Tumori Journal

The carcinogenic and cocarcinogenic action of phenobarbital sodium was investigated in adult BALB/c mice of both sexes when administered alone at a concentration of 0.05 % in drinking water for life or after the animals had been treated with a single hydrazine sulphate dose of 5.65 mg. The results demonstrated that phenobarbital sodium is not carcinogenic in this strain of mice, but, since a single dose of hydrazine sulphate was carcinogenic, does not clarify whether it is a cocarcinogen in the lung.

The induction of stress proteins was studied in two human and two murine melanoma cell lines. Exposure for 1 h to heat (42 °C), to ethanol (6%), to arsenate (100 μM) and to disulfiram (50 μM) induced the expression of SPs with apparent molecular weights of 100, 86, 70-72 and 24-26 Kd. Quantitation of the single SPs indicated that the basal level as well as the enhanced synthesis following the various stressors were different in each cell line. The induction of the 100 Kd species occurred in only one murine melanoma and not in the others. The 86 and in particular the 70-72 Kd species were the most prominent groups, whereas the 24-26 SPs were induced only following arsenate and disulfiram exposure in the three melanoma cell lines. In one of the murine melanomas, the expression of SPs was markedly reduced compared to the other cell lines. No definite specific patterns of SP expression could be identified in tumors of the same histologic type.

In 19 patients with monoclonal gammopathy, plasma cell proliferative activity was evaluated using 5-bromo-2-deoxyuridine (BrdUrd) incorporation, as revealed by an anti-BrdUrd monoclonal antibody. A simultaneous standard labelled thymidine incorporation was carried out in all patients as reference test. The BrdUrd method was confirmed as a reliable test and is recommended for routine clinical application in monoclonal gammopathies.

We studied urinary excretion levels of neopterin in 30 cancer patients affected by non-Hodgkin's lymphomas, Hodgkin's disease and multiple myeloma compared to 30 healthy subjects. Mean value of neopterin excretion in cancer patients (576.01 ± 620.37) appeared significantly increased (p < 0.001) compared to normal controls (134.40 ± 41.65). A neopterin excretion above the upper normal limit was observed in 23/28 (82%) patients with active disease. A trend to an increased urinary level of neopterin with more advanced stage was observed, namely in patients with bone marrow involvement and constitutional symptoms. We suggest that the evaluation of urinary neopterin levels may be of value in the diagnosis and follow-pu of hematologic malignancies.

Death certification rates from various cancers or groups of cancers in broad Italian geographical areas (North/Center/South) over the period 1975-1977 were analyzed. In both sexes, there was a clear North/South gradient, with considerably higher rates in the North for total cancer mortality as well as for most common neoplasms. The geographical variation was more marked in males (North/South ratio for total cancer mortality = 1.75 at all ages and 1.70 truncated 35-64 years) than in females (ratio = 1.48 at all ages and 1.28 truncated 35-64). Although, in general terms, the present results confirm previous analyses of cancer mortality in Italy, a few interesting tendencies should be noted. First, the geographical differences in the mid-late 1970's were much more marked for tobacco-related cancers (a factor of over two in males in the North/South ratio) than for other chiefly epithelial carcinomas or nonepithelial cancers. In general, variations for nontobacco-related cancers tended to level off over more recent calendar periods. However, there was little tendency towards decreasing differences in gastric cancer mortality (which was markedly elevated in the North and Center), at least in males. During the 1970's death certification rates from cancer of the (cervix) uteri decreased in northern and central more than in southern Italy. This pattern of trends may have been influenced by a different impact of cervical screening in various areas of the country.

Ten patients with hairy cell leukemia are being treated at our institution with a therapeutic schedule of α₂(r) interferon (2 × 10⁶ IU/m² s.c. three times per week). Five patients underwent splenectomy from 4 to 108 months before treatment; nonsplenectomized patients had spleens palpable 6 to 12 cm UCM. According to Quesada's response criteria, at the sixth month of therapy, one patient was considered a complete responder, 8 partial responders and one a minor responder, with no differences between splenectomized and nonsplenectomized patients. In nonsplenectomized patients the spleen returned to normal. Our data confirm that interferon, even at low dosages, is a very effective approach for hairy cell leukemia. No evidence was found to contraindicate such therapy.

Twelve patients affected by different types of acute leukemia received idarubicin (4-demethoxy-daunorubicin) by oral route at the total dosage of 45, 60 or 90 mg/m’ distributed over three consecutive days. Drug response was assessed by the decrease in blast cells in peripheral blood and showed some variations between the different types of leukemia. Acute myelogenous leukemia patients and those with blastic crisis of chronic myeloid leukemia appeared to be the more responsive groups; however, the lower dose schedule could explain the less satisfactory results obtained in lymphatic leukemia patients. Data suggest that idarubicin is absorbed rapidly after oral ingestion, in spite of nausea and vomiting, which appeared 3-4 h later and were easily controlled by antiemetic therapy. The purpose of fractionating the drug dosage over three consecutive days is to prolong in the blood an elevated concentration of the main idarubicin metabolite (13-dihydro-derivative), which presents in experimental models an antileukemic potency similar to the parent compound. This study confirms that idarubicin is effective in acute leukemia also by oral route. This formulation could offer some advantages for subjects who cannot tolerate parenteral chemotherapy and it could be proposed in maintenance leukemia protocols.

GFAP (glial fibrillary acidic protein) distribution was investigated in selected areas of glioblastomas and astrocytomas. The proliferating cell population of glioblastomas was GFAP negative and contained many mitoses which were also negative. The old, deeply located areas were composed of cells with visible cytoplasm, intensely GFAP-positive; mitoses in these areas were both GFAP-positive and negative. GFAP-positive reactive astrocytes, once trapped in the tumor, were no longer distinguishable from positive tumor cells. They sometimes contained mitoses. In astrocytoma, anaplasia was due to the development of a GFAP-negative population with negative mitoses. The problem of dedifferentiation and differentiation of malignant gliomas in discussed taking into account the possiblity that malignancy may be due to increasing mutation rates of tumors. The problem of redifferentiation of already dedifferentiated cells is also discussed.

The relative DNA content of cellular samples from 54 patients affected by breast carcinomas and 20 affected by benign breast lesions (including 11 fibroadenomas) was measured by flow cytometry. All normal tissue samples and 17/20 (85%) specimens from benign lesions exhibited a cytometrically diploid DNA distribution, 3/20 (15%) benign lesions an abnormal DNA content, and 35/54 (65%) carcinomas at least one aneuploid cell subpopulation. Furthermore, 9/54 (17%) tumors were characterized by the presence of more than one aneuploid cell subpopulation. The results also indicate that flow cytometry can be used to recognize lymph nodes infiltrated by aneuploid cells. Statistically significant correlations were evidenced between the occurrence of aneuploidy or the ploidy level measured as DNA index and the nodal infiltration status. The percentage of S cells can also be extracted from DNA content distribution histograms. Statistically significant differences (p < 0.01) were also observed for the percentage of S cells between normal tissues (6.2±3.2 SD) and benign lesions (11.1±6.6 SD), normal tissues (6.2 ± 3.2 SD) and aneuploid tumors (19.7 ± 10.3 SD), benign lesions (11.1 ± 6.6 SD) and aneuploid tumors (19.7 ± 10.3 SD), and diploid (7.9 ± 4.0 SD) and aneuploid tumors (19.7 ± 10.3 SD).

Two hundred human breasts removed for clinical cancer by radical mastectomy were analyzed to determine whether apocrine metaplasia and apocrine cysts have predilective sites in the four mammary quadrants. One block of tissue randomly removed for each quadrant was examined in one or more histologic sections. The results showed a concentration of apocrine metaplasia and apocrine cysts in the lower mammary quadrants (17.5% versus 8.2%), which is highly significant (x² = 15.25; P < 0.001). The different distribution between breast cancer (showing predilection for the upper quadrants) and apocrine metaplasia is emphasized, together with the higly significant association between apocrine metaplasia and breast cancer. Based on these data, the usefulness of the clinical detection of cysts in the lower mammary quadrants and needle aspiration of their fluid for the morphologic or biochemical diagnosis of apocrine metaplasia in the screening and management of women at risk is suggested.

