Estradiol and cognition during androgen deprivation in men with prostate carcinoma.

BACKGROUND: The adverse effects of hormonal manipulation in prostate carcinoma need to be established in view of its increasing use as an adjuvant treatment. This prospective study investigated the association of androgen deprivation-induced estradiol decline with cognition in prostate carcinoma. METHODS: Cognitive testing of prostate carcinoma patients was carried out at baseline and at 6 and 12 months on androgen deprivation (AD). Cognitive performances were evaluated with standardized measures of information processing, including working memory and attention, visual and verbal skills, and memory performances in 31 tests. Testosterone and estradiol changes during AD were measured with the DELFIA (PerkinElmer, Inc., Wellesley, MA) system. Associations between changes in cognitive performances and estradiol decline were studied. RESULTS: Cognitive performances, which were significantly associated with decline in estradiol, included visual memory of figures (r = -0.52; P = 0.022) and recognition speed of numbers, which were impaired, (r = -0.57; P = 0.030) at 6 months, and improvement in verbal fluency (r = -0.52; P = 0.019) at 12 months. Other cognitive domains appeared unaffected by estradiol decline. The character of change (impairment or improvement) depended on the magnitude of estradiol decline. CONCLUSIONS: The cognitive domains of verbal fluency, visual recognition, and visual memory were associated with decline in estradiol during androgen deprivation. The results suggest selective associations among testosterone decline, estradiol, and cognitive performance. Documentation of these associations has implications for informed patient support in hormonally treated prostate carcinoma.

Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer.

SUMMARY: Fibroblast growth factor 8 (FGF-8) is implicated in growth of prostate cancer. Alternative splicing of the human FGF-8 gene potentially allows coding for four protein isoforms (a, b, e, and f). These isoforms differ in their binding to FGF receptors (FGFR) and in their mitogenic and transforming capacity in transfection assays. Here, we used RT-PCR and immunohistochemistry to study the expression of FGF-8 and FGFR isoforms in human prostate cancer (n = 31). Nonmalignant prostate specimens from cystoprostatectomies (n = 24) were examined as controls. Most prostate cancer samples and some control prostates also contained prostatic intraepithelial neoplasia (PIN) lesions. FGF-8a and e were expressed at significantly higher frequencies in prostate cancer (FGF-8a, 55%; FGF-8e, 45%) than in control samples (FGF-8a, 17%, p = 0.0052; FGF-8e, 8%, p = 0.0031). On the contrary, FGF-8b was found at an equal frequency in prostate cancer (55%) and in control prostates (50%). Furthermore, a combination of two or three FGF-8 isoforms (a, b, and/or e) was also expressed at a higher frequency in prostate cancer than in control samples (45% and 8%, respectively, p = 0.0031). Immunohistochemistry with an antibody recognizing all FGF-8 isoforms was more strongly immunoreactive in prostate cancer cells and PIN lesions than in normal-type epithelium. The receptor splicing variants FGFR1IIIc and FGFR2IIIc, which are activated by FGF-8, were found both in prostate cancer and control samples. Interestingly, immunoreactivity for FGFR1 and FGFR2 was much stronger in prostate cancer cells and PIN than in normal epithelium. These results demonstrate, for the first time, that FGF-8 isoforms and their receptors FGFR1IIIc and FGFR2IIIc are expressed at an increased level not only in prostate cancer but also in premalignant PIN lesions. These data suggest that FGF-8 may have an important autocrine role in the development of human prostate cancer. In addition to FGF-8b, the FGF-8 isoforms a and e may be involved in this process.

Cathepsin H expression distinguishes oncocytomas from renal cell carcinomas.

BACKGROUND: Because the differential diagnosis of oncocytoma and renal cell carcinoma lacks specificity, new methods supporting correct diagnostic decisions are welcome. MATERIAL AND METHODS: Sixteen cases of renal oncocytoma, and 16 sex-, age-, and stage- matched controls of renal cell carcinoma (T1-2N0M0) were studied. The minimum follow up exceeded ten years. There were no deaths due to neoplasm among oncocytomas, but 4 patient died with metastatic disease among cancer patients. Immunohistochemical staining for cathepsin H was quantified by 3 histoscores. The histoscores evaluated: 1) even cytoplasmic staining of neoplastic cells, 2) granular staining, or 3) total staining. RESULTS: 100% distinction was possible with the even cytoplasmic staining score. Total staining distinguished 87.5%, and granular staining 25% of neoplasms. CAM 5.2 cytokeratin, or vimentin distinguished 84.4% or 56.6% of these tumors, respectively. CONCLUSIONS: Cathepsin H histoscore on even cytoplasmic immunostaining is an excellent method for the distinction of oncocytomas and renal cell carcinomas.

Nuclear morphometry in differential diagnosis of renal oncocytoma and renal cell carcinoma.

PURPOSE: Morphometric distinction of renal oncocytoma and renal cell carcinoma was attempted. MATERIALS AND METHODS: Nuclear morphometric measurements were done from sections of 16 histologically diagnosed renal oncocytomas and renal cell carcinoma controls (grade 1 or 2, stage T1 to 2N0M0). RESULTS: Oncocytomas could be distinguished from carcinomas on the basis of nuclear morphometry in more than 80% of the cases. Especially, the shape descriptors (form factors) were significantly different between oncocytomas and carcinomas. CONCLUSIONS: Morphometrically determined nuclear shape descriptors can be used to support diagnostic decisions in problematic cases.

Ultrastructure and immunohistochemistry of a fetal-type Leydig cell tumor.

A symptomless scrotal mass was removed from a 34-year-old man. The lesion was 7 cm in diameter and it was grossly a hemorrhagic cyst with indurated walls. By light microscopy tumor cell clusters and cords were seen infiltrating the testicle, tunica albuginea, and paratesticular tissue. In the immunohistochemical analysis the tumor cells were immunoreactive with anti-S-100 protein and anticarcinoembryonic antigen, but they did not express cytokeratin or alpha-fetoprotein as tested with paraffin sections. Tumor cell clusters were enveloped by a laminin-positive basement membrane. Electron microscopy revealed abundant smooth endoplasmic reticulum, lipid droplets, and membranous whorls in the cytoplasm. Lamellar whorled bodies were also seen in mitochondria, which contained tubulovesicular cristae. The presence of a well-developed, often multilayered basement membrane was confirmed at ultrastructural level. The activity of 3-beta-hydroxysteroid dehydrogenase suggested that the tumor cells were capable of androgen synthesis. The morphological features are reminiscent of fetal-type Leydig cells and are distinctly different from the Leydig cell tumors described so far.

Intravesical dimethyl sulfoxide instillations in the treatment of secondary amyloidosis of the bladder.

A-22-year-old woman with long-standing rheumatoid arthritis and secondary amyloidosis of the bladder had recurrent profuse macroscopic hematuria. She was treated with intravesical dimethyl sulfoxide instillation every 2 weeks for 1 year. She remained asymptomatic during the treatment and at 6 months. Progressive disappearance of amyloid from the superficial mucosa of the bladder was demonstrated in sequential histological examinations.

Results of cystectomy with and without preoperative radiotherapy in carcinoma of the urinary bladder.

During a period of 13 years, 84 patients underwent total cystectomy for transitional cell carcinoma of the bladder. The corrected 5-year survival rate was 58%. The operative mortality was 5 patients (6%). The 5-year survival rate of 42 patients who were treated by surgery alone was 53%, whereas that of 42 patients who received preoperative radiation of 30-40 Gy was 65%. The prognoses of the patients were dependent on the histological differentiation and the extent of the primary tumour within each treatment group.

Secondary amyloidosis of the bladder: a cause of massive hematuria.

Secondary amyloidosis of the bladder is a rare cause of hematuria, with only 10 previous reports. Findings and treatment in 5 patients with histologically verified bladder amyloidosis secondary to long-standing rheumatoid arthritis are presented. All patients were hospitalized for massive hematuria. One patient died before cystoscopy. Clot evacuation and fulguration through a cystoscope stopped the bleeding in 1 patient. In the other 3 patients hemostasis was achieved by cystotomy, bilateral percutaneous nephrostomy and continuous alum irrigation of the bladder, respectively.

Flow cytometric analysis of the DNA profile of renal cell carcinoma.

DNA flow cytometry was applied to one hundred consecutive renal cell carcinomas from years 1974-1979. Single cell suspensions were prepared from paraffin-embedded tissue. From 96 evaluable tumours 34 were considered diploid and 62 aneuploid. Ploidy did not correlate statistically significantly with local growth, venous invasion, nodal or distant metastatic spread, or nuclear grade of renal cell carcinomas. Also the survival of the patients with diploid and aneuploid tumours was not significantly different, but, excluding patients with distant metastases at the time of extrafascial nephrectomy, 83% of the patients with diploid tumour survived for five years, while only 57% of the patients with aneuploid tumour were alive after the same time interval. The difference between survival curves is statistically almost significant (p less than 0.05). The cytologic nuclear grade predicted the prognosis more significantly (p less than 0.01), and the combination of these methods is recommended for the prognostication of renal cell carcinoma.

Diagnosis and treatment of renal angiomyolipoma.

A series of nine patients surgically treated for histologically verified renal angiomyolipoma is presented. Only one patient had extrarenal stigmata of tuberous sclerosis. No evidence of malignancy was found. In three cases a preoperative diagnosis was achieved with computed tomography (CT), use of which is recommended in evaluation of renal tumours. Six angiomyolipomas were solitary and three bilateral. Abdominal or flank pain was present in eight cases and perirenal haemorrhage in four. Solitary tumours were treated with nephrectomy. For bilateral tumour, nephrectomy and conservative renal surgery were used in two cases and bilateral nephrectomy and kidney transplantation were performed in the third case. When adipose tissue containing renal tumour is demonstrated at CT, conservative surgery should be considered.

Aspiration biopsy cytology of renal oncocytoma.

The fine needle aspiration biopsy findings in four cases of renal oncocytomas were reviewed. The cytologic smears contained many large, well-demarcated, eosinophilic cells with prominent nucleoli. Some of the cells were binucleated. The findings in these cases indicate that renal oncocytoma may be suggested preoperatively on the bases of renal angiography and aspiration biopsy cytology. The differential diagnosis between renal adenocarcinoma and carcinomas with oncocytic differentiation is discussed.

Transabdominal and lumbar nephrectomy for renal adenocarcinoma.

The results of 178 transabdominal and 79 lumbal nephrectomies were compared, based on a consecutive series of patients with renal adenocarcinoma. The corrected 5-year survival rate for patients without distant metastases was 64% for transabdominal and 57% for lumbar nephrectomy. This difference is not statistically significant. The transabdominal approach made possible a more extensive operation in patients with tumours extending to neighbouring organs, but none has survived as long as three years. Duration of surgery, need for blood transfusion and duration of postoperative hospital care were similar. Splenic injury occurred in 9.6% of the patients with transabdominal nephrectomy, but this did not result in additional morbidity or mortality. There were a few other sporadic complications.

Renal oncocytoma: the incidence of 18 surgical and 12 autopsy cases.

The material of 562 surgically removed renal cell carcinomas or adenomas was reviewed, and 18 tumors were diagnosed as renal oncocytomas. The incidence seemed to increase strikingly during recent years. Similarly, among 112 renal cell tumours from 8489 autopsies, 12 oncocytomas were found. Immunoperoxidase staining for alpha-I-antichymotrypsin was positive in all the tumours studied speaking for the origin from proximal tubular cells. All the tumours behaved in a benign fashion despite the large size and/or moderate histological atypia. The recognition of renal oncocytoma is urged, because its incidence seems to be increasing, and the prognosis is much better than that of renal cell carcinoma.

Prognostic factors in renal carcinoma. An evaluation of operative findings.

A consecutive series of 257 patients with renal carcinoma treated by radical nephrectomy is presented. The crude 5-year and 10-year survival rates for all patients were 47 and 31% respectively and for patients without distant metastases 62 and 50%. The importance of factors relating to prognosis was investigated with multivariate survival analysis. Metastases, nodal involvement and histological grade were strongly and independently associated with survival, but the influence of venous invasion was less important. When these factors are taken into consideration, direct extension, size and cell type of the tumour or sex and age of the patient give no significant additional prognostic information.