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Biomedical subjects

R Molinari

Publications and source records attributed to R Molinari.

At least 55 records · Page 3Linked to original sources
PubMed1991

Randomised EORTC head and neck cooperative group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma.

Between February 1978 and January 1984, 222 eligible patients were randomised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma. Patients were randomised between either surgery or preoperative chemotherapy. This latter group received vincristine and bleomycin for 12 days. Patients were stratified according to the primary site: floor of the mouth (FM) versus posterior oral cavity or oropharynx (POC) and institution. The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement, when it was systematically applied in the POC group. Tumour regression after chemotherapy either complete (CR) or partial (PR greater than 50%) was observed in 48% in the FM group and 41% in the POC group, and lymph-node regression (CR + PR) was respectively 15% and 23%. Some discrepancies appeared between clinical regression and pathological response, and the number of cases without histological response was clearly higher than the number of cases without clinical response. The overall survival showed a statistically significant difference (P = 0.048) between FM and POC groups. In the FM group, median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm. In the POC group, median survival was estimated at 3 years in both treatment arms. Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group. These differences do not exist in the POC group, which may be due to the systematically postoperative radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cell kinetics and response to primary intra-arterial chemotherapy in patients with advanced oral cavity tumors.

The relationship was analyzed between cell kinetics, defined as 3H-thymidine labeling index (3H-TdR LI), and clinical responses for 35 previously untreated patients with locally advanced oral cavity squamous cell carcinomas. Patients were treated with three cycles of vincristine and bleomycin (VB) or of VB plus methotrexate (VBM), given by intra-arterial infusion followed by surgery. The objective clinical response rate was higher after VBM treatment than after VB, whereas overall clinical response rates were similar for patients with slowly or rapidly proliferating tumors. The probability of relapse-free survival at 4 yr and overall survival was significantly higher for patients with high 3H-TdR LI tumors given VBM than for those given VB. For patients with slowly proliferating tumors, there were no differences in relapse-free survival and overall survival between the two treatments. These data suggest that patients with rapidly proliferating tumors benefit from primary intensive chemotherapy treatment including methotrexate and that cell kinetics can be used to formulate rational clinical protocols for oral cavity cancers.

Adult↗
PubMed1990

Local adoptive immunotherapy of advanced head and neck tumors with LAK cells and interleukin-2.

Since October 1987 a pilot phase I-II study on the effect of loco-regional injections of recombinant interleukin 2 (rIL-2) in association with LAK cells has been performed in advanced, recurrent head and neck cancer patients. Fourteen patients were treated with autologous LAKs and rIL-2 (Glaxo) given peritumorally and in the mastoid region (rIL-2 only in the latter site). LAKs (2-70 x 10(7)) + rIL-2 were injected on the first day of therapy, followed by 9 daily injections of rIL-2 only. The total daily dose of rIL-2 was escalated from 2,400 to 1.8 x 10(6) IU. Clinical evaluation was performed 30 days from the onset of therapy; 3 partial (95%, 66% and 50% reduction) and 3 minor responses were seen in the evaluated patients. All the other patients with a progressive disease after the first cycle were shifted to palliative chemotherapy. The partial responses were found in patients with a tumor burden less than 20 cm2. Cervical node metastasis did not respond to treatment. No relevant side effects occurred. These results indicate that loco-regional immunotherapy with rIL-2 and LAK cells can produce clinical responses in advanced head and neck cancer patients.

Aged↗
PubMed1990

In vivo interleukin 2-induced activation of lymphokine-activated killer cells and tumor cytotoxic T-cells in cervical lymph nodes of patients with head and neck tumors.

