The role of urinary aldosterone for the diagnosis of primary aldosteronism.

When diagnosing primary aldosteronism, the measurement of urinary aldosterone after oral sodium loading is one of the currently recommended confirmatory tests. The aim of the study was to assess the repeatability and interpretation of urinary aldosterone in patients examined for suspected primary aldosteronism. Sixty-four hypertensive patients with suspected primary aldosteronism were prospectively enrolled and examined according to the study protocol. After antihypertensive medications interfering with renin-angiotensin-aldosterone system were withdrawn for at least 2 weeks, the confirmatory testing was performed: oral sodium loading preceded the collection of 24-h urine sample and subsequent saline infusion test. The identical procedures were repeated after 2 weeks. The concordant results of both saline infusion tests served for confirmation/exclusion of primary aldosteronism. Forty-nine patients were included in data analysis. Primary aldosteronism was excluded in 16, and confirmed in 33 individuals. The repeatability of urinary aldosterone was evaluated in 44 patients: the difference of urinary aldosterone levels ranged between 1 and 88% (median 31%). Ninety-three urine samples from 49 patients were used to validate the interpretation of urinary aldosterone in respect to the diagnosis of primary aldosteronism made by saline infusion testing; 96% sensitivity was characterized by urinary aldosterone ≥19 nmol/day, and 96% specificity was associated with urinary aldosterone ≥92 nmol/day. In 22 (45%) patients, urinary aldosterone remained in the "gray" zone between 19 and 92 nmol/day in all provided samples. The estimation of urinary aldosterone excretion after oral sodium loading is associated with marked intraindividual variability, and significant number of inconclusive results.

Thyroid hormone abnormalities in hemodialyzed patients: low triiodothyronine as well as high reverse triiodothyronine are associated with increased mortality.

Numerous abnormalities of thyroid hormones in end-stage renal disease (ESRD) have been described. Our aim was to analyze the impact of these abnormalities on survival. In 167 hemodialyzed ESRD patients, TSH and thyroid hormone levels (T4, fT4, T3, fT3, rT3) were determined. The patients were then prospectively followed up for up to 5 years and the possible impact of any observed abnormalities on their mortality was studied. Only 16.8 % patients had all six tests within the reference range. The pattern of nonthyroidal illness syndrome was found in 56.3 %. Low T3 was particularly common (44.3 %), and clearly associated with increased 6- and 12-month mortality and decreased overall survival (log rank test, P=0.007). Independent of T3 levels (Spearman correlation, NS), increased rT3 was more frequently observed (9.9 %) than expected from the literature, and was also related to increased mortality and decreased survival (log rank test, P=0.021). Increased rT3 may be more common in ESRD patients than previously described, and together with decreased T3 it may serve as an indicator of poor prognosis in subsequent months.

Hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin in patients with liver metastases from colorectal carcinoma.

PURPOSE: Limited data are available regarding the efficacy of hepatic arterial infusion (HAI) of oxaliplatin in patients with liver metastases from colorectal carcinoma (CRC). The aim of the present study was to evaluate the results of HAI of oxaliplatin combined with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with such metastases. METHODS: A retrospective analysis of 22 CRC patients treated with HAI of combination of oxaliplatin and 5-FU and LV was performed. RESULTS: Partial response (PR) was observed in 4 (18%) patients and stable disease (SD) in 7, with an overall disease control rate of 50%. The median progression-free (PFS) and overall survival (OS) were 7 and 11 months, respectively. Two patients treated with first-line treatment underwent subsequent liver resection. In 2 patients, HAI of oxaliplatin, 5-FU and LV was combined with systemic administration of bevacizumab. CONCLUSION: Our data demonstrate reasonable efficacy of HAI with oxaliplatin, 5-FU and LV in patients with liver metastases from CRC.

Repeat chemosensitivity of epithelial ovarian carcinoma in a BRCA1 mutation carrier to paclitaxel/platinum combination chemotherapy.

We present here a case of a BRCA1 mutation carrier with repeat responsiveness of recurrent EOC to paclitaxel/platinum. The patient had complete response to the combination of paclitaxel/platinum in the first line. Subsequent four recurrences also showed a complete response to this combination. The chronic toxicity, including hypersensitivity and nephrotoxicity could be controlled by modifying the regimen. In conclusion, recurrent EOC in BRCA1 mutation carriers may retain sensitivity to paclitaxel/platinum combination chemotherapy, and this combination could be therapy of first choice in this patient population.

Meningeal carcinomatosis as a late complication of brain metastases of epithelial ovarian carcinoma.

The brain represents a rare site of metastasis in patients with epithelial ovarian carcinoma (EOC). In recent decades there has been an apparent increase in the number of EOC patients diagnosed with brain metastases, probably as a result of improved prognosis of patients with advanced tumors, but cases of meningeal carcinomatosis complicating EOC remain rare. A patient with Stage III EOC had brain metastases diagnosed 31 months after primary surgery. The isolated brain metastases were controlled with radiosurgery, surgery and chemotherapy. Forty-five months after the diagnosis of brain metastases, meningeal carcinomatosis was diagnosed which led, despite intrathecal therapy, to a fatal outcome. At autopsy, the disease was limited to the central nervous system. Meningeal carcinomatosis may represent a late fatal complication of brain metastases of EOC.

Urinary neopterin in patients with advanced colorectal carcinoma.

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.

Inhibition of hormone secretion in GH-secreting pituitary adenomas by receptor-subtype specific somatostatin analogues in vitro.

The aim of the study was to determine the inhibitory effects of somatostatin analogues with relative specificity to somatostatin receptor subtype 2 (SSTR2) (BIM-23197), subtype 5 (SSTR5) (BIM-23268), and their combination on GH and PRL secretion in acromegalic adenomas in vitro. Three types of answer were observed: 1. In one resistant adenoma no inhibition was achieved. 2. The GH secretion in six adenomas was suppressed significantly more (p < 0.01 or p < 0.001 using Mann-Whitney U-test in concentration range of 10(-12) to 10(-8) mol/l) with SSTR2 specific analogue BIM-23197 with no additive effect of compounds combination. 3. In three adenomas the potency of BIM-23197 and BIM-23268 was almost equal and the combination of these SSTR2 and SSTR5 specific compounds had statistically significant additive effect (p < 0.05 or p < 0.01 in concentration range of 10(-12) to 10(-8) mol/l). PRL secretion of five adenomas was more suppressed with SSTR5 specific BIM-23268 (statistically significant in concentrations 10(-10) to 10(-8) mol/l). In conclusion the somatostatin analogue BIM-23268 had an additive effect on suppression of GH secretion in a subset of adenomas, where both SSTR2 and SSTR5 were involved. This effect was not observed in the majority of tumours, where the inhibitory effect seems to be mediated via SSTR2 only.

Regional administration of irinotecan in combination with 5-fluorouracil and leucovorin in patients with colorectal cancer liver metastases--a pilot experience.

BACKGROUND/AIMS: Regional chemotherapy represents an effective approach for the control of isolated liver metastases of colorectal cancer. Fluoropyrimidines have been the basis of systemic and regional chemotherapy of this disease for several decades, but recent studies have demonstrated that the addition of irinotecan (CPT-11) ameliorates the results of systemic treatment. METHODOLOGY: Fifteen patients with isolated liver metastases of colorectal carcinoma were treated with regional administration of CPT-11 in combination with 5-fluorouracil/folinic acid (5-FU/FA). CPT-11 (100-200 mg, mean: 93 +/- 25, range: 51-125 mg/m2) was administered weekly in combination with 5-FU (1000-2000 mg, 857 +/- 182, range: 538-1301 mg/m2) and FA (100-350 mg). Peripheral blood leukocyte phenotype was examined during the treatment in selected patients. RESULTS: One patient achieved complete response, 4 patients had partial response, 7 patients had stable disease, 1 patient progressed and 2 patients were not evaluable. The response rate was 38% in evaluable patients, and a more than 50% decrease in serum carcinoembryonic antigen levels was observed in 12 out of 14 patients. The treatment was generally well tolerated. All patients, except one, are currently alive at mean follow-up of 11 +/- 6 (median: 10, range: 5-24) months. The therapy is still being continued in 8 patients. CONCLUSIONS: Weekly CPT-11/5-FU/FA is highly effective in the treatment of patients with metastatic colorectal cancer limited to the liver, even after failure of previous 5-FU/FA. The present regimen should be tested as a first line treatment in phase III trial.

Increased urinary zinc excretion in cancer patients is linked to immune activation and renal tubular cell dysfunction.

Urinary zinc excretion is known to be increased in cancer patients, but the pathogenesis of this phenomenon remains uncertain. Both skeletal muscle catabolism and renal tubular cell dysfunction have been proposed to explain this observation. We have investigated urinary zinc and N-acetyl-beta-D-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction, as well as serum neopterin, an index of systemic immune activation, in 22 patients with cancer and seven controls. Both serum neopterin and urinary zinc were significantly elevated in cancer patients (15.8 +/- 12.7 versus 7.3 +/- 2.3 nmol l-1 and 1.77 +/- 0.80 versus 1.21 +/- 0.41 mmol mol-1 creatinine, P < 0.02 and P < 0.05, respectively), while NAG was similar in cancer patients and the controls (13.58 +/- 13.80 versus 13.68 +/- 12.19 mu kat mol-1 creatinine). A significant correlation was observed between serum neopterin and urine zinc (rs = 0.5119, P < 0.02), serum neopterin and urine NAG (rs = 0.6761, P < 0.002), and urinary zinc and NAG (rs = 0.6348, P < 0.002). In conclusion, the present data indicate a link between urinary zinc excretion and immune activation as well as renal tubular cell dysfunction. In addition, renal tubular cell dysfunction appears to be linked to immune activation.

Gastric juice neopterin in Helicobacter pylori infection.

Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori, a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 +/- 15.6 vs. 2.1 +/- 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 +/- 12.0 vs. 11.1 +/- 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 +/- 3.2 vs. 1.3 +/- 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 +/- 4.6 vs 1.6 +/- 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.