Androgen Deprivation therapy for Oligo-recurrent Prostate cancer in addition to radioTherapy (ADOPT): study protocol for a randomised phase III trial.

BACKGROUND: More than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome. METHODS: Two hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included. DISCUSSION: This phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1-4 recurrent oligometastatic lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04302454 . Registered 10 March 2020.

Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol.

BACKGROUND: Salvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases. METHODS: The PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of < 1.0 ng/mL and a recent negative PSMA PET/CT scan. Participants will be randomised in a 1:1 ratio between the conventional fractionated treatment arm (35 × 2 Gy) and the experimental hypofractionated treatment arm (20 × 3 Gy). The primary endpoint is the 5-year progression-free survival after treatment. The secondary endpoints include toxicity, quality of life and disease specific survival. DISCUSSION: Firstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Identifier: NCT04642027 ). Registered on 24 November 2020 - Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants.

Cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy, a randomized controlled trial (CAPTURE) protocol.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the standard surgical treatment method for large kidney stones. Its aim is to achieve a stone-free status, since any residual fragments (RFs) after PCNL are likely to cause additional morbidity or stone growth. Enhancing intraoperative detectability of RFs could lead to increased stone-free rates and decreased re-intervention rates. Cone beam computed tomography (CBCT) has recently been introduced in urology as a feasible method for intraoperatively imaging RFs. The aim of this trial is to determine the added value of CBCT in percutaneous nephrolithotomy, by measuring differences in stone-related morbidity for patients with procedures in which a CBCT is used versus patients with procedures without the use of CBCT. METHODS: The CAPTURE trial is an investigator-initiated single-center, randomized controlled trial (RCT) in adult patients who have an indication for percutaneous nephrolithotomy. A contemporary percutaneous nephrolithotomy is performed. Once the surgeon is convinced of a stone-free status by means of fluoroscopy and nephroscopy, randomization allocates patients to either the study group in whom an intraoperative CBCT scan is performed or to the control group in whom no intraoperative CBCT scan is performed. The main endpoint is the stone-free status as assessed four weeks postoperatively by low-dose non-contrast abdominal CT, as a standard follow-up procedure. Secondary endpoints include the number of PCNL procedures required and the number of stone-related events (SREs) registered. The total study population will consist of 320 patients that undergo PCNL and are eligible for randomization for an intraoperative CBCT scan. DISCUSSION: We deem a randomized controlled trial to be the most effective and reliable method to assess the efficacy of CBCT in PCNL. Though some bias may occur due to the impossibility of blinding the urologist at randomization, we estimate that the pragmatic nature of the study, standardized circumstances, and follow-up methods with pre-defined outcome measures will result in a high level of evidence. TRIAL REGISTRATION: Netherlands Trial Register (NTR) NL8168 , ABR NL70728.042.19. Registered on 15 October 2019. Prospectively registered.

Intraoperative cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy: a feasibility study.

Cone beam computed tomography (CBCT) provides multiplanar cross-sectional imaging and three-dimensional reconstructions and can be used intraoperatively in a hybrid operating room. In this study, we investigated the feasibility of using a CBCT-scanner for detecting residual stones during percutaneous nephrolithotomy (PCNL). Intraoperative CBCT-scans were made during PCNL procedures from November 2018 until March 2019 in a university hospital. At the point where the urologist would have otherwise ended the procedure, a CBCT-scan was made to image any residual fragments that could not be detected by either nephroscopy or conventional C-arm fluoroscopy. Residual fragments that were visualized on the CBCT-scan were attempted to be extracted additionally. To evaluate the effect of this additional extraction, each CBCT-scan was compared with a regular follow-up CT-scan that was made 4 weeks postoperatively. A total of 19 procedures were analyzed in this study. The mean duration of performing the CBCT-scan, including preparation and interpretation, was 8 min. Additional stone extraction, if applicable, had a mean duration of 11 min. The mean effective dose per CBCT-scan was 7.25 mSv. Additional extraction of residual fragments as imaged on the CBCT-scan occurred in nine procedures (47%). Of the follow-up CT-scans, 63% showed a stone-free status as compared to 47% of the intraoperative CBCT-scans. We conclude that the use of CBCT for the detection of residual stones in PCNL is meaningful, safe, and feasible.

Insulin-like factor 3, luteinizing hormone and testosterone in testicular cancer patients: effects of ß-hCG and cancer treatment.

BACKGROUND: Primary hypogonadism (low testosterone and high luteinizing hormone, LH) is present in approximately 20% of testicular cancer (TC) survivors after orchidectomy with or without chemotherapy. OBJECTIVES: We investigated insulin-like factor 3 (INSL3), a novel marker of Leydig cell function, in TC patients. MATERIALS AND METHODS: We analyzed: (I) a cross-sectional cohort of TC patients after orchidectomy with or without chemotherapy (1988-1999) at long-term follow-up (median 36 and 35 years of age at follow-up, respectively) and healthy men of similar age; (II) a longitudinal cohort of chemotherapy-treated TC patients (2000-2008), analyzed before and 1 year after chemotherapy (median 29 years of age at chemotherapy). INSL3, testosterone, and LH were compared between groups and over time and related to pre-chemotherapy ß-hCG levels. RESULTS: In the cross-sectional cohort, TC patients at median 7 years after orchidectomy and chemotherapy (n = 79) had higher LH (p < 0.001), lower testosterone (p = 0.001), but similar INSL3 as controls (n = 40). After orchidectomy only (n = 25), higher LH (p = 0.02), but no differences in testosterone or INSL3 were observed compared to controls. In the longitudinal cohort, patients with normal pre-chemotherapy ß-hCG (≤5 mU/L, n = 35) had increased LH 1 year after chemotherapy compared to pre-chemotherapy (p = 0.001), and no change in testosterone or INSL3. In contrast, patients with high ß-hCG pre-chemotherapy (n = 42) had suppressed LH, markedly elevated testosterone, and low INSL3 at start of chemotherapy, with increased LH, decreased testosterone, and increased INSL3 1 year later (all p < 0.001). DISCUSSION: Changes in LH show that gonadal endocrine function is disturbed before chemotherapy, 1 year later, and at long-term follow-up in chemotherapy-treated TC patients. CONCLUSION: Pre-chemotherapy, ß-hCG-producing tumors affect the gonadal endocrine axis, demonstrated by increased testosterone and decreased LH. INSL3 did not uniformly follow the pattern of testosterone.

[Asymptomatic microscopic haematuria: usually not a problem]. / Asymptomatische microscopische hematurie.

Asymptomatic microscopic haematuria is a common finding and can have many different causes. Only a small fraction of patients referred for microscopic haematuria have an underlying urological malignancy or serious nephrogenic disease. It is important that only those patients with microscopically confirmed microscopic haematuria are referred. Often no cause can be found even after thorough diagnostic work-up. The work-up of microscopic haematuria can include urethrocystoscopy, ultrasound, multi-phase CT and cytology. These procedures are not only costly, but can have associated health risks and may also cause patients anxiety and distress. There is no evidence to support the hypothesis that microscopic haematuria is the precursor of macroscopic haematuria, