PubMed Health⌕ Search

Biomedical subjects

Giuseppe Viale

Publications and source records attributed to Giuseppe Viale.

At least 37 records · Page 2Linked to original sources
PubMed2006

A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer.

PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. RESULTS: Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Adult↗
PubMed2006

A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and increased serum levels of alkaline phosphatase intestinal isoenzyme.

Malignant extragonadal germ cell tumors primary to the lung are quite uncommon lesions, but pure yolk sac tumor is even more exceptional. This is believed to be the first reported case of yolk sac tumor of the lung in which an intense and diffuse immunoreactivity for CDX2, a marker of intestinal differentiation reportedly expressed also in gonadal yolk sac tumor, was associated with increased serum levels of the alkaline phosphatase intestinal isoform. Nine months after radical surgery and adjuvant chemotherapy, the patient is alive and well without evidence of recurrent or metastatic disease and with serum levels of the alkaline phosphatase intestinal isoform within normal limits. The pathologist should be aware of yolk sac tumor arising in the lung and that alkaline phosphatase intestinal isoform could become an additional serum marker for such a tumor.

Alkaline Phosphatase↗
PubMed2006

The rete mirabile of the cranial base: a millenary legend.

The rete mirabile, a vascular network assumed to give origin to the intracranial segments of the internal carotid arteries, was interpreted by Galen as the key station for the conversion of the "vital spirit" into the "animal spirit." According to this interpretation, the rete was determinant either in sustaining the cerebral functions, or in controlling the reproductive process in humans. This belief was a firm point of the medical doctrine for centuries, accepted by the Islamic and Christian scholars of the Middle Ages. The new anatomy of Vesale, though having stated that the rete does not exist in humans, was unable to settle the discussion on its actual occurrence and function because it could not provide an alternative hypothesis on the mechanisms of support of the cerebral functions. Uncertainties still lasted in the late 17th century, when progress in knowledge on the circulation of blood and the minute anatomy marked the beginning of the new era in the medical science.

Anatomy↗
PubMed2005

Oncocytic modifications in rectal adenocarcinomas after radio and chemotherapy.

The purpose of the study is to highlight oncocytic modifications in rectal adenocarcinomas and evaluate a possible correlation with preoperative radiochemotherapy (RCT). Twenty-eight cases of advanced rectal carcinoma, treated preoperatively by 5-fluorouracil (200-225 mg/m(2)) and 44-46 Gy in 22-23 fractions, were studied. All patients underwent biopsy before RCT. Surgery was performed within 6 weeks after RCT. In all cases oncocytic modifications were searched for on hematoxylin and eosin (H&E) and at immunohistochemistry using an antimitochondrial antibody. In addition, in two cases, both pre- and post-RCT tissues were examined at electron microscopy. All tumors were adenocarcinomas. In pre-RCT biopsies, oncocytic changes were difficult to find on H&E, while the antimitochondrial antibody strongly stained numerous neoplastic cells (mean 48.4%). In post-RCT surgical specimens, oncocytic changes were detected in 24 out of 28 cases on H&E and the antimitochondrial antibody stained most of the residual neoplastic cells (mean 76.7%). Ultrastructural examination revealed large and bizarre mitochondria inside tumor cells both in pre- and post-RCT tissues. In conclusion, the present data suggest that rectal adenocarcinomas are "mitochondrion-rich" tumors. After preoperative RCT, residual neoplastic cells acquire a definite oncocytic phenotype.

Adenocarcinoma↗
PubMed2005

Pathologic examination of the axillary sentinel lymph nodes in patients with early-stage breast carcinoma: current and resolving controversies on the basis of the European Institute of Oncology experience.

Several controversial aspects of sentinel lymph node biopsy (SLNB) for patients with early-stage, node-negative breast carcinoma have been dealt with and resolved in the past decade since its introduction. Unfortunately, however, there is still no consensus on how best to examine sentinel lymph nodes (SLN) histologically. As a consequence, the protocols for SLN examination are remarkably variable in different institutions, leading to a very poor reproducibility of the data stemming from investigations on series of patients whose SLNs have been evaluated according to diverse protocols. Patient outcomes, however, can be optimised only by standardization of the whole procedure of SLNB, with particular reference to the histopathologic scrutiny. Lack of a standardized histopathologic protocol likely derives also from the uncertainties about the clinical implications of minimal lymph node involvement (isolated tumour cells and micrometastases) with regard both to the risk of additional metastases to non-sentinel lymph nodes of the same basin and to the prognostic value for patients' survival. This review aims at highlighting some of the controversial issues of the histopathologic examination of the SLNs, including the number of sections and cutting intervals, the use of immunohistochemistry and the role of molecular biology assays.

Academies and Institutes↗
PubMed2005

Pulsed dose-rate perioperative interstitial brachytherapy for soft tissue sarcomas of the extremities and skeletal muscles of the trunk.

BACKGROUND: This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment. METHODS: Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was <5 cm in 20 cases and >5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy. RESULTS: With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%. CONCLUSIONS: PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.

Adult↗
PubMed2005

Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients.

Human telomerase reverse transcriptase (hTERT), the catalytic subunity of telomerase, a marker of cell immortalization, is upregulated in most tumors, including nonsmall cell lung cancer (NSCLC). However, little is known about the role of assessing cell-free plasma circulating hTERT mRNA for tracing these tumors. We investigated by RT-polymerase chain reaction (PCR) and real-time quantitative PCR the prevalence and functional implications of hTERT mRNA in both tumor tissue and paired plasma samples in 34 (27 males and 7 females) stages I-IIIB NSCLC patients (21 adenocarcinomas and 13 squamous-cell carcinomas) by using intron- and exon-spanning primers. Plasma samples of ten healthy volunteers and normal lung tissue were used as negative controls. We detected hTERT mRNA in the plasma of 4 out of 34 (12%) tumor patients, but none was detected in the ten plasma samples of healthy volunteers. Normal lung tissue was completely devoid of hTERT mRNA. No association was found between hTERT plasma mRNA and clinicopathologic variables of the patients' population. We conclude that cell-free circulating hTERT mRNA is detectable in a subset of patients, whereas it is consistently absent in healthy volunteers. It can be added to the panel of multiple genetic tracers to detect lung cancer in the plasma of patients, although, per se, it is not specific for this tumor.

Adenocarcinoma↗
PubMed2005

Second biopsy of axillary sentinel lymph node for reappearing breast cancer after previous sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. METHODS: Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. RESULTS: In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. CONCLUSIONS: Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.

Adult↗
PubMed2005

Histopathology of primary breast cancer 2005.

Major efforts have been recently devoted to a better definition of intraductal proliferative lesions with atypia. The new WHO classification of tumors of the breast highlights the morphological features of flat epithelial atypia (DIN 1A) and atypical duct hyperplasia (DIN 1B). Flat epithelial atypia now encompasses lesions previously designated as clinging carcinoma (monomorphous type) and atypical columnar changes. Atypical ductal hyperplasia (ADH) is characterized by the same cytological changes as low-grade DCIS, involving a very small portion of the ductal tree. Minimal lymph node involvement includes true micrometastases (from 0.2 to 2 mm in size) and isolated tumor cells (ITC). ITC have been defined as individual tumor cells or small clusters of cells, not more than 0.2 mm in size, that do not typically show evidence of metastatic activity or penetration of vascular or lymphatic sinus walls. The biological and clinical implications of ITC remain to be elucidated.

Breast Neoplasms↗
PubMed2005

A subset of high-grade pulmonary neuroendocrine carcinomas shows up-regulation of matrix metalloproteinase-7 associated with nuclear beta-catenin immunoreactivity, independent of EGFR and HER-2 gene amplification or expression.

Nuclear translocation of beta-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation in non-small cell lung cancer. Less is known on beta-catenin transactivation in high-grade pulmonary neuroendocrine tumors and on the status of beta-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or beta-catenin target genes cyclin D1 and matrix metalloproteinase-7 (MMP-7). beta-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for beta-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. beta-catenin was expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated with EGFR and HER-2 protein expression. beta-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These cases, however, did not show beta-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear beta-catenin and any clinicopathological variable including patients' survival. The subcellular compartmentalization of beta-catenin is profoundly altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows beta-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression.

Adult↗
PubMed2005

Accuracy of computed tomography and magnetic resonance imaging in the detection of lymph node involvement in cervix carcinoma.

UNLABELLED: Lymphnodes status in cervical carcinoma is important in therapeutic planning, and the role of Computed Tomography (CT) and Magnetic Resonance (MR) is controversial: this paper aims to evaluate their accuracy in diagnosing nodal metastases in patients with cervical carcinoma. We reviewed, retrospectively and blindly, CT and MR of 62 patients, before surgical lymphnode resection: 45 of these patients had pre-surgical chemotherapy. Lymphnodes were defined metastatic by CT and MRI when larger than 1 cm short axis. Both diagnoses by the original routine reports and by a second blind expert were compared with pathological reports. RESULTS: combining the reading results of both observers CT showed a sensitivity of 64.6% and specificity of 93.3%; MRI a sensitivity of 72.9% and specificity of 93.1%. Positive Predictive Value was 50.8% for CT and 53% for MR, while Negative Predictive Value was 96% both for CT and MR. The expert Radiologist reviewing the films obtained better results. Inter-observer variability in the lower quadrants was high for each imaging technique (kappa for CT: 0.71; kappa for MRI: 0.84). Both imaging techniques showed similar screening accuracy in identifying nodal metastases. The radiologist's experience is important in determining the performance of the imaging technique. Anyway, CT and MRI are only moderately sensitive for detection of nodal metastases and the clinical impact of their results in patient's management is limited.

Carcinoma↗
PubMed2005

Expression of amino acid sequences of the chromogranin A molecule and synaptic vesicle protein 2 in neuroendocrine tumors of the lung.

Chromogranin A (CgA) and its valuable complement synaptic vesicle protein 2 (SV2) are neuroendocrine (NE) markers. Post-translational processing of CgA has been reported to vary in different NE cell types and tumors, but little is known regarding the expression of various CgA epitopes and SV2 in NE pulmonary tumors. We studied the immunoreactivity to six CgA epitopes and SV2 in ten typical (TC) and ten atypical (ACT) carcinoids, five large-cell NE carcinomas (LCNEC) and five small-cell carcinomas (SCLC), also comparing the results with clinicopathological characteristics of tumors. The sequences CgA 17--38 (vasostatin), 176--195 (chromacin), 375--384 (parastatin) and 411--424 (C-terminal parastatin) and SV2 were relevant markers for the CT/ATC group, whereas the antibody to CgA 176--195 was a better marker for the LCNEC/SCLC group. An inverse correlation was found between proliferative activity and granule-related markers in the CT/ACT group, and a direct correlation in poorly differentiated tumors. The expression of granule-related markers did not correlate with hormone content or clinical characteristics of NE tumors. The expression of CgA epitopes and SV2 occurs in all NE tumors, differing between better differentiated and poorly differentiated tumors but not within the respective groups.

Adult↗
PubMed2005

Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells.

The control of damaging inflammation by the mucosal immune system in response to commensal and harmful ingested bacteria is unknown. Here we show epithelial cells conditioned mucosal dendritic cells through the constitutive release of thymic stromal lymphopoietin and other mediators, resulting in the induction of 'noninflammatory' dendritic cells. Epithelial cell-conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, even after exposure to a T helper type 1-inducing pathogen. This control of immune responses seemed to be lost in patients with Crohn disease. Thus, the intimate interplay between intestinal epithelial cells and dendritic cells may help to maintain gut immune homeostasis.

Cell Differentiation↗
PubMed2005

Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids.

BACKGROUND: To the authors' knowledge, little is known regarding the role of E-cadherin/beta-catenin system dysregulation in pulmonary neuroendocrine tumors. METHODS: E-cadherin and beta-catenin immunoreactivity was evaluated in 10 hyperplastic neuroendocrine tumorlets and 210 neuroendocrine tumors, including 96 typical carcinoids (CTs), 35 atypical carcinoids (ACTs), 49 large cell neuroendocrine carcinomas (LCNECs), and 30 small cell lung carcinomas (SCLCs). RESULTS: Normal and hyperplastic bronchial neuroendocrine cells expressed E-cadherin/beta-catenin with an orderly distribution along the cell membrane. Neuroendocrine tumors retained beta-catenin expression in all tumors and E-cadherin in most tumors, with the exception of 2% of LCNECs, 3% of SCLCs and 9% of ACTs. E-cadherin showed a prevalent membrane-associated, linear immunoreactivity in CTs, whereas membrane-disarrayed and cytoplasmic staining was seen in most ACTs, LCNECs, and SCLCs (P < 0.001). beta-Catenin exhibited similar immunoreactivity patterns according to tumor type and a close association with E-cadherin subcellular distribution (P < 0.001). Nuclear accumulation of beta-catenin was found only in seven LCNECs and in two SCLCs. In ACTs, disarrayed immunoreactivity for E-cadherin and/or beta-catenin was associated with a nontrabecular growth pattern, altered expression of the cell-motility marker fascin, and lymph node metastases. Furthermore, a disarrayed E-cadherin distribution pattern was associated with the pathologic lymph node classification and the number of involved lymph nodes. Multivariate analysis confirmed that a disarrayed E-cadherin or beta-catenin pattern was an independent predictor of lymph node metastases in patients with ACT. CONCLUSIONS: The subcellular compartmentalization of the E-cadherin/beta-catenin complex was altered in pulmonary neuroendocrine tumors. This likely affects the tumor growth pattern and cell motility of ACT and was correlated with the occurrence of lymph node metastases.

Adult↗
PubMed2005

Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement.

BACKGROUND: Overt ipsilateral axillary lymph node metastases of breast cancer are the most significant prognostic indicators for women who have undergone surgery, yet the clinical relevance of minimal involvement (isolated tumor cells and micrometastases) of these nodes is uncertain. PATIENTS AND METHODS: We evaluated biologic features, adjuvant treatment recommendations, and prognosis for 1,959 consecutive patients with pT1-3, pN0, minimal lymph node involvement (pN1mi or pN0i+), or pN1a (single positive node) and M0, who were operated on and counseled for medical therapy from April 1997 to December 2000. RESULTS: Patients with pN1a and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often prescribed anthracycline-containing chemotherapy (39.1% v 33.2% v 6.1%, respectively; P < .0001) and were less likely to receive endocrine therapy alone (9.8% v 19.4% v 41.9%, respectively; P < .0001). At the multivariate analysis, a statistically significant difference in disease-free survival (DFS) and in the risk of distant metastases was observed for patients with pN1a versus pN0 disease (hazard ratio [HR] = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32; 95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases). CONCLUSION: Even minimal involvement of a single axillary node in breast cancer significantly correlates with worse prognosis compared with no axillary node involvement. Further studies are required before widespread modification of clinical practice.

Adult↗
PubMed2005

Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution.

BACKGROUND: Reliable predictors of metastatic involvement would enable a better selection of candidate patients for sentinel lymph node biopsy (SLNB) and possibly allow identification of patients with such a low risk of axillary sentinel lymph node (SLN) involvement to be even spared SLNB. METHODS: The authors evaluated 4351 consecutive patients surgically treated for breast carcinoma who also underwent SLNB. Clinicopathologic features significantly associated with SLN metastases by univariate analysis were included in a multivariate model. RESULTS: By multivariate analysis, the prevalence of SLN metastases was associated directly with tumor size, multifocality, and with the occurrence of peritumoral vascular invasion (PVI; all P < 0.0001), and was associated inversely with a favorable histotype (P = 0.0007) and lack of progesterone receptors (P = 0.004). A predictive model based on the features more closely associated with SLN status documented that the patients with a favorable tumor type </= 1 cm in size and without PVI (n = 178 [4% of the population]) had the lowest risk of SLN metastases (9.5%) whereas patients with tumors > 2 cm and with PVI (n = 250 [5.7% of the population]) had the highest risk (77.2%) of SLN involvement. CONCLUSIONS: Tumor size and PVI emerged as the most powerful independent predictors of SLN metastases. Although no combination of features identified patients with a < 9.5% risk of SLN metastases, the current data may be used to tailor the management of patients with breast carcinoma with the aim of minimizing as much as possible the diagnostic and therapeutic procedures, thus improving the quality of life of the patients without any adverse effect on their survival rates.

Adolescent↗
PubMed2005

Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung.

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.

Adenocarcinoma↗