Pilot Study to Optimize Goal-directed Hemodynamic Management During Pancreatectomy.

INTRODUCTION: Intraoperative goal-directed hemodynamic therapy (GDHT) is a cornerstone of enhanced recovery protocols. We hypothesized that use of an advanced noninvasive intraoperative hemodynamic monitoring system to guide GDHT may decrease intraoperative hypotension (IOH) and improve perfusion during pancreatic resection. METHODS: The monitor uses machine learning to produce the Hypotension Prediction Index to predict hypotensive episodes. A clinical decision-making algorithm uses the Hypotension Prediction Index and hemodynamic data to guide intraoperative fluid versus pressor management. Pre-implementation (PRE), patients were placed on the monitor and managed per usual. Post-implementation (POST), anesthesia teams were educated on the algorithm and asked to use the GDHT guidelines. Hemodynamic data points were collected every 20 s (8942 PRE and 26,638 POST measurements). We compared IOH (mean arterial pressure <65 mmHg), cardiac index >2, and stroke volume variation <12 between the two groups. RESULTS: 10 patients were in the PRE and 24 in the POST groups. In the POST group, there were fewer minimally invasive resections (4.2% versus 30.0%, P = 0.07), more pancreaticoduodenectomies (75.0% versus 20.0%, P < 0.01), and longer operative times (329.0 + 108.2 min versus 225.1 + 92.8 min, P = 0.01). After implementation, hemodynamic parameters improved. There was a 33.3% reduction in IOH (5.2% ± 0.1% versus 7.8% ± 0.3%, P < 0.01, a 31.6% increase in cardiac index >2.0 (83.7% + 0.2% versus 63.6% + 0.5%, P < 0.01), and a 37.6% increase in stroke volume variation <12 (73.2% + 0.3% versus 53.2% + 0.5%, P < 0.01). CONCLUSIONS: Advanced intraoperative hemodynamic monitoring to predict IOH combined with a clinical decision-making tree for GDHT may improve intraoperative hemodynamic parameters during pancreatectomy. This warrants further investigation in larger studies.

Association Between Preoperative Angioembolization and Bleeding Complications in Patients With Benign Liver Tumors: Analysis of a National Database.

INTRODUCTION: The role of angioembolization (AE) in patients with benign liver diseases is an area of active research. This study aims to assess any difference in liver resection outcomes in patients with benign tumors dependent on utilization of preoperative AE. METHODS: A retrospective cohort study of patients undergoing elective liver resections for benign liver tumors was performed using the National Surgical Quality Improvement Program database (2014-2019). Only tumors of 5 cm in size or more were included in the analysis. We categorized the patients based on preoperative AE (AE + versus AE -). The primary outcome measured included bleeding complications within 72 h. The secondary outcomes were to determine predictors of bleeding. RESULTS: After propensity score matching, there were 103 patients in both groups. There was no difference in intraoperative or postoperative blood transfusions within 72 h of surgery (14.6% versus 12.6%; P = 0.68), reoperation (1.9% versus 1.9%; P = 1), or mortality (1.0% versus 0.0%; P = 1) between the two groups. Multivariate regression analysis revealed an open surgical approach (odds ratio [OR]: 4.59 confidence interval [CI]: 2.94-7.16), use of Pringle maneuver (OR: 1.7, CI: 1.26-2.310), preoperative anemia (OR: 2.79, CI: 2.05-3.80), and preoperative hypoalbuminemia (OR: 1.53 [1.14-2.05]) were associated with the need for intraoperative or postoperative blood transfusions within 72 h of surgery. CONCLUSIONS: Preoperative AE was not associated with reducing intraoperative or postoperative bleeding complications or blood transfusions within 72 h after surgery.

Significance of Lymph Node Resection After Neoadjuvant Therapy in Pancreatic, Gastric, and Rectal Cancers.

OBJECTIVE: Gastrointestinal cancers are increasingly being treated with NAT before surgical resection. Currently, quality metrics are linked to the number of LNs resected to determine subsequent treatment and prognosis. We hypothesize that NAT decreases LN metastasis, downstages patients, and decreases overall lymph node yields (LNY) compared to initial surgical resection. With increasing use of NAT, this brings into question the validity of quality metrics. METHODS: Gastric (stage II/III), pancreatic (stage I/II/III), and rectal cancers (stage II/III) (2010-2015) treated with surgery with/without NAT were identified in National Cancer Database. We evaluated total LNY and LN metastasis with/without NAT and clinical and pathological stage to evaluate rates of downstaging. RESULTS: A total of 7934 gastric, 15,908 pancreatic, and 21,354 rectal cancer patients were included of which 61.1%, 21.2%, and 85.7% received NAT, respectively. NAT patients were more likely to be downstaged (39.9% vs 11.1% gastric P< 0.001, 30.6% vs 3.2% pancreatic P< 0.001, 52.0% vs 16.3% rectal P< 0.001), have lower LNYs (18.8 vs 19.1 gastric P = 0.239, 18.4 vs 17.5 pancreatic P< 0.001, 15.7 vs 20.0 rectal P< 0.001) and have N0 pathologic disease (43.6% vs 26.7% gastric P< 0.001, 51.1% vs 30.9% pancreatic P< 0.001, 65.9% vs 49.4% rectal P< 0.001) when compared to initial surgical resection. CONCLUSION: NAT for gastrointestinal cancers results in overall lower LN yields, lower LN metastases, and significant downstaging of tumors. As all patients undergoing NAT receive multimodality therapy, LN yield recommendations may not be true quality metric changing.

Trends and disparities in access to minimally invasive distal pancreatectomy (midp): an eight-year analysis from the national cancer database.

Laparoscopic and robotic approaches to distal pancreatectomy are becoming the standard of care. The aim of our study was to evaluate the trends of utilization and disparities in access to minimally invasive approaches in distal pancreatectomy. We queried the National Cancer Database (NCDB) and analyzed all the patients who underwent distal pancreatectomy from 2010 to 2017. Patients were divided into groups of those with open distal pancreatectomy (ODP) and those with laparoscopic or robotic distal pancreatectomy (MIDP = minimally invasive distal pancreatectomy). Our outcome measures were trends of MIDP and disparities in access to MIDP. Cochran Armitage trend analysis and multivariate regression analysis were used to evaluate outcomes. A total of 13,537 patients with distal pancreatectomy were identified in the NCDB from 2010 to 2017. 7548 (55.8%) underwent ODP, while 5989 (44.2%) underwent MIDP. The MIDP rates increased from 25% in 2010 to 52% in 2017 (p < 0.01). On regression analysis, when controlled for age, gender, diagnosis, tumor size, grade, staging, and chemoradiotherapy, African American patients were 30% less likely to undergo MIDP than White (OR 0.7, 95% CI [0.5-0.8], p < 0.01). Similarly, Hispanic patients were 25% less likely to undergo MIDP than non-Hispanic patients OR 0.75, 95% CI [0.6-0.9], p = 0.02). Compared to Medicare/private insured patients, uninsured patients were 50% less likely to undergo MIDP (OR 0.5, 95% CI [0.4-0.7], p < 0.01). Based on the medium household income, compared to patients in the fourth quartile, patients in the third quartile OR 0.9, 95% CI [0.3-0.9], p = 0.03). Second OR 0.8, 95%CI [0.5-0.9], p < 0.01), first quartile OR 0.7, 95% CI [0.5-0.8], p < 0.01) were less likely to undergo MIPD as well. Utilization of MIDP has increased from one in every four patients in 2010 to every other patient in 2017. However, African Americans, Hispanics, the uninsured, and those from low-income quartiles are less likely to undergo MIDP. Efforts should be made to ensure access to minimally invasive approches are available to minorities.

Concurrent Stage III Unresectable Duodenal Adenocarcinoma and Metastatic Gastrointestinal Stromal Tumor Treated With Combination of Imatinib and mFOLFIRI.

Cases of concurrent duodenal adenocarcinoma and gastrointestinal stromal tumors (GISTs) are rare, and only a few have been reported. While some cases of other synchronous primary tumors with GIST have been reported, no shared mutations have been consistently found, creating challenges in selecting chemotherapy in cases of inoperable tumors. Here, we presented a case of a stage IIIA locally advanced/unresectable duodenal adenocarcinoma with concurrent metastatic small bowel GIST successfully being treated with combined imatinib and modified folinic acid, 5-fluorouracil, and irinotecan (mFOLFIRI) regimen.

Feeble, fallen, and forgetting: association of cognitive impairment and falls on outcomes of major intra-abdominal surgeries in older adults.

BACKGROUND: Both cognitive impairment/dementia (CID) and falls occur more commonly in older adults than in younger patients. This study aimed to analyze the association of a history of CID or falls with the postoperative outcomes of older adults undergoing major intra-abdominal surgeries on a national level. METHODS: We retrospectively analyzed the American College of Surgeons-National Surgical Quality Improvement Program 2022 Participant Use Data File. Our primary outcome was postoperative mortality. Statistical analysis was performed using the Chi-square test and multivariate regression analysis. RESULTS: On multivariable regression analyses, a history of both CID (odds ratio [OR] = 1.9; CI: 1.5-2.5; P < .01) and a fall (OR = 1.8; CI: 1.4-2.3; P < .01) were independently associated with higher adjusted odds of mortality. History of CID or falls was also a predictor of overall complications, major complications, and discharge to a care facility. CONCLUSION: A history of CID or falls in older adults before major intra-abdominal surgeries was associated with a high risk of postoperative mortality and morbidity. Further studies are required to establish the causal relation of these factors and the steps to mitigate the risk of associated adverse outcomes.

Improving communication in level 1 trauma centers: replacing pagers with smartphones.

INTRODUCTION: Communication among healthcare providers continues to change, and 90% of healthcare providers are now carrying cellular phones. Compared with pagers, the rate and amount of information immediately available via cellular phones are far superior. Wireless devices such as smartphones are ideal in acute trauma settings as they can transfer patient information quickly in a coordinate manner to all the team members responsible for patient care. SUBJECTS AND METHODS: A questionnaire survey was distributed among all the trauma surgeons, surgery residents, and nurse practitioners who were a part of the trauma surgery team at a Level 1 trauma center. Answers to each question were recorded on a 5-point Likert scale. The completed survey questionnaires were analyzed using Statistical Package for Social Sciences software (SPSS version 17; SPSS, Inc., Chicago, IL). RESULTS: The respondents had an overall positive experience with the usage of the third-generation (3G) smartphones, with 94% of respondents in favor of having wireless means of communication at a Level 1 trauma center. Of respondents, 78% found the device very user friendly, 98% stated that use of smartphones had improved the speed and quality of communication, 96% indicated that 3G smartphones were a useful teaching tool, 90% of the individuals felt there was improvement in the physician's response time to both routine and critical patients, and 88% of respondents were aware of the rules and regulations of the Health Insurance Portability and Accountability Act. CONCLUSIONS: Smartphones in an acute trauma setting are easy to use and improve the means of communication among the team members by providing accurate and reliable information in real time. Smartphones are effective in patient follow-up and as a teaching tool. Strict rules need to be used to govern the use of smartphones to secure the safety and secrecy of patient information.

Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions.

In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.

Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study.

BACKGROUND: Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established. We aimed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery. METHODS: We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College of Surgeons' National Surgical Quality Improvement Program database (a prospective validated outcomes registry from 211 hospitals worldwide in 2008). We obtained anonymised data for 30-day mortality and morbidity (cardiac, respiratory, CNS, urinary tract, wound, sepsis, and venous thromboembolism outcomes), demographics, and preoperative and perioperative risk factors. We used multivariate logistic regression to assess the adjusted and modified (nine predefined risk factor subgroups) effect of anaemia, which was defined as mild (haematocrit concentration >29-<39% in men and >29-<36% in women) or moderate-to-severe (≤29% in men and women) on postoperative outcomes. FINDINGS: We obtained data for 227,425 patients, of whom 69,229 (30·44%) had preoperative anaemia. After adjustment, postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia (odds ratio [OR] 1·42, 95% CI 1·31-1·54); this difference was consistent in mild anaemia (1·41, 1·30-1·53) and moderate-to-severe anaemia (1·44, 1·29-1·60). Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia (adjusted OR 1·35, 1·30-1·40), again consistent in patients with mild anaemia (1·31, 1·26-1·36) and moderate-to-severe anaemia (1·56, 1·47-1·66). When compared with patients without anaemia or a defined risk factor, patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone. INTERPRETATION: Preoperative anaemia, even to a mild degree, is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery. FUNDING: Vifor Pharma.

Natural orifice transluminal endoscopic surgery (NOTES): assessment of peritoneal bacterial load after intraperitoneal antimicrobial wash and evaluation of hemodynamic changes in a porcine model.

AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is a promising newly developed procedure; however, it is associated with many complications. The main aim of our study is to assess whether peritoneal wash with antibiotics decreases the bacterial load contamination related to the transgastric approach. METHODS: Ten female farm pigs underwent transgastric peritoneoscopy with fallopian tubal ligation. Five pigs were randomized to antibiotic wash of the peritoneal cavity and five to placebo. All animals were given one intravenous dose of antibiotic before the procedure. Hemodynamic variables were continuously monitored throughout the procedure. The next day, peritoneal cultures were taken. The fallopian tubes were inspected to determine the success of ligation and the gastric incision sites were assessed for leakage. RESULTS: No significant difference was noted between the antibiotic peritoneal wash group and the placebo group in terms of peritoneal bacterial load with respective median colony-forming units per ml (CFU/ml) of 0 [0; 1] vs. 0 [0; 4], p = 0.637. No clinically significant hemodynamic changes were noted during the procedure. CONCLUSIONS: The results of our study indicate that NOTES carries minimal risk of peritoneal bacterial contamination, regardless of the use of intraperitoneal antibiotics, and is not associated with hemodynamic compromise.

Mobile primary renal vein lipoma with an accelerated growth pattern.

Primary intravascular lipoma is a rare proliferation of adipose tissue originating from the wall of blood vessels. We have described an unusual case of a benign, but fast-growing, primary intravascular lipoma of the left renal vein with the mobile edge extending to the cavoatrial junction within just a few months. We have discussed the surgical indications, management, and technical considerations and highlighted the importance of surgical planning for similar cases.

Frailty Predicts Loss of Independence After Liver Surgery.

BACKGROUND: Loss of independence (LOI) is a significant concern in patients undergoing liver surgery. Although the risks of morbidity and mortality have been well studied, there is a dearth of data regarding the risk of LOI. Therefore, this study aimed to assess predictors of LOI after liver surgery. METHODS: This study utilized the National Surgical Quality Improvement Program (NSQIP) data from 2015 to 2018 from a retrospective cohort study of patients undergoing liver resections. LOI was defined as the change from preoperative functional independence to the postoperative discharge requirement in a post-care facility. Frailty was defined using the modified frailty index-5 (mFI-5). RESULTS: A total of 22,463 patients underwent hepatectomy via the NSQIP during the study period. In total, 22,067 participants were included in the analysis. A total of 4.7% of patients had LOI after surgery and were discharged to a rehabilitation center or nursing facility. mFI-1 was an independent predictor of LOI (OR:2.2 [1.9-4.3]). However, the odds for LOI were higher (OR:5.1[2.5-8.2]) in patients with mFI ≥ 2. CONCLUSION: LOI is an important outcome of liver surgery. Frailty is a predictor of LOI and should be used as a guide to inform patients about the potential outcomes.

The Impact of Frailty on Patients Undergoing Liver Resection for Colorectal Liver Metastasis.

BACKGROUND: The aim of this study is to assess the impact of frailty on short-term outcomes after hepatectomy for colorectal liver metastasis (CRLM). METHODS: Patients were identified using the National Surgical Quality Improvement Program (NSQIP). Patients were divided into 3 categories using the 5-item Modified Frailty Index (mFI). RESULTS: There were 5230 patients included. 52%, 35%, and 13% had mFI scores of 0, 1, and ≥ 2 respectively. Patients with a ≥ 2 mFI score were more likely to experience minor complication (OR 1.34, 95% CI 1.06-1.69), major complication (OR 1.56, 95% CI 1.15-2.12), readmission (OR 1.55, 95% CI 1.12-2.14), unfavorable discharge (OR 2.48, 95% CI 1.62-3.80), 30-day mortality (OR 3.02, 95% CI 1.02-8.95), prolonged length of stay (OR 1.47, 95% CI 1.18-1.83), and bile leak (OR 1.51, 95% CI 1.02-2.24). CONCLUSION: Frailty is associated with increased post-operative complications. The 5-item mFI can guide risk stratification, optimization, and counseling.

Does Preoperative Estimated Glomerular Filtration Rate (eGFR) Predict Short-Term Surgical Outcomes in Patients Undergoing Pancreatic Resections?

INTRODUCTION: Preoperative eGFR has been found to be a reliable predictor of post-operative outcomes in patients with normal creatinine levels who undergo surgery. The aim of our study was to evaluate the impact of preoperative eGFR levels on short-term post-operative outcomes in patients undergoing pancreatectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) pancreatectomy file (2014-2017) was queried for all adult patients (age ≥ 18) who underwent pancreatic resection. Patients were stratified into two groups based on their preoperative eGFR (eGFR < 60 mL/min/1.73m2 and eGFR ≥ 60 mL/min/1.73m2). Outcome measures included post-operative pancreatic fistula, discharge disposition, hospital length of stay, 30-day readmission rate, and 30-day morbidity and mortality. Multivariate logistic regression analysis was performed. RESULTS: A total of 21,148 were included in the study of which 12% (n = 2256) had preoperative eGFR < 60 mL/min/1.73m2. Patients in the eGFR < 60 group had prolonged length of stay, were less likely to be discharged home, had higher minor and major complication rates, and higher rates of mortality. On logistic regression analysis, lower preoperative eGFR (< 60 mL/min/1.73m2) was associated with higher odds of prolonged length of stay [aOR: 1.294 (1.166-1.436)], adverse discharge disposition [aOR: 1.860 (1.644-2.103)], minor [aOR: 1.460 (1.321-1.613)] and major complications [aOR: 1.214 (1.086-1.358)], bleeding requiring transfusion [aOR: 1.861 (1.656-2.091)], and mortality [aOR: 2.064 (1.523-2.797)]. CONCLUSION: Preoperative decreased renal function measured by eGFR is associated with adverse outcomes in patients undergoing pancreatic resection. The results of this study may be valuable in improving preoperative risk stratification and post-operative expectations.

HIV-1 infected humanized DRAGA mice develop HIV-specific antibodies despite lack of canonical germinal centers in secondary lymphoid tissues.

