Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

BACKGROUND: CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. METHODS: IDO-1 expression in mice and human vessels was examined. IDO-1-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. RESULTS: Both global IDO-1-/- CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. CONCLUSION: Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.

Does Aspartate Aminotransferase to Alanine Aminotransferase Ratio Predict Acute Kidney Injury After Cardiac Surgery?

BACKGROUND: Aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT) frequently is used in the diagnosis and prognosis of liver diseases, however it is also used in the diagnosis and prognosis of many other diseases, such as myocardial infarction, acute ischemic stroke, and peripheral artery disease. Acute kidney injury (AKI) is one of the most important complications after cardiac surgery and is one of the main causes of morbidity and mortality. The purpose of the study was to analyze the relationship between AST to ALT and AKI after isolated coronary artery bypass graft surgery (CABG). METHODS: We retrospectively reviewed the prospectively collected data of 253 adult patients, who underwent isolated CABG surgery with normal renal function (baseline serum creatinine value <1.4 mg/dL). Preoperative (T0) and postoperative day 1 and day 3 (T1 and T2) serum AST and ALT levels were analyzed, and AST/ALT was calculated. A preoperative AST/ALT of 1.22 was found to be the best cutoff point for predicting postoperative AKI. Kidney injury was interpreted, according to RIFLE classification. The effect of AST to ALT ratio on AKI after CABG was determined using logistic regression analysis, and the results were expressed as odds ratio (OR) with a 95% confidence interval (CI). A P value < .05 was considered statistically significant. RESULTS: Postoperative AKI occurred in 40 patients (15.8%). On logistic regression analysis, higher AST/ALT both preoperatively and postoperatively were associated with an increased incidence of postoperative AKI (T0: OR, 3.983; 95% CI, 1.940-8.180, P < .001, T1: OR, 2.760; 95% CI, 1.381-5.515, P = .004, T2: OR, 2.515; 95% CI, 1.195-5.294, P = .015). CONCLUSION: Preoperative and postoperative elevated AST to ALT ratio seems to be associated with an increased incidence of AKI after elective isolated CABG surgery.

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail.

Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL-6, IL-1ß, TNF-α, and IFN-γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL-6, and TNF-α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform-specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.

Intraoperative amylase level of pancreatic juice as a simple predictor of pancreatic fistula after pancreaticoduodenectomy.

INTRODUCTION: A soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD. METHOD: This study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF. RESULTS: Twenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 105 IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%) CONCLUSIONS: The intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.

Phospholipase A2 group XV activity during cardiopulmonary bypass surgery.

OBJECTIVES: All patients who undergo cardiopulmonary bypass (CPB) experience some degree of ischemia reperfusion injury (IRI). Severe IRI-induced acute kidney injury (AKI) occurs in approximately 1-2% of patients undergoing CPB. Previous studies using activity-based protein profiling of urine identified group XV phospholipase A2, PLA2G15/LPLA2, as potentially associated with patients who develop AKI post CPB. The present study examined urinary PLA2G15/LPLA2 activity during CPB and in the near postoperative period for associations with subsequent AKI development. DESIGN & METHODS: Samples were collected in a nested case controlled cohort of 21 patients per group who either did (AKI) or did not (non-AKI) develop AKI post-operatively. Serum and urine samples from each patient before, during and after CPB were assayed for PLA2G15/LPLA2 activity. RESULTS: Urine activity significantly increased during the intra operative period. In contrast the activities in paired sera were markedly decreased during CPB. There was no correlation between the serum and urine activity levels of patients. There were no significant differences in activity levels of PLA2G15/LPLA2 in the urine or sera from patients that did and did not develop AKI. CONCLUSIONS: The lack of correlation between serum and urine activity levels suggests that the rapid intraoperative increases in PLA2G15/LPLA2 activity may originate from the kidney and as such offer an intraoperative indicator of early renal response to CPB associated stressors.

Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection.

OBJECTIVE: We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs). SUMMARY BACKGROUND DATA: An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis. METHODS: Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice. RESULTS: Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice. CONCLUSIONS: Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

Expression of xylosyltransferases I and II and their role in the pathogenesis of arthrofibrosis.

