Stefano S. Stefani

The Impact of Current Staging Procedures in Assessing Disease Extent of Prostatic Adenocarcinoma

We studied 454 patients with prostatic adenocarcinoma who were assigned a preliminary clinical stage on the basis of serum acid phosphatase, routine bone survey and physical examination. Subsequently, they were assigned a final clinical stage after radioisotopic bone scanning, lymphangiography and staging pelvic lymph node dissection. Only 53, 54, 57 and 26 per cent, respectively, of patients initially assigned the preliminary clinical stage of IB, II, III or IVA remained at that stage after the additional studies.

Radiation Therapy Versus Delayed Androgen Deprivation for Stage C Carcinoma of the Prostate

Seventy-three patients with prostatic adenocarcinoma who were believed to have disease limited to the pelvis without evidence of node or bone extension were assigned randomly to either full-field pelvic radiation (40) or delayed hormonal therapy (33). The interval to first evidence of treatment failure was used as the end point of the study. Failures occurred in 13 patients who received radiation therapy and 11 who received delayed hormonal therapy. No difference in disease response could be identified between the 2 treatment groups.

A possible mode of formation of tubuloreticular structures

Serial electron micrographs of a cell containing tubuloreticular structures or undulating tubules associated with endoplasmic reticulum (ER), as they were previously designated, suggested that these structures are derived from ER. The endoplasmic reticulum forms paired or compound reticulum when two or more elements of this organelle come close together. In such a juxtaposition, the inner paired lamellae lose the attached ribonucleoprotein (RNP) granules and the lamellae and material between them become more electron opaque. The outermost lamellae of the compound reticulum retain RNP granules. Although the mechanism of tubule formation is not known, the paired lamellae form undulating tubules in the dilated cisterna of ER. The amount of undulation and the packing of tubules which produce various profiles seen in the electron microscope probably depend on the physiopathologic state of the cell. A three-dimensional reconstruction of one of the possible modes of formation of tubuloreticular structure is provided.

Ultrastructural events in the cytoplasmic death of lethally-irradiated human lymphocytes.

Normal human peripheral-blood lymphocytes were irradiated with a dose of X-rays and processed for electron microscopic examination at different times after irradiation. A localized protrusion of the plasma membrane of the irradiated lymphocytes was observed in samples fixed as early as 15 min after irradiation, suggesting that the injury to the plasma membrane could have occurred during or immediately after irradiation. This was followed by fenestration of the plasma membrane, rarefaction of the cytoplasm and accumulation of cytoplasmic organelles in the centrosphere region. Localized distention of the outer nuclear envelope occurred after 2 hours and invagination of the inner nuclear membrane after 4 hours of irradiation. By 24 hours, the cytoplasmic and nuclear ultrastructural integrity was lost. The study suggested that, for high doses of X-radiation, the plasma membrane of the human peripheral-blood lymphocytes was the most sensitive target.

Lymphocyte Mediated Natural Cytotoxicity in Neoplasia

Peripheral blood lymphoid cells from normal donors, patients with non-malignant diseases, and patients with malignant diseases were evaluated for cytotoxicity against a cultured carcinoma cell line, using a chromium release assay. The natural spontaneous lymphocyte-mediated cytotoxicity was significantly higher in tumor-free groups. The observed decreased response in patients with malignancies correlated with depressed responsiveness to phytohemagglutinin stimulation. Removal of cell subpopulations bearing Fc receptors significantly decreased the cytotoxicity, while depletion of phagocytic mononuclear cells did not. We suggest that natural cytotoxicity is a measure of cell membrane integrity of lymphocytes and should be included as a routine test for evaluation of general immune competence.

Relationship between in vitro and in vivo radiosensitivity of lymphocytes in chronic lymphocytic leukemia.

A significant positive correlation was obtained between the in vitro radiosensitivity of the blood lymphocytes of patients with chronic lymphocytic leukemia (CLL) and the in vivo response of the total leukocyte count subsequent to radiation therapy. Four types of equations were used to represent and measure the effect of in vitro X-irradiation on lymphocytes from CLL patients and measure the response of patients to a course of radiotherapy. For the in vivo analysis we used data from 10 patients who were routinely treated with a total of 16 courses of radiation therapy. The total leukocyte count showed a uniform exponential decline during a course of therapy. According to the literature, about 25% of all CLL patients and about 50% of CLL patients with advanced disease are resistant to chemotherapy. The equations and indices of the present study may be useful to diagnose CLL patients who are prone to be resistant to chemotherapy.

Ultrastructure of granulofilamentous bodies in pathologic spleen and lymph node.

An electron microscope study of granulofilamentous (GF) bodies in the spleens and lymph nodes of two patients, one with lymphosarcoma and the other with macroglobulinemia, suggests a new substructure for the filaments constituting the wall of these bodies. The filaments may not be single, as previously described, but may consist of twin filaments about 2.5 nm in width and separated by approximately 10.5 nm. The twin filaments are attached either on the inside or on the outside of a spiral membrane about 2 nm in thickness. This attachment may render spatial strength to the filaments which are always seen rigid and straight. The wall of the GF bodies does not always contain ribonucleoprotein (RNP) granules between its various layers, and if this occurs the layers are separated by about 21 nm instead of 45 nm when the RNP granules are present. The study speculates that one or both ends of the GF bodies are closed and hemispherical in shape.

Cytarabine: Cytocidal effect on normal and leukemic lymphocytes: Synergism with X rays and comparison with mechlorethamine☆

Abstract To study the in vitro toxicity of cytarabine to nondividing lymphocytes from normal persons and from patients with chronic lymphocytic leukemia, the cells were incubated with the drug at 37°C for 3–7 days and the number of viable lymphocytes was counted before and after incubation. Cytarabine produced a cytocidal effect on normal and leukemic lymphocytes, and the leukemic lymphocytes were more sensitive than the normal cells. Both deoxycytidine and incubation at 27°C protected the cells from the cytotoxicity of the drug. The combination of cytarabine and X irradiation produced a synergistic cytocidal effect on normal lymphocytes. In contrast, mechlorethamine was usually less toxic to leukemic than to normal lymphocytes and produced an additive, not a synergistic effect with X irradiation.

Effects of Alcohol and Hyperthermia on Normal and Leukemic Lymphocytes

By the method of viable lymphocyte counts, ethanol was found (1) to have a cytocidal effect on normal and leukemic lymphocytes; (2) to be more toxic to leukemic than to normal lymphocytes; (3) to be synergistic with hyperthermia, and (4) to decrease the critical temperature of normal lymphocytes from 43 to 41.5 degree C.

Search for Blocking Factors in Sera of Patients with Prostatic Cancer

Sera from patients with carcinoma of the prostate were screened for the presence of blocking factors by measuring the inhibition of phytohemagglutinin-induced blastogenesis of normal lymphocytes. The blastogenic index obtained in cancer sera is not significantly different from that obtained in sera of patients with benign prostatic hypertrophy (control group). Determination of alpha-2-globulins in the cancer sera by cellulose acetate electrophoresis revealed slightly elevated levels in patients with metastatic disease but it did not correlate with the inhibitory blocking activity of the serum.