To study whether regional injection of recombinant interleukin 2 (rIL-2) can induce an in vivo lymphocyte activation in cervical lymph nodes (LNs) of patients with head and neck carcinoma, 12 patients, candidates for prophylactic dissection, were treated for 7-10 days prior to surgery with rIL-2, 10(5) units/day, injected in the perimastoid region. A marked induction of cytotoxic activity against allogeneic (K562 and Daudi lines) and autologous target cells (fresh spindle cell carcinomas of the tongue) was observed in lymphocytes obtained from jugular, spinal, and, to a lesser extent, submandibular LNs of all treated patients. An increase of cytotoxicity was also present in LNs contralateral to the rIL-2 injection side. On the other hand, only a borderline increase in spontaneous proliferation was detected. Moreover, in the two cases tested, a marked and apparently autologous tumor (Auto-Tu)-specific lysis was found in CD5+ lymphocytes obtained from LNs, whereas lymphokine-activated killer activity was mainly exerted by CD16+ natural killer cells. T-lymphocytes, when cultured with irradiated Auto-Tu cells and low doses of rIL-2, showed an increased Auto-Tu lysis, while cytotoxicity against allogeneic tumor cells (including K562) was not observed. These data indicate that regional injection of rIL-2 can activate lymphokine-activated killer cells from LN lymphocytes but also induce and/or expand a T-cell population expressing a restricted Auto-Tu cytotoxicity.

Aged↗
PubMed1990

Follow-up of oral leukoplakia after carbon dioxide laser surgery.

We evaluate the 3-year result of 145 oral leukoplakias operated on by outpatient carbon dioxide laser surgery at the Istituto Nazionale Tumori, Milan, Italy. The surgical technique that was used consisted of excision in 140 patients and vaporization in 5 patients. Cancer was found in 14 out of 140 patients who underwent excision (10%). In the analysis of the disease-free survival rate and of the unfavorable pattern of events, only 131 patients with benign postoperative histologic diagnosis were considered. Fifty-eight patients developed unfavorable events. The probabilities of remaining free of disease or of developing local relapses or new lesions at 3-year survival was 0.57, 0.27, and 0.19, respectively. Two patients had oral carcinomas after the operation. Forty patients modified their alcohol or tobacco habits or their teeth and/or prosthesis. Moreover, only two patients modified these factors before the unfavorable events occurred.

Adult↗
PubMed1988

Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

[Usefulness of gallium 67 in research into the need for radical cervical lymph node dissection in patients with head and neck carcinomas].

Fifty-nine patients with head and neck carcinoma were examined with 67Ga scintigraphy. All patients had undergone lymph node dissection of the neck. They were followed for a minimum of 2 years after the examination. The primary tumor, treated prior/contemporaneously to the lymph node dissection, did not evolve in this interval. Metastatic involvement of the lymph node capsule was observed in all 44 cases with metastatic lymph nodes; macroscopic radicality was surgically obtained since involvement of the capsule was only microscopic. Nevertheless, complementary radiotherapy was given. The whole of 17 recurrences in the soft tissues of the neck were found, within 2 years, in the group of 26 patients who had undergone dissection of lymph nodes with metastatic capsular involvement and whose postoperative 67Ga scintigraphy was positive. On the contrary, no recurrences in the soft tissues of the neck were observed in the group of 18 patients who had undergone dissection of lymph nodes with metastatic capsular involvement and whose scintigraphy was negative. This result proves (P less than 0.001) 67Ga capable of evidencing eventual microscopic diffusion. Such a possibility has not yet been realized in vivo with any other investigation technique. Scintigraphy was negative in a control group of 15 patients who had undergone lymph node dissection, and with nonmetastatic lymph nodes. This finding leads us to exclude that the use of 67Ga might result in misinterpreted findings in the exploration of relatively superficial tissues. In fact, the eventual accumulation of radioisotope in nonneoplastic pathologies is quite easily recognizable in the neck. We can therefore conclude that in those 9 cases with positive scintigraphy and in whom no recurrence was found, microscopic diffusion was probably present, but local recurrence of the disease was prevented by complementary radiotherapy.

Carcinoma↗
PubMed1987

Chemically Defined Medium for the Accumulation of Intracellular Malate Dehydrogenase by Streptomyces aureofaciens.

