Biomedical subjects

C Di Gregorio

Publications and source records attributed to C Di Gregorio.

At least 37 records · Page 2Linked to original sources

PubMed1997

Vinorelbine, cisplatin, and 5-fluorouracil as initial treatment for previously untreated, unresectable squamous cell carcinoma of the head and neck: results of a phase II multicenter study.

BACKGROUND: The combination of vinorelbine (VNR), cisplatin (CDDP), and 5-fluorouracil (5-FU) has previously been shown to be active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCHNC). This multicenter Phase II study was carried out with the aim of evaluating the effectiveness of this combination in patients with previously untreated, unresectable locally advanced SCHNC. METHODS: Sixty patients with previously untreated, unresectable SCHNC were treated with CDDP 80 mg/m2 on Days 1, 5-FU 600 mg/m2 as a 4-hour infusion on Days 2-5, and VNR 25 mg/m2 i.v. bolus on Days 2 and 8. There were 15 patients with laryngeal carcinoma, 19 patients with oropharyngeal carcinoma, 15 with carcinoma in the oral cavity, 5 with carcinoma in the hypopharynx, and 4 with carcinoma in the maxillary sinus. Most patients (78%) had Stage IV disease. After achievement of the best possible objective response, patients were subjected to definitive locoregional treatment, i.e., radiotherapy and/or surgery, as appropriate. RESULTS: All patients completed the induction chemotherapy. After a mean of 3.86 cycles per patient, the overall response rate was 88% (95% confidence interval [CI], 82-94%), with a complete response rate of 23% (95% CI, 14-26%). Complete responses were more frequently seen in patients with N0-1 disease than in those with N2-3 disease (P = 0.037). No other statistically significant correlation between type of response and extent of disease was noted. Toxicity consisted mainly of myelosuppression and gastrointestinal side effects. After definitive locoregional treatment, 58% of patients were clinically free of disease. These patients included those who had complete response after induction chemotherapy, 19 of 39 patients who had partial response, and 2 with stable disease. Median disease free survival was 16 months, and median overall survival was 23 months. CONCLUSIONS: The combination regimen of CDDP, 5-FU, and VNR was very active in previously untreated SCHNC. It was well tolerated in most cases, and neurotoxicity was not a major side effect. This regimen, which does not require hospitalization, should be compared with standard chemotherapy, such as the combination of CDDP and continuous-infusion 5-FU.

Aged↗

PubMed1997

K-ras and p53 mutations in hereditary non-polyposis colorectal cancers.

Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). To test that the targets of genetic instability could include critical transforming genes involved in colon tumor progression, we examined 23 colorectal carcinomas in patients with HNPCC in order to detect somatic mutations in K-ras and p53 genes. Using single strand conformation polymorphism followed by direct DNA sequencing, we detected 4 mutations in K-ras gene (17%) and 3 in p53 gene (13%) which change the amino acid sequence of the protein p53. This is significantly lower than in sporadic cancer. Our data suggest that colon cancer in HNPCC might partly involve a distinct pathogenetic mechanism that involves other genes than those altered in sporadic tumors.

Adult↗

PubMed1997

Histology of aberrant crypt foci in the human colon.

Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5-10 min. The strips were measured, put on a glass slide and observed under a light microscope at x25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.

Aged↗

PubMed1996

Survival for colon and rectal cancer in a population-based cancer registry.

Dukes' stage is the most powerful indicator of patient outcome for colorectal cancer. Several cancer survival studies have considered other prognostic variables, but results are often conflicting. We sought to assess the independent value of several clinical and morphological variables in defining colorectal cancer specific survival. 397 colorectal cancer patients diagnosed from 1984 to 1986, and registered in a large bowel cancer registry instituted in a local health district of Northern Italy, were actively followed-up until 31 December 1991. Univariate and multivariate survival analyses were carried out in colon and rectal cancer cases, separately, using the actuarial life-table method and Cox proportional hazard regressions. Crude and specific 5-year survival rates were 37.5 and 41.4%. In univariate analysis, TNM (tumour, nodes and metastases) stage was the strongest predictor of prognosis in both sites. Other variables significantly related to survival were age of patient at diagnosis and pattern of tumour growth in colon cancer, type of differentiation and pattern of tumour growth in rectal cancer. In multivariate analyses, after adjusting for stage, age had a weak but significant negative effect on colon cancer survival, whereas rectal tumours with the infiltrating type of growth had a significantly worse prognosis than those with the expanding type. Colorectal cancer survival should be analysed in the main large bowel subsites in order to define high-risk groups within each TNM stage category.

Aged↗

PubMed1996

Clinical features, frequency and prognosis of Dukes' A colorectal carcinoma: a population-based investigation.

The main aim of this study was, through the data of a population-based Registry, to establish the incidence of Dukes' A lesions by year of registration and the main clinical features, and to assess cancer-specific survival. One hundred and eighteen Dukes' A colorectal tumours were diagnosed (in 117 patients) out of 1337 registered between 1984 and 1992 in the Health Care District of Modena, Northern Italy; 94 patients were treated with surgery and 23 with endoscopic polypectomy. The frequency of Dukes' A tumours ranged between 4.8% and 18% by year of registration. Dukes' A carcinomas were significantly more frequent in the distal colon. Only 5 patients (4%) died of their cancer, and in all patients the tumour was localised in the rectum. Carcinomas associated with a poor prognosis did not show any of the biological variables usually associated with an unfavourable outcome, but, our data suggest the possibility of incomplete removal of tumours at surgery.

Aged↗

PubMed1996

[Pilomatrixoma associated with anetoderma].

The authors describe a pilomatricoma with perilesional anetoderma in a young woman. The papillary dermis showed a complete lack of elastic fibres and epidermal atrophy. Clinical diagnosis of pilomatricoma is possible but histologic examination is required to differentiate it from cystic lesions or other benign appendage tumors. At different rates shadow and basophilic cells must be found. The association of a pilomatricoma with anetoderma appears more frequent than usually reported and is important for clinical diagnosis. The histogenesis of this cutaneous lesion is controversial: probably there is a relation between inflammatory processes of pilomatricomas and lack of elastic fibres.

Adult↗

PubMed1996

Clinico-pathological correlation and prognostic significance of nuclear p53 protein in colorectal cancer. Colorectal Cancer Study Group of the University and Health Care District of Modena.

Overexpression of p53 protein was studied in neoplastic specimens of 150 patients registered for colorectal adenocarcinoma in the Health Care District 16 of Modena, Italy, from 1984 to 1986. We selected Dukes' stage B (92) and C (58) patients whose survival and recurrence rates are not easily predictable, with the purpose of defining subgroups of patients at high risk of recurrence. Monoclonal antibody PAb 1801 was used on formalin-fixed, paraffin embedded specimens. Nuclear staining was assessed to divide tumours into three groups: a) negative, b) low expressors, c) high expressors. Histomorphological variables of tumours, major clinical features of the patients and 5-year specific survival, were evaluated and related to p53 status. p53 was found in 71 out of 150 cases (47.3%); 50 tumours were high and 21 low expressors. No correlation was found between p53 overexpression and clinico-pathological variables. No difference in survival was found between patients with p53 positive and negative tumours in the entire series or within Dukes' stage B and C patients. However, the subgroup of patients with stage C rectal cancer seemed to have a better prognosis if the tumour was p53 negative (of borderline significance, p = 0.15). The same results were obtained by grouping low expressor tumours alternatively with negative or high expressors. We conclude that p53 nuclear overexpression does not seem to influence the prognosis of Dukes' stage B or C colorectal cancer patients.

Adenocarcinoma↗

PubMed1995

Biologic characterization of hereditary non-polyposis colorectal cancer. Nuclear ploidy, AgNOR count, microvessel distribution, oncogene expression, and grade-related parameters.

The identification of hereditary non-polyposis colorectal cancer (HNPCC) is important not only for the patient, but also for family members who are at increased risk of developing cancer. To determine if measuring various pathobiologic features of the colon carcinomas is useful in separating sporadic from HNPCC tumors, the authors studied tumor tissues from 46 patients with HNPCC and compared them to 70 with sporadic colorectal carcinoma. Parameters investigated included DNA ploidy (flow cytometry), AgNOR count (by silver staining), microvessel density (immunohistochemistry), p53 and K-ras expression, and grade-related parameters. Diploid tumors were more frequent in patients with HNPCC (65% vs 40%, P < .02), thus confirming previous observations concerning such an association. Higher AgNOR counts and greater AgNOR areas were observed in sporadic tumors than in HNPCC (5.2 +/- 1.5 vs 4.5 +/- 1.8, P < .01). Hereditary tumors tended to be less vascularized, whereas oncogene expression and grade-related parameters did not show appreciable differences between the two types of tumors. In conclusion, some of the investigated parameters may contribute to defining the biologic profile of HNPCC. In addition, these findings support the clinical impression of a more favorable outcome that is frequently seen in HNPCC patients.

Adult↗

PubMed1995

Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck.

Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response rates was carried out separately for previously untreated patients, and those with recurrent disease after surgery and/or radiotherapy. In the group of 20 patients with recurrent disease the overall response rate was 55% (95% CL 44-66%), with 3 patients (15%) showing a complete response with a mean duration of 6.2+ months and 8 patients showing a partial response with a mean duration of 8.6+ months. In the group of patients with previously untreated unresectable disease, 13 patients (87%, 95% CL 78-96%) had a major objective response with a complete response rate of 27%. This regimen was quite well tolerated, with meyelosuppression and vomiting being the most frequent toxicities. The occurrence of an acute pain syndrome following vinorelbine administration in 4 patients is noteworthy. In conclusion, this combination is active in advanced squamous cell head and neck carcinoma. However, although it may be recommended in recurrent carcinoma, the complete response rate achieved in previously untreated patients is lower than that reported with other more intensive regimens.

Adult↗

PubMed1994

Expression of p53 protein in prostate cancers of different histologic types.

Mutations and overexpression of p53 gene in prostate carcinoma have been found but their significance in the development and progression of cancer is so far unknown. We investigated the prevalence of abnormalities of p53 protein in a heterogeneous group of prostate carcinoma to verify whether acinar and non acinar carcinomas have a different expression of p53 protein. Paraffin sections of 45 prostate carcinomas (39 acinar, 3 ductal papillary, 1 transitional cell, 1 mucinous and 1 pure small cell) were examined for the expression of p53 protein using a panel of antibodies (monoclonal antibodies Pab 1801, D07 and polyclonal antibody CM1). No p53 expression was observed in any acinar carcinomas independent of grade and stage. For non acinar carcinomas only small cell and transitional cell carcinomas exhibited detectable amounts of p53 protein in tumour cell nuclei. The prevalence of p53 overexpression in prostate carcinoma is relatively low compared with that found in many other tumours. In the present study, the overexpression of p53 in a small cell carcinoma and in a transitional cell carcinoma suggest that the loss of suppressing role of p53 gene may be an important mechanism in the genesis and in the development of these uncommon tumours.

Aged↗

PubMed1994

Rare prostatic carcinomas: histogenesis and morphologic pattern.

Most prostate cancers (90%) are acinar adenocarcinomas, originating in the peripheral or other prostatic regions. In a series of 650 cases of prostate carcinoma we found 7 cases of prostate carcinoma with unusual features, including 3 pure duct papillary carcinomas, 1 pure transitional cell carcinoma, 1 mucinous adenocarcinoma and 2 pure small cell carcinomas. Ductal papillary carcinoma consists of papillary fronds and branching, fibro-connective tissue, covered by a single layered to multilayered lining of columnar cells. Also the tumours located in central portions of the prostate derive from periurethral prostatic ducts. Primary transitional cell carcinoma of the prostate implies no pre-existing bladder cancer and arises from indifferent or reserve cells, lying between the luminal epithelium and the basement membrane of the periurethral ducts. The diagnosis of mucinous carcinoma should be reserved for these cases in which a sufficient quantity of extracellular mucin is seen to form pools and lakes. True mucinous carcinoma is likely to be a variant of prostate carcinoma. Classic oat cell carcinomas are composed of small, fairly uniform tumour cells only slightly larger than lymphocytes, arranged in solid nests wherein central necrosis is commonly observed. The pathological finding, clinical course and immunohistochemical studies, indicate that the small cell carcinoma of the prostate is most likely to be a neuroendocrine neoplasm.

Adenocarcinoma, Mucinous↗

PubMed1993

Cell kinetic evaluation of human colonic aberrant crypts. (Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, Modena, Italy).

Foci of aberrant crypts (ACF) have been observed on the unsectioned, methylene blue-stained mucosal surface of the human colon. Experimental evidence and the histological features of the lesions suggest that they might be early events in colon cancer development. The main objective of the present study was to evaluate cell kinetic properties of ACF in the human colon. Five samples of colon mucosa were collected immediately after operation following the administration of 500 mg of 5'-bromo-2'-deoxyuridine prior to surgery. ACF were then identified on the fixed, unsectioned, methylene blue-stained mucosal surface under a light microscope. Some specimens containing ACF were serially sectioned perpendicular to the luminal surface of the intestine, along with specimens of normal-appearing mucosa. Several sections were prepared for the immunohistochemical identification of 5'-bromo-2'-deoxyuridine-incorporating cells (in the S phase of the cell cycle). The results of this study demonstrated that aberrant crypts have more cells per crypt than normal glands. Total labeling index and labeling index values in each of the five longitudinal compartments in which each crypt was divided showed an increased total proliferative activity in all ACF examined, although limited to the lower crypt compartments in almost all aberrant crypts evaluated. These findings are in keeping with previous cell kinetic studies and observations in experimental animals and provide evidence of the involvement of human aberrant crypts in the stepwise process leading from normal mucosa to colon cancer.

Aged↗

PubMed1993

Tumour spectrum in hereditary non-polyposis colorectal cancer (HNPCC) and in families with "suspected HNPCC". A population-based study in northern Italy. Colorectal Cancer Study Group.

Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up.

Adult↗

PubMed1993

Descriptive epidemiology of colorectal cancer in Italy: the 6-year experience of a specialised registry.

The Colorectal Cancer Registry of Modena recorded 838 malignancies of the large bowel between 1984 and 1989. Crude Incidence rates were 59.5 new cases per 100,000 per year in men and 47.4 in women (age-standardised values 33.1 and 20.6, respectively). 35 incident cases (4.2%) had multiple colorectal tumours, whereas 42 (5.1%) had extraintestinal malignancies (mainly breast, endometrium and stomach). Although 90.5% of the patients underwent surgery, this was "curative" in 634 (77.6% of the total), while 105 individuals (12.8%) had palliative operations; 78 patients (9.5%) were not operated, mainly because of metastatic disease or poor clinical condition. Finally, emergency operations--due to intestinal obstruction, perforation or massive bleeding--were carried out in 46 patients (6.1%). A total of 659 tumours (79%) were accurately staged. Among first-degree relatives of the registered patients a significant excess of cases of colorectal cancer was found in each year of the study. 5-year survival was evaluated in 132 (out of 140) patients registered in 1984 and followed-up until 1989. Overall 5-year survival was 37%, but rose to 43% when only colorectal cancer related deaths were taken into consideration. As expected, survival was strongly influenced by stage (P < 0.0001 by log-rank test). In conclusion, this study confirms previously reported data about incidence and mortality rates for colorectal cancer in northern Italy. The particular approach--limited to the large bowel--allowed the evaluation of the frequency of multiple tumours and of the marked aggregation of cancer among first-degree relatives. Finally, survival figures are comparable to those of many other studies and confirm that the clinical outcome of this neoplasm remains unfavourable in more than 50% of the affected patients.

Adult↗

PubMed1993

Are routine duodenal and antral biopsies useful in the management of "functional" dyspepsia? A diagnostic and therapeutic study.

Fifty-three patients with previously uninvestigated chronic dyspepsia symptoms in the absence of gastrointestinal or extra-gastrointestinal disease (functional dyspepsia) underwent antral and duodenal mucosal biopsies to detect the role of such samplings in the presence of normal endoscopic findings. Patients were enrolled in a randomized, placebo-controlled, double-blind trial, receiving either eradicating treatment (colloidal bismuth subcitrate plus metronidazole) or placebo if they had Helicobacter pylori-associated gastritis (20 patients), or cisapride or placebo if they had normal antral mucosa (28 cases). Unsuspected celiac sprue was found in one patient. Eradicating treatment ameliorated histological gastritis (p = 0.01). However, owing to great placebo efficacy, symptom remission rates following a 1-month wash-out period in both treatment groups were no higher than that in controls. Independent of the initial randomization, an extremely low symptom recurrence rate was observed during a drug-free follow-up study equivalent to the mean duration of symptoms before enrollment. We conclude that in functional dyspepsia, bulbar and antral biopsies are not useful in clinical management, equivalent symptom relief can be achieved in patients randomly assigned to both drugs and placebos, and such improvement can be long lasting in the absence of any maintenance treatment. We believe the prevalence of unsuspected villous atrophy and the therapeutic role of investigation-based reassurance deserve further assessment.