A major barrier in the use of humanized mice as models of HIV-1 (HIV) infection is the inadequate generation of virus-specific antibody responses. Humanized DRAGA (hDRAGA) mice generate antigen-specific class switched antibodies to several pathogens, but whether they do so in HIV infection and the extent to which their secondary lymphoid tissues (sLT) support germinal center responses is unknown. hDRAGA mice were evaluated for their ability to support HIV replication, generate virus-specific antibody responses, develop splenocyte subsets, and organize sLT architecture. hDRAGA mice supported persistent HIV replication and developed modest levels of gp41-specific human IgM and IgG. Spleens from uninfected and HIV infected hDRAGA mice contained differentiated B and CD4+ T cell subsets including germinal center (GC) B cells and T follicular helper cells (TFH); relative expansions of TFH and CD8+ T cells, but not GC B cells, occurred in HIV-infected hDRAGA mice compared to uninfected animals. Immunofluorescent staining of spleen and mesenteric lymph node sections demonstrated atypical morphology. Most CD4+ and CD8+ T cells resided within CD20hi areas. CD20hi areas lacked canonical germinal centers, as defined by staining for IgD-Ki67+cells. No human follicular dendritic cells (FDC) were detected. Mouse FDC were distributed broadly throughout both CD20hi and CD20lo regions of sLT. HIV RNA particles were detected by in situ hybridization within CD20+ areas and some co-localized with mouse FDC. Viral RNA+ cells were more concentrated within CD20hi compared to CD20lo areas of sLT, but differences were diminished in spleen and eliminated in mesenteric lymph nodes when adjusted for CD4+ cell frequency. Thus, hDRAGA mice recapitulated multiple aspects of HIV pathogenesis including HIV replication, relative expansions in TFH and CD8+ T cells, and modest HIV-specific antibody production. Nevertheless, classical germinal center morphology in sLT was not observed, which may account for the inefficient expansion of GC B cells and generation of low titer human antibody responses to HIV-1 in this model.

Role of magnetic resonance imaging in Bouveret's syndrome: A case report with review of the literature.

Bouveret's syndrome is a rare form of gallstone ileus occurring due to obstructing gallstone into the proximal duodenum through a cholecystoduodenal fistula. We report the case of a 72-year-old female presenting with abdominal pain secondary to a large gallstone in the region of the duodenal bulb, causing the upstream gastric obstruction. Here we discuss the clinical features, imaging technologies, and surgical management of Bouveret's syndrome.

Outcomes with Preoperative Biliary Stenting After Pancreaticoduodenectomy In the Modern Era.

BACKGROUND: Previous studies have documented increased complications following pancreaticoduodenectomy in patients who undergo preoperative biliary stenting (PBS). However, in the modern era, the vast majority of patients with jaundice are stented. We hypothesized that there is no difference in short-term postoperative outcomes between PBS and no PBS in patient with obstructive jaundice undergoing pancreaticoduodenectomy. METHODS: We performed an analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) participant use file (2014-2017). Patients who received neoadjuvant chemotherapy and required stenting were excluded from the analysis. A propensity-matched analysis was performed to select obstructive jaundice patients who underwent PBS and those who did not with similar characteristics prior to pancreaticoduodenectomy. Short-term postoperative outcome measures included superficial surgical site infection (S-SSI), deep surgical site infection (D-SSI), hospital length of stay (LOS), postoperative pancreatic fistula (POF), hospital readmission, minor morbidity (Clavien-Dindo I-II), major morbidity (Clavien-Dindo III, IV, V), and 30-day mortality. RESULTS: A total of 5851 patients with obstructive jaundice underwent pancreaticoduodenectomy without neoadjuvant chemotherapy. 81.6% underwent PBS. Based on the propensity-matched analysis, 927 patients who received PBS and 927 patients who did not were selected for comparing the outcomes between the two groups. There was no significant difference in outcome measures between the two groups with respect to S-SSI (OR 1.30 , 95% CI = 0.94-1.80, p = 0.12), D-SSI (OR 1.07, 95% CI = 0.81-1.41, p = 0.62), POF (OR 1.11, 95% CI = 0.87-1.42, p = 0.40), hospital readmission (OR 0.99, 95% CI = 0.77-1.27, p = 0.94), minor morbidity (OR 0.91, 95% CI = 0.76-1.11, p = 0.36), major morbidity (OR 0.84, 95% CI = 0.67-1.06, p = 0.14), and 30-day mortality (OR 1.05, 95% CI = 0.57-1.95, p = 0.87). Patients who underwent PBS were more likely to have shorter LOS (RR 0.87, 95% CI = 0.81-0.93, p < 0.0001). CONCLUSION: Contrary to previously reported studies, there was no increased risk of short-term postoperative outcomes after pancreaticoduodenectomy between PBS and N-PBS in a propensity-matched analysis. Preoperative biliary stenting is safe and does not need to be avoided before surgical intervention in patients who present with obstructive jaundice.

