Post-Pancreatoduodenectomy Outcomes and Epidural Analgesia: A 5-Year Single Institution Experience

Introduction Optimal pain control post-pancreatoduodenectomy is a challenge. Epidural analgesia (EDA) is increasingly utilized despite inherent risks and unclear effects on outcomes. Methods All pancreatoduodenectomies (PD) performed from 1/2013-12/2017 were included. Clinical parameters were obtained from retrospective review of a prospective clinical database, the ACS NSQIP prospective institutional database and medical record review. Chi-Square/Fisher’s Exact and Independent-Samples t-Tests were used for univariable analyses; multivariable regression (MVR) was performed. Results 671 consecutive PD from a single institution were included (429 EDA, 242 non-EDA). On univariable analysis, EDA patients experienced significantly less wound disruption (0.2% vs. 2.1%), unplanned intubation (3.0% vs. 7.9%), pulmonary embolism (0.5% vs. 2.5%), mechanical-ventilation >48hrs (2.1% vs. 7.9%), septic shock (2.6% vs. 5.8%), and lower pain scores. On MVR accounting for baseline group differences (gender, hypertension, pre-operative transfusion, labs, approach, pancreatic duct size), EDA was associated with less superficial wound infections (OR 0.34; CI 0.14-0.83; P=0.017), unplanned intubations (OR 0.36; CI 0.14-0.88; P=0.024), mechanical ventilation >48 hrs (OR 0.22; CI 0.08-0.62; P=0.004), and septic shock (OR 0.39; CI 0.15-1.00; P=0.050). EDA improved pain scores post-PD days 1-3 (P<0.001). No differences were seen in cardiac or renal complications; pancreatic fistula (B+C) or delayed gastric emptying; 30/90-day mortality; length of stay, readmission, discharge destination, or unplanned reoperation. Conclusion Based on the largest single institution series published to date, our data support the use of EDA for optimization of pain control. More importantly, our data document that EDA significantly improved infectious and pulmonary complications

Partial splenectomy in children: Long-term reoperative outcomes

PURPOSE: Partial, or subtotal, splenectomy (PS) has become an accepted alternative to total splenectomy (TS) for management of hematologic disorders in children, but little is known about its long-term outcomes. Here, we present our institutional experience with partial splenectomy, to determine rate of subsequent TS or cholecystectomy and identify if any factors affected this need. METHODS: All patients who underwent partial splenectomy at a single tertiary children's hospital were retrospectively reviewed from 2002 through 2019 after IRB approval. Primary outcome of interest was rate of reoperation to completion splenectomy (CS) and rate of cholecystectomy. Secondary outcome were positive predictor(s) for these subsequent procedures. RESULTS: Twenty-four patients underwent PS, at median age 6.0 years, with preoperative spleen size of 12.7 cm by ultrasound. At median follow up time of 8.0 years, 29% of all patients and 24% of hereditary spherocytosis (HS) patients underwent completion splenectomy at median 34 months and 45 months, respectively. Amongst HS patients who did not have a cholecystectomy with or prior to PS, 39% underwent a delayed cholecystectomy following PS. There were no significant differences in age at index procedure, preoperative splenic volume, weight of splenic specimen removed, transfusion requirements, preoperative or postoperative hematologic parameters (including hemoglobin, hematocrit, total bilirubin, and reticulocyte count) amongst patients of all diagnoses and HS only who underwent PS alone compared to those who went on to CS. There were no cases of OPSS or deaths. CONCLUSION: Partial splenectomy is a safe alternative to total splenectomy in children with hematologic disease with theoretical decreased susceptibility to OPSS. However, families should be counseled of a 29% chance of reoperation to completion splenectomy, and, in HS patients, a 39% chance of delayed cholecystectomy if not performed prior to or with PS. Further studies are needed to understand predictors of these outcomes

Pancreatic Fluid Interleukin-1β Complements Prostaglandin E2 and Serum Carbohydrate Antigen 19-9 in Prediction of Intraductal Papillary Mucinous Neoplasm Dysplasia

