A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of endocrine hypertension that is diagnosed following a two-step process: an initial screening test, based on the serum aldosterone-to-renin ratio (ARR), followed by a relatively laborious and time-consuming confirmatory test to document autonomous aldosterone (ALD) secretion. OBJECTIVE: The aim of this study is to develop a simple overnight test for the early and definite diagnosis of PA. PATIENTS AND METHODS: Totally, 148 hypertensive patients underwent a fludrocortisone-dexamethasone suppression test (FDST) and the new overnight diagnostic test (DCVT) using pharmaceutical RAAS (renin-angiotensin-aldosterone system) blockade with dexamethasone, captopril and valsartan. RESULTS: Of the 148 patients, 45 were diagnosed as having PA and they all normalized their elevated blood pressure (BP) after administration of spironolactone or eplerenone. The remaining 103 patients were considered as having essential hypertension and served as controls. Using ROC analysis, the estimated sensitivity and specificity were 91 and 100%, respectively, for the post-FDST ARR, whereas 98% and 89% and 100% and 82% for the post-DCVT ARR and post-DCVT ALD, respectively, with selected cutoffs of 0.32ng/dL/µU/mL and 3ng/dL respectively. However, considering these cutoffs simultaneously, the estimated sensitivity and specificity were 98 and 100% respectively. Applying these cutoffs, the diagnosis of PA was confirmed in 44 (98%) of the 45 patients who were considered to have the disease. CONCLUSIONS: In this study, a highly sensitive and specific, low-cost, rapid, safe, and easy-to-perform diagnostic test (DCVT) for PA is described, which could be utilized on an outpatient basis potentially substituting conventional laborious testing.

Inducible nitric oxide synthase expression and its prognostic significance in colorectal cancer.

Nitric oxide synthases (NOS) are expressed in colorectal cancer. The aim of this study was to examine the inducible NOS (iNOS) expression in colorectal cancer and to investigate its prognostic relevance. Tissue sections of primary tumors from 132 patients undergoing curative resection for colorectal cancer were immunohistochemically examined for iNOS expression. The expression pattern of iNOS was correlated with various clinicopathological characteristics and survival. iNOS immunoreactivity was observed in the cytoplasm of tumor epithelial cells in 60 patients (45.5%) and positively correlated with lymph node involvement (p = 0.019). No significant correlation was found between iNOS expression and various clinicopathological characteristics, including age, gender, tumor location, tumor size, tumor grade, T stage, and Union International Contra la Cancrum (UICC) stage. Survival analysis showed a significant correlation between iNOS-positive tumors and poor disease-specific survival (p < 0.0001), with independent prognostic significance in multivariate analysis (HR = 4.42; p < 0.0001). Patients with stage II disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p < 0.0001). In addition, patients with stage III disease and iNOS-positive tumors had significantly worse disease-specific survival than those with iNOS-negative tumors (p = 0.001). The ability of iNOS to predict outcome in colorectal cancer patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility.

Prognostic value of COX-2 immunohistochemical expression evaluated by quantitative image analysis in colorectal cancer.

Epidemiological studies have shown that the inducible form of cyclooxygenase (COX-2) may be involved in colorectal carcinogenesis, but it is controversial whether its expression is a prognostic factor for colorectal cancer. The aim of the study was to examine the expression of COX-2 in colorectal cancer and investigate its prognostic relevance. Tissue sections of primary tumors from 132 patients undergoing curative resection for colorectal cancer were immunohistochemically examined for COX-2 expression. The levels of intensity and extent of COX-2 staining were quantified by use of a computerized image analysis system and correlated with various clinicopathological characteristics and survival. COX-2 immunoreactivity was observed in the cytoplasm of tumour epithelial cells of all colorectal cancer tissues examined. No significant correlation was found between levels of intensity and extent of COX-2 staining and various clinicopathological characteristics, including age, gender, tumor location, tumor size, tumor grade, depth of invasion, lymph node status and TNM stage. There was an inverse correlation between intensity and extent of COX-2 staining scores (Spearman's rho=-0.414; p<0.001). To analyze the prognostic value of intensity and extent of COX-2 staining, the patients were divided into four groups with respect to quartiles (< or =25; >25 to < or =50; >50 to < or =75; and >75). No significant disease-specific survival difference among the quartiles was found based on analysis of intensity (p=0.689) and extent (p=0.975) of COX-2 staining. These results suggest that the expression of COX-2 protein has no significant impact on the outcome of patients with colorectal cancer.

Prognostic significance of VEGF expression evaluated by quantitative immunohistochemical analysis in colorectal cancer.

BACKGROUND: The prognostic value of vascular endothelial growth factor (VEGF) expression in colorectal cancer is still unclear, as shown by the discordant results still reported in the literature. The aim of the study was to examine the expression of VEGF in colorectal adenocarcinomas and investigate its prognostic relevance. MATERIALS AND METHODS: VEGF expression was investigated by immunohistochemistry performed on tissue microarrays, in a series of 117 colorectal cancer specimens. The VEGF staining intensity in the cytoplasm of tumor cells was quantified using a semi-automated computerized image analysis and correlated with various clinicopathological characteristics and survival. RESULTS: All tumors evaluated showed expression of VEGF, which were further divided into 49 high expression and 68 low expression tumors by their staining intensity. In tumors with lymph node metastasis, the intensity of staining of VEGF was more intense than in those without (P < 0.0001). Furthermore, the intensity of VEGF staining was more intense in Stage III tumors than those in Stage I/II (P < 0.0001). The mean number of involved lymph nodes in tumors with high VEGF staining intensity was significantly greater than in those with low staining intensity (P = 0.031). Survival analysis showed a significant correlation between high levels of VEGF staining intensity and poor disease-specific survival (P < 0.0001), with independent prognostic significance in multivariate analysis (RR = 3.5, P < 0.0001). In addition, patients with Stage II disease and high staining intensity of VEGF had a significantly worse disease-specific survival than those with low staining intensity (P = 0.001). CONCLUSIONS: VEGF expression in colorectal cancer seems to be an independent prognostic marker of tumor behavior and may be useful to identify patients with unfavorable clinical outcome.

Total thyroidectomy for the treatment of thyroid diseases in an endemic area.

INTRODUCTION: Thyroidectomy is a common operation with very low mortality and an acceptable morbidity rate. Total thyroidectomy has become the predominant type of surgery used today for the treatment of thyroid diseases. In this retrospective study, we analyzed the complications of thyroid surgery according to the operative technique used in our department. MATERIAL AND METHODS: A retrospective analysis was performed for all patients who underwent thyroid surgery during the previous 11 years. The period under study was divided into two sections: phase A (1995-1999) and phase B (2000-2005). Patient characteristics, type of operation, histologic diagnoses and postoperative complications were compared in the two study periods according to the type of surgery. RESULTS: A total of 264 patients between the ages of 18 and 89 underwent thyroid surgery during the study period (133 in phase A and 131 in phase B). Overall histopathological diagnoses were nodular goiter (54.9%), hyperplastic nodules (14.7%), adenoma (8.3%), thyroid cancer (18.2%), and Hashimoto thyroiditis (3.8%). Total thyroidectomy was performed in 91 patients in phase A versus 115 patients in phase B (P < 0.001), whereas the use of subtotal thyroidectomy and lobectomy decreased over time. A trend toward increased morbidity was noted in phase B. Seven patients had hypocalcemia in phase A, whereas 11 patients had hypocalcemia in phase B. Similarly, 5 patients had some degree of vocal cord paralysis in phase A, compared with 7 in phase B (P > 0.05). Morbidity was significantly increased in the case of cancer or reoperation. CONCLUSION: Despite the slightly higher risk of complication associated with total thyroidectomy, this has gradually replaced more conservative approaches for the treatment of both benign and malignant thyroid diseases. Reoperations and surgery for thyroid cancer carried a higher risk of complications.