A chemically defined medium was developed for the production of intracellular malate dehydrogenases by Streptomyces aureofaciens NRRL-B 1286. The composition of the medium (per liter) was as follows: 50 g of starch, 4 g of ammonium sulfate, 7.32 g of l-aspartic acid, 13.8 g of MgSO(4) . 7H(2)O, 1.7 g of K(2)HPO(4), 0.01 g of ZnSO(4) . 7H(2)O, 0.01 g of FeSO(4) . 7H(2)O, 0.01 g of MnSO(4) . H(2)O, and 0.005 g of CoSO(4) . 7H(2)O. The pH of the medium was adjusted to 6.7 to 7.0 after sterilization. The activity of the intracellular malate dehydrogenases of the crude cell extract was greatest after 40 h of mycelium growth in a rotary shaker at 30 degrees C. The best temperature for the enzyme reactions was approximately 35 degrees C for NAD activity at pH 9.7 and 40 degrees C for NADP -linked enzyme at pH 9.0. The NAD activity required Mg, and both activities were sensitive to SH-group reagents. The NADP -dependent activity remained completely stable, and the NAD -dependent activity decreased to a very low residual level after 30 min at 60 degrees C.

Journal Article↗
PubMed1986

Cell kinetics to monitor radioresponsivity in human epidermoid carcinoma.

The clinical relevance of proliferative activity as an indicator of radioresponsivity was investigated in advanced epidermoid carcinomas of the oral cavity. Proliferative activity, determined in vitro as 3H-thymidine labeling index, was assessed before starting radiotherapy and after 10 Gy. In a series of 35 patients, pretreatment proliferative activity was not indicative of response to radiotherapy. Conversely, in the same series of patients, an association was observed between an early variation of proliferative activity induced by 10 Gy and the response to the full course of radiotherapy. The effect on proliferative activity was not related to tumor volume reduction but to long-term clinical response. An inhibition of more or less than 70% was significantly correlated with long-term clinical outcome at 36 months in terms of the probability of local recurrence (29% vs 90%; p = 0.002) and overall survival (55% vs 16%; p = 0.006) at 36 months.

Carcinoma, Squamous Cell↗
PubMed1984

Short-term variation in labeling index as a predictor of radiotherapy response in human oral cavity carcinoma.

In vitro determination of [3H]thymidine labeling index (LI) was carried out on squamous cell carcinomas of the oral cavity from 52 patients before and during radiotherapy. Pretreatment LI values ranged from 0.01% to 50%. After administration of the first 10 Gy in five consecutive daily fractions, a decrease in LI was observed in 39 cases and an enhancement in 13 cases, with an overall median 70% decrease in the initial value. The type of variation induced by radiotherapy was not related to pretreatment LI except for tumors with a very low proliferative activity (LI less than or equal to 1.9%), which all showed a marked increase in LI. Pretreatment LI was not indicative of short- or long-term response to radiotherapy, whereas the variation induced on LI after 10 Gy was related to the clinical outcome. A variation in LI of more or less than 70% was not significantly associated (p = 0.077) with clinical objective response (respectively, 85 and 53%). However, all 8 patients who reached a complete regression, notwithstanding an enhancement or a slight decrease in LI, had a local recurrence within 19 months. Conversely, the probability of disease-free survival was 82% for the 11 patients whose tumors had a significant decrease in LI (greater than or equal to 70%) after the first 10 Gy.

Aged↗
PubMed1983

VBM chemotherapy before curietherapy in the treatment of T2 oral carcinomas.

According to previous personal experience with conventional 226-Ra sources, in T2 oral carcinomas treated with curietherapy alone the incidence of local failures was 23%. Moreover, 50% of the local relapses were marginal with respect to the treated volume. From May 1980 to November 1981, 29 T2 oral carcinomas suitable for correct curietherapy received 3 weekly courses of VBM chemotherapy: i.e., vincristine, 1 mg i.v.; bleomycin, 15 mg i.m. after 6 and 24 h; and methotrexate, 30 mg p.o. after 48 h. A full dose curietherapy was performed 2 weeks after the completion of VBM. Twenty-seven patients have had a minimum follow-up of 12 months. The overall treatment was well tolerated and immediate results were encouraging. However, the local failure rate does not seem to have decreased by the combined treatment in comparison with curietherapy alone in historical series.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Recurrences in the soft tissues of the neck after surgery or radiotherapy plus surgery on regional lymph nodes in patients bearing carcinomas of the head and neck.

