The 3rd Annual Lady Grace Revere Osler Lecture in Surgical Quality

Optimal Pancreatic Surgery At the conclusion of this presentation the participant should be able to: 1. Understand the role of hospital and surgeon volume in pancreatic surgery 2. Report the relative risk of various pancreatic operations 3. Acknowledge the importance of chain management in outcomes. Presentation: 57 minute

An Analysis of Infectious Failures in Acute Cholangitis

To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninetyfour (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin ≥ 2.2 mg/dl, ≥ 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level ≥ 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest. In conclusion, patients with acute cholangitis who have an increased chance to fail initial therapy can be identified, and treatment altered accordingly

Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism

INTRODUCTION: Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. MATERIAL AND METHODS: Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p < 0.05 considered significant. RESULTS: Wild-type preadipocyte CM accelerated Pan02 and TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p < 0.01, respectively). Knockdown of preadipocyte HGF resulted in attenuated proliferation vs. wild type CM in Pan02 cells (35 ± 5% vs. 68 ± 14% greater than control; p < 0.05), but proliferation in TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p < 0.05). Inhibition of HGF receptor, c-met, resulted in attenuated proliferation versus control in Pan02 cells, but not TGP-47 cells. CONCLUSIONS: These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation

Leakage of an invagination pancreaticojejunostomy may have an influence on mortality

Purpose: No consensus exists regarding the most effective form of pancreaticojejunostomy (PJ) following pancreaticoduodenectomy (PD). Methods: Data were gathered through the American College of Surgeons-National Surgical Quality Improvement Program, Pancreatectomy Demonstration Project. A total of 1781 patients underwent a PD at 43 institutions. After appropriate exclusions, 890 patients were analyzed. Patients were divided into duct-to-mucosa (n = 734, 82%) and invagination (n = 156, 18%) groups and were compared by unadjusted analysis. Type of PJ was included in eight separate morbidity and mortality multivariable analyses. Results: Invagination patients had higher serum albumin (p &lt; 0.01) and lower body mass index (p &lt; 0.01), were less likely to have a preoperative biliary stent (p &lt; 0.01), and were more likely to have a soft gland (p &lt; 0.01). PJ anastomosis type was not associated with morbidity but was associated with mortality (duct-to-mucosa vs. invagination, odds ratio = 0.22, p &lt; 0.01). Among patients who developed a clinically relevant pancreatic fistula, none of the 119 duct-to-mucosa, compared with 5 of 21 invagination, patients died (p &lt; 0.01). Conclusion: Patients who undergo a PJ by duct-to-mucosa or invagination differ with respect to preoperative and intraoperative variables. When an invagination PJ leaks, there may be a greater influence on mortality than when a duct-to-mucosa PJ leaks

Pancreatic Fistula Following Pancreaticoduodenectomy: Clinical Predictors and Patient Outcomes

Pancreatic fistula continues to be a common complication following PD. This study seeks to identify clinical factors which may predict pancreatic fistula (PF) and evaluate the effect of PF on outcomes following pancreaticoduodenectomy (PD). We performed a retrospective analysis of a clinical database at an academic tertiary care hospital with a high volume of pancreatic surgery. Five hundred ten consecutive patients underwent PD, and PF occurred in 46 patients (9%). Perioperative mortality of patients with PF was 0%. Forty-five of 46 PF (98%) closed without reoperation with a mean time to closure of 34 days. Patients who developed PF showed a higher incidence of wound infection, intra-abdominal abscess, need for reoperation, and hospital length of stay. Multivariate analysis demonstrated an invaginated pancreatic anastomosis and closed suction intraperitoneal drainage were associated with PF whereas a diagnosis of chronic pancreatitis and endoscopic stenting conferred protection. Development of PF following PD in this series was predicted by gender, preoperative stenting, pancreatic anastomotic technique, and pancreas pathology. Outcomes in patients with PF are remarkable for a higher rate of septic complications, longer hospital stays, but in this study, no increased mortality

Economic Evaluation of the Randomized Aldactone Evaluation Study (RALES): Treatment of Patients with Severe Heart Failure

Purpose : To use data from the Randomized Aldactone Evaluation Study (RALES) to compare clinical outcomes and costs as part of the assessment of the economic implications of spironolactone treatment of advanced heart failure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44576/1/10557_2004_Article_405789.pd

Ideal Outcome After Pancreatoduodenectomy:A Transatlantic Evaluation of a Harmonized Composite Outcome Measure

OBJECTIVE: The aim of this study is to define and assess Ideal Outcome in the national or multicenter registries of North America, Germany, the Netherlands, and Sweden. BACKGROUND: Assessing outcomes after pancreatoduodenectomy among centers and countries requires a broad evaluation that cannot be captured by a single parameter. Previously, 2 composite outcome measures (textbook outcome and optimal pancreatic surgery) for pancreatoduodenectomy have been described from Europe and the United States. These composites were harmonized into ideal outcome (IO). METHODS: This analysis is a transatlantic retrospective study (2018-2020) of patients after pancreatoduodenectomy within the registries from North America, Germany, The Netherlands, and Sweden. After 3 consensus meetings, IO for pancreatoduodenectomy was defined as the absence of all 6 parameters: (1) in-hospital mortality, (2) severe complications-Clavien-Dindo ≥3, (3) postoperative pancreatic fistula-International Study Group of Pancreatic Surgery (ISGPS) grade B/C, (4) reoperation, (5) hospital stay &gt;75th percentile, and (6) readmission. Outcomes were evaluated using relative largest difference (RLD) and absolute largest difference (ALD), and multivariate regression models. RESULTS: Overall, 21,036 patients after pancreatoduodenectomy were included, of whom 11,194 (54%) reached IO. The rate of IO varied between 55% in North America, 53% in Germany, 52% in The Netherlands, and 54% in Sweden (RLD: 1.1, ALD: 3%, P &lt;0.001). Individual components varied with an ALD of 2% length of stay, 4% for in-hospital mortality, 12% severe complications, 10% postoperative pancreatic fistula, 11% reoperation, and 9% readmission. Age, sex, absence of chronic obstructive pulmonary disease, body mass index, performance status, American Society of Anesthesiologists (ASA) score, biliary drainage, absence of vascular resection, and histologic diagnosis were associated with IO. In the subgroup of patients with pancreatic adenocarcinoma, country, and neoadjuvant chemotherapy also was associated with improved IO. CONCLUSIONS: The newly developed composite outcome measure "Ideal Outcome" can be used for auditing and comparing outcomes after pancreatoduodenectomy. The observed differences can be used to guide collaborative initiatives to further improve the outcomes of pancreatic surgery.</p