Growth hormone-releasing factor and fibroblast growth factor regulate somatostatin gene expression.

A multiple peptide-synthesizing clonal rat cell line was used to study the effect(s) of GRF and basic fibroblast growth factor (bFGF) on the synthesis and secretion of somatostatin (SS). The presence of SS-specific mRNA in 44-2C cells was shown morphologically by in situ hybridization. The release and cellular content of SS increased significantly after treatment with rat hypothalamic GRF (rGRF), the ED50 for rGRF stimulation of intracellular SS was 1.9 X 10(-11) M. GRF stimulated SS production in serum-supplemented and serum-free cultures. Results obtained after incubation of 44-2C cells with 125I-labeled rGRF indicated uptake and nuclear localization of rGRF by 44-2C cells. FGF stimulated the secretion and cellular content of SS. We propose that bFGF regulates the short term secretion and accumulation of SS and mediates rGRF-stimulated SS expression.

The surgeon's attitude to malignant lymphomas of the breast. Analysis of eight cases.

Eight cases of malignant lymphomas of the breast were considered. The age of the patients ranged from 26 to 57 years. All the cases were staged according to the Ann Arbor classification system; the distribution was 2 Ie, 2 IIe, 1 IIIe and 3 IVe. Surgery was limited to excisional biopsy in all patients, one of whom had been operated on elsewhere. Six patients had radiotherapy following limited surgery. All of them received chemotherapy. The treatment resulted in complete local control of the disease in all cases and only 2 patients died from disseminated disease. Six patients were alive and free of disease from 34 to 84 months after the diagnosis. Our experience and analysis of the literature allow us to conclude that the role of surgery in the diagnosis and treatment of malignant lymphomas with breast involvement should be limited to removal of the nodule, when possible, or to incisional biopsy in the case of massive involvement of the breast. In effect, aggressive surgery with a radical aim is not presently justified; in contrast, systemic chemotherapy should always be administered.

Surgical treatment of 43 retroperitoneal sarcomas.

Forty-three cases of primary retroperitoneal sarcomas, observed and treated from 1970 to 1983 at this Institute, were analysed. The series consisted of 16 liposarcomas (37%), 10 leiomyosarcomas (23%), 7 rhabdomyosarcomas (16%), 5 fibrosarcomas (12%), 2 malignant histiocytomas (5%), 2 sarcomas NOS (5%) and 1 mesenchymoma (2%). All the patients underwent surgery. In order to evaluate the results of surgery, the patients were divided into three groups, according to the type of operation performed, that is open biopsy, resection and excision. Survival of the patients in the first group never exceeded 24 months. The symptom-free period for the patients treated by incomplete removal of the tumour (second group) lasted 3-24 months. Further surgery, in three cases for this group, did not result in a useful control of the disease. As regards radically treated cases, local recurrence was observed in 3 of the 7 liposarcomas, 2 of the 5 leiomyosarcomas, 1 of the 2 rhabdomyosarcomas and 1 fibrosarcoma. Out of 16 cases of the third group, regularly followed up, only 3 patients (liposarcomas) were alive and free of disease at 5 years from first operation. Overall 5-year survival for this group was 31.9%; disease-free survival was 18.7%. For the whole series of 43 cases, overall 5-year survival was 11.4%. As far as histology was concerned, liposarcomas showed the highest operability rate: out of 16, 7 were resected and 9 radically excised. There is a lack of convincing evidence for the utility of post-operative chemotherapy. On the contrary, post-operative radiotherapy seems to be worthwhile for liposarcomas, especially after non-radical operations.

Mesothelioma of the pericardium: report of a case.

One case of cardiac tamponade from malignant mesothelioma of the pericardium is reported. The tumor was diagnosed by cytology of the fluid drained by pericardial centesis. Necroscopy and histology confirmed the diagnosis.

Endocrine differentiation in basal cell carcinoma.

Argyrophilic cells have been found in 2 different basal cell carcinomas (BCC), and membrane-bound endocrine-like granules, in the carcinoid range, have been observed in 4 consecutive cases of such tumors. It is postulated that BCC can occasionally display cells showing an endocrine differentiation.

Prognostic factors in operable breast cancer.

A series of 743 consecutive cases of operable breast cancer, admitted and treated at the Istituto Nazionale Tumori of Milan from 1969 to 1970, was analyzed by a multivariate statistical method to evaluate a) the variables of the host and the primary tumor associated with the frequency of nodal metastases, b) the variables that significantly affect survival, and c) the identification of homogeneous risk groups. As regards the frequency of regional node metastases, they were more frequently observed in young than in old patients with large tumors (P values 10(-5) and 3 X 10(-5), respectively). Tumors that originated in the axillary tail, upper, outer and central quadrants were significantly associated with a higher rate of node metastases (P = 0.002). Each of these variables maintained its significant value when adjusted by the other two. Survival was affected at a statistically significant level by the age of the patients (P = 2 X 10(-4) ), the pathologic diameter of the primary tumor (P less than 10(-6) ), and the number of metastatic regional nodes (P less than 10(-6) ). The number of involved nodes appears to be the most relevant factor in the assessment of prognosis of patients with positive nodes, Age of the patients, size of the primary tumor, and number of involved nodes maintain their own statistical significance when each is adjusted by the remaining two. The site of origin of the primary tumor, even if associated with the frequency of regional node metastases, did not affect survival. Three groups with a significantly different risk of death were identified in patients with negative lymph nodes and three groups in patients with positive nodes. It is concluded that age, size of the primary, and number of involved lymph nodes are important pieces of information that clinicians should have at hand following radical surgery, not only to make a prognosis, but also to identify groups of patients with high risk of death on which the role of adjuvant treatment should be evaluated.

Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression.

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDC-E2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelium may be the earliest lesion in PBC.

Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes.

The results of the analysis carried out on data on 1119 patients with operable breast cancer treated at the National Cancer Institute of Milan from 1965 to 1979 with enlarged mastectomy are reported. Metastases to internal mammary chain were found to be significantly associated with the maximum diameter of primary (16.1% for tumors less than 2 cm and 24.5% for larger tumors, p = 0.007), the age of the patients (27.6% in patients younger than 40 years, 19.7% in patients between 41-50 years, and 15.6% in patients older than 50 years, p = 0.01). The site of origin of the cancer had no impact on internal mammary node metastases. Patients with positive axillary nodes showed metastases to internal mammary nodes in 29.1% of the cases, while 9.1% of patients with axillary negative nodes had positive retrosternal nodes. Survival was significantly affected by the presence of positive internal mammary nodes: the percentage of 10-year survival varied from 80.4% in patients with axillary and internal mammary negative nodes to 30.0% in patients with both nodal basins involved. Intermediate survival rates (54.6% and 53.0%) were found when one or the other of the nodal stations (axillary and internal mammary) was separately affected. Maximum diameter of the primary significantly affected the survival of each group identified by the status of both axillary and internal mammary nodes. In conclusion, the information on the presence or absence of internal mammary node metastases would be of great importance in formulating the prognosis of breast cancer patients. To obtain this information, a biopsy at the first intercostal space may be reasonable in selected patients (age, maximum diameter, and axillary node involvement being the basis for selection) as long as noninvasive methods of diagnosis are available.

Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients.

The risk of internal mammary chain metastases according to some parameters and its prognostic relevance was evaluated on the basis of the experience collected at the National Cancer Institute of Milan where, from January 1965 to December 1980, 1085 patients were submitted to Halsted mastectomy plus internal mammary chain dissection. A multivariate analysis was carried out, resorting to a multiple linear regression with logistic transformation of the dependent variable. The selection of prognostic factors has been performed with a step-down approach. The frequency of metastases to internal mammary chain nodes was evaluated according to four criteria: age, site and size of primary tumor, and presence of axillary metastases. Data of this series indicate that the frequency of internal mammary node metastases is significantly associated with the age of the patients (younger patients have a higher risk) (p = 0.006) with the size of primary tumor (p = 0.006) with the presence of axillary node metastases (p = 10(-9). Patients with both axillary and internal mammary positive nodes have a very poor prognosis (10-year survival 37.3%) while patients with either axillary metastases only or internal mammary metastases only have an intermediate less grave prognosis (59.6% and 62.4%, respectively). As regards the risk of internal mammary nodes involvement, it appears that knowing the age, the size, and the axillary nodes status, it is possible to calculate with good approximation the probability of their invasion.

Prognosis of breast cancer with axillary node metastases after surgical treatment only.

Out of 753 patients with breast cancer treated with radical mastectomy from 1968 to 1970 at the National Cancer Institute of Milan, Italy, 308 had histologically proven positive nodes. The number of positive nodes was not dependent on the location of the primary tumour, its diameter and the patient's age. Extracapsular invasion was related to the number of positive nodes at a statistically significant level: P value 2 X 10(-9). Survival was influenced by the number of positive nodes and extension of metastases beyond their capsule and age. Each of these criteria had an independent impact on survival. Three subgroups with different prognosis were identified in patients older than 40: (a) with a single involved node and 69.9% 10 year survival rate, (b) patients with two or more nodes with metastatic deposit still confined within node capsule and 47.4% 10 year survival rate, (c) patients with two or more involved nodes and extracapsular invasion and 25.3% 10 year survival rate. In patients younger than 40 no subgroup was identified: this group had an intermediate 10 year survival rate (50.9%). The authors conclude that there is a need (a) of re-consideration of the prognosis of patients with positive nodes and (b) to agree on the definition of "high-risk patients".