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Biomedical subjects

S Tomao

Publications and source records attributed to S Tomao.

At least 19 recordsLinked to original sources

The colorectal malignant polyp: scoping a dilemma.

Colorectal adenomas containing invasive carcinoma represent the majority of early colorectal cancers. The malignant polyp carries a significant risk of lympho-haematic metastasis and mortality due to the penetration of cancerous cells into the submucosal layer. The therapeutic dilemma is whether to perform endoscopic or surgical resection. A thorough assessment of the endoscopic, histological and clinical variables is needed to unravel the best treatment for each patient. In particular, a unique staging of such lesions, based on certain histopathological features, has been deeply implicated in the therapeutic choice. Aim of this article is to review the main endoscopic, histological and clinical features of the malignant polyp in order to propose a systematic management of this lesion.

Adenomatous Polyps↗

BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models.

BACKGROUND: Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both genetic and non-genetic factors. A combination of BRCA1 and BRCA2 gene mutations appears responsible for about 20%-30% of the cases with breast cancer familial history. The prevalence of BRCA1/2 pathogenic mutations largely varies within different populations; in particular, the rate of mutations in Italian breast and/or ovarian cancer families is rather controversial and ranges from 8% to 37%. PATIENTS AND METHODS: Of the 152 breast/ovarian cancer families counseled in our centre, 99 were selected for BRCA1/2 mutation screening according to our minimal criteria. The entire coding sequences and each intron/exon boundary of BRCA1/2 genes were screened by direct sequencing (PTT limited to BRCA1 exon 11). For each proband, the a priori probability of carrying a pathogenic BRCA1/2 germline mutation was calculated by means of different mutation prediction models (BRCApro, IC and Myriad Table) in order to evaluate their performances. RESULTS: Our analysis resulted in the identification of 25 and 52 variants in the BRCA1 and BRCA2 genes, respectively. Seventeen of them represent novel variants, including four deleterious truncating mutations in the BRCA2 gene (472insA, E33X, C1630X and IVS6+1G>C). Twenty-seven of the 99 probands harbored BRCA1 (n = 15) and BRCA2 (n = 12) pathogenic germline mutations, indicating an overall detection rate of 27.3% and increasing by more than 15% the spectrum of mutations in the Italian population. Furthermore, we found the lowest detection rate (19.4%) in pure hereditary breast cancer family subset. All of the prediction models showed praises and faults, with the IC software being extremely sensitive but poorly specific, compared to BRCApro. In particular all models accumulated most false-negative prediction in the HBC subset. Interestingly preliminary results of a study addressing the presence of genomic rearrangements in HBC probands with BRCApro or IC prediction scores >/=95%, provided evidence for additional mutations undetectable with our conventional screening for point mutations. CONCLUSIONS: Altogether our results suggest that HBC families, the largest pool in our series, represent an heterogeneous group where the apparently faulty performances of the prediction models might be at least partially explained by the presence of additional kinds of BRCA1/2 alteration (such as genomic rearrangements) or by mutations on different breast cancer related genes.

Adult↗

Retroperitoneal schwannoma presenting as an ovarian tumor.

A mass in the left annexal zone was discovered in a 56-year-old woman at the Department of General Surgery and was diagnosed as ovarian cancer. After the operation the mass appeared histologically to be retroperitoneal leyiomiosarcoma and because of residual disease, confirmed by computed tomography (CT) and nuclear magnetic resonance (NMR), complementary radiotherapy was carried out. Restaging supported the persistence of the tumor and so a second laparotomy was performed with complete tumor resection; the pathologic diagnosis was retroperitoneal benign schwannoma. The importance of careful preoperative imaging, such as echography, CT, NMR, arteriography and urography should be stressed for a correct clinical and surgical approach. Moreover, considering that in some selected clinical cases these tumors could be confused with others deriving from contiguous organs and structures, a different surgical approach may be needed together with dedicated and expert surgeons.

Diagnosis, Differential↗

Trastuzumab in metastatic breast cancer.

Metastatic breast cancer is an incurable disease in a very high percentage of patients. Despite new progress in endocrine and other systemic therapies, this evidence remains challenging for patients and clinicians. HER2 protein is a member of the epidermal growth factor family of transmembrane receptors. HER2 is overexpressed in approximately 20% to 30% of breast cancers. Overexpression of HER2 has been shown to be associated with increased tumor proliferation and relative resistance to some types of chemotherapy and hormonal therapies. Trastuzumab, a humanized monoclonal antibody directed against HER2 protein, has been shown to be an efficacious and well tolerated treatment for HER2-overexpressing metastatic breast cancer, both as a single agent and when it is used in combination with chemotherapy.

Antibodies, Monoclonal↗

Gastric cancer prevalence in patients with liver cirrhosis.

An increased risk for gastric cancer in patients with liver cirrhosis has recently been reported in epidemiological studies. The present endoscopic study was performed to further evaluate whether people with cirrhosis are at increased risk for gastric cancer development. We reviewed the medical records of all cirrhotic patients referred to our Endoscopic Service for portal hypertension screening and, therefore, cases of latent gastric cancer were observed. For a comparison, the prevalence (age and sex standardized) of latent gastric cancer in the general population was estimated hypothesizing a latency period of 5 years. Overall, 1379 patients with cirrhosis were selected from a total of 15 791 endoscopically examined different patients observed during the period 1982-1997. Histological assessment revealed the presence of gastric cancer in 10 patients (9 males and 1 female). There was a significant 2.6-fold (P<0.01) increase in prevalence of gastric cancer compared with that expected in our cirrhotic patients. In conclusion, our findings confirm that liver cirrhosis would seem to be a risk factor for the development of gastric cancer. Other studies are needed to evaluate the pathogenic mechanisms involved.

Adult↗

Gastric epithelial cell proliferation in patients with liver cirrhosis.

An increased risk for gastric cancer in patients with liver cirrhosis has recently been reported. This study was performed in order to determine gastric epithelial cell proliferation in cirrhotic patients and to evaluate the role of congestive gastropathy (CG) and Helicobacter pylori infection in this process. Thirty-six cirrhotic patients and 18 controls were enrolled in the study. All patients underwent endoscopy and three biopsies were performed in the antrum and three in the gastric body. The presence of H. pylori infection was assessed by a rapid urease test and histology. The antral biopsies were used for gastric cell proliferation assessment by an immunohistochemical analysis (Ki-67). There was no significant difference in epithelial cell proliferation between cirrhotics and controls. Gastric proliferation values were higher in patients with H. pylori infection compared with uninfected patients, both in cirrhotic (P = 0.003) and in control groups (P = 0.06). Among the cirrhotic group, we found a progressive increase in gastric cell proliferation values related to the degree of CG, the highest values being observed in cirrhotic patients with severe CG. Moreover, cirrhotics with both severe CG and H. pylori infection had the highest proliferation values when compared with all other subgroups. In conclusion, this study found that: (1) CG significantly affects epithelial cell proliferation in gastric mucosa in cirrhotic patients, (2) H. pylori infection plays a similar role in gastric cell proliferation in both cirrhotic and non-cirrhotic patients, and (3) CG and H. pylori could act synergistically in this process.

Adult↗

[Chemotherapy in gastroenterologic neuroendocrine tumors].

Gastrointestinal neuroendocrine tumors (carcinoids tumors and endocrine islet cell tumors) are a family of rare malignancies with many typical characteristics by a biologic, epidemiologic and clinical point of view. In this category of neoplasia an integrated clinical and therapeutic approach is mandatory, whereas for too many years these tumors were investigated and treated in an empirical way without considering an integrated approach. The singular features of this class of malignancies, with different and complex symptomatology, with enigmatic clinical presentation and outcome and with conflicting therapeutic options, oblige the clinicians to give different treatment to the patients. Chemotherapy has a marginal role in gastrointestinal neuroendocrine tumors mostly because it is used in patients with advanced disease not suitable for other therapeutic approach (surgery, thermoablation, chemoembolization, biotherapy). Unfortunately in the past it was not possible to establish the efficacy of chemotherapy in these malignancies because most of the studies pooled without distinction carcinoids, pancreatic tumors and hepatic metastases from unknown primary. The most extensively studied drugs have been streptozotocin, doxorubicin, mitoxantrone, dacarbazine, used alone or in combination; the gold standard today is considered the association of streptozotocin with doxorubicin or 5-fluorouracil, but there is strong evidence that the disappointing results in the treatment of these rare malignancies could be improved in a multidisciplinary fashion; in this field the combination of new drugs with aggressive surgery, radionuclide therapy, biotherapy and local therapeutic approach will give new opportunities to better control the symptoms and the clinical course of gastrointestinal neuroendocrine tumors.

Gastrointestinal Neoplasms↗

[Chemotherapy in the elderly patient].

In the past, the clinical approach in elderly cancer patients was different than in younger ones; the natural history of neoplastic disease and the chemotherapy-related toxicity were the main reasons for this behaviour, and frequently over 65 years patients were excluded from chemotherapeutic treatments and from clinical trials. In the last years, according to clinical data, this approach changed and now there is evidence that also old patients (70-80 ys) can be treated with full dose chemotherapy, on condition that no poor performance status and no severe associated disease are present. Nevertheless, because of the increasing number of cancer patients with advanced age, in future it will be necessary to optimize the antineoplastic treatments individualizing chemotherapy and improving the clinical surveillance in this subset of patients. Moreover it will be strategic to identify optimal schedules of treatment in elderly cancer patients.

Age Factors↗

Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients.

PURPOSE: To evaluate the endocrinological and clinical activity of a new slow-release formulation of leuprolide acetate in breast cancer patients. METHODS: A total of 50 pre- or perimenopausal patients with early- or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either 3.75 mg of leuprolide acetate every month or 11.25 mg of leuprolide acetate every 3 months. Patients were treated until disease recurrence or progression or for a maximum of 24 months. Treatment outcome, side effects, and serum levels of gonadotrophins, estradiol, progesterone, and delta4-androstenedione were analyzed at different time points. RESULTS: In all, 23 patients were allocated to the monthly formulation and 27, to the 3-monthly formulation. The median time on treatment was comparable. There was no evidence of any difference in clinical outcome or drug-induced side effects, hot flushes being recorded in about 50% of patients in both groups. Altogether, 35 patients were actively menstruating at the beginning of treatment; all of them became amenorrhoic after 3 months and remained so until treatment with leuprolide was continued, irrespective of the allocated treatment. All endocrine parameters, particularly estradiol levels, were suppressed to a similar extent. CONCLUSIONS: The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients.

Adult↗

Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline-resistant metastatic breast cancer: A phase I-II clinical trial.

BACKGROUND: Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC) and has shown an overall response rate of 40%-50% as first-line treatment. In vitro, a synergy has been observed between this drug and ifosfamide (IFX). In addition, the pharmacokinetics of IFX suggest that it may have greater activity when given by continuous-intravenous infusion (C.I.V.I.). The aim of this study was therefore to assess the antitumor efficacy and toxicity of the combination of bolus VNR and C.I.V.I. IFX as second-line therapy in anthracycline-resistant breast cancer patients. PATIENTS AND METHODS: Forty-two patients with MBC who had already received anthracycline-based chemotherapy were treated with a regimen consisting of IFX, by C.I.V.I. for 72 hours and bolus VNR. The courses were repeated every three weeks for a maximum of eight cycles. Four dose intensification steps were planned. IFX, 1.5 g/m(2) on days 1-3 + VNR, 30 mg/m(2) on day 1 (six patients); IFX, 2 g/m(2) on days 1-3 + VNR, 25 mg/m(2) on day 1 (six patients); IFX, 1.8 g/m(2) on days 1-3 + VNR, 25 mg/m(2) on days 1 and 8 (six patients); IFX, 2 g/m(2) on days 1-3 + VNR, 25 mg/m(2) on days 1 and 8 (24 patients). Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion ratio of 1:1 and, once the infusion was completed, per os every four hours for three times. RESULTS: All of the 42 patients entered were assessable for toxicity, and 41 of them for response. Neutropenia was the most frequently-occurring toxicity, but only five patients at the highest dose level (11.9%) presented grade 4, and none of those at the first three steps. Other significant toxic effects were mild (only grade I-II). The median relative dose intensity was 95% at the highest dose level and all the treatments were administered on an out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8% (two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of 41 patients). The median response duration was 7.0 months (range 2-13 months). CONCLUSIONS: The present phase I-II study shows that the IFX and VNR combination is an active and well-tolerated treatment in MBC and provides an alternative to taxanes for patients previously treated with anthracyclines.