BACKGROUND: Arthrofibrosis is a painful and restraining complication that occurs after about 10% of total knee arthroplasty and cruciate ligament surgery. The pathogenesis of arthrofibrosis has not yet been fully understood. Stress signals stimulate immune cells, and fibroblast differentiates into myofibroblast, which produce a large amount of collagen. Xylosyltransferases also appear to be involved in these pathways. They catalyze proteoglycan biosynthesis, which is involved in tissue remodeling and myofibroblast differentiation. The aim of this study was to investigate the relationship between the disease arthrofibrosis and the expression of the two isoforms of xylosyltransferases I and II. METHODS: Tissue samples from 14 patients with arthrofibrosis were compared with tissue samples from seven healthy controls. The xylosyltransferases were detected by immunohistochemistry. The tissues were divided into four different areas of interest: vessels, synovialis, cell-poor and cell-rich fibrosis, or cell-poor and cell-rich areas in the control group. A quantification of the results was performed by modification of the immunoreactive score according to Remmele and Stegner. RESULTS: Xylosyltransferase I was expressed in the various tissue types at varying rates. Xylosyltransferase I expression was considerably and significantly stronger than that of xylosyltransferase II. The following sequences of xylosyltransferase I and xylosyltransferase II expression were determined as follows: vessels >> cell-rich fibrosis > cell-poor fibrosis > synovialis. A positive correlation between the number of positive fibroblasts and the immunoreactive scoring system (IRS) was documented. CONCLUSIONS: The significant positive correlation of xylosyltransferase -I expression with increasing number of fibroblasts demonstrates a high myofibroblast differentiation rate, which implies a gradual event as the pathogenesis of arthrofibrosis.

Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study.

OBJECTIVES: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium. DESIGN: Prospective observational study. SETTING: Single-centre at a European academic hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD. RESULTS: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD. CONCLUSIONS: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.

[Postpartum depression: association with genetic polymorphisms of noradrenaline metabolic enzymes and the risk factors].

OBJECTIVE: To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section. METHODS: A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom? Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors. RESULTS: The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression (P < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression (P < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression. CONCLUSIONS: The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.

Urinary Neutrophil Gelatinase Associated Lipocalins (NGALs) predict acute kidney injury post liver transplant.

BACKGROUND: Acute Kidney Injury, a common complication of liver transplant, is associated with a significant increase in the risk of morbidity, mortality and graft loss. Current diagnostic criteria leaves a delay in diagnosis allowing further potential irreversible damage. Early biomarkers of renal injury are of clinical importance and Neutrophil Gelatinase Associated Lipocalins (NGALs) and Syndecan-1 were investigated. METHODS: AKI was defined according to the Acute Kidney Injury Network criteria. Urine and blood samples were collected pre-operatively, immediately post-op and 24 h post reperfusion to allow measurement of NGAL and Syndecan-1 levels. RESULTS: 13 of 27 patients developed an AKI. Patients who developed AKI had significantly higher peak transaminases. Urinary NGAL, plasma NGAL and Syndecan-1 levels were significantly elevated in all patients post reperfusion. Urinary NGAL levels immediately post-op were significantly higher in patients who developed an AKI than those that didn't [1319 ng/ml vs 46.56 ng/ml, p ≤ 0.001]. ROC curves were performed and urinary NGAL levels immediately post-op were an excellent biomarker for AKI with an area under the curve of 0.948 (0.847-1.00). CONCLUSIONS: Urinary NGAL levels measured immediately post-op accurately predict the development of AKI and their incorporation into clinical practise could allow early protocols to be developed to treat post transplant AKI.

A retrospective pilot study to examine the potential of aspartate aminotransferase to alanine aminotransferase ratio as a predictor of postoperative acute kidney injury in patients with hepatocellular carcinoma.

BACKGROUND: The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT) is an independent predictor of hepatic disease. OBJECTIVES: To evaluate the association between preoperative AST/ALT and postoperative acute kidney injury in hepatocellular carcinoma patients. METHODS: A total of 422 hepatitis B- or C- virus-associated hepatocellular carcinoma patients, who underwent hepatectomy between September 2012 and April 2018, were enrolled this retrospective study. From all patients, aspartate aminotransferase and alanine aminotransferase parameters were collected, and the AST/ALT ratio was calculated. For diagnostic criteria of postoperative acute kidney injury, the Kidney Disease Improving Global Outcomes (KDIGO) criteria guidelines were used. RESULTS: In 48 patients (11.4%), postoperative acute kidney injury was confirmed. In patients with postoperative acute kidney injury, the mean preoperative serum AST/ALT was significantly higher when compared with patients without postoperative acute kidney injury. After multivariate logistic regression analysis, AST/ALT, haemoglobin, age, hypertension, Child-Turcotte-Pugh classification and the Milan criteria were all confirmed as predictive factors of postsurgical acute kidney injury. We found that an AST/ALT of 1.29 was the best cut-off point for predicting postoperative acute kidney injury. The positive predictive value (23.9%) of the cut-off is actually poor. After matching the propensity score, AST/ALT ≥1.29 was still confirmed as an independent predictor of postoperative acute kidney injury by multivariate analysis. CONCLUSION: Preoperative elevated serum AST/ALT may be a potential independent predictor of postoperative acute kidney injury in hepatocellular carcinoma patients who have undergone hepatectomy. This needs to be tested in further prospective studies.

