Marathon running and immunity to atherosclerosis.

This is an interim report of an on-going study of deaths in 42-km men. The absence of fatal ASCVD in these athletes can not be construed as evidence for the protective role of exercise alone. The ability to run 42 km depends on many factors. Exercise is only one. Avoiding tobacco is another. Dietary factors also play a role. It has not been feasible to remove one of these factors while maintaining the ability to cover the 42 km distance. Some 42-km men claim that megadoses of ascorbic acid protect them from collagen injury. This is supported by animal studies that show increased collagen synthesis proportional to ascorbic acid intake up to dosage levels that would equal 10 grams per day for humans. Their self-selected macrobiotic diet contains a high ratio of peanuts:steak resulting in a high P/S ratio (polyunsaturates/saturates). Dietary manipulation quickly effects their ability to train. Smoking is so rare among these runners that it must be related to specific effects, such as a catalytic agent in tobacco smoke converting linoleic acid into a toxic lipid oxide. Noakes and Opie recently confirmed again (May, 1976) that no cases of "death due to coronary atherosclerosis" have been recorded in marathon finishers. If this holds true for the second 10-year period of this study, then marathon runners will have joined the longshoremen by earning life-long protection against ASCVD. These longshoremen burned 1,876 kcals on the job, equivalent to a 30-km run. Roberts and Straus suggest that many factors can cause atherosclerosis. Only time will tell whether the marathoner is protected from all of them.

Most prostate cancers missed by raising the upper limit of normal prostate-specific antigen for men in their sixties are clinically significant.

OBJECTIVES: To evaluate the efficacy of applying an age-specific prostate-specific antigen (PSA) reference range to determine whether prostate biopsies are warranted in men 60 to 69 years of age. We estimated the incidence of clinically significant prostate cancer in men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal digital rectal examinations (DRE). METHODS: We reviewed 203 sextant prostate biopsies of men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE. Tumors were considered clinically significant if the cancer on biopsy was poorly differentiated (Gleason score of 7 or more), involved more than one core, or included a single focus measuring more than 3 mm. RESULTS: The positive biopsy rate was 31.5%. More than 80% of the cancers detected satisfied criteria that almost always predict clinically significant cancer. Thus, among men in their sixties with PSA levels of 4.01 to 4.50 ng/mL and normal DRE, the risk of detecting clinically significant cancer on biopsy was approximately 25%. CONCLUSIONS: Most nonpalpable cancers detected by sextant biopsies in men 60 to 69 years of age with PSA levels of 4.01 to 4.5 ng/mL are clinically significant. Applying an age-specific PSA reference range that increases the upper limit of normal PSA to 4.5 ng/mL results in the failure to detect a substantial number of clinically significant cancers.

Adenosquamous carcinoma of the prostate: case report with DNA analysis, immunohistochemistry, and literature review.

We diagnosed prostatic adenosquamous carcinoma by prostate core needle biopsy in a 55-year-old man with no history of prostate cancer. The prognosis, DNA analysis, and histogenesis of this extremely rare tumor are controversial. To our knowledge, this is the first case of adenosquamous carcinoma diagnosed by core needle biopsy in a patient with no history of prostate cancer or hormonal therapy. We performed immunohistologic and DNA analysis to further characterize this cancer. The clinical presentation and abnormal DNA analysis portend an aggressive course.

Diagnosis of "suspicious for malignancy" in prostate biopsies: predictive value for cancer.

OBJECTIVES: Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for but not diagnostic of malignancy. The predictive value of ASAP for cancer has not been studied in a large series. METHODS: To determine the reproducibility and clinical significance of ASAP in a large urologic reference laboratory, we retrospectively studied 295 patients with ASAP diagnosed from 1991 to 1995. Each patient had at least one follow-up biopsy. Mean patient age was 68.0 years (range 40 to 89). Numerous clinical and histologic features were assessed to determine their predictive value for malignancy on subsequent biopsy. RESULTS: Adenocarcinoma was identified on follow-up biopsy in 125 patients (42%), with a median follow-up of 5.7 months (range 0.1 to 43). Gleason score varied from 4 to 9 (mean 6.2). Cumulative detection of 125 cancers was 90% after second biopsy and 99% after third biopsy. Serum prostate-specific antigen, digital rectal examination result, and patient age were not predictive of cancer on follow-up biopsy. Likewise, the number of biopsy cores and histologic findings including number of acini per focus of ASAP, number of foci of ASAP, degree of nuclear and nucleolar enlargement, and presence of luminal pink granular secretions, mucin, or crystalloids were not predictive of cancer. Stratifying our level of suspicion into three categories (favor benign, uncertain, and favor carcinoma) did not differentially predict subsequent cancer (44%, 44%, and 41% of patients, respectively; P = 0.86) nor the percentage of tissue involved by cancer. No clinical or pathologic feature affected the likelihood of subsequent cancer. In 39% of patients, cancer was only contralateral to or in a different sextant site from the initial ASAP site. CONCLUSIONS: The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. Sampling should include multiple sites in the prostate.

