Prostate cancer detected by uPM3: radical prostatectomy findings.

uPM3 is the first urine-based genetic test that is highly specific for detecting prostate cancer. The histopathologic characteristics of uPM3-detected cancer in radical prostatectomy specimens have not been previously described. We evaluated a consecutive series of radical prostatectomies to determine the extent, zonal distribution and other features of prostate cancer following uPM3 detection. A total of 24 whole-mounted, totally embedded radical prostatectomy specimens were evaluated. All patients had clinically localized cancer and none received preoperative therapy. Zonal location of cancer, distance to the urethra, cancer volume, Gleason grade and multicentricity were recorded; volume of cancer was measured using the grid-counting method. Patients ranged in age from 43 to 75 years (mean 65 years). In 21/24 cases, cancer involved the transition and peripheral zones and was multicentric (87%). Mean cancer volume was 3.96 cm3 (range 0.08-16.86 cm3). Mean distance to the urethra was 0.50 cm for the closest cancer and 0.61 cm for the most distant cancer. Mean Gleason score was 7 (range 5-9); pathologic stage was pT2 for 17 cases and pT3 for seven cases. The uPM3 is an independent and specific biomarker that detects prostate cancers of similar volume, location, extent and grade as other tests for early detection. uPM3 does not preferentially identify large or aggressive prostate cancers.     

Genetic and chromosomal alterations in prostatic intraepithelial neoplasia and carcinoma detected by fluorescence in situ hybridization.

OBJECTIVE: In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques. METHODS AND RESULTS: FISH is a commonly used technique for the determination of gene and chromosome dosage. In tissue sections, FISH allows precise histopathologic correlation of multiple foci of normal epithelium, premalignant lesions, and carcinoma within a single specimen, including study of intratumoral heterogeneity. PIN and prostatic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common genetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, particularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncogenes in these regions may be important for the initiation and progression of prostate cancer. CONCLUSIONS: FISH is a useful technique to determine genetic relationships between cancer and its precursors. PIN and prostatic carcinoma foci have a similar proportion of genetic alterations, suggesting that PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progression of prostatic carcinoma.     

Human hematopoiesis in SCID mice implanted with human adult cancellous bone

The persistence of hematopoietic cells from human adult cancellous bone fragments implanted subcutaneously into CB-17 scid/scid mice was studied. Recipient mice received either no pretreatment (control group) or pretreatment with 3 Gy total-body irradiation and anti-asialo GM1 sera (ASGM1; pretreated group) before implantation. Pretreated severe combined immunodeficient (SCID) mice implanted with human bone were subsequently given ASGM1 every 7 days for the duration of the experiments. At 12 weeks postimplantation, flow cytometry of cells from pretreated and control animal tissues detected human CD45+ cells in the mouse spleen (mean, 7.8% and 3.4% positive cells, pretreated and control animals, respectively), bone marrow (BM; mean, 16.5% and 4.8% positive cells, respectively), and blood (mean, 5.5% and < 2% positive cells, respectively), and in the implanted human bone (73% and 8.9% positive cells, respectively). At 12 weeks, pretreated mice had human granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming units-erythrocyte (BFU-E) in the implanted human bone in the murine BM and in some of the spleens. The spleens also had extensive infiltration of human B cells and macrophages. Mean serum levels of human IgG in pretreated animals were 14 micrograms/mL during weeks 6 to 12, compared with trace levels (< 1 microgram/mL) in control mice. Bone from patients with acute myeloblastic leukemia (AML) was also implanted in pretreated SCID mice, and retrieved at 8 weeks for analysis. Comparison of preimplantation and implanted samples showed that the original histology was maintained, and massive infiltration of human CD68+ cells was observed in the mice spleens and BM. Implantation of AML bone in SCID mice facilitates analysis of in situ AML cell interaction with stromal cells in the leukemic state, and therapies against AML can be tested in this system, especially the selective killing of AML cells in the presence of other BM cells. Furthermore, this model requires no exogenous administration of cytokines to maintain human hematopoiesis with both normal or AML bone. Because the structure and function of both normal and diseased human adult bone is maintained, this animal model should facilitate investigation of both normal human hematopoiesis and hematopoietic malignancies.     

Occlusion during iliac angioplasty: a salvageable complication

During transluminal dilation of the iliac artery, occlusion resulting from dissection occurred in four patients. In all four, the deteriorating clinical findings prompted surgical intervention. In three patients, Fogarty balloon catheters easily passed the occluded segments and specimens much the same as surgical endarterectomy specimens were retrieved. A clamp was used to retrieve the dissected portion of the vessel wall in the fourth patient. Three of four vessels have remained patent for 18 months, 18 months, and 6 months, respectively. One patient underwent bypass surgery 4 months after the occlusion episode for recurrent stenosis in a segment of vessel above the occluded segment, which had also been dilated during the same procedure. It is therefore possible in some cases to salvage vessels occluded during angioplasty, making it unnecessary to resort to aortofemoral or other type of bypass.     

Bronchobiliary fistula: complete percutaneous treatment with biliary drainage and stricture dilation

Percutaneous transhepatic cholangiography was performed on an 18-year-old man who presented with jaundice and cholangitis 19 months after right hepatic lobe resection. The cholangiogram demonstrated a bronchobiliary fistula and a stricture of the common hepatic duct. Percutaneous therapy consisting of biliary drainage and balloon dilation cholangioplasty was successful in eradicating the fistula and reestablishing normal bile flow.