D-dopachrome tautomerase predicts outcome but not the development of acute kidney injury after orthotopic liver transplantation.

BACKGROUND: Elevated concentrations of D-dopachrome tautomerase (D-DT) were associated with adverse outcome in various clinical settings. However, no study assessed D-DT concentrations in patients requiring orthotopic liver transplantation (OLT). The aim of this observational study was to measure serum D-DT concentrations in patients undergoing OLT and associate D-DT with survival and acute kidney injury (AKI). METHODS: Forty-seven adults with end-stage liver disease undergoing OLT were included. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of D-DT for outcome and AKI after OLT. Survival was analyzed by Kaplan-Meier curves. RESULTS: Serum D-DT concentrations were greater in non-survivors than in survivors prior to OLT (86 [50-117] vs. 53 [31-71] ng/ml, P = 0.008), and on day 1 (357 [238-724] vs. 189 [135-309] ng/ml, P = 0.001) and day 2 (210 [142-471] vs. 159 [120-204] ng/ml, P = 0.004) following OLT. Serum D-DT concentrations predicted lethal outcome when measured preoperatively (AUC = 0.75, P = 0.017) and on postoperative day 1 (AUC = 0.75, P = 0.015). One-year survival of patients with preoperative D-DT concentrations >85 ng/ml was 50%, whereas that of patients with preoperative D-DT concentrations <85 ng/ml was 83% (Chi2 = 5.83, P = 0.016). In contrast, D-DT was not associated with AKI after OLT. CONCLUSION: In patients undergoing OLT, serum D-DT might predict outcome after OLT.

[Anti-scarring effect of rapamycin in rabbits following glaucoma filtering surgery].

OBJECTIVE: To study the anti- scarring effect of rapamycin in rabbits receiving glaucoma filtering surgery. METHODS: Ninety-six Chinchilla rabbits were randomized equally into 3 rapamycin treatment groups and one control group. All the rabbits underwent trabeculectomy, after which the rabbits in the 3 rapamycin groups were treated with eye drops containing 1%, 3%, or 5% rapamycin in the operated eyes, and those in the control groups were given castor oil 4 times a day. The intraocular pressure (IOP) and inflammatory reaction in the treated eyes were observed, and the PCNA-positive cells in the filtering bleb were detected using immunohistochemistry. RTFs isolated from the Tenon's capsule of the rabbits were cultured in vitro, and the expressions of caspase-3, caspase-8, and caspase-9 in the fibroblasts were detected after treatment with different concentrations of rapamycin. RESULTS: The IOP was significantly lower in rapamycin-treated group than in the control group after the surgery (P < 0.05). The counts of the PCNA-positive cells were significantly lower in rapamycin-treated rabbits than in the control group (P < 0.05). Rapamycin treatment dose-dependently increased the expressions of caspase-3 and caspase- 9 at both the mRNA (P < 0.001) and protein (P < 0.001) levels without causing significant changes in the expressions of caspase-8. CONCLUSIONS: Rapamycin can inhibit excessive proliferation of the fibroblasts in the filtering bleb to reduce scar formation after glaucoma filtration surgery in rabbits. Rapamycin also increases the expressions of caspase-3 and caspase-9 to induce apoptosis of the RTFs.

Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy.

PURPOSE: To evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. MATERIALS AND METHODS: We conducted a retrospective analysis of our multi institutional database. Preoperative ChoE was evaluated as continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with biochemical recurrence (BCR)-free survival. We assessed its association with perioperative clinicopathologic characteristics and outcomes. Multivariable models established its independent prognostic value for BCR. Cox proportional hazard coefficients were used to build nomograms for the prediction of early and late BCR. Decision curve analysis was used to assess the clinical impact on decision making of preoperative ChoE. RESULTS: In all, 6,041 patients were available for the analysis. Decreased ChoE was associated with higher biopsy Gleason score, preoperative PSA levels, pathologic Gleason score, pathological stage, lymph node metastasis, positive surgical margin, and lymphovascular invasion at radical prostatectomy (all P < 0.01). Preoperative ChoE ≤ 6.52 U/ml was associated with higher probability of BCR (HR 1.72, 95% CI 1.48-1.99, P < 0.001). Preoperative and postoperative multivariable models that adjusted for the effects of established clinicopathologic features confirmed its independent association with BCR. In decision curve analysis inclusion of preoperative ChoE did not improve the net benefit of preoperative and postoperative models for the prediction of BCR. CONCLUSIONS: Despite independent association with clinicopathologic features and BCR, preoperative serum ChoE has no impact on clinical decision making. Future studies should investigate the possible relationship between ChoE activity and neoplastic cell transformation with a rational for targeting.

Predictive value of drain pancreatic amylase concentration for postoperative pancreatic fistula on postoperative day 1 after pancreatic resection: An updated meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a potentially fatal complication following pancreaticoduodenectomy. Early prediction and exclusion of POPF may be highly advantageous to enhance patient outcomes, and accelerate recovery. In this meta-analysis, we sought to assess the prediction of drain pancreatic amylase concentration on postoperative day 1 (DPA1) for POPF. METHODS: By searching online databases up to April 2018, all researches mentioned DPA1 for detecting POPF were analyzed. STATA 12.0 was used to analyze pooled predictive parameters. RESULTS: Seventeen studies were finally analyzed including 4676 patients in total. The pooled sensitivity and specificity of DPA1 were respectively 0.85 (95% CI: 0.71, 0.93), 0.80 (95% CI: 0.74, 0.85) to predict overall POPF, and 0.70 (95% CI: 0.53, 0.82), 0.88 (95% CI: 0.86, 0.90) to predict CR-POPF. If pretest probability was 50%, corresponding post-test (+) were respectively 81%, 86% for overall POPF and CR-POPF when DPA1 was above cutoffs, while the post-test (-) were respectively 16%, 26% when DPA1 was under cutoffs. In subgroup analysis, sensitivities of cutoff >5000 group, 1000< cutoff <5000 group, and cutoff <1000 group were respectively 0.65 (0.43-0.82), 0.82 (0.71-0.89), 0.87 (0.78-0.92); and specificities were respectively 0.88 (0.83-0.92), 0.83 (0.77-0.88), 0.71 (0.62-0.79). Positive LR was 5.5 (3.4-8.8), 4.8 (3.4-6.7), and 3.0 (2.3-4.0) respectively. Negative LR was 0.40 (0.22-0.72), 0.22 (0.13-0.37), and 0.19 (0.11-0.32) respectively. CONCLUSION: DPA1, which has good sensitivity and specificity, is useful for predicting overall POPF and CR-POPF, according to the present studies. Meanwhile, it should be cautious to apply because there is a wide range in cutoffs between different studies.

EARLY DRAIN FLUID AMYLASE IS USEFUL TO PREDICT PANCREATIC FISTULA AFTER PANCREATODUODENECTOMY: LESSONS LEARNED FROM A SOUTHERN BRAZILIAN CENTER.

BACKGROUND: Pancreatic fistula represents the most feared complication after pancreatoduodenectomies, being the major responsible for the high morbidity and mortality after this operation. Its incidence remains around 10% to 30%. In recent years, several authors have studied the value of amylase in abdominal drains fluid, measured at an early stage after the surgical procedure, as a useful tool to identify patients at risk of developing pancreatic fistula. OBJECTIVE: To analyze the value of early drain fluid amylase as a method to predict the occurrence and severity of postoperative pancreatic fistula in patients undergoing pancreatoduodenectomies. METHODS: We evaluated 102 prospective patients submitted to pancreatoduodenectomies from January 2013 to June 2017. The mensuration of amylase in abdominal drains was performed on days 1, 3, 5 and 7 in all patients. Patients were divided into three groups according to postoperative day 1 (POD1) results: values <270 U/L (group 1); between 271 and 5.000 U/L (group 2); and values >5.000 U/L (group 3). RESULTS: The incidence of pancreatic fistula was 25.5%, being 3.33%, 27.3% and 41.02% in the three groups, respectively. Compared with group 1, the risk of developing pancreatic fistula increased with increasing amylase values on POD1. Amylase values on POD1 and POD3 of patients with pancreatic fistula were higher than in the other ones without this complication (P<0.001). In addition, in group 3, 37.5% of patients with pancreatic fistula evolved to death (P<0.001). Finally, in this group, patients who died had drain fluid amylase values on POD1 significantly higher than the others in the same group (P<0.001). CONCLUSION: Early drain fluid amylase value is a useful test to stratify patients in relation to the risk of developing pancreatic fistula after pancreatoduodenectomies, in addition to correlate with the severity of this complication.

