Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications

Cribriform neoplasia of the prostate can be recognized easily. However, controversy persists regarding terminology, particularly with the intraductal spread of cribriform neoplasia; some consider this "intraductal carcinoma," whereas consensus meetings defined these lesions as high-grade cribriform prostatic intraepithelial neoplasia (HGCP). This study attempts to identify the incidence and clinical significance of HGCP and cribriform carcinoma (CC) by evaluating 114 radical prostatectomy specimens. Cases were divided into three histologic groups for statistical analysis: (1) pure acinar carcinoma: infiltrating acinar carcinoma without evidence of cribriform neoplasia; (2) CC: acinar carcinoma with CC; and (3) HGCP: acinar carcinoma with HGCP. High-grade cribriform prostatic intraepithelial neoplasia was defined as the presence of neoplastic cells spanning the entire lumen in a cribriform configuration in which a basal cell layer could be shown by immunohistochemistry. Similar areas in which no basal cell layer could be seen were diagnosed as CC. The incidence of cribriform neoplasia was 38% (43 of 114). The incidences of HGCP and CC were 13% (15 of 114) and 25% (28 of 114), respectively. Univariate analysis showed a strong association between HGCP and CC both and several preoperative and final pathology results, including digital rectal examination, pathology tumor stage, extraprostatic extension, surgical margin positivity, high Gleason sum (GS), and high tumor volume. Kaplan-Meier analysis showed HGCP to have a 61% cumulative prostate-specific antigen (PSA) failure rate in contrast with CC and pure acinar cancer, which had cumulative PSA failure rates of 15% and 13%, respectively (p = 0.0001, log-rank test). Multivariate Cox's proportional-hazards analysis found preoperative serum PSA, GS, tumor stage, and volume to be important predictors of PSA failure. In a second regression model that included serum PSA, GS, and pathology tumor stage, HGCP was an independent predictor of PSA failure. Both HGCP and CC are closely associated with several poor prognostic indicators, including advanced pathology tumor stage, a high GS, and serum PSA. Multivariate analysis showed HGCP as an independent prognostic indicator. The close association between high tumor volume and HGCP supports the theory that the development of HGCP is a late event in tumor progression, more compatible with the intraductal spread of tumor than dysplasia.     

Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer

BACKGROUND: The combination of low concentrations of sclerosing solution and the Nd:YAG, Q-switched laser with multiple (quadruple) frequency provides good results in the treatment of telangiectases and reticular varicose veins of the lower extremities, as well as pigmentation that may appear during sclerotherapy. OBJECTIVE: This paper is based on a series of patients with telangiectases and reticular veins who were treated with sclerotherapy and the Nd:YAG, Q-switched laser with quadruple frequency. METHODS: Patients with telangiectases and reticular veins received two or three treatment sessions with polydocanol and the Nd:YAG, Q-switched laser with quadruple frequency. Then, they were assessed a clinical score corresponding to the level of improvement achieved. Residual hematic pigmentation lesions were also eliminated with the laser. RESULTS: Excellent improvement was evident in 90% of the patients with minimal residual lesions. CONCLUSIONS: The combined technique of sclerosing solution and the Nd:YAG laser with multiple frequency is a valid alternative for the elimination of telangiectases and reticular veins of the lower limbs. This technique has several advantages, such as the use of low concentrations of sclerosing solution, high patient acceptance levels due to minimal disturbances, and the fact that local anesthesia is unnecessary. Good results are obtained without complications and minimal residual pigmentation. These mild pigmentation can be treated with the Nd:YAG laser.     

Molecular biology of prostatic intraepithelial neoplasia

Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of chronic alcohol abusers even after decades of abuse. The clinical spectrum of disease varies from asymptomatic hepatomegaly to florid hepatocellular failure with gastrointestinal bleeding and hepatic encephalopathy. Corresponding variation is observed both in morbidity and mortality. The majority of individuals with mild to moderate alcoholic hepatitis improve significantly following abstinence from alcohol and the provision of a diet sufficient to meet their nutritional requirements; their long-term outcome is determined largely by their ability to maintain abstinence from alcohol. Individuals with severe alcoholic hepatitis require intensive nutritional support and vigorous management of the complications of their liver injury; their outcome is generally poor. A small, carefully selected subgroup of these very sick patients may benefit, at least in the short-term, from treatment with corticosteroids; the place of orthotopic hepatic transplantation, in this patient group, is still the subject of debate. No other treatment modalities have been shown to confer benefit consistently. A number of new therapeutic approaches have been proposed and need to be explored.     

Do prostate specific antigen and prostate specific antigen density enhance the detection of prostate carcinoma after initial diagnosis of prostatic intraepithelial neoplasia without concurrent carcinoma?

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is considered to be a precursor of prostate carcinoma in which serum levels of prostate specific antigen (PSA) have been correlated with PIN grades. The aim of this study was to determine whether PSA and prostate specific antigen density (PSAD), obtained at the time of initial diagnosis of PIN without concurrent carcinoma, can be used as predictive factors to discriminate patients with subsequent cancer on repeat biopsy. METHODS: We studied, retrospectively, the records of 93 patients with PIN (low and high grade) without concurrent carcinoma at the time of their first needle biopsy. We assessed the relationship between initial PIN grade, PSA, and PSAD with later detection of carcinoma on repeat biopsy. Patients were divided into 3 subgroups for analysis according to their initial PSA level (0-4, 4.1-10, >10 ng/mL). RESULTS: Carcinoma detection rate on repeat biopsy was 13.3% for patients with low grade PIN and 47.7% for patients with high grade PIN (P < 0.006). High grade PIN was frequently associated with subsequent carcinoma whatever the PSA level (33.3-61.9%). Low grade PIN was associated with subsequent carcinoma in 42.8% of the cases when PSA was greater than 10 ng/mL. When PSA was between 4 and 10 ng/mL, low grade PIN carcinoma was found on repeat biopsies in only 10.7% of the cases (P = 0.05). In none of the PSA subgroups did PSAD enhance later cancer detection. CONCLUSIONS: For patients with high grade PIN, the incidence of subsequent carcinoma is high, whatever the PSA values. For these cases repeat biopsies should be recommended. Patients with low grade PIN and PSA greater than 10 ng/mL should have repeat biopsies because the incidence of subsequent carcinoma is high and comparable to high grade PIN. PSAD did not provide additional information.     

重复穿刺活检中高级别上皮内瘤对前列腺癌的预测价值

Objective: The significance of isolated high-grade prostatic intraepithelial neoplasia in initial biopsy as an predictor for prostate cancer has been extensively research, and the true relationship remnant is no clear till now. The aim of this study is to evaluate prediction value of cancer on repeat biopsy in patients with high-grade prostatic intraepithelial neoplasia,using multivariate analysis. Methods: Thirty-eight men with a diagnosis of isolated high-grade prostatic intraepithelial neoplasia in initial needle biopsy were studies, in the Fist Affiliated Hospital of Medical School of Xi'an Jiaotong University, from January 2003 to March 2009. These samples were using immunostaining of p63 and 34βE12 and P504s, with a median follow-up of 525 (range, 7 to 1650) days, and to researched the incidence of subsequent prostate cancer, and to predicted the risk of prostate cancer in clinicopathological parameters of isolated high-grade prostatic intraepithelial neoplasia on repeat biopsies by logistic regression analysis. Results: There were 10 of 38 (26.3%) men with prostate cancer on repeat biopsies after diagnosis isolated high-grade prostatic intraepithelial neoplasia in initial biopsy, of the rates of prostate cancer were 80% for micropapillary and 75% for cribriform high-grade prostatic intraepithelial neoplasia (P < 0.05), respectively. The positive cores of isolated high-grade prostatic intraepithelial neoplasia was the important for the risk of prostate cancer using Multifactor logistic regression analysis. The time range in 30 to 690 days was stronger risk for prostate cancer detection after diagnosis isolated HGPIN in initial biopsy. p63 and 34βE12 were disrupted positive expression, and P504S was weak positive expression in the 61% isolated high-grade prostatic intraepithelial neoplasia. Conclusion: Isolated high-grade prostatic intraepithelial neoplasia on repeat biopsy conferred a 26.3% risk of prostate cancer, and this risk level is lower than the previously reported risk of 24% to 58%. The number of positive cores and the histopathological pattern with high-grade prostatic intraepithelial neoplasia on initial biopsy was significantly associated with the risk of cancer.     

Allelic loss of 8p sequences in prostatic intraepithelial neoplasia and carcinoma

PURPOSE: The purpose of the study is to report the outcome and postoperative topographic analysis of seven patients who underwent small-diameter, round, eccentric penetrating keratoplasty. METHODS: Seven patients underwent small-diameter, round, eccentric penetrating keratoplasty for a variety of corneal disorders (cataract wound necrosis and dehiscence or fistula, three patients; penetrating keratoplasty wound infection, two patients; corneal rheumatoid melt and perforation, one patient; localized fungal keratitis, one patient). Full-thickness corneal transplants ranged in size from 3.0 to 5.5 mm. The graft wound and sutures spared the visual axis in all cases. Patients were observed for 7 to 42 months (mean, 21 months). All patients had postoperative topographic analysis. One of these also had preoperative analysis. RESULTS: All grafts tectonically were effective in treating the intended condition. Best-corrected visual acuity was 20/30 or better in the four patients without pre-existing corneal transplants or dry eyes; 20/60 and 5/200 in the patients with previous central penetrating keratoplasties; and 20/40 in the patient with rheumatoid melt. There was no clinically significant regular or irregular astigmatism induced centrally by the eccentric graft in the four patients where visual acuity was 20/30 or better. Irregular astigmatism was noted in the other three patients. CONCLUSION: Small-diameter, eccentric penetrating keratoplasties may be used successfully to treat various peripheral corneal disorders. In some cases, this can be performed without inducing high or irregular astigmatism or both centrally.     

DNA quantitation of intraepithelial neoplasia and invasive carcinoma of the prostate

Head-restrained rats were conditioned to perform a CNV task: to press a lever in response to an imperative auditory stimulus (S2) given 1.5 sec after a warning stimulus (S1) for a drop of jelly food. With an electrode on the surface of the forelimb cortex, (1) sharp wave complexes immediately after S1 and S2, and (2) a negative slow potential (SP) between S1 and S2, on which early and late components were discernible, were recorded in association with performance of this task. With the electrode at a depth of 2 mm in the same cortical area, the corresponding field potential showed a long-lasting positive shift in addition to the components of the surface potential. These monopolar recordings were obtained with respect to a common reference at the frontal sinus. The surface-minus-depth potential (the transcortical potential), consequently, showed a surface-negative tonic wave, confirming Pirch's report (1980). During extinction of this conditioning, the SP between S1 and S2 disappeared, while the sharp waves following S1 and S2 remained with little modification, suggesting that the sharp waves are a kind of evoked potential (EP) elicited by the stimuli. Recording from 5 surface electrodes set in an array over the left hemisphere contralateral to the used forelimb during development of the conditioning revealed not only a spatial distribution of the SP but also a transition of the potentials. As the conditioning progressed, the negativity of the early SP component tended to increase, while that of the late component tended to decrease and was confined to the sensorimotor cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of microdissected specimens

BACKGROUND: Because so many common surgical problems can now be addressed by the laparoscopic approach, the issue of sterile processing has to be reconsidered. METHODS: Selected laparoscopic instrumentation was analyzed regarding wear and tear and decontamination after sterile processing following 6,000 surgical laparoscopies carried out between 1990 and 1996 at the Academic Hospital Moabit, Berlin. RESULTS: Fewer than 7.9 (parts of) instruments failed per 100 laparoscopies. Most of the repairs involved scissors. The main problems were blunting, burnt or disconnected electromechanical components, defective insulation, and damaged or lost parts of dismantable instruments. Residues of human blood proteins were detected on a few instruments. The effect of intraluminal rinsing was documented by measuring the iron content (as an indicator for blood contamination). A comparison of costs showed that it was >10 times cheaper to use instrumentation with reusable components. CONCLUSIONS: The sterile processing of economic reusable instrumentation for laparoscopies needs staff well trained in sterile supply. Instrument design should allow easy dismantling and rinsing of internal parts. Insulating compounds present a problem for decontamination. Disinfection with aldehydes before cleaning the lumina of instruments must be avoided because protein coagulation will occur. A tube-in-tube concept for tubular instruments offering compatibility should be favored.     

Interobserver variability in the diagnosis of high-grade prostatic intraepithelial neoplasia and adenocarcinoma

High-grade prostatic intraepithelial neoplasia (PIN) is a strong predictor of carcinoma when identified in small-needle biopsy specimens. However, the diagnostic variability of PIN is unknown. Eight pathologists reviewed 321 prostatic biopsy specimens to assess the variability of the diagnosis of high-grade PIN and carcinoma. All of the specimens were classified as negative, high-grade PIN, suspicious for high-grade PIN, carcinoma, or suspicious for carcinoma, more than one diagnosis was permitted, except for negative. We compared diagnoses made by two observers by pairing them for negative versus high-grade PIN, negative versus carcinoma, high-grade PIN versus carcinoma, and all diagnostic categories together. Mean kappa coefficient values for 28 interobserver combinations were 0.451, 0.845, 0.669, and 0.482, respectively, for each of the four comparison combinations considered. Our results indicate a high level of agreement, "almost perfect" (kappa = 0.81-1.0) for carcinoma, "moderate" (kappa = 0.41-0.60) for high-grade PIN, and "substantial" (kappa = 0.61-0.81) for high-grade PIN versus carcinoma. We found that variability was related to the level of interest in prostatic pathology, the conditions of the study, the subjective application of diagnostic criteria, and the influence of peers and clinical colleagues.     

Digital image analysis of proliferative index: two distinct populations of high-grade prostatic intraepithelial neoplasia in close proximity to adenocarcinoma of the prostate

For the past 50 years, psychologists have wrestled with questions regarding the relationship between conscious awareness and human conditioned behavior. A recent proposal that the hippocampus mediates awareness during trace conditioning (Clark, Squire, Science 1998;280:77-81) has extended the awareness-conditioning debate to the neuroscience arena. In the following commentary, we raise specific theoretical and methodological issues regarding the Clark and Squire study and place their finding into a broader context. Throughout our discussion, we consider the difficulties in assessing subjective awareness, the importance of establishing necessary and sufficient conditions for cognitive mediation effects, the influence of conditioned response modality, and the nature of hippocampal requirements across conditioning protocols. It is clear that trace eyeblink conditioning is a hippocampal-dependent task, but whether awareness is a necessary component of trace conditioning is not definitively proven. We propose that future functional neuroimaging studies and behavioral experiments using on-line measures of awareness may help clarify the relationship among classical conditioning, awareness, and the hippocampus.     

Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia

The current definition, diagnostic criteria, grading, and approach to assessment of extent of ductal carcinoma in situ (DCIS) are presented. The problem areas, particularly the difficulties in separating low-grade DCIS from atypical intraductal hyperplasia (AIDH), accurate assessment of size and/or extent of DCIS, and their impact on patient management are critically reviewed. On the basis of the route of progression of DCIS, recently confirmed by three-dimensional reconstructed models, an optimal and simple approach to uniform excision, orientation, and processing of biopsy samples is presented. Emphasis is placed on the role of intraductal proliferative lesions (IDH, AIDH, and DCIS) as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. It is proposed that these proliferations should be classified as "mammary intraepithelial neoplasia, ductal type" or as "ductal intraepithelial neoplasia" (DIN); the rational for the application of this classification system is provided. This approach obviates the current separation of AIDH and low-grade DCIS into two very drastically different categories of cancer and non-cancer without interfering with appropriate management of the various lesions. The DIN classification is presented in a simple translational table, along with the current terminology for various lesions.     

Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia

OBJECTIVE: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time. METHODS: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively. Pathologic specimens were analyzed concurrently. RESULTS: In the 1965-1974 cohort, only one of 56 patients was younger than 50 years of age at the time of presentation, whereas in the 1990-1994 cohort, 12 of 57 (21%) were younger than 50 years of age (P = .001). Ten of 13 women younger than 50 years of age, compared with 13 of 100 of women 50 years of age or older, had warty or basaloid VIN associated with their invasive carcinoma (P < .001). Cigarette smoking and multiple lower genital tract neoplasia were both significantly more common in women younger than 50 years of age (P < .001). CONCLUSION: Over the past 2 decades, a subset of women younger than 50 years of age with squamous cell carcinoma of the vulva has emerged. Most of these carcinomas appear to arise in a field of warty or basaloid VIN. This suggests that the increasing incidence of VIN seen in young women during the past 2 decades is being reflected now in VIN-associated squamous cell carcinoma of the vulva in younger women.     

Prostate specific antigen in the expressed prostatic fluid of men with benign prostatic hyperplasia and prostate carcinoma

PURPOSE: We tested the hypothesis that the histochemically demonstrated prostate specific antigen (PSA) content of prostate carcinoma cells does not necessarily reflect PSA production and secretion by evaluating expressed prostatic fluid. MATERIALS AND METHODS: Expressed prostatic fluid and serum from 152 men with clinical benign prostatic hypertrophy (BPH), 132 with histologically proved BPH and 46 with prostate carcinoma were analyzed with the Hybritech PSA assay. RESULTS: Expressed prostatic fluid PSA levels from carcinoma patients (median 1.70 mg./ml., mean 2.25) were significantly higher than in the histologically proved BPH group (median 1.28 mg./ml., mean 1.42, p < 0.05). CONCLUSIONS: PSA concentration is increased in the expressed prostatic fluid of prostates of men with carcinoma compared to those with histological BPH. This finding may be a functional manifestation of a field change or paracrine effects within the prostate.     

Evaluation of the prostate and prostatic carcinoma with gadolinium-enhanced endorectal coil MR imaging

Thirteen patients who underwent subsequent radical prostatectomy for prostate cancer were studied with spin-density-T2-weighted and gadolinium-enhanced and unenhanced T1-weighted magnetic resonance (MR) imaging performed with an endorectal surface coil. With gadopentetate dimeglumine, the central gland showed inhomogeneous enhancement due to benign hyperplasia, whereas the peripheral zone demonstrated more uniform and less intense enhancement. With the T1-weighted sequence, depiction of the zonal anatomy, prostate capsule, surgical capsule, fibromuscular stroma, and periprostatic venous plexus was better with contrast enhancement, but these were best demonstrated on T2-weighted images. The trend was similar for prostatic tumor extent and capsular integrity. The seminal vesicles had a septal enhancement pattern and in several patients were best evaluated with enhanced T1-weighted images. These findings suggest that gadopentetate dimeglumine is not warranted for routine use in endorectal MR imaging of the prostate but may be useful for evaluation of the seminal vesicles in selected patients.     

Treatment of intraepithelial cervical neoplasia with REP Radiosurgical Excision Procedure)

Radiosurgical cervical excision has been performed in 59 patients affected by CIN of various stages. This non-traumatic method uses 3.8 MHz radio waves to cut and/or coagulate without postoperative pain and tissue destruction. The radiosurgical excision has been performed in local anesthesia by a loop electrode or microneedle according to the seat of the lesion. The therapy was "effective" in 98% of cases (58/59) whereas the "incomplete excision" of CIN was observed in 6.7% (4/59). Complications (postoperative and late bleeding) occurred in 3.2% of the patients (2/59). Therefore, the Radiosurgical Excision Procedure (REP) can be considered an easy technique in ambulatory surgery; this method is effective in the treatment of CIN with either therapeutic and economic advantages and guarantee the functional and anatomic integrity of the cervix.     

Transition zone prostate specific antigen density: lack of use in prediction of prostatic carcinoma

PURPOSE: Among the new approaches to enhance the performance of prostate specific antigen (PSA) testing in a biopsy population is the use of the free-to-total PSA as well as the transition zone density, which is calculated by dividing the PSA by the transition zone volume. We compare these manipulations of the PSA to PSA alone in a biopsy population. MATERIALS AND METHODS: We evaluated 917 consecutive men who underwent ultrasound guided biopsy for an elevation in serum PSA or abnormality on digital rectal examination. Total PSA was measured using the Tandem-E or Tandem-R method. Prostate gland volume and transition zone were measured with ultrasound and calculated using the prolate ellipsoid formula. RESULTS: In the overall PSA range 276 men had carcinoma (30.0% of the population), while in the PSA 4.0 to 10.0 ng./ml. range 141 of 477 had cancer (29.6%). Receiver operating characteristics analysis and analysis of variance were performed. In the overall PSA series the Tandem total PSA performed as well as any PSA index to predict carcinoma. In the restricted range of total PSA 4.0 to 10.0 ng./ml. total PSA density as well as transition zone density were more predictive than PSA alone. In both PSA ranges the volume of benign glands was significantly larger than in the prostates exhibiting carcinoma. There was no statistically significant difference in outcomes of analyses between different investigators or different sites of investigation (Veterans Affairs versus university based hospitals). CONCLUSIONS: In this biopsy population transition zone PSA density did not add to the information available with total PSA and gland volume. Neither investigator nor site bias contributed to the failure of transition zone PSA density or PSA density to predict prostatic carcinoma.     

Immunohistochemical analysis of beta-tubulin isotypes in human prostate carcinoma and benign prostatic hypertrophy

This paper is devoted to the practical aspects of pediatric nuclear medicine, particularly the controversy about drug sedation. The authors conclude that drug sedation should be exceptionally used. There is an alternative way, consisting in an adequate approach of the patient: good information to the parents and the child; taking care of the child's environment, starting from the first contacts in the waiting room; specific education of technologists: this includes injections and blood sampling, but also proper handling of the child during the procedure and adequate psychological attitudes toward child and parents. Taking these factors into account, it is exceptional that a test has to be postponed because of the lack of collaboration of the patient; good quality images, using the recommended paediatric amounts of radioactivity can be achieved even for procedures of prolonged duration.     

The value of prostatic acid phosphatase and prostate specific antigen as serum markers in carcinoma of the prostate

The value of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) as serum markers in carcinoma of the prostate (CaP) was investigated in this study. A group of 75 patients entered this trial, 25 with CaP, 25 with benign prostatic hyperplasia (BPH) and 25 with urologic disorders other than prostatic diseases. In the CaP group, PAP was above normal levels in 48% of the patients and PSA in 92%. In the BPH group these rates were 20% and 72%, respectively. No elevation was detected in the third group. In CaP patients with capsular invasion, PAP and PSA levels were above normal in 25 and 87.5%. In metastatic carcinoma, PAP was high in 75% and PSA in 100%. Our study reveals that neither of these markers is useful in the initial diagnosis of CaP. Though PSA seems to be more sensitive, it is not more specific than PAP.