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Biomedical subjects

D Giannarelli

Publications and source records attributed to D Giannarelli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Use of discriminant analysis to assess disease activity in pulmonary tuberculosis with a panel of specific and nonspecific serum markers.

Several cell activation markers, acute phase reactants, enzymes, and antituberculous antibody serum levels have been proposed as possible markers to monitor disease activity in patients with tuberculosis. They have all shown limited sensitivity or specificity. The authors therefore attempted to generate a canonical variable using discriminant analysis, including sensitive and specific parameters, to be a reliable marker in classifying patients correctly during the course of pulmonary tuberculosis. The following parameters were selected: two soluble cell activation markers (soluble interleukin-2 receptor and sCD8); the levels of immunoglobulin (Ig) G and IgM antibodies against the A60 antigen complex; and the presence of specific antibodies directed to eight different A60 components, revealed by Western blot analysis. The tests were performed on sera from three groups of patients with pulmonary tuberculosis. The first group comprised 25 patients with onset tuberculosis, clinically active (OTCA), evaluated at the time of admission. The second group included 28 patients with chemotherapy-treated tuberculosis, clinically active (CTCA), 2 months after therapy had begun. The third group included 20 patients with tuberculosis, nonclinically active (TNCA), who had had at least 1 year of effective therapy. The authors obtained an 80.9% rate of correct classification for the three groups and a rate of 100% when OTCA and TNCA were compared. The patients with CTCA were scarcely differentiated and tended to be distributed into the two other groups. To improve the separation between patients with CTCA and those with OTCA, a second canonical variable was generated with a 91.7% rate of correct classification, as compared with 71% obtained using the sCD8 as the best single variable. The mean values of the last canonical variable were statistically different (Mann-Whitney test, P = .049) when stratified for acid fast bacilli-positive or negative CTCA patients (microscopic detection). Three patients, followed during the entire course their disease, were, as expected, correctly positioned with respect to the subsequent disease phases.

Adult↗
PubMed1994

A randomized phase II study comparing sequential versus simultaneous chemo-radiotherapy in patients with unresectable locally advanced squamous cell cancer of the head and neck.

BACKGROUND: Single-modality radiotherapy is still considered standard treatment for patients with locally advanced unresectable cancer of the head and neck. As treatment outcome is poor, attempts to integrate chemotherapy into the overall management of these patients are ongoing. PATIENTS AND METHODS: A randomized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program. Between February 1986 and February 1991, 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS, T and N class and primary site and then randomized to receive either three courses of neoadjuvant chemotherapy with cisplatin (100 mg/m2 i.v. d 1) and 5-fluorouracil 1000 mg/m2/days 1-5 by continuous i.v. infusion every 3 weeks prior to definitive conventional radiotherapy of 65-70 Gy (sequential treatment), or cisplatin 100 mg/m2 on days 1, 22, 43 given simultaneously for the duration of the same conventional radiotherapy (simultaneous treatment). RESULTS: At the end of the entire treatment 18 complete responses (47%) in the sequential-treatment arm and 18 (41%) in the simultaneous treatment arm were obtained. No statistically significant differences in the 5-yr progression-free survival, in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed. Leukopenia was more frequent in the simultaneous than in the sequential arm (p = 0.03), whereas alopecia (p = 0.008) and phlebitis (p < 0.0001) were more frequent in the sequential-treatment arm. A better compliance was associated with the concomitant treatment, with 87% of the patients completing the entire radiotherapy program versus 63% of those in the sequential arm (p = 0.01). CONCLUSIONS: In the present study, the two treatment arms showed similar activity (complete response, progression-free and overall survival rates). Compliance to treatment was better in the concomitant arm. These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck. Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone.

Adult↗
PubMed1994

High dose-intense chemotherapy alone or in combination with interleukin-2 for small cell lung cancer: a pilot study.

Given the antitumor activity of interleukin-2 (IL-2) against some drug-resistant cancer cells, 17 previously untreated patients with small cell lung cancer entered a pilot study to evaluate the feasibility, efficacy, and immunological effects of combining 12-week high dose-intense chemotherapy based on a modified Evans regimen (CAV/PE) with different IL-2 schedules (6-12 MU/m2 week as a 48-72-h infusion using the same cumulative dose, 72 MU/m2). Despite significant myelotoxicity, up to 70% of the intended dose intensity was delivered, showing no differences with regard to the IL-2 schedule used. Immunotherapy-induced toxicity was usually mild and manageable. No limiting effects were observed in patients receiving immunotherapy except for a very poor compliance to the 12-week IL-2 regimen. The low-dose 72-h infusion was the optimal IL-2 schedule. As given in this study, neither of the alternating CAV/PE regimens abrogated the effects of IL-2 on T-cell and NK-cell subsets, showing typical kinetics with rebound in lymphocytes following each discontinuation of the IL-2. While immunological changes cannot predict the antitumor effect of IL-2, they are consistent with those described for IL-2 alone, suggesting its compatibility with high dose-intense chemotherapy. Although no definite advantages have been demonstrated in this small pilot study with significant unbalanced prognostic factors (12% 2-year survival), both the preserved immunostimulatory effects and the lack of limiting overlapping toxicity make this combined approach promising and worthy of further clinical investigation.

Adult↗
PubMed1993

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for infiltrating transitional cell carcinoma of the bladder.

BACKGROUND: Based on the excellent results with combination chemotherapy such as M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in patients with advanced disease, neoadjuvant chemotherapy has been advocated to improve survival and in some cases to permit bladder conservation. METHODS: A Phase II study of neoadjuvant M-VAC chemotherapy was performed in patients with T2-T4N0M0 bladder tumors. After clinical staging, three cycles of M-VAC were given. After patients underwent postchemotherapy clinical restaging, pathologic restaging (partial or radical cystectomy) was planned. RESULTS: Forty-six patients are evaluable. A clinical response was attained in 78%. Six patients (13%) had stable disease, and four (9%) had progression. After chemotherapy, 17 patients underwent radical cystectomy, none of whom were pTO. In this group, 10 of the 17 (59%) are alive at a median follow-up of 37+ months (range, 8-62+ months). Eleven patients had a partial cystectomy; 7 of the 11 (64%) are alive, 6 (55%) with a preserved bladder. Eighteen patients had clinical restaging only, and did not have pathologic staging. Median follow-up for this group is 36+ months (11-65+ months). Twenty-one of the 29 (72%) patients managed with conservative surgery or transurethral resection of the bladder alone are alive with a functional bladder. Median survival for all patients has not yet been reached. Two-year survival is 82%, and 3-year survival is 70%. CONCLUSIONS: The current study is of interest in terms of bladder conservation. Assessment of the true success of any bladder-preserving treatment will require longer follow-up.

Aged↗
PubMed1993

Flow cytometric analysis of ploidy in colorectal cancer: a multicentric experience.

Ploidy and cell proliferation determined by flow cytometry were assessed on colorectal cancers from patients admitted to two Italian cancer research centres. A total of 181 patients were followed prospectively for 4 years at the Istituto Regina Elena (IRE) of Rome and at the Istituto Nazionale Tumori (INT) of Milan. Fresh (at the IRE) or frozen (at the INT) tumour material and similar procedures were used for subsequent sample preparation. Similar frequencies of aneuploid tumours (63% vs 66%) and superimposable median DNA indices (1.6) were observed for the two case series. In both series, DNA ploidy was generally unrelated to clinico-pathological factors, except for a higher frequency of aneuploid tumours in Dukes' D (88%) than in Dukes' A stage (33%) in the IRE experience. DNA ploidy was a weak prognostic indicator at 3 years but not at 4 years in the IRE case series, and it never exhibited a clinical relevance in the INT experience. Conversely, multiploidy was an indicator of worse relapse-free and overall survival at 4 years in the IRE and INT case series.

Aneuploidy↗
PubMed1993

Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors.

BACKGROUND: The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with advanced urothelial tract cancer. Growth factors may provide the possibility of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an escalated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiated. PATIENTS AND METHODS: 23 patients were treated with an escalated dose of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4-10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. Adriamycin and cisplatin were given at 2.5 times the dose of standard M-VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Adriamycin and cisplatin were both given at 2.9 times the dose. CONCLUSIONS: The response rate was 70% (95% CI 60%-80%). Seven patients (30%) had CR, and 9 (39%) had a PR. Five (22%) patients had stable disease and 2 (9%) had progression. Of the CR patients, 3 had the CR confirmed pathologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Dose level II was too toxic due to thrombocytopenia. Non-hematologic toxicity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to be initiated by the Genitourinary Group of the EORTC.

Aged↗
PubMed1992

Hyperthermic antiblastic perfusion for the treatment of soft tissue limb sarcoma.

Eighty patients with locally advanced, high grade soft tissue sarcoma of the extremities were studied prospectively in order to determine the efficacy of hyperthermic antiblastic perfusion (H.A.P.) as the first step of a combined multimodality therapy. All of the patients have been evaluated in terms of functional results, loco-regional control and survival according to the different treatment schedules adopted. The first clinical trial employed H.A.P., followed by surgery alone. Because the results obtained were unsatisfactory, the protocol was modified to include a continuous intra-arterial (i.a.) infusion of doxorubicin (dx) or radiotherapy before surgery. The best results have been obtained with the radiotherapy-including protocol showing a conservative surgery rate of 100% and a 94% rate of loco-regional control. The disease-free, distant disease-free and overall survival rates were 68%, 75% and 70%, respectively. The importance of the treatment protocol has been confirmed in a multivariate analysis which demonstrated that the treatment protocol adopted is one of the prognostic factors with an independent value (p = 0.06).

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1992

Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.

PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.

Actuarial Analysis↗
PubMed1991

Transurethral resection of the prostate and metastatic prostate cancer.

Demonstration of malignant cells in blood specimens collected during transurethral resection of the prostate (TURP) has implicated TURP in the dissemination of prostatic cancer. Of 153 patients who underwent radiation therapy for prostate cancer between January 1977 and June 1990 and were retrospectively analyzed, 93 were evaluable. Fifty-nine patients required TURP before radiation therapy for prostatic obstruction (BPH and/or cancer); the remaining 34 patients underwent radiation therapy after fine-needle aspiration biopsy. No statistically significant difference in failure rate could be detected between these groups, with a failure rate of 47% (28 of 59 patients) at a median follow-up time of 49 months (range, 8 to 146 months) in the TURP group versus a failure rate of 47% (16 of 34 patients) at a median follow-up time of 50 months (range, 3 to 122 months) in the group who underwent biopsy only (Fisher's exact test, P = 0.23). Within the confines of this retrospective study, it appeared that TURP did not enhance the development of metastatic disease.

Adenocarcinoma↗
PubMed1991

Tumor progression in human malignant melanoma is associated with changes in alpha 6/beta 1 laminin receptor.

Cells of the melanocytic lineage have been shown to be capable of producing laminin and to lose this property during transformation. In the present study, we have evaluated immunohistochemically whether these changes are paralleled by an altered expression of the alpha 6/beta 1 laminin receptor. Results of this analysis have shown that while nevic cells display high levels of the receptor, this heterodimer undergoes a progressive decrease in expression in cutaneous melanomas of increasing invasiveness. A loss or unco-ordinated expression of the alpha 1/beta complex is present in the majority of the metastatic foci at different body sites. The present results show that during transformation the alpha 6/beta 1 laminin receptor undergoes quantitative alterations and deregulated expression of the 2 subunits. Although the functional relevance of these changes remains unknown, their occurrence in association with modifications of other cellular and extracellular macromolecules associated with tumor progression, strongly suggests a role in human melanoma progression.

Humans↗
PubMed1991

Local recurrence after curative resection for colorectal cancer: frequency, risk factors and treatment.

Analysis of 498 patients with colorectal carcinoma was retrospectively reviewed to evaluate the incidence, risk factors and therapy of local recurrent carcinoma following curative resection. Complete follow-up information was obtained in all but four patients (99.2%). After a median follow up of 42 months, 64 out of 469 (13.6%) patients developed local recurrence (LR). The incidence of LR was higher in rectal than in colon cancer patients (18.3% vs 8.9%) (P less than 0.005). Separate univariate and Cox analyses for rectal patients showed tumor site (P less than 0.02). Dukes stage (P less than 0.002), and adjuvant radiotherapy (P = 0.05) determined risk of LR. For colon cancer patients risk of LR was determined by histological tumor grade (P less than 0.01). Out of 64 patients, 5 (7.8%) underwent radical excision of LR. Forty percent of these survived at 5-year (P less than 0.08). Palliative treatment (radio-chemotherapy) obtained a 5-year survival of 15.3%, with no survivors in no-treatment group. These results suggest that local recurrent colorectal carcinoma remain a difficult treatment problem. More effective combinations of surgery and adjuvant therapy are therefore mandatory to reduce the incidence of local failure in high risk colorectal patients.

Adenocarcinoma↗
PubMed1991

Definitive radiation therapy for localized prostatic adenocarcinoma.

From 1974 to 1987, a total of 199 patients with prostatic carcinoma localized to the pelvis were treated with definitive external beam radiation therapy at the Istituto Medico e di Ricerca Scientifica. The median follow-up for all 126 surviving patients was 60 months. Actuarial 5-(and 10-) year overall survival rates for U.I.C.C. clinical Stage T1-2, T3 and T4 disease were 76.1% (58.5), 66% (42.5), and 27.6%, respectively. The corresponding 5- and 10-) year disease-specific survival rates were 81.7% (73), 72.5% (57.4), and 36.2%. The corresponding values of disease-free survival were 81.3% (76.8), 59.2% (57), and 17%, respectively. In 120 patients with more than 5 years of follow-up, local failure was seen alone in eight patients (6.6%) and associated with distant metastases in 19 patients (15.8%). In 28 patient (23.3%), distant metastases were observed alone. The median survival from the first evidence of metastases was 20 months, with no patient surviving beyond 5 years. The incidence of complications was acceptable. Serious complications, consisting of stenosis of both ureters and sigmoid colon requiring both urinary and intestinal diversion, occurred in two patients (1.3%). This study reveals that external radiotherapy is an efficacious and safe modality for locoregional control of prostate cancer.

Aged↗
PubMed1991

Detection of Helicobacter pylori carriers by discriminant analysis of urea and pH levels in gastric juices.

An alternative approach to the problems inherent in current methods for detecting Helicobacter pylori carriers--that of being generally time-consuming, expensive, and not sufficiently sensitive--was devised by using the urea concentration and pH levels of gastric juices. A linear discriminant analysis of these variables, measured in 54 patients submitted to digestive endoscopy for gastritis, provided a mathematical formula for assigning the subjects (previously classified by other standard methods) to groups of either positive or negative H pylori carriers. The results obtained showed a correct classification in 52 out of 54 cases with only one false negative and one false positive case.

Adult↗
PubMed1991

Fractional incorporation of radionucleotides, a marker of in vitro tumor cell chemosensitivity in colorectal cancer.

Working with the antimetabolic chemopredictivity assay on short term cultures we evidenced a correlation between in vitro chemosensitivity of colorectal cancer and fractional incorporation of radionucleotides. Four different drugs (5-FU, mitomycin C, 4'-iododeoxydoxorubicin and ruboxyl, a nitroxyl derivative of daunorubicin) were tested on 102 tumor cultures. The extent of 3H-TdR and 3H-UdR incorporation into DNA and RNA in the related control cultures was in relationship with the chemosensitivity of the tumor. Along with the labeling index this simple metabolic-kinetic trait may gain a role for the screening of tumor phenotypes sensitive to chemotherapy.

Antineoplastic Agents↗
PubMed1991

Second primary cancer following Hodgkin's disease: updated results of an Italian multicentric study.

The risk of second primary cancer (SPC) was evaluated in 947 patients treated for Hodgkin's disease (HD) during the period January 1969 to December 1979. The median follow-up of this series was 10.5 years (range, 9 to 19). Treatment categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and salvage treatment for resistant or relapsing HD (290 patients, 30.6%). Fifty-six SPCs were observed, occurring between 1 and 17 years from initial treatment. Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent SPC (23 cases). Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients, whereas a secondary solid tumor (s-ST) was observed in 28 patients. The calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and 23.1% (+/- 5.8%) at 10 and 19 years, respectively. Concerning treatment modalities and s-ANLL risk, no cases were observed in the radiotherapy group, whereas CHT plus RT and salvage groups showed the highest actuarial risk. This was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter. A statistically significant difference was observed when the CHT plus RT group was compared with CHT and RT groups (P = .04). Concerning the relationships with chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus RT. A statistically significant difference of s-ANLL actuarial risk was found comparing patients receiving MOPP plus RT to all other treatment groups (P = .04). With respect to s-ST, the actuarial risk at 10 and 19 years was 2.0% (+/- 0.6%) and 13.0% (+/- 3.8%), respectively. No significant differences were found among groups treated with different modalities. These data were confirmed by a multivariate analysis, which indicated treatment modality and age as independent variables for s-ANLL and s-ST development, respectively. Based on the prolonged follow-up analysis, the actuarial SPC risk at 10 years hereby reported should reflect the real SPC incidence in our series.

Actuarial Analysis↗