Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation and Promotes Infection.

Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures. We identified fundamental macrophage reprogramming events that parallel E-cadherin-dependent mesenchymal-epithelial transitions. Macrophage-specific disruption of E-cadherin function resulted in disordered granuloma formation, enhanced immune cell access, decreased bacterial burden, and increased host survival, suggesting that the granuloma can also serve a bacteria-protective role. Granuloma macrophages in humans with tuberculosis were similarly transformed. Thus, during mycobacterial infection, granuloma macrophages are broadly reprogrammed by epithelial modules, and this reprogramming alters the trajectory of infection and the associated immune response.

Can Radiologic Staging With Multiparametric MRI Enhance the Accuracy of the Partin Tables in Predicting Organ-Confined Prostate Cancer?

OBJECTIVE: The purpose of this study is to investigate the accuracy of multiparametric MRI with endorectal coil and Partin tables in predicting organ-confined (OC) prostate cancer in a contemporary cohort undergoing radical prostatectomy (RP) and to assess the possible added value of radiologic staging based on multiparametric MRI to the predictive accuracy of Partin tables. MATERIALS AND METHODS: One hundred fifty-eight consecutive subjects underwent 3-T multiparametric MRI with endorectal coil before RP between November 2010 and November 2013. Data were randomly split 60% and 40% into derivation (n = 95) and validation (n = 62) datasets. Multiparametric MRI was used to assess the radiologic stage, and logistic regression models were created using the derivation dataset and were fit on the independent validation dataset using multiparametric MRI staging alone and with prostate-specific antigen (PSA) level as the covariate. The probability of each patient to harbor OC disease was calculated using an updated version of Partin tables, using either clinical staging from digital rectal examination (DRE) or radiologic staging (multiparametric MRI). The AUC was calculated to evaluate accuracy of these predictive methods. RESULTS: The accuracy of multiparametric MRI to predict OC disease on pathologic analysis was greater (AUC, 0.88) than that of Partin tables (AUC, 0.70) and improved when multiparametric MRI was combined with PSA level (AUC, 0.91). The accuracy of Partin nomograms to predict OC disease decreased (AUC, 0.63) when staging was based on multiparametric MRI versus DRE. CONCLUSION: The superior predictive accuracy of multiparametric MRI compared with Partin tables to predict OC disease validates the results of smaller previously published studies. Although there is no added benefit of substituting multiparametric MRI stage for clinical stage when using Partin tables, multiparametric MRI staging information is valuable as a stand-alone test.

Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

OBJECTIVE: The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. MATERIALS AND METHODS: The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. RESULTS: The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 ± 197 × 10(-6) mm(2)/s) and benign TZ (1429 ± 180 × 10(-6) mm(2)/s). Although the ADC of index tumors (1042 ± 134 × 10(-6) mm(2)/s) was significantly lower (p = 0.002) than the ADC of benign CZ there was no significant difference (p = 0.225) between benign CZ and tumors with a Gleason score of 6 (1119 ± 87 × 10(-6) mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors with a Gleason score greater than 6, the ADC was lower in benign CZ than in the index tumor. The AUC of ADC for the differentiation of benign CZ from index tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

Small renal mass biopsy--how, what and when: report from an international consensus panel.

To discuss the use of renal mass biopsy (RMB) for small renal masses (SRMs), formulate technical aspects, outline potential pitfalls and provide recommendations for the practicing clinician. The meeting was conducted as an informal consensus process and no scoring system was used to measure the levels of agreement on the different topics. A moderated general discussion was used as the basis for consensus and arising issues were resolved at this point. A consensus was established and lack of agreement to topics or specific items was noted at this point. Recommended biopsy technique: at least two cores, sampling different tumour regions with ultrasonography being the preferred method of image guidance. Pathological interpretation: 'non-diagnostic samples' should refer to insufficient material, inconclusive and normal renal parenchyma. For non-diagnostic samples, a repeat biopsy is recommended. Fine-needle aspiration may provide additional information but cannot substitute for core biopsy. Indications for RMB: biopsy is recommended in most cases except in patients with imaging or clinical characteristics indicative of pathology (syndromes, imaging characteristics) and cases whereby conservative management is not contemplated. RMB is recommended for active surveillance but not for watchful-waiting candidates. We report the results of an international consensus meeting on the use of RMB for SRMs, defining the technique, pathological interpretation and indications.

Bone marrow biopsy: RNA isolation with expression profiling in men with metastatic castration-resistant prostate cancer--factors affecting diagnostic success.

PURPOSE: To determine the rate at which computed tomographically guided pelvic percutaneous bone biopsy in men with metastatic castration-resistant prostate cancer (mCRPC) yields adequate tissue for genomic profiling and to identify issues likely to affect diagnostic yields. MATERIALS AND METHODS: This study was institutional review board approved, and written informed consent was obtained. In a phase II trial assessing response to everolimus, 31 men with mCRPC underwent 54 biopsy procedures (eight men before and 23 men both before and during treatment). Variables assessed were lesion location (iliac wing adjacent to sacroiliac joint, iliac wing anterior and/or superior to sacroiliac joint, sacrum, and remainder of pelvis), mean lesion attenuation, subjective lesion attenuation (purely sclerotic vs mixed), central versus peripheral lesion sampling, lesion size, core number, and use of zoledronic acid for more than 1 year. RESULTS: Of 54 biopsy procedures, 21 (39%) yielded adequate tissue for RNA isolation and genomic profiling. Three of four sacral biopsies were adequate. Biopsies of the ilium adjacent to the sacroiliac joints were more likely adequate than those from elsewhere in the ilium (48% vs 28%, respectively). All five biopsies performed in other pelvic locations yielded inadequate tissue for RNA isolation. Mean attenuation of lesions with inadequate tissue was 172 HU greater than those with adequate tissue (621.1 HU ± 166 vs 449 HU ± 221, respectively; P = .002). Use of zoledronic acid, peripheral sampling, core number, and lesion size affected yields, but the differences were not statistically significant. Histologic examination with hematoxylin-eosin staining showed that results of 36 (67%) biopsies were positive for cancer; only mean attenuation differences were significant (707 HU ± 144 vs 473 HU ± 191, negative vs positive, respectively; P < .001). CONCLUSION: In men with mCRPC, percutaneous sampling of osseous metastases for genomic profiling is possible, but use of zoledronic acid for more than 1 year may reduce the yield of adequate tissue for RNA isolation. Sampling large low-attenuating lesions at their periphery maximizes yield.

Appropriate and safe utilization of helicopter emergency medical services: a joint position statement with resource document.

This position statement with accompanying resource document is the result of a collaborative effort of a writing group comprised of members of the Air Medical Physician Association (AMPA), the American College of Emergency Physicians (ACEP), the National Association of EMS Physicians (NAEMSP), and the American Academy of Emergency Medicine (AAEM). This document has been jointly approved by the boards of all four organizations. Patients benefit from the appropriate utilization of helicopter emergency medical services (HEMS). EMS and regional health care systems must have and follow guidelines for HEMS utilization to facilitate proper patient selection and ensure clinical benefit. Clinical benefit can be provided by Meaningfully shortening the time to delivery of definitive care to patients with time-sensitive medical conditions Providing necessary specialized medical expertise or equipment to patients before and/or during transport Providing transport to patients inaccessible by other means of transport The decision to use HEMS is a medical decision, separate from the aviation determination whether a transport can be completed safely. Physicians with specialized training and experience in EMS and air medical transport must be integral to HEMS utilization decisions, including guideline development and quality improvement activities. Safety management systems must be developed, adopted, and adhered to by air medical operators when making decisions to accept and continue every HEMS transport. HEMS must be fully integrated within the local, regional, and state emergency health care systems. HEMS programs cannot operate independently of the surrounding health care environment. The EMS and health care systems must be involved in the determination of the number of HEMS assets necessary to provide appropriate coverage for their region. Excessive resources may lead to competitive practices that can affect utilization and negatively impact safety. Inadequate resources will delay receipt of definitive care. National guidelines for appropriate utilization of HEMS must be developed. These guidelines should be national in scope yet allow local, regional, and state implementation. A National HEMS Agenda for the Future should be developed to address HEMS utilization and availability and to identify and support a research strategy for ongoing, evidence-based refinement of utilization guidelines.

Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly.

Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved.

Clinical predictors of renal mass pathological features.

OBJECTIVE: • To evaluate the influence of radiographic tumour size and other preoperative variables on the pathological characteristics of the lesion to determine the distribution of pathological features and assess preoperative risk factors for potentially aggressive versus probably indolent renal lesions. PATIENTS AND METHODS: • Retrospective review of records for 768 patients who underwent surgery for single, sporadic renal mass between 2000 and 2008 in a tertiary academic institution. • Demographic, radiographic and pathological variables were recorded and analysed with regression analyses for risk factors for potentially aggressive pathological features (malignant pathology, high Fuhrman grade, lymphovascular invasion and extracapsular extension). RESULTS: • Malignancy was pathologically confirmed in 628 (81.8%) specimens. • Radiographic size was significantly associated with malignancy (versus benign pathology; OR = 1.13, P= 0.001), high Fuhrman grade (OR = 1.21, P < 0.0001), vascular invasion (OR = 1.19, P < 0.0001) and extracapsular extension (OR = 1.23, P < 0.0001). • Age, symptomatic presentation, solid appearance and radiographic size were independent predictors of potentially aggressive disease, whereas for male gender (OR = 1.43, P= 0.062) a trend toward statistical significance was noted. CONCLUSIONS: • Age, male gender, radiographic size and appearance, as well as symptomatic presentation, are associated with an increased risk of malignant, potentially aggressive disease. • These factors should be considered when evaluating management options for a solitary enhancing renal mass.

Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer.

PURPOSE: Radical prostatectomy is potentially curative in patients with clinically localized prostate cancer. However, biochemical recurrence affects 15% to 30% of men who undergo radical prostatectomy. We previously reported the prognostic potential of PITX2 gene promoter methylation using conventional assays. In the current study we validated PITX2 methylation status as a biochemical recurrence predictor after radical prostatectomy using a novel microarray based platform in a multi-institutional setting. MATERIALS AND METHODS: PITX2 methylation status was assessed in formalin fixed, paraffin embedded prostatectomy tumor tissue samples from 476 patients from a total of 4 institutions on customized EpiChip PITX2 microarrays. Associations between PITX2 methylation and biochemical recurrence were assessed using the log rank test and Cox regression controlling for prostate cancer features. RESULTS: On multivariate analysis men with high methylation status were at significantly higher risk for biochemical recurrence than those with low methylation status (HR 3.0, 95% CI 2.0-4.5, p <10(-5)). The biochemical recurrence-free survival rate 5 years after surgery was 85% and 61% in the low and high methylation groups, respectively. In men with pathological Gleason 7 tumors the relative risk of biochemical recurrence was twice as high for high than for low PITX2 methylation (HR 2.0, 95% CI 1.2-3.3, p = 0.005). CONCLUSIONS: PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.

Metastatic Urothelial Carcinoma from Transplanted Kidney with Complete Response to an Immune Checkpoint Inhibitor.

BACKGROUND: Donor-derived malignancy is a rare complication in patients who undergo organ transplant. Approaches to treatment have largely been individualized based on clinical circumstances given the lack of evidence-based guidelines, with therapeutic options ranging from discontinuation of immunosuppression and transplantectomy to the addition of chemotherapy or radiotherapy. Case Presentation. Herein, we describe a 60-year-old woman with metastatic donor-derived upper tract urothelial carcinoma (UTUC) discovered nine years postrenal transplant. Molecular diagnostic studies using polymerase chain reaction amplification of short tandem repeat alleles and HLA tissue typing proved that the urothelial carcinoma originated from donor tissue. She achieved sustained complete remission with transplant nephroureterectomy, retroperitoneal lymphadenectomy, immunosuppression withdrawal, and immunotherapy with pembrolizumab. Routine radiologic surveillance has demonstrated 15-month progression-free survival to date off pembrolizumab, and she is now under consideration for retransplantation. CONCLUSIONS: Immunotherapy using checkpoint inhibitors can serve as a novel treatment option for patients in the clinical predicament of having a solid organ transplant and simultaneous metastatic malignancy. In this report, we also discuss the oncogenic potential of BK virus, the use of checkpoint inhibitors in urothelial carcinoma, and the feasibility of retransplant for this patient population.

Phase 2 clinical trial of TORC1 inhibition with everolimus in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Activation of the PI3K-Akt-mTOR signaling pathway is common in advanced castration resistant prostate cancer (CRPC), typically through PTEN loss. Preclinical studies suggest that Akt-driven CaP cells are genetically susceptible to mammalian target of rapamycin (mTOR, or TORC1) inhibition. Everolimus is a Food and Drug Administration-approved inhibitor of TORC1. MATERIALS AND METHODS: We performed a phase II study of everolimus in patients with mCRPC, who were refractory to standard of care hormonal and chemotherapeutic agents. Patients received everolimus 10 mg daily until unacceptable adverse events or disease progression. The primary efficacy outcome was confirmed 50% or greater prostate-specific antigen (PSA) response, using a 2 stage design with futility rules. Paired biopsies were utilized to assess for treatment effect on downstream TORC1 targets as well as tumor cell proliferation and apoptosis. RESULTS: Out of 35 men enrolled with heavily pretreated mCRPC, 32 were evaluable for clinical efficacy. No PSA responses were observed, the median progression-free survival time was 3.6 months (95% confidence interval = 2.9-4.8) and the median overall survival time was 10.4 months (95% confidence interval = 5.8-15.8). Several patients had declines in serum PSA upon cessation of everolimus. Thus, the study was closed due to clinical futility. The most common toxicities were mucositis, fatigue, anorexia, hypertriglyceridemia, and thrombocytopenia and were largely low grade. Pathologic evaluation of paired metastatic biopsies demonstrated consistent inhibition of pS6, a downstream mTOR pharmacodynamics biomarker, but the tumor proliferation marker Ki-67 increased with therapy. CONCLUSIONS: Everolimus demonstrated predictable toxicity in advanced and heavily pretreated patients with mCRPC. No clinical or clear pathologic effects despite downstream TORC1 target inhibition, suggesting that single agent everolimus has no clinical utility in men with mCRPC.

Use of 111in-capromab pendetide immunoscintigraphy to image localized prostate cancer foci within the prostate gland.

PURPOSE: We compared the results of a preoperative (111)In-capromab pendetide scan co-registered with computerized tomography with pathological findings in the surgically excised prostate to determine whether the scan can efficiently detect cancer in the prostate. MATERIALS AND METHODS: This prospective trial included 25 hormone naïve men with clinically localized prostate cancer who underwent (111)In-capromab pendetide single photon emission computerized tomography/computerized tomography as part of the preoperative evaluation. In addition to routine histological analysis, representative prostate sections were stained for prostate specific membrane antigen using the same antibody used in the scan. A pathologist and a radiologist were blinded to pathology and imaging findings, respectively. Prostate specific membrane antigen immunohistochemistry was correlated with the 3-dimensional location of the prostate specific membrane antigen signal detected by scan. RESULTS: Scan sensitivity was 37% to 87% for 4 quadrants (right vs left and apical vs basal) with 0% to 50% specificity, as validated by final pathological assessment of the same quadrants. Stratifying positive scan signal strength did not statistically improve specificity (p = 0.35). There was no significant correlation between prostate specific membrane antigen over expression and tumor stage distribution (p = 0.23). CONCLUSIONS: The scan did not localize prostate cancer to a particular quadrant based on comparison with radical prostatectomy specimen pathology. The antibody used has affinity for benign and malignant prostatic glands in excised, formalin fixed prostate tissue, which may contribute to low scan specificity in vivo. The scan cannot be used to reliably detect or image cancer foci in the prostate.

Focal therapy for prostate cancer: pathologic basis.

PURPOSE OF REVIEW: To summarize pathologic features of low-volume, low-risk prostate cancer relevant to the development of patient selection criteria and treatment strategies for focal therapy of prostate cancer, as an alternative to whole-gland radical treatments. RECENT FINDINGS: Prostate cancer characteristically presents as a multifocal lesion within the prostate gland. Diagnosis of prostate cancer at an early stage has led to a recognition of subsets of patients whose disease may be either unifocal or multifocal, yet is unilateral or of small aggregate volume. Parenchyma-preserving partial-gland ablation may become a potentially feasible option in future treatment of early-stage, localized prostate cancer. CONCLUSION: Even for moderately selective protocols such as hemiablation, however, appropriate patient selection will be challenging because of the imperfect correlation among unifocality, unilaterality, low volume and low grade. Extended multicore biopsy protocols under imaging guidance may be required to map the tumor process with sufficient accuracy for treatment planning. Further research in molecular determinants and more precise imaging techniques should be pursued to optimize selection and treatment.

Utility of a 3-dimensional transrectal ultrasound-guided prostate biopsy system for prostate cancer detection.

The 3-D transrectal ultrasound (TRUS)-guided prostate biopsy system is a novel device that allows precise needle placement in a template fashion. We evaluate its utility for prostate cancer (PCa) detection. A retrospective analysis was performed evaluating 68 prospective patients at the Duke Prostate Center who underwent a prostate biopsy using a 3-D TRUS-guided system. After creation of a three-dimensional map of the prostate, a computer algorithm identified an ideal biopsy scheme based on the measured dimensions of the prostate. The system then used a fixed template that allowed prostate biopsy at specific locations with the ability to target the same region of the prostate in the future if needed. For all patients, a 12-core biopsy pattern was used to cover medial and lateral areas of the base, mid-gland, and apex. In total, 68 patients underwent 3-D TRUS-guided prostate biopsies between April 2006 and November 2007 for prostate cancer detection. The indication for prostate biopsy was PSA > or = 4.0 ng/ml in 47 (69%) patients, abnormal digital rectal examination (DRE) in 17 (25%), and atypia on previous biopsy in 4 (6%) patients. Prostate cancer was detected in 18 patients (26.5%) and 7 (10.3%) had atypical small acinar proliferation (ASAP). The highest frequency (55.5%) from all cases of cancer detected was identified when 3-D TRUS biopsy was used as the initial biopsy. This study demonstrates that a 3-D TRUS-guided biopsy system translates to a more frequent detection of prostate cancer among patients undergoing an initial prostate biopsy than a subsequent one. More comprehensive studies are warranted to corroborate and extend the results of this study.

Utilization of (111)In-Capromab pendetide SPECT-CT for detecting seminal vesicle invasion with recurrent prostate cancer after primary in situ therapy.

The aim of this study was to evaluate the diagnostic value of a hybrid (111)In-capromab pendetide fused computed tomography (CT) scan in detecting seminal vesicle invasion (SVI) in the setting of recurrent prostate cancer following primary in situ therapy. The study population comprised 59 patients, who biochemically failed primary in situ treatment based on American Society for Therapeutic Radiology and Oncology criteria. The patients underwent an (111)In-capromab pendetide/CT scan at the time of biochemical failure with a prostate (12-core) and seminal vesicle (SV) (8-core) biopsy. The diagnostic properties of the scan and magnetic resonance imaging (MRI) in detecting SVI compared to an SV biopsy were calculated. In total, eight (14%) patients had a positive SV biopsy after primary in situ prostate cancer treatment. Nine (15%) patients had positive uptake of the scan in the SV. When comparing the SV scan results to the SV biopsy, the sensitivity, specificity, positive predictive value, and negative predictive value were 37.5%, 88.2%, 33.3%, and 90.0% (95% confidence interval: 0.44-0.81), respectively. In contrast, the ability of MRI to detect SVI was 50.0%, 81.3%, 40.0%, and 86.7% (95% confidence interval: 0.46-0.85), respectively. Although the sensitivity and positive predictive value of the (111)In-capromab pendetide/CT scan are low, its specificity and negative predictive value are high. Based on these findings, the ability of the (111)In-capromab pendetide/CT scan to detect SVI seems to be comparable with MRI.

Pathologic stage T2a and T2b prostate cancer in the recent prostate-specific antigen era: implications for unilateral ablative therapy.

BACKGROUND: Early detection of small volume prostate cancer (PCa) has led to the concept of focal therapy to treat in an organ-sparing manner. We evaluated trends in pathologic staging among patients with localized PCa undergoing radical prostatectomy (RP), defining the frequency of unilateral cancers during 1988-1995, 1996-2000 and 2001-2006. METHODS: Data were abstracted from the Duke Prostate Cancer Outcome database selecting 3,676 men with available pathology treated with RP. Based on surgical pathology, trends in as pathological T (pT) stage, pathological Gleason Score (pGS), and percent tumor involvement (PTI) were evaluated. RESULTS: pT2a increased from 2.8% of men undergoing RP in 1988-1995 to 13.0% during 2001-2006 (P < 0.0005). PTI analysis shifted towards low volume disease, e.g. PTI

Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery.

BACKGROUND: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. METHODS: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and low-density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. RESULTS: Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67-positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) versus 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serologic endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P = 0.048). CONCLUSIONS: Findings suggest that flaxseed is safe and associated with biological alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.

Low-Grade Papillary Schneiderian Carcinoma of the Sinonasal Cavity and Temporal Bone.

OBJECTIVES:: The aim of this study was to further characterize a newly described neoplasm, low-grade papillary Schneiderian carcinoma, occurring simultaneously in the sinonasal cavity and mastoid. Additionally, the authors review the only 2 similar cases within the literature and describe the common clinical features, radiographic findings, and pathologic characteristics of this exceptionally rare disease process. METHODS:: Chart review for single patient, review of literature. RESULTS:: The patient presented with bilateral nasal obstruction. Computed tomography revealed a left sinonasal mass with skull base hyperostosis, and follow-up magnetic resonance imaging showed a concomitant olfactory groove meningioma. Examination showed a bilateral, completely obstructing sinonasal mass with skip areas, and biopsy confirmed inverted papilloma (human papilloma virus strains 16 and 18 indeterminate). The patient underwent bilateral endoscopic sinus surgery, left medial maxillectomy, and left partial nasopharyngectomy. Given her multifocal disease, she was advised that she would require additional excision, but was lost to follow up. One year later she developed acute left facial paralysis. Magnetic resonance imaging demonstrated an enhancing mass in the left mastoid with enhancement along the Eustachian tube in addition to her known recurrent sinonasal disease. Simultaneous endoscopic sinus surgery and mastoidectomy were performed. Polypoid tissue was removed from the nasopharynx, mesotympanum, epitympanum, and retrofacial air cells. Immunohistochemistry showed that cells stained positive for p63 and dermCK and negative for synaptophysin. Morphologically, cells were bland, without classic stromal invasion, retaining their smooth, cystic, and papillary features, despite their increased depth within the tissue. Upon further review and consultation with an outside pathologist, a diagnosis of low-grade papillary Schneiderian carcinoma was made. The patient was referred for radiation therapy and is disease free at 3-month follow-up, with return of her facial function. CONCLUSIONS:: This case represents the first report of concurrent low-grade papillary Schneiderian carcinoma of both the nasal cavity and mastoid. It emphasizes the importance of recognizing this new entity through pathologic analysis and suspecting it when the clinical course does not follow an expected pattern.

Analysis of laterality and percentage of tumor involvement in 1386 prostatectomized specimens for selection of unilateral focal cryotherapy.

In total, 1386 paraffin embedded radical prostatectomy specimens from patients with clinically localized prostate cancer (PCa) excised between 2002-06 were analyzed. Pathologic assessment paid particular attention to laterality and percentage of tumor involvement (PTI) along with pathologic Gleason Score (pGS). Completely unilateral cancers were identified in 254 (18.3%) patients, and in 39% cases of them the signs of clinically significant PCa were revealed. The majority of unilateral tumors (72%) were low volume with a PTI of < or =5. This study suggests that only a select group of men diagnosed with PCa have completely unilateral cancers that would be amenable to focal ablation therapy targeting 1 lobe. Further study is needed to develop predictive models for those patients likely to have small, unilateral cancers that may be amenable to focal therapy.

Malignant cystic nephroma.

AIM: To describe a malignant cystic nephroma in an asymptomatic man. METHODS: Case report and review of the literature. RESULTS: A 60 year old white male presented with an incidentally discovered right perirenal mass. An MRI demonstrated a large perinephric encapsulated mass with diffuse heterogeneity. Patient underwent a radical nephrectomy and retroperitoneal node dissection. Histopathological analyses of the resected specimen revealed malignant cystic nephroma. CONCLUSION: This represents the first published report of this rare tumor in an adult patient.