Adult↗

PubMed1993

Gastric dysplasia. A follow-up study.

Gastric dysplasia is generally accepted as a precancerous lesion. Ninety-nine patients with an initial diagnosis of gastric dysplasia, based on examination of endoscopic biopsies taken because of symptoms of dyspepsia, were followed to define the magnitude of the neoplastic risk. The degree of dysplasia in the initial biopsy was mild in 73 cases, moderate in 16, and severe in 10. Mild dysplasia was no longer detected in 74% of patients, persisted in 19%, and progressed in 7% (in four cases, to carcinoma). Moderate dysplasia regressed to mild dysplasia in 31% of cases, it was no longer found in 56%, and progressed to cancer in 13%. Our data show that both lesions can progress slowly, although in most instances they remain stable or regress. Thus, annual endoscopic and histologic controls appear to be advisable. Severe dysplasia was no longer detected in 20% of cases, regressed to moderate in 10%, persisted in 10%, and progressed to cancer in 60%; in half of these patients, carcinoma was detected within 3 months. Thus, severe dysplasia indicates a high risk of cancer, often a synchronous one, and it requires gastrectomy when it persists in repeated biopsies.

Adult↗

PubMed1992

Cell kinetics evaluation of colorectal tumors after in vivo administration of bromodeoxyuridine.

Although several biomarkers have been tested, Dukes' (or TNM) stage at diagnosis is still considered the only prognostic factor of clinical relevance in colorectal cancer. Among the various biomarkers, the fraction of cells engaged in DNA synthesis has been extensively investigated as an indicator of tumor aggressiveness. Bromodeoxyuridine (BUdR) is a non-radioactive thymidine analogue which is incorporated into DNA during the S-phase of cycling cells. In order to evaluate the relationships between cell kinetics and morphologic variables, 500 mg of BUdR were given i.v. to 46 patients with colorectal cancer prior to surgery. After operation, a large tumor sample was taken and processed for immunohistochemical detection of BUdR-labeled cells in various regions of the neoplasm and in normal colorectal mucosa. Smaller superficial tumor specimens were also incubated with 3H-thymidine (3H-TdR) for the autoradiographic identification of labeled cells. In the 43 evaluable tumors, the overall BUdR labeling index (BLI, percent of labeled cells) was significantly higher in carcinoma (20.30 +/- 0.86%, SEM) than in normal colonic mucosa (6.51 +/- 0.49%). BLIs in central and peripheral regions of carcinoma were closely correlated (r = 0.48, p = 0.003). In 21 neoplasms a high correlation between overall BUdR and 3H-TdR labeling index in the same tumor was observed (r = 0.57, p = 0.007). No evident association between overall BLI and clinical or morphologic parameters of the tumor was seen, including number of capillaries and ras-p21 protein expression. We conclude that BUdR immunostaining after in vivo administration of BUdR is a simple method for studying cell kinetics in various regions of colorectal cancer. BUdR labeling data are comparable to those obtained with in vitro incorporation of 3H-TdR.

Adult↗

PubMed1992

Clinical and pathologic prognostic indicators in colorectal cancer. A population-based study.

The institution of a colorectal Cancer Register in a health care district of Northern Italy gave the authors the opportunity to evaluate the prognostic relevance of several morphologic and clinical variables by univariate and multivariate analyses. Of the 134 patients registered in 1984, 132 were followed up until the end of 1989. Overall 5-year survival was 37%, but the figure increased to 43% when only colorectal cancer-related deaths were considered. Univariate analysis for clinical variables showed that TNM staging and age at diagnosis were significantly related to prognosis, whereas none of the other parameters were indicative of the clinical outcome. With a similar analysis, among the various morphologic variables, pattern of growth (infiltrating versus expanding) and extent of fibrosis (extensive versus little or absent) appeared to be indicators of prognosis. When the variables that were significant (stage, age, pattern of growth, and fibrosis) in the univariate analysis were entered into the Cox model of multivariate analysis, TNM staging was the only parameter that maintained an independent prognostic importance. The authors state that their results confirm the importance of stage in predicting survival for cancer of the large bowel and suggest that the possible prognostic value of clinical and morphologic variables should be investigated within each of the major TNM or Dukes' classes.

Age Factors↗