Grażyna Poznańska

Very high concentration of D-dimers in portal blood in patients with pancreatic cancer.

UNLABELLED Nowadays, increasing attention has been focused on relation between increased D-dimer levels and cancer among patients without detectable thrombosis. The aim of the study was to measure plasma D-dimer levels in portal and peripheral blood in pancreatic cancer patients with absence of venous thromboembolism. MATERIAL AND METHODS Fifteen consecutive patients hospitalized in the Department of General and Transplant Surgery of Medical University in Łódź, from January to March 2012 who underwent surgery due to a pancreatic cancer were enrolled. At laparotomy, portal and peripheral blood were sampled concurrently. D-dimer and fibrinogen levels were measured. Moreover, to investigate overall coagulation function prothrombin time (PT), prothrombin index (PI), international normalized ratio (INR), thrombin time (TT), activated partial thromboplastin time (APTT), TT and APTT index were evaluated. RESULTS Peripheral plasma D-dimmer levels above normal range were found in 10/15 patients (66,67%), whereas D-dimer above normal values were confirmed in all portal blood samples. Mean D-dimer values were higher in portal than in peripheral blood (3279.37 vs 824.64, by 297%, p=0,025). These discrepancies were accompanied by normal limits of portal and peripheral levels of fibrinogen and comparable coagulation function indexes. CONCLUSION Our preliminary study showed the close relation between activation of hemostasis, reflected by elevated D-dimers in portal blood and presence of pancreatic cancer. These data suggest that measurement of portal blood D-dimer levels may be a potentially useful technique for screening the pancreatic cancer.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration in urine is superior to CA19-9 and Ca 125 in differentiation of pancreatic mass: Preliminary report.

BACKGROUND Currently pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Because of its late manifestation and consequent dismal prognosis, there is an urgent need to develop highly sensitive and specific marker. Neutrophil Gelatinase-Associated Lipocalin (NGAL) recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE Our aim was to assess the potential of urine and bile concentration of NGAL in differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS Forty-two patients operated on due to pancreatobiliary lesions were enrolled in this study. All enrolled patients had eGFR within reference range. Levels of CEA, CA 125 and Ca19-9 were assessed using standard laboratory protocols. A sample of urine was collected prior to the surgery. Intraoperatively a 5 ml sample of bile was collected directly from the common bile duct. Bile and urine levels of NGAL were measured using a ELISA kit. After standard pathological examination of specimens obtained during surgery, patients were divided into 2 groups: 21 patients with pancreatic adenocarcinoma and 15 patients with focal chronic pancreatitis. RESULTS NGAL concentration in bile in patients with PDAC vs CP was 75.72 ± 16.05 ng/mL vs 62.62 ± 18.6 ng/mL respectively (p= 0,011). NGAL concentration in urine was 43.26 ± 21.21 ng/mL vs 17.96 ± 14.58 ng/mL (p= 0.002) respectively. In order to compare these markers with routinely used ones, ROC curve was built for Ca125 to establish cutoff point and in case of CA19-9 clinically used cutoff (≥ 37U/mL) was applied. Sensitivity and specificity for NGALurine with cutoff value of 27 ng/mL was 80.95% and 80% respectively, while these values for NGALbile were 71.43% and 80% respectively. Ca19-9 measured in plasma with clinically used cutoff value had sensitivity of 71.43% and specificity of 73.33%. Sensitivity and specificity for Ca 125 measured in plasma with cutoff value of 13 U/mL were 85.71% and 66.67% respectively. CONCLUSIONS In conclusion, NGAL in urine and bile are remarkably accurate in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Therefore, NGAL concentrations in bile and urine should be further investigated in order to assess their usefulness in early pancreatic adenocarcinoma diagnosis.

D-dimers revisited: a new marker of pancreatic cancer.

To the Editor: The excellent article of Sun et al elucidated the clinical and prognostic significance of coagulation assays in pancreatic cancer (PC) patients with absence of venous thromboembolism. The manuscript, with a review of the literature, comes to the conclusion that the pretreatment level of plasma D-dimers (DD) was a potential predictor of prognosis in PC patients without venous thromboembolism. Various solid tumors including lung, prostate, cervical, and colorectal cancer are found to have elevated DD levels in the peripheral plasma. However, we found a very high concentration in portal blood, but only a moderately elevated value of DD in peripheral blood of patients with PC and without detectable DVT (n = 89, 3738.4 ± 3999.8 vs. 1217.7 ± 1718.9, respectively, P < 0.001). On this basis, we hypothesized that the site of blood sampling for DD assessment influences the laboratory results and may be of great clinical importance. Portal, but not peripheral blood DD level may help to better differentiate malignant from benign pancreatic tumors. We confirmed this hypothesis in another analysis comparing the DD level in portal and peripheral blood of patients with PC (n = 89) and chronic pancreatitis (ChP, n = 28) (in peripheral blood, the DD levels were 1100.4 ± 1856.9 for the PC group and 1217.7 ± 1718.9 for the ChP group, P = 0.504; in portal blood the DD levels were 3738.4 ± 3999.8 vs. 1141.2 ± 1847.5, for the PC and ChP groups, respectively, P < 0.001). High DD are associated with a poor prognosis in cancer patients; therefore, we have carried out another study on DD portal and peripheral blood levels in patients with metastatic pancreatic cancer (mPC, n = 19) and nonmetastatic pancreatic cancer (nmPC, n = 70). The results of the study showed that the mean DD value in peripheral blood was higher in mPC when compared with nmPC patients (2139.3 ± 2752.5 vs. 963.9 ± 1213.2, P < 0.001). Portal blood DD concentration in both the groups studied (mPC and nmPC) remained at a very high level (3128.2 ± 3565.1 vs. 3908.9 ± 4121.4, respectively, P = 0.573). Therefore, we hypothesized that the liver might contribute toward elimination of DD from portal blood. To determine whether the liver acts as a “levee” for this marker, we attempted a study to elucidate DD in bile of patients with PC. Our analysis found a higher DD level in bile of patients with PC (n = 52) when compared with the control group of ChP (n = 29) (2583.3 ± 3455.2 vs. 654.5 ± 1054.5, respectively, P = 0.006). From the above study, we concluded that the hepatic barrier for DD may be responsible for only moderately elevated values of this marker in patients with nonmetastatic pancreatic adenocarcinoma. In contrast, in metastatic disease DD by-pass hepatic sieve and its concentration becomes very high in the general circulation of blood. Therefore, peripheral blood DD might be a novel marker in the diagnostic algorithm for the exclusion of occult hepatic metastases before surgery of patients with PC. All our studies were approved by the local Ethics Committee and written informed consents were obtained from all patients. After the dissection of the hepatoduodenal ligament, samples of portal blood and bile were taken, as described earlier. Peripheral blood from the central line was sampled. Portal, peripheral plasma, and bile DD levels were measured using commercial kits (VIDAS D-Dimer Exclusion II, bioMérieux, France). All statistical calculations were carried out using the SigmaPlot version 12.0 (Systat Software Inc., San Jose, CA) with the level of statistical significance at P < 0.05. As described by Sun et al plasma coagulation parameters including DD may be associated with tumor progression, metastasis, and prognosis. However, measurement of plasma DDs has limited specificity in cancer diagnosis as many conditions are associated with fibrin formation. Nonetheless, to date, only peripheral blood has been investigated in cancer patients. Our analyses on various novel sites of assessing DD levels indicate that it may help overcome the limitations of this assay. Further multicenter studies to assess clinical applicability of portal blood, bile, and urine DD levels for the diagnosis of PC are definitely needed. Adam Durczynski, MD, PhD* Anna Kumor, MD, PhDw Piotr Hogendorf, MD, PhD* Dariusz Szymanski, MD, PhD* Grazyna Poznanska, MDz Piotr Grzelak, MD, PhDy Janusz Strzelczyk, MD, PhD* Departments of *General and Transplant Surgery wAllergology and Pulmonary Diseases yRadiology and Diagnostic Imaging, Medical University of Lodz zDepartment of Anesthesiology and Intensive Care, Barlicki Teaching Hospital, Lodz, Poland

A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the Differential Diagnosis of the Pancreatic Lesion

Background. Proper diagnosis of pancreatic lesion etiology is a challenging clinical dilemma. Studies suggest that surgery for suspected pancreatic ductal adenocarcinoma (PDAC) reveals a benign lesion in 5% to 13% of cases. The aim of our study was to assess whether routinely used biomarkers such as CA19-9, Ca125, Ca15-3, and CEA, when combined, can potentially yield an accurate test predicting pancreatic lesion etiology. Methods. We retrospectively analyzed data of 326 patients who underwent a diagnostic process due to pancreatic lesions of unknown etiology. Results. We found statistically significant differences in mean levels of all biomarkers. In logistic regression model, we applied levels CA19-9, Ca125, and Ca15-3 as variables. Two validation methods were used, namely, random data split into training and validation groups and bootstrapping. Afterward, we built ROC curve using the model that we had created, reaching AUC = 0,801. With an optimal cut-off point, it achieved specificity of 81,2% and sensitivity of 63,10%. Our proposed model has superior diagnostic accuracy to both CA19-9 (p = 0,0194) and CA125 (p = 0,0026). Conclusion. We propose a test that is superior to CA19-9 in a differential diagnosis of pancreatic lesion etiology. Although our test fails to reach exceptionally high accuracy, its feasibility and cost-effectiveness make it clinically useful.

Neutrophil-lymphocyte ratio and creatinine reduction ratio predict good early graft function among adult cadaveric donor renal transplant recipients. Single institution series

Background Delayed graft function (DGF) is a common complication following kidney transplantation and is associated with ischemia-reperfusion injury (IRI). Lymphocytes contribute to the pathogenesis of IRI and ischemia-reperfusion related delayed graft function Materials and Methods 135 Caucasian patients received a kidney graft from deceased heart-beating organ donors. We divided patients into 2 groups- patients with the eGFR>=30 on the 21st day post-transplantation (n=36) and patients with the eGFR<30 on the 21st day post-transplantation (n=99) to assess kidney graft function. We measured the serum creatinine levels on 1st and 2nd post-transplant day and preoperative levels of monocytes, lymphocytes, platelets and neutrophils and their ratios. Results We have found statistically significant differences between the eGFR<30 and the eGFR>=30 groups in the average lnLymphocytes (0,36 +/-0,6 vs -0,016 +/-0,74 respectively p=0,004) lnNLR ( 1,27 +/-0,92 vs. 1,73+/-1,08 p=0,016) lnLMR (1,01 +/-0,57 vs. 0,73 +/-0,64 p=0,02), lnPLR (4,97 +/-0,55 vs. 5,26 +/- 0,67 p=0,023) and CCR2% (-20,20 +/- 21,55 vs. -4,29 +/- 29,62 p=0,004 . On univariate analysis, factors of lnLymphocytes >=0,22 (OR=0,331 95%CI 0,151-0,728 p=0,006), lnLMR>=1,4 (OR=0,255 95%CI 0,072-0,903 p=0,034) were associated with worse graft function while lnNLR>=1,05 (OR=2,653 95%CI 1,158-6,078 p=0,021), lnPLR>=5,15 (OR=2,536 95%CI 1,155-5,566 p=0,02) and CRR2 (OR=3,286 95% CI 1,359-7,944 p=0,008) indicated better graft function Conclusion Higher absolute lymphocyte count (lnLymphocytes) and lnLMR as well as lower lnNLR and lnPLR were associated with lower eGFR on the 21st day after kidney transplantation. On multivariate analysis CRR2 in combination with either lnLymphocytes, lnNLR or lnPLR improved the accuracy of detecting patients with poor graft function.

Successful hemihepatectomy following chemotherapy for primary liver lymphoma: case report and review of literature

Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of B-cell and T-cell neoplasms. Diffuse large B-cell lymphoma (DLBCL), the most common type of NHL, accounts for around 30-40% of NHL cases. However, primary hepatic location of NHLs is rare and constitutes 0.01% of all NHL cases. Due to this rarity and a lack of large randomized trails, it is still unclear what treatment should be used for primary hepatic DLBCLs. In this study, we report of a female patient with primary hepatic DLBCL who was successfully treated with neoadjuvant chemotherapy and surgery. We also shortly review the literature regarding surgical treatments for primary GI tract NHLs. Taking into account our experience and the current literature, surgical treatment with postoperative chemotherapy seems to be a feasible option for patients with focal primary hepatic DLBCLs.

Ruptured Hemangioma of a Native Kidney: An Unusual Cause of Postoperative Hemorrhage in Kidney Transplant Recipients

BACKGROUND Retroperitoneal bleeding as a consequence of non-traumatic kidney or allograft rupture is well known, but there are no reports on hemorrhagia from a native kidney after allogeneic renal transplantation. Therefore, we present the first such case to be published and highlight the possibility of this complication after renal transplantation. CASE REPORT We report the case of a 28-year-old male patient who developed early post-transplant hemorrhagia from a ruptured native kidney. The patient underwent left-sided nephrectomy. Histopathological examination revealed ruptured hemangioma of the patients native left kidney. The further postoperative period was not complicated. The patient was discharged on the 18th postoperative day, with good transplant function. CONCLUSIONS Transplantologists should be aware of the fact that in patients with uncontrolled blood pressure, native kidney hemangioma may rupture in the early post-transplant period, and it can be a life-threating and difficult to diagnose complication.