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.

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.

Roux-en-Y gastric bypass as a cure of iatrogenic - steroid induced diabetes.

BACKGROUND: Steroid-induced diabetes (SIDM) is a frequently found clinical condition since steroid-based therapies continue to be widely used in hospital and ambulatory care. Recommended optimal treatment of SIDM includes similar glucose lowering strategies as in type 2 diabetes. This typical management cannot cure the disease, it can only control blood glucose. Recently, bariatric surgery has emerged as an effective treatment for type 2 diabetes mellitus. However, up to now, the usefulness of bariatric surgery in treatment of SIDM has not been evaluated. CASE REPORT: A 49-year-old female oncologic patient with steroid induced diabetes was referred for surgical treatment to the Department of General and Transplant Surgery in November 2009. Six years earlier, she underwent successful oncologic treatment with cladribine and high doses of steroids due to hairy cell leukemia. Finally complete hematologic remission with normalization of morphology and reduction of spleen size has been obtained. Prior to steroid treatment, blood glucose and urine examinations were within normal range. The patient was non-obese and had no family history of diabetes. Nevertheless, the patient developed diabetes secondary to corticosteroid therapy, poorly controlled by oral hypoglycemic agent (acarbosum), successfully converted to insulin therapy. Upon admission to the Department of General and Transplant Surgery, the patient was treated with 58 units of insulin per day. The patient was scheduled for Roux-en-Y gastric bypass (RYGB). Insulin was withdrawn immediately after the surgery and within six months after the surgery, plasma glucose and glycated hemoglobin (HbA1c-5.5%) levels reached and remained within normal range. Currently, eight years after surgery, body weight and BMI are 80 kg and 27.68 kg/m2, respectively. Plasma glucose and glycated hemoglobin are also normal. Importantly, from an oncological point of view, the patient has remained in continuous complete remission since October 2003. CONCLUSIONS: Our report is the first to our knowledge describing the effect of gastric bypass surgery on SIDM in a patient with prior hematologic malignancy. It proves that surgically altered anatomy of the small intestine improves glucose homeostasis previously disturbed with pro-diabetic medication.

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.

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.

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 patient's 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.

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.

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.

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 Lódz, 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.