Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

Peripheral neural lesion-induced stress urinary incontinence in anaesthetized female cats

OBJECTIVES

To characterize the effect of acute unilateral and bilateral lesion of the pelvic and pudendal nerves, and nerves innervating the iliococcygeous and pubococcygeous muscles during sneezing in anaesthetized female cats, on intravesical pressure (IVP), urethral pressure (UPs) and external urethral sphincter (EUS) activity.

MATERIALS AND METHODS

In seven anaesthetized female cats UPs along the urethra (UPs1–4) and IVPs were recorded in the emptied bladder during sneezing before and after unilateral and then bilateral peripheral neural lesions. UPs were measured using microtip transducer catheters with UP4 positioned in the distal urethra where the EUS is located. Urine leakage was also noted, after urethral catheter removal and bladder filling.

RESULTS

During sneezing, in intact cats, the magnitude of UP4 was larger than those of IVP and UPs1–3. The area under the curve of both anal sphincter and EUS electromyography was increased. There was no urine leakage. After unilateral neural lesions, the mean magnitude of response was similar all along the urethra and in the bladder. The distal UP response was significantly lower than that recorded in intact cats. In addition, there was urine leakage in six of the seven cats. Bilateral neural lesions caused permanent urine leakage and significant decreases in all the UP responses.

CONCLUSION

In female cats, during sneezing, neurally driven reflex contractions of EUS leading to an increase in distal UP contribute to active urethral closure mechanisms and ensure urinary continence.     

Chondroid cystic malformation of the lung with trisomy 8 mosaicism: a new cystic lung malformation

Neonatal cystic disorders of the lungs are a heterogeneous malformative group including giant lobar hyperinflation, congenital pulmonary airway malformations, intralobar pulmonary sequestration, and bronchogenic cyst. Here, we describe a giant cystic pulmonary malformation in a 5-year-old girl, morphologically characterized by a highly disorganized proliferation of numerous cartilage islands, abundant mesenchymal tissue with abundant adipose differentiation, and epithelium-lined cysts. Cytogenetic analysis revealed an isolated trisomy 8, as the sole karyotype anomaly, a finding further confirmed by a whole-genome single nucleotide polymorphism array genotyping. The trisomy 8 was observed by fluorescent in situ hybridization within the malformation, and also in adjacent pulmonary parenchyma. A search of the literature revealed only 2 cases having similarities with the present case, but bearing different names. We believe that this lesion differs from congenital pulmonary airway malformations and from adult-type pulmonary hamartomas. We propose for this malformative mass the name "chondroid cystic malformation of the lung."     

Osteoblastoma in the skeletally immature

BACKGROUND: Osteoblastoma is a rare benign and sometimes locally aggressive tumor with peak incidence in the second decade. None of the available series addresses specifically the differences in presentation, management, and outcome between the pediatric and adult patient populations. METHODS: The medical records and radiographs of all children diagnosed with osteoblastoma during a 17-year period were reviewed. We recorded demographic information, time until diagnosis, location, clinical and radiographic characteristics, treatment, complications, and outcome at a minimum 2-year follow-up (range, 2-5 years). RESULTS: Seventeen children met the inclusion criteria. There were 10 boys and 7 girls, with an average age at diagnosis of 11 years (range, 20 months-15 years). The average time delay between onset of symptoms and diagnosis was 6.5 months (range, 2 months-2 years). There were 7 lesions in the lower extremity, 5 in the spine, 4 in the upper extremity, and 1 in the sternum. Pain at the tumor site was present in all cases. Two of the 5 patients with spine lesion had scoliosis. All patients underwent open incisional biopsy with intraoperative frozen section. In 16 cases, this was followed by a 4-step approach (extended curettage, high-speed burring, electrocauterization of cavity wall, and phenol 5% solution). Four of the 5 patients with spine lesions had instrumented posterior spine fusion after tumor removal. Two patients were referred to our institution with recurrent lesion after surgery elsewhere. Only 1 (6%) of 15 children initially treated at our institution had recurrence. All recurrences occurred in children younger than 6 years; all were successfully treated with a 4-step approach. CONCLUSIONS: Osteoblastomas can be successfully treated with a 4-step approach. Children younger than 6 years may have a higher likelihood of recurrence.     

Immediate skin-sparing mastectomy reconstruction with deep inferior epigastric perforator (DIEP) flap. Technical aspects and outcome

Although breast reconstruction with deep inferior epigastric perforator (DIEP) flap is a well-described technique, few publications have specifically reported the technical aspects and the outcome following skin-sparing mastectomy (SSM). The aim of this study is to analyse the feasibility of its immediate application and to describe the operative planning, outcome and complications after SSM. 27 patients underwent 30 DIEP flap breast reconstructions with all immediate and 3 bilateral. Mean time of follow-up was 29 months. Breast skin, DIEP Flap and donor-site complications were evaluated. Information on patient satisfaction was collected. 70% had tumors measuring 2 cm or less (T1) and 74% were stage 0 and I according to American Joint Committee on Cancer. Breast skin complications occurred in 7.4%, all represented by small areas of skin necrosis. Partial losses were observed in two (7.4%) patients (less than 15% of total area) and total DIEP loss in 1 (3.7%). Donor-site complications represented by bulging occurred in only one patient (3.7%). The majority of patients were either very satisfied or satisfied. One local recurrence was observed. All complications except 2 were treated by a conservative approach. The DIEP flap is a reliable technique for SSM reconstruction. Success depends on patient selection, coordinated planning with the oncologic surgeon and careful intraoperative and postoperative management. The main advantage is that patients can safely undergo dual procedures with the added aesthetic benefits in breast and abdominal donor site.     

Microvascular tumor invasion, tumor size and Fuhrman grade: a pathological triad for prognostic evaluation of renal cell carcinoma

PURPOSE: The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. MATERIALS AND METHODS: We studied 230 patients with renal cell carcinoma (stages T(1-4) N(x) M(0)) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. RESULTS: The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. CONCLUSIONS: Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma.     

The combination of antagonists of LHRH with antagonists of GHRH improves inhibition of androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancers

BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) could extend the duration of response of androgen sensitive prostate cancers to androgen deprivation. METHODS: We investigated the effect of new GHRH antagonists MZ-J-7-118 and MZ-J-7-138 and luteinizing hormone-releasing hormone (LHRH) antagonist Cetrorelix or castration on androgen sensitive MDA-PCa-2b and LuCaP-35 prostate cancer models xenografted into nude mice. Animals bearing androgen-independent LuCaP-35V prostatic cancer model were also treated with MZ-J-7-118. RESULTS: Receptors for LHRH and GHRH were present in MDA-PCA-2b, LuCaP-35, and LuCaP-35V tumors. GHRH antagonists increased the inhibitory effect of surgical castration and LHRH antagonists on androgen sensitive MDA-PCa-2b and LuCaP-35 tumors. The time to relapse of androgen-dependent LuCaP-35 tumors was extended by GHRH antagonists. Growth of androgen-independent LuCaP-35V xenografts was also significantly inhibited by MZ-J-7-118. In MDA-PCa-2b tumors treatment with MZ-J-7-118 caused a significant decrease of VEGF and Cetrorelix or its combination with MZ-J-7-118 reduced EGF. The B(max) of EGF receptors was significantly reduced by Cetrorelix, MZ-J-7-118 and their combination. CONCLUSIONS: Our findings suggest that the use of a combination of antagonists of GHRH and LHRH could improve the therapy for androgen sensitive prostate cancer. Antagonists of GHRH could be also considered for treatment of androgen-independent prostate cancers.     

Predicting the outcome of physeal fractures of the distal femur

BACKGROUND:: Distal femoral epiphyseal fractures are uncommon but have a high incidence rate of complications. It is not clear whether there are any reliable predictor factors and whether the type of fracture, displacement (degree and direction), and treatment method alter the outcome. METHODS:: We retrospectively reviewed the medical charts and images of all patients who sustained a distal femoral epiphyseal fracture and were treated at 2 large level I pediatric centers during the past 10 years. RESULTS:: The selected group included 73 patients (boys, 59; mean age, 10 years). On the basis of the Salter-Harris classification (SH), 43 fractures (59%) were of type II. Fifty-nine percent of the fractures were displaced; 36 fractures were managed conservatively with long leg cast (with or without pelvic band) in 33 patients, cylinder cast in 2, and posterior splint in 1. Thirty-seven patients underwent surgery, and 34 underwent closed reduction followed by percutaneous fixation (crossed Steinman pins, 20; cannulated screws, 13; open reduction, 3; external fixation, 1). The overall complication rate was 40% (29/73), and growth arrest was the most frequent. The SH classification significantly correlated with the incidence of complications (P = 0.031). There was also a significantly higher (P < 0.0001) incidence rate of complications among displaced fractures (48.8% vs 26.6%); the amount and direction of displacement did not correlate with the outcome (P > 0.05). The group treated conservatively had a lower incidence rate of complications (25%) than did the surgical group (54%) (P < 0.05). Among the surgical group, a higher incidence rate of complications occurred when the physis was violated by hardware (65% vs 30%; P = 0.06). CONCLUSIONS:: Both SH classification and displacement of the fracture are significant predictors of the final outcome. The degree and the direction of displacement do not statistically correlate with outcome. The treatment method may influence the final outcome.     

Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: new insights from anatomic study

OBJECTIVE: The purpose of this study was to analyze the behavior of the mitral valve ring and the left ventricle in dilated cardiomyopathy. METHODS: We analyzed 68 fixed adult human hearts, divided into 48 hearts with dilated cardiomyopathy of ischemic or idiopathic origin and 20 hearts free of pathologic heart conditions. Digital images of the mitral ring perimeter, attachment of the anterior and posterior leaflets, and fibrous and muscular portions were collected. We also measured the internal perimeter of the left ventricle, the distance from the septum to the anterior and posterior papillary muscles, the distance between the papillary muscles, and the extension of interventricular septum. RESULTS: The analysis of the results showed proportional distribution of the ring's fibrous portion (r2 = 0.98) and muscular portion (r2 = 0.99) according to the degree of mitral valve dilation. Linear regression revealed that the perimeters of anterior and posterior leaflet attachments (r2 = 0.96 and r2 = 0.98, respectively) also had a proportional relation. We did not observe proportionality between the degree of dilation of the mitral ring and the left ventricle. It was observed that dilation of the left ventricle takes place globally in its segments. CONCLUSION: Differently from what was thought, in ischemic or idiopathic dilated cardiomyopathy, dilation of mitral ring is proportional and does not exclusively affect the posterior portion. The degree of left ventricular dilation does not determine the degree of dilation of the mitral ring because they are independent processes. These observations shed new light on the techniques used to correct mitral valve insufficiency in dilated cardiomyopathy.     

The impact of a cardioprotective protocol on the incidence of cardiac complications after aortic abdominal surgery

We analyzed a local database including 468 consecutive patients who underwent elective aortic abdominal surgery over an 8-yr period in a single institution. A new cardioprotective perioperative protocol was introduced in January 1997, and we questioned whether perioperative cardiac outcome could be favorably influenced by the application of a stepwise cardiovascular evaluation based on the American College of Cardiology/American Heart Association guidelines and by the use of antiadrenergic drugs. Clonidine was administered during surgery, and beta-blockers were titrated after surgery to achieve heart rates less than 80 bpm. We compared data of two consecutive 4-yr periods (1993-1996 [control period] versus 1997-2000 [intervention period]). Implementation of American College of Cardiology/American Heart Association guidelines was associated with increased preoperative myocardial scanning (44.3% vs 20.6%; P < 0.05) and coronary revascularization (7.7% vs 0.8%; P < 0.05). During the intervention period, there was a significant decrease in the incidence of cardiac complications (from 11.3% to 4.5%) and an increase in event-free survival at 1 yr after surgery (from 91.3% to 98.2%). Multivariate regression analysis showed that the combined administration of clonidine and beta-blockers was associated with a decreased risk of cardiovascular events (odds ratio, 0.3; 95% confidence interval, 0.1-0.8), whereas major bleeding, renal insufficiency, and chronic obstructive pulmonary disease were predictive of cardiac complications. In conclusion, cardiac testing was helpful to identify a small subset of high-risk patients who might benefit from coronary revascularization. Sequential and selective antiadrenergic treatments were associated with improved postoperative cardiac outcome. IMPLICATIONS: Implementation of American College of Cardiology/American Heart Association guidelines and use of antiadrenergic drugs were associated with better cardiac outcomes after major vascular surgery.