Rapidly progressive primary undifferentiated ovarian carcinoma: presentation of a rare case.

Ovarian cancer is the second most common gynecologic malignancy and is one of the leading causes of death among women. The disease course and the accurate diagnosis are correlated with the early detection of the lesion. About 5% of ovarian cancers are poorly differentiated and difficult to be classified, and are referred to as undifferentiated carcinomas. They are usually large, solid with haemorrhage and necrosis, bilateral, and very difficult to be histologically classified. Generally, cases with undifferentiated components are very rare. The authors present a case of a young female patient with a rapidly progressive undifferentiated ovarian carcinoma and a final unfortunate clinical result.

VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2.

BACKGROUND: Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites. METHODS: T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed. RESULTS: The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells. CONCLUSION: Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.

Does hormone therapy, tibolone or raloxifene modify VEGF expression in cervical epithelial cells?

AIM: Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. METHOD: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17ß-estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 0-3). RESULTS: Concerning endogenous hormones, higher Δ4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). CONCLUSION: Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis.

Fallopian tube cancer presenting as inflammatory breast carcinoma: report of a case and review of the literature.

Metastases of ovarian or fallopian tube carcinomas to the breast and axillary lymph nodes are quite uncommon and usually occur in advanced stages. These metastases may represent a pitfall for the pathologist, because they may mimic primary breast carcinoma. A 56-year-old woman was admitted to the hospital with a left-sided pelvic tumor, redness and swelling of the right breast and palpable right axillary nodes and left lower neck and supraclavicular lymphadenopathy. The imaging, surgical and pathologic findings were those of a papillary serous carcinoma of the fallopian tube with metastases to the breast, axillary and neck lymph nodes. It is important that metastasis to the breast be differentiated accurately from primary breast cancer, because prognosis and treatment differ significantly. Imaging, immunohistochemical analysis and pathology can help in making the correct diagnosis.

Prognostic impact of HER2/neu protein in urothelial bladder cancer. Survival analysis of 80 cases and an overview of almost 20 years' research.

PURPOSE: This study was conducted to evaluate the quantitative assessment of HER2/neu immunohistochemical expression in urothelial bladder cancer in order to determine its prognostic significance. MATERIALS AND METHODS: Archival tumor tissue from 80 patients with primary urothelial carcinoma were analysed for HER2/neu immunohistochemical expression. A highly reproducible standardized procedure on a Bond-X automated slide stainer was used. RESULTS: HER2 protein was overexpressed in 41 of 80 patients (51.25%), demonstrating an increase in the expression rate corresponding to progressively advanced tumor stage (p=0.032) and tumor grade (p=0.0001). Kaplan-Meier analyses showed that positive membranous expression of HER2/neu was not associated with an increased probability of tumor recurrence (p=0.362). In contrast, HER2 scores correlated strongly with specific survival probability (p=0.002) and overall survival (p=0.025). Multivariate analysis revealed that only stage was an independent predictor of specific survival (p=0.016). HER2 expression was an independent predictor of specific survival with borderline statistical significance (p=0.08). CONCLUSION: HER2 overexpression represents a prognostic factor for adverse disease outcome.

Altered expression of adhesion molecules in inflammatory cervical smears.

OBJECTIVE: The aim of the present study was to evaluate the expression of pan-cadherin and beta-catenin in cervical smears with various types of infectious agents. PATIENTS AND METHODS: Cervical smears obtained from 53 women, aged 21-65 years, with a diagnosis of specific inflammation were examined in our study. Eighteen subjects were infected by Candida albicans, 18 by Gardnerella vaginalis, nine by Bacteroides spp. and eight by Chlamydia trachomatis. All infectious agents found in the smears were at the same time confirmed by the microbiological laboratory methods. We performed a biotin-streptavidin-peroxidase immunocytochemical method using anti-beta-catenin (Clone 12F7) and anti-pan-cadherin (pan, polyclonal) antibodies. RESULTS: Aberrant expression of pan-cadherin was found in the cytoplasmic membrane of glandular, metaplastic, superficial and intermediate squamous cells in all types of infections. With regard to beta-catenin, this was expressed in majority (90%) of glandular and metaplastic cells in all types of infections and in a small proportion (15%) of superficial and intermediate squamous cells in infections caused by C. albicans and G. vaginalis. CONCLUSION: Our data show that infectious agents may cause alterations in the expression and distribution of these adhesive molecules, which can be recognized in cervical smears. Additional studies in larger sets of patients should help clarify this issue further.

Asthma and panic attacks.

Panic disorder (PD) and asthma share many common characteristics and have been found in epidemiological studies to be significantly comorbid. To investigate possible reasons for this overlapping, the authors evaluated 51 patients with asthma, assessing the prevalence of PD and sporadic panic attacks, the temporal relationship between these two disorders, and the familial risk for PD in the families of asthmatics. The results showed significantly higher prevalences of PD, sporadic panic attacks, and social phobia in asthmatics than those reported for the general population. In 9 (90%) of the asthmatics with PD, asthma appeared first. Finally, the morbidity risk for PD in families of asthmatics with PD (13.5%) was significantly higher than in families of asthmatics without evidence of panic (2%). Our results suggest that the high prevalence of PD in asthmatics might be related to a facilitating effect of asthma on the development of PD in subjects with familial predisposition to PD.

Age at onset of panic disorder: influence of familial liability to the disease and of childhood separation anxiety disorder.

OBJECTIVE: The authors investigated the relation of age at onset of panic disorder to liability to panic disorder and agoraphobia. METHOD: Two hundred thirty-one outpatients with panic disorder were compared with 131 surgical outpatients on demographic variables and familial risk of psychiatric disorders. The distribution of patients' ages at onset of panic disorder and several covariates were entered in a stepwise survival analysis. RESULTS: The patients with panic disorder had a significantly higher rate of childhood separation anxiety disorder and higher familial risks of panic disorder/panic disorder with agoraphobia and alcoholism. A family history of panic disorder with agoraphobia and the presence of childhood separation anxiety disorder influenced age at onset of panic disorder. CONCLUSIONS: Age at onset of panic disorder may reflect genetic penetrance, and separation anxiety disorder may be an individual predictor of earlier onset of panic disorder.

Functional promoter polymorphism of the human serotonin transporter: lack of association with panic disorder.

To probe the hypothesis of a role for a functionally relevant 44 bp insertion/deletion of the serotonin transporter promoter in the aetiopathogenesis of panic disorder, we determined the allele frequency of the variant in two samples (combined n = 158) of panic disorder patients (DSMIII-R) and compared it with its allele frequency in two ethnically matched control samples (combined n = 169). The fact that no difference could be observed (x 2 analysis) argues against a major role for this serotonin transporter promoter polymorphism in the aetiopathogenesis of panic disorder.

Hearing loss in Sjögren's syndrome patients. A comparative study.

OBJECTIVE: In an attempt to investigate the presence of hearing loss in primary Sjögren's syndrome (SS) patients and to determine the factors that might be involved in its pathogenesis, we prospectively evaluated 45 female SS patients with a mean age of 56.8 +/- 9.23 years and a mean disease duration of 8.32 +/- 5.39 years. METHODS: Forty patients underwent a complete ear-nose-throat physical examination and audiological evaluation with: (a) pure tone audiometry thresholds at octave frequencies of 250 to 8000 Hz; (b) impedance audiometry (tympanogram, static compliance, acoustic reflexes, reflex decay; and (c) speech audiometry and auditory brainstem response where indicated. In addition, glandular and extraglandular manifestations of the disease and drug therapy were recorded. Finally, all patients were tested for the presence of autoantibodies, including: rheumatoid factor, antinuclear antibodies, antibodies to Ro(SSA), La(SSB) nuclear antigens, anticardiolipin antibodies and antineutrophil cytoplasmatic antibodies. The results were compared with those of 40 healthy, age-matched women. RESULTS: We found sensorineural hearing loss (SNHL) in 9 patients (22.5%): 4 patients bilaterally, 4 patients in the left ear only and one in the right ear only. In all cases the site of the ear damage was cochlear. A correlation between SNHL and the duration of the disease was found, while there was no correlation with age, systemic manifestations of the disease or the presence of autoantibodies. In addition, no correlation was found between SNHL and drug therapy. CONCLUSION: Approximately one-fourth of our SS patients presented SNHL of cochlear origin affecting mainly the high frequencies. This prevalence was lower than that reported by other investigators. SNHL was associated only with disease duration. Further investigation is needed to attain a better understanding of the mechanism of inner ear involvement in SS patients.

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study.

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.

Polymorphic MAO-A and 5-HT-transporter genes: analysis of interactions in panic disorder.

Recurrent panic attacks, anticipatory anxiety and phobic avoidance characterise panic disorder. The influence of genetic factors on liability to the disease has been the object of several linkage and association studies and appears to relate to an oligo- or polygenic rather than a monogenic mode of inheritance. Recently, an excess of high activity monoamine oxidase A (MAO-A) gene promoter alleles was found in female patients with panic disorder. An analysis of possible synergistic effects of the MAO-A gene promoter variant and the short serotonin transporter (5-HTT) gene promoter variant in panic disorder was performed in a German and an Italian sample (combined panic disorder n = 144, combined controls n = 175). There was no significant difference in odds ratios, suggesting that the observed increase of genetic liability by the long MAO-A gene promoter allele is not modified by the 5-HTT gene promoter polymorphism.

A neural network approach to the outcome definition on first treatment with sertraline in a psychiatric population.

Therapy decision is one of the most important tasks clinicians have to perform in their clinical practice. The decision process requires taking into account many different factors. The Authors have proposed a neural computing approach for supporting clinical decision analysis. The mathematical model of artificial neural network (ANN) has been applied on a pool of clinical information gathered through case description freely filled by senior psychiatrists into 416 clinical charts. Sertraline, as drug for treatment, has been chosen since its clinical uses range from treatment of depression to that of many other psychiatric clinical conditions so that it has been thought to be a good candidate to this type of study. The ANN performance in forecasting successful and unsuccessful treatment cases showed an overall accuracy of classification of 97.35%. This result suggests a possible future application of this method to obtain a reliable prediction of a given psychiatric patient outcome during a specific psychopharmacological therapy, optimising the decisional making process.

Hearing loss in progressive systemic sclerosis patients: a comparative study.

OBJECTIVE: To investigate the middle and inner ear involvement in patients with progressive systemic sclerosis (PSS). STUDY DESIGN AND SETTINGS: We prospectively evaluated 34 PSS patients. All patients underwent a complete ear-nose-throat physical examination and audiological evaluation with pure tone, impedance, and speech audiometry. In addition, systemic manifestations of the disease and drug therapy were recorded. Finally, all patients were tested for the presence of autoantibodies. The results were compared with those of 45 age-matched healthy subjects. RESULTS: We found a sensorineural hearing loss in 20% and mixed type hearing loss in 3.3% of the patients. There was no correlation of hearing loss with age, systemic manifestations of the disease, presence of autoantibodies, and drug therapy. Ten percent of the patients had patulous eustachian tubes. CONCLUSION: One fourth of PSS patients had a hearing loss affecting the middle and mainly the high frequencies. This is a lower percentage than that reported by other investigators. A significant prevalence of bilateral patulous eustachian tubes was noticed as well. Further investigation is needed for a better understanding of the mechanism of ear damage in PSS patients.

Polycyclic aromatic hydrocarbons (PaHs) in subcutaneous biopsies of Mediterranean cetaceans.

The aim of the present study was to measure polycyclic aromatic hydrocarbon (PAH) levels in free-ranging Mediterranean cetaceans as they are likely to cause chemical stress in the organisms of this basin. Blubber samples were collected from live specimens of fin whales (Balaenoptera physalus) and striped dolphins (Stenella coeruleoalba) by means of biopsies, a non-destructive biological method. Fin whales were sampled in the Ligurian Sea, whereas striped dolphins were collected in the Ligurian and the Ionian Seas. A fingerprint of 14 PAHs was obtained for both species. In whales, the median value of total PAHs was 1970 ppb fresh weight (f.w.) while median carcinogenic PAH values were 89.80 ppb f.w.; in dolphins, the median values of total and carcinogenic PAHs were 29,500 and 676.00 ppb f.w., respectively. The different PAH values between the two species can be attributed to the different positions they take in the Mediterranean food web. The sampling period significantly influenced PAH concentrations of fin whales.

Skin biopsy of Mediterranean cetaceans for the investigation of interspecies susceptibility to xenobiotic contaminants.

Various studies on Mediterranean cetaceans have revealed bioaccumulation of contaminants such as organochlorines (OCs) and heavy metals. The susceptibility of these animals to organic pollutants and the relationship between bioaccumulation and population decline (as in the case of Delphinus delphis) are unexplored fields. In this study, we used a non-destructive approach (skin biopsy) to explore OC bioaccumulation processes and mixed-function oxidase activity (BPMO) in four species of cetaceans: striped dolphin (Stenella coeruleoalba), bottlenose dolphin (Tursiops truncatus), common dolphin (D. delphis) and fin whale (Balaenoptera physalus). Significant differences in BPMO induction and OC levels were found between odontocetes and mysticetes, the former having mixed-function oxidase activities four times higher than the latter, binding with levels of OCs one order of magnitude higher in odontocetes. A significant correlation (P < 0.05) between BPMO activities and OC levels was found in B. physalus. In an ongoing project, fibroblast cultures have been used as an alternative in vitro method of evaluating interspecies susceptibility to contaminants such as OCs and polycyclic aromatic hydrocarbons (PAHs). These results suggest that cetacean skin biopsies are a powerful non-invasive tool for assessing ecotoxicological risk to Mediterranean marine mammals species.

Fine-needle aspiration cytology of primary renal angiosarcoma with histopathologic and immunocytochemical correlation: a case report.

Primary renal angiosarcoma is an extremely rare neoplasm, with fewer than 28 cases reported thus far in the English literature. We report for the first time the cytomorphology and immunocytochemistry of this tumor in liquid-based (ThinPrep) fine-needle aspiration (FNA) samples in correlation with the conventional cytologic and histopathologic findings. Conventional smears showed pleomorphic tumor cells focally arranged in structures suggesting anastomosing vascular channels, while ThinPrep smears were less cellular with fewer and smaller tumor cells arranged in clusters or rosette-like formations. Immunocytochemical staining demonstrated positive results for vimentin, CD31, and CD34 and negative staining for epithelial markers, thus supporting the diagnosis of a mesenchymal tumor of vascular origin. The diagnosis of primary renal angiosarcoma was established after histopathologic evaluation of a metastatic liver nodule. The cytological differential diagnosis of this neoplasm and the utility of the ThinPrep method as a diagnostic adjunct to conventional FNA cytology are further discussed.