DNA ploidy in seminal vesicle cells. A potential diagnostic pitfall in urine cytology.

OBJECTIVE: To verify that abnormal DNA ploidy in urine cytology can occasionally be attributed to contamination by seminal vesicle cells. STUDY DESIGN: In the first part of this study, we analyzed the DNA content of six urine cytology specimens containing seminal vesicle cells. In the second part, we evaluated 21 Feulgen-stained prostate core biopsies containing seminal vesicle-type epithelium using a CAS-200 system. DNA index, proliferative activity (S + G2M) and degree of hyperploidy (> 5C) were determined in each case. RESULTS: All six urine cytology specimens were diploid, with all but one containing hyperploid cells (range, 0-16%; mean, 6.3%). Seminal vesicle cells from prostate biopsies showed a broad range of ploidy abnormalities. Ten cases (48%) showed an aneuploid peak, two cases (9%) showed a tetraploid peak, and nine cases (43%) showed only a diploid peak. All but one case showed both an elevation in proliferative activity (mean S + G2M, 24.2%) and some hyperploid cells (mean, > 5C; 4.5%). CONCLUSION: Seminal vesicle cells, although rarely seen in urine cytology, can cause abnormal DNA ploidy measurements. Morphologic criteria remain vital to an accurate cytologic diagnosis.

Case report 749: Primary glomus tumor of bone.

We report a case of primary intraosseous glomus tumor in a 30-year-old man who was found to have an expanding, lytic lesion in the distal phalanx of his left thumb. The histological appearance was atypical in that areas of myxoid stroma resembled chondroid material. The unusual location and microscopic appearance caused diagnostic problems. Immunohistochemical studies, including strong positive staining for MSA and negative staining for keratin and S-100 protein, were helpful in establishing the correct diagnosis.

Superficial urothelial (umbrella) cells. A potential cause of abnormal DNA ploidy results in urine specimens.

OBJECTIVE: To determine the DNA ploidy distribution in urothelial superficial (umbrella) cells and to assess the value of the image analysis operator's experience. STUDY DESIGN: DNA ploidy was assessed in 12 cytologically negative bladder washes stained with Feulgen stain. All 12 cases were evaluated independently by three operators with different levels of cytopathology experience and different goals. Operator 1 (experienced) selected only nuclei of urothelial cells, avoiding nuclei of superficial cells; operator 2 (experienced) selected only nuclei of superficial cells; operator 3 (inexperienced) selected the largest and most-atypical-looking nuclei. Each operator measured a total of 100 nuclei per case. RESULTS: Operator 1 found all cases to be diploid (97% of nuclei on average). Operators 2 and 3 showed a wide range of results. Almost half the nuclei (47%) analyzed by operator 2 were in the diploid region, a third (35%) were in the tetraploid region, and the remaining (18%) ones had a DNA index (DI) in the range of 1.2-1.8 or > 2.5. Operator 3 obtained the most abnormal results. Only 9% of the nuclei were diploid, while 37% were in the tetraploid region, 18% were in the hyperploid region, and 35% had a DI in the range of 1.2-1.8. Differences among results obtained by each operator were statistically significant. CONCLUSION: The nuclei of superficial (umbrella) cells often have abnormal DNA content, which may cause abnormal DNA ploidy results in cytomorphologically normal bladder washes. Consequently, the nuclei of superficial cells should be avoided in the evaluation of urine samples. DNA analysis of urine specimens requires selection of nuclei only of deep urothelial cells by an experienced operator.