Objectives: We sought to determine if interleukin (IL)-1β and prostaglandin E2 (PGE2) (inflammatory mediators in pancreatic fluid) together with serum carbohydrate antigen (CA) 19–9 could better predict intraductal papillary mucinous neoplasm (IPMN) dysplasia than individual biomarkers alone. Methods: Pancreatic cyst fluid (n = 92) collected via endoscopy or surgery (2003–2016) was analyzed for PGE2 and IL-1β (Enzyme-Linked Immunosorbent Assay). Patients had surgical pathology-proven IPMN. Threshold values (PGE2 [>1100 pg/mL], IL-1β [>20 pg/mL], serum CA 19–9 [>36 U/mL]) were determined. Results: Levels of IL-1β were higher in high-grade (HGD)/Invasive-IPMN (n = 42) compared to Low/Moderate-IPMN (n = 37) (median [range], 54.6 [0–2671] vs 5.9 [0–797] pg/mL; P < 0.001; Area Under Curve [AUC], 0.766). Similarly, PGE2 was higher in HGD/Invasive-IPMN (n = 45) compared to Low/Moderate-IPMN (n = 47) (median [range], 1790 [20–15,180] vs. 140 [10–14,630] pg/mL; P < 0.001; AUC, 0.748). Presence of elevated PGE2 and IL-1β (AUC, 0.789) provided 89% specificity and 82% positive predictive value (PPV) for HGD/Invasive-IPMN. Elevated levels of all three provided 100% Specificity and PPV for HGD/Invasive-IPMN. Conclusion: Cyst fluid PGE2, IL-1β, and serum CA 19–9 in combination optimize specificity and PPV for HGD/Invasive-IPMN and may help build a panel of markers to predict IPMN dysplasia

Preoperative stroke before cardiac surgery does not increase risk of postoperative stroke

The optimal time when surgery can be safely performed after stroke is unknown. The purpose of this study was to investigate how cardiac surgery timing after stroke impacts postoperative outcomes between 2011–2017 were reviewed. Variables were extracted from the institutional Society of Thoracic Surgeons database, statewide patient registry, and medical records. Subjects were classified based upon presence of endocarditis and further grouped by timing of preoperative stroke relative to cardiac surgery: Recent (stroke within two weeks before surgery), Intermediate (between two and six weeks before), and Remote (greater than six weeks before). Postoperative outcomes were compared amongst groups. 157 patients were included: 54 in endocarditis and 103 in non-endocarditis, with 47 in Recent, 26 in Intermediate, and 84 in Remote. 30-day mortality and postoperative stroke rate were similar across the three subgroups for both endocarditis and non-endocarditis. Of patients with postoperative stroke, mortality was 30% (95% CI 4.6–66). Timing of cardiac surgery after stroke occurrence does not seem to affect postoperative stroke or mortality. If postoperative stroke does occur, subsequent stroke-related mortality is high

High Rates of Readmission in Necrotizing Pancreatitis: Natural History or Opportunity for Improvement?

Background Necrotizing pancreatitis (NP) is a complex and heterogeneous disease with a protracted disease course. Hospital readmission is extremely common; however, few data exist regarding the cause of readmission in NP. Methods A retrospective review of NP patients treated between 2005 and 2017 identified patients readmitted both locally and to our hospital. All patients with unplanned hospital readmissions were evaluated to determine the cause for readmission. Clinical and demographic factors of all patients were recorded. As appropriate, two independent group t tests and Pearson’s correlation or Fisher’s exact tests were performed to analyze the relationship between index admission clinical factors and readmission. p values of < 0.05 were accepted as statistically significant. Results Six hundred one NP patients were reviewed. Median age was 52 years (13–96). Median index admission length of stay was 19 days (2–176). The most common etiology was biliary (49.9%) followed by alcohol (20.0%). Unplanned readmission occurred in 432 patients (72%) accounting for a total of 971 unique readmissions (mean readmissions/patient, 2.3). The most common readmission indications were symptomatic necrosis requiring supportive care and/or intervention (31.2%), infected necrosis requiring antibiotics and/or intervention (26.6%), failure to thrive (9.7%), and non-necrosis infection (6.6%). Patients requiring readmission had increased incidence of index admission renal failure (21.3% vs. 14.2%, p = 0.05) and cardiovascular failure (12.5% vs. 4.7%, p = 0.01). Discussion Readmission in NP is extremely common. Significant portions of readmissions are a result of the disease natural history; however, a percentage of readmissions appear to be preventable. Patients with organ failure are at increased risk for unplanned readmission and will benefit from close follow-up

Performance of Candidate Urinary Biomarkers for Pancreatic Cancer - Correlation with Pancreatic Cyst Malignant Progression?

Background Intraductal papillary mucinous neoplasms (IPMN) are precursors of pancreatic cancer. Potential biomarkers of IPMN progression have not been identified in urine. A few urinary biomarkers were reported to be predictive of pancreatic ductal adenocarcinoma (PDAC). Here, we seek to assess their ability to detect high-risk IPMN. Methods Urine was collected from patients undergoing pancreatic resection and healthy controls. TIMP-1(Tissue Inhibitor of Metalloproteinase-1), LYVE-1(Lymphatic Vessel Endothelial Receptor 1), and PGEM(Prostaglandin E Metabolite) levels were determined by ELISA and analyzed by Kruskal-Wallis. Results Median urinary TIMP-1 levels were significantly lower in healthy controls (n = 9; 0.32 ng/mg creatinine) compared to PDAC (n = 13; 1.95) but not significantly different between low/moderate-grade (n = 20; 0.71) and high-grade/invasive IPMN (n = 20; 1.12). No significant difference in urinary LYVE-1 was detected between IPMN low/moderate (n = 16; 0.37 ng/mg creatinine) and high/invasive grades (n = 21; 0.09). Urinary PGEM levels were not significantly different between groups. Conclusions Urinary TIMP-1, LYVE-1, and PGEM do not correlate with malignant potential of pancreatic cysts

Visceral artery pseudoaneurysm in necrotizing pancreatitis: incidence and outcomes

Background: Visceral artery pseudoaneurysms (VA-PSA) occur in necrotizing pancreatitis; however, little is known about their natural history. This study sought to evaluate the incidence and outcomes of VA-PSA in a large cohort of patients with necrotizing pancreatitis. Methods: Data for patients with necrotizing pancreatitis who were treated between 2005 and 2017 at Indiana University Health University Hospital and who developed a VA-PSA were reviewed to assess incidence, presentation, treatment and outcomes. Results: Twenty-eight of 647 patients with necrotizing pancreatitis (4.3%) developed a VA-PSA between 2005 and 2017. The artery most commonly involved was the splenic artery (36%), followed by the gastroduodenal artery (24%). The most common presenting symptom was bloody drain output (32%), followed by incidental computed tomographic findings (21%). The median time from onset of necrotizing pancreatitis to diagnosis of a VA-PSA was 63.5 days (range 1-957 d). Twenty-five of the 28 patients who developed VA-PSA (89%) were successfully treated with percutaneous angioembolization. Three patients (11%) required surgery: 1 patient rebled following embolization and required operative management, and 2 underwent upfront operative management. The mortality rate attributable to hemorrhage from a VA-PSA in the setting of necrotizing pancreatitis was 14% (4 of 28 patients). Conclusion: In this study, VA-PSA occurred in 4.3% of patients with necrotizing pancreatitis. Percutaneous angioembolization effectively treated most cases; however, mortality from VA-PSA was high (14%). A high degree of clinical suspicion remains critical for early diagnosis of this potentially fatal problem

Preoperative Nomogram Predicts Non-home Discharge in Patients Undergoing Pancreatoduodenectomy

Background In patients undergoing pancreatoduodenectomy, non-home discharge is common and often results in an unnecessary delay in hospital discharge. This study aimed to develop and validate a preoperative prediction model to identify patients with a high likelihood of non-home discharge following pancreatoduodenectomy. Methods Patients undergoing pancreatoduodenectomy from 2013 to 2018 were identified using an institutional database. Patients were categorized according to discharge location (home vs. non-home). Preoperative risk factors, including social determinants of health associated with non-home discharge, were identified using Pearson’s chi-squared test and then included in a multiple logistic regression model. A training cohort composed of 80% of the sampled patients was used to create the prediction model, and validation carried out using the remaining 20%. Statistical significance was defined as P < 0.05. Results Seven hundred sixty-six pancreatoduodenectomy patients met the study criteria for inclusion in the analysis (non-home, 126; home, 640). Independent predictors of non-home discharge on multivariable analysis were age, marital status, mental health diagnosis, functional health status, dyspnea, and chronic obstructive pulmonary disease. The prediction model was then used to generate a nomogram to predict likelihood of non-home discharge. The training and validation cohorts demonstrated comparable performances with an identical area under the curve (0.81) and an accuracy of 84%. Conclusion A prediction model to reliably assess the likelihood of non-home discharge after pancreatoduodenectomy was developed and validated in the present study

The Physics of Core-Collapse Supernovae

Supernovae are nature's grandest explosions and an astrophysical laboratory in which unique conditions exist that are not achievable on Earth. They are also the furnaces in which most of the elements heavier than carbon have been forged. Scientists have argued for decades about the physical mechanism responsible for these explosions. It is clear that the ultimate energy source is gravity, but the relative roles of neutrinos, fluid instabilities, rotation and magnetic fields continue to be debated.Comment: Review article; 17 pages, 5 figure

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal