Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUNDInflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors.AIMTo investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC).METHODSWe retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTSThe optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSIONThe increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.     

TNFα in ischemia/reperfusion injury and heart failure

Abstract. During myocardial ischemia, both the myocardial and serum TNF concentrations are rapidly increased within the area at risk. With prolongation of ischemia and development of cardiomyocyte necrosis, the TNF concentration increases also in the surrounding viable portions of the myocardium. Indeed, in the scenario of myocardial ischemia/reperfusion, treatment with TNF antibodies reduced the extent of myocardial infarction in rabbits and attenuated the contractile dysfunction following microembolization in dogs. In the latter studies, the serum TNF concentration remained unaltered thereby supporting the notion of a direct action of TNF at the level of cardiomyocytes during ischemia/reperfusion.In heart failure, the serum TNF concentration is also increased, and in patients with advanced heart failure the serum TNF concentration is an independent predictor of mortality. The origin of the increased serum TNF concentration is not clearly identied yet, but TNF derived from the heart and peripheral organs contributes to the increased serum TNF concentration. Treatment with TNF antibodies in the clinical scenario, however, did not improve the prognosis of heart failure patients.     

The Relationship Between HRCT and Pulmonary Function in Behcet’s Disease

The purpose of this study was to compare the pulmonary functions in female Behcets patients with or without pathological pulmonary lesions using high resolution computerized tomography (HRCT). Twenty-nine female patients aged 19–54 yrs and 20 healthy females aged 19–50 yrs (control group) were accepted into the study. HRCT images were taken and according to HRCT patients were divided into HRCT (+) and HRCT (–) groups (18 patients in each). Pulmonary function tests (PFT) through a spirometer were performed and FVC, FEV₁, FEF_25–75%, PEF, VC, RV, FRC, DLCO and DLCO/VA were determined. No statistically significant difference was observed when the PFT values were compared between HRCT (+) and HRCT (–) patients for the obtained results and the percentage of the expected values. When the PFT values were compared for both HRCT (+) and HRCT (–) patients with the control group separately there was no statistical difference between the best values. A statistically low DLCO/VA value was observed between the percentage of the expected values. It is concluded that though there is a pulmonary restriction in Behcets disease, this restriction has no relation to pulmonary functions. It would be useful to perform pulmonary function tests in the patients with Behcets disease both with or without any pathological findings in HRCT for obtaining information about pulmonary functions. We suggest that even when the results of the pulmonary function tests are normal, considering some pathological changes in HRCT, HRCT investigations may be useful for following up the disease.     

Chronic effects of streptozotocin diabetes on myocardial sensitivity in the rat

Summary One month after streptozotocin treatment, basal rate in spontaneously beating right atria was decreased and basal developed force in electrically-driven right ventricular tissue was increased. Atrial sensitivity to the chronotropic effects of isoproterenol was not altered. In contrast, sensitivity in ventricular tissue to the inotropic effects of isoproterenol was decreased while sensitivity to calcium was increased. Associated with these changes was a decrease in myocardial-adrenoceptor density. Data obtained 3 and 6 months after streptozotocin treatment were similar to the observed alterations at 1 month. These results suggest that alterations in the chronotropic and inotropic responses that are expressed within 1 month after streptozotocin treatment do not significantly progress during the 6 months following induction of diabetes. They therefore reveal the independence of myocardial alterations from age of the animal and duration of diabetes (up to 6 months).     

The place of cladribine in the treatment of chronic lymphocytic leukemia: a 10-year experience in Poland

Cladribine (2-CdA) is structurally similar to another purine analog, fludarabine (FA), recently accepted in several centers as the first-line treatment in chronic lymphocytic leukemia (CLL). Unfortunately, there is less experience with the use of 2-CdA than with FA in patients with CLL in the majority of Western countries. In the last decade we performed several phase II studies and two phase III randomized trials to evaluate the activity and toxicity of 2-CdA in previously treated and untreated patients with CLL. We have also compared the results of Polish studies with the data presented by other investigators. Similarly to FA this agent has been found to be more effective in previously untreated CLL than in patients refractory to or relapsed after conventional therapy with alkylating agents. In different studies the overall response (OR) rate ranged from 70 to 85% and complete response (CR) from 10 to 47%. Higher CR and OR rates in CLL patients treated with 2-CdA and prednisone than with chlorambucil and prednisone were confirmed in our multicenter, randomized study. Subsequently, we performed a multicenter, randomized study comparing 2-CdA alone with a combination of 2-CdA and cyclophosphamide (CC) or cyclophosphamide and mitoxantrone (CMC). Our updated results seem to indicate that the CC program used as a first-line therapy in CLL gives higher CR and OR and better elimination of minimal residual disease (MRD) than 2-CdA alone. CC is also less myelotoxic than CMC. More recently, we have undertaken a phase II study to determine the efficacy and toxicity of 2-CdA combined with the anti-CD20 monoclonal antibody rituximab in CLL and other refractory or relapsed indolent lymphoproliferative disorders. The preliminary results seem to be better than in similar patients previously treated in our institution with 2-CdA alone. In conclusion, the studies performed in the last decade in Poland and other countries have shown that 2-CdA used alone or in combination with other agents is, similarly to FA, a highly active and relatively safe agent in previously treated and untreated patients with CLL.     

Changes of systemic prostacyclin and thromboxane A2 in sodium taurocholate-and cerulein-induced acute pancreatitis in rats

Systemic prostacyclin and thromboxane A₂ production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F₁ and 2,3-dinor thromboxane B₂, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 g/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F₁ and 2,3-dinor thromboxane B₂ were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A₂ activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.This work was supported by the Fondo de Investigación Sanitaria (89/386).     

Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats

Summary Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9, 3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P<0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P<0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P<0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.Abbreviations HPLC high performance liquid chromatography - NAB N-nitrosoanabasinc - NAT N-nitrosoanatabine - NNK 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone - NNN N-nitrosonornicotine Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthdayThis is No. XXVII of A Study of Tobacco Carcinogenesis. The study is supported by U.S. National Cancer Institute Grant CA-29580We thank Ms. Maria Nicholais and Mr. Joel Reinhardt from the Research Animal Facility for their excellent technical assistance