The concentration of D-dimers in portal blood positively correlates with overall survival in patients with non-resectable pancreatic cancer.

BACKGROUND: Several recent studies provide evidence that D-dimer (DD) concentration in peripheral blood correlates negatively with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). Contrarily, there are recent evidence indicating that preoperative plasma fibrinogen, but not D-dimer might represent a prognostic factor in non-metastatic gastrointestinal cancers. METHODS: In a single-center prospective study, we enrolled 62 patients undergoing surgery for pathologically confirmed PDAC without detectable venous thrombosis. Intraoperatively, the sample of the blood from the portal vein was obtained. DD concentration in these samples was measured. Patients were followed postoperatively until time of death from any cause. RESULTS: We found that OS for patients with portal blood DD values above 2700 (ng/mL) (n = 22 from 62 patients) was higher by 158% than that for the patients (n = 42) with DD values ≤ 2700 (416 days versus 161 days, p = 0.05). On the contrary to the studies investigating DD concentration in peripheral blood, we have found that patients with higher DD level in the portal vein had longer mean OS than patients with lower ones. CONCLUSIONS: Further investigation is necessary both to confirm our results in a larger patient population and to elucidate the mechanism for the correlation between portal blood D-dimer concentrations and survival time. Along with other authors, we conclude that portal circulation is characterized by unique, biological environment that requires further evaluation.

[Proinflammatory markers serum concentrations in patients with adenomatous colon polyps]. / Ocena stezenia czynników prozapalnych w surowicy chorych z polipami gruczolakowatymi jelita grubego.

BACKGROUND: It has been shown that local chronic inflammation may lead to colorectal carcinogenesis via adenomatous polyps. Tumor necrosing factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) are biomarkers of inflammation and indicators of the immune response to tumors. Their elevated levels were observed in patients with colon adenomas, however their clinical significance is unclear. METHODS: The study included sixty patients with the colorectal adenomatous polyps found on colonoscopy and confirmed pathologically. The control group consisted of 30 individuals with no positive findings on colonoscopy. The aim of our study was to determine the serum levels of TNF-alpha, IL-6 and CRP in colorectal adenomas patients and to assessed the relationships between them and colorectal adenoma location, dysplasia grading, histological type, and size. RESULTS: One hundred nine adenomas (6-40 mm of size) were found in 60 study patients. The average age of patients with multiple polyps was significantly higher than of those with single pathologies (61.1 vs 56.7 years respectively (p < 0.05)). The prevalence of colon adenomas were observed in distal part of colon (83.3%), compared to the proximal part (16.7%; p < 0.01). The TNF-alpha concentration was similar in both group (24.51 +/- 13.50 pg/ml versus 29.61 +/- 14.94 pg/ml; p > 0.05) and not related to clinical data of patients. In contrast, CRP serum concentrations were higher in patients with adenomas located proximally (8.674 +/- 9.19 microg/ml) compared to control group (4.94 +/- 5.53 microg/ml; p < 0.05). There was also no differences between IL-6 serum level in patients with colon adenomas (19.80 +/- 7.44 pg/ml) and control group (20.46 +/-11.83 pg/ml; p > 0.05). Analyzed cytokines serum levels were not associated with size, number, degree of dysplasia and histological type of colon adenomas. CONCLUSION: Our results indicate that CRP may be associated with development of tumors of proximal part of colon.

Gender-Specific Coagulation Profiles of Peripheral and Portal Blood May Help to Differentiate Malignant from Benign Pancreatic Tumour-Pilot Study.

Objective: Pancreatic adenocarcinoma (PDAC) and mass forming chronic pancreatitis (CP) can be easily misdiagnosed due to their resemblances in clinical, radiological, and biochemical criteria. In our previous study, we reported a very high concentration of D-Dimers in portal blood in patients with pancreatic cancer which may help to differentiate malignant from benign pancreatic tumours. In this study, we aim to describe other portal and peripheral coagulation profiles of PDAC in comparison to CP patients, as well to test the hypothesis; thus, it is possible to distinguish pancreatic malignancy and benign tumour based on these parameters. Methods: We included retrospectively 115 patients with the absence of venous thromboembolism (VTE), qualified to surgical treatment due to pancreatic tumours, both PDAC and CP. Patients underwent surgery in General and Transplant Surgery Unit of Medical University of Lodz between December 2011 and February 2014. Patients with distant metastases diagnosed before or during the surgery were excluded. The coagulation profile, which includes fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT), was determined in blood samples from the portal and peripheral vein taken intraoperatively. Results: The fibrinogen level was higher and the aPTT index shortened in the peripheral and portal blood of the PDAC group, which reflects the well-known link between PDAC and general hypercoagulability. Furthermore, these effects are sex-specific. The mean age in the CP group was lower than in the PDAC group (54.63 ± 12.37 vs. 63.77 ± 3.23, p < 0.001) and correlated with the fibrinogen distribution in male patients with CP (portal r = 0.34; p = 0.07; peripheral r = 0.39; p = 0.04). We calculated sex-specific logistic regression models (male: peripheral aPTT and age, AUC: 0.795, female: portal fibrinogen and age, AUC: 0.805), both maintaining the good discrimination properties after V-fold cross validation (0.759, 0.742). Conclusions: Our study shows that the differences between coagulation profiles in PDAC and CP patients not only seems to be a reflection of gender-specific biological features, but also helps to discriminate between them. The main goal of the study was to explore the biology of pancreatic cancer and lay a solid base for further investigations of PDAC biomarkers. This paper is the first to describe the detailed coagulation profile in portal blood in patients with pancreatic solid tumors. At present, the clinical application of our results is not clear; however, we hope that it may improve our understanding of this complex disease.

The application of Montreal classification in different clinical and serological IBD subtypes.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) represents the heterogeneous group of disorders with a wide variety of clinical manifestations. The Montreal classification has been developed recently and its accuracy in categorizing of IBD phenotypes needs to be investigated. The aim of the study was to assess the usefulness of the Montreal classification compared to CAI and CDAI in various disease activity, serological and clinical manifestations of IBD. METHODOLOGY: The study was performed in 125 IBD patients: 71 patients with ulcerative colitis, 31 with Crohn's disease and 23 with IBD unclassified (indeterminate colitis). Disease activity and clinical course were assessed using Montreal classification, Clinical Activity Index and Crohn's Disease Activity Index. pANCA and ASCA were measured with ELISA, using widely used, commercial antibody panel (Cogent Diagnostics and Genesis Diagnostics and MedTek kits). RESULTS: No significant correlation has been found between pANCA/ASCA presence and disease activity using CAI and CDAI. ASCA and pANCA-/ASCA+ antibodies pattern had been detected more often in patients with Crohn's disease after surgery, with localization in small or small and large intestine, without perianal lesions and with early disease onset. CONCLUSIONS: Correlations between serotype and certain clinical phenotype are present, which could potentially be of value in the classification of patients particular treatment regimen. We have noticed that clinical course assessment using Montreal classification shows precisely real CD patients state.

Elevated preoperative levels of CA 19-9 and CA 125 predicts overall survival time in the pancreatic adenocarcinoma. Single institution series.

<b>Introduction: </b>Pancreatic cancer is a devastating disease, being the seventh cause of cancer-related deaths worldwide. Its aggressiveness is due to its specific biology and the late diagnosis of cancer. Therefore, the prognosis for patients suffering from this cancer is dismal, with 5-year overall survival rate of around 6-10%. Up to date, only a complete surgical resection of the cancerous entity warrants a significant improvement in patients' survival. Nevertheless, the pancreatic cancer's biology is still not fully elucidated, so that the accuracy of prognosis for certain patients is highly uncertain. Consequently, the importance of both clinical and basic research aiming to reveal the crucial molecular factors affecting long-term prognosis should be highlighted. There is a growing number of evidence that biomarkers of PC not only reflect the presence of tumor itself but also present a "hint" regarding its physiology. Thus the aim of this study was to assess the levels of commonly measured biomarkers and their influence on patients' overall survival. <br><b>Materials and methods: </b>The retrospective analysis of data on 129 patients admitted to our Department due to the diagnosis of pancreatic cancer was carried out. On the day of admission all the patients had their levels of CA_19-9, CA₁₂₅, CEA and CA_15-3 measured. The overall survival (OS) was defined as time elapsing from the day of admission to the day of death. The Kaplan- Meier curves were built for all potential factors, Cox regression model was applied to carry out a multivariate analysis. <br><b>Results: </b>We retrospectively analyzed 129 patients with a mean age of 62 years. As many as 95 of them had an unresectable lesion and 34 underwent curative operation. In total, the analyzed patient group was characterized by a median survival of 7 months and 12 days. Cumulative 1-year, 2-year and 4-year survival rates were 35%, 16% and 15%, respectively. In univariate analysis, factors such as age >= 60, inoperable lesion, CA_19-9 >= 200, CA₁₂₅ >= 20 and Neutrophile to Lymphocyte Ratio (NLR) >= 5 were associated with a lower median OS. In multivariate analysis, three factors, CA_19-9 >= 200, CA₁₂₅ >= 20 and age >= 60, were found to be statistically significant. Indeed, patients possessing all of them noted much poorer outcomes regarding OS factors: 89 days versus 235 days for the other patients (log rank test P = 0.02). <br><b>Conclusions: </b>Our study fortifies the evidence that preoperative levels of CA_19-9 and CA₁₂₅ have a direct influence on the longterm OS. Interestingly, in our patient group, the correlation of biomarkers with OS was higher than that of resectability. However, our study has some limitations regarding, for instance, the lack of data on chemotherapy, comorbidities etc. In the view of recent molecular studies on mucin involvement in PC development, it provides a strong clinical evidence to prove their importance.

