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1.
J Surg Res ; 288: 315-320, 2023 08.
Article in English | MEDLINE | ID: mdl-37058988

ABSTRACT

INTRODUCTION: The purpose of this study is to examine pancreatoduodenectomy (PD) perioperative outcomes and consider how age may be related to overall survival in an integrated health system. MATERIALS AND METHODS: A retrospective review was performed of 309 patients who underwent PD between December 2008 and December 2019. Patients were divided into two groups: aged 75 y or less and more than 75 y, defined as senior surgical patients. Univariate and multivariable analyses of predictive clinicopathologic factors associated with overall survival at 5 y were performed. RESULTS: In both groups, the majority underwent PD for malignant disease. The proportion of senior surgical patients alive at 5 y was 33.3% compared to 53.6% of younger patients (P = 0.003). There were also statistically significant differences between the two groups with respect to body mass index, cancer antigen 19-9, Eastern Cooperative Oncology Group performance status, and Charlson comorbidity index. On multivariable analysis, disease type, cancer antigen 19-9, hemoglobin A1c, length of surgery, length of stay, Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status were found to be statistically significant factors for overall survival. Age was not significantly related to overall survival on multivariable logistic regression and when the analysis was limited to pancreatic cancer patients. CONCLUSIONS: Although the difference in overall survival between patients aged less than and more than 75 years was significant, age was not an independent risk factor for overall survival on multivariable analysis. Rather than a patient's chronological age, his/her physiologic age including medical comorbidities and functional status may be more correlated to overall survival.


Subject(s)
Delivery of Health Care, Integrated , Pancreatic Neoplasms , Humans , Male , Female , Aged , Treatment Outcome , Pancreaticoduodenectomy/methods , Pancreatic Neoplasms/pathology , Retrospective Studies
2.
Perm J ; 27(2): 9-12, 2023 06 15.
Article in English | MEDLINE | ID: mdl-36336674

ABSTRACT

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.


Subject(s)
Carcinoma, Adenosquamous , Carcinoma, Pancreatic Ductal , Delivery of Health Care, Integrated , Pancreatic Neoplasms , Humans , Retrospective Studies , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/surgery , Pancreatectomy , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/therapy , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms
3.
HPB (Oxford) ; 25(1): 124-135, 2023 01.
Article in English | MEDLINE | ID: mdl-36323594

ABSTRACT

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) has been associated with soft gland texture and/or small pancreatic duct. We hypothesized that selective use of pancreaticogastrostomy (PG) over pancreaticojejunostomy (PJ) in those scenarios would decrease the rate of CR-POPF. METHODS: Review of prospective database of all PD's performed at a single institution between 2009 and 2019 was performed. The pancreatic remnant was deemed "high risk" if soft gland and/or small duct were present. RESULTS: PJ was performed in 199 (147 "low-risk" and 52 "high-risk") cases, and 110 patients (all "high-risk") had a PG. Overall CR-POPF rate was 11.9% with no difference between the groups. Risk-stratified analysis within PJ group showed CR-POPF rate of 5.4% versus 36% in "low-risk" versus "high risk" scenarios, respectively; the use of PG significantly decreased CR-POPF rate (9.1%, p < 0.0001). Gastrointestinal bleeding was more likely to occur following PG than PJ. Soft gland texture and gastrointestinal bleeding were the strongest predictors of CR-POPF in PJ and PG groups, respectively. CONCLUSION: Selective use of PG after PD in "high-risk" scenarios mitigates the risk of CR-POPF. Increased rate of gastrointestinal bleeding calls for further refinement of the technique and heightened postoperative vigilance.