Survival after Margin-Positive Resection in the Era of Modern Chemotherapy for Pancreatic Cancer: Do Patients Still Benefit?

BACKGROUND: R0 resection for pancreatic cancer is considered standard of care, but is not always achieved. This study looks at R1/R2 resection outcomes compared with chemotherapy alone. Our hypothesis is that patients with margin-positive disease have better outcomes than those receiving chemotherapy alone. STUDY DESIGN: Stage II pancreatic cancer patients who underwent R1/R2 surgery with/without neoadjuvant chemotherapy, from the National Cancer Database (NCDB) 2010 to 2017 were identified and compared with similar staged patients who received chemotherapy alone. The surgical group was then analyzed by subset based on receipt of chemotherapy: upfront surgery (+/- adjuvant therapy) and neoadjuvant therapy followed by surgery (+/- adjuvant therapy). RESULTS: There were 11,699 Stage II pancreatic cancer patients included, 9,521 (81.4%) of whom were treated with chemotherapy alone, 15.7% (n = 1,836) had upfront surgery, and 2.9% (n = 342) had neoadjuvant therapy with surgery. R1/R2 neoadjuvant patients had the best overall survival at a mean of 19.75 months (95% CI 17.91, 22.28) compared with the upfront surgery group (17.77 months, 95% CI 15.64, 19.55) and the chemotherapy alone group (10.12 months, 95% CI 8.97, 11.50) (hazard ratio [HR] 0.46 upfront surgery and 0.32 neoadjuvant group, respectively, p < 0.0001). Even with R2 resection, survival was better in surgical patients compared with patients who underwent chemotherapy only (15.76 mo vs 10.22 mo, p = 0.06). Patients with R1/R2 resections had improved survival if they received neoadjuvant/adjuvant chemotherapy, though the survival rates were significantly lower than those with standard R0 resections (n = 16,129). CONCLUSIONS: R1 resection has benefit over chemotherapy alone in pancreatic cancer. Pancreatic cancer patients who are left with microscopic R1 disease have better survival than without surgery, particularly in the setting of neoadjuvant therapy.

Murine- and Human-Derived Autologous Organoid/Immune Cell Co-Cultures as Pre-Clinical Models of Pancreatic Ductal Adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has the lowest five-year survival rate of all cancers in the United States. Programmed death 1 receptor (PD-1)-programmed death ligand 1 (PD-L1) immune checkpoint inhibition has been unsuccessful in clinical trials. Myeloid-derived suppressor cells (MDSCs) are known to block anti-tumor CD8+ T cell immune responses in various cancers including pancreas. This has led us to our objective that was to develop a clinically relevant in vitro organoid model to specifically target mechanisms that deplete MDSCs as a therapeutic strategy for PDAC. Method: Murine and human pancreatic ductal adenocarcinoma (PDAC) autologous organoid/immune cell co-cultures were used to test whether PDAC can be effectively treated with combinatorial therapy involving PD-1 inhibition and MDSC depletion. Results: Murine in vivo orthotopic and in vitro organoid/immune cell co-culture models demonstrated that polymorphonuclear (PMN)-MDSCs promoted tumor growth and suppressed cytotoxic T lymphocyte (CTL) proliferation, leading to diminished efficacy of checkpoint inhibition. Mouse- and human-derived organoid/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of arginase 1-expressing PMN-MDSCs within these co-cultures rendered the organoids susceptible to anti-PD-1/PD-L1-induced cancer cell death. Conclusions: Here we use mouse- and human-derived autologous pancreatic cancer organoid/immune cell co-cultures to demonstrate that elevated infiltration of polymorphonuclear (PMN)-MDSCs within the PDAC tumor microenvironment inhibit T cell effector function, regardless of PD-1/PD-L1 inhibition. We present a pre-clinical model that may predict the efficacy of targeted therapies to improve the outcome of patients with this aggressive and otherwise unpredictable malignancy.