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.

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.

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.

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.

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.

[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.

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.

Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation.

OBJECTIVE: To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. METHODS: 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×108/pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. RESULTS: Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. CONCLUSION: Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation.

Omega-loop gastric bypass is more effective for weight loss but negatively impacts liver enzymes: a registry-based comprehensive first-year analysis.

BACKGROUND: The impact of omega-loop gastric bypass (OLGB) on weight loss and liver enzymes remains inconclusive. OBJECTIVE: The aim of this study was to compare the impact of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and OLGB on weight loss and liver enzyme levels. SETTING: National Bariatric Surgery Registry. METHODS: The study included 10,675 cases of SG, 1590 cases of RYGB, and 469 cases of OLGB that had available baseline and 1-year (12 ± 2 mo) follow-up data. RESULTS: The highest percentage of excess weight loss was achieved by the OLGB group (84.5% ± 26.7%), followed by the SG (78.5% ± 26.0%) and RYGB (72.0% ± 26.5%) groups (P<.05). The data show that 10% of OLGB cases, 5.2% of RYGB cases, and 1.9% of SG cases (P<.001) had increases in alanine aminotransferase levels, from a normal baseline mean of 23.9 ± 7.5 U/L to an abnormal mean of 64.8.7 ± 66.0 U/L, at follow-up. Similar trends were observed for aspartate aminotransferase and alkaline phosphatase. A regression analysis showed that OLGB was a predictive risk factor for normal baseline alanine aminotransferase levels becoming abnormal postoperatively compared with SG (odds ratio [OR] = 5.65) or RYGB (OR = 2.08) (P<.001). Similarly, OLGB was a predictive risk factor for baseline aspartate aminotransferase and alkaline phosphatase levels becoming abnormal postoperatively. Female sex was the only other meaningful predictive risk of alanine aminotransferase (OR = 2.45) and aspartate aminotransferase (OR = 1.82) becoming abnormal postoperatively. CONCLUSION: This study confirmed the strengths of OLGB weight loss outcomes but also demonstrated its negative impact on liver enzymes. Thus, patients and caregivers should be informed of the risks, and close follow-up is warranted.

Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery.

BACKGROUND: Postoperative ileus (POI) is observed in 20-30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle. METHODS: This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty-eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery. RESULTS: ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03). CONCLUSION: The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients.

Reduced serum cholinesterase activity indicates splenic modulation of the sterile inflammation.

BACKGROUND: Sterile inflammation is an immediate and well-coordinated immune response to surgical injury. The cholinergic system plays a pivotal role in the inflammatory response. Induced inflammation stimulates the vagus nerve, which in turn activates anti-inflammatory nonneuronal processes. Serum cholinesterase (butyrylcholinesterase [BChE]) is an enzyme that hydrolyzes acetylcholine. Measuring the activity of the BChE in blood might indicate the level of the nonneuronal cholinergic activity. The spleen is a major organ of the immune system playing an important role during inflammation. A functional connection of the neuroimmune reflex has thus far been described only in experimental settings. MATERIALS AND METHODS: In 48 patients receiving major pancreatic surgery, BChE activity was measured by applying point-of-care-testing, in addition to standard laboratory tests. RESULTS: The BChE activity decreased in patients receiving surgery. This reduction emerged much earlier than changes in C-reactive protein concentration, an inflammatory biomarker broadly used in the clinical environment. A milder reduction in the BChE activity was observed in patients subjected to surgery with splenectomy than in those with a preserved spleen. CONCLUSIONS: The use of the point-of-care-testing system for quick bedside diagnostics and the rapid effects of inflammation on BChE levels provide a method and a marker to facilitate the early detection of systemic inflammation. Furthermore, this study provides evidence that the experimentally documented neuroimmune interaction is part of the physiological response to surgery-induced sterile inflammation. Splenic function plays an essential role in modulating the cholinergic anti-inflammatory response.

Cyclooxygenase 2 contributes to bradykinin-induced microvascular responses in peripheral arterioles after cardiopulmonary bypass.

BACKGROUND: Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. METHODS: Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 µm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10-10 to 10-6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10-5M). RESULTS: The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). CONCLUSIONS: Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery.