The multidisciplinary clinic approach to prostate cancer counseling and treatment.

The optimum management for an individual patient with prostate cancer is not well defined. Patients with localized disease may be offered options ranging from observation, hormonal therapy, cryotherapy, radiation therapy, or surgery. Each option may have unique aspects to consider when counseling a patient often leading to multiple physician visits over an extended period of time. Since 1996, the Kimmel Cancer Center of Thomas Jefferson University has offered newly diagnosed urologic cancer patients the opportunity to be evaluated in a multidisciplinary clinic. Here, multiple physician consultative visits, including pathologic and radiologic evaluation and protocol evaluation, are provided during the session. Herein we report on our experience with this multidisciplinary approach for patients with prostate cancer.

Chemotherapy in advanced prostate cancer.

In the United States, prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men. Prostate cancer is a rare disease before age 40; however, the prevalence increases quickly to 80% by the age of 80, and with increasing life expectancy, hormone-refractory prostate cancer (HRPC) will soon represent the most common cancer in the male population in the United States and other Western countries. The evolution of early prostate cancer is variable and extends over many years; some tumors progress slowly or not at all, whereas others may progress more rapidly and be fatal after a few years. A widely held view is that chemotherapy has no role in HRPC because no single agent or combination has been shown to prolong survival in a randomized trial. This concept may be obsolete, as preliminary results for a number of approaches, mostly derived from laboratory observations, show that prostate cancers are not as resistant to chemotherapy as traditionally believed. The population of early "geriatric" HRPC patients is rapidly increasing, posing an even greater challenge to oncologists in coping with this difficult-to-manage patient population. In this article, we analyze the most novel chemotherapeutic combinations for the treatment of HRPC in otherwise healthy elderly men.

Expression of Fas(APO-1/CD95) in tumor-infiltrating and peripheral blood lymphocytes in patients with renal cell carcinoma.

The functional expression of Fas-ligand on tumor cells reported in a variety of neoplasms has been proposed by several groups as a mechanism of tumor escape from immunological detection. To better support this hypothesis, we have evaluated and quantified for the first time the presence of the Fas(CD95)-R molecule on tumor-infiltrating lymphocytes and on matched peripheral blood lymphocytes (PBLs) of renal cell cancer patients. By two-color flow cytometry we have detected a significant increase in the Fas(CD95)-R expression on tumor-infiltrating lymphocytes compared with matched patient and normal volunteer PBLs. We also observed a decreased expression of the Fas(CD95)-R expression on PBLs from renal cell cancer patients compared with normal healthy controls. The Fas(CD95)-R expression was observed predominantly on the CD4+ subset in all three groups. These different distributions of the Fas(CD95)-R molecule support the hypothesis that the Fas(CD95)-R/Fas(CD95)-L pathway and tumor microenvironment play a major role in the modulation of T-cell function and differentiation to either memory and activation or apoptosis.

T-cell receptor zeta-chain expression on tumor-infiltrating lymphocytes from renal cell carcinoma.

Loss of the T-cell receptor-associated zeta chain in tumor-infiltrating lymphocytes (TILs) has been proposed as one mechanism of acquired immunosuppression in cancer patients. Recent reports suggest that zeta-chain loss may be related to contaminating monocyte/macrophage protease activity. Using flow cytometry and Western blot analysis, we have confirmed the expression of zeta chain in matched peripheral blood mononuclear cells and TILs from eight patients with primary renal cell carcinoma, when the cells were exposed to sufficient quantity of protease inhibitors. A small decrease in zeta-chain expression was found in three TIL samples. The loss of zeta-chain expression that was noted by others may be related to differences in laboratory method, and the small changes we have noted are unlikely to be sufficient in explaining the immunosuppression of TILs.

[Stromal tumors of the stomach. Review of the literature and description of a case of "uncommitted" stromal tumor]. / Tumori stromali dello stomaco. Revisione della letteratura e descrizione di un caso di tumore stromale "uncommitted".

Non-epithelial non-lymphomatous neoplasms of the gastrointestinal tract are known as stromal tumors (GISTs) because of the tissues in which they originate (4), (16). These neoplasms are rare and account for about 4% of all the tumors of the stomach. Their malignancy and biological and anatomopathological behaviour are related to clinical problems, since their histopathological picture is both complex and controversial. Modern immunohistochemical and ultrastructural (12), (26) studies have identified forms of myogenic or neural origin, which are more differentiated, as well as mixed types with both components, and types, though surely stromal, of uncertain origin, therefore called "uncommitted" (22), (25). The latter are extremely rare and, since it is not yet possible to classify them, some Authors use the term GIST only for these groups. A report of a clinical case of "uncommitted" GIST offers the opportunity to review the literature, highlighting the increased incidence of these tumors (which is probably related partially to the improved diagnostic techniques (3)), their potential malignancy and the difficulty of a correct classification and, therefore, a clear prognosis.

Depletion of T-cells with the CD4+CD45R+ phenotype in lymphocytes that infiltrate subcutaneous metastases of human melanoma.

We studied the phenotypes of lymphocytes extracted from 22 specimens of human melanoma, 11 s.c. metastases and 11 lymph node metastases, by two-color flow cytometry. Lymphocytes extracted from s.c. metastases were characterized by a significantly reduced ratio of CD4+ to CD8+ T-cells, as compared with peripheral blood lymphocytes from the same patients. Ten of 11 tumor-infiltrating lymphocytes from s.c. metastases, but only 1 of 11 peripheral blood lymphocytes, had a CD4/CD8 ratio of less than 1.0. This alteration was not observed for lymphocytes obtained from nodal metastases. Furthermore, almost all of the CD4+ T-cells in s.c. metastases expressed the antigen CD29w and were negative for the complementary antigen CD45R. In contrast, the CD29w/CD45R ratio of tumor-infiltrating lymphocytes from lymph node metastases was similar to that of matched peripheral blood lymphocytes. Thus tumor-infiltrating lymphocytes from s.c. metastases have the phenotype associated with true helper or antigen-committed T-cells, which could reflect their sensitization to tumor antigens, while tumor-infiltrating lymphocytes from lymph node metastases may represent merely an expanded residua of lymph node lymphocytes. Since tumor-infiltrating lymphocytes expanded in vitro are being tested as therapy for patients with advanced cancer, these observations may have important therapeutic implications.

[Carcinoma of the endometrium in young women]. / II carcinoma dell'endometrio nella donna giovane.

Eighteen cases of endometrial cancer under 45 years were clinically and pathologically reviewed. Epidemiological analysis confirmed obesity as an effective risk factor for this neoplasia. In only three cases the association of adenomatous hyperplasia with endometrial cancer was discovered. These data support the theory that in young women endometrial cancer is not an endocrine related neoplasia.

Nasopharyngeal carcinoma: the diagnostic value of the antibody-dependent, cellular cytotoxicity test and of EBV serology.

In the present study we report the results of the EBV-specific antibody response in 30 Italian NPC patients, 20 other head and neck tumor patients and 20 healthy controls. Histopathologically, the tumors were classified as squamous cell carcinoma (WHO 1), nonkeratinizing carcinoma (WHO 2) and undifferentiated carcinoma (WHO 3). Immunofluorescence tests were performed in order to evaluate the antibodies against VCA, EA and the EBV nuclear antigen (EBNA), and the antibody dependent cellular cytotoxicity test was used to detect the EBV specific antibodies against membrane antigens. IgG and IgA antibodies to EBV VCA and IgG antibodies to EA were significantly and consistently higher in the NPC patients than in other patients or controls. Moreover, only the WHO 2 and WHO 3 histological types of NPC resulted associated with EBV. ADCC titers ranging from 1:480 to 1:15360 have been determined; low ADCC titers were prevalent among the VCA-IgA positive donors, while VCA-IgA negative donors presented high ADCC titers. Our results look consistent with other previous results in low-risk and high-risk areas. In conclusion, EBV serology seems to be extremely useful for diagnostic purposes; however, in order to assess a prognostic value of the above markers, a greater number of patients followed for a longer period is needed.

Epstein-Barr virus serology in nasopharyngeal carcinomas and other head and neck neoplasms in Italy.

This paper reports the results of the EBV-specific antibody response in 17 Italian nasopharyngeal carcinoma (NPC) patients, 15 other head and neck tumor patients and 15 normal controls. Nucleic acid hybridization has been performed on the biopsy tissue from 4 of the NPC patients, and EBV-DNA was present in two undifferentiated (WHO 3) tumors, and absent in two samples of the keratinizing (WHO 1) type. EBV serology appears to be specifically related to NPC, more evidently for VCA-IgA and EA-IgG antibodies, and useful as an aid in diagnosis of NPC. However, in order to assess a prognostic value of the above markers, a greater number of patients followed for a longer period of time (at least 5 years) is needed, and is currently being pursued.