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Biomedical subjects

L Mariani

Publications and source records attributed to L Mariani.

At least 91 records · Page 5Linked to original sources
PubMed1999

The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial.

The lymph nodes of the internal mammary chain represent a primary station draining the lymph from the breast and their removal or their irradiation has been considered an important step in breast cancer treatment. From January 1964 to January 1968, 737 patients with breast cancer were randomised at the National Cancer Institute in Milan to undergo either Halsted mastectomy or extended mastectomy with internal mammary node dissection. Patients with non-disseminated carcinoma classified as T1, T2, T3, N0, N1 were eligible for the study. No patients received postoperative radiotherapy or systemic therapy. After 30 years of follow-up, the overall survival curves and the specific survival curves do not show any difference between the patients of the two groups. Among the 558 patients who died in the 30 year interval period, 395 (71%) died from breast carcinoma (201 in the Halsted group and 194 in the extended mastectomy group) and 163 from other causes. This study shows that the removal of internal mammary nodes does not improve the survival of patients treated for breast carcinoma. This finding supports the theory that treatment of regional nodes does not influence the survival of cancer patients. The prognostic value of internal mammary node status is, however, high and a biopsy on a selected lymph node should be considered for staging purposes.

Adult↗
PubMed1999

Transient transfection of a synthetic hammerhead ribozyme targeted against human MGMT gene to cells in culture potentiates the genotoxicity of the alkylation damage induced by mitozolomide.

Unmodified and chemically modified forms of a synthetic hammerhead ribozyme with the mRNA of methylguanine-DNA methyltransferase (MGMT) gene as substrate were characterized for their in vitro and in vivo activities. The unmodified ribozyme efficiently cleaved in vitro a short synthetic substrate, and it was rapidly degraded in fetal bovine serum (FBS). The introduction of phosphorothioates and the substitution of uridine with thymidine at probable nuclease-sensitive sites slightly increased the nuclease resistance of the ribozyme. Conversely, pyrimidine nucleoside substitution with 2'NH2 and 2'F nucleosides strongly enhanced nuclease resistance. The in vivo activity was determined by measuring the genotoxicity induced by the alkylating drug mitozolomide, the damage of which is repaired by MGMT enzyme. CHO/47 cells, temporarily depleted of the MGMT protein, were first transfected with the various synthetic ribozymes and subsequently treated with mitozolomide. At equivalent concentration of the drug, the induction of sister chromatid exchanges was higher in ribozyme-transfected than in untransfected cells, indicating that the synthetic ribozymes potentiated the genotoxicity of mitozolomide. Moreover, the concomitant occurrence of messenger RNA reduction in ribozyme-transfected cells indicated that the inhibition of MGMT resynthesis was the basis of the enhanced genotoxicity.

Alkylating Agents↗
PubMed1999

[HPV infection as a disease of couples. Prevalence of the infection in the male partner].

BACKGROUND: The role of males who are sexual partners of females with genital human papillomavirus (HPV) infection and premalignant lesions is explored in the present study. METHODS: In a period of 6 years, 845 females with genital premalignant and HPV-associated lesions were examined and treated at the Sexual Transmitted Disease Center of S. Gallicano Hospital. The male partners of were asked to attend this Center, and 163 (70%) of them responded. All participants underwent sexual anamnesis, genital inspection and colposcopic examination. RESULTS: Macroscopic lesions were found in 7.4% of the males enrolled. The colposcopic prevalence of HPV infection among the male partners was 21.8% 3 months later among 28 negative patients to the first colposcopic control, 2 were found positive. CONCLUSIONS: These data confirm that the colposcopic evaluation of male partners during an HPV infection of the couple is to be considered for the therapeutic assessment and evolution control of the infection in each couple.

Colposcopy↗
PubMed1998

The sensitization of cells treated with O6-methylguanine to alkylation damage is affected by the number of O6-methylguanine-DNA methyltransferase molecules escaped from inactivation.

O6-Methylguanine (MeG) can bind to the active site of O6-methylguanine-DNA methyltransferase (MGMT) as a free base. The subsequent methyl transfer reaction inactivates the repair protein. Hence, MeG is used to deplete the active MGMT pools in Chinese hamster cell lines (CHO) transfected to express varying amounts of human MGMT. After treatment with the free base, a residual population of active protein molecules remains localized mostly in the cytoplasm. Depleted cells are then challenged with the alkylating drug mitozolomide. Genotoxicity of this agent varied among the cell lines, and the compound sensitivity seemed to be regulated by a steady state equilibrium of residual MGMT molecules between nucleus and cytoplasm.

Animals↗
PubMed1998

[Surgical versus medical treatment of idiopathic trigeminal neuralgia].

The primary treatment of idiopathic trigeminal neuralgia is medical. Surgery is reserved for unresponsive patients or in case of long lasting, tedious or dangerous side effects of the medication. The surgeon has to inform the patient about risks and benefits of the different surgical methods and consider the patient's expectations and fears in order to choose the best surgical alternative. We describe the clinical picture of trigeminal neuralgia, the steps leading to the diagnosis. We also discuss the pathogenesis and the different treatment modalities with emphasis on surgical methods.

Elective Surgical Procedures↗
PubMed1998

Oral doxifluridine plus levoleucovorin in elderly patients with advanced breast cancer.

BACKGROUND: There currently is no agreement regarding the appropriate treatment of elderly patients with advanced breast carcinoma (ABC). Doxifluridine (5-dFUR), a prodrug of 5-fluorouracil, has been found to be effective in this entity, but its use is limited by neurotoxicity and cardiotoxicity that are not observed when the oral formulation is used. The objective of this Phase II trial was to evaluate the effectiveness and tolerability of oral 5-dFUR, biomodulated with levoleucovorin (1-leucovorin), in elderly patients (age > 70 years) with ABC. METHODS: 5-dFUR was administered orally at 600 mg/m2 twice daily for 4 consecutive days every 12 days, and oral 1-leucovorin was administered as 25 mg 2 hours before each 5-dFUR administration. Response was assessed every five cycles according to the World Health Organization criteria. In the presence of response or stable disease, the patients were treated for a maximum of 15 cycles. RESULTS: Seventy-three eligible patients were enrolled, 27 of whom had been pretreated with chemotherapy and/or hormonotherapy; all were assessable for response and toxicity after a median follow-up of 15 months. The objective response rate was 26% (95% confidence interval, 17.4-45.4). Regression predominantly occurred in the presence of soft tissue involvement (skin, lymph nodes, and breast). The median time to response was 2 months (range, 1-2 months) and the median response duration was 7 months (range, 2-17+ months). The median survival was 24 months (range, 2-42+ months). The treatment was very well tolerated, and the side effects were manageable and always reversible. CONCLUSIONS: The results of the current study show that 5-dFUR plus 1-leucovorin, both given orally, are associated with excellent patient compliance. Although the results are suboptimal in terms of an objective response, this characteristic could allow 5-dFUR to be used in elderly patients considered unsuitable for "aggressive" chemotherapy.

Administration, Oral↗
PubMed1998

5-Fluorouracil, dacarbazine, and epirubicin in the treatment of patients with neuroendocrine tumors.

BACKGROUND: For patients with surgically untreatable neuroendocrine tumors (NETs), the optimal therapeutic approach remains undefined. Somatostatin analogs and interferons have failed to control neoplastic growth, and chemotherapy has been only moderately more effective. The authors' previous study of the combination of 5-fluorouracil (FU), dacarbazine (DTIC), and epirubicin (EPI) (the FDE regimen) documented good tolerability, but the results for tumor growth control were disappointing. In an attempt to improve these results, the authors conducted a preliminary trial of an intensified FDE regimen (FU 500 mg/m2 administered intravenously [i.v.], DTIC 200 mg/m2 i.v., and EPI 30 mg/m2 i.v. on Days 1, 2, and 3 every 3 weeks). METHODS: Thirty NET patients (15 male, 15 female; median age, 55 years; age range, 19-72 years) were enrolled, none of whom had previously been given chemotherapy. The histologic types of disease were gastroenteropancreatic (GEP) tumors (n = 21, 6 carcinoid tumors and 15 pancreatic NETs), other carcinoid tumors (n = 3), other NETs (n = 4), medullary thyroid carcinoma (MTC) (n = 1), and Merkel cell carcinoma (n = 1). Six patients had a syndrome related to endocrine hypersecretion. One hundred fifty-four therapy cycles were delivered (median, six per patient), and all patients could be evaluated for response on the basis of intent-to-treat analysis. RESULTS: There were 9 objective responses: 2 complete responses (in 1 patient with Merkel cell carcinoma and 1 with pancreatic NET) and 7 partial responses (in 3 patients with pancreatic NETs, 2 with other NETs, 1 with GEP carcinoid tumor, and 1 with MTC). The median duration of response was 10 months (range, 5+ to 24+ months). No reduction in symptoms was achieved among the six patients with endocrine hypersecretion syndrome. Levels of urinary 5-hydroxyindoleacetic acid and serum chromogranin A were decreased in 50% and 14% of patients, respectively, who presented with abnormal baseline values. Treatment toxicity was acceptable and included nausea and vomiting, alopecia, leukopenia, and mucositis. CONCLUSIONS: This trial demonstrated that the FDE regimen may be at least as effective as other systemic regimens. Comparison of this experience with the authors' previous trial revealed a noteworthy increase in the activity of the intensified regimen, especially in GEP NETs (the most chemoresistant tumors). Continued clinical research to improve these results is highly justified.

Adult↗
PubMed1998

Feed forward neural networks for the analysis of censored survival data: a partial logistic regression approach.

Flexible modelling in survival analysis can be useful both for exploratory and predictive purposes. Feed forward neural networks were recently considered for flexible non-linear modelling of censored survival data through the generalization of both discrete and continuous time models. We show that by treating the time interval as an input variable in a standard feed forward network with logistic activation and entropy error function, it is possible to estimate smoothed discrete hazards as conditional probabilities of failure. We considered an easily implementable approach with a fast selection criteria of the best configurations. Examples on data sets from two clinical trials are provided. The proposed artificial neural network (ANN) approach can be applied for the estimation of the functional relationships between covariates and time in survival data to improve model predictivity in the presence of complex prognostic relationships.

Clinical Trials as Topic↗
PubMed1998

Vulvar squamous carcinoma: prognostic role of DNA content.

DNA nuclear content was evaluated on 46 paraffin-embedded blocks of vulvar cancer by means of flow cytometry. Fifteen of 44 evaluable samples (34%) were found to have an aneuploid DNA pattern. Aneuplody showed a statistically significant relationship with tumor grading (P = 0.0004) and defined a subset of patients who have pathological characteristics of high risk, such as advanced stage of disease, deepest stromal invasion, or positive inguinal nodes. However, when a multivariate regression model was used, ploidy status did not have any prognostic role, while FIGO staging system was confirmed to be the strongest independent prognostic factor (P = 0.009). The integration of a panel of cell kinetic parameters with traditional features is worth investigating on a larger population.

Adult↗
PubMed1998

Is steroid receptor profile in contralateral breast cancer a marker of independence of the corresponding primary tumour?

We compared oestrogen receptor (ER) and progesterone receptor (PgR) profiles between primary and corresponding contralateral breast cancer (CBC) to investigate whether CBC should be considered relapse of a primary or as a feature of the multicentric origin of breast cancer. We adjusted for patient age, menopausal status, histology and adjuvant therapy. In spite of the general application of a cut-off value to dichotomise ER and PgR, we considered them as continuous variables. Moreover, we considered as synchronous cancers only simultaneously occurring lesions. For 399 patients, ER and PgR receptor levels in primary and CBC did not differ significantly, but were significantly correlated within the same patient. The correlation was higher for synchronous than for metachronous lesions when considering ER, but not PgR. The correlation between ER and PgR levels in the same tumour (primary or CBC) appeared stronger than the correlation of either receptor type (ER or PgR) between primary and CBC. Age, histology and adjuvant treatment affected ER concentration, whereas age, menopausal status and histology affected PgR concentration. The analysis indicated that primary and CBC tend to be characterised by a similar steroid receptor profile. The finding may support the hypothesis of CBC as a second primary arising in a common predisposing milieu, rather than a primary-dependent contralateral lesion. In this light, the clinical management of patients with a bilateral breast cancer should be similar to that of a unilateral breast cancer.

Adult↗
PubMed1998

Ten year results of a randomised trial comparing two conservative treatment strategies for small size breast cancer.

We report the 10-year results of a randomised clinical trial in which two different breast conservation treatment strategies were compared in women with small, non-metastatic primary breast cancer: quadrantectomy, axillary dissection and radiotherapy (QUART) versus tumorectomy and axillary dissection followed by external radiotherapy and a boost with 192Ir implantation (TART). No second surgery was given to women with affected surgical margins. Axillary node positive women received adjuvant medical therapy. From 1985-1987, this trial accrued 705 patients, 360 in the QUART and 345 in the TART arm. Crude cumulative incidence curves for intrabreast tumour recurrence (IBTR) and metastases as first events and mortality curves in each of the two treatment arms were computed. A crude cumulative incidence curve of IBTR as a second event (in women who had already had a local recurrence) was also computed. The two groups were compared in terms of hazard for IBTR, metastases or death occurrence by using Cox regression models, both with and without adjustment for patient age, tumour size, number of metastatic axillary nodes and histology. Possible interactions between the aforementioned prognostic factors and the type of surgery were also investigated. The two groups were well matched for baseline patient and tumour characteristics, the only exception being resection margins, which were more often positive in the TART group. At the Cox model, a significant difference between groups was detected for IBTR (P < 0.0001), but not for distant metastases and overall survival. In particular, 5- and 10-year estimates of crude cumulative incidence of IBTR were 4.7 and 7.4% in the QUART group and 11.6 and 18.6% in the TART group. The difference was not substantially affected by patient or disease characteristics. Likewise, the status of resection margins in women who underwent TART treatment did not significantly influence the risk of occurrence of IBTRs. Finally, the rate of second IBTR occurrence was relatively high, when compared with the rate of IBTR occurrence as first event. In summary, the results of this trial show that a better local control of the disease can be obtained with the more extensive surgical resection, i.e. QUART.

Adult↗
PubMed1998

FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer, with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO) study.

The new regimens developed over the last few years have led to an improvement in the treatment of advanced gastric cancer, and our previous experience confirmed the fact that the combination of etoposide, doxorubicin and cisplatin (EAP regimen) is an active treatment that leads to interesting complete remission rates. The primary end point of the present multicentre, randomized, parallel-group phase II study was to determine the activity of the simplified 2-day EAP schedule in patients with locally advanced or metastatic gastric cancer, and to verify whether the addition of low doses of granulocyte-macrophage colony-stimulating factor (GM-CSF) made it possible to increase dose intensity. Of the 62 enrolled patients, 30 were randomized to receive epirubicin 35 mg m(-2), etoposide 120 mg m(-2) and cisplatin 45 mg m(-2) (FEP) on days 1 and 2 every 28 days and 32 to receive the same schedule plus subcutaneous GM-CSF (molgramostin) 150 microg day(-1) on days 5-14 every 21 days. The patients were stratified by age and the number of disease sites. The characteristics of the patients were well balanced between the two groups. The objective response rate of the patients as a whole was 34% (21 out of 62; 95% confidence interval 22-46), with only one complete remission. The median response duration was 4.5 months (range 1-24 months). The median time to treatment failure was 5 months (range 1-14 months), without any difference between the two groups. The median survival of the patients as a whole was 9 months. Full doses were administered in 92% and 94% of the cycles in the control and GM-CSF arms respectively. The average dose intensity calculated for all drugs was 0.96% in the control and 1.27% in the GM-CSF group. CTC-NCI grade 3-4 neutropenia was reported in 39% vs 45% of patients, thrombocytopenia in 11% vs 35% (P = 0.020) and anaemia in 7% vs 35% (P = 0.014). The FEP combination is as active (OR: 34%) in the treatment of patients with advanced gastric cancer as the EAP regimen, although it leads to fewer complete remissions. The patients randomized to receive low-dose GM-CSF achieved a significantly higher dose intensity than controls (P = 0.0001).

Adult↗
PubMed1998

Cutaneous tuberculosis: a rare presentation in an immigrant.

The increased incidence of tubercular diseases in industrialized countries appears to be due to several factors, including development of resistance to the most commonly used specific chemotherapeutic substances, unsuitable control programmes, HIV infection, the increased influx of immigrants, and homelessness. Different forms of cutaneous tuberculosis are caused by different species of mycobacteria (e.g., Mycobacterium tuberculosis, M. bovis, M. avium). Determining the species of mycobacteria is relevant when disease is suspected to be linked to the type of employment of the patient, mainly because the clinical features do not always indicate which species is the cause of the infection. Mycobacterium tuberculosis (MT) usually infects through the lung, but in rare cases can penetrate the skin or mucous membranes. Skin transmission can be exogenous by inoculation, or endogenous by diffusion (lymphatic or hematic) or by contiguity. The immunologic status of the patient is a crucial factor which influences the clinical variants and the course of disease itself. Here we report a case of an illegal immigrant who presented with a bilateral, symmetrical ulcer on the neck.

Adult↗
PubMed1998

Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.

PURPOSE: The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS: Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS: Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION: Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.

Adult↗
PubMed1998

RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features.

The papillary carcinoma family (PCF) of thyroid tumors includes a wide variety of neoplastic entities regarded as well-differentiated, poorly differentiated, and undifferentiated papillary thyroid carcinomas. Recent studies have established the presence of alternative oncogenic rearrangements of the RET and NTRK1 genes in a consistent fraction (< or = 50%) of papillary thyroid tumors. RET oncogenic rearrangements are also very frequent (approximately 60%) in Chernobyl radiation-associated papillary thyroid neoplasias, which show an increased aggressiveness in terms of pathological stage at disease onset. These observations prompted us to study the relationship between the presence or absence of RET and NTRK1 oncogenes and the clinicopathological features (age, sex, histopathology, and pTNMC2 staging) of 76 consecutive, non-radiation-related tumors of the PCF. As previously reported, statistical univariate analysis revealed a correlation between the combination of RET and NTRK1 (RET/NTRK1) positivity and young age of patients at diagnosis. In addition, a significant association was found between RET/NTRK1 positivity and locally advanced stage of disease at presentation (pT4: P < 0.015). The multivariate analysis confirmed that RET/NTRK1 activation parallels an unfavorable disease presentation, which may correlate with a less favorable disease outcome. Furthermore, within the PCF, the frequency of RET/NTRK1 positivity was not influenced by the different neoplastic subtypes or the tumor versus degree of differentiation.

Adolescent↗
PubMed1998

Leiomyosarcomas of the small intestine misdiagnosed as ovarian masses: report of three cases.

Leiomyosarcomas of the small intestine are rare lesions. Because of their aspecific symptoms, diagnosis is often made at a late stage and, in women, must be distinguished from ovarian tumors. Three cases of large, abdominal masses, evaluated preoperatively as being ovarian tumors, are presented. At histology all three were diagnosed as leiomyosarcomas of the small intestine.

Aged↗
PubMed1998

Vulvar hemangiopericytoma. Case report.

A rare case of a hemangiopericytoma of the vulva, observed in a 55-year old woman, is presented. So far, only six cases of this uncommon disease--which continues to be a source of uncertainty from both a prognostic and therapeutic point of view--have been reported. The case is described along with a review of international literature.

Female↗