Subject(s)
Pancreas , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/methods , Pancreas/surgery , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Pancreaticojejunostomy/adverse effects , Pancreaticojejunostomy/methods , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreatic Fistula/surgery , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/surgery
4.
Surg Endosc ; 36(12): 9329-9334, 2022 12.
Article in English | MEDLINE | ID: mdl-35411457

ABSTRACT

INTRODUCTION: Implementing enhanced recovery after surgery (ERAS) protocols for major abdominal surgery has been shown to decrease length of stay (LOS) and postoperative complications, including mortality and readmission. Little is known to guide which patients undergoing pancreaticoduodenectomy (PD) should be eligible for ERAS protocols. METHODS AND PROCEDURES: A retrospective chart review of all PD performed from 2010 to 2018 within an integrated healthcare system was conducted. A predictive score that ranges from 0 to 4 was developed, with one point assigned to each of the following: obesity (BMI > 30), operating time > 400 min, estimated blood loss (EBL) > 400 mL, low- or high-risk pancreatic remnant (based on the presence of soft gland or small duct). Chi-squared tests and ANOVA were used to assess the relationship between this score and LOS, discharge before postoperative day 7, readmission, mortality, delayed gastric emptying (DGE), and pancreatic leak/fistula. RESULTS: 291 patients were identified. Mean length of stay was 8.5 days in those patients who scored 0 compared to 16.2 days for those who scored 4 (p = 0.001). 30% of patients who scored 0 were discharged before postoperative day 7 compared to 0% of those who scored 4 (p = 0.019). Readmission rates for patients who scored 0 and 4 were 12% and 33%, respectively (p = 0.017). Similarly, postoperative pancreatic fistula occurred in 2% versus 25% in these groups (p = 0.007). CONCLUSION: A simple scoring system using BMI, operating time, EBL, and pancreatic remnant quality can help risk-stratify postoperative PD patients. Those with lower scores could potentially be managed via an ERAS protocol. Patients with higher scores required longer hospitalizations, and adjunctive therapy such as medication and surgical technique to decrease risk of delayed gastric emptying and pancreatic fistula could be considered.


Subject(s)
Gastroparesis , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/methods , Pancreatic Fistula/etiology , Pancreatic Fistula/complications , Retrospective Studies , Patient Readmission , Patient Discharge , Gastroparesis/etiology , Recovery of Function , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology
5.
Pancreas ; 51(10): 1332-1336, 2022.
Article in English | MEDLINE | ID: mdl-37099775

ABSTRACT

OBJECTIVES: Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival. METHODS: Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS). RESULTS: Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001). CONCLUSIONS: Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.


Subject(s)
Delivery of Health Care, Integrated , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neuroendocrine Tumors/surgery , Pancreatic Neoplasms/surgery , Survival Analysis , Retrospective Studies , Survival Rate
6.
Am J Surg ; 223(6): 1035-1039, 2022 06.
Article in English | MEDLINE | ID: mdl-34607651

ABSTRACT

BACKGROUND: Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS: We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS: Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis. CONCLUSIONS: Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients.


Subject(s)
Delivery of Health Care, Integrated , Pancreatic Neoplasms , Humans , Kaplan-Meier Estimate , Neoadjuvant Therapy , Pancreatectomy , Pancreatic Neoplasms/surgery , Retrospective Studies , Pancreatic Neoplasms
7.
Innate Immun ; 17(3): 283-92, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20423922

ABSTRACT

Triglyceride-rich lipoprotein-bound endotoxin (CM-LPS) inhibits the host innate immune response to sepsis by attenuating the hepatocellular response to pro-inflammatory cytokine stimulation. This 'cytokine tolerance' in hepatocytes is a transient, receptor-dependent process that correlates with internalization of CM-LPS via low density lipoprotein (LDL) receptors. Since endothelial cells are integral to the immune response and similarly express LDL receptors, we hypothesized that CM-LPS could be internalized and ultimately attenuate the deleterious effects of pro-inflammatory molecules like tumor necrosis factor-α (TNF-α) and platelet activating factor (PAF) on endothelial permeability. Here, we show that CM-LPS complexes induce cytokine tolerance in endothelial cells. In rats, TNF-α increased hydraulic conductivity 2.5-fold over baseline and PAF increased it 5-fold; but, pretreatment with CM-LPS or an attenuated analog (CM-LPS*) inhibited these changes. Nuclear/cytoplasmic levels of p65 were reduced after TNF-α-stimulation in endothelial cell monolayers pretreated with CM-LPS, a finding consistent with inhibition of nuclear factor (NF)-κB translocation. Also consistent with inhibition was stabilized intercellular adhesion, as illustrated with antibody to VE-cadherin using confocal microscopy. These results provide additional support for the integral role of lipoproteins in the innate immune response to infection and lend further credence to developing lipid-based therapy for Gram-negative sepsis.


Subject(s)
Chylomicrons/pharmacology , Endothelial Cells/drug effects , Endotoxins/pharmacology , Gram-Negative Bacteria/immunology , Sepsis/immunology , Animals , Antigens, CD/immunology , Antigens, CD/metabolism , Cadherins/immunology , Cadherins/metabolism , Capillary Permeability/drug effects , Cell Adhesion/drug effects , Cell Membrane Permeability/drug effects , Cells, Cultured , Chylomicrons/chemistry , Chylomicrons/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endotoxins/chemistry , Endotoxins/metabolism , Immunity, Innate , Immunosuppression Therapy , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism , eIF-2 Kinase/metabolism
8.
Liver Transpl ; 16(11): 1296-302, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21031545

ABSTRACT

Controversies exist with respect to the mortality of patients undergoing liver transplantation at the extremes of the body mass index (BMI). For pediatric liver transplantation, weight is usually the only factor considered in survival analysis. A review of the United Network for Organ Sharing database (1987-2007) revealed 9701 pediatric patients (<18 years old) who underwent primary liver transplantation. Patients were stratified into 5 BMI categories established by the World Health Organization according to their Z score, which was based on age, gender, and BMI: -3, -2, 0, +2, and +3. The survival rates in these 5 categories were compared with Kaplan-Meier survival curves and log-rank testing. Patients with thinness (Z score = -2) and severe thinness (Z score = -3) had significantly (P < 0.0001) lower survival at 1 year (84.4%) versus the survival (88.7%) of the normal and overweight groups (Z score = 0 and Z score = + 2, respectively). For patients with obesity (Z score = +3), there was no significant difference in survival early after transplantation, but their mortality gradually increased in the later years after transplantation. By 12 years after liver transplantation, the obese group had significantly (P = 0.04) lower survival (72%) than the normal and overweight groups (77%). In conclusion, liver transplantation holds increased risk for obese pediatric patients. Thin pediatric patients experience early mortality after liver transplantation, and obese pediatric patients experience late mortality after liver transplantation. Transplant management can be modified to optimize the care of these patients.


Subject(s)
Graft Rejection , Liver Diseases/surgery , Liver Transplantation , Obesity , Thinness , Adolescent , Biomarkers/analysis , Body Mass Index , Body Weight , Child , Female , Graft Rejection/etiology , Graft Rejection/mortality , Graft Survival , Humans , Liver/physiopathology , Liver/surgery , Liver Diseases/complications , Liver Diseases/physiopathology , Liver Transplantation/mortality , Male , Multivariate Analysis , Obesity/complications , Obesity/mortality , Retrospective Studies , Risk Factors , Survival Analysis , Survival Rate , Thinness/complications , Thinness/mortality , Transplantation, Homologous
9.
HPB (Oxford) ; 12(3): 166-73, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20590883

ABSTRACT

BACKGROUND: We hypothesized that operative variables might predict survival following liver transplantation. METHODS: We examined perioperative variables from 469 liver transplants carried out at the University of Washington during 2003-2006. Logistic regression determined the variables' contributions to survival at 30, 90 and 365 days. RESULTS: Portal vein blood flow (>1 l/min) was significant to patient survival at 30, 90 and 365 days. Complete reperfusion was only a significant predictor of survival at 30 days. This provided model receiver operating characteristic (ROC) area under the curve (AUC) statistics of 0.93 and 0.87 for 30 and 90 days, respectively. At 365 days, hepatic artery blood flow (>250 ml/min) combined with portal vein blood flow was significantly predictive of survival, with an AUC of 0.74. A subset analysis of 110 transplants demonstrated improved 1-year survival with more aggressive vascular revisions. DISCUSSION: Portal vein blood flow is a significant predictor of survival after liver transplantation. Initially, the liver's survival is based on portal vein blood flow; however, subsequent biliary problems and patient demise result from both poor portal vein and inadequate hepatic artery blood flow.


Subject(s)
Graft Survival , Liver Circulation , Liver Transplantation/mortality , Portal Vein , Blood Flow Velocity , Female , Hepatic Artery , Humans , Intraoperative Period , Male , Middle Aged , ROC Curve , Reperfusion , Retrospective Studies , Time Factors , Transplantation, Homologous
10.
Liver Transpl ; 16(7): 874-84, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20583086

ABSTRACT

To expand the donor liver pool, ways are sought to better define the limits of marginally transplantable organs. The Donor Risk Index (DRI) lists 7 donor characteristics, together with cold ischemia time and location of the donor, as risk factors for graft failure. We hypothesized that donor hepatic steatosis is an additional independent risk factor. We analyzed the Scientific Registry of Transplant Recipients for all adult liver transplants performed from October 1, 2003, through February 6, 2008, with grafts from deceased donors to identify donor characteristics and procurement logistics parameters predictive of decreased graft survival. A proportional hazard model of donor variables, including percent steatosis from higher-risk donors, was created with graft survival as the primary outcome. Of 21,777 transplants, 5051 donors had percent macrovesicular steatosis recorded on donor liver biopsy. Compared to the 16,726 donors with no recorded liver biopsy, the donors with biopsied livers had a higher DRI, were older and more obese, and a higher percentage died from anoxia or stroke than from head trauma. The donors whose livers were biopsied became our study group. Factors most strongly associated with graft failure at 1 year after transplantation with livers from this high-risk donor group were donor age, donor liver macrovesicular steatosis, cold ischemia time, and donation after cardiac death status. In conclusion, in a high-risk donor group, macrovesicular steatosis is an independent risk factor for graft survival, along with other factors of the DRI including donor age, donor race, donation after cardiac death status, and cold ischemia time.


Subject(s)
Fatty Liver/diagnosis , Liver Transplantation/standards , Liver/pathology , Risk Assessment/trends , Tissue Donors , Tissue and Organ Procurement/standards , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Biopsy , Child , Child, Preschool , Cold Ischemia , Death , Fatty Liver/pathology , Female , Graft Rejection , Humans , Infant , Infant, Newborn , Male , Middle Aged , Proportional Hazards Models , Registries , Retrospective Studies , Risk Factors , Young Adult
11.
Liver Transpl ; 15(8): 968-77, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19642131

ABSTRACT

Controversies exist regarding the morbidity and mortality of patients undergoing liver transplantation at the extremes of the body mass index (BMI). A review of the United Network for Organ Sharing database from 1987 through 2007 revealed 73,538 adult liver transplants. Patients were stratified into 6 BMI categories established by the World Health Organization: underweight, <18.5 kg/m(2); normal weight, 18.5 to <25 kg/m(2); overweight, 25 to <30 kg/m(2); obese, 30 to <35 kg/m(2); severely obese, 35 to <40 kg/m(2); and very severely obese, > or =40 kg/m(2). Survival rates were compared among these 6 categories via Kaplan-Meier survival curves with the log-rank test. The underweight and very severely obese groups had significantly lower survival. There were 1827 patients in the underweight group, 1447 patients in the very severely obese group, and 68,172 patients in the other groups, which became the control. Groups with extreme BMI (<18.5 and > or =40) were compared to the control to assess significant differences. Underweight patients were more likely to die from hemorrhagic complications (P < 0.002) and cerebrovascular accidents (P < 0.04). When compared with the control, the very severely obese patients had a higher number of infectious complications and cancer events (P = 0.02) leading to death. In 3 different eras of liver transplantation, multivariable analysis showed that underweight and very severe obesity were significant predictors of death. In conclusion, liver transplantation holds increased risk for patients at the extremes of BMI. Identifying these patients and instituting aggressive new policies may improve outcomes. Liver Transpl 15:968-977, 2009. (c) 2009 AASLD.


Subject(s)
Liver Transplantation/methods , Obesity/complications , Adult , Body Mass Index , Female , Graft Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Overweight , Retrospective Studies , Risk , Thinness , Treatment Outcome
12.
HPB Surg ; 2008: 825940, 2008.
Article in English | MEDLINE | ID: mdl-18475317

ABSTRACT

HYPOTHESIS: Smaller and lower-volume hospitals can attain surgical outcomes similar to high-volume centers if they incorporate the expertise and health care pathways of high-volume centers. SETTING: The academic tertiary care center, Moffit-Long Hospital (ML); the community-based Mount Zion Hospital (ZION); the San Francisco County General Hospital (SFGH); and the Veterans Affairs Medical Center of San Francisco (VAMC). PATIENTS: 369 patients who underwent pancreaticoduodenectomy between October 1989 and June 2003 at the University of California, San Francisco (UCSF) affiliated hospitals. INTERVENTIONS: Pancreaticoduodenectomy. DESIGN: Retrospective chart review. To correct for the potentially confounding effect of small case volumes and event rates, data for SFGH, VAMC, and ZION was combined (Small Volume Hospital Group; SVHG) and compared against data for ML. MAIN OUTCOME MEASURES: Complication rates; three-year and five-year survival rates. RESULTS: The average patient age and health, as determined by ASA score, were similar between ML and the SVHG. The postoperative complication rate did not differ significantly between ML and the SVGH (58.8% versus 63.1%). Patients that experienced a complication averaged 2.5 complications in both groups. The perioperative mortality rate was 4% for patients undergoing pancreaticoduodenectomy at either ML or the SVGH. Although the 3-year survival rate for patients with adenocarcinoma of the pancreas was nearly twice as high at ML (31.2% versus 18.3% at SVHG), there was no significant difference in the 5-year survival rates (19% at ML versus 18.3% at SVHG). CONCLUSIONS: Low-volume hospitals can achieve similar outcomes to high-volume tertiary care centers provided they import the expertise and care pathways necessary for improved results.

13.
Surgery ; 143(3): 305-12, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18291250

ABSTRACT

BACKGROUND: Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs). CONCLUSIONS: Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.


Subject(s)
Anticoagulants/adverse effects , Heparin/adverse effects , Humans , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/therapy
14.
Surgery ; 139(3): 283-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16546490

ABSTRACT

HYPOTHESIS: If (1) 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors (statins) block the rate-limiting step in cholesterol synthesis and promote the expression of low-density lipoprotein receptors, (2) "Gram-negative sepsis" results from an abundant systemic response to bacterial lipopolysaccharide (endotoxin), (3) triglyceride-rich lipoproteins can bind endotoxin and low-density lipoprotein receptors enhance the uptake of both of these molecules, and (4) low-density lipoprotein receptor internalization of lipoproteins and endotoxin co-opts a common transcriptional regulatory system (NF-kappaB) that results in reduced cell vulnerability to inflammation, then statins, in addition to their lipid-lowering capacity, enhance endotoxin clearance from the circulation and attenuate the septic response.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipopolysaccharides/metabolism , Low Density Lipoprotein Receptor-Related Protein-1/physiology , Sepsis/drug therapy , Cholesterol/biosynthesis , Gram-Negative Bacterial Infections/complications , Humans , Sepsis/physiopathology
15.
Ann Surg ; 243(3): 380-8, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16495704

