Prostate biopsy: targeting cancer for detection and therapy

Despite improvements in cancer detection, prostate biopsy still lacks the ability to accurately map locations of cancer within the prostate. Improvements in prostate imaging may allow more accurate mapping of overall disease volume. Magnetic resonance (MR) spectroscopy allows improved specificity in detecting even small foci of disease within the peripheral zone. Improvements in MR-guided biopsy techniques may allow this technology to be adapted to therapeutics as well. Computer modeling of individual prostates serves as a means of designing optimized plans for prostate biopsy. The use of novel targeted biopsy schemes may allow an integration of available technologies in detection and localization of prostate cancer. Computer-directed needle biopsies based on anatomic landmarks within the prostate and computerized three-dimensional reconstruction of the gland may allow a highly reproducible means of identifying small foci of cancer, targeting them for therapy, and monitoring for recurrence. The TargetScan(R) system (Envisioneering Medical Technologies, St. Louis, MO) is the first technology to integrate available targeting methodologies in a systematic fashion.     

Optimizing prostate biopsy strategies for the diagnosis of prostate cancer

The importance of prostate biopsy in urologic practice has been magnified by the routine use of serum prostate-specific antigen in prostate cancer screening. Given the potential impact of the procedure on both patient care and health care costs, an optimal strategy for accurate and judicious detection of early prostate cancer is imperative. Maintaining maximal sensitivity and negative predictive value are equally important to the patient. In this article, we review recent modifications in prostate biopsy indications and techniques that may allow for a systematic biopsy approach to the patient in whom prostate cancer is suspected.     

Using Biopsy to Detect Prostate Cancer

Transrectal ultrasound-guided systemic biopsy is the recommended method in most cases with suspicion of prostate cancer. Transrectal periprostatic injection with a local anesthetic may be offered as effective analgesia; periprostatic nerve block with 1% or 2% lidocaine is the recommended form of pain control. On initial biopsy, a minimum of 10 systemic, laterally directed cores is recommended, with more cores in larger glands. Extended prostate biopsy schemes, which require cores weighted more laterally at the base (lateral horn) and medially to the apex, show better cancer detection rates without increasing adverse events. Transition zone biopsies are not recommended in the first set of biopsies, owing to low detection rates. One set of repeat biopsies is warranted in cases with persistent indication. Saturation biopsy (≥20 cores) should be reserved for repeat biopsy in patients who have negative results on initial biopsy but who are still strongly suspected to have prostate cancer.Key words: Prostate cancer, Biopsy, Transrectal ultrasound, Prostate-specific antigen, Anesthesia, NomogramsProstate cancer rarely causes symptoms until it is advanced. Thus, suspicion of prostate cancer resulting in a recommendation for prostatic biopsy is most often raised by abnormalities found on digital rectal examination (DRE) or by serum prostate-specific antigen (PSA) elevations. Although there is controversy regarding the benefits of early diagnosis, it has been demonstrated that an early diagnosis of prostate cancer is best achieved using a combination of DRE and PSA.Transrectal ultrasound (TRUS)-guided, systematic needle biopsy is the most reliable method, at present, to ensure accurate sampling of prostatic tissue in men considered at high risk for harboring prostatic cancer on the basis of DRE and PSA findings. In very rare circumstances, a biopsy of a metastatic site (bone lesion) or a suspicious lymph node may be easier and more advantageous. There are also circumstances in which the usual transrectal route is not feasible (eg, status post-anteroposterior resection of the rectosigmoid; see Tissue Diagnosis in Patients with No Rectal Access section, below). As nearly universal as the approach, as nearly universal is the technique, namely a TRUS-guided biopsy using an 18-gauge needle to obtain a tissue core. To be certain, the same biopsy device and needle may be used to perform a finger-guided biopsy, but this is reserved for unusual circumstances (eg, TRUS imaging not available, finger-guided directed biopsy of suspicious nodule not seen on TRUS). Last, whereas in decades past physicians in many countries performed fine-needle aspiration of the prostate, today this technique is less and less often used, although advocates claim that it is cheaper, faster, easier to perform, and results in lower morbidity than any other technique developed to date. Appropriate training in performing transrectal fine-needle aspiration of the prostate and in interpreting the smears is, of course, essential.¹ Fine-needle aspiration plays a major role in the aforementioned situations in which diagnosis is established from nonprostatic tissue sources, such as lymph nodes and others.^2,3Since the landmark study by Hodge and colleagues⁴ demonstrating the superiority of TRUS guidance compared with digitally guided biopsy, the TRUS-guided biopsy technique has become the worldwide accepted standard in prostate cancer diagnosis. Statistical performance (sensitivity, specificity, positive and negative predictive values) of all other diagnostic tests (eg, DRE and PSA assay) is calculated according to the assignment (cancer present vs absent) made by prostate biopsy. Recognizing the fact that all sampling procedures, including prostate biopsies, incur the risk of returning false-negative results (ie, cancer is present but missed by the biopsies), calculation of the statistical performance characteristics of all other tests using biopsy outcomes as the gold standard are inherently incorrect and biased. Similarly, when comparing the statistical performance of various biopsy strategies, usually the most extensive strategy is chosen as the gold standard to define disease presence or absence, and the performance of all other strategies is calculated on the basis of that particular strategy, again incurring a significant bias due to the remaining falsenegative rate of even the most extensive sampling strategy.     

Transrectal sonography in prostate cancer detection--our 25 years experience of implementation

Prostate cancer is a leading public health problem of male population in developed countries. Gold standard for prostate cancer diagnosis is true cut biopsy guided by transrectal ultrasound. Aim of this study was to determine sensitivity, specificity, accuracy, positive and negative predictive value of transrectal sonography (TRUS) in prostate cancer detection. The analysis was made for two time periods, before and after routine implementation of prostate specific antigen (PSA) in prostate cancer diagnostics. From 1984 to 1993 TRUS guided prostate biopsy was performed in 564, and from 1994 to 2008 in 5678 patients. In the second period PSA was routinely used in prostate cancer diagnostics. In the first period by TRUS we have made an exact diagnosis of prostate cancer in 18.97% of patients what was confirmed by biopsy. 4.61% ware false positive and 11.34% ware false negative. In the second period prostate cancer was recognized in 30.34% of patients, confirmed by biopsy. False positive cases ware 6.11% and false negative 29.31%. Sensitivity of transrectal sonography in the first period was 62.57%, specificity 94.2%, accuracy 86.2%, positive predictive value 80.45% and negative predictive value 87.72%. In the second period sensitivity was 50.87%, specificity 91.93%, accuracy 73.84%, positive predictive value 83.24% and negative predictive value 70.39%. Based on our experience we can conclude that prostate cancer is mostly found in the peripheral zone. Smaller tumors are hypoechoic and bigger tumors are hyperechoic. Prostate cancer lesions are impossible to differentiate from chronic prostatitis only by TRUS. Implementation of PSA has significantly decrease sensitivity, accuracy and negative predictive value of TRUS in prostate cancer detection. TRUS guided true cut biopsy is a gold standard in prostate cancer diagnostics.     

Prostate cancer: risk assessment and diagnostic approaches

The successful treatment of prostate cancer relies on detection of the disease at its earliest stages. Although prostate-specific antigen (PSA)-based screening has been a significant advance in the early diagnosis of prostate cancer, identifying specific genetic alterations in a given family or patient will allow more appropriate screening for early disease. Mapping and identification of specific prostate cancer susceptibility genes is slowly becoming a reality. Other prostate cancer risks include a family history, race, and possibly serum markers such as insulin-like growth factor-I (IGF-I). Once a high-risk man is identified, transrectal ultrasound (TRUS)-guided biopsies are the standard to diagnose prostate cancer. Although TRUS is an advance over traditional digitally directed biopsies, it represents a random sampling of the prostate since most lesions cannot be visualized. Newer modalities such as ultrasound contrast agents, pattern recognition, and artificial neural networks (ANNs), applied to TRUS images, may improve diagnostic accuracy. If a man at risk for prostate cancer has undergone a negative TRUS biopsy, the decision for the need for additional biopsies is problematic. Use of PSA derivatives such as free and total PSA and the initial biopsy abnormalities such as atypia or high-grade prostatic intraepithelial neoplasia may define those patients in need of follow-up biopsy.     

Efficient public verification proof of retrievability scheme in cloud

Cloud storage is an important service of cloud computing. After data file is outsourced, data owner no longer physical controls over the storage. To efficiently verify these data integrity, several Proof of Retrievability (POR) schemes were proposed to achieve data integrity checking. The existing POR schemes offer decent solutions to address various practical issues, however, they either have a non-trivial (linear or quadratic) communication cost, or only support private verification. And most of the existing POR schemes exist active attack and information leakage problem in the data checking procedure. It remains open to design a secure POR scheme with both public verifiability and constant communication cost. To solve the above problems , we propose a novel preserving-private POR scheme with public verifiability and constant communication cost based on end-to-end aggregation authentication in this paper. To resist information leakage, we include zero-knowledge technique to hide the data in the integrity checking process. Our scheme is shown to be secure and efficient by security analysis and performance analysis. The security of our scheme is related to the Computational Diffie–Helleman Problem and Discrete logarithm problem. Finally, we also extend the POR scheme to support multi-file integrity checking and simulation results show that the verifier only needs less computational cost to achieve data integrity checking in our extended scheme.     

Review of the literature: PCA3 for prostate cancer risk assessment and prognostication

Prostate cancer antigen 3 (PCA3) is a novel urine-based prostate cancer biomarker that has recently been studied extensively for the prediction of prostate biopsy results and treatment outcomes. Numerous studies have demonstrated that urinary PCA3 scores are predictive of prostate cancer detection on both initial and repeat biopsy. There is conflicting evidence on the relationship between PCA3 with aggressive tumor features and treatment outcomes. This article reviews the current evidence on PCA3 as a marker for prostate cancer detection and prognosis.     

Computerized planning of prostate cryosurgery using variable cryoprobe insertion depth

The current study presents a computerized planning scheme for prostate cryosurgery using a variable insertion depth strategy. This study is a part of an ongoing effort to develop computerized tools for cryosurgery. Based on typical clinical practices, previous automated planning schemes have required that all cryoprobes be aligned at a single insertion depth. The current study investigates the benefit of removing this constraint, in comparison with results based on uniform insertion depth planning as well as the so-called “pullback procedure”. Planning is based on the so-called “bubble-packing method”, and its quality is evaluated with bioheat transfer simulations. This study is based on five 3D prostate models, reconstructed from ultrasound imaging, and cryoprobe active length in the range of 15-35 mm. The variable insertion depth technique is found to consistently provide superior results when compared to the other placement methods. Furthermore, it is shown that both the optimal active length and the optimal number of cryoprobes vary among prostate models, based on the size and shape of the target region. Due to its low computational cost, the new scheme can be used to determine the optimal cryoprobe layout for a given prostate model in real time.     

Efficient and Anonymous Two-Factor User Authentication in Wireless Sensor Networks: Achieving User Anonymity with Lightweight Sensor Computation

A smart-card-based user authentication scheme for wireless sensor networks (hereafter referred to as a SCA-WSN scheme) is designed to ensure that only users who possess both a smart card and the corresponding password are allowed to gain access to sensor data and their transmissions. Despite many research efforts in recent years, it remains a challenging task to design an efficient SCA-WSN scheme that achieves user anonymity. The majority of published SCA-WSN schemes use only lightweight cryptographic techniques (rather than public-key cryptographic techniques) for the sake of efficiency, and have been demonstrated to suffer from the inability to provide user anonymity. Some schemes employ elliptic curve cryptography for better security but require sensors with strict resource constraints to perform computationally expensive scalar-point multiplications; despite the increased computational requirements, these schemes do not provide user anonymity. In this paper, we present a new SCA-WSN scheme that not only achieves user anonymity but also is efficient in terms of the computation loads for sensors. Our scheme employs elliptic curve cryptography but restricts its use only to anonymous user-to-gateway authentication, thereby allowing sensors to perform only lightweight cryptographic operations. Our scheme also enjoys provable security in a formal model extended from the widely accepted Bellare-Pointcheval-Rogaway (2000) model to capture the user anonymity property and various SCA-WSN specific attacks (e.g., stolen smart card attacks, node capture attacks, privileged insider attacks, and stolen verifier attacks).     

Contrast-enhanced ultrasound imaging of prostate cancer

Ultrasound imaging of the prostate is commonly used to assess the size of the gland and for needle placement during systematic biopsy. Ultrasound evaluation of prostate cancer is limited by difficulty in distinguishing benign from malignant tissue. Although Doppler techniques may provide some improvement in the detection of prostate cancer, targeted biopsy based on conventional ultrasound with Doppler is not sufficient to replace systematic biopsy. Contrast-enhanced ultrasound imaging techniques that employ microbubble contrast agents represent an innovative approach to imaging of the neovascularity associated with prostate cancer. This review describes the application of contrast-enhanced ultrasound to improve detection and assessment of prostate cancer.     

86例超声引导下经会阴前列腺穿刺体会

目的分析86例经直肠超声(TRUS)引导下经会阴前列腺穿刺病理,提高前列腺癌活检阳性率。方法86例(年龄71-89岁,PSA.>10 ng/ml,PSAD>0.3),直肠超声(TRUS)引导下经会阴前列腺穿刺,6+X法。结果前列腺癌39例,前列腺增生46例,前列腺炎1例。前列腺癌阳性中:有可疑病灶32例,无可疑病灶7例,前列腺癌敏感性82%(32/39),其中第二次穿刺病例8例,阳性4例,第三次穿刺2例,阳性2例。结论对70岁以上高老人的前列腺穿刺活检病人,因个性化对待,重点对可疑病灶点和外周带的穿刺。     

On the clinical usefulness of the free-to-total prostate-specific antigen ratio

The free-to-total prostate-specific antigen ratio (F/T PSA) is associated with the presence of prostate cancer and is thus used as an indicator for suspicion of prostate cancer and as a determinant for biopsy. We reviewed a recent retrospective series of 966 consecutive prostate biopsies where F/T PSA was blindly determined and did not influence biopsy indication. We simulated the association of F/T PSA with biopsy outcome and its impact as a biopsy determinant. When adopting an F/T PSA cutoff of 10%, 13%, 16% or 20% among random sextant biopsies in the 4-10 ng/mL total PSA range, the sensitivity was 15%, 37%, 55% and 72% and the specificity 89%, 80%, 64% and 44%, respectively. Using F/T PSA as a biopsy determinant, from 1.7 to 2.6 cancer biopsies would have been delayed to avoid 10 benign biopsies. As this balance is not acceptable, F/T PSA has no role as a biopsy indicator and its clinical use is questionable.     

Is Repeat Biopsy for Isolated High-Grade Prostatic Intraepithelial Neoplasia Necessary?

Numerous studies have cited the positive predictive value of isolated highgrade prostatic intraepithelial neoplasia (HGPIN) to the detection of cancer. Epidemiological, morphological, and molecular data support the potential for malignant transformation of HGPIN, yet no current method can discriminate which lesions will progress to clinically significant prostate cancer versus more latent lesions. Recent analyses of multiple retrospective studies have found similar rates of cancer detection following either diagnosis of isolated HGPIN or an initial negative biopsy. This may reflect increased use of extended biopsy techniques involving 10 or more cores rather than the true ability of HGPIN to undergo malignant transformation. This article discusses controversies surrounding management of an isolated diagnosis of HGPIN and whether repeat biopsy of HGPIN should be mandatory or selective in the context of other predictive values such as rising prostate-specific antigen or lesion on digital rectal examination.     

Novel neutral network approach to call admission control in high-speed networks

This paper presents a novel Call Admission Control (CAC) scheme which adopts the neural network approach, namely Minimal Resource Allocation Network (MRAN) and its extended version EMRAN. Though the current focus is on the Call Admission Control (CAC) for Asynchronous Transfer Mode (ATM) networks, the scheme is applicable to most high-speed networks. As there is a need for accurate estimation of the required bandwidth for different services, the proposed scheme can offer a simple design procedure and provide a better control in fulfilling the Quality of Service (QoS) requirements. MRAN and EMRAN are on-line learning algorithms to facilitate efficient admission control in different traffic environments. Simulation results show that the proposed CAC schemes are more efficient than the two conventional CAC approaches, the Peak Bandwidth Allocation scheme and the Cell Loss Ratio (CLR) upperbound formula scheme. The prediction precision and computational time of MRAN and EMRAN algorithms are also investigated. Both MRAN and EMRAN algorithms yield similar performance results, but the EMRAN algorithm has less computational load.     

Utilization Trends and Positive Biopsy Rates for Prostate Biopsies in the United States: 2005 to 2011

This article assesses the positive biopsy rate and core sampling pattern in patients undergoing needle biopsy of the prostate in the United States at a national reference laboratory (NRL) and anatomic pathology laboratories integrated into urology group practices, and analyzes the relationship between positive biopsy rates and the number of specimen vials per biopsy. For the years 2005 to 2011 we collected pathology data from an NRL, including number of urologists and urology practices referring samples, total specimen vials submitted for prostate biopsies, and final pathologic diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia, or atypical small acinar proliferation. Over the same period, similar data were gathered from urology practices with in-house laboratories performing global pathology services (urology practice laboratories; UPLs) as identified by a survey of members of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials per biopsy were calculated in aggregate and separately for each site of service. From 2005 to 2011, 437,937 biopsies were submitted in > 4.23 million vials (9.4 specimen vials/biopsy); overall positive biopsy rate was 40.3%-this was identical at both the NRL and UPL (P = .97). Nationally, the number of specimen vials per biopsy increased sharply from a mean of 8.8 during 2005 to 2008 to a mean of 10.3 from 2009 to 2011 (difference, 1.5 specimen vials/biopsy; P = .03). For the most recent 3-year period (2009–2011), the difference of 0.6 specimen vials per biopsy between the NRL (10.0) and UPL (10.6) was not significant (P = 0.08). Positive biopsy rate correlated strongly (P < .01) with number of specimen vials per biopsy. The positive prostate biopsy rate is 40.3% and is identical across sites of service. Although there was a national trend toward increased specimen vials per biopsy from 2005 to 2011, from 2009 to 2011 there was no significant difference in specimen vials per biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10 to 12 unique specimen vials has been widely adopted by urologists across sites of service.Key Words: Prostate cancer, Prostate biopsy, Utilization trends, National reference laboratory, Urology practice laboratoriesPublished data over the past decade suggesting that prostate cancer detection rates are enhanced with additional sampling of the prostate have resulted in modifications to the traditional 6-core (sextant) biopsy regimen^1,2 such that recent clinical guidelines recommend that extended biopsy schemes with 10 to 12 specimens be obtained.^3–5 There are also data that suggest that segregation of prostate biopsy tissue specimens into individual vials improves specimen handling, enhances tissue representation, and improves diagnostic accuracy.^6–8 Furthermore, focal prostate cancer treatment strategies gaining recent popularity are dependent on more precise tumor mapping, requiring even greater tissue sampling.⁹Over approximately the same time frame, there has been an increase in consolidation of medical practices into larger single- or multispecialty group practices. By incorporating efficiencies of scale, these groups afford physicians the opportunity to retain the characteristics of traditional medical practices while improving their ability to adapt to changing health care circumstances.¹⁰ These groups often integrate additional capabilities beyond professional services, including anatomic and clinical pathology, diagnostic imaging, and radiation therapy. Proponents of these arrangements argue that integration of medical services facilitates the development of coordinated clinical pathways, improves communication between specialists, offers better quality control of ancillary services, and enhances data collection—all of which can improve patient care and lead to lower costs.^11–13 Specifically with regard to anatomic pathology, recent data suggest that certain specimen handling errors are significantly lower (P = .018) at urology practices with integrated in-house pathology laboratories (urology practice laboratories [UPLs]) than at other sites of service¹⁴; however, some contend that group practice integration creates conflicts of interest and self-referral issues, which ultimately leads to increased utilization of services.^15–19 A recent study based on analysis of Medicare claims data purported that positive prostate biopsy rates and the number of samples submitted per biopsy are significantly different across sites of service²⁰; however, this study has been criticized as both methodologically flawed and scientifically inaccurate.²¹ Also problematic is the fact that calculation of prostate cancer incidence has been identified as particularly susceptible to error when determined by analysis of outpatient claims data alone.²²We sought to determine positive biopsy rates and utilization trends in the United States via direct analysis of laboratory records from both a national reference laboratory (NRL) and UPLs, and to determine if there was a correlation between positive biopsy rates and number of specimen vials submitted.     

Variations in prostate biopsy recommendation and acceptance confound evaluation of risk factors for prostate cancer: Examining race and BMI

BackgroundProstate cancer is ubiquitous in older men; differential screening patterns and variations in biopsy recommendations and acceptance will affect which man is diagnosed and, therefore, evaluation of cancer risk factors. We describe a statistical method to reduce prostate cancer detection bias among African American (n = 3398) and Non-Hispanic White men (n = 22,673) who participated in the Selenium and Vitamin E Cancer Prevention trial (SELECT) and revisit a previously reported association between race, obesity and prostate cancer risk.MethodsFor men with screening values suggesting prostate cancer but in whom biopsy was not performed, the Prostate Cancer Prevention Trial Risk Calculator was used to estimate probability of prostate cancer. Associations of body mass index (BMI) and race with incident prostate cancer were compared for observed versus imputation-enhanced outcomes using incident density ratios.ResultsAccounting for differential biopsy assessment, the previously reported positive linear trend between BMI and prostate cancer in African American men was not observed; no BMI association was found among Non-Hispanic White men.ConclusionsDifferential disease classification among men who may be recommended to undergo and then consider whether to accept a prostate biopsy leads to inaccurate identification of prostate cancer risk factors. Imputing a man’s prostate cancer status reduces detection bias. Covariate adjustment does not address the problem of outcome misclassification. Cohorts evaluating incident prostate cancer should collect longitudinal screening and biopsy data to adjust for this potential bias.     

Operator Dependent Choice of Prostate Cancer Biopsy Has Limited Impact on a Gene Signature Analysis for the Highly Expressed Genes IGFBP3 and F3 in Prostate Cancer Epithelial Cells

Background

Predicting the prognosis of prostate cancer disease through gene expression analysis is receiving increasing interest. In many cases, such analyses are based on formalin-fixed, paraffin embedded (FFPE) core needle biopsy material on which Gleason grading for diagnosis has been conducted. Since each patient typically has multiple biopsy samples, and since Gleason grading is an operator dependent procedure known to be difficult, the impact of the operator''s choice of biopsy was evaluated.

Methods

Multiple biopsy samples from 43 patients were evaluated using a previously reported gene signature of IGFBP3, F3 and VGLL3 with potential prognostic value in estimating overall survival at diagnosis of prostate cancer. A four multiplex one-step qRT-PCR test kit, designed and optimized for measuring the signature in FFPE core needle biopsy samples was used. Concordance of gene expression levels between primary and secondary Gleason tumor patterns, as well as benign tissue specimens, was analyzed.

Results

The gene expression levels of IGFBP3 and F3 in prostate cancer epithelial cell-containing tissue representing the primary and secondary Gleason patterns were high and consistent, while the low expressed VGLL3 showed more variation in its expression levels.

Conclusion

The assessment of IGFBP3 and F3 gene expression levels in prostate cancer tissue is independent of Gleason patterns, meaning that the impact of operator''s choice of biopsy is low.     

Identification of CD166 as a Surface Marker for Enriching Prostate Stem/Progenitor and Cancer Initiating Cells

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model. To further improve this enrichment scheme, we searched for cell surface molecules upregulated upon castration of murine prostate and identified CD166 as a candidate gene. CD166 encodes a cell surface molecule that can further enrich sphere-forming activity of WT LSC(hi) and Pten null LSC(hi). Importantly, CD166 could enrich sphere-forming ability of benign primary human prostate cells in vitro and induce the formation of tubule-like structures in vivo. CD166 expression is upregulated in human prostate cancers, especially CRPC samples. Although genetic deletion of murine CD166 in the Pten null prostate cancer model does not interfere with sphere formation or block prostate cancer progression and CRPC development, the presence of CD166 on prostate stem/progenitors and castration resistant sub-populations suggest that it is a cell surface molecule with the potential for targeted delivery of human prostate cancer therapeutics.     

Prostatic intraepithelial neoplasia: an overview

Prostatic intraepithelial neoplasia (PIN) is the most established precursor of prostatic carcinoma. The presence of prominent nucleoli within an existing duct structure is an easy way to identify the disorder. Four main patterns of high-grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and flat. In addition to exhibiting similar cytologic features, both HGPIN and prostatic carcinoma are associated with increased incidence and severity with age, and with high rates of occurrence in the peripheral zone of the prostate. HGPIN and prostate cancer share genetic and molecular markers as well, with PIN representing an intermediate stage between benign epithelium and invasive malignant carcinoma. The clinical significance of HGPIN is that it identifies patients at risk for malignancy. With the increased use of extended biopsy protocols, clinicians are more likely to identify HGPIN and less likely to miss concurrent carcinoma. Androgen deprivation therapy decreases the prevalence and extent of PIN, and may play a role in chemoprevention. Preliminary studies suggest that selective estrogen receptor modulators may also prevent the progression of HGPIN to prostate cancer.     

PCG-Cut: Graph Driven Segmentation of the Prostate Central Gland

Prostate cancer is the most abundant cancer in men, with over 200,000 expected new cases and around 28,000 deaths in 2012 in the US alone. In this study, the segmentation results for the prostate central gland (PCG) in MR scans are presented. The aim of this research study is to apply a graph-based algorithm to automated segmentation (i.e. delineation) of organ limits for the prostate central gland. The ultimate goal is to apply automated segmentation approach to facilitate efficient MR-guided biopsy and radiation treatment planning. The automated segmentation algorithm used is graph-driven based on a spherical template. Therefore, rays are sent through the surface points of a polyhedron to sample the graph’s nodes. After graph construction – which only requires the center of the polyhedron defined by the user and located inside the prostate center gland – the minimal cost closed set on the graph is computed via a polynomial time s-t-cut, which results in the segmentation of the prostate center gland’s boundaries and volume. The algorithm has been realized as a C++ module within the medical research platform MeVisLab and the ground truth of the central gland boundaries were manually extracted by clinical experts (interventional radiologists) with several years of experience in prostate treatment. For evaluation the automated segmentations of the proposed scheme have been compared with the manual segmentations, yielding an average Dice Similarity Coefficient (DSC) of 78.94±10.85%.