Search

The objective of the present study was to investigate in healthy young women the fluctuations in serum concentration of human epididymal secretory protein human epididymis-specific protein 4 (HE4) and CA125 during the phases of the menstrual cycle and the correlation between HE4 and CA125 values and age. Forty women with regular menstrual cycles were included in the study. Pelvic and transvaginal ultrasound were performed in order to exclude ovarian pathologies. Blood samples were collected at follicular (FP), ovulatory (OP), and luteal (LP) phases of the hormonal cycle. The values of HE4 (expressed as picomoles per liter) observed were (mean ± SEM) 39.1 ± 1.1 (FP), 45.3 ± 1.19 (OP), and 42.0 ± 1.3 (LP). The difference between FP and OP was statistically significant (p = 0.0002). By contrast, serum CA125 levels (expressed as units per milliliter) were 14.35 ± 0.66 (FP), 13.15 ± 0.54 (OP), and 13.70 ± 0.54 (LP), respectively. The levels of HE4 observed in serum samples of women below 35 years were 37.5 ± 1.28 in the FP, 46.6 ± 1.4 in the OP, and 42.8 ± 1.49 in the LP. In this group, a statistically significant difference was observed in the FP compared with the OP (p < 0.0001), whereas no statistically significant difference was observed during the different hormonal phases in the group of women over 35. In conclusion, the correct interpretation of laboratory data is essential to define a threshold of normality, and for what concerns HE4 levels, the menstrual cycle phase-dependent variability appears indicated in the interpretation of the results.

Human epididymis protein 4 (HE4) has recently been described as a new marker for the early diagnosis of ovarian cancer (OC). The objective of this study was to evaluate (a) the expression of HE4 vs. OC mucin CA125 in 32 patients with OC compared to 163 patients with other malignant or benign pathologies (b) HE4 as indicator of the recurrence of the disease in eight patients followed-up for 20 months after OC diagnosis. Serum HE4 and CA 125 levels were determined by ELISA and IRMA, respectively. At diagnosis, the patients with OC demonstrated high levels of both biomarkers with 96.9% sensitivity for HE4 and 85.7% for CA125. In the other pathologies there was 3.7% positivity for HE4 and 21.0% for CA125. The follow-up study showed an increase of HE4 5-8 months before CA125 increment in five of the eight patients, this early expression being strictly associated to a relapse of the disease. In conclusion, this study showed that HE4, compared to CA125, potentially is a better marker for the diagnosis of OC and could be an important early indicator of the recurrence of the disease.

In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 +/- 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 +/- 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT.

Pheochromocytomas are catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglionic system that show 2 distinctive features, rarity and clinical variability. Pheochromocytoma occasionally is associated with pathological lesions of the adrenal cortex. We present 2 cases of patients referred to our hospital with a finding of clinical suspected pheochromocytoma. Both of them were hypertensive; the first patient with typical symptoms of pheochromocytoma and the second patient with chest pain and hypertension resistant to pharmacological treatment. The diagnosis of pheochromocytoma was confirmed in both cases with laboratory analysis and the lesion was achieved by employing 3 imaging techniques: computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy with (123)I-metaiodobenzilguanidine (MIBG). The patients underwent adrenalectomy and in the same adrenal gland we found a pheochromocytoma associated with a nonfunctioning cortical adenoma. As far as we know few cases with this association are available in the literature.

Aims and Background: The aim of our study was to investigate the plasma chromogranin A (CgA) and adrenomedullin (AM) levels in patients with pheochromocytomas., Methods and Study Design: We collected blood samples for measurement of plasma CgA and AM in 21 patients with pheochromocytomas, 43 healthy subjects and 26 patients with solid non-functioning adrenocortical adenomas. In 11 patients with pheochromocytomas plasma CgA and AM were measured again four weeks after tumor removal. CgA and AM were measured by means of a novel solid-phase two-site immunoradiometric assay based on monoclonal antibodies (CgA-RIA CT, CIS bio international) and by a specific radioimmunoassay (RIA, Phoenix Pharm. Inc.), respectively., Results: The mean plasma CgA level (+/- SD) in patients with pheochromocytomas (204 +/- 147.9 ng/mL) was significantly higher (P < 0.001) than that in healthy subjects (41.6 +/- 10.7 ng/mL) and in patients with non-functioning adrenocortical adenomas (47.3 +/- 17.6 ng/mL). The mean plasma AM concentration (+/- SD) in patients with pheochromocytomas (27.5 +/- 10.4 pg/mL) was significantly higher (P < 0.001) than that in HS (13.8 +/- 4.5 pg/mL) and in patients with non-functioning adrenocortical adenomas (16.6 +/- 7.3 pg/mL). Plasma CgA levels correlated with plasma AM levels (r = 0.501; P < 0.02) and with plasma metanephrine levels (r = 0.738; P < 0.0001) in patients with pheochromocytomas. In 11 patients with pheochromocytomas plasma CgA and AM concentrations significantly decreased after tumor removal (P < 0.001 for both). Circulating CgA and AM had a sensitivity of 76.2% and 81%, a specificity of 97.7% and 90.7%, and an accuracy of 91% and 88%, respectively., Conclusion: This study demonstrates that circulating CgA and AM levels are increased in pheochromocytoma patients compared with healthy subjects and patients with non-functioning adrenocortical adenomas. Moreover, at the time of diagnosis plasma CgA levels correlated with plasma AM levels and with plasma metanephrine levels in all patients with pheochromocytomas. In conclusion, plasma CgA and AM concentrations may represent additional biochemical parameters for clinical monitoring of patients with pheochromocytomas.

Increased levels of the gliofibrillar S100b protein can be detected during carotid endarterectomy (CEA). Whether the S100b protein increase is marker of brain ischemic sufferance and predictor of cognitive decline is controversial. Twenty-eight patients underwent clinical assessment and cranial computed tomography (CT) 24-48 hours before and 3 months after CEA. S100b serum levels were evaluated before surgery, at cross-clamping, 10 minutes later, at declamping, and 24-48 hours and 10-12 weeks after CEA. Increased S100b levels were detected in 11 patients (39%); eight (73%) of these patients had symptomatic carotid artery disease. Increased S100b level correlated with history of TIA or stroke ( p=0.005), low mini-mental state examination score ( p=0.02), and ischemic infarctions at preoperative CT ( p=0.03). Slight and transient increased S100b levels were detected in 39% of patients during CEA. The protein levels increased despite the absence of clinical events during surgery. Our findings suggest a failure of compensatory hemodynamic or metabolic mechanisms in peri-ischemic tissue, whose longterm effects on cognition remain to be investigated.

Background: Sarcoidosis is a chronic systemic disease, characterized by an imbalance of immunity processes and the presence of granuloma. Endothelin-1, a new vasoactive and bronchoconstrictive peptide, is a powerful mitogen for smooth muscle cells and fibroblasts and plays a role in the inflammation state. We postulate that endothelin-1 has a role in sarcoidosis., Methods: We studied the behaviour of circulating levels of endothelin-1 in 20 patients with sarcoidosis and its correlation with some biochemical parameters of activity disease, such as erythrocyte sedimentation rate (ESR) and serum angiotensin-converting enzyme (SACE). We measured serum levels of ESR, SACE, calcium and plasma endothelin-1 levels in all patients at the beginning of the study and one again in 9 patients with clinical-biochemical remission of disease after steroid treatment., Results: In patients with sarcoidosis, circulating levels of endothelin-1, SACE and ESR were significantly higher (p<0.001) than those of healthy subjects. Moreover, in patients with pulmonary involvement, there was a significant statistical difference (p<0.001) between endothelin-1 levels and radiological stage compared to normal subjects. In the 9 patients with remission of disease, both endothelin-1 levels and parameters of activity disease normalized., Conclusions: Our results seem to suggest that the increase of plasma endothelin-1 levels in active sarcoidosis can represent an expression of the endothelial dysfunction and reflect the picture of cellular activation.

Serum concentrations of prolactin, a trophic hormone produced by the pituitary gland, have been shown to be raised in certain group of patients with cancer. Prolactin was detected in 0-20% of the colon cancer by immunohistochemistry and in plasma in 6-53% of the patients. These conflicting results do not support the hypothesis of an ectopic prolactin production by colon carcinoma. The aim of this study was to confirm the reported incidence of hyper-prolactinemia in colorectal cancer and to find further evidence for an ectopic prolactin production by the tumor. Thirty consecutive patients with colon carcinoma were studied. Before surgery all the patients underwent blood sample collection to assay plasma prolactin levels. All patients underwent colectomy. All the neoplastic specimens were tested with antiprolactin antibody. In none of the patients were significantly high preoperative levels of plasma prolactin found. Prolactin immunostaining was not identified in any of the tumor specimens. We could not confirm previous reports of frequent hyperprolactinemia in patients with cancer. This is the first report in which the incidence of both hyperprolactinemia and prolactin positive immunostaining was 0%. Our study was unable to demonstrate the synthesis of prolactin by colorectal cancers. The tumor is unlikely to be the source of hormone production. Our results suggest that circulating prolactin levels cannot be used as prognostic marker in patients with colon cancer.

A 35-year-old woman was admitted to our hospital with the following complaints, headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension. The technical images (abdominal CT, scintigraphic octreotide scan and renal arteriography) revealed the presence of a left adrenal pheochromocytoma and stenosis of the renal artery. Ten days following adrenalectomy, watery diarrhea appeared. The long-acting somatostatin analogue octreotide (LAR, 30 mg/month, i.m.), was started, and after 2 weeks diarrhea decreased and gradually disappeared. In conclusion, we were confronted with an unusual case of pheochromocytoma associated with renal artery stenosis and the appearance of watery diarrhea some days after surgical treatment. Treatment with octreotide brought about the remission of diarrhea in this patient., (Copyright 2002 S. Karger AG, Basel)

Background: The growing use of sensitive non-invasive methods to image the abdomen such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), have resulted in increasing recognition of adrenal incidentalomas., Methods: In this study, we report the clinical, endocrine and radiologic evaluation of 75 patients (50 women and 25 men, mean age 56 +/- 14 years) with adrenal incidentaloma (size 1 to 18 cm, mean 3 +/- 2.5 cm). None of the patients showed any symptoms or clinical signs that might indicate the existence of adrenal dysfunction. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, CT and MRI scan and Iodo-cholesterol (NP-59) scintigraphy were performed., Results: The endocrine evaluation indicated 11 cases of pre-clinical Cushing's syndrome, 2 cases of pheochromocytoma and 62 not-functionally adrenal masses. On the basis of endocrine and morphologic data, 29 patients underwent surgical treatment: 20 adrenocortical adenoma, 2 pheochromocytomas, 2 not-cortisol-secreting adrenal carcinomas, 1 adrenal lymphoma, 1 adrenal metastasis, 1 myelolipoma, 1 hemorrhage and 1 pseudocystis., Conclusions: In conclusion, patient with an incidentally discovered mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment.

In order to define the most useful tumor marker panel in breast cancer patients' follow-up and in monitoring treatment response, serological levels of CEA, MCA, Ca 15-3 and Ca 27-29 were evaluated in 220 patients. 180 patients had no evidence of disease (NED) after primary treatment, and 40 had metastases at first diagnosis time; in a 4 years follow-up, 30 of the NED patients relapsed, and were then included in the group of metastatic patients subjected to anticancer treatment. Overall sensitivity in metastatic patients was: CEA 40%, MCA 35%, Ca 15-3 79%, Ca 27-29 70%, with the highest percentages and mean values in liver and bone localizations. Combination of Ca 15-3 and Ca 27-29 improved sensitivity in bone lesion (85% vs 80%), in locoregional relapses only association with CEA increased sensitivity (60% vs 40%). Ca 15-3 and Ca 27-29 values increased on average 3 months before clinical diagnosis. In treated patients there was a better correlation with a clinical course of disease for Ca 15-3 and Ca 27-29 (both 81%) as compared to the other determined markers.

75 patients with breast gross cystic disease and no cancer have been included in the study. For each patients serous and intracystic concentrations of MCA have been measured. The aim of the study is to assess whether if a relation between intracystic concentration of the marker and resistance and capability of cellular reproduction exists (confirmed by the release of the cyst). The analysis of intracystic values shows that synthesis of MCA is an intrinsic peculiarity of cytologic kind. It is apparently independent from inflammatory or hemorrhagic contemporary processes.

PSA has been measured out with highly sensitive method both in liquid of mammary cysts and in cytosol of neoplastic cells. Our data point out that dysplastic, metaplastic and anaplastic breast epithelial cells produce PSA. Such production is, probably, related to expression of hormonal receptors.

IAP marker was detected by radio-immunodiffusion in breast gross cyst fluid and in serum. No correlation was found between this antigen and cyst' cytological type, serum concentrations and acute phlogosis. In most cysts IAP was not valuable; on the other hand, high levels of glycoprotein were found only in the subgroup on relapsed class of apocrine cysts.

Ca 125 was assayed in serum and in breast cyst fluid of 78 patients with GCD. Levels of the marker in cyst fluid are generally < 30 U/ml. More significative results were found in relation to cysts relapse. In apocrine cysts relapse levels were higher than 270 U/ml, in serum cysts not relapsed levels were between 31-270 U/ml. Ca 125 could have a significative role in cell differentiation and its control.

The present study was carried out on 152 patients divided into three groups: A) 73 underwent radical surgery for breast carcinoma without signs of metastases; B) 31 patients with radiologic and scintigraphic evidence of bone metastases originating from malignant mammary neoplasia (14 with only one and 17 with two or more localizations); C) 48 affected by simple mammary cysts. No patients had a previous history of primary or secondary bone pathologies or renal, hepatic or endocrine ones. Besides this, no patient took drugs influencing the metabolic turnover of the bony tissue in the three months preceding the study. After surgery all patients underwent standard clinical and laboratory follow-up, the latter including, every 3 months, the evaluation of serum CA 15.3, CA 27.29 MCA, and ostase. The ostase cut-off, obtained by the statistical elaboration of the serum values of the 48 patients with benign mammary cysts and the 73 disease free patients, was 17 microg./L. The mean concentration in the three groups and two subgroups was: 13.76 microg./L (patients without metastases), 31.84 (patients with metastases), 18.4 (limited bony metastases), 40.04 (diffused bony metastases) and 5.36 (mammary cists). The diagnostic sensitivity of ostase proved superior to that of CA 15.3 (84% vs 75%) except when considering the subgroup with limited metastases (71.4% vs 72.7%), while the specificity was similar (around 78%). CA 27.29 and MCA were not useful as markers of metastasis. In a longitudinal-perspective study it was possible periodically to test these markers in 13 patients, at first, disease free and then with signs of bone progression evidence by skeletal scintigraphy. In 11 of these patients ostase and CA 15.3 showed increased values, an average 136 and 131 days respectively, before instrumental evidence of progression. None of the 13 patients, at the time of bone progression diagnosis, showed clinical, laboratory or instrumental signs of disease in other organs. The precocity of the serum increase of ostase could have a triple role: 1) accomplishment of a closer follow-up in patients at "high risk" of bone disease; 2) aid in the interpretation "in a neoplastic sense" of an "uncertain image of hypercaptation"; 3) accomplishment of a supporting or specific oncology treatment at an earlier stage which may be of some advantage as regards quality of life.

Ca 15-3 was assayed in serum and in breast cysts fluid of 78 non neoplastic patients presenting Gross Cysts (GCD). In apocrine cysts and in the mixed type (serous and apocrine, class III) relapse was indicated by high serum and intracystic levels of the marker. Ca 15-3, therefore, may discriminate in a group of cysts a higher cellular resistance as well as an increased cell proliferation. Results suggest an important role of the marker in the follow up of patients with GCD and for the early detection of cyst relapse.

Immunoradiometric determination of the bone isoenzyme of alkaline phosphatase with a method provided by Hybritech Inc., San Diego CA (USA) was carried out in 145 female patients, 97 of whom with radically operated breast cancer and 48 with benign mammary cysts, in order to evaluate the correlation of serum levels with the metabolic process of bone rearrangement in patients with bone metastases. This study shows that skeletal ALP, having high specificity (86.48%) and sensitivity (78.6%) for early progression (the average anticipation time compared to scintigraphic detection was 101 days) could represent a valid marker for bone metastases in association with mucinous markers in the follow-up of patients operated for breast cancer. In addition, dynamic serum determination of skeletal ALP could be a valid help in monitoring the efficacy of therapy in patients with bone progression.

The aim of our study was to evaluate the usefulness of the tumor markers CA 72.4, CEA and CA 19.9 in the monitoring of gastrointestinal carcinomas. Our experience demonstrated the usefulness of the determination of CA 72.4 in the follow up of patients with gastrointestinal neoplasms.

Renal calculosis associated with urinary tract infections due to urease-positive or -negative microorganisms poses difficult therapeutic problems. The introduction of monobactam antibiotics such as aztreonam offers a valid therapeutic alternative thanks to the action of this drug on the gram-negative organism often at the root of these infections. The above study has been carried out in 10 patients with infections due to organisms sensitive to aztreonam and aminoglucosides. Treatment with aztreonam (1 g i.m. 3 times daily) brought about sterilization lasting from 3 weeks to permanently in 5 cases. In one case sterilization was transitory and in 4 cases treatment was unsuccessful. Creatinine blood level and other biochemical parameters did not vary. Aminoglucosides alone brought about transitory sterility in 2 cases and was unsuccessful in 6. At the end of treatment, creatinine blood level had increased significantly. Given the absence of toxicity the definitely better therapeutic result, and the absence of induced resistance, aztreonam should be considered the drug of choice and should be preferred to aminoglucosides for the management of urinary tract infections due to microorganisms sensitive to both types of drugs in patients with urinary calculosis.