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Twenty-three cases of basal-cell tumor of the skin arising in the lumbar-sacral region after repeated irradiations in anti-inflammatory doses for arthrosis are discussed. The involved cutaneous region had been submitted to a number of roentgenotherapy cycles, varying from a minimum of 2 to a maximum of 10. The total dose absorbed at skin level varied between 14.4 and 72.0 Gy, administered over 2 to 6 years. Thirteen to 30 years (median, 19) had elapsed since the end of the irradiations. This observation compels a critical re-evaluation to be made concerning certain radiotheraphy indications. The treatment of these lesions involves some problems: radiotherapy is made difficult by the coexistence of often serious dystrophic lesions on the surrounding skin, and surgery is often unsuccessful. The topic application of a 5-fluorouracil ointment seems to achieve good results.

Physical examination, mammography and fine-needle aspiration cytology were performed in 1498 consecutive cases with a solitary solid lump of the female breast. The intent was to verify the validity of this diagnostic triplet in the accuracy of the preoperative diagnosis of breast cancer. Clinically sure cancers were excluded from the study. The collected data were evaluated in terms of sensitivity, specificity and predictivity of any procedure alone or in combination. In 1138 cases confirmed by histology (514 carcinomas and 669 benign or non-neoplastic lesions), the physical examination and mammography were very sensitive (respectively 96% and 84%) but with a high rate of false-positive reports (respectively 20% and 18%). The cytologic diagnosis was less sensitive (65%), mostly due to many inadequate smears, but highly specific (93%) and predictive for malignancy (99%) when the cytologic report was frankly positive. Any single procedure improved the overall sensitivity, and taken together this triplet appears to be the most effective noninvasive diagnostic combination that provides in a short time with minimal cost and discomfort, a diagnosis of certain malignancy in about 50% of carcinomas with a predictivity close to 100%, when cytology detected malignancy.

We report our preliminary clinical experience with hematoporphyrin derivative (HpD) injection and argon or dye laser irradiation for the treatment of 61 surface neoplastic lesions in 7 patients. Forty-three sites were multiple basal cell carcinoma in 5 patients, and the remaining 18 were cutaneous and subcutaneous recurrent breast carcinoma after mastectomy in the thoracic wall. The patients were selected on the basis of the lack of indication for conventional therapeutic modalities. The selection of irradiation procedures and laser source was based on the thickness of the lesion and extension of the disease. The photochemical reaction between HpD injected i.v. at a dose of 3 mg/kg body weight and the laser beam at a dose of 60 to 120 J/cm2 resulted in 75 % favorable responses at the treated sites. Optimal therapeutic effects appeared to be critically dependent on total light dose and tumor infiltration patterns. The phototherapeutic technique proved to be effective in selected cases of neoplastic lesions, especially when conventional treatment modalities were poorly indicated or contraindicated.

The doubling time (DT) of 196 consecutive breast cancers was studied by means of a double mammographic examination (average time between the 2 mammographies, 30 days) and calculated with the formula of exponential growth. On the basis of DT values the case series was divided into 3 groups of growth: fast (DT from 1 to 30 days), 31 cases (15.8 %), intermediate (DT from 31 to 90 days), 84 cases (42.9 %), slow (DT more than 90 days), 81 cases (41.3 %). No relationship was found between growth rate and size of tumor, or menopausal status of the patient. After mastectomy fast and slow cases were equally distributed in the N− and N+ groups, whereas for the intermediate cases the N−: N+ ratio was 1: 2. One hundred and thirty-four cases were followed for a period of 12 to 52 months. Evaluation was done on the basis of the subdivision into N− and N+, and the latter group into N+ (1–3) and N+ (> 3). For N− tumors the course of the disease was apparently not affected by the growth rate. However, the case of fast growing tumors showed a higher proportion of recurrences with respect to N+ slow growing tumors. This difference was even more noticeable the higher the number of involved lymph nodes, but not statistically significant. The course of slow growing tumors was identical in the N− and N+ groups, but all the N+ tumors were subjected to adjuvant chemotherapy.

The correlations between the thermal gradient of superficial breast cancer lesions (before and 15 days after starting treatment) and the end results of hormonal therapies with estrogen and antiestrogens were investigated. Forty-four women with a median age of over 70 with locally advanced breast cancer and/or metastases mainly located in soft tissues entered the study. Twenty-two patients were treated with diethylstilbestrol sodium diphosphate (20 mg/day i.m.) and the other 22 with tamoxifen (20 mg/day orally). The initial iperthermia was reduced after 15 days in more than 50% of the cases and remained stationary in the others. The cases with a thermal gradient more than 2 degrees C of the tumors did better, in terms of remission, following therapy (64.7% versus 37.0%. However, an early decrease of the same gradient in the course of therapy appears scantily related to the response. The therapeutic results in the 2 groups were very similar: 45.5% complete or partial regression, with a median duration of more than 8 months, in those treated with diethylstilbestrol and 50%, with a median duration of more than 11 month, in those treated with tamoxifen. Only in some cases of the first group of patients the treatment was discontinued due to severe side effects.The ability to detect neoplastic changes in tissue by thermography is known. In this study, correlations between the thermal gradient of superficial breast cancer lesions at various times before and during ablative therapy and the end results of hormonal therapies with estrogens and antiestrogens both were investigated. 22 of 44 patients (median age, 70 years) were treated with diethylstilbestrol sodium diphosphate intramuscularly (20 mg/day) and the other 22 received tamoxifen treatment (20 mg/day orally). Thermal gradients of breast lesions were measured before treatment and after 15 days of ablative therapy. After 15 days of either treatment, the initial iperthermia was reduced in more than 50% of the cases and remained stationary in all others. Tumors with thermal gradients of more than 2 degrees centigrade had more remissions (64.7 vs. 37%) after therapy than tumors with lower thermal gradients. In terms of therapeutic agent efficacy, the results were very similar in the 2 groups: 45.5% showed complete or partial regression (median duration of regression of more than 8 months) in diethylstilbestrol-treated cases and 50% (with median regression time of over 11 months) of tamoxifen-treated cases showed complete or partial regression.

From June 1978 to December 1980 at the Istituto Nazionale Tumori of Milano, a fine-needle aspiration biopsy was performed on each of 4834 cases of palpable mammary nodules, the large majority of which were clinically and mammographically suspicious for cancer and only a small part clinically definitely positive. Of these, 1173 underwent surgery at this institution, and 534 (45.5%) had a histologically proven carcinoma. The aspirations were performed by individuals different from those who read the cytologic smears. The aspirations were never repeated, and methods for the retrieval of cells were never applied. Under the circumstances, sensitivity was 0.67, specificity 0.98, and the predictive value for positive results 0.97. The high percentage of inadequate samples (25.5%) influenced the low sensitivity. The few false-positive results occurred exclusively during the first year. Frozen sections can be avoided in those cases (about 50%) with definitely positive cytologic diagnosis by the application of strict criteria. The intrinsc incapability of cytology to yield any information on the extent and the invasiveness of a malignant lesion does not seem to effect its pre-operatory conclusiveness.

The usefulness of 131Cs scanning in preoperative diagnosis of 131I cold nodules of the thyroid that present no clear clinical sign of malignancy is discussed. The results of clinical examination of 283 thyroid nodules, associated in 139 cases with 131Cs scanning, are correlated with the histologic nature. In nodules that were classified as cold, warm or hot in the 131Cs scan, the incidence of malignancy was 2.6, 12.3 and 25 %, respectively. In the nodules that, on the basis of clinical examination, were classified as probably benign, dubious or suspected for malignancy, the incidence of cancer was, respectively, 3.6, 26.3 and 72.7 %. Malignancy ocurred in 16 of 144 patients that were selected for surgical treatment only on the basis of clinical data and in 17 of 139 patients that were selected on the basis of clinical examination associated with 131Cs scanning. The accuracy of clinical preoperative diagnosis of thyroid cold nodules does not seem to be significantly improved by association of 131Cs scanning.

The medical records of 84 postmenopausal women treated with oral norethisterone acetate (NTA) for advanced breast cancer were retrospectively analyzed. Treatment was devoid of significant toxicity. Twenty-one patients were not evaluable for treatment response either because of insufficient data or inadequate treatment trial. Complete plus partial response was obtained in 21 (33.3 %) of the 63 evaluable patients, with a median duration of 10 months. Disease stabilization was observed in 16 (25.4 %) patients for a median duration of 5 months, while 26 patients (41.3 %) showed progressive disease while on treatment. The best response was observed in women with dominant soft part disease and an age over 70 (CR+PR 48 %). The literature on norethisterone acetate is reviewed and compared with present results. The role of progestational agents in the treatment of advanced mammary carcinoma is discussed.

Sixty-five postmenopausal patients with metastatic or surgically unresectable primary breast cancer, all estrogen receptor (ER) positive, were treated with tamoxifen 20–40 mg a day. Overall objective response rate was 58%, with a median duration time of 13 months. The correlation between response rate and ER levels appears positive, although not statistically significant. The analysis of the data was also performed in the subgroups « locally advanced tumors » and « recurrences and metastases ».

A research on the degree of knowledge about the problem of breast self-examination was carried out in a group of 500 women in the Out-patients Department of the Cancer Institute in Milan. The women were given a questionnaire to fill up at home and to return at the moment of the medical examination. The analysis of data showed that, though the level of education of the subjects was fairly good, the knowledge and the practise of the periodical self-examination as a method for an early diagnosis was very low. 70% of the women declared to have some knowledge about the method, but only 9% declared to practise it regularly.

Long-term results of 100 cases of Hodgkin's disease, treated with chemotherapy associated or not with X-ray therapy from 1949 to 1900, are reported. The median, survival rate was of 36 months: at 5 years the rate was 25 %. The survival rate at 5 years was 34,2 % for the 38 women and 19.3 % for the 62 men treated. Of 66 cases of the third clinical stage 31.6 % was alive at 5 years; the corresponding value for the 40 cases of the fourth stage was 15 %. The best survival rate was observed in the group of women of the third clinical stage with involvement of ilo-mediastinic lymph nodes in the first period of the disease (52.6% at 5 years). As to the four histological varieties of our cases, one can observe that the «paragranuloma» and the «scleronodular» types show a fairly good survival rate, not depending on the clinical stage, whereas the «polymorphous» and «sarcomatous» ones cause a more severe prognosis for the patients of the fourth clinical stage. The age of the patients, evidence or not of « systemic » symptoms, and the duration of the disease before the first treatment don't seem to have any significant influence on the survival rate. The best results were obtained with chemotherapy-X-ray therapy association in the group of patients of the third stage (survival rate of 39.5 % at 5 years). No difference is noted, on the contrary, between long-term results of chemotherapy alone and those of chemotherapy associated with X-therapy in the fourth stage.

27 cases of primary retroperitoneal tumours are described. They are divided into: 1) mesenchimal tumours; 2) lymphoglandular tumours; 3) nervous tumours; 4) tumours from embryonal rests. Considerations are briefly exposed on the spreading and metastases of such tumours, on the anamnestic and clinical data and on the radiological method which may be utilized for a diagnosticai ascertainment. The treatment of election is the surgical one, completed by radiological therapy in the radiosensitive cases. A table is reported in which the performed treatments and the late results are summarized.

The survival rate of 106 cases of advanced lymphosarcoma and reticulum cell sarcoma that had received chemotherapy, with or without radiotherapy, between 1951 and 1962 is reported. The course of both diseases was initially highly malignant, with a median survival of 20 months for lymphosarcoma and 6 months for reticulum cell sarcoma. Cases surviving for over 3 years, however, have a good chance of long survival. Male sex and an age of under 40 (there were no cases of under 13 in our series) seem to be favorable prognostic factors. A long pre-treatment interval is favorable for lymphosarcoma and adverse for reticulum cell sarcoma. The clinical stage (3 or 4 according to the classification of Banfi et al.) does not significantly affect the prognosis of lymphosarcoma whereas in reticulum cell sarcoma survival is strongly correlated with clinical stage. Chemotherapy (with alkylating agents) yielded a 5-year survival rate of 20.8% in lymphosarcoma; with radiotherapy the rate rose to 32.3%. In reticulum cell sarcoma the 5-year survival rate was 20% for chemotherapy alone and 14.2% for chemotherapy in association with radiotherapy. Our data seem to confirm the usefulness of chemotherapy, with or without radiotherapy, in diffuse forms of lymphosarcoma and reticulum cell sarcoma, especially with regard to long-term survival.

Hydroxyurea has been adequately evaluated in 27 patients with inoperable or advanced lung cancer (group A). The drug was also given to 13 patients with miscellaneous metastatic solid tumors (group B). Four different dosages of hydroxyurea were administered: 40 mg/kg/day p.o. (15 patients of group A and 7 patients of group B); 10 mg/kg/day i.v. (3 patients of group A and 1 patient of group B); 100 mg/kg/week (3 patients of group A and 2 patients of group B); 100 mg/kg i.v. on alternate days (6 patients of group A and 3 patients of group B). The total daily dose was given in two administrations with an interval of 12 hours. None of the patients had been previously treated with radiotherapy or chemotherapy; their performance status was not less than 40. Subjective and objective responses, evaluated on the Karnofsky's categories, were seen in patients with advanced lung cancer, but only one patient of the miscellaneous group showed an objective response to hydroxyurea. The therapeutic responses were achieved in group A with dosages of 40 mg/kg/day p.o. (5/15 cases) and of 100 mg/kg i.v. on alternate days (4/6 cases). Relief of symptoms and objective regressions were short-lived. No maintenance treatment in responsive cases was given. There was no definite change in the basic course of the disease. The other patients treated respectively with 10 mg/kg/day and with 100 mg/kg/week were very few and received a smaller total dose of hydroxyurea. Bone marrow toxicity occurred mainly with patients receiving higher doses of hydroxyurea (40 mg/kg by mouth and 100 mg/kg i.v. on alternate days respectively). In these patients progressive leukopenia and anemia developed in almost every case, often requiring multiple blood transfusions. Megaloblastosis was checked in 3 cases. Five patients after 2–3 weeks of treatment had nasal bleeding, which disappeared spontaneously after 3–6 days. Only 2 patients, while receiving hydroxyurea by mouth, complained of nausea and epigastric distress and the drug was discontinued temporarily. Two patients showed a mild hyperuricemia after the first week of treatment. The administration of intravenous hydroxyurea at the dose of 100 mg/kg on alternate days in lung cancer deserves a more extensive trial.

