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"Sulzer, Jesse K."
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Endocannabinoid Degradation Inhibition Improves Neurobehavioral Function, Blood–Brain Barrier Integrity, and Neuroinflammation following Mild Traumatic Brain Injury
by
Rogers, Emily K.
,
Impastato, Renata A.
,
Teng, Sophie X.
in
Animals
,
Arachidonic Acids - metabolism
,
Benzamides - pharmacology
2015
Traumatic brain injury (TBI) is an increasingly frequent and poorly understood condition lacking effective therapeutic strategies. Inflammation and oxidative stress (OS) are critical components of injury, and targeted interventions to reduce their contribution to injury should improve neurobehavioral recovery and outcomes. Recent evidence reveals potential protective, yet short-lived, effects of the endocannabinoids (ECs), 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA), on neuroinflammatory and OS processes after TBI. The aim of this study was to determine whether EC degradation inhibition after TBI would improve neurobehavioral recovery by reducing inflammatory and oxidative damage. Adult male Sprague-Dawley rats underwent a 5-mm left lateral craniotomy, and TBI was induced by lateral fluid percussion. TBI produced apnea (17±5 sec) and a delayed righting reflex (479±21 sec). Thirty minutes post-TBI, rats were randomized to receive intraperitoneal injections of vehicle (alcohol, emulphor, and saline; 1:1:18) or a selective inhibitor of 2-AG (JZL184, 16 mg/kg) or AEA (URB597, 0.3 mg/kg) degradation. At 24 h post-TBI, animals showed significant neurological and -behavioral impairment as well as disruption of blood–brain barrier (BBB) integrity. Improved neurological and -behavioral function was observed in JZL184-treated animals. BBB integrity was protected in both JZL184- and URB597-treated animals. No significant differences in ipsilateral cortex messenger RNA expression of interleukin (IL)-1β, IL-6, chemokine (C-C motif) ligand 2, tumor necrosis factor alpha, cyclooxygenase 2 (COX2), or nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and protein expression of COX2 or NOX2 were observed across experimental groups. Astrocyte and microglia activation was significantly increased post-TBI, and treatment with JZL184 or URB597 blocked activation of both cell types. These findings suggest that EC degradation inhibition post-TBI exerts neuroprotective effects. Whether repeated dosing would achieve greater protection remains to be examined.
Journal Article
Effect of Margin Status on Survival After Resection of Hilar Cholangiocarcinoma in the Modern Era of Adjuvant Therapies
by
Martinie, John B.
,
Watson, Michael D.
,
Sulzer, Jesse K.
in
Adjuvant therapy
,
Bile ducts
,
Chemotherapy
2021
Introduction
Studies have shown that for patients with hilar cholangiocarcinoma (HC), survival is associated with negative resection margins (R0). This requires increasingly proximal resection, putting patients at higher risk for complications, which may delay chemotherapy. For patients with microscopically positive resection margins (R1), the use of modern adjuvant therapies may offset the effect of R1 resection.
Methods
Patients at our institution with HC undergoing curative-intent resection between January 2008 and July 2019 were identified by retrospective record review. Demographic data, operative details, tumor characteristics, postoperative outcomes, recurrence, survival, and follow-up were recorded. Patients with R0 margin were compared to those with R1 margin. Patients with R2 resection were excluded.
Results
Seventy-five patients underwent attempted resection with 34 (45.3%) cases aborted due to metastatic disease or locally advanced disease. Forty-one (54.7%) patients underwent curative-intent resection with R1 rate of 43.9%. Both groups had similar rates of adjuvant therapy (56.5% vs. 61.1%, P = .7672). Complication rates and 30 mortality were similar between groups (all P > .05). Both groups had similar median recurrence-free survival (R0 29.2 months vs. R1 27.8 months, P = .540) and median overall survival (R0 31.2 months vs. R1 38.8 months, P = .736) with similar median follow-up time (R0 29.9 months vs. R1 28.5 months, P = .8864).
Conclusions
At our institution, patients undergoing hepatic resection for HC with R1 margins have similar recurrence-free and overall survival to those with R0 margins. Complications and short-term mortality were similar. This may indicate that with use of modern adjuvant therapies obtaining an R0 resection is not an absolute mandate.
Journal Article
Retrospective Validation of an Algorithmic Treatment Pathway for Necrotizing Pancreatitis
2019
The role of surgical intervention for necrotizing pancreatitis has evolved; however, no widely accepted algorithm has been established to guide timing and optimal modality in the minimally invasive era. This study aimed to retrospectively validate an established institutional timing- and physiologic-based algorithm constructed from evidence-based guidelines in a high-volume hepatopancreatobiliary center. Patients with necrotizing pancreatitis requiring early (≤six weeks from symptom onset) or delayed (>six weeks) surgical intervention were reviewed over a four-year period (n = 100). Early intervention was provided through laparoscopic drain-guided retroperitoneal debridement (n = 15) after failed percutaneous drainage unless they required an emergent laparotomy (due to abdominal compartment syndrome, bowel necrosis/perforation, or hemorrhage) after which conservative, sequential open necrosectomy was performed (n = 47). Robot-assisted (n = 16) versus laparoscopic (n = 22) transgastric cystgastrostomy for the delayed management of walled-off pancreatic necrosis was compared, including patient factors, operative characteristics, and 90-day clinical outcomes. Major complications after early debridement were similarly high (open 25% and drain-guided 27%), yet 90-day mortality was low (open 8.5% and drain-guided 7.1%). Patient and operative characteristics and 90-day outcomes were statistically similar for robotic versus laparoscopic transgastric cystogastrostomy. Our evidence-based algorithm provides a stepwise approach for the management of necrotizing pancreatitis, emphasizing minimally invasive early and late interventions when feasible with low morbidity and mortality. Robot-assisted transgastric cystogastrostomy is an acceptable alternative to a laparoscopic approach for the delayed treatment of walled-off pancreatic necrosis.
Journal Article
Minimally Invasive Surgical Management as Effective First-Line Treatment of Large Pyogenic Hepatic Abscesses
by
Martinie, John B.
,
Sulzer, Jesse K.
,
Vrochides, Dionisios
in
Abscesses
,
Algorithms
,
Antibiotics
2019
Management of pyogenic hepatic abscesses (PHA) varies among surgeons and institutions. Recent studies have advocated for first-line percutaneous drainage (PD) of all accessible hepatic abscesses, with surgery reserved as rescue only. Our study aimed to internally validate an established multimodal algorithm for PHA at a high-volume hepatopancreatobiliary center. Patients treated by the hepatopancreatobiliary service for PHA were retrospectively reviewed from 2008 through 2018. The algorithm defined intended first-line treatment as antibiotics for type I abscesses (<3 cm), PD for type II (≥3, unilocular), and surgical intervention (minimally invasive drainage or resection, when possible) for type III (≥3 cm, multilocular). Outcomes were compared between patients who received first-line treatment following the algorithm versus alternate therapy. Of 330 patients with PHA, 201 met inclusion criteria. Type III abscesses had significantly lower failure following algorithmic approach with surgery compared with PD (4% vs 28%, P = 0.018). Type II abscesses failed first-line PD in 27 per cent (13/48) with 11 patients requiring surgical rescue, whereas first-line surgery failed in only 13 per cent (2/15). No deaths occurred after any surgical intervention, and there was no statistical difference in major complications between first-line surgical intervention and PD for type II or III abscesses. These results support the algorithmic approach and demonstrate that minimally invasive surgical intervention is a safe and effective modality for large PHA. We recommend that select patients with large, complex abscesses should be considered for a first-line minimally invasive surgical approach depending on surgical experience and available resources.
Journal Article
Modifying Interhospital Hepatopancreatobiliary Transfers Based on Predictive Analytics: Moving from a Center of Excellence to a Health-Care System of Excellence
by
Martinie, John B.
,
Murphy, Keith
,
Sulzer, Jesse K.
in
Analytics
,
Clinical outcomes
,
Complications
2019
Regionalization of complex surgical care has increased interhospital transfers to quaternary centers within large health-care systems. Risk-based patient selection is imperative to improve resource allocation without compromising care. This study aimed to develop predictive models for identifying low-risk patients for transfer to a fully integrated satellite hepatopancreatobiliary (HPB) service in the northeast region of the health-care system. HPB transfers to the quaternary center over 15 months from hospitals in proximity to the satellite HPB center. A predictive tool was developed based on simple pretransfer variables and outcomes for 30-day major complications (Clavien grade ≥ 3), readmission, and mortality. Thresholds for “low risk” were set at different SDs below mean for each model. Predictive models were developed from 51 eligible northeast region patient transfers for major complications (Brier score 0.1948, receiver operator characteristic (ROC) 0.7123, P = 0.0009), readmission (Brier score 0.0615, ROC 0.7368, P = 0.0020), and mortality (Brier score 0.0943, ROC 0.7989, P = 0.0023). Thresholds set from 2 SD below the mean for all models identified 2 as “low risk.” Adjusting the threshold for the serious complication model to only 1 SD below the mean increased the “low-risk” cohort to five patients. These models demonstrate an easy-to-use tool to assist surgeons in identifying low-risk patients for diversion to a fully integrated satellite center. Improved interhospital transfers within a region could begin a transition from centers of excellence toward health-care systems of excellence.
Journal Article
Clinically Meaningful Laboratory Protocols Reduce Hospital Charges Based on Institutional and ACS-NSQIP® Risk Calculators in Hepatopancreatobiliary Surgery
2019
Postoperative laboratory testing is an underrecognized but substantial contributor to health-care costs. We aimed to develop and validate a clinically meaningful laboratory (CML) protocol with individual risk stratification using generalizable and institution-specific predictive analytics to reduce laboratory testing and maximize cost savings for low-risk patients. An institutionally based risk model was developed for pancreaticoduodenectomy and hepatectomy, and an ACS-NSQIP®–based model was developed for distal pancreatectomy. Patients were stratified in each model to the CML by individual risk of major complications, readmission, or death. Clinical outcomes and estimated cost savings were compared with those of a historical cohort with standard of care. Over 34 months, 394 patients stratified to the CML for pancreaticoduodenectomy or hepatectomy saved an estimated $803,391 (44.4%). Over 13 months, 52 patients stratified to the CML for distal pancreatectomy saved an estimated $81,259 (30.5%). Clinical outcomes for 30-day major complications, readmission, and mortality were unchanged after implementation of either model. Predictive analytics can target low-risk patients to reduce laboratory testing and improve cost savings, regardless of whether an institutional or a generalized risk model is implemented. Broader application is important in patient-centered health care and should transition from predictive to prescriptive analytics to guide individual care in real time.
Journal Article
Pancreatic Head Resection Following Roux-en-Y Gastric Bypass: Operative Considerations and Outcomes
2020
Purpose
This study aimed to identify optimal management decisions for surgeons preforming pancreatic head resection on patients with altered anatomy due to a previous Roux-en-Y gastric bypass (RYGB).
Methods
A multi-national (4), multi-center (28) collaborative of 55 pancreatic surgeons who have performed pancreatoduodenectomy or total pancreatectomy following RYGB for obesity (2005–2018) was created. Demographics, operative details, and perioperative outcomes from this cohort were analyzed and compared in a propensity-score matched analysis with a multi-center cohort of 5533 pancreatoduodenectomies without prior RYGB.
Results
Ninety-six patients with a previous RYGB undergoing pancreatic head resection were assembled. Pathologic indications between the RYGB and normal anatomy cohorts did not differ. Propensity score matching of RYGB vs. patients with unaltered anatomy demonstrated no differences in major postoperative outcomes. In total 20 distinct reconstructions were employed (of 37 potential options); the three most frequent reconstructions accounted for 52.1%, and none demonstrated superior outcomes. There were no differences in outcomes observed between original biliopancreatic limb use (66.7%) and those where a secondary Roux limb was created for biliopancreatic reconstruction. Remnant stomachs were removed in 54.7% of cases, with no outcome differences between resected and retained stomachs. Venting gastrostomy tubes were used in 36.2% of retained stomachs without obvious outcome benefits. Jejunostomy tubes were used infrequently (11.7%).
Conclusions
Pancreatic head resection after RYGB is an infrequently encountered, unique and challenging scenario for any given surgeon. These patients do not appear to suffer higher morbidity than those with unaltered anatomy. Various technical reconstructive options do not appear to confer distinct benefits.
Journal Article