[Proposal of a screening method for the preclinical diagnosis of colo-rectal carcinoma].
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Biomedical subjects
Publications and source records attributed to F Puglisi.
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Numerous pathologic and biologic factors have been assessed for their ability to predict clinical behaviour and response to therapy in breast cancer patients. Currently, traditional morphological features such as lymph node status, tumour size, histological type and tumour grade remain the leading prognostic factors. Steroid receptors are also important, but their main role consists in predicting response to hormonal therapy. Although several new indicators have been proposed to refine the value of the above-mentioned proven parameters, interpretation of their impact is not conclusive. In particular, immunohistochemical evaluation of p53, c-erbB-2 and MIB-1 appears to be potentially useful and considerable efforts are currently being made to technically and clinically validate them.
In spite of major advances in early detection and adjuvant therapy, metastatic breast cancer remains a major clinical problem affecting a significant number of patients. Metastatic disease is generally considered incurable and conventional therapy is used mainly with palliative intent. Therefore, the choice of appropriate therapeutic approach requires a reasoned evaluation of the likelihood of benefit from therapy balanced with the impact of therapy on the patient's quality of life. The estimated aggressiveness of the tumour and indicators of response to therapy (e.g. the status of hormonal receptors) are useful parameters to take into account before selecting a given treatment. Endocrine therapy is an important option in the management of stage IV disease, with tamoxifen the most widely used first-line drug in postmenopausal women. For progressing patients, the third generation of aromatase inhibitors (letrozole, anastrazole) are considered good second-line endocrine agents. The LH-RH agonists represent the initial choice in premenopausal patients candidate to receive hormonal therapy, with the use of tamoxifen as a valuable alternative. Combination chemotherapy regimens (e.g. CMF or CAF) are usually used for first-line treatment of patients with aggressive, steroid receptor-negative disease. Recently, several relatively new agents have shown significant activity in metastatic breast cancer. In particular, the taxanes (paclitaxel and docetaxel) are particularly promising as single agents but also in combination with other drugs, especially anthracyclines. Finally, another class of agents, the d mention because they represent an important new treatment modality in the management of metastatic.
BACKGROUND: Immunohistochemical expression of the transcription factor Pax-8 in human thyroid diseases has never been investigated. The relationship between Pax-8, bcl-2 and p53 in thyroid neoplasms is also matter of interest. MATERIALS AND METHODS: Seventy-three thyroid tissue samples were evaluated for the expression of Pax-8, p53 and bcl-2 using the immunoperoxidase technique. The series included 11 follicular adenomas, 11 goitres, 23 papillary carcinomas, 16 follicular carcinomas, 6 undifferentiated carcinomas and 6 medullary carcinomas. RESULTS: The percentage of Pax-8 positive cells ranged from 14.9 to 27.1% and 10.1 to 39% in goitres and follicular adenomas, respectively. Among differentiated carcinomas, follicular histotype showed a Pax-8 immunoreactivity ranging from 0 to 26.5% of the neoplastic cells whereas in papillary carcinomas the percentage of positive cells ranged from 0 to 16.8%. None out of the six undifferentiated carcinomas showed Pax-8 immunoreactivity. The same negative pattern was noticed in medullary carcinomas. A statistically significant difference in Pax-8 expression was observed between non-malignant and malignant diseases (p < 0.0001). A different reactivity for Pax-8 was also noticed between differentiated carcinomas and undifferentiated carcinomas (p = 0.07). None of the benign tissues stained for p53 whereas among malignant specimens different percentages of p53 expression were observed with all undifferentiated carcinomas expressing the highest positivity (range 24.1-88.6%). Finally, when a combined analysis of bcl-2 and Pax-8 reactivity was carried out, some carcinomas proved to be Pax-8 negative and bcl-2 positive whereas others showed a similar immunoreactive pattern for both Pax-8 and bcl-2. CONCLUSIONS: Pax-8 is mainly expressed in benign rather than in malignant thyroid diseases and, among neoplasms, differentiated carcinomas express Pax-8 more frequently than undifferentiated carcinomas. An inverse pattern was observed for p53. Bcl-2 seems to be partially related to Pax-8 expression. However, a Pax-8 independent bcl-2 expression is also evident.
Evaluation of functional damage is the main aspect in the diagnosis of whiplash injury, therefore some type of instrumental testing is strongly needed. We describe an instrumental protocol to test subjects with whiplash, to support clinical evaluation, in order to solve the difficulty of evaluating the functional injury and the lack of fixed parameters capable of identifying this kind of injury. Eighty subjects suffering from after effects of whiplash and seventy five normal subjects undergo two instrumental tests: kinematic examination of neck mobility, and measurements of extension-flexion X-rays of the cervical spine. The results exhibited by the traumatized patients have been compared with the normal range of motion obtained from the data bank of the normal subjects. This is a report in progress of a larger research on whiplash evaluation in a clinical setting.
Trauma and surgical procedures can induce immune depression, related to the prevalent impairment of cell-mediated immunity, which may predispose to infections. The early recovery following laparoscopic cholecystectomy without infectious complications seems to be related to a lesser degree of surgical trauma and to only minimal impairment of immune functions. The present study was conducted in 20 patients with symptomatic gallstone disease, all undergoing laparoscopic cholecystectomy. Blood samples taken before operation and at 3 and 6 days postoperatively were tested for lymphocyte subsets (CD4+, CD8+, CD19+, CD57+), blood chemistry parameters (IgG, IgA, IgM, CH-50, C3, C4) and haemochrome. A group of 10 normal volunteers, matched for age and sex, were also examined twice at an interval of 48 h. Student's "t"-test was used for statistical comparisons. The findings showed only minimal changes in immune functions after operation (slight increase in CD57+ cells, and very slight decreases in IgM and C4 factor) and a slow reduction of serum haemoglobin levels as compared with preoperative values. All parameters returned to baseline levels within 6 days of the operation. This study demonstrates that laparoscopic cholecystectomy does not significantly affect immune functions, suggesting that immunity is preserved in the postoperative period.
PURPOSE: To evaluate the prognostic value of the DNA repair/redox-protein Ape1/ref-1 in a retrospective series of consecutive non-small cell lung carcinomas (NSCLC). PATIENTS AND METHODS: Sections from 91 radically resected NSCLC were analyzed for immunohistochemical expression of Ape1/ref-1. For each case 1,000 tumor cells were evaluated to detect nuclear and cytoplasmic reactivity scored as a percentage of positive cells. With respect to sub-cellular localization and percentage of immunoreactive cells, each tumor was classified as "cytoplasmic" or "non cytoplasmic". The survival rate according to Ape1/ref-1 sub-cellular localization was calculated. RESULTS: The main pattern of Ape1/ref-1 expression was nuclear. No significant difference was observed in Ape1/ref-1 pattern according to histotype (squamous vs adenocarcinoma). Among adenocarcinomas, a cytoplasmic expression of Ape1/ref-1 was significantly associated with poor survival rate in univariate (p=0.01) and multivariate (p=0.07) analyses. In addition, a cytoplasmic expression of the DNA repair protein was also predictive of worse prognosis (log-rank test, p=0.02) in cases with lymph node involvement, regardless of histotype. CONCLUSION: The results suggest a potential role of Ape1/ref-1 sub-cellular localization as a prognostic indicator in patients with NSCLC. In particular, cytoplasmic localization of the protein seems to confer a poor outcome in subgroups of patients with nodal involvement or adenocarcinoma histotype.
The authors, after a dissertation on the aetiopathogenesis of "Barrett's oesophagus", dwell on the precancerous nature of this pathology involving the oesophageal-gastric junction. Its frequent association with cancer explains the necessity for an accurate follow-up in these patients: many investigations can be useful, the radiological study of oesophagus and stomach, manometry, pH-metry, but an irrefutable diagnosis can only be achieved through endoscopy, which makes possible a histological examination of the bioptic fragments. The authors also deal with the ideal therapeutic strategy and differentiate the cases in which the pharmacological therapy is more appropriate from those that need a surgical approach.
OBJECTIVE: To value LCNB accuracy in the determination of morphobiological parameters and as an alternative to the open SB diagnostic procedure of breast lesions. SETTING: University Hospital, Italy. SUBJECTS: From May 1992 to February 1995 196 biopsies have been performed. The diameter of the neoplasms examined varied from 0.6 to 7 cm with an average of 1.9 cm. MAIN OUTCOME MEASURES: The accuracy of the two methods in the evaluation of histological degree, receptor state, protein c-erb B2 and p53 were compared. RESULTS: No inadequate sampling were ever recorded. LCNB has shown values of 97% sensitivity and 100% specificity. The positivity and negativity predicted values obtained were 100% and 89% respectively. Retrospectively 70 sample-cases of carcinoma were selected and the morphobiological parameters evaluated. The correlation coefficients for the data obtained with SB and LCNB in the evaluation of Progesteron and Oestrogen receptor expression, protein c-erb B2 and p53 were excellent. Furthermore it was noted that LCNB allows a saving of at least 1/3 of the cost vs intraoperative SB. CONCLUSIONS: Percutaneous LCNB has high diagnostic accuracy for histological classification. LCNB has the same accuracy as SB for morphobiological parameters. The cost of LCNB is markedly lower than SB.
A blind test of measurement reliability was performed in vitro using lateral x-rays of cervical vertebrae. Dry specimens of C3 and C4 were mounted in a movable frame and flexion/extension was simulated. Lateral x-rays were taken for each degree from 15 degrees flexion to 15 degrees extension. Then the x-rays were measured by four raters. The results show a high level of absolute measurement error. This suggests caution in accepting existing literature data on cervical x-ray measurements unless some indicator of the personal measuring accuracy of the rater is specified. The procedure described in this paper can be used to ascertain such accuracy.