Organ-confined clear cell renal cell carcinoma: the prognostic impact of microvascular invasion, nuclear grade and tumour size.

The frequency of diagnosed and treated organ-confined renal cell carcinoma is increasing. The prognosis of this group of tumours is difficult to predict. The main purpose of this study was to examine the prognostic significance of microvascular invasion, tumour size and nuclear grade in a complete cohort of 76 consecutive patients with organ-confined clear cell renal cell carcinoma treated with radical nephrectomy. Patient ages ranged from 39 to 88 years (mean 66 years). Median follow-up was 10.2 years (range 0.1-19.4 years). The tumours were graded according to Fuhrman. Representative histological sections were stained for CD31, which decorates endothelial cells, in order to assess microvascular invasion (MVI). In univariate analysis, microvascular invasion (p<0.01), tumour size (TS) (p=0.01), TNM stage (p=0.01) and Fuhrman nuclear grade (p=0.02) were significant predictors of cancer-specific survival. Multivariate analysis, adjusted for age, revealed that microvascular invasion, tumour size and nuclear grade were independent covariates. According to our findings microvascular invasion is a strong independent prognostic predictor, and including this in the histopathology report should be considered together with nuclear grade and tumour size.

Cushing's syndrome in prostate cancer. An aggressive course of prostatic malignancy.

We report a case with an initial diagnosis of adenocarcinoma of the prostate in whom Cushing's syndrome developed. The disease did not respond to estrogen treatment and the patient died of severe septicemia. Histopathologic examination of the autopsy specimens revealed a small cell carcinoma intermingled with a moderately differentiated adenocarcinoma in the prostate and widespread metastases of small cell carcinoma. Immunoreactivity for neuroendocrine differentiation was found only in the small cell carcinoma. Determination of different tumor markers in plasma samples showed markedly elevated levels of prostate-specific antigen as well as carcinoembryonic antigen prior to treatment, with no significant changes after treatment. The concentration of the neuroendocrine marker chromogranin A was initially within the normal range, but increased during estrogen treatment, whilst neuron-specific enolase was moderately elevated throughout the observation period.

Surgical management of chylous fistula after retroperitoneal lymph node dissection.

Conservative treatment with low-fat diet, medium-chain triglyceride or total parenteral nutrition, depending on the general condition of the patient, is the mainstay in the treatment of chylous ascites. In patients with persistent chylous fistula direct surgical closure is a valid treatment option.

Effects of diethylstilbestrol and estramustine phosphate (estracyt) on natural killer cell activity and tumor susceptibility in male mice.

The effects of estramustine phosphate (EMP) and diethylstilbestrol (DES) on natural killer (NK) cell activity, tumor growth, and artificial metastases were investigated in male C57BL/6 mice. Kinetic analysis and studies at the single-cell level indicated that EMP did not influence the number of NK cells but interfered with their lytic activity thereby reducing the actual killer capacity. NK cells from EMP-exposed animals responded normally to the interferon inducer Poly I:C which restored NK activity to control levels. Spleen cells from DES-treated animals had lytic activity comparable to that of control animals. However, more detailed analysis showed that DES reduced the number of lymphocytes able to recognize target cells, while the individual NK cell had an increased lytic activity and recycling capacity. Moreover, NK cells from DES-treated animals were refractory to poly-I:C stimulation, suggesting that they were prestimulated in vivo. The pertubations of the NK cell system induced by both EMP and DES were reversible and normalization of NK activity was reached within a week. The incidence of tumor takes after subcutaneous inoculation of the syngeneic Lewis lung carcinoma was increased in EMP as well as DES-treated animals. Artificial lung metastasis produced by intravenous injection of the same tumor was increased in EMP but not in DES-exposed animals.

Suppression of antibody response of male mice exposed to diethylstilbestrol or estramustine phosphate (Estracyt).