Methotrexate (MTX) was given by weekly rapid intravenous injections to 27 patients with inoperable oropharyngeal carcinoma. 9 cases were untreated while 18 had received radiotherapy or chemotherapy before administration of MTX. In 20 cases the dose was 40 mg/m2/week (patients over 50 years) and in 7 cases 60 mg/m2/week (table 1). In responsive patients, maintenance treatment was given at the dose of 15 mg/m2 every 4 days either orally or intramuscularly. 23 cases were adequately evaluable, i.e. they received treatment for a minimum of 3 weeks. Response to treatment was evaluated according to Karnofsky's scale. Considering only category 1 regressions, 11/16 (75%) patients adequately treated with 40 mg/m2 showed objective improvement and respectively 4/7 (57%) given 60 mg/m*. 8 out of 15 cases (41%) with category 1 response showed a regression greater than 50%. The mean duration of response for category 1 patients was 3.5 months, while the longest regression lasted 9 months (table 2). 18 patients had one or more side effects: 9 had oral lesions or gastroenteritis, 12 bone marrow depression, 3 hepatic and 1 renal toxicity. One patient died from hepatic and renal toxicity; in the remaining cases the side effects were quickly reversible (table 3). The percent regression rate for category 1 response and its average duration obtained with intravenous MTX seems comparable to intraarterial infusion (table 4). Systemic toxicity seems also comparable (table 5). Furthermore, intravenous administration obviates the typical local complications occurring with intra-arterial treatment and therapy can be given also at outpatients. For this reason, intravenous administration of MTX is preferred to intra-arterial infusion in the control of primary inoperable oropharyngeal carcinomas, provided no severe depression of liver, kidney and bone marrow is present.

The cases of advanced head and neck tumors treated with palliative chemotherapy by prolonged arterial infusion at the National Cancer Institute of Milan, Italy, between 1960 and 1970 are reviewed. The drugs most frequently used were: Methotrexate (alone or associated with Daunorubycin), Daunorubycin and Adriamycin. 97 infusions were performed in 92 patients and 63 had lesions suitable for evaluation. Regression occurred in 43 (68.3%): over 50% of the starting size of the tumor in 15 and under 50% in 28; 13 patients died as a result of the treatment. Side-effects were numerous and frequent and the incidence of local complications was high, especially in cases of direct cannulation, which also ensured the biggest decreases in tumor size. Cancer of the movable part of the tongue was most responsive to the treatment. Adriamycin with 88 % of regressions and Methotrexate with 73 % were the most effective drugs. The results of this series show that prolonged intra-arterial chemotherapy can yield a high regression rate in head and neck cancer but is is not devoid of serious side-effects and the incidence of local toxic and technical complications is high. Because of this and of the short duration of regression, it is doubtful whether arterial infusion represents an advance over other modes of administering chemotherapy.

A summary of the results obtained by the Italian Breast Cancer Group in 122 patients with advanced breast cancer randomized over four different treatments: testosterone propionate, given i.m. 3 times a week at the dose of 100 mg per injection; cyclophosphamide, administered i.m. 25 times a month at the dose of 100 mg/day; testosterone + cyclophosphamide i.m. at the above doses; HMNT (4-hydroxy-17 methyl-19-nortestosterone) given i.m. 3 times a week at the dose of 100 mg/day. The criteria for patient selection and methods of evaluation were, with some modifications, these used by the American Breast Cancer Group. Objective improvements were observed in 26.9% of patients treated with testosterone propionate, in 15.6% of patients treated with cyclophosphamide, in 23.5% of those treated with testosterone + cyclophosphamide and in 20% of patients treated with HMNT. The most interesting result, worth of further evaluation, is that observed with the combined testosterone + cyclophosphamide therapy, which yielded the highest number of objective improvements in patients in menopause for less than one year.

