Anna Kumor

Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients

IntroductionLeptin, adiponectin, and resistin are the proteins secreted by adipocytes, which affects the metabolism. While the role of leptin in colon carcinogenesis is documented, the effect of adiponectin and resistin remains unclear. It has been indicated that while leptin may potentiate the cancer cells growth, adiponectin and resistin may act oppositely.AimThe aim of this study is to determine the concentration of leptin, adiponectin, and resistin in patients with adenomatous polyps and colorectal cancer.MethodsThe serum concentration investigated adipohormones had been measured with ELISA in 37 patients with colorectal adenomas, 36 with colorectal cancer (CC) and in 25 controls with no colorectal pathology. Endoscopically removed polyps and CC biopsies had been evaluated with histopathology. Mean BMI value was calculated for all patients.ResultsAmong 37 adenomas, 25 revealed high-grade dysplasia (HGD) and 12 low-grade dysplasia (LGD). All cases of CC were adenocarcinomas. No difference in the level of investigated adipohormones in serum between patients with HGD and LGD polyps was observed. The serum concentration of leptin and adiponectin in CC patients was lower than in patients with adenomas (p < 0.05; p < 0.05, respectively) as well as in controls (p < 0.01; p < 0.05, respectively). The concentration of resistin in CC was not significantly different in the adenoma group (p > 0.05) but higher than in controls (p < 0.05). There was a correlation between adiponectin and leptin serum concentration (r = 0.61).ConclusionWe conclude that serum concentration of adiponectin and resistin may play an important role in colon carcinogenesis. We also assume that leptin may possibly have the prognostic value useful in clinical practice and its concentration is independent of BMI value.

Prostaglandin E2 (PGE2) in Portal Blood in Patients with Pancreatic Tumor—A Single Institution Series

ABSTRACT Background: Cyclooxygenase-2 (COX-2) may play a significant role in the development of pancreatic cancer. One of COX-2 main metabolites is prostaglandin E2 (PGE2), which is involved both in inflammation and carcinogenesis. As PGE2 is inactivated in the lungs and the liver we assumed that the best medium to assess the level of PGE2 is not peripheral but portal blood. Patients and methods: Fifty-seven patients with pathologically verified diagnosis of pancreatic ductal adenocarcinoma (PDAC group, n = 38) and chronic pancreatitis (CP group, n = 19) were enrolled in this study. Sample of blood from central line was collected before surgery. Intraoperatively portal vein was identified and sampled. PGE2 levels were determined using ELISA test. All the patients were followed-up for 1–35 months. Results: PGE2 portal blood levels in patients with PDAC were higher than in patients with CP (190.55 ± 149.86 versus 120.23 ± 132.60; p = .04). PGE2 concentration at a cut-off value of 94.46 pg/ml had a sensitivity of 91.67%, specificity of 50%, AUC = 0.631 (95% CI, 0.489–0.758). Conclusion: The PGE2 portal blood levels in PDAC patients are higher than in those with CP. The PGE2 portal concentration cannot be a single marker in diagnosing PDAC due to low specificity.

Preoperative high level of D-dimers predicts unresectability of pancreatic head cancer.

AIM To assess the value of D-dimer level in determining resectability of pancreatic cancer. METHODS Preoperative prediction of pancreatic head cancer resectability remains inaccurate. The use of hemostatic factors may be of potential help, since D-dimers correlate with tumor stage. Single center clinical trial study comprised patients with potentially resectable pancreatic head tumor and without detectable venous thrombosis (n = 64). Resectability was defined as no evidence of nodal involvement, distant spread and no invasion of mesenteric vessels. Final decision of resectability was confirmed intraoperatively. Experienced pancreatic surgeon performed all surgeries. Following the dissection of hepatoduodenal ligament, samples of portal blood and bile were taken. Peripheral blood via central line and urine via Foley catheter were sampled. D-dimer levels were further measured. RESULTS At laparotomy only 29 (45.3%) tumors were found to be resectable. Our analysis showed higher by 57.5% (P < 0.001) mean D-dimer values in peripheral and 43.7% (P = 0.035) in portal blood of patients with unresectable pancreatic cancer. Significant differences were not observed when analyzing D-dimer levels in bile and urine. Peripheral D-dimer level correlated with pancreatic cancer resectability. When cut-off D-dimer value of 570.6 μg/L was used, the sensitivity for assessment of tumor unresectability was 82.8%. Furthermore, D-dimer level in peripheral blood of metastatic disease (n = 15) was significantly higher when compared to locally advanced (n = 20) pancreatic cancer (2470 vs 1168, P = 0.029). The area under ROC curve for this subgroup of patients was 0.87; for determination of unresectable disease when threshold of 769.8 μg/L was used, sensitivity and specificity was 86.6% and 80%, respectively. CONCLUSION Patients with resectable pancreatic head cancer based on preoperative imaging studies and high D-dimer level may be considered unresectable due to occult hepatic metastases. These patients may benefit from diagnostic laparoscopy to avoid exploratory laparotomy.

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

Pancreatic head carcinoma and vascular endothelial growth factor (VEGF-A) concentration in portal blood: its association with cancer grade, tumor size and probably poor prognosis.

Introduction Vascular endothelial growth factor (VEGF) is overexpressed in pancreatic cancer. Although VEGF has been shown to be a probable marker for poor prognosis, the VEGF concentration in portal blood has not yet been clinically reported in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to measure VEGF-A portal blood concentration in patients with PDAC and to evaluate its performance as a prognostic marker. Material and methods Thirty-six consecutive patients out of 57 operated on for pancreatic head lesion with pathologically verified diagnosis of PDAC were enrolled in this study. We evaluated the VEGF concentration in portal blood samples obtained intraoperatively and associated their values with tumor size, stage, grade and survival. Results The portal VEGF-A concentration was associated with tumor grade (G1: 80.52 ±43.05 vs. G2: 185.39 ±134.98, p = 0.006, G2: 185.39 ±134.98 vs. G3: 356.46 ±229.12, p = 0.08), and there was a positive correlation with tumor size (r = 0.42, p < 0.05). In the multivariate regression analysis high levels of VEGF-A were not correlated with poor survival (HR = 5.22, 95% CI = –0.6457 to 3.9513, p = 0.19). Conclusions The portal VEGF-A concentration is associated with tumor grade and size. The correlation of portal VEGF-A with poor survival is not clear and needs further investigation.

Insulin, insulin-like growth factor 1 and insulin-like growth factor binding protein 3 serum concentrations in patients with adenomatous colon polyps

Introduction Insulin stimulates colonic mucosal cells proliferation directly and by influencing the concentration of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3). Aim To estimate serum concentrations of insulin, IGF-1, and IGFBP-3 and to determine the relationships between them and colorectal adenoma location, dysplasia grading, histological type, and size. Material and methods The study included 60 patients with colorectal adenomatous polyps found on colonoscopy and confirmed pathologically. The control group consisted of 30 individuals with no positive findings on colonoscopy. All patients had their blood drawn for assessment of insulin, IGF-1, and IGFBP-3 serum concentrations. Results One hundred and nine adenomas (6–40 mm in size) were found in 60 study patients. The average age of patients with multiple polyps was significantly higher than that of patients with single pathologies (61.1 vs. 56.7 years respectively (p < 0.05)). A higher adenoma incidence rate was observed in the distal portion of the colon than the proximal one (50 vs. 10 polyps respectively (p < 0.01)). Higher serum levels of IGF-1 and IGFBP-3 were found in patients with adenomatous polyps than in the control group. The average IGF-1 concentration in patients with adenomas located proximally was also significantly higher compared to those located distally (p < 0.05). The insulin concentration was similar in both groups and not related to clinical data of patients. Conclusions The results indicate the role of IGF-1 and IGFBP-3 in early carcinogenesis of the large intestine, and IGF-1 particularly in malignant transformation in the proximal part of the organ.

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.