O valor da amilase, obtido precocemente nos drenos abdominais, é teste útil em prever a ocorrência de fístula pancreática após duodenopancreatectomia: lições aprendidas de um centro do Sul do Brasil / Early drain fluid amylase is useful to predict pancreatic fistula after pancreatoduodenectomy: lessons learned from a southern brazilian center

ABSTRACT BACKGROUND: Pancreatic fistula represents the most feared complication after pancreatoduodenectomies, being the major responsible for the high morbidity and mortality after this operation. Its incidence remains around 10% to 30%. In recent years, several authors have studied the value of amylase in abdominal drains fluid, measured at an early stage after the surgical procedure, as a useful tool to identify patients at risk of developing pancreatic fistula. OBJECTIVE: To analyze the value of early drain fluid amylase as a method to predict the occurrence and severity of postoperative pancreatic fistula in patients undergoing pancreatoduodenectomies. METHODS: We evaluated 102 prospective patients submitted to pancreatoduodenectomies from January 2013 to June 2017. The mensuration of amylase in abdominal drains was performed on days 1, 3, 5 and 7 in all patients. Patients were divided into three groups according to postoperative day 1 (POD1) results: values <270 U/L (group 1); between 271 and 5.000 U/L (group 2); and values >5.000 U/L (group 3). RESULTS: The incidence of pancreatic fistula was 25.5%, being 3.33%, 27.3% and 41.02% in the three groups, respectively. Compared with group 1, the risk of developing pancreatic fistula increased with increasing amylase values on POD1. Amylase values on POD1 and POD3 of patients with pancreatic fistula were higher than in the other ones without this complication (P<0.001). In addition, in group 3, 37.5% of patients with pancreatic fistula evolved to death (P<0.001). Finally, in this group, patients who died had drain fluid amylase values on POD1 significantly higher than the others in the same group (P<0.001). CONCLUSION: Early drain fluid amylase value is a useful test to stratify patients in relation to the risk of developing pancreatic fistula after pancreatoduodenectomies, in addition to correlate with the severity of this complication.

RESUMO CONTEXTO: A fístula pancreática representa a complicação mais temida após as duodenopancreatectomias, sendo a grande responsável pela elevada morbi-mortalidade após esta operação. Sua incidência permanece em torno de 10% a 30%. Nos últimos anos, diversos trabalhos têm estudado o valor da amilase nos drenos abdominais, medido de forma precoce após o procedimento cirúrgico, como ferramenta útil para a identificação dos pacientes sob risco de desenvolver fístula pancreática. OBJETIVO: Avaliar o valor da amilase no fluido dos drenos abdominais, obtido precocemente no pós-operatório, como método para prever a ocorrência e severidade da fístula pancreática nos pacientes submetidos a duodenopancreatectomias. MÉTODOS: Foram avaliados 102 pacientes prospectivos submetidos a duodenopancreatectomias no período de janeiro de 2013 a junho de 2017. A dosagem da amilase nos drenos abdominais foi realizada nos dias 1, 3, 5 e 7 em todos os pacientes. Os pacientes foram divididos em três grupos conforme os resultados do 1o PO: valores <270 U/L (grupo 1); entre 271 e 5.000 U/L (grupo 2); e valores >5.000 U/L (grupo 3). RESULTADOS: A incidência de fístula pancreática foi de 25,5%, sendo 3,33%, 27,3% e 41,02% nos três grupos, respectivamente. Comparados ao grupo 1, o risco de desenvolver fístula pancreática foi crescente com o aumento da amilase no 1o PO. Os valores das amilases no 1o PO e 3o PO dos pacientes com fístula pancreática foram maiores do que nos pacientes sem essa complicação (P<0,001). Além disso, no grupo 3, 37,5% dos pacientes com fístula pancreática evoluíram para óbito (P<0,001). Por fim, neste grupo, os pacientes que evoluíram para óbito tiveram valores de amilase no 1o PO significativamente maiores do que os demais pacientes (P<0,001). CONCLUSÃO: O valor da amilase, medido de forma precoce nos drenos abdominais no pós-operatório de duodenopancreatectomias, é teste útil para estratificar pacientes em relação ao risco de apresentar fístula pancreática, além de se correlacionar com a severidade dessa complicação.