116 cases of parotid tumours are examined from the histological, clinical and therapeutical point of view. The difficulty of diagnosis between benign and malignant tumours, the relative frequency of the latter, the latent malignancy of mixed tumours and their frequent recurrences after simple surgical removal are considered. The total parotidectomy with preservation of the facial nerve is proposed. By this surgical technique a radical removal of the tumour is obtained without damaging the function of the nerve. A restricted or a more radical surgical treatment as well as irradiation may be adopted in some cases.

The antineoplastic activity of tris-ethylene-iminobenzoquinone was studied on 15 patients (3 reticulum-cell sarcomas, 2 Hodgkin's diseases, 2 multiple mielomas, 1 chronic lymphatic leukemia, 1 fibrosarcoma, 6 carcinomas). The drug was administered either intravenously or by mouth. In 10 cases there was a subjective improvement, while objective improvement was obtained in 7 cases, with slight side-effects and a temporary mild depression of the blood picture.

Methotrexate (MTX) was given by weekly intravenous injections to 43 patients with inoperable or metastatic lung cancer (32 cases were untreated while 11 received radiotherapy or chemotherapy prior to administration of MTX). In 35 cases the dose was 40 mg/m2/week and in 8 cases 60 mg/m2/week. 36 patients were adequately evaluable. In most cases it was possible to continue the administration of MTX for 6–8 weeks (table 1). In responsive cases maintenance treatment was given at the dose of 15 mg/m2 every 4 days either orally or intramuscularly. Response to treatment was evaluated according to Karnofsky's scale. Considering only the category I responses 12/30 patients adequately treated with 40 mg/m2 showed objective improvement and 2/6 of those given 60 mg/m2. Regressions were short-lived and in no case did they last longer than 5 months (table 2). Regressions were seen in practically all histologic types (table 3). Of 43 patients receiving MTX 30 (70%) had one or more side-effects: 27 showed oral or gastrointestinal toxicity, 8 varying degrees of bone marrow depression, 6 hepatic and 4 renal toxicity. Four patients died because of toxicity, renal damage being present in all cases (table 4). The relatively small number of consistent objective regressions (about 40%), their short duration and the high incidence of severe toxicity, as observed in the present series, indicate that weekly high-dose intravenous MTX is of moderate therapeutic usefulness in lung cancer.