Fourty-one patients underwent breast reconstruction after mastectomy for cancer and reduction plasty of the second breast, over a 36-month period. These plasties were performed only for reasons of asymmetry, in the absence of any positive preoperative finding. Histologic examination using semiserial sectioning of the whole excised sample detected a high frequency of unsuspected cancer 14/41 (34%). There was a strong predominance of in situ carcinomas 11/41 (27%) over invasive carcinomas 3/41 (7%). These results were compared with those of other bilateral cancer series. When such cancers were detected by random biopsies or mastectomies, the rate of in situ carcinomas was much greater than in cancers detected only by physical and mammographic examination.

The first reported case in the world literature of a ductal carcinoma in situ located within a phyllodes tumor of the breast is presented. Previously reported cases of carcinoma in phyllodes tumors are reviewed, and the relationship between carcinoma arising in fibroadenomas and phyllodes tumors is discussed.

Thirty-six patients with stage III-IV ovarian cancer, bulky disease, were treated with adriamycin and cyclophosphamide administered in two different dosages. Three or four cycles of chemotherapy were administered before the first surgery to facilitate the surgical debulking. After surgery, 6 additional cycles of chemotherapy were administered, and a second look was performed. Clinical CR+PR was observed in 19/30 (63%) evaluable patients after the first part of chemotherapy, but pathologic CR+PR was confirmed in only 13 (43%) patients. After the second part of chemotherapy and the second surgery, 5/30 (17%) patients had pathologic CR and 3/30 (10%) showed residual disease. The two regimens demonstrated similar activity (67% vs 56% clinical CR+PR) but a very different toxicity. In fact, 50% of patients treated with higher doses showed severe leukopenia and 25% severe thrombocytopenia, and 2/13 died of sepsis. The significant activity of adriamycin plus cyclophosphamide in ovarian cancer was confirmed, and increasing the dosage of the two drugs did not increase their activity but only their toxicity.

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) ≥ 200 mg/m². DDP was administered alone or in combination at a dose of 50-70 mg/m² in 91 patients, and at a dose of 100 mg/m² in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m² for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m² (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m². Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

Cardiotoxicity is rarely observed during cisplatin chemotherapy. A possible synergistic toxic effect of cisplatin with etoposide on cardiac electrical activity is discussed. A case of a 60-year-old woman with squamous cell lung carcinoma who developed paroxysmal supraventricular tachycardia during cisplatin chemotherapy is reported. The potential cardiotoxicity should be considered when cisplatin is combined with other cardiotoxic agents or used in patients with cardiac disease.

Thyroid function was assessed in a total of 15 cases, 7 of whom had choriocarcinoma and 8 hydatidiform mole, by measuring free T3, free T4, thyroxin-binding globulin (TBG), basal thyroid-stimulating hormone (TSH) and after the thyrotropin-releasing hormone test (ΔTSH). Free T3, free T4 and TBG were investigated in the same number of healthy women within the first three months of pregnancy. Only 13.4% of the cases presented elevated levels of free T3 and T4 and TBG; TSH and ΔTSH were within normal limits. Both thyroid hormones and TBG returned to within normal limits when β-human chorionic gonadotropin became undetectable. One patient was found to be hypothyroid. Comparison with the control group showed no significant differences except in TBG levels, which were higher in controls. A significant, direct correlation was found between levels of free T3 and T4 and TBG and the pattern of human chorionic gonadotropin.

The authors studied a case of mucin-producing adenoma of the thyroid gland. The tumor consisted almost entirely of signet-ring cells containing mucin, which was strongly positive with PAS, with and without diastase pre-treatment, and Alcian blue stain at pH 2.5. Immuno-peroxidase staining for thyreoglobulin was clearly positive within the cytoplasm of signet-ring cells and also in the follicle material, which indicates that the tumor derived from follicular epithelium.

This is a report on a case of 2 concurrent neoplasms of different histology within the same kidney: a renal cell carcinoma and a transitional cell carcinoma of the renal pelvis in a patient affected by chronic renal failure due to abuse of phenacetin. There was also a transitional cell carcinoma of the urinary bladder.