Tumori Journal

BALB/Mo mice are characterized by early expression of « endogenized » M-MuLV and are resistant to M-MuSV tumor induction. Furthermore, compared to normal BALB/c mice, sera from BALB/Mo mice exhibit a significant reactivity which is specific for M-MuLV when tested in a ¹²⁵I-labelled Staphylococcus protein A binding assay. The possible significance of this reactivity in conferring tumor resistance is explored.

New daunorubicin-protein conjugates were prepared by covalently linking the antitumor drug to various test proteins via its methylketone side chain. Attachment of daunorubicin to proteins was achieved by nucleophylic substitution reaction of the 14-bromo derivative of the drug, under mild coupling conditions. In contrast to conventional methods, this procedure did not involve reaction or modification of the amino sugar. As expected, the covalent linkage of the drug was generally associated with an appreciable reduction in the drug cytotoxicity to HeLa cells in vitro. The possible advantages of this method for coupling to specific protein carriers are discussed.

Thirty-six patients with severe aplastic anemia or acute leukemia undergoing bone marrow transplantation or intensive hematologic treatments were randomized to receive gentamicin (1 mg/kg/iv q8h) or tobramycin (1 mg/kg/iv q8h) in combination with carbenecillin (500 mg/kg/day i.v. in 4 doses) and cephalotin (200 mg/kg/day i.v. in 6 doses), at the onset of fever during granulocytopenia. Patients in the gentamicin group were treated for a total of 541 patient days (minimum 5, maximum 106), and patients in the tobramycin group for 426 patient days (minimum 9, maximum 48). All patients received oral decontamination, which included the amino glycoside (either gentamicin or tobramycin) given intravenously. This study showed that 1) no patient had an increase in creatinine level above 1.3 mg % and no patient developed renal failure, 2) there was no difference between gentamicin and tobramycin in the efficacy of treating febrile episodes and/or major infections, 3) prolonged intravenous administration (up to 48 consecutive days in the tobramycin group and 106 consecutive days in the gentamicin group) was well tolerated and effective in treating fever of unknown origin in granulocytopenic patients: 45 of 72 febrile episodes resolved while the patients had a granulocyte count below 500/mm³.

The levels of adriamycin in plasma, ascitic fluid and normal and neoplastic tissues sampled during surgery of 3 patients with advanced pelvic cancer were measured by fluorimetry. The highest content of fluorescent compounds was found in tumoral masses in necrotic or scarcely viable tissue; viable and invasive tumor areas scored fluorescence levels comparable with normal adnexa. Ascitic fluid contained levels of fluorescence comparable to the last observed phase of plasma levels. Adipose and cutaneous tissue scored the lowest concentrations.

Since most patients with Hodgkin's disease benefit from splenectomy, a study was designed to explore whether these beneficial effects could be attributed to the recovery of patients’ immunologic reactivity. Using a series of ordinary skin test (PPD-tuberculine, Varidase and Candidin) determination of absolute T and B lymphocyte counts in peripheral blood and their mitogenic responsiveness, assessment of immunologic reactivity was performed in 28 Hodgkin's disease patients, prior to and 14 days after splenectomy. The results showed that overall immunologic reactivity of these patients was suppressed as judged by low absolute lymphocyte counts (1747.2 ± 171.9), lower counts of T (592.0 ± 92.1) and B cells (295.9 ± 40.5) and their poor capacity to respond to phytohemagglutinin (PHA) (20342.6 ± 3662.8 cpm), although the reactivity towards skin test antigens seemed to be well preserved. After splenectomy the reactivity improved, absolute lymphocyte counts raisd to 2654.9 ± 468.8 and were parallelled by an increase in T (936.7 ± 138.0) and B cell counts (402.2 ± 81.2). PHA reactivity recovered as well (26965.5 ± 4035.6 cpm), however, its remained lower than in control cultures. Furthermore, the immunocompetence of patients’ spleens was assessed. The possible influence of some suppressive mechanisms such as serum-blocking factor and prostaglandins is discussed.

Histology and cytometrics were evaluated in 50 cases of human breast infiltrating carcinomas (44 ductal, 6 lobular) assayed for the presence of prolactin receptors (PR). The tumors were considered PR positive when the level of specific binding reached or exceeded 0.5 %. Twenty-six ductal infiltrating carcinomas and 4 lobular ones were PR positive. No strict correlation was found between PR and degree of histologic differentiation (expressed in grades) or menopausal status. Better differentiated (grade I) ductal carcinomas were, however, mostly PR negative. Evaluation of the mean nuclear diameter (MND) and of the maximal epithelial cellularity (MEC) revealed that in ductal carcinomas a high level of PR (> 3 % specific binding) was significantly correlated with a high MND. It is concluded that, contrary to that observed in estrogen receptor-positive tumors, PR-positive human ductal carcinomas are more likely to have large nuclei, i.e., cytologically anaplastic, whereas better differentiated (grade I) carcinomas are generally PR negative.

The authors evaluate the combined use of liver scan and the CEA test in the diagnosis of hepatic metastases of carcinoma of the gastrointestinal tract. Association of the two tests is justified by the fact that the liver scan is very specific but not very sensitive, whereas the CEA test is more sensitive and not very specific. The sensitivity of the CEA test, on the other hand, can be increased by increasing the threshold of normality. However, the associated diagnostic use of the liver scan and the CEA test gives a loss of specificity with respect to the use of the liver scan alone. The present study, carried out on a series of 376 patients affected by gastrointestinal tumors of which 79 were of the stomach (9 with hepatic metastases), 133 of the colon and higher sigmoid (25 with hepatic metastases), and 164 of the lower sigmoid and rectum (29 with hepatic metastases), proposed to establish by use of a statistical method the optimal threshold of the CEA test that would give the best diagnostic specificity of the combined CEA test and liver scan without any relevant loss of sensitivity. A threshold of 26 ng/ml of the CEA test gave a specificity of 92 %, a sensitivity of 80 %, and an accuracy of 90 %. The authors think that in the detection of liver metastases of gastrointestinal tumors, the combined test can be more helpful the less the probability, for a given patient, for other metastatic localizations.

Forty-four patients with central nervous system metastases were treated with combination chemotherapy (adriamycin, VM 26 and CCNU). The best results were obtained in breast adenocarcinoma and small cell lung carcinoma with multiple, small cerebral metastases and without concomitant visceral involvement at other sites. The potential effectiveness of this regimen to prevent cerebral metastases is discussed.

The modality of lung cancer treatment was retrospectively evaluated in an unselected population. All the lung cancer cases diagnosed among the residents in a Local Sanitary Unit of Lombardy during four years (1974–1979), were identified. The clinical records of the 235 collected patients were reviewed and on this basis the anatomical extent of disease was retrospectively classified in stages according to the TNM of UICC (1978). The relative frequency of clinical stages resulted 29 % for stage I, 17 % II, 20 % III and 32 % IV. Only 57 % of all the subjects had been treated; 11 % by resection, 22 % by radiotherapy and 24 % by chemotherapy. For the stages I and II the operability rates were 35 % and 26 % respectively, while the resectability rates were 29 % and 17 %. An objective reason of exclusion from surgery was found in no more than a quarter of stage I and II lung cancers, while the remaining (40 %) had probably been excluded from exploration owing to a subjective prognostic evaluation. If compared with similar reports from other countries, these data show a striking defect in the choice of curative treatment for a high proportion of the examined cases.

Monitoring with anti-idiotypic sera has been applied to identify tumoral cells in a myeloma patient still alive in complete remission 9 years after diagnosis. Monoclonal plasma cells displayed a labeling index that decreased in complete remission below 1 %. The great majority of B lymphocytes belonged to the tumoral clone even in complete remission and were therefore not affected by conventional chemothrapy. Some aspects of this myeloma patient are discussed in the light of these immunologic and kinetic findings. In addition, it is suggested that the therapeutic management of the complete remission should be re-examined, by considering a lymphocytolytic therapy.

A review of a series of 245 ovarian teratomas disclosed 6 cases (2.4 %) of immature teratoma. The tumors were FIGO stage IA(i) and histologic grade 1 (3 cases) or 2 (3 cases). With the exception of 2 specimens, all tumors were larger than 9 cm in the greatest diameter. All patients underwent conservative surgery alone and are alive without evidence of disease from 2.2 to 10.6 years (average, 7.9 years). Our data support the view that conservative surgery is the treatment of choice for patients with stage IA(i), grade 1, immature teratoma, as well as for those with stage IA(i), grade 2 tumors, 9 cm or less in the greatest diameter.

One struma ovarii with agregates of epithelial nests indistinguishable from Brenner tumor was studied. The presence of a communication between the nests and the follicles and the association of Brenner, mucinous and respiratory epithelium in the lining of 1 cyst in the same tumor strongly support the germ cell theory of Brenner tumors associated with teratomatous elements.

We report a new case of ataxia-telangiectasia (AT) and acute lymphoblastic leukemia (ALL) and review all 21 known cases of AT and ALL. Leukemia in these patients is associated with a male predominance, age older than 10 years at diagnosis, a white blood cell count higher than 50,000 mm³, and a fatal course. Four patients have been reported who developed T-cell leukemia, 3 null-cell leukemia and 1 B-cell leukemia. The AT-ALL patients appear to be at risk for infections related to their immunodeficient status and ALL chemotherapy. In addition, neurologic deterioration has been noted during the early phase of therapy.

To define the frequency of gastric epithelial dysplasia (precancerous lesion), 1463 biopsies from 842 endoscopically studied patients were reassessed. Mild dysplasia was found in 19.9 % of the cases, moderate in 4.1 %, severe in 0.95 %. Since the clinical and biological significance of the lesion is still an open question, indications for follow-up are discussed in the light of personal views, together with a critical evaluation of the recently proposed classifications.

A case of primary oat cell carcinoma of the esophagus is described. The oat cell pattern appeared intermingled with small areas of squamous carcinoma. The origin of this mixed tumor is discussed together with the literature on esophageal carcinomas with an oat cell pattern.

Gli autori espongono i risultati di uno studio statistico concernente le correlazioni tra quadro istopatologico e durata di sopravvivenza, in 41 bambini affetti da neuroblastoma. Dopo aver accennato alla significatività di alcuni elementi clinici, vengono descritti i reperti istologici che possono fornire indicazioni sul comportamento della neoplasia. Tali reperti sono rappresentati dal grado di differenziazione e dal grado di infiltrazione linfocitaria del tessuto neoplastico. Infatti dal confronto dell'incidenza di tali reperti nei soggetti deceduti ed in quelli sopravvissuti si sono rilevate differenze statisticamente significative (p < 0.001). Gli autori sottolineano, inoltre, che il grado di differenziazione cellulare si identifica con il numero degli elementi in evoluzione maturativa e non con il numero delle cellule del tutto mature.