The Committee for the Study of Malignant Lymphomas of the National Cancer Institute of Milano in cooperation with the Institute of Radiology, University of Milano presents a new clinical classification for lymphosarcoma and reticulum cell sarcoma as well as the method of treatment adopted in these Institutes. For primary lymph node lesions the staging is identical to that already proposed for Hodgkin's disease. Stage I: disease limited to a single peripheric lymphatic region. Within this stage two groups can he distinguished: a) involvement of one single lymph node or few nodes limited to a small area of the region (unifocal lesions); b) involvement of many nodes spread throughout the region (uniregional lesions). Stage II: disease limited to two contiguous peripheric lymphatic regions, or to few deep nodes (mediastinal, retroperitoneal). Stage III: disease limited to two non contiguous peripheric lymphatic regions, or to many peripheric and/or deep (mediastinal, retroperitoneal) regions, provided the involvement is either above or below the diaphragm. Stage IV: generalized disease with involvement of lymph nodes above and below the diaphragm, or involvement of one or more lymphatic regions with concomitant involvement of visceral organs, bones, marrow, nervous system and skin. For primary pharyngeal lesions the T.N.M. nomenclature has been adopted. T1: unifocal lesion (e.g. nasopharynx, tonsil, uvula); T2: multifocal lesions (e. g. nasopharynx and tonsil, tonsils, tonsil and base of the tongue); T3: unifocal lesion with extension beyond the anatomical confine of the site of origin (e. g. base of the skull, paranasal sinuses, jaw, orbit); T4: multifocal lesions with extension beyond the anatomical confine of the site of origin. N0: no adenopathy; N1: ipsilateral contiguous adenopathy (submental and/or cervical); N2: bilateral contiguous adenopathy; N3: bilateral contiguous and/or supravicular adenopathy (unilateral or bilateral); N4: distant adenopathy. M–-: absence of metastases; M+: presence of metastases (visceral, osseous, nervous, cutaneous). The remaining primary extranodal lesions (visceral, osseous, cutaneous, etc.) are classified as local, regional and diffuse. Systemic symptoms and signs (fatigue, fever, night sweats, more than 10% weight loss, itching, anemia, leukocytosis, lymphocytopenia, high erythrosedimentation rate) must be recorded in each case to evaluate prognosis and proper treatment but are not important for staging the disease. In all stages with primary lymph node lesions endolymphatic radiotherapy with Lipiodol F I131 is indicated (10 ml in each foot with 2–5 mc/ml giving a tissue-dose of 15-20,000 rads). This is considered as radical as well as prophylactic treatment for those lymph nodes adequatelly filled with the contrast medium. In case of non filling or incomplete filling of part of the lymph node chains, treatment will be completed with external radiation therapy. Stage I and II are treated with radical radiation therapy. No prophylactic radiotherapy is given. If systemic symptoms and signs are still present after radiotherapy a course with anticancer drugs will be administered. Radiation therapy is given with high voltage or Co60 units. In radical treatments tumor doses of at least 3,000 rads within 3–4 weeks are administered to all involved lymphatic regions. In stage III radical radiotherapy follows a course of chemotherapy. In stage IV chemotherapy is the treatment of choice. Palliative radiotherapy is given to any bulk of tumors, wherever the location, when specific symptoms can be attributed to the masses. For primary pharyngeal lesions the primary focus (T1, T2, T3, T4) is always treated with radical radiation therapy (Co60 unit) which includes in the whole Waldeyer's ring. Prophylactic radiotherapy (Co60 unit with doses not less than 3,000 rads in 3–4 weeks) is given in N0 to the ipsilateral and in N1 to the contralateral submental and cervical lymphatic regions. In N1 and N2 the lymph node bearing areas are given radical radiation therapy. In N3 are irradiated prophylactically also the contralateral submental, cervical and supraclavicular lymphatic regions if clinically free of disease. Endolymphatic radiotherapy is performed only in T1 T2 T3 T4, N3 N4, M–- or M+ cases; otherwise diagnostic lymphangiography is performed and when pathologic nodes are present or suspected they are irradiated with Co60. Chemotherapy is given after the course of radiotherapy in N2 cases only if radical treatment has not been accomplished, while is always administered in combination with radical radiotherapy in N3 cases, and is considered the treatment of choice with palliative radiation therapy in N4 and M+ cases. The drug of choice is methyl-bis-(β-chloro-ethyl)-amine HCl (HN2) 0.4 mg/kg i.v. (single dose) for those patients who did not receive any previous course of chemotherapy. Otherwise, as well as during the course of the disease and in maintenance therapy, other polyfunctional alkylating agents, but chiefly chlorambucil (0.1–0.2 mg/kg/die, p. o.), vinblastine (0.10–0.15 mg/kg/week, i.v.), alone or every two weeks in combination with small daily doses of chlorambucil (5 mg/die, p. o.), methylhydrazine, hydroxyurea, and corticosteroids will be administered according to each clinical situation. Relapses in oropharynx can be treated with intraarterial infusions of amethopterine, vinblastine and cyclophosphamide. Radical surgery followed by a course of radiotherapy is reserved for primary lymphatic involvement only in specially selected patients in Stage I with unifocal lesions. Primary involvement of stomach, small bowel and colon is treated by surgical extirpation and radiotherapy. Splenectomy, lobectomy or pneumonectomy is indicated when these viscus are the only site of involvement. During pregnancy radiation therapy is not administered below the diaphragm and chemotherapy is not given during the first 4 months. The need for one internationally accepted clinical classification for lymphosarcoma and reticulum cell sarcoma is stressed.

The authors refer on a clinical trial conducted on a group of 32 women with advanced breast cancer, in order to evaluate the effects of the combined hormonal and cytotoxic treatment of the disease. An androgen compound (2 α-methyl-dihydrotestosterone or n-ottil-enolic ether of dihydrotestosterone) and a cytotoxic substance (Cyclophosphamide) were administrated i. m.; the dose of Cyclophosphamide was 100 mg a day, whereas the dose of the hormonal compound was 100 mg 3 times a week. The treatment was continued over a period of time ranging from 2 to 23 months; the administration of Cyclophosphamide was discontinued for a short period only in case of marked leukopenia: in the course of the therapy the expected side-effects were noted, but they were never of great importance. An objective improvement was obtained in 18 patients; the mean duration of this improvement was of 8,5 months. In 8 women the neoplastic lesions remained unchanged, while in 6 patients a progression of the disease was noted. After a review of the most important records of the world literature on the subject, the authors come to the conclusion that this form of combined therapy may be of some use, particularly in those patients who are not responsive to endocrine ablation. Moreover, the possibility of long term treatments is emphasized, for the lack of any notable, unwanted side-effect.

The treatment with 4-chloro-testosterone acetate exerted, in 10 patients bearing malignant tumours or operated upon, a manifest proteoanabolic effect, with increase in the body weight, augmented proteinemia, retention of urea and of the other catabolites of the protein turnover and improvement of the general conditions. No unpleasant side effects were observed.

Adriamycin, a new antitumor antibiotic of the anthracycline group, was given by arterial infusion to 20 patients with different types of advanced cancer. Two doses and schedules were used: 0.3 mg/kg daily for 10 consecutive days and 0.4 mg/kg on alternate days for 20 days. The drug was used for inducing the first remission. In responsive cases maintenance treatment was given with methotrexate. 15 patients were adequately evaluable. 12 patients adequately treated showed objective improvement and 5/15 regression > 50%. Head and neck cancer and undifferentiated reticulosarcoma of the liver were the diseases most sensitive to adriamycin by arterial infusion. Melanoma, metastatic liver cancer and pelvic cancer showed little improvement. Of 20 patients receiving adriamycin, 15 (75%) had one or more side effects: 12 had stomatitis with oral ulcerations, 17 varying degrees of bone marrow depression, 10 alopecia, 5 hyperthermia. Complications are observed in 11 patients. Adriamycin at 0.3 mg/kg daily by prolonged arterial infusion appears to be a potent growth-inhibiting compound useful for inducing the first remission only in head and neck cancer.

The activity of 2 α-methyl-dihydrotestosterone propionate, was evaluated on 20 women with advanced breast cancer. The age of the patients ranged from 31 to 74 years; the compound was administered i.m. 100 mg 3 times a week, over a period of time ranging from 2 weeks to 8 months. An objective improvement was obtained in 6 patients; the mean duration of the improvement was of 5.8 months (with a maximum of 8 months). In 9 patients the lesions remained unchanged, while in 5 there was a progression of the disease during the treatment. The neoplastic lesions of breast, skin and lymph nodes appeared to be much more responsive to the treatment than the osseous and visceral lesions. The highest percentage of improvement was obtained in early postmenopausal women. The compound proved to be practically free of virilizing action, one woman only showing a marked virilization. No other notable side effects were observed.

772 carcinomas of the tongue, observed in the Cancer Institute of Milano from 1928 to 1951, are considered from a statistical, clinical and therapeutical standpoint. Their incidence corresponds to the 3,5 per cent of all malignant tumours observed in the same period. Male patients represent the 84 per cent; mean age 62 years.. Tabagism, dental or prosthetic trauma, leukoplakia and papillomatosis, syphilis, are to be looked upon as pathogenetic factors. In the 70 per cent the neoplasm is arising from the lingual margins, in the 15 per cent from the base. The 95 per cent of cases were spinocellular carcinomas. The subjective symptomatology is often moderate, even in relatively advanced stages. A bioptical examination is always advised, notwithstanding the rather easy diagnosis. Interstitial radium therapy, by needles and cells implant, is still the most used treatment; a reawakened interest in surgery, either alone or in combination with radiation, is however observed, especially as concerns a block removal of the tumour and node metastases with or without mandibular resection. The 77 per cent of patients showed a satisfactory response to the therapy. 5 years survivals were observed in the 21,4 per cent of the cases treated from 1928 to 1935 and in the 38,6 per cent of those treated from 1936 to 1950. Curability rate was higher in the forms involving the tongue dorsum, and in women. Cervical lymph nodes metastases are frequent (about 60 per cent of cases) and often difficult to detect at early stages; the prevailing seat is the homolateral jugular chain. Such metastases are only treated by surgical operation, consisting in homolateral neck dissection which must be systematically carried out after treatment of the tongue cancer. A radical dissection can be performed, being operatory risk unsignificant and late results good (42 per cent 5 years survivals out of 212 operated patients in comparison with 35,3 per cent ouf of 181 less advanced cases not submitted to dissection). The importance of a precautionary neck dissection is emphasized. Further improvements in the treatment of the primary tumour and a larger adoption of a block removal of tumour and metastases in the most advanced cases are advocated.

In 23 women (12 in menopause) with advanced mammary cancer, the vaginal cytological examination was performed during treatment with oestrogens and androgens. Therapy attained a regression of the neoplastic process when hormones were administered in such doses to maintain the presence of picnotic eosinophilic cells (with oestrogen therapy) or of intermediate cells with active nucleus (with androgen therapy). When higher doses were administered, the disappearance of normal epithelial elements (picnotic eosinophilic cells and active intermediate cells) was remarked in the vaginal smear, associated with a pronounced vaginal hypotrophy (occurrence of eosinophilic basal cells and of vacuolized anucleated cells). In these cases the neoplastic process resumed its evolution.

Bilateral oophoro-adrenalectomy was carried out in 12 cases of inoperable disseminated breast cancer. Results are referred. Subjective and objective improvements and particularly interesting laboratory data are exposed and discussed. The conclusion is drawn that oophoro-adrenalectomy may be considered as a sure though not decisive progress in the palliative therapy of advanced breast cancers.

Fifteen women with advanced breast cancer underwent chemotherapeutical treatment with continuous arterial infusion of 5-Fluorouracile. The age of the patients ranged from 36 to 68 years; the patient of 36 had been previously ovariectomized. For cancer of internal or central quadrants of the breast, internal mammary artery was incannulated, while for those of the external ones, the tip of the catheter was led into subclavian artery through an arterotomy of brachial artery. In the cases in which the tumor was extended to the whole breast two vessels were incannulated, namely internal mammary and brachial artery. The drug was administered in a dose of 1 g a day, for a period of time ranging from 2 to 8 days, in 1000 ml of dextrose solution. The results of the treatment are the following: regression of more than 50% in 4 cases; regression of less than 50% in 5 cases; in 5 cases poor or no result was obtained. One woman died after one day of treatment from coma cerebralis. In 7 cases complications were observed, mainly spasm and thrombosis of the arteries and flittenular dermatitis; in 2 cases a decrease of WBC down to 3000/cmm was observed. In our experience, this method of chemotherapy seems to be indicated in a limited number of cases in which the tumor, though locally advanced, is still contained within the limits of the anatomic region. It is also indicated in case of local recurrences of tumors previously operated and expecially in carcinomatous mastitis.

A case of diffuse mesothelioma of the pleura was twice successfully treated with cyclophosphamide, and is still in partial remission one year and half after the first treatment.

Bilateral oophoro-adrenalectomy appears, at present, to be the best among methods of endocrine treatment in inoperable or metastatic mammary carcinoma. Statistical results concerning 42 women treated with bilateral oophoro-adrenalectomy during 2 years are referred. Objective improvements have been obtained in the 59 per cent of the cases and subjective improvements in the 83 per cent. Both clinical and laboratory findings are, however, still lacking for the prediction of beneficial results in each patient.

The clinical results obtained with a colchicine derivative, the trimethylcolchicinic acid methyl ether, are refrerred. 20 cases were treated, and respectively 14 Hodgkin's diseases, 3 reticulosarcomas, 3 carcinomas. The compound showed a considerable antitumoral activity and a scarce toxicity in general and on the hemopoietic function in particular. It may be considered as possessing the most important requisite for a cytostatic drug actually, that is the possibility of a prolonged and efficient administration without secondary toxical phaenomena. The association of trimethylcolchicinic acid methyl ether with other chemotherapeutical and radiotherapeutical means seem to be of interest and worth of further development.

The paper deals with 100 cases of Hodgkin's disease, treated at the National Cancer Institute of Milan from 1949 to 1958, all submitted to clinical follow-up until the end of November 1966 or death. Histologically, the 100 cases were grouped as follows: 14 paragranulomas, 15 nodular scleroses, 49 polymorphous granulomas and 22 Hodgkin's sarcomas. Paragranulomas showed the best average median and 10-year survivals, nodular sclerosis the best 5-year survivals; Hodgkin's sarcomas showed the worst clinical evolution, without 10-year survivals. The behaviour of the disease was found to be more unfavourable in the third and fourth decades of life, more favourable in the fifth decade. In men the evolution was slower, after an initial unfavourable course; no 10-year survival was observed in women. Nodular sclerosis prevailed in early diagnosed patients, paragranuloma and Hodgkin's sarcoma in late diagnosed cases. Eighty-eight of the 100 patients were at III and IV clinical stage at admission, only 12 at I or II stage. Nearly all cases of nodular sclerosis concerned patients at the III stage, with mediastinal involvement; Hodgkin's sarcoma was more frequent in patients at the IV stage. Five-year survival at the IV stage was observed only in patients with paragranuloma or nodular sclerosis; these two histological types prevailed also in patients without general symptoms. Polymorphous granuloma and Hodgkin's sarcoma were more frequent in patients with general symptoms.

A case of breast cancer was treated with mastectomy followed by cyclical combination chemotherapy with CMF for a year. In the course of chemotherapy cancer developed in the contralateral breast. Mastectomy was followed within two months by lung metastases. After ovariectomy the lung metastases cleared almost completely. The case shows how the hormone dependence of a breast cancer can remain unimpaired even after prolonged chemotherapy and notwithstanding its failure and secondly that amenorrhea due to chemotherapy need not mean endocrine failure of the ovary.