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Introduction To evaluate the impact of design features of the synthetic mid-urethral slings on tissue integrity and inflammatory responses. Material and methods In total 30 female Sprague-Dawley rats were implanted with type I monofilamentous, macroporous polypropylene meshes: Gynecare TVT-Obturator tape® (Ethicon Inc., Johnson & Johnson, Somerville, NJ, USA) and I-STOP® (CL Medical Inc., Lyon, France). All animal groups were sacrificed at set time intervals - 6 weeks, 3 months, 6 months, 9 months and 12 months - and the abdominal wall was harvested with mesh strips for histological evaluation. Results All mesh strips appeared to be well incorporated into the abdominal wall, and no signs of shrinkage was noticed. All specimens showed a thin/delicate, loose, fibrous interface between the synthetic graft plate and abdominal wall, along with mild inflammatory reactions from 6 weeks to 12 months. Conclusions Both mesh brands induced comparable, minimal foreign body reactions and integrated well into the host tissues despite differences in architectural features. TVT-O® and I-STOP® evoked similar low-grade inflammatory responses up to 12 months in this animal model. Structural differences and architectural features of polypropylene slings used in this study have had no impact on tissue integrity and inflammatory responses.

The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a Z65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus, "the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in

The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

Diet affects the risk and progression of prostate cancer, but the interplay between diet and genetic alterations in this disease is not understood. Here we present genetic evidence in the mouse showing that prostate cancer progression driven by loss of the tumor suppressor Pten is mainly unresponsive to a high-fat diet (HFD), but that coordinate loss of the protein tyrosine phosphatase Ptpn1 (encoding PTP1B) enables a highly invasive disease. Prostate cancer in Pten−/−Ptpn1−/− mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding. Prostate-specific overexpression of PTP1B was not sufficient to initiate prostate cancer, arguing that it acted as a diet-dependent modifier of prostate cancer development in Pten−/− mice. Our findings offer a preclinical rationale to investigate the anticancer effects of PTP1B inhibitors currently being studied clinically for diabetes treatment as a new modality for management of prostate cancer. Cancer Res; 76(11); 3130–5. ©2016 AACR.

Background Microsatellite instability (MSI) is a form of genomic instability that has recently been implicated in the pathogenesis of thyroid cancer. The purpose of this study was to further define the distribution of MSI in both normal and neoplastic thyroid follicular epithelium. Design Using laser capture microdissection, cells from both normal and tumor tissue were individually collected. Polymerase chain reaction amplification of the DNA was then performed using six dinucleotide and two mononucleotide microsatellite markers. Results Forty benign and malignant thyroid tumors were compared with their adjacent normal thyroid follicular tissue and were analyzed for MSI. Nine of 14 papillary thyroid carcinomas and 10/16 of follicular thyroid carcinomas demonstrated MSI at ≥30–40% of loci tested. For benign follicular adenomas, 9/10 demonstrated microsatellite stability or low-frequency MSI. Conclusion MSI appears to play a role in thyroid pathogenesis as evidenced by the high frequency of MSI in malignant thyroid neoplasms. In addition our study showed a significant difference in MSI frequency between follicular adenomas and follicular carcinomas. More importantly, the technique of laser capture microdissection allows for more accurate selection of benign, malignant, and normal DNA.

BACKGROUND. Active surveillance (AS) with deferred treatment is an established management option for patients with prostate cancer and favorable clinical parameters. The impact of repeat biopsy after diagnosis was examined in a cohort of men with prostate cancer on AS. METHODS. In all, 186 men with prostate cancer with favorable parameters or who refused treatment were conservatively managed by AS. Of these, 92 patients had at least 1 biopsy after diagnosis. Patients were followed every 3 to 6 months with prostate-specific antigen (PSA) and physical examination and were offered rebiopsy annually or if there were any changes on physical examination or in the PSA value. Disease progression while on AS was defined as having ≥1 of the following: ≥cT2b disease, ≥3 positive cores, >50% of cancer in at least 1 core, or a predominant Gleason pattern of 4 in rebiopsies. RESULTS. The median age of the patients at the time of diagnosis was 67 years (range, 49–78 years). The median follow-up was 76 months (range, 20–169 months). Of the 92 patients who underwent repeat biopsies, 42 patients, 25 patients, 13 patients, 10 patients, and 2 patients had 1, 2, 3, 4, and 5 rebiopsies, respectively. A total of 34 patients (36%) demonstrated disease progression on rebiopsy. The first rebiopsy was positive for cancer in 48 patients (52.2%) and negative in 44 patients (47.8%). The 5-year actuarial progression-free probability was 82% for patients with a negative first repeat biopsy compared with 50% for patients with a positive first rebiopsy (P = .02). A PSA doubling time

Purpose: Cluster-of-differentiation antigen 9 (CD9) protein, a member of the tetraspanin family, has been implicated in carcinogenesis of various human tumors. Although decreased expression of the CD82 tetraspanin protein, a close CD9 relative, is associated with prostate cancer progression, CD9 expression has not been analyzed in this malignancy. Experimental Design: CD9 expression in human prostatic adenocarcinoma was analyzed by immunohistochemistry on 167 primary tumors and 88 lymph node or bone metastases. CD9 cDNA was sequenced from two human prostate cancer cell lines, prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and normal prostatic tissues. Results: Although CD9 was detected in the epithelium of normal prostatic tissues, reduced or loss of CD9 expression within neoplastic cells was observed in 24% of 107 clinically localized primary adenocarcinomas, 85% of 60 clinically advanced primary adenocarcinomas, 85% of 65 lymph node metastases, and 65% of 23 bone metastases. Difference in CD9 expression between clinically localized and advanced diseases was highly significant (P < 1 × 10−7). Whereas there was no alteration of CD9 cDNA in normal tissues, all PC-3–derived cell lines, one PIN, and four prostatic adenocarcinomas harbored deletions in their CD9 cDNAs. Recurring CD9 point mutations were also found in PC-3M-LN4 cells, one PIN, and seven prostatic adenocarcinomas. Conclusions: CD9 expression is significantly reduced and even lost during prostate cancer progression. Moreover, deletions and mutations of the CD9 mRNA may be associated with loss of protein expression observed in tumor cells. Our data suggest that CD9 inactivation may play an important role in prostate cancer progression.

