Correlation of [11C]choline PET-CT with time to treatment and disease-specific survival in men with recurrent prostate cancer after radical prostatectomy.

AIM: Radiotherapy following radical prostatectomy should be considered in men with high risk features who have a life expectancy of more than 10 years. So far no effect on prostate cancer specific survival has been proven by 3 randomized controlled trials (RCTs) on adjuvant radiotherapy. At present the optimal timing of radiotherapy is not defined. Identifying the site of recurrence is difficult at low PSA levels. [11C]choline PET-CT studies in biochemical recurrent prostate cancer after prostatectomy show a higher frequency of (false) negative cases compared to restaging after EBRT. It is uncertain if this reflects low volume of disease and/or low grade as biopsies fail to prove recurrent cancer in 50% of cases. We followed the clinical course of men with recurrent prostate cancer after radical prostatectomy and investigated treatment and survival. PET-CT data were correlated with clinical data, PSA kinetics and disease specific and overall survival. We also studied relative survival comparing an age matched group from the Central Dutch Statistical Office (CBS). METHODS: Sixty-four patients underwent [11C]choline PET-CT on PSA relapse. All patients were initially treated with radical prostatectomy and reached PSA nadir of <0.1 ng/mL. Recurrent disease was defined as PSA increase <0.2 ng/mL after nadir. Patients were either treated with watchful waiting, salvage radiotherapy and/or androgen deprivation therapy based on individual assessments by the treating urologists. Statistic: χ2, log-rank and Mann-Whitney-U tests were used to compare the [11C] choline PET/CT groups. RESULTS: The 64 patients had median PSA of 1.4 ng/mL. Median follow-up period of patients was 50 (6-124) months. Ten patients died during the course of follow-up of which 5 due to metastasized disease. No significant differences were seen in age, time to recurrence, total PSA at recurrence and PET-CT results. Patients with abnormal PET had higher PSAVel (median 3.09 ng/mL/yr versus 10.17, P=0.002) and shorter PSADT (med 4.83 months vs. 0.53, P=0.016). Median time to treatment was significantly lower in the PET-CT negative group. Age of patients at death from the whole group did not differ from the age of death in an age matched group. Disease specific survival was significantly higher in the PET-CT negative group (P=0.05). CONCLUSION: [11C]choline PET-CT showed that a negative PET/CT correlated with a higher disease specific survival and a lower treatment rate in men with a biochemical recurrence after radical prostatectomy. Overall survival of the total group was equal to the age matched cohort emphasizing the limited effect of a biochemical recurrent prostate cancer on overall survival. The optimum timing (adjuvant or early salvage) must be answered in running trials before adjuvant RT is used as standard of care.

Restaging prostate cancer patients with biochemical failure with PET/CT and radiolabeled choline.

PET/CT with either [11C]choline or [18F]fluorocholine represents a powerful technique for restaging prostate cancer (PCa) patients with biochemical failure. The availability of dedicated PET/CT scanners allows fusioning of morphological and functional images, which enables accurate localization of sites of pathological tracer uptake and ease the differentiation between malignant and benign findings. A noteworthy advantage of this whole-body technique is that it provides information on multiple anatomic sites at a single time. As such, the technique has the capability of distinguishing between local relapse and distant metastases, and therefore has the potential to guide the medical treatment. The positive detection rate of [11C]choline PET/CT varies substantially in relation to the inclusion criteria. Studies which included unselected consecutive patients reported a positive detection rate ranging between 40% and 70%. Serum PSA level represents the single, most important factor affecting the rate of positive scans. Other positive predicitive factors include fast PSA kinetics (PSA velocity, PSA doubling time), advanced pathological state at initial staging, previous biochemical failure, hormone resistance and older age. Recent studies indicate that [11C]choline PET/CT has the potential to early restaging PCa patients for PSA levels lower than 1-1.5 ng/mL. However, more studies are necessary to better define the potential of this technique for low PSA levels. The previously cited risk factors can be used to identify patients that are at greater risk and that might best benefit from PET/CT scans. Patients that develop biochemical failure during androgen deprivation therapy (hormone resistance) have a higher likelihood for a positive [11C]choline PET/CT scan in comparison to patients that are drug naïve (hormone sensitive) and are not required to withdraw the anti-androgenic treatment before PET/CT.

[11C]choline PET for the intraprostatic tumor characterization and localization in recurrent prostate cancer after EBRT.

AIM: This study focuses on the potential role of [11C]choline positron emission tomography (PET) for the intraprostatic tumor characterization and localization in recurrent prostate cancer after EBRT. METHODS: This retrospective study was conducted in patients who were being followed up after EBRT for histological proven prostate cancer. We selected the patients with a local recurrence by [11C]choline PET/CT fusion. The results of PET were compared with the results of histology and with clinical follow-up. RESULTS: Forty-two patients with a local recurrence suggested by PET were included in this study. According to PET results: of the 42 patients, 15 (36%) had a focal recurrence, 27 (64%) showed a diffuse recurrence. The overall concordance of PET with histology concerning detection of recurrence was 76% (32 patients had positive PET results and positive biopsies). We confirmed the local recurrence as visualized by PET in 37/42 (88%) patients using a composite reference with histology and clinical follow up after local salvage treatment. The concordance of the intraprostatic distribution of the tumor with PET with histology from transrectal prostate biopsies (median biopsies 7, range 4-12) was 47% (7/15) in unilateral cases and 41% (11/27) in bilateral cases. No significant differences were seen between the 2 groups in serum PSA at time of PET (P=0.509) and SUV (P=0.739) using Student's t-test. CONCLUSION: Intraprostatic characterization of recurrent prostate cancer after EBRT with 11C-choline PET is feasible at present but shows a moderate concordance with routine transrectal prostate biopsies. The accuracy is too low for the routine use of this modality in the present scenario.

PET/CT and radiotherapy in prostate cancer.

Radiotherapy is one of the corner stone treatments for patients with prostate cancer. Especially for locally advanced tumors radiotherapy +/- adjuvant androgen deprivation treatment is standard of care. This brings up the need for accurate assessment of extra prostatic tumor growth and/or the presence of nodal metastases for selection of the optimal radiation dose and treatment volume. Morphological imaging like transrectal ultra sound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used but are limited in their accuracy in detecting extra prostatic extension and nodal metastases. In this article we present a structured review of the literature on positron emission tomography (PET)/CT and radiotherapy in prostate cancer patients with emphasis on: 1) the pretreatment assessment of extra prostatic tumor extension, nodal and distant metastases; 2) the intraprostatic tumor characterization and radiotherapy treatment planning; and 3) treatment evaluation and the use of PET/CT in guidance of salvage treatment. PET/CT is not an appropriate imaging technique for accurate T-staging of prostate cancer prior to radiotherapy. Although macroscopic disease beyond the prostatic capsule and into the periprostatic fat or in seminal vesicle is often accurately detected, the microscopic extension of prostate cancer remains undetected. Choline PET/CT holds a great potential as a single step diagnostic procedure of lymph nodes and skeleton, which could facilitate radiotherapy treatment planning. At present the use of PET/CT for treatment planning in radiotherapy is still experimental. Choline PET based tumor delineation is not yet standardized and different segmentation-algorithms are under study. However, dose escalation using dose-painting is feasible with only limited increases of the doses to the bladder and rectum wall. PET/CT using either acetate or choline is able to detect recurrent prostate cancer after radiotherapy but stratification of patients for any local salvage treatment has not been addressed in the current literature.

Serum bone turnover markers (PINP and ICTP) for the early detection of bone metastases in patients with prostate cancer: a longitudinal approach.

PURPOSE: An increase in bone turnover markers in patients with prostate cancer may predict bone metastases but it can also reflect the effects of androgen deprivation treatment. To assess the diagnostic efficacy of early detection of skeletal metastases we retrospectively performed serial measurements of a bone formation marker (PINP) and a bone resorption marker (ICTP) in serum of patients with prostate cancer. MATERIALS AND METHODS: Residual serum samples from 64 patients with prostate cancer treated between 1999 and 2004 were selected from our prostate specific antigen serum archive, and divided into 3 groups of patients with no metastases (N0M0), with lymph node metastases only (N1M0) and with skeletal metastases (M1). In the M1 group the T(1) sample was collected near the first positive bone scintigraph. RESULTS: The N1M0 and M1 groups showed increased PINP levels (ANOVA T(0) p = 0.035, T(1) p <0.001). The PINP levels in the M1 group increased further (paired t test p = 0.028), while no increase was found in the other groups. There was no significant difference between the number of patients receiving androgen deprivation therapy in the N1M0 and the M1 groups. Increased PINP levels in the M1 group were detectable 8 months before the first positive bone scintigraph. The increase in ICTP in the M1 group differed significantly from the other groups (the Student t test in 45 patients p = 0.029). The increases in PINP and ICTP differentiated between patients with or without skeletal metastases (AUC 0.71, p = 0.002 and AUC 0.64, p = 0.045, respectively). CONCLUSIONS: Followup measurement of serum PINP and ICTP is useful in the early assessment of skeletal metastases in patients with prostate cancer regardless of the confounding role of androgen deprivation treatment. The bone formation marker is the most indicative.

Torsion of the spermatic cord after orchiopexy.

The cases of spermatic cord torsion reported here show that this condition may occur even some time after fixation. Three men, aged 22, 30 and 35 years, visited the urologist with complaints of an acute scrotum following earlier orchiopexy for spermatic cord torsion. Different techniques are employed to fixate the testicles after spermatic cord torsion. These cases confirm that Jaboulay's bottleneck procedure is the method of choice for bilateral fixation in patients presenting with this condition.

[Diagnostic image (192). A man with intermittent gross hematuria. Urogenital schistosomiasis]. / Diagnose in beeld (192). Een man met intermitterende macroscopische hematurie. Urogenitale schistosomiasis.

In a 17-year-old boy from Angola with intermittent gross haematuria, intravenous urography and cystoscopy revealed obstructive uropathy due to schistosomiasis.

[Surprises during urological interventions due to incomplete medical histories]. / Verrassingen bij urologische ingrepen door onvolledige informatie over de medische voorgeschiedenis.

Two men, aged 37 and 47 years old, visited the urologist because of secondary infertility. These underwent an examination whilst under general anaesthesia; the examination was converted to a vasovasostomy, as in both cases it was found that a vasectomy had previously been performed. A third man, 56 years old, wished to undergo vasovasostomy; a few months later he appeared to have pre-existent retrograde ejaculation after an earlier bladder neck incision. For various reasons, no adequate information about the psychosocial and medical history was available. These case histories stress the importance of all of the patient records being available prior to an intervention.

On the inheritance of intersexuality in swine.

Data of Breeuwsma (1970) were analyzed in an attempt to discriminate between major gene vs. multifactorial modes of inheritance of intersexuality in swine. Of 3708 females, 160 were intersexes with external phenotypes ranging from normal female (normal overlap) to testicular pseudohermaphrodite. Environment (litter size, parity, hormone treatment of dam) influenced detection of carriers but not origin of intersexes. Normal overlaps lowered penetrance, partly due to deaths in competition with male littermates. Phenocopies (intersex with unusual genotype or with karyotype other than 38,XX) were rare. Sex ratio variation between mating types could be ascribed to the ascertainment method. Segregation ratio estimates for female sibships increased from those with at least one to those with at least two intersexes less than expected for polygenic inheritance. The latter could not be ruled out (heritability of liability by three methods was 78%), but duplicate epistasis provided a more parsimonious explanation. Separation of litters from retrospectively known carriers into identifying and post-identifying groups produced patterns of segregation estimates supporting inheritance by few rather tha many genes. Crossbred intersexes indicate homology of genes for intersexuality in several European breeds of pigs.

[Comparative studies on the effectiveness of intramammary treatment of clinical mastitis cattle (author's transl)]. / Een vergelijkend onderzoek naar de effectiviteit van intramammaire behandeling van klinische mastitis bij het rund

To study the effectiveness of intramammary treatment of clinical mastitis in cattle, three different suspensions containing antibiotics for intramammary injection were compared in a field trial in the provinces of Friesland and North Brabant. Milk samples from the clinically abnormal as well as from the clinically normal quarters were examined for pathogenic bacteria and cell counts were made prior to treatment, within one week after treatment and within three weeks after treatment. The clinical diagnosis was confirmed by laboratory studies in approximately 90 per cent of the cases in which quarters were abnormal. However, 50 per cent of the clinically normal quarters also showed increased cell counts and/or bacterial infection. Treatment of these quarters should therefore be considered. Apart from regional variations as regards the character of the mastitis and the results of treatment, there were no significant differences between the effects of the three suspensions. Clinical recovery occurred in approximately 90 per cent of the cases, the pathogenic bacteria disappeared in approximately 75 per cent of the cases and the increased cell counts were restored to normal in approximately 60 per cent of the abnormal quarters.