A series of 45 recurrences in the soft tissues of the neck following lymph node dissection in 497 patients bearing carcinoma of the upper aerodigestive passages is reported. Only 22 cases that presented perilymph node metastases and/or in which there were reasons to indicate insufficient surgical radicality had been subjected to radiotherapy after surgical lymph node dissection; the other 23 cases had not been subjected to radiotherapy because the aforementioned premises had been lacking. All the recurrences therefore occurred in patients with clinically and histologically ascertained metastatic lymph nodes. The presence of perilymph node metastases and the judgment of surgical radicality was thus found insufficient criteria to plan future complementary postoperative radiotherapy. However, even in those cases in which postoperative radiotherapy was performed, there was a rather high incidence of recurrences, as high as 64.7% in patients with carcinoma of the tongue. Our data indicate the opportunity of a clinical trial with preoperative radiation therapy in patients with clinically evident lymph node metastases. Thirty-six of these recurrences were situated in the upper parts of the cervical region. The prognosis is very poor in such cases, so much so that only 2 of our series were disease free at 3 years after the treatment.

Carcinoma↗
PubMed1982

Arguments in favor of precautional treatment of cervical nodes in clinically N0 oral cancer.

Our retrospective and unrandomized clinical study covers 317 squamous cell carcinomas of the oral cavity initially N0 and treated with curietherapy from January 1959 to December 1970. Upon conclusion of the treatment of T, a radical dissection of the neck was performed only on 110 patients (34.7%) and the other 207 were not submitted to surgery. The incidence of N0 N+ cases was 27.3% (30/110). The clinical evolution showed that in the group not submitted to radical dissection 53 of 179 cases (29.6%) with adequate follow-up had lymph nodal relapses; 15/69 of these were initially T1 (21.7%) and 38/110 initially T2,3 (34.5%). The data concerning clinical evolution and analysis of the survival curves for the 2 groups supply arguments in favor of the systematic treatment of the lymphatic areas of the neck in initially N0 oral carcinomas.

Humans↗
PubMed1982

Radiotherapy as initial treatment for carcinomas of tonsillar region.

For this study we have reviewed 186 carcinomas of the tonsillar region, i.e., the lateral wall of the oropharynx, treated from January 1959 to December 1973 at this Institute. In 148 patients (79.6%) the primary tumor and the lymphatic areas were treated with 60Co-teletherapy (TCT). In 15 cases (8.1%) the primary lesion was removed by transoral surgery, followed by irradiation of the tonsillar region and lymphatic areas with TCT. In 23 patients (12.3%) the primary tumor was treated with interstitial curietherapy, after which a radical homolateral neck dissection was performed on 10 of them; the neck was not treated in the remaining 13 cases, initially N0. As far as the case initially treated with TCT alone are concerned, disease-free survival at 5 years was 42.5% for T1 cases and under 30% for T2, T3, whereas it was only 6.5% for T4. The most frequent failure cause of TCT was local relapse, isolated or associated with a nodal relapse. Local failures were nearly always central. On the contrary, if the field extension was adequate, there were very few nodal failures, at least in initially N0 or N1 cases. Our study recommends a revision of the current attitude towards the treatment of carcinomas of the tonsillar region.

Aged↗
PubMed1982

Curietherapy of oral cancer.

This work concerns 406 oral carcinomas treated with curietherapy (interstitial applications and surface molds) from January 1959 to December 1970. There were 65 (16.0%) carcinomas of the mucosal surface of checks, 15 of the retromolar areas, alveolus and gingiva, and hard palate (3.7%), 211 of the mobile tongue (51.9%), and 115 of the floor of mouth (28.4%). There were 132 (32.5%) T1 cases, 245 (60.3%) T2 and 29 (7.2%) T3. In 376 cases with adequate follow-up (92.6%) there were 93 (24.7%) local relapses: 83 isolated and 10 associated with a lymph nodal relapse; 49.5% of the local relapses were peripheral with respect to the treated volume (46/93). The incidence of local relapses only slightly differed for initially T1 and T2 cases (respectively 21.8% and 22.7%), whereas it was more than twice as much for initially T3 cases (53.6%). The overall incidence of radionecrotic complications was 22.0% (83/376 cases with adequate follow-up). Altogether the disease-free survival was 41.1% and 31.4% at 5 and 10 years, respectively. We think that local control of practically all treatable oral carcinomas can be obtained with a combined treatment.

Adult↗