ABSTRACT

OBJECTIVE: We sought to develop a simple yet accurate prognostic scoring system to determine the severity of acute pancreatitis at admission. SUMMARY BACKGROUND DATA: Because acute pancreatitis has a variable and frequently unpredictable course, identifying individuals at greatest risk for significant, life-threatening complications and stratifying their care appropriately remain a concern. Previous prognostic scoring systems predict severity reasonably well but are limited by time constraints, are unwieldy to use, or both. METHODS: Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model. We then compared the model's ability to predict the severity of acute pancreatitis with the Ranson, Glasgow, and APACHE II systems. RESULTS: The model (BALI), which included BUN >or=25 mg/dL, Age >or=65 years, LDH >or=300 IU/L, and IL-6 >or=300 pg/mL, measured at admission, was similar to the Ranson, Glasgow, and APACHE II systems in its ability to identify increased mortality from acute pancreatitis. The receiver operating characteristic curve area for the BALI model was >or=0.82 +/- 0.03 (mean +/- SD) versus 0.75 +/- 0.04 (Ranson), 0.80 +/- 0.03 (Glasgow), and 0.79 +/- 0.03 (APACHE II). Furthermore, at a prevalence of 15%, the positive and negative predictive values for increased mortality were similar for all systems. CONCLUSION: The prognostic ability of the BALI 4-variable model was similar to the Ranson, Glasgow, and APACHE II systems but is unique in its simplicity and ability to accurately predict disease severity when used at admission or anytime during the first 48 hours of hospitalization.


Subject(s)
Models, Theoretical , Pancreatitis, Acute Necrotizing/diagnosis , Severity of Illness Index , APACHE , Female , Follow-Up Studies , Humans , Imidazoles/therapeutic use , Leucine/analogs & derivatives , Leucine/therapeutic use , Male , Middle Aged , Pancreatitis, Acute Necrotizing/drug therapy , Pancreatitis, Acute Necrotizing/mortality , Platelet Activating Factor/antagonists & inhibitors , Prognosis , ROC Curve , Randomized Controlled Trials as Topic , Survival Rate
17.
J Gastrointest Surg ; 9(7): 928-33, 2005.
Article in English | MEDLINE | ID: mdl-16137586

ABSTRACT

We wondered whether nonenhanced computed tomography (CT) within 48 hours of admission could identify individuals at risk for higher mortality from acute pancreatitis. Data from the international phase III study of the platelet-activating factor-inhibitor Lexipafant was used to analyze noncontrast CT versus acute pancreatitis mortality. Nonenhanced CT examinations of the abdomen from the trial were classified by disease severity (Balthazar grades A-E) and then correlated with patient survival. Among the 477 individuals who underwent CT within 48 hours of admission and 220 individuals who did so over the subsequent 6 days, higher CT grades were associated with increased mortality. Each unit increase in Balthazar grade during the initial 48 hours was associated with an estimated increase in the risk of mortality of 33%, and this trend increased to 50% if pancreatic enlargement and peripancreatic stranding (grades B and C) were combined (P<0.05). CT grade correlated minimally with Ranson, Glasgow, or APACHE II score during the initial 48 hours; however, this correlation improved over 3-8 days. Early nonenhanced abdominal CT in patients with acute pancreatitis is a valuable prognostic indicator of mortality in acute pancreatitis, even among patients without clinical features of severe acute pancreatitis.


Subject(s)
Pancreatitis/diagnostic imaging , Radiography, Abdominal , Tomography, X-Ray Computed/methods , APACHE , Acute Disease , Cause of Death , Double-Blind Method , Female , Forecasting , Humans , Imidazoles/therapeutic use , Leucine/analogs & derivatives , Leucine/therapeutic use , Male , Middle Aged , Pancreatitis/classification , Pancreatitis/drug therapy , Placebos , Platelet Activating Factor/antagonists & inhibitors , Prospective Studies , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Rate , Treatment Outcome
18.
J Surg Res ; 129(1): 90-3, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16139305

ABSTRACT

BACKGROUND: The heat shock response (HSR) attenuates NF-kappaB mediated activation of the acute inflammatory response by inhibiting IkB degradation. The HSR also confers a protective phenotype upon cells through production of heat shock proteins (HSP). However, the exact conditions that induce the HSR and stimulate the production of protective HSP are poorly defined. Consequently, we hypothesized that the inhibition of NF-kappaB activation through the HSR is dependent both on the degree of cellular injury and the length of the recovery period from the heat shock. METHODS: RAW 264.7 murine macrophages were heated to 43 degrees C for 15 (mild heat shock), 45 (moderate heat shock), or 90 min (severe heat shock), allowed to recover at 37 degrees C for 0 to 24 h, and then exposed to 100 ng/ml of Escherichia coli (055:B5) lipopolysaccharide (LPS). Cellular viability, HSP expression, and the activation of NF-kappaB after LPS exposure were determined by alamarBlue assay, immunoblot, and electrophoretic mobility shift assay, respectively. RESULTS: Transient attenuation of NF-kappaB activation and IkappaB preservation was observed only with moderate heat shock and 1 h of recovery. Mild heat shock had no effect on LPS-induced NF-kappaB activation or IkappaB degradation. Severe heat shock completely inhibited NF-kappaB activation and preserved IkappaB protein levels. Heat shock proteins were detectable 30 min after moderate heat shock, with maximal and sustained levels 2 to 24 h after heat shock. CONCLUSION: The attenuation of NF-kappaB activation after heat shock is both dose- and time-dependent.


Subject(s)
Heat-Shock Response/physiology , NF-kappa B/physiology , Animals , Cell Line , Electrophoretic Mobility Shift Assay , Escherichia coli , Heat-Shock Proteins/metabolism , I-kappa B Proteins/metabolism , Immunoblotting , Inflammation , Kinetics , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice
19.
Arch Surg ; 139(3): 262-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15006882

ABSTRACT

HYPOTHESIS: An anatomic classification system for paraspinal tumors that identifies complexity of regional anatomy, morbidity in complete or partial resection of anatomic structures, and potential complications may assist surgeons in preoperative planning. DESIGN: Application of a 6-level anatomic classification system for paraspinal tumors by retrospective medical record analysis. The classification system is defined by the following divisions of the vertebral column: I (C3-T3), II (T3-T10), III (T10-L2), IV (L1-L5, anterior to spine), V (L2-L5, lateral to spine), and VI (S1-S5). PATIENTS: All patients seen by us who underwent paraspinal tumor resection between 1997 and 2002. SETTING: Tertiary referral facility. MAIN OUTCOME MEASURES: Level-specific preoperative and surgical procedures and expected and unexpected vascular and neurologic morbidity caused by surgical intervention. RESULTS: Twenty-six patients met the inclusion criteria, and each of the levels (I through VI) of the classification system was represented by at least 2 patients. Expected morbidity that occurred because of surgical intervention included laryngeal paralysis in 1 patient with a level I tumor, femoral nerve palsy in 1 patient with a level V tumor, and neurogenic bladder and rectal dysfunction in 2 patients with level VI tumors. No unexpected neurologic deficit developed in any patient. Unanticipated intestinal ischemia and infarction occurred in 1 patient, who died after undergoing level IV surgery. Follow-up period ranged from 3 months to more than 5 years. CONCLUSION: Application of this 6-level anatomic classification system based on paraspinal tumor location may allow surgeons to anticipate specific surgical problems and to evaluate risks of resection and potential complications on the basis of regional anatomy.


Subject(s)
Spinal Cord Neoplasms/classification , Spinal Neoplasms/classification , Spine/anatomy & histology , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Spinal Cord Neoplasms/surgery , Spinal Neoplasms/surgery , Spine/diagnostic imaging , Tomography, X-Ray Computed
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