Impact of angiotensin-converting enzyme 2 levels on postoperative pneumonia after esophagectomy.

BACKGROUND: Pulmonary complications after esophagectomy are often fatal. The prediction of postoperative pulmonary complications remains a challenge. Accumulating evidence demonstrates a physiological and pathological role for angiotensin-converting enzyme 2 (ACE2) in the respiratory system. The purpose of this study was to evaluate the predictive value of ACE2 levels for the development of postoperative pneumonia. METHODS: To evaluate the association between serum ACE2 levels and pneumonia after esophagectomy, we retrospectively reviewed the medical records of 80 patients who underwent thoracoscopic esophagectomy for esophageal cancer from 2009 to 2014. RESULTS: Nineteen patients (23.8%) developed pneumonia after esophagectomy. Patients with pneumonia had significantly higher levels of ACE2 from the preoperative day to postoperative day (POD) 3, white blood cell count (POD7), and C-reactive protein (POD3, POD5, and POD7) than patients without pneumonia. Patients with postoperative pneumonia had higher serum ACE2 levels on POD3 than patients without pneumonia. CONCLUSIONS: The elevation of ACE2 levels on POD3 may predict the incidence of pneumonia.

Surgeon volume and hospital volume in endocrine neck surgery: how many procedures are needed for reaching a safety level and acceptable costs? A systematic narrative review.

The relationship between quality of care and provider's experience is well known in all fields of surgery. Even in thyroidectomies and parathyroidectomies, the emphasis on positive volume-outcome relationships is believed. It led us to an evaluation of volume activity's impact in terms of quality of care. A systematic narrative review was performed. According to the PRISMA criteria, we selected 87 paper and, after the study selection was performed, 22 studies were finally included in this review. All articles included were unanimous in attributing to activity volume of surgeons as well as centers a substantial importance. Some differences in outcomes between these investigated categories have been found: best results of the high volume surgeon is evident expecially in terms of complications, on the contrary best outcomes of a high volume center are mainly economics, such as hospital stay and general costs of the procedures. A cut-off of 35-40 thyroidectomies per year for single surgeon, and 90-100 thyroidectomies for single center appears reasonable for identifying an adequate activity. Concerning parathyroidectomy, we can consider reasonable a cut off at 10-12 operations/year. More studies are needed in a European or more circumscribed perspective.

Impact of anatomical position of the pancreas on postoperative complications and drain amylase concentrations after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic surgery for gastric cancer requires traction or compression of the pancreas, with the extent depending on the anatomical position of the pancreas. This study investigated the impact of the position of the pancreas on postoperative complications and drain amylase concentrations after laparoscopic distal gastrectomy (LDG). METHODS: Gastric cancer patients who underwent LDG were assessed retrospectively. The following anatomical parameters were measured retrospectively in preoperative computed tomography sagittal projections: the length of the vertical line between the pancreas and the aorta (P-A length), representing the height of the slope looking down the celiac artery from the top of the pancreas, and the angle between a line drawn from the upper border of the pancreas to the root of the celiac artery and the aorta (UP-CA angle), representing the steepness of the slope. Correlations between each parameter and postoperative complications were analyzed by logistic regression analysis. Pearson's product-moment correlation coefficients were calculated for scatter diagrams for each parameter and drain amylase concentration on postoperative day 1. RESULTS: Analyses were performed in 394 patients. P-A length [odds ratio (OR) 1.905; 95% confidence interval (CI) 1.100-3.300; P = 0.021] was significantly correlated with pancreatic fistula. P-A length (OR 2.771; 95% CI 1.506-5.098; P = 0.001), UP-CA angle (OR 2.323; 95% CI 1.251-4.314; P = 0.008), and low preoperative serum albumin (OR 2.082; 95% CI 1.050-4.128; P = 0.036) were significantly correlated with overall postoperative complications defined as Clavien-Dindo ≥ grade II. P-A length and UP-CA angle showed significant positive correlations with drain amylase concentration on postoperative day 1. CONCLUSION: The position of the pancreas is an independent predictor of pancreatic fistula and/or postoperative complications and correlates with drain amylase concentration after LDG for gastric cancer.