Adenocarcinoma↗

Gastric pathology in patients with common variable immunodeficiency.

BACKGROUND/AIMS: Common variable immunodeficiency (CVID) is an immunological disorder characterised by defective antibody production. Patients with CVID have a high risk of gastric cancer. It has been suggested that gastric cancer results from an interaction between environmental factors and a genetic predisposition. The role of Helicobacter pylori as an environmental factor in gastric carcinogenesis is of current interest. Moreover, p53 gene mutations have been reported in gastric cancer. This study focuses on the gastric pathology of patients with CVID and correlation with H pylori infection. METHODS: Thirty four consecutive dyspeptic patients with CVID (mean age 49.6 years, range 14-72; 17 men) were included in the study. An upper gastrointestinal endoscopy was performed and biopsy specimens were taken from the antrum, incisura angularis, and gastric body. Biopsies were used for histological assessment, to identify the presence of H pylori, and to evaluate p53 overexpression. RESULTS: H pylori infection was detected in 14/34 (41%) patients. Chronic active gastritis involving both antrum and body was observed more frequently in H pylori positive (79%) than H pylori negative (20%) patients (p = 0.001). Similarly, a histological feature of multifocal atrophic gastritis was found more frequently in infected (50%) than uninfected patients (10%) (p = 0.012). In addition, one case of gastric adenocarcinoma and another of notable dysplasia were observed in the H pylori positive group. Overexpression of p53 was found in six (18%) patients, including one with normal gastric mucosa. CONCLUSIONS: It can be hypothesised that both H pylori and p53 alterations play a role in the gastric carcinogenesis of patients with CVID.

Adolescent↗

Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline-resistant metastatic breast cancer: a phase I-II clinical trial.

BACKGROUND: Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC) and has shown an overall response rate of 40%-50% as first-line treatment. In vitro, a synergy has been observed between this drug and ifosfamide (IFX). In addition, the pharmacokinetics of IFX suggest that it may have greater activity when given by continuous-intravenous infusion (c.i.v.i.). The aim of this study was, therefore, to assess the antitumor efficacy and toxicity of the combination of bolus VNR and c.i.v.i. IFX as second-line therapy in anthracycline-resistant breast cancer patients. PATIENTS AND METHODS: Forty-two patients with MBC who had already received anthracycline-based chemotherapy were treated with a regimen consisting of IFX, by c.i.v.i. for 72 hours and bolus VNR. The courses were repeated every three weeks for a maximum of eight cycles. Four dose intensification steps were planned: IFX, 1.5 g/m2 on days 1-3 + VNR, 30 mg/m2 on day 1 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on day 1 (six patients); IFX, 1.8 mg/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (six patients); IFX, 2 g/m2 on days 1-3 + VNR, 25 mg/m2 on days 1 and 8 (24 patients). Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion ratio of 1:1 and, once the infusion was completed, per os every four hours for three times. RESULTS: All of the 42 patients entered were assessable for toxicity, and 41 of them for response. Neutropenia was the most frequently-occurring toxicity, but only five patients at the highest dose level (11.9%) presented grade 4, and none of those at the first three steps. Other significant toxic effects were mild (only grade I-II). The median relative dose intensity was 95% at the highest dose level and all of the treatments were administered on an out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8% (two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of 41 patients). The median response duration was 7.0 months (range 2-13 months). CONCLUSIONS: The present phase I-II study shows that the IFX and VNR combination is an active and well-tolerated treatment in MBC and provides an alternative to taxanes for patients previously treated with anthracyclines.

Adult↗

Prevalence of human papillomavirus, cytomegalovirus, and Epstein-Barr virus in the cervix of healthy women.