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

INTRODUCTION: Leptin, 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. AIM: The aim of this study is to determine the concentration of leptin, adiponectin, and resistin in patients with adenomatous polyps and colorectal cancer. METHODS: The 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. RESULTS: Among 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). CONCLUSION: We 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.

Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass.

BACKGROUND: Pancreatic cancer (PDAC) will have been the second leading cancer-related death in the United States by 2020, according to current estimation. Its late manifestation and the lack of good early detection methods are the cause of extremely low survival rates. Therefore, there is an urgent need to develop highly sensitive and specific marker. GDF-15, a member of TGFbeta family, has recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE: Our aim was to assess the potential of GDF-15, IL-17, IL-23 serum concentration, and the panel of PDAC markers in differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Sixty-three consecutive patients operated on due to pancreatobiliary lesions were enrolled in this study. Levels of CEA, CA125 and Ca19-9 were assessed using standard laboratory protocols. A sample of serum was collected prior to the surgery via central line. Levels of GDF-15, Il-17, Il-23 were measured using a ELISA kit. After standard pathological examination of specimens obtained on surgery, patients were divided into 2 groups: 42 patients with pancreatic adenocarcinoma and 21 patients with focal chronic pancreatitis. RESULTS: Mean GDF-15 concentration in patients with CP vs PDAC was 2247.95 (± 179.27) vs 7694.58 (± 1878.94) [pg/mL] respectively (p= 0.011). Mean concentration of Il-17, Il-23, Ca19-9, Ca125, Ca15-3, CEA in patients with CP and PDAC was 862.36 (± 30.84) vs 841.83 (± 33.94) p= 0.833; 127.85 (± 5.87) vs 127.51 (± 9.74) p= 0.175; 34.95 (± 23.34) vs 266.62 (± 49.7) p= 0.001; 13.4 (± 1.6) vs 39.27 (± 6.85) p= 0.005; 18.4 (± 1.48) vs 20.2 (± 1.38) p= 0.416; 1.96 (± 0.38) vs 5.93 (± 1.74) p= 0.004 respectively. In order to compare these markers with the routinely used ones, ROC curve was built. CA19-9 with clinically used cut-off point of ⩾ 36 IU/mL has specificity of 90.5% and sensitivity of 57.14%. At the same time GDF-15 with the optimal cut-off point of 2.7 ng/mL has specificity of 76.19% and sensitivity of 73.8%. Although in our research group CA19-9 has an excellent specificity, its usefulness is hampered by its low sensitivity. On the other hand, GDF-15 parameters are well-balanced making it a more useful biomarker of PDAC. CONCLUSIONS: In conclusion, GDF-15 is more accurate than Ca19-9 in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Interleukin 17 and 23 cannot be considered as PDAC biomarkers. GDF-15 concentration in serum should be further investigated in order to assess their usefulness in pancreatic adenocarcinoma diagnosis.

Predicting maximum Roux-en-Y gastric bypass-induced weight reduction--preoperative plasma leptin or body weight?

BACKGROUND: Weight loss after bariatric surgery varies between patients, and predicting the extent thereof is often inaccurate. The aim of this study was to assess the potential of preoperative plasma leptin and body weight in predicting the maximum weight loss within 2 years after Roux-en-Y gastric bypass (RYGBP). METHODS: The study comprised 68 subjects (39 women, 29 men; mean age 36.4 +/- 10.2 years, body weight 130.3 +/- 24.8 kg, BMI 44.4 +/-6.8 kg/m2) undergoing RYGBP who were followed for 2 years. Baseline and maximum follow-up plasma leptin and weight were assessed. RESULTS: Mean maximum weight reduction of 50.5 +/- 19.1 kg (38.0 +/- 9.0%, range 24-100 kg) was noted at 15 +/- 4 months after RYGBP. Baseline plasma leptin was 37.9 +/- 14.5 ng/ml, and decreased to 17.4 +/- 8.1 ng/ml (P < 0.001) at maximum weight reduction. No significant correlation between baseline plasma leptin and absolute or relative weight reduction or minimum body weight achieved was noted. No significant plasma leptin threshold which would be predictive for any consistent extent of weight loss was found. However, baseline body weight was a strong determinant of minimum body weight attained (r = 0.67; P < 0.01) and of maximum absolute weight reduction (r = 0.81; P < 0.01). CONCLUSION: Preoperative plasma leptin concentration cannot be used as a predictor of weight reduction following RYGBP. Preoperative body weight is a reliable predictor of post-RYGBP weight loss.

[Serum concentration of insulin, C-peptide and insulin-like growth factor I in patients with colon adenomas and colorectal cancer]. / Stezenie insuliny, C-peptydu i insulinopodobnego czynnika wzrostu I w surowicy chorych z polipami i rakiem jelita grubego.

UNLABELLED: Colon carcinogenesis is a multi-steps process in which many growth factors are involved. In some studies the increased risk of colon cancer development was observed in patients with diabetes mellitus type 2 with accompanying hyperinsulinemia. It is also known that insulin-like growth factor I (IGF-I) plays an important role in proliferation, growth, differentiation and inhibiting apoptosis of both epithelial and carcinoma cells. The aim of the study was to evaluate the serum concentration of insulin, C-peptide and IGF-I in patients with colon adenomas and colorectal cancer. MATERIALS AND METHODS: In 17 patients with colon cancer, 32 patients with colon adenomas and in 12 healthy persons the serum concentration of insulin, C-peptide and IGF-I was determined using ELISA kits. RESULTS: In patients with colon cancer significantly higher serum IGF-I concentration comparing to the control group was observed (85.66 ng/ml vs. 60.96 ng/ml; p < 0.05). Higher IGF-I concentration was also observed in patients with distal tumors comparing to the proximal localisation (95.40 ng/ml vs. 64,65 ng/ml, p < 0.05) and in more differentiated tumors (84.36 ng/ml vs. 75.24 ng/ml). Similarly, higher C-peptide concentrations were observed in distal tumors (635.64 pmol/ I vs. 578.69 pmol/l) and in well-differentiated carcinoma (671.32 pmol/ I vs. 575.66 pmol/l). In patients with colon adenomatous polyps we also observed higher serum IGF-I concentrations I comparing to the control group (82.1 ng/ml vs. 60.96 ng/ml), in high dysplasia adenomas (84.12 ng/ml vs. 79.67 ng/ml) and in smaller adenomas to 1 cm diameter (97.98 ng/ml vs. 73.28 ng/ml), but the differences were not significant. We also observed higher concentration of C-peptide in patients with low grade dysplasia adenomas (665.24 pmol/l vs. 498.13 pmol/l) and with small polyps (611.51 pmol/l vs. 514.89 pmol/l). There were no differences in serum concentration of IGF-I and C-peptide between patients with tubular and villous adenomas. There was no statistical difference observed in insulin serum concentration in all groups of patients. CONCLUSIONS: IGF-I is probably involved particularly in the early stage of colon carcinogenesis.

[Resistin-- a new laboratory marker useful in diagnosis of acute pancreatitis?]. / Rezystyna--nowy marker laboratoryjny przydatny w rozpoznaniu ostrego zapalenia trzustki?

UNLABELLED: Acute pancreatitis (AP) is the severe disease with high mortality and morbidity which pathomechanism is still not clearly elucidated yet. Serum pro-inflammatory cytokines like Interleukin-18, TNF alpha, and C-reactive protein (CRP) are elevated in patients with AP, particularly of severe clinical course. Adipocytes hyperplasia is a trigger factor that initiates chronic inflammatory state which release adipocytokines, like TNF alpha or leptin or resistin. The aim of the present study was to assesses the serum resistin concentrations in AP patients and evaluate the correlation between resistin and the well known inflammation marker--CRP. MATERIAL AND METHODS: The study group comprised 30 patients with acute pancreatitis class B according to Balthazar scale, aged 35-82, in which during first 24h of hospitalization serum resistin and CRP has been assessed. Control group consisted of 30 healthy volunteers, aged 33-76. RESULTS: The mean serum resistin concentration was significantly higher in AP patients than in controls (8,38 +/- 4.87 ng/ml vs. 3.58 +/- 1.51 ng/ml) (fig. 1). The positive correlation between serum resistin and CRP concentrations has been observed (r = 0.57, p < 0.05) (fig. 2). CONCLUSIONS: The results of our study suggest, that the serum concentration of resistin may represent the useful additionary marker of inflammatory response in AP

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 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.

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.

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.

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.

Prostaglandin E2 (PGE2) in portal blood in patients with pancreatic tumor--a single institution series.

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.