Background SPINK1, ERG, and PTEN are proposed prognostic biomarkers in prostate cancer (PCA). However, their relations and patterns of expression in primary and metastatic lymph node (LN) PCAs are not fully explored. Methods A tissue microarray of matched primary PCA and LN metastasis was constructed from 36 patients. SPINK1, ERG, and PTEN expression statuses were assessed by immunohistochemistry and correlated with each other. Results SPINK1 and ERG were expressed in 25% and 42.7% of primary PCA cases, respectively. PTEN loss of any degree was observed in 91.7% of primary PCA cases, with 54.2% showing complete loss. In primary PCA, 12.5% of the cases showed SPINK1+/ERG−phenotype, 16.7% showed SPINK1+/ERG+phenotype, 25.0% showed SPINK1−/ERG+phenotype, and 45.8% showed SPINK1−/ERG−phenotype. All PCAs with expression of either SPINK1 or ERG also exhibited PTEN loss, whereas PCA without PTEN loss (2 cases) expressed neither SPINK1 nor ERG. In primary PCA, evaluation of combined ERG and SPINK1 status, but not SPINK1 individually, was associated with a significant difference in proportion of Gleason patterns ( P = 0.013), with the SPINK1+/ERG+and SPINK1−/ERG−phenotypes represented more in Gleason pattern>7 PCAs. In LN metastases, the overall SPINK1 protein expression frequency was significantly lower (6.5% of cases) compared with primary PCA ( P = 0.03). Only 16.7% of cases with positive SPINK1 expression in primary PCA maintained expression in LN metastases. The down-regulated SPINK1 expression in LN was primarily because of a reduction in the SPINK1+/ERG+PCA subpopulation to 3.5% of cases ( P = 0.16 compared with primary PCA). The frequencies of ERG expression and PTEN loss were relatively stable in primary PCA and LN metastases. Conclusion SPINK1 expression is dynamically regulated with up-regulation in primary sites of nodal metastatic PCA and down-regulation in LN metastases. The increased SPINK1 expression in primary site of nodal metastatic PCA is secondary to an increased frequency of SPINK1+/ERG+tumors. In primary PCAs, the SPINK1+/ERG+phenotype is associated with higher Gleason grade, suggesting that this phenotype may mark a more aggressive PCA subpopulation with higher risk of LN metastases.

The current series presents 12 cases of invasive urothelial carcinoma (UC) with inverted growth pattern that fulfill the architectural criteria of the recently described "large nested" variant of UC, but which display a wider spectrum of morphologic and cytologic changes. All cases had an associated component of usual invasive UC, and 10 had an associated surface papillary component. Although many areas within the tumors were indistinguishable from a noninvasive endophytic growth pattern, at least some had an irregular ragged contour, and all showed haphazard arrangement with variable amount of intervening stroma at least focally. Inflammatory stromal reaction was noted in 11 cases, and desmoplasia and retraction artifact were present in 8 cases each. Although major areas showed mild atypia, many tumors showed marked hyperchromasia, prominent nucleoli, marked irregular nuclear membranes, and brisk mitotic activity. Final pathological stage on cystectomy specimens was T2 in 4 cases, T3 in 2 cases, and T4 in 3 cases. In 3 cases, lymph node metastases were documented histologically. Review of the literature shows that the "large nested," "inverted," "endophytic," and "inverted papilloma-like" variants of invasive UC are interrelated entities and should probably be considered as one variant with a wide spectrum of cytoarchitectural features. They should also be separated from the "nested" variant with which they rarely coexist and which shows different characteristics at the morphologic level.

OBJECTIVE To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer. PATIENTS AND METHODS The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 − specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4–6 or 4–10 ng/mL were evaluated. RESULTS Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4–10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4–6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios. CONCLUSIONS The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.

Purpose: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied. Experimental Design: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum. Results: BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (Pintercept = 0.0002, Pslope = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (Pslope = 0.98). Conclusions: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.

OBJECTIVE To examine the relationship of serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3) with histological cancer characteristics in men undergoing transrectal ultrasonography (TRUS)-guided biopsy. PATIENTS AND METHODS Patients (652), with either an elevated serum prostate-specific antigen level or an abnormal digital rectal examination, were initially evaluated by TRUS and sextant prostatic needle biopsy. Blood was drawn before biopsy, serum extracted and stored frozen until IGF-1 and IGFBP-3 were measured. In all, 241 patients had prostate cancer (37%) and were included in this study. The number of positive biopsies, the volume of tumour in each positive biopsy and the Gleason score were recorded. RESULTS Of the 241 patients, 37 had five or six positive biopsies (from six), 128 had two to four and 76 had one. Serum IGF-1 did not correlate with the number of positive biopsies, with means of 176.7, 178.3 and 164.4 ng/mL, respectively (P = 0.3), while the mean IGFBP-3 was 2695, 2795 and 2572 ng/mL, respectively (P = 0.09). The additive percentiles of tumour volume in positive biopsies were assessed for each patient but serum IGF-1 and IGFBP-3 did not correlate (P = 0.7 and 0.9, respectively). In all, 92 patients had a Gleason score of 7; the mean (sd) IGF-1 levels for the three groups were 181 (39), 174.6 (35) and 176 (26) ng/mL, and the mean IGFBP-3 2798 (240), 2735 (284) and 2647 (221) ng/mL, respectively, none of the differences being statistically significant. CONCLUSIONS Serum IGF-1 and IGFBP-3 do not correlate with quantity of cancer or Gleason score in biopsy samples from patients with prostate cancer.

BACKGROUND A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas. METHODS The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size. RESULTS A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20). CONCLUSIONS The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma. Cancer 2003. ©2003 American Cancer Society. DOI 10.1002/cncr.11688

Objectives To compare the histological tissue reactions of urinary bladder in close contact with polypropylene mesh tension-free vaginal tape (TVT) or porcine small intestinal submucosal (SIS) grafts, as the commercial availability of various materials has considerably simplified sling procedures for treating urinary incontinence, but erosion and infection after using artificial sling materials remain an important concern. Materials and methods Thirty female New Zealand rabbits were randomized to three groups, i.e. group A (TVT, 12 animals), group B (SIS, 12) and group C (surgical control, six). Through a laparotomy under anaesthesia and an aseptic technique, the bladder was approached at its dome, where a 0.5 × 1 cm piece of TVT or SIS was fixed in direct contact with the bladder wall. The control group underwent only bladder manipulation with no material applied. Half the animals in each group were killed after 6 weeks and the other half after 12 weeks. The urinary bladder was harvested and examined histologically. Results The grafts in both groups were characterized by dense foreign-body type reactions and were mostly attached loosely to the bladder wall by a thin layer of fibrovascular tissue. More importantly, the bladder wall reactions showed no inflammation in all 12 animals in group A (TVT) but three of them had various grades of fibrosis. There was severe transmural inflammation in one animal in group B (SIS); one rabbit had grade I and two had grade II fibrosis. The controls, as expected, showed no bladder wall reactions. Conclusion In this descriptive analysis of reaction types elicited on the urinary bladder by these grafts, both materials appeared to be safe. Although TVT elicited fewer and less severe adverse reactions, no statistical conclusions can be drawn. The clinical significance of these findings should emerge from long-term clinical data when they become available.

Objectives. To compare the performance of prostate-specific antigen (PSA), the free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer detection. Methods. Five hundred thirty-five patients evaluated at the UROMED prostate cancer detection clinic had total PSA, free PSA, and cPSA measured before undergoing transrectal ultrasonography and sextant prostate biopsies. A direct comparison was performed between the different PSA assays to evaluate their ability to detect prostate cancer. Results. Of the 535 patients evaluated, 38.1% had prostate cancer detected. The mean age of the entire population was 63.6 years (range 35 to 86). Abnormal digital rectal examination findings were present in 33.4% of the patients. The mean and median values of PSA and cPSA were significantly higher and the F/T PSA ratio was lower in patients with prostate cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A higher specificity was observed with the F/T PSA ratio than with cPSA using either the entire patient population or subsets of patients with PSA levels between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. Conclusions. The use of the F/T PSA ratio offers improved prostate cancer detection compared with either cPSA or total PSA.

The I1307K polymorphism in APC has been found to predispose to colorectal cancer in Ashkenazi Jews, and has recently been associated with an increased risk for breast cancer in the same population. In that study, we genotyped 205 paraffin-embedded breast cancers from Ashkenazi Jewish women diagnosed below the age of 65. We now present an extended analysis, with clinicopathological correlations between carriers of I1307K and non-carriers. Twenty-four of 209 cases (11.5%, 95% confidence interval 7.5–16.6) were found to carry the I1307K polymorphism. When stratifying the data by other relevant clinicopathological variables, we observed no association between the presence of this polymorphism and age at diagnosis (P = 0.52), grade (P = 0.074), tumour size (P = 0.99), lymph node status (P = 0.82), oestrogen receptor status (P = 0.23) or P53 immunoreactivity (P = 0.80). The breast-cancer specific 5-year survival for women with I1307 K polymorphism was 88.9% compared with 81.6% in women without I1307K (P = 0.34). Using microdissected samples and direct sequencing, no somatic mutations were observed in any of the 24 I1307K-positive cases. Single-strand conformation analysis of 158 of the I1307K-negative breast cancers that were available for study revealed no mobility shifts. We conclude that the presence of the I1307K polymorphism does not appear to be associated with any particular clinicopathological feature of breast cancer and importantly, does not affect the prognosis. © 1999 Cancer Research Campaign

Adenocarcinomas represent approximately 2% of primary bladder epithelial malignancies. Of these, the signet ring-cell variant is the rarest form. We report such a case, with the unusual presentation of oliguria, including radiologic and histopathologic findings. The current literature is reviewed.

We report the case of a primary renal carcinoid tumor associated with a horseshoe malformation in a 43-year-old man who presented with testicular pain. The tumor was centrally located and purely solid and had features ascribed to hindgut neuroendocrine neoplasia. The relative risk of developing a carcinoid tumor in a horseshoe kidney is estimated to be x82.

Malignancy metastasis to the penis is an uncommon clinicopathological entity. We present two cases of malignant priapism following penile metastasis, in which the diagnosis was established by core needle biopsy of the corpus cavernosum. Primary tumors were urothelial carcinoma of the urinary bladder in one case (the patient having concomitant high-grade prostatic adenocarcinoma) and prostatic adenocarcinoma in the other. The clinicopathological features of 51 previously reported cases of penile metastasis in the recent literature are reviewed.

Objectives Intracavernous needle injection is an effective delivery method for pharmacotherapy of erectile dysfunction. Needle phobia, pain, and concern about local tissue injury have stimulated the search for new, less invasive means of inducing penile erection. In this preliminary communication, we evaluate a jet injector as an alternative to needle injection for intracavernous delivery of vasoactive drugs. Methods Jet injection was evaluated in three groups of rats receiving either India ink, saline, or papaverine into the penis. The ability of the jet injection to penetrate through the tunica albuginea and deliver liquid to the corpora cavernosa smooth muscle was assessed by the degree of staining within the corpus cavernosum (ink group), histologic change (saline group), and rise in intracavernous pressure (papaverine group). Erectile capacity following cavernous nerve electric stimulation was compared before and 1 hour after injection of saline or papaverine. Results Ink traversed the skin and tunica albuginea with extensive deposition noted within the cavernous spaces. Varying degrees of subcutaneous hemorrhage were seen with saline jet injection; however, the corpus cavernous smooth muscles showed no evidence of injury. Jet injection of papaverine 3250 gmg significantly increased cavernous pressure (39.4 ± 4.6 cm H2O) compared with saline injection (2.8 ± 1.3 cm H2O). Conclusions We conclude that acute jet injection is an effective method for intracavernous delivery of drugs. Long-term effects should be evaluated prior to clinical use.

Benign thyroid disease is a risk factor for nonmedullary thyroid carcinoma [Houlston and Stratton: Q J Med 88:685-693, 1995]. We report on a family with 7 members with benign and/or malignant thyroid neoplasia; one affected female died of a paravertebral alveolar rhabdomyosarcoma at age 20. The occurrence of thyroid nodular hyperplasia, nonmedullary thyroid cancer, and rhabdomyosarcoma in the same family may be due to chance, common environmental factors, or, most likely, genetic predisposition.

Hepar lobatum is an acquired liver deformity mostly known as the end-stage of tertiary syphilis. The authors report two cases of hepar lobatum resulting from metastatic mammary ductal carcinoma in the liver and reassess the clinicopathologic features of seven previously reported cases (two in the German language). A liver of near-normal weight with an irregularly lobulated contour, capsular indentations/crevices from which intersecting (carcinoma-bearing) fibrous septa extended deep into the parenchyma, a predominant centrifugal distribution of lesional areas, and many septa abutting on the degenerated center of tumor nodules were the salient gross features. No significant tumor/fibrous occlusion of intrahepatic branches of portal or hepatic veins, nor cirrhotic type nodular hepatocellular regeneration was observed. Both of these patients experienced a drastic decrease in CEA serum levels during multiagent palliative chemotherapy. In one patient, abundant macrophages in conjunction with minimal residual tumor were present within intrahepatic septa. The pathogenesis of this condition appears largely related to an active phase of chemo-induced tumor regression with subsequent tissue collapse, followed by an organizing phase of healing and scar contraction.

Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P0.001), overall BCR (P0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.

Objective To compare ERG expression and gene rearrangements rates in metastatic and castration-resistant prostate cancer (CRPC) to localized disease as ERG is the most common genetic event in early prostate cancer (PCa) with potential prognostic and therapeutic implications. Methods We evaluated ERG protein expression in 344 patients with PCa in 3 cohorts including localized, metastatic, and castration-resistant disease using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results ERG protein expression was detected exclusively in the neoplastic epithelium and was found in 6.8% and 46.3% of high-grade prostatic intraepithelial neoplasia (HGPIN) and localized PCa, respectively. In metastatic and locally advanced CRPC, ERG expression was significantly lower, occurring at 36.1% and 37.2%, respectively. In PCa with foamy gland morphology, ERG protein expression was detected in only 18.6% compared with reported rates of about 42%-48% in acinar PCa. Moreover, ERG protein expression and gene rearrangements showed an overall consistency rate of 90.6% (P

A 63-year-old black man of Caribbean origin, seropositive for human T-cell lymphoma virus type I (HTLV-I), presented with a 4-week history of progressive dyspnea, and was found to have a tumor of the anterior mediastinum. Incisional biopsy revealed a malignant neoplasm with a solid pattern of glycogen-rich clear cells. Diffuse expression of vimentin was observed, whereas only rare cells were immunoreactive for muscle-specific actin and desmin. Ultrastructure revealed a large amount of mono-particulate glycogen in most cells and features of rhabdomyogenic differentiation in occasional cells. The autopsy revealed a 23 x 14-cm (1,345 g), soft and white mediastinal neoplasm bulging in the right thorax with right pleural metastases. HTLV-1 proviral genome was not detected within tumor cells by polymerase chain reaction. This rhabdomyosarcoma is best classified as the solid subtype of the alveolar variant, with an unusually large amount of cytoplasmic glycogen. Clear cell rhabdomyosarcoma could be potentially confused with more commonly encountered clear cell tumors, particularly in the mediastinum.

Balloon dilation of the right ureterovesical junction (UVJ) and distal ureter to three times its normal caliber was performed in 12 pigs. A right double-J (D-J) stent was inserted after dilation in 6 pigs. Bilateral upper tract dynamics with different perfusion rates (0.5, 2 and 4 ml. per minute) were recorded before dilation, immediately after dilation, and then 4 and 7 weeks after dilation. Immediate and late antegrade nephrostograms as well as suprapubic cystograms were taken. Grade 3 reflux occurred in 100% of animals at 7 weeks on the dilated, stented ureter and no reflux on the dilated, nonstented ureter. At 7 weeks on the dilated, stented side, significant growth (> 100,000, colonies) of Pseudomonas species was noted in all animals. Creatinine clearance was significantly reduced on the dilated, stented side when compared to the dilated, nonstented side at 7 weeks. Histologic examination of the dilated, stented and dilated, nonstented ureters at 4 weeks revealed a segmental muscular defect with muscular regeneration starting from the edge of the defect, particularly in the innermost region. At 7 weeks, there was a more advanced, but similar, pattern of muscular regeneration in both groups. However, at 7 weeks, metaplastic changes of the ureter and chronic pyelonephritis were evident on the dilated, stented ureter. Electron microscopy showed that myofibroblasts played a major role in the healing process with new muscle formation. At 4 weeks, no significant morphologic difference was found between the dilated, stented and dilated, nonstented ureters. At 7 weeks, however, it appeared that the ureteric stent resulted in damage and deterioration of renal function without affecting muscular regeneration of the ureter. We conclude that the changes observed could be entirely due to the infection associated with the stent rather the stent itself.

A 74-year-old man was found to have a 1 cm, slightly elevated and flat, red mucosal lesion of the descending colon. An endoscopic biopsy showed a structure characteristic of a tubular adenoma. The surgical specimen revealed an inverted, transmural, solid and cystic lesion. The superficial (intra-mucosal) component of the neoplasm was histologically characteristic of a flat adenoma, showing epithelial dysplasia. However, the contiguous deep component was a well-differentiated adenocarcinoma extending to the serosa and demonstrating the unusual features of a circumscribed lobulated topography and the absence of an inflammatory/desmoplastic stromal reaction. Endophytic malignant transformation within a flat adenoma should be distinguished from conditions of misplaced glandular epithelium such as localized colitis cystica profunda. Complete and full mucosal thickness endoscopic snare removal is indicated in order to assess the degree of epithelial dysplasia and detect endophytic malignant transformation.

Background. The appropriateness of resection in patients from whom polyps with invasive adenocarcinoma were excised has been questioned. Methods. To determine the results of this policy, the authors reviewed the outcome of 42 patients from whom 44 such polyps were removed. Each polyp was categorized for the level of invasion according to the classification of Haggitt. Results. Level 1 invasion was found in 27%; level 2, in 9%; level 3, in 11%; level 4, in 39%; and uncertain, in 14%. The histologic grade was well differentiated in 48% of patients and moderately differentiated in 52%. No polyps contained poorly differentiated adenocarcinoma; lymphatic and vascular invasion were not encountered. Excision was judged complete in 23 patients; 11 underwent resection, and in none was residual adenocarcinoma identified. In 14 patients, margins could not be evaluated; of 12 patients who underwent resection, residual adenocarcinoma was found in 1. Of the seven patients with positive margins who underwent resection, residual adenocarcinoma was found in only two. In the resected specimens in which residual carcinoma was encountered, all original lesions were designated level 4. None of the patients treated by polypectomy alone has experienced a recurrence at a mean follow-up time of 66 months (range, 12-152 months). Conclusions. The authors conclude that only patients with level 4 invasion require resection.

Spinal column distraction is a known cause of spinal cord injury. Laplace's law predicts that cord interstitial pressure will elevate during spinal cord distraction. To determine the significance of the Laplace predictions a series of in vitro and in vivo experiments examining spinal cord distraction were performed. In vitro experiments were carried out on 10 dog spinal cords in a specially designed distraction apparatus. These experiments verified the Laplace's law demonstrating a close correlation (R(avg) = 0.99) between the tension applied to the cord, and cord interstitial pressure. Cord interstitial pressure strain (elongation) curves show that initial elongation is accompanied by negligible elevations of cord interstitial pressure; the final 20% elongation being responsible for 80% of the elevation in cord interstitial pressure. In vivo experiments were carried out on five beta-blocked dogs. Significant elevations in cord interstitial pressure were obtained during stepwise spinal column distraction. Spinal cord blood flow and somatosensory evoked potentials were well maintained during distraction until cord interstitial pressure reached 47 mm Hg. At this point a simultaneous fall in spinal cord blood flow and somatosensory evoked potentials was noted. Release of the distracting force resulted in return of spinal cord blood flow, somatosensory evoked potentials, and cord interstitial pressure to baseline. The authors conclude that significant elevations in cord interstitial pressure occur with spinal cord distraction and that these cord interstitial pressure elevations are associated with a reversible ischemic response in the cord.

Most neoplasms of the testis are of germ cell origin. More than half of germ cell tumors contain more than one histologic type and are referred to as malignant mixed germ cell tumors. The American Cancer Society estimates that 8,400 new cases of testicular germ cell tumors will be diagnosed in 2009 in the United States (American Cancer Society. http://www.cancer.org). The incidence varies by country and socioeconomic status and ranges from one to ten per 100,000 (Eble et al. 2004) with the highest incidence in developed European countries such as Germany, Denmark, Norway, and Switzerland (Ferlay et al. 2001). The incidence of testicular germ cell tumors, specifically, seminoma has been increasing in populations of European descent (Coleman et al. 1993). There is speculation that the increased incidence in developed countries is related to a high-fat western diet and lack of physical activity associated with higher socioeconomic status. Due to advances in treatment, the overall 5-year survival rate for testicular germ cell tumors is 96% and is even greater for localized disease (American Cancer Society. http://www.cancer.org). This chapter deals exclusively with adult germ cell tumors; however, excellent reviews of pediatric germ cell tumors are available elsewhere (Wojno and Bloom 1997).

Background As immunomodulatory therapies such as recombinant human interferon beta gain clinical applicability, patients are likely to experience some of their numerous cutaneous adverse effects at injection sites. We describe a case of interferon beta–induced septal panniculitis. Observations A 43-year-old woman with multiple sclerosis treated with subcutaneous interferon beta presented with right lower abdominal quadrant pain, fever, and an indurated McBurney point. An abdominal computed tomographic scan showed an inflammatory subcutaneous fat infiltration reaching the surface of the right lateral rectus muscle. The patient was brought to the operating room, where a laparoscopic appendectomy was performed. She returned a week later unimproved. The infiltration near a site of subcutaneous injection progressed with areas of liquefaction. Histologic examination of a deep cutaneous biopsy specimen revealed a septal panniculitis without vasculitis. Conclusions Panniculitides encompass various clinical syndromes characterized by inflammation of the fibrous septae, fatty lobules, or both components of the subcutaneous tissue. Interferon beta-1b should be considered among the list of putative agents.

In search for a more reliable prognostic discriminant, a retrospective analysis of 100 cases of colorectal carcinoma having undergone curative resection and followed for at least 5 years were assessed by nuclear morphometry. Each case was staged according to the Dukes' classification as well as graded histologically. For all patients in this series, the perimeter, area, and nuclear shape factor of 50 interphase nuclei were determined for each carcinoma. The information was obtained through the use of an image analysis system by tracing the nuclear profiles (magnification 1000x) as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. A nuclear shape factor greater than 0.84 was associated with poor outcome. Multiple regression models showed that the single nuclear parameter of the shape factor was the most highly significant predictor of survival (P less than 0.0001). This variable remained highly significant even when corrected for sex, age, histologic grade, and Dukes' classification. These findings indicate that a nuclear shape factor greater than or equal to 0.84 as determined by nuclear morphometry is an independent morphometric nuclear variable of great importance in the prognosis of large bowel carcinoma.

Minor salivary gland neoplasms with mesenchymal-like features are uncommon in the sinonasal tract. We herein report a case of spindle cell myoepithelioma of the nasal cavity in a 69-year-old woman who presented with a rapidly expanding tumor accompanied by episodes of epistaxis. Although initially considered as a mesenchymal neoplasm, ultrastructural and immunophenotypical characterization demonstrated its myoepithelial nature. In the sinonasal setting, this unusual neoplasm may be confused with soft tissue tumors showing spindle cell or myxoid features. Staining for cytokeratin is found to be the most useful adjunct to diagnosis.

OBJECTIVE To address, by co-assessing cytoplasmic and nuclear androgen receptor (AR) expression in prostate tissues, the contribution of the AR throughout the stages of prostate cancer (PC) and its value as a marker for predicting biochemical recurrence (BCR) after radical prostatectomy (RP). PATIENTS AND METHODS Archival prostate specimens from patients who were cancer-free (43), with hormone-sensitive prostate cancer (HSPC, 62), and with androgen-independent prostate cancer (AIPC, 30) were used to construct tissue microarrays (total 135). Prostatic intraepithelial neoplasia (PIN) and non-neoplastic tissues (NA) found adjacent to HSPC were also included. Nuclear and cytoplasmic AR expression was scored by two observers using a composite scale, after immunohistochemical detection of the AR. The nuclear/cytoplasmic AR expression ratio was also calculated. Univariate Kaplan-Meier plots, and multivariate Cox and survival-tree analyses, were then used to assess the ability of the AR to predict BCR in the patients with HSPC. RESULTS There was markedly greater nuclear AR staining intensity in NA than in normal prostate tissues from cancer-free patients. Cytoplasmic AR expression was highest in AIPC and markedly more than in HSPC. The nuclear/cytoplasmic AR expression ratio was highest in NA and PIN. In univariate analyses, a low nuclear AR, low cytoplasmic AR, and a high nuclear/cytoplasmic AR expression ratio were associated with BCR. Although cytoplasmic AR was an independent predictor of BCR in a Cox multivariate model (hazard ratio 2.736, 95% confidence interval 1.228–6.091, P = 0.014), survival-tree analyses suggested a complex relationship between AR expression and clinicopathological features. CONCLUSION We propose that increased nuclear AR expression might be a precursor to PC and that cytoplasmic AR could contribute to the AIPC phenotype. The predictive ability of the AR might be closely linked to clinicopathological features.

A mucosubstance-rich myxoid meningioma that recurred twice is reported. This rare form of meningioma is a potential source of confusion with other myxoid neoplasms such as metastatic adenocarcinoma or chordoma. In addition to the usual stigmata of meningial cell differentiation, ultrastructural examination revealed spaces delineated by a network of cellular processes and enclosing loose granular and fibrillar material. This neoplasm is probably linked to the so-called microcystic meningioma but has an overt production of acid muco-substance.

Purpose: To assess the expression of proapoptotic NOXA and PUMA in prostate tissues and delineate their association with prostate cancer (PCa) recurrence. Experimental Design: Normal, prostatic intraepithelial neoplasia (PIN), hormone-sensitive (HS) PCa, and hormone-refractory (HR) PCa tissues were used to build tissue microarrays encompassing a total of 135 patients. Two observers assessed the intensity of NOXA and PUMA immunohistochemical staining using a composite color scale. One hundred and eighty recursive partitioning and regression tree (RPART) models were generated to predict biochemical recurrence (BCR) within HS cancer patients using NOXA, PUMA, and clinical parameters. Models were then ranked according to the integrated Brier score (IBS). Results: Increasing NOXA expression was associated with PCa progression, reaching the highest levels in HR PCa. Increased NOXA expression was observed in 68% of HS cancer patients and was predictive of BCR (LR = 8.64; P = 0.003). In contrast, PUMA expression was highest in HS cancer, and although 70% of HS cancer patients exhibited increased PUMA expression, PUMA alone could not predict the onset of BCR. Interestingly, the top-ranking RPART model generated [IBS = 0.107; 95% confidence interval (95% CI), 0.065-0.128] included surgical margin status and NOXA and PUMA expression, although recurrent prognostic classification schemes obtained in the top 10 models favored a survival tree model containing margin status, NOXA expression, and preoperative prostate-specific antigen (PSA) (IBS = 0.114; 95% CI, 0.069-0.142). Conclusion: We conclude that NOXA and PUMA expression may be linked to PCa progression and propose further validation of a survival tree model including surgical margin status, NOXA expression, and preoperative PSA for predicting BCR.

Purpose: The ErbB1 and ErbB2 receptors have been implicated in prostate cancer progression, but less is known about the role and biology of other ErbB receptor family members in prostate cancer. The aim of this study was to analyze the expression and localization of ErbB3 in prostate tissues and prostate cancer cell lines.Experimental Design: Immunohistochemistry of ErbB3 was done on prostate cancer tissue sections from 143 patients and on a tissue microarray containing 390 cores of radical prostatectomy-derived specimens representing normal, prostatic intraepithelial neoplasia, and malignant tissues from 81 patients. ErbB3 subcellular localization was studied by Western blot analysis in LNCaP, 22Rv1, PC-3, and DU145 prostate cancer cell lines.Results: Immunohistochemistry analysis of prostate cancer tissues revealed that >90% of prostate cancer tissues displayed cytoplasmic ErbB3 staining. Minimal ErbB3 nuclear staining was observed in normal prostate tissues and benign prostatic hyperplasia tissues; in contrast, ErbB3 was frequently localized in the nucleus of cancerous tissues. This nuclear localization was more frequent (P < 0.001) in hormone-refractory tissues (17 of 17, 100%) compared with hormone-sensitive samples (37 of 92, 40.2%). Additionally, in the tissue microarray, increased nuclear ErbB3 was associated with increasing Gleason grade. Interestingly, Western blot analysis of cytoplasmic and nuclear subcellular fractions showed that ErbB3 nuclear localization was more prevalent in hormone-sensitive prostate cancer cell lines (LNCaP and 22Rv1) compared with hormone-insensitive cell lines (PC-3 and DU145).Conclusions: ErbB3 nuclear localization discriminates normal from malignant prostate tissues and between tumors from hormone-sensitive versus hormone-refractory prostate cancer. ErbB3 nuclear staining seems to be associated with risk of disease progression. The high frequency of ErbB3 nuclear localization in hormone-refractory tissues indicates that ErbB3 warrants further study to understand its association with prostate cancer disease progression.

Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.

Purpose: Radical prostatectomy (RP) patients with positive surgical margins are at increased risk for recurrence, emphasizing the need for prognostic markers to stratify probable outcome for optimal patient management decisions. We tested the hypothesis that nuclear localization of nuclear factor (NF)-κB, a transcription factor involved in the regulation of cell growth, angiogenesis, invasion, and apoptosis, is associated with an increased risk of biochemical recurrence after RP. Experimental Design: Analyses addressed data from 42 patients (age range, 52–72 years; mean age, 63.7 years) who exhibited positive surgical margins after RP. Immunohistochemical analysis of NF-κB (p65) was performed on the positive margin tissue. A nuclear staining cutoff of >5% was considered positive. The relation between nuclear NF-κB expression and biochemical recurrence (prostate-specific antigen >0.3 ng/mL and rising) after RP was tested in univariate and multivariate Cox regression models. Results: Biochemical recurrence was recorded in 23 patients (54.8%; median follow-up, 3.2 years). Univariate Cox regression demonstrated a 4.9-fold (95% confidence interval, 1.5–16.7; P = 0.01) higher rate of recurrence in men with NF-κB > 5%. In the multivariate model, after controlling for primary (P = 0.004) and secondary (P = 0.7) Gleason patterns, lymph node (P = 0.06) and seminal vesicle invasion (P = 0.2), and preoperative prostate-specific antigen (P = 0.009), NF-κB > 5% was associated with a 6.2-fold higher risk of biochemical recurrence (95% confidence interval, 1.7–23.5; P = 0.007). Conclusions: In univariate and multivariate analysis, NF-κB nuclear expression was strongly predictive of biochemical recurrence in patients with positive surgical margins after RP. We propose that nuclear NF-κB may serve as a useful independent molecular marker for stratifying patients at risk for recurrence.

Glomeruloid microvascular proliferation (GMP) in breast cancer independently adversely affected survival (relative risk 1.9, 95% CI: 1.2–3.0), particularly among women who received adjuvant chemotherapy (10-year survival 27 vs 69%, P=0.0003), and was significantly associated with p53 overexpression and BRCA1 germline mutations. The presence of GMP may influence treatment decisions.

Objectives. To evaluate the prostate-specific antigen (PSA) changes and the ability of PSA doubling time (PSADT) to predict disease progression in untreated patients with clinically localized prostate cancer. Methods. A total of 104 patients with localized prostate cancer were followed up expectantly with serial PSA measurements and digital rectal examination (DRE). PSADT was calculated by linear regression analysis for the 94 patients who had a minimum of three PSA measurements and 12 months of follow-up. The median follow-up was 33 months. Of the 94 patients, 45 underwent repeat prostate biopsy to evaluate whether tumor progression occurred during the observation period. Results. Twenty-seven percent of patients had rapid PSADTs (less than 48 months). Only the presence of palpable disease on DRE correlated with a PSADT of less than 48 months (P

The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 microg/30 microl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.

Objectives Neoadjuvant androgen ablation (NAAA) causes significant cytoarchitectural changes in both benign and malignant prostatic epithelial cells that may contribute to underdetection of prostate cancer capsular involvement and positive surgical margins. Methods The aim of this study is to determine the ability of cytokeratin immunohistochemistry to enhance the determination of pathologic stage of prostate cancer following NAAA. Results Cytokeratin AE1/AE3 immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%) cases of organ-confined disease, capsule penetration, positive surgical margin, and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10 (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining, respectively. Two cases without detectable tumor by H&E staining had demonstrable residual tumor by cytokeratin immunohistochemical staining. Conclusions Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular, and extracapsular tumor involvement and higher rate of positive surgical margin than did conventional H&E staining. Therefore, the beneficial pathologic effects of NAAA observed may, in part, be attributable to the artifact of observation.

To reassess positive rate of sextant biopsy according to gland size.We evaluated 1974 consecutive men with systematic sextant biopsy, among whom we examined biopsy yield according to gland-volume intervals of 10 cc.Decreasing yield of sextant biopsy is strongly associated with increasing gland volume (P0.001). Highest biopsy rate (39.6%) was recorded among men with prostates smaller than 20 cc. The lowest biopsy rate (10.1%) was recorded among men with prostates between 80 and 89.9 cc. Among men with biopsy-proven cancer, age, serum prostate-specific antigen, and Gleason grade were comparable (P0.05) throughout the range of gland-volume intervals.Our findings suggest that gland size represents an important determinant contributing to the yield of sextant biopsy in men at risk of harboring a nonpalpable, isoechoic cancer. Consequently, an individualized sector biopsy approach, based on prostate volume, may warrant consideration because it may ensure superior detection of clinically significant disease among all men at risk, regardless of prostate size.

Objectives To assess the accuracy and reproducibility of nonplanimetric transrectal ultrasound (TRUS) volume estimates because inaccurate volume estimates may potentially undermine the value of serum prostatespecific antigen density (PSAD) in early prostate cancer detection. Methods We prospectively evaluated 535 consecutive male patients with two consecutive volume determinations performed by the same ultrasonographer at the time of the same visit. Results Pearson correlation coefficients between two consecutive gland volume estimates ranged from 0.82 to 0.85 depending on the formula used; however, these correlation coefficients corresponded to an average 25% difference between the first and second gland volume estimates. Conclusions Although two consecutive nonplanimetric TRUS volume estimates show statistically good correlation, clinically up to a 25% volume difference should be expected between two such volume estimates. In consequence, nonplanimetric TRUS volume estimates should be interpreted with caution, especially when used for PSAD calculation, in the early detection of prostate cancer.

Objective To determine whether a defect in vasoactive intestinal peptide (VIP)-mediated vasodilatation underlies diabetic impotence Materials and methods Rats treated with streptozotocin for 8 weeks developed diabetes, as shown by hyperglycaemia and glycosuria, and had significant impairment of sexual function, as determined by tests of sexual behaviour. The VIP content of the penis and major pelvic ganglion, the VIP release by the penis in vitro and the responsiveness of the vasculature of the penis in vivo to intracavernous VIP injection were determined. Results In diabetic rats, the VIP content of the major pelvic ganglion and penis was markedly increased, while the acetylcholine content of the penis was normal. The amount of VIP released in vitro by high potassium concentration or veratridine was similar for penile tissue slices of normal and diabetic rats. Intracavernous injection of VIP induced erection in the control rats but not in diabetic rats, whereas intracavernous injection of the adenylate-cyclase activator forskolin produced erection in both control and diabetic rats. Conclusion Because VIP induces vasodilatation by activating adenylate cyclase, and forskolin produced erection in the diabetic rats, the failure of VIP to produce erection in these rats is unlikely to be due to a defect in the second-messenger mechanism or in the properties of vascular smooth muscle. Thus, a defect at the level of the VIP receptor or of the associated G-protein possibly explains the failure of intracavernous VIP to produce erection in the diabetic rats. Hence, an abnormality in VIP is a component of sexual dysfunction in the diabetic rat and the defect is at the level of the VIP receptor or associated G-protein.

Early detection efforts identify prostate cancer at lower clinical and pathologic stages, often resulting in smaller volumes of tumor in radical prostatectomy specimens. In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma reveals minimal or no residual cancer. We evaluated the clinical and pathologic findings in 13 such cases in an effort to document this finding, which we refer to as the "vanishing cancer phenomenon." The mean number of prostate slides examined per case was 79 (range, 34-248). Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. Mean cancer volume in the 10 cases with residual tumor was 0.019 cc (range, 0.003-0.038); the largest single dimension of any tumor focus was 3 mm. All cancers were well differentiated or moderately differentiated in the biopsy and prostatectomy. Our results indicate that in some cases cancer may be extremely difficult or impossible to find in the prostatectomy specimen despite exhaustive sampling. The incidence of this "vanishing cancer phenomenon" is probably increasing because more low-stage cancers are being treated by prostatectomy. The inability to identify cancer in a prostate removed for needle biopsy-proven carcinoma may not indicate technical failure.