The prevalence of some sexually transmitted viruses, possibly involved in cervical carcinogenesis, was studied in the cervix of women with normal cytology. The presence of human papillomaviruses (HPV) type 16 and 18, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) genomes in cervical cells taken from 143 healthy Italian women was investigated using the polymerase chain reaction (PCR). The study population was divided into four groups with respect to age as follows: group I, 17 to 25 years, n = 48 women; group II, 26 to 35 years, n = 30; group III, 36 to 50 years, n = 32; and group IV, 51 to 70 years, n = 33. In the first age group prevalence rates of HPV 16, CMV and EBV infection of 23%, 21% and 19% were found respectively. The infection rates of HPV 16 and CMV were shown to decrease with age, with prevalences of HPV 16 at 10% in the second group, 6% in the third and 3% in the fourth and of CMV at 13% in the second and third and 6% in the fourth groups. The prevalence of EBV infection did not decrease with increasing age (19% in the first and third groups, 20% in the second and 18% in the fourth). The occurrence of HPV 18 genome was very low (0-3%) and independent of age. In the first age group a higher percentage of double infections (16.6%) was found than in the three other age groups (6% in the second and third and 3% in the fourth). The finding of multiple infections in younger women requires further study in order to clarify the implications of such viral infections in healthy women and their contribution to the development of genital tract malignancies.

Adult↗

A phase II trial of vinorelbine and thiotepa in metastatic breast cancer.

BACKGROUND: Vinorelbine as single-agent has achieved an overall response rate of > 20% as second-line treatment and 40%-50% as first-line treatment. The aim of this study was to evaluate the activity and toxicity of the combination of vinorelbine and thiotepa as second-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-three patients (31: anthracycline-based chemotherapy, 16: high-dose epirubicin) were given vinorelbine 30 mg/m2 and thiotepa 12 mg/m2 d 1 and 8 every 21 days. RESULTS: Among the 32 evaluable patients two complete responses and seven partial responses were observed, for an overall response rate of 28% (C.I. 12-44). The median duration of response was 9 months and the median time to progression 6 months. Significant toxicity was primarily leukopenia (72%); anemia was also frequent (48%) as well as local phlebitis (39%). CONCLUSION: The present study has shown this combination to be active as second-line treatment, and its toxic effects have been well tolerated. It should be considered a reasonable option for patients with metastatic disease who have already been treated with anthracyclines.

Adult↗

Complete resolution of breast cancer bone metastasis through the use of beta-interferon and tamoxifen.

A case report is described referring to a patient affected by single bone metastasis to the cranium from breast cancer. A traditional pharmacological approach was tried but proved clinically disappointing, though radiological and scintigraphic investigation confirmed a complete regression of the metastasis following a combined therapy with beta-interferon and tamoxifen for six months. Results suggest that beta-interferon and tamoxifen may offer an alternative effective approach in treating metastatic breast cancer.

Aged↗

Ovarian cancer and dietary habits.

One hundred seven patients with epithelial ovarian cancer and one hundred fifty healthy women, categorized according to age, were evaluated for constitutional characteristics and also for dietary habits. No significant differences were observed between patients and controls in menarchal and menopausal history. Daily intake of proteins, glycides, lipids and calories was significantly higher in patients than in controls. However obesity was not confirmed as a risk factor for ovarian cancer. These conflicting data confirm that in ovarian neoplasia, although the exact mechanism is unknown (direct action or indirect effect), dietary factors may play an important role, suggesting a new mechanism in the etiology of this disease.

Case-Control Studies↗

[Medical emergencies in oncology: hypercalcemia. II. Diagnosis and therapy].

The acute metabolic abnormalities associated with cancer may cause symptoms that require urgent medical treatment and may constitute a more dangerous threat to life than the cancer itself. Hypercalcaemia is probably the most common metabolic complication of neoplastic disease (occurring in up to 30% of cancer patients) and its timely treatment may often save the patient and may permit subsequent chemotherapy. In this communication we focused our attention on the pathogenetic mechanism (part 1), diagnosis and subsequent treatment of this metabolic disorder (part 2).

Diagnosis, Differential↗

[Metabolic emergencies in oncology: hypercalcemia. I. Pathogenesis].

The acute metabolic abnormalities associated with cancer may cause symptoms that require urgent medical treatment and may constitute a more dangerous threat to life than the cancer itself. Hypercalcaemia is probably the most common metabolic complication of neoplastic disease (occurring in up to 30% of cancer patients) and its timely treatment may often save the patient and may permit subsequent chemotherapy. In this communication we focused our attention on the pathogenetic mechanism (part 1), diagnosis and subsequent treatment of this metabolic disorder (part 2).

Bone Neoplasms↗