The effects of treatment of male mice with diethylstilbestrol (DES) or estramustine phosphate (EMP) on the primary antibody response to sheep red blood cells (SRBC) and lipopolysaccharide (LPS) were investigated using a hemolytic plaque assay for enumeration of antibody-producing cells. DES treatment at a daily dose of 1.4 or 5.6 mg/kg from 2 days prior to and up to 3 days after immunization significantly reduced the number of anti-SRBC as well as anti-LPS-producing cells per 10(6) spleen cells. The 100 mg/kg EMP given as daily intraperitoneal injections significantly diminished the antibody response to both SRBC and LPS. No alteration in the number of anti-SRBC-producing cells per 10(6) spleen cells was detected in spleens from mice receiving 30 mg/kg/day EMP, while the number of anti-LPS-producing cells was reduced. The immunoregulatory effects of EMP are apparently not a pure estrogen effect, since treatment with doses of estradiol-17 beta equivalent to the amounts of estradiol linked to the cytotoxic moiety in 100 mg/kg/day of EMP were without effect. EMP-induced functional impairment in the T-cell population is inferred from the reduced ability of adoptively transferred T cells from EMP-exposed animals to support an antibody response to SRBC in syngeneic nude mice.

Effects of diethylstilbestrol and estramustine phosphate (Estracyt) on lymphoid cell populations and mitogen responsiveness in male mice.

Concentrations of diethylstilbestrol phosphate (DES-P) and estramustine phosphate (EMP) above 10(-5) M in cultures of spleen lymphocytes from adult male mice resulted in a dose related inhibition of both Con A and LPS induced lymphocyte proliferation. Male mice injected with 5.6 mg./kg. DES daily for 7 days had a significantly reduced responsiveness to both Con A and LPS compared to mice injected with olive oil only. Spleen lymphocytes from male mice treated with 100 mg./kg. EMP showed a reduction of Con A induced mitogenesis whereas they exhibited a significantly enhanced response to LPS. The effects of DES and EMP on Con A and LPS induced blastogenesis were abolished within 2 weeks after cessation of treatment. DES treatment resulted in preferential depletion of splenic and lymph node T lymphocytes and a disproportionate T lymphocyte subpopulation with respect to Ly subclasses. Exposure to 30 or 100 mg./kg. EMP resulted in a dose related loss of mononuclear cells both in spleen and lymph nodes. T lymphocytes predominantly of the Ly 1 phenotype were most sensitive to EMP. Co-cultures of spleen lymphocytes from normal mice and Mitomycin C blocked spleen cells from either normal of treated mice (DES or EMP) gave no convincing evidence of suppressor cell activity in the population of spleen mononuclear cells.

Augmentation of natural killer cell activity after arterial embolization of renal carcinomas.

Preoperative embolization of the renal artery has been reported to improve the survival of patients with advanced renal carcinomas compared to operative treatment only. To investigate possible immunological consequences of tumor embolization, natural killer (NK) cell activity in peripheral blood was investigated immediately before and at different time intervals after occlusion of the renal artery by insertion of a metal coil. A slight increase in NK activity could be observed 24 hr postembolization while a marked augmentation was seen after 48 hr. The high NK activity persisted up to 96 hr after embolization, the last time period included in the study. Two patients undergoing the same procedure but in whom embolization was unsuccessful showed no alteration in NK activity. It is suggested that interferon produced by macrophages activated by the necrotizing tumor might be responsible for the augmentation of NK activity.

Effect of diethylstilbestrol and estramustine phosphate (Estracyt) on delayed hypersensitivity response to oxazolone in male mice.

The effects of diethylstilbestrol (DES) and estramustine phosphate (EMP) on delayed hypersensitivity response (DTH) to oxazolone in male mice were investigated using a radioisotopic ear method. DES significantly inhibited the ability to express a DTH response and was most effective when given during the effector phase of the reaction. EMP had no effects when the animals were exposed to the drug during the effector phase, while it resulted in a strong and dose-dependent depression of the DTH response when applied in the sensitization phase. Possible involvement of suppressor cells was investigated by pretreatment of animals with cyclophosphamide or by adoptive transfer of tentative suppressor cells from spleen, lymph nodes, or peritoneal cavity. However, no evidence of cellular or humoral suppressor factors induced by drug treatment was found.