The Predictive Ability of the Glasgow Prognostic Score and Variants in Both Deceased Donor and Living Donor Liver Transplantation for Hepatocellular Cancer.

AIM: Liver transplantation (LT) is the most promising treatment method in hepatocellular cancer (HCC). Due to the shortage of organ donors and the possible risks associated with living donation, the selection of patients for LT is critical. The aim of this study is to investigate the predictive ability of the Glasgow Prognostic Score (GPS), modified GPS (mGPS), and hepatic GPS (hGPS) on prognoses in a patient group who underwent deceased donor LT (DDLT) or living-donor LT (LDLT) for HCC. PATIENTS AND METHODS: This study includes 62 DDLT and 55 LDLT patients who underwent LT for HCC between 1998 and 2016 in a single center. The study endpoints were recurrence, 0- to 1-year mortality, 0- to 3-year mortality, mortality, and overall survival (OS). RESULTS: The median follow-up time was 70.24 ± 48.47 months. GPS and hGPS positivity were found to be prognostic indicators of 0- to 3-year mortality and overall mortality in DDLT (P = .012, P = .006; P = .044 and P = .022 respectively). In the LDLT group, GPS was found to be effective in predicting 0- to 1-year and 0- to 3-year mortality (P = .045, P = .022 respectively); GPS and hGPS were also found to be effective in predicting overall mortality (P = .001 and P = .046 respectively). The OS was significantly longer in the GPS 0 group and hGPS 0 group compared to the GPS 1-2 and hGPS 1-2 group in both DDLT and LDLT. CONCLUSION: The findings of this study and the literature indicate that using GPS and hGPS is appropriate in selecting patients with HCC who are candidates for LT.

Incidence of Late Acute Rejection in Living Donor Liver Transplant Patients, Risk Factors, and the Role of Immunosuppressive Drugs.

INTRODUCTION: Late acute rejection (LAR) is a clinical manifestation that occurs 6 months after liver transplantation, shows histopathologic features different from those of acute rejection, and is the cause of a high prevalence of morbidity and mortality. METHODS: In this study, hospital records of 211 living donor liver transplantation (LDLT) patients who underwent surgery in our clinic between June 2000 and February 2014 were reviewed retrospectively. The patients were ≥ 18 years old and were followed for ≥ 6 months. RESULTS: Of the 211 patients, 21 (9.9%; 16 males, 5 females) developed LAR. The mean age of the patients was 46 years (range, 33-58). The mean follow-up period was 61.2 months (range, 6-152) and the median time to development of LAR was 26.4 months (range, 7-77). In our study, patients who received cyclosporine and mycophenolate mofetil (MMF) treatment developed more LAR than did patients who received tacrolimus and MMF therapy (P = .05). In addition, the incidence of LAR in patients who underwent LDLT was significantly greater in the ABO-matched groups than in the ABO identical group (P = .028). CONCLUSIONS: Development of LAR and serious complications related to it can be avoided if liver transplant recipients are followed regularly and closely in outpatient clinics after transplantation.

Hypoglycemia induced by long-acting somatostatin analogues in a patient with nonfunctional neuroendocrine tumor.

Somatostatin and its long-acting analogues are effective in symptom control in patients with functional neuroendocrine tumors; they are also able to control tumor growth. Somatostatin analogues are safe and generally well tolerated. In some cases they may cause serious complications. Somatostatin analogues are potent inhibitors of growth hormone (GH) and glucagon secretion. They cause impairment of hepatic glucose output and delay in intestinal absorption of carbohydrates. Patients with huge tumor mass and multiple liver metastases have increased risk of tumor-induced hypoglycemia. In these patients, long-acting octreotide may trigger serious hypoglycemia. The patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia. Herein, we present a patient with severe and prolonged hypoglycemia after long-acting octreotide treatment.

Synchronous appearance of male breast cancer and pancreatic cancer 15 years after the diagnosis of testicular cancer--report of a case.

The frequency of new neoplastic diseases among patients cured of testicular cancer is higher than in normal population. For these patients, synchronous occurrence of multiple neoplasms is not common. Also, less than 1% of all cases of breast cancer occur in males. We present herein a case having both breast and concurrent pancreatic cancer after being effectively treated for testicular cancer. To the best of our knowledge, this is the first case of synchronous breast and pancreatic cancer in a male patient following testicular cancer. Second cancer is the most severe long-term complication of chemotherapy or radiotherapy for patients with testicular cancer and the possibility of multiple cancers has to be taken into consideration when multiple lesions are present.

Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor levels in non-alcoholic steatohepatitis.

AIM: This study was conducted to demonstrate the plasminogen activator inhibitor- 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag) levels in non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Twenty-seven patients with biopsy-proven NASH and 18 healthy controls (HC) were recruited for the study. Anthropometric data, liver histology (no.=20) and laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded. RESULTS: When compared with HC, patients with NASH had higher body weight, higher waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG) levels and higher homeostasis model assessment (HOMA) scores. The mean plasma PAI-1 levels of patients was found to be higher than HC (87.60 ng/ml vs 30.84 ng/ml p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly lower (8.69 microg/ml vs 12.19 microg/ml p=0.000). PAI-1 levels were correlated with systolic blood pressure, age, body weight, transaminases, waist circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to be negatively correlated with transaminases, waist circumference, and body weight. In multiple regression analysis, BMI was the independent variable effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag, disease activity score and fibrosis score. HOMA was the independent variable effecting liver fibrosis in our patients. CONCLUSION: In this study we demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence of insulin resistance state. Lower TAFI-Ag levels may be related to the overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver function disturbances may impair TAFI production in NASH. We also showed that NASH patients even with slight elevations of transaminases feature marked insulin resistance and components of metabolic syndrome.

MDCT findings in neuroendocrine carcinoma of the gallbladder: case report.

Neuroendocrine tumors are commonly seen in the gastrointestinal tract, but they are extremely rare in the gallbladder. In this study, sonographic and multidetector-row computed tomographic findings of a patient with neuroendocrine tumors of the gallbladder are presented.

Protective effects of carnitine in an experimental ischemia-reperfusion injury.

BACKGROUND/AIMS: We aimed to determine the role of exogenous carnitine to prevent ischemia-reperfusion damage in liver tissue in experimental model. METHODS: Rats were divided into four groups as Sham (SG), 30% Hepatectomy (HG), ischemia-reperfusion +30% hepatectomy (IRHG) and ischemia-reperfusion+30% hepatectomy+carnitine (IRHCG). Serum AST, ALT and GGT levels have been determined in systemic blood samples (post-hepatic vena cava) and liver tissue and serum carnitine levels in blood samples from portal vein (pre-hepatic blood samples). RESULTS: Serum carnitine levels were significantly higher in IRHCG compared to SG (P < 0.01). Each of the serum AST, ALT and GGT levels were statistically higher in HG, IRHG and IRHCG than SG (P < 0.001). While these values in IRHG were also higher than those in HG (P < 0.001), in IRHCG enzyme levels were significantly lower than IRHG (P < 0.001). Liver tissue damage was less in IRHCG than IRHG statistically (P < 0.001). CONCLUSIONS: This animal model implies that exogenous carnitine supplementation may be helpful in preventing free oxygen radical damage and inflammatory reactions in liver tissue.

Prognostic significance of nuclear morphometry in renal cell carcinoma.

OBJECTIVE: To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study included 65 consecutive patients with RCC who underwent radical nephrectomy and were followed up for a median (range) of 80 (27-138) months. Nuclear morphometry was assessed using a computer-assisted image analysis system on histological sections and characterized by five nuclear variables (area, perimeter, major and minor diameter, and form factor). From the patients' records and pathology specimens, the clinicopathological prognostic variables (histological type, Fuhrman grade and pathological stage) were recorded. The proliferative activity was assessed using immunohistochemical staining with Ki-67 antibody. RESULTS: Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher nuclear grade, proliferative activity and advanced tumour stage. They were significant predictors of disease progression and survival, together with grade, stage, sarcomatoid histology and proliferative activity. Of all significant prognostic factors predicting progression-free survival, only stage was independent (T4 vs T1, hazard ratio 6.55, 95% CI 1.63-26.13, P=0.008). CONCLUSION: Although the significance of these preliminary results must not be overstated, nuclear morphometry might provide significant prognostic information in predicting survival and tumours at high risk of progression in RCC.

CT findings of non-functioning neuroendocrine pancreatic tumors.

Neuroendocrine tumors are rare neoplasms of the pancreas, representing 0.5% of all pancreatic tumors. Approximately, one-third of neuroendocrine tumors are hormonally inactive and called non-functioning neuroendocrine tumors. As these tumors remain clinically silent in their course of growth, they may attain great sizes without causing apparent clinical findings and commonly present in advanced stage. We report three cases of non-functioning neuroendocrine tumors with large sizes and discuss the radiological findings.

Prognostic significance of nuclear morphometry in superficial bladder cancer.

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.

Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas.

OBJECTIVE: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. METHODS: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells. RESULTS: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.

Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder?

OBJECTIVES: To investigate the role of angiogenesis in predicting tumor recurrence and its correlation with established clinicopathologic prognostic factors in superficial transitional cell carcinoma of the bladder. METHODS: The paraffin sections of 80 superficial papillary transitional cell bladder carcinoma specimens were stained with CD31 antibody to label the vascular endothelium using the standard streptavidin-biotin-immunoperoxidase method. The vascular surface density (VSD) equivalent to the vascular surface area per unit of tissue volume and number of vessels per square millimeter of stroma (NVES) were assessed by means of stereology, and these morphometric parameters of angiogenesis were statistically analyzed to interpret the relation to tumor recurrence in addition to tumor stage, grade, size, and number and the presence of carcinoma in situ. RESULTS: VSD and NVES values showed no statistically significant difference between pTa and pT1 tumors or patients with and without recurrence. In contrast, VSD and NVES values were found to increase in higher grade tumors (P = 0.019). VSD values were also higher in patients with coexisting carcinoma in situ in pTa tumors (P <0.001). Tumor number and size and recurrence number and time to the first recurrence did not correlate with any vascular parameters. CONCLUSIONS: Stereologic assessment of angiogenesis does not help to predict recurrence in superficial bladder cancer. Angiogenic parameters appeared to be well correlated with the conventional histologic grading system. Otherwise, the present study did not show any correlation of angiogenesis with any potential prognostic factors. This may be due to the diverse angiogenic pathways occurring in invasive and superficial tumors.

Pancreatic adenocarcinoma: detection and staging with dynamic MR imaging.

OBJECTIVE: To compare the efficacy of dynamic contrast-enhanced MR imaging and spin-echo T1-weighted with and without fat-saturated MR imaging in the detection and staging of pancreatic adenocarcinoma. METHODS AND MATERIAL: Spin-echo T1-weighted, fat-saturated T1-weighted and dynamic breath-hold 2D-FLASH MR imaging were performed in 25 patients with pancreatic adenocarcinoma. MR images were analysed by calculating the CNR between tumor and normal portion of the pancreas. The CNRs calculated at each sequences were compared. A total of 16 out of 25 patients underwent surgery. Preoperative staging according to TNM classification was also done in patients undergoing surgery. RESULTS: The CNR was significantly different (P<0.05) in the arterial phase of dynamic MR images. The accuracy of 'T' staging was 75% for SE T1-W, fat-saturated T1-W and arterial phase of dynamic MR images. CONCLUSION: The CNRs between pancreatic carcinoma and normal pancreas is significantly higher in dynamic MR sequences than the SE T1-W, fat-saturated T1-W sequences. However, the accuracy of tumor staging according to TNM is equivocal to SE T1-W and fat-saturated T1-W images.

Quantification of tumor cellularity and mitotic index in invasive ductal carcinoma of the breast.

OBJECTIVE: To evaluate the use of stereologically estimated tumor cell counts in the mitotic index as well as to investigate its correlation with the currently used method and test the reproducibility of the method. STUDY DESIGN: The stereologic method described by Simpson et al was used to estimate tumor cellularity in 50 invasive ductal carcinomas. Mitotic counts were also performed, and the mitotic index was calculated by the use of estimated tumor cell counts. Estimated cell counts and the mitotic index calculated were compared statistically with the actual cell counts and the traditional mitotic grades, respectively. Interobserver reproducibility of the method was also tested. RESULTS: Stereologically estimated tumor cell counts had a good correlation with actual cell counts (r = .891, P < .001). Besides, the mitotic indices calculated with tumor cell counts (calculated with both estimated and actual cell counts) in the denominator of the fraction of the mitotic index were in agreement with the currently used method (P < .01 for both). There was no statistically significant difference between the counts of two observers (P = .068). CONCLUSION: The suggested method, considering tumor cellularity as an influencing factor, was practical, reproducible and in agreement with the traditional method. This method should be studied in a large group of patients with follow-up data to determine the threshold values for different grades and determine its prognostic value during the disease course.

Immunohistochemical analysis of epidermal growth factor receptor in cyclosporin A-induced gingival overgrowth.

Cyclosporin A (CsA)induced gingival overgrowth represents a tissue of fibrosis and epidermal growth factor (EGF) has been shown to induce extracellular matrix synthesis by fibroblasts. The purpose of this study was to evaluate the expression of EGF-receptor (EGF-r) in frozen sections of CsA-induced overgrown gingival tissue using immunohistochemical and semiquantitative techniques. Gingival biopsies were obtained from 12 renal transplant patients receiving CsA as well as 9 systemically and periodontally healthy individuals. Immunohistochemical staining procedures were carried out in frozen sections of gingival tissue and the expression of EGF-r was compared between the two study groups. The expression of EGF-r was more pronounced in the oral gingival epithelium of CsA-induced overgrown gingiva as compared to those of the clinically healthy gingival specimens. The reactivity in the inflammatory infiltrate and connective tissue cells of both of the study groups was similar. In conclusion, the results of the present study may suggest that CsA affects EGF-r metabolism in gingival keratinocytes resulting in an increased number of cell surface receptors, which may eventually play a role in the pathogenesis of gingival tissue alterations.

Stereologically estimated mean nuclear volume and histopathologic malignancy grading as predictors of disease extent in non-small cell lung carcinoma.

The aim of this study was to investigate the value of the architectural grade, cytologic atypia, mitotic counts and stereologically estimated mean nuclear volume in predicting the stage of disease in non-small cell lung carcinomas. Hematoxylin-Eosin-stained sections from 53 non-small cell lung carcinomas were evaluated in terms of the morphologic and morphometric features mentioned above. Mean nuclear volume was estimated stereologically. Operable and inoperable tumor stages were compared concerning the parameters examined. There was no significant difference between operable and inoperable tumor stages in terms of the architectural grade in both squamous cell carcinomas and adenocarcinomas, although we found a positive correlation between architectural grades and increasing stages in SCC. Significant differences were found concerning atypia, mitosis grades, and the score combining both variables (C2) when comparing operable with inoperable tumor stages in squamous cell carcinomas but not in adenocarcinomas (Chi square, p = 0.013, p = 0.008 and p = 0.008 for squamous cell carcinomas respectively). The mean nuclear volumes of tumor cells in both squamous cell carcinomas and adenocarcinomas showed statistically significant differences between operable and inoperable stages (p = 0.05 and 0.02 respectively). We conclude that an assessment of the proliferative activity and the degree of cell atypia, as well as an estimation of mean nuclear volume in conjunction with architectural grade, may contribute to predicting the extent of the disease and outcome, particularly in SCC. On the other hand, only mean nuclear volume appears to be a useful parameter for determining the course of the disease in adenocarcinomas.

Primary non-Hodgkin's T-cell lymphoma of the thyroid gland complicating Hashimoto's thyroiditis: case report.

This case report presents an extremely rare case of primary non-Hodgkin's T-cell lymphoma of the thyroid gland complicating Hashimoto's thyroiditis and discusses the clinical history, findings, treatment, and prognosis. Although the place of surgery in the treatment of thyroid lymphoma is controversial, in this case, surgery followed by three rounds of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone, and radiation therapy to neck and mediastinum were a very effective treatment for the disease so that no relapse has been detected during 3-year follow-up.

Tumor angiogenesis as a prognostic predictor in pancreatic cancer.

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm2 stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival.