To identify the frequency of different types of oral clefts and presence of known risk factors among patients., Methods: The retrospective review of 292 patients, presenting with oral clefts between 1992 and 2011, was conducted at the Aga Khan University Hospital, Karachi. A pre-designed questionnaire was used to collect details, including demographics, type of cleft, presence of known risk factors, surgical details, and follow-up visits. SPSS 16 was used for data analysis. Chi-square test and analysis of variance was used: whenever applicable., Results: Of the total, 168 (57-53%) patients had cleft lip with or without cleft palate, and 124 (42.5%) had cleft palate alone. The most common defect was left-sided complete cleft lip and palate and midline incomplete cleft palate in the two groups respectively. Consanguinity among the parents was found to be the most common risk factor (n = 50; 17.1%). Median age of repair was 4 months for cleft lip and 10 months for cleft palate in the first group. For the other group, the median age of primary repair was 13 months. First-week follow-up after surgery was 50% (n = 84) for the lip repair, and 65% (n = 81) for palate repair., Conclusion: Our review revealed that most patients had cleft lip with or without cleft palate (CL/P). The most common risk factor was consanguinity among parents. Delay in seeking care, low follow-up rates after surgical repair of the anomaly and lack of involvement of speech therapist and orthodontist was observed.