Comparison of clinical usefulness of serum Ca125 and CA19-9 in pancreatic adenocarcinoma diagnosis: meta-analysis and systematic review of literature.

INTRODUCTION: Pancreatic adenocarcinoma remains one of the most lethal cancers. The only recommended biomarker CA19-9 proves to be not accurate enough to establish a certain diagnosis. Therefore, a determination of usefulness of other biomarkers is essential. Our aim was to compare the specificity and sensitivity of Ca125 and CA19-9 by means of meta-analysis. The systematic review of combined tests (CA19-9 + Ca125) was also performed. METHODS: We conducted a systematic search of Medline (via PubMed) and Ovid. After screening of abstracts and the assessment of full-texts, nine studies (number of patients, n = 1599) were included. Hierarchical summary receiver under operator curve (hsROC) model was applied to estimate the diagnostic accuracy. RESULTS: CA19-9 sensitivity and specificity were 0.748 (95%CI 0.676-0.809) and 0.782 (95%CI 0.716-0.836), respectively. These values were estimated on 0.593 (95%CI 0.489-0.69) and 0.754 (95%CI 0.817-0.668) for Ca125. Regarding the heterogeneity of studies, a strong threshold effect for Ca125 and moderate one for CA19-9 were found. CONCLUSIONS: Our meta-analysis did not prove the superiority of Ca125. It should be nevertheless noted that the sparsity of studies precludes accurate analysis of various factors' influence. The review of proposed combined tests shows that CA19-9 + Ca125 models are generally characterized by higher sensitivity.

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.

Thyroid hormones concentration in portal and peripheral blood in patients with pancreatic cancer: Preliminary study.

BACKGROUND: The prognostic value of D-dimers concentration in portal blood in patients with pancreatic cancer has been established in several studies. Thyroid hormones and their receptors, especially T3 also seems to have a specific role in process of neoplasia and metastatic spread. OBJECTIVE: The aim of the study was to look for changes of thyroid hormones concentration between portal and peripheral blood. METHODS: We included prospectively 8 patients with pancreatic cancer, without liver dysfunction, qualified to surgical treatment. D-dimers, THS, fT3, fT4 concentration was determined in blood samples from portal and peripheral vein taken intraoperatively. RESULTS: The difference and quotient of portal and peripheral concentration of D-dimers, THS, fT3 and fT4 was calculated (D-dimer-; THS-; fT3-; fT4-d and -q). The level of D-dimers measured in portal blood was > 2700 ng/mL in 3 patients. The peripheral fT3 level was significantly higher In high portal D-dimers group. FT3 change coefficients showed strong statistically significant negative correlation with portal D-dimer concentration level. CONCLUSIONS: We suggest that fT3 or its receptors can influence progression of pancreatic malignancies. The results of this study are also a new evidence that both fT3 and portal D-dimers are biologically linked to intensity of local neoplastic process. Nevertheless, deeper knowledge about portal circulation probably constitute missing part in understanding nature of pancreatic neoplasia. Investigations both on larger group and in the field of basic sciences are needed.

Comparison of Endoscopic Submucosal Dissection for Primary and Recurrent Colorectal Lesions: A Single-Center European Study.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is an acknowledged endoscopic technique for the management of early gastrointestinal neoplasia. The clinical experience and the research from the Eastern ESD centers show that experienced endoscopists can successfully treat even the most demanding recurrent colorectal lesions. AIM: The aim of this study was to analyze the clinical outcomes of the management of recurrent colorectal lesions in comparison with those of primary lesions in the setting of high-volume European center. METHODS: A retrospective analysis of 298 cases (228 primary lesions and 70 recurrent lesions) performed by a single endoscopist was carried out. Evaluating learning curves for both primary and recurrent lesions, cumulative sum analysis was performed. RESULTS: Primary lesions had ∼9% higher R0 resection rate (86.84% versus 78.51%). Yet, this difference did not reach statistical significance (P = .091). The presence of recurrent lesion and lengthy procedure (≥150 min) are risks factors of R1 resection, whereas rectal localization of the lesion was associated with lower risk of R1 resection. The cumulative R0 of 80% was achieved at 36th procedure in the primary lesions group, whereas for the recurrent lesions it was reached at 50th procedure (overall 229 procedures). CONCLUSIONS: Our study underlines the importance of proper experience in ESD before the management of recurrent lesions. Even after the completion of high volume of primary lesions, first recurrent lesions can pose a challenge. Nevertheless, the final outcomes are promising, as the complications do not pose a serious risk to the patients and high R0 resection rate can be achieved in a reasonable timeframe.

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.

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.

One stage onlay hernia repair with abdominoplasty in patients following gastric bypass surgery

PURPOSE: 1. Evaluation of results after one-time incisional hernia repair (IHR) modo on-lay and abdominoplasty (Ab-pl) in patients after loss of weight following previous Roux-en-Y Gastric Bypass ­ RYGB. 2. Analysis of differences in quality of life (QL) changes in bariatric patients before RYGB, as well as before and after abdominal contouring operation.tion. MATERIAL AND METHODS: Clinical analysis involved 20 patients with abdominal disfigurement (following RYGB, and massive weight loss) who underwent one-time IHR using on-lay method together with abdominoplasty. We estimated postoperative results, as well as changes in QL, before RYGB and before and after abdominal contouring procedure (based on DAS 24 and SF-36 scales) in comparison with stage before surgeries. RESULTS: Complications - abnormal wound healing (infection, local necrosis) and pneumonia were found in two persons, seroma in two cases, whereas dysesthesia in four patients. We confirmed QL improvement in all aspects after each stage of treatment. CONCLUSIONS: 1. One-stage on-lay hernia repair and abdominoplasty is a safe method improving the functioning of patients. 2. All stages of bariatric treatment resulted in gradual improvement of the quality of life. 3. High BMI in patients before onlay incisional hernia repair with abdominoplasty increases the risk of complications, which is connected with longer hospital stay.

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.

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.

Colorectal endoscopic submucosal dissection (ESD) in the West - when can satisfactory results be obtained? A single-operator learning curve analysis.

OBJECTIVES: Up to date we lack a detailed description of the colorectal endoscopic submucosal dissection (ESD) learning curve, that would represent the experience of the Western center. The aim of this study was to define the critical points of the learning curve and to draw up lesions qualification guidelines tailored to the endoscopists experience. MATERIALS AND METHODS: We have carried out a single center prospective study. Between June 2013 and December 2016, 228 primary colorectal lesions were managed by ESD procedure. In order to create a learning curve model and to carry out the analysis the cases were divided into six periods, each consisting of 38 cases. RESULTS: The overall en bloc resection rate was 79.39%. The lowest en bloc resection rate (52.36%) was observed in the first period. After completing 76 procedures, the resection rate surged to 86% and it was accompanied by the significant increase in the mean procedure speed of ≥9 cm2/h. Lesions localization and diameter had a signification impact on the outcomes. After 76 procedures, en bloc resection rate of 90.9 and 90.67% were achieved for the left side of colon and rectum, respectively. In the right side of colon statistically significant lower resection rate of 67.57% was observed. CONCLUSION: We have proved that in the setting of the Western center, colorectal ESD can yield excellent results. It seems that the key to the success during the learning period is 'tailoring' lesions qualification guidelines to the experience of the endoscopist, as lesions diameter and localization highly influence the outcomes.

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.

Toxins vapC and pasB from prokaryotic TA modules remain active in mammalian cancer cells.

Among the great number of addictive modules which have been discovered, only a few have been characterized. However, research concerning the adoption of toxins from these systems shows their great potential as a tool for molecular biology and medicine. In our study, we tested two different toxins derived from class II addictive modules, pasAB from plasmid pTF-FC2 (Thiobacillus ferrooxidans) and vapBC 2829Rv (Mycobacterium tuberculosis), in terms of their usefulness as growth inhibitors of human cancer cell lines, namely KYSE 30, MCF-7 and HCT 116. Transfection of the pasB and vapC genes into the cells was conducted with the use of two different expression systems. Cellular effects, such as apoptosis, necrosis and changes in the cell cycle, were tested by applying flow cytometry with immunofluorescence staining. Our findings demonstrated that toxins VapC and PasB demonstrate proapoptotic activity in the human cancer cells, regardless of the expression system used. As for the toxin PasB, observed changes were more subtle than for the VapC. The level of expression for both the genes was monitored by QPCR and did not reveal statistically significant differences within the same cell line.