18F-DCFPyL PET/CT for primary staging in 160 high-risk prostate cancer patients; metastasis detection rate, influence on clinical management and preliminary results of treatment efficacy.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT shows better diagnostic performance for detection of lymph node and bone metastases as compared to conventional imaging. Studies of PSMA PET/CT in primary staging comprise highly selected patient cohorts. This study evaluates 18F-DCFPyL PET/CT as first-line imaging modality for primary staging of high-risk prostate cancer. MATERIAL: From February 2018 until April 2019, all patients with high-risk prostate cancer received 18F-DCFPyL PET/CT for staging of prostate cancer. Baseline characteristics, findings at 18F-DCFPyL PET/CT, number and type of required additional diagnostic procedures, findings at additional diagnostic procedures, and effects of therapy on PSA levels for all patients treated with curative intent were collected and evaluated. RESULTS: One hundred-sixty patients were included in the study of which 90 (56%) had evidence of metastasized disease (N1, M1a, M1b and, M1c in 49%, 28%, 31%, and 3% respectively). Additional diagnostic imaging was needed in 2/160 patients (1%) because of equivocal findings on 18F-DCFPyL PET/CT. Eighty-one patients had evidence of PSMA-positive lymph node metastases, of whom 39 (48%) had no enlarged lymph nodes on CT; 18F-DCFPyL PET detected additional metastatic lymph nodes in 41/42 patients that had evidence of lymph node metastases on CT. 18F-DCFPyL PET altered patients' management in 17% of patients. CONCLUSION: 18F-DCFPyL PET/CT can be used as first-line imaging modality for therapy selection in patients with primary high-risk prostate cancer, without need for further diagnostic imaging procedures in the majority of patients.

Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences.

STUDY QUESTION: What is the prevalence of chromosomal abnormalities in azoospermic men and what are the clinical consequences in terms of increased risk for absent spermatogenesis, miscarriages and offspring with congenital malformations? SUMMARY ANSWER: The prevalence of chromosomal abnormalities in azoospermia was 14.4%, and the number of azoospermic men needed to be screened (NNS) to identify one man with a chromosomal abnormality with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739 and to prevent one child with congenital malformations 4751-23 757. WHAT IS KNOWN ALREADY: Infertility guidelines worldwide advise screening of non-iatrogenic azoospermic men for chromosomal abnormalities, but only few data are available on the clinical consequences of this screening strategy. STUDY DESIGN, SIZE, DURATION: This retrospective multicentre cross-sectional study of non-iatrogenic azoospermic men was performed at the University Hospital Brussels, Belgium, and the University Medical Centre Groningen, The Netherlands, between January 2000 and July 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Analysis of clinical registries retrospectively identified 1663 non-iatrogenic azoospermic men with available results of karyotyping and FSH serum levels. Iatrogenic azoospermia was an exclusion criterion, defined as azoospermia after spermatotoxic medical treatment, exogenous androgen suppletion or vasectomy and/or vasovasostomy. Also, men with a clinical diagnosis of anejaculation or hypogonadotropic hypo-androgenism and/or FSH values <1.0 U/l were excluded. Chromosomal abnormalities were categorized according to their (theoretical) impact on clinical consequences for the patient (i.e. an increased risk for absence of spermatogenesis) and adverse pregnancy outcomes (i.e. miscarriage or offspring with congenital malformations), in both normogonadotropic (FSH < 10 U/l) and hypergonadotropic (FSH ≥ 10 U/l) azoospermia. We estimated the NNS for chromosomal abnormalities to identify one man with absence of spermatogenesis and to prevent one miscarriage or one child with congenital malformations, and calculated the surgical sperm retrieval rates per chromosomal abnormality. MAIN RESULTS AND THE ROLE OF CHANCE: The overall prevalence of chromosomal abnormalities in azoospermia was 14.4% (95% CI 12.7-16.1%), its prevalence being higher in hypergonadotropic azoospermia (20.2%, 95% CI 17.8-22.7%) compared to normogonadotropic azoospermia (4.9%, 95% CI 3.2-6.6%, P < 0.001). Klinefelter syndrome accounted for 83% (95% CI 77-87%) of abnormalities in hypergonadotropic azoospermia. The NNS to identify one man with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739, and to prevent one child with congenital malformations 4751-23 757. There was no clinically significant difference in NNS between men with normogonadotropic and hypergonadotropic azoospermia. The surgical sperm retrieval rate was significantly higher in azoospermic men with a normal karyotype (60%, 95% CI 57.7-63.1%) compared to men with a chromosomal abnormality (32%, 95% CI 25.9-39.0%, P < 0.001). The sperm retrieval rate in Klinefelter syndrome was 28% (95% CI 20.7-35.0%). LIMITATIONS, REASONS FOR CAUTION: The absolute number of chromosomal abnormalities associated with clinical consequences and adverse pregnancy outcomes in our study was limited, thereby increasing the role of chance. Further, as there are currently no large series on outcomes of pregnancies in men with chromosomal abnormalities, our conclusions are partly based on assumptions derived from the literature. WIDER IMPLICATIONS OF THE FINDINGS: The NNS found can be used in future cost-effectiveness studies and the evaluation of current guidelines on karyotyping in non-iatrogenic azoospermia. STUDY FUNDING/COMPETING INTEREST(S): None to declare.

Postprostatectomy ultrasound-guided transrectal implantation of gold markers for external beam radiotherapy. Technique and complications rate.

BACKGROUND AND PURPOSE: Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed. PATIENTS AND METHODS: Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain. RESULTS: In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified. CONCLUSION: Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.

The expression profile of C19MC microRNAs in primary human trophoblast cells and exosomes.

The largest gene cluster of human microRNAs (miRNAs), the chromosome 19 miRNA cluster (C19MC), is exclusively expressed in the placenta and in undifferentiated cells. The precise expression pattern and function of C19MC members are unknown. We sought to profile the relative expression of C19MC miRNAs in primary human trophoblast (PHT) cells and exosomes. Using high-throughput profiling, confirmed by PCR, we found that C19MC miRNAs are among the most abundant miRNAs in term human trophoblasts. Hypoxic stress selectively reduced miR-520c-3p expression at certain time-points with no effect on other C19MC miRNAs. Similarly, differentiation in vitro had a negligible effect on C19MC miRNAs. We found that C19MC miRNAs are the predominant miRNA species expressed in exosomes released from PHT, resembling the profile of trophoblastic cellular miRNA. Predictably, we detected the similar levels of circulating C19MC miRNAs in the serum of healthy pregnant women at term and in women with pregnancies complicated by fetal growth restriction. Our data define the relative expression levels of C19MC miRNAs in trophoblasts and exosomes, and suggest that C19MC miRNAs function in placental-maternal signaling.

Plasma of pregnant and preeclamptic women activates monocytes in vitro.

OBJECTIVE: The objective of the study was to test the hypothesis that factors circulating in the plasma of pregnant women and women with preeclampsia activate monocytes. STUDY DESIGN: Blood samples were taken from patients with early-onset severe preeclampsia (n = 9), healthy pregnant women (n = 9), and healthy nonpregnant women (n = 9). A monocytic cell line was incubated with the plasma for 4, 16, and 24 hours. After the incubation, reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM)-1 expression (protein and messenger ribonucleic acid) were measured. RESULTS: Plasma of both pregnant women and women with preeclampsia, as compared with plasma from nonpregnant women, increased the mean channel brightness (MCB) of ROS after 4 hours of incubation, whereas only plasma of pregnant women increased the percentage of cells producing ROS (after 4 and 24 hours of incubation). Plasma of pregnant women and women with preeclampsia up-regulated the percentage of ICAM-1-expressing cells after 4 hours and down-regulated the percentage of ICAM-1-expressing cells and MCB after 24 hours. CONCLUSION: Plasma of both pregnant women and women with preeclampsia activated monocytes in vitro.

Treatment planning aids in prostate cancer: friend or foe?

BACKGROUND: Rectal barium is commonly used as a treatment planning aid for prostate cancer to delineate the anterior rectal wall. Previous research at the Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results in a systematic shift of the prostate. We postulated that rectal barium could also cause prostate motion. PURPOSE: The study was designed to evaluate the effects of rectal barium on prostate position. METHODS AND MATERIALS: Thirty patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were placed in the prostate. During simulation, baseline posterior-anterior and lateral films were taken. Repeat films were taken after rectal barium opacification. The prostate position (identified by the fiducials) relative to bony landmarks was compared before and after rectal barium. Films were analyzed using PIPsPro software. RESULTS: The rectal barium procedure resulted in a significant displacement of the prostate in the anterior and superior direction. The mean displacement of the prostate measured on the lateral films was 3.8 mm (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior direction. CONCLUSIONS: Rectal barium opacification results in a systematic shift of the prostate. This error could result in a geographic miss of the target; therefore, alternate methods of normal tissue definition should be used.

Effects of urethrography on prostate position: considerations for radiotherapy treatment planning of prostate carcinoma.

PURPOSE: Retrograde urethrography is commonly used to define the prostate apex at simulation. This study evaluated the hypothesis that urethrography causes prostate displacement, resulting in an error in treatment planning. METHODS AND MATERIALS: Forty-five patients with carcinoma of the prostate were evaluated. Gold seeds were placed in the apex, posterior wall, and base of the gland. In the first 20 patients, the position of the seed-defined apex was compared at simulation (with urethrogram) and on day 1 of treatment (without urethrogram). In the second cohort of 25 patients, the effects of urethrography on prostate position were evaluated directly at simulation by comparing the position of apex pre- and post-urethrography. An analysis was performed to estimate the possible impact of urethrogram-induced prostate motion on target coverage. RESULTS: The mean superior displacement in the first and second cohort was 5.2 mm and 6.8 mm, respectively (combined mean shift 6.1 mm). With a 10-mm field margin below the tip of the urethrogram cone, 56% of patients in this study would have inadequate planning target volume (PTV) coverage. CONCLUSION: Retrograde urethrography causes a significant superior shift of the prostate. Strict reliance on urethrography in determining the inferior field margin could result in inadequate treatment.

Clinical characteristics and the impact of surgery and chemotherapy on survival of patients with advanced and metastatic bronchioloalveolar carcinoma: a retrospective study.

We retrospectively analyzed data from the clinical charts of 126 patients with bronchioloalveolar carcinoma (BAC) referred to the Ottawa Regional Cancer Center. The patient group consisted of 49 men (39%) and 77 women (61%). The mean age at diagnosis was 64 years. Most patients were smokers (85%). At diagnosis, 53% were stage Ia-IIIa and 47% were stage IIIb and IV. Forty-one percent of the patients with advanced and metastatic stages (IIIb, IV) underwent surgery. Multifocal disease was present at diagnosis in 41% of the patients, including 6% who had stage IIIb multifocal disease confined to a single lobe. Surgery was associated with prolonged survival in patients with multifocal unilobar or multilobar disease (P = 0.0001). While this apparent benefit of surgery may have been due to selection bias, it supports further exploration of surgery as therapy for multifocal disease. While patients receiving chemotherapy for advanced disease did not survive longer than patients not receiving chemotherapy, chemotherapy was used primarily in patients with more aggressive disease, suggesting that selection bias may have contributed to its apparent lack of benefit. Of the 30 patients treated with chemotherapy, only 3 (10%) achieved an objective response. One third of the patients (34%) developed distant metastases, with a predilection for the brain and bone.

The iron triangle and the chrome pentagon.

Like the arms race, the healthcare system is built on a framework of incentives driven by fear and finance--also like the arms race, it will not admit to piecemeal reform.

Heat-stress influences on antibody production in chicken lines selected for high and low immune responsiveness.

The effect of heat stress on antibody production to sheep red blood cells (SRBC) was investigated during three experiments using chicken lines selected over six generations for high (H) or low (L) plasma-antibody titer to SRBC after primary intramuscular immunization. The chickens were immunized 24 h after a heat-stress treatment (HS) of four periods of 30 min each at a temperature of 42 C with an intervening 30-min period at a temperature of 22 C. For the control treatment (CT), the chicks were handled the same, but at a temperature of 22 C. Antibody titers were measured on 3, 5, 7, 10, and 14 days postimmunization. The intramuscular immunizations, .25 mL of SRBC, were given in all three experiments; an additional intravenous immunization of .5 mL of 14% SRBC was given in Experiment 2 and of .5 mL of 5% SRBC in Experiment 3. A significant effect of the HS treatment on antibody titers (P less than .05 on Days 3, 5, 7, and 10 after immunization) was found only in Experiment 1. The titers decreased in the H line only. The differences between the H and L lines were significant (P less than .001) in all three experiments after both the intramuscular and the intravenous immunizations. Heat stress was found to have little or no effect on antibody production in the lines studied in the present experiments.

Effect of corticosterone infusion on plasma corticosterone concentration, antibody production, circulating leukocytes and growth in chicken lines selected for humoral immune responsiveness.

The effect of corticosterone on antibody production was studied in chicken lines selected for humoral immune response. 2. Twelve cockerels (33 days old) from lines selected for high or low antibody responses after immunisation with sheep red blood cells (SRBC) were implanted with mini-infusion pumps delivering corticosterone or vehicle continuously for 14 d. 3. Three days after implantation, the chickens were immunised intramuscularly with 0.25 ml packed SRBC. Blood samples were taken before implantation, before immunisation and 3, 5, 7 and 11 d after immunization. 4. Corticosterone infusion induced higher plasma corticosterone concentrations and heterophil/lymphocyte ratios than infusion of vehicle only. Growth was considerably depressed and relative weights of the thymus, bursa of Fabricius and spleen were less in the corticosterone-infused chickens. 5. An effect of corticosterone on antibody production could not be demonstrated, and differences between selection lines were unaffected.

Embryonic survival in the pig after insemination with antigen-enriched semen.

Ninety-two first-litter Dutch Landrace sows were inseminated at their first oestrus after weaning with diluted semen containing 2.3 x 10(9) motile sperm cells. Immediately before insemination of 46 randomly chosen sows, 2 x 10(8) fresh bovine leucocytes were added to the semen. All sows were slaughtered on Day 8, 9, or 10 after insemination. In the control group and leucocyte-treated group respectively, 41 and 39 sows were pregnant at slaughter. The average number of corpora lutea (+/- SEM) in pregnant animals was 15.72 +/- 0.60 and 15.22 +/- 0.61, respectively. The average number of embryos was 10.66 +/- 0.79 and 10.36 +/- 0.80, respectively. The addition of bovine leucocytes to semen had neither influence on the pregnancy rate, nor on the number of embryos during early pregnancy.

Chromosome mapping in cattle using mouse myeloma/calf lymph node cell hybridomas.

A study correlating the presence of bovine isozymes in mouse myeloma/calf hybridomas with specific banded chromosomes of their bovine complement has enabled tentative assignments to be made of the bovine isozyme locus for peptidase C (PEP C) to chromosome 5 and the syntenic group lactate dehydrogenase B/peptidase B (LDH B/PEP B) to chromosome 19. There was some evidence for the association of LDH A with one of the last seven small pairs (23-29) of the complement and of superoxide dismutase 1 (SOD 1) with chromosome 13.

Specific bovine monoclonal antibody produced by a re-fused mouse/calf hybridoma.

Hybridomas made by fusing NSO (subline NSI Ag 4-1) mouse myeloma cells with lymph node cells from a calf immunized with sheep red blood cells failed to maintain antibody secretion in culture. However, when two of these hybridomas were selected in 8-azaguanine and then re-fused with immunized calf lymph node cells, several lines were obtained that secreted bovine Ig. One cloned line, producing bovine IgG1 (strongly lytic in the presence of rabbit complement and presumed to be an anti-Forssman) was maintained in culture for five months. Cytogenetic studies confirmed that the mouse/calf hybridomas lost bovine chromosomes as they proliferated, but that re-fusion increased the bovine complement from a mean of 5 (2 n) to 11 (2 n) bovine chromosomes per cell. It is proposed that the selected hybridoma lines may be suitable fusion partners for the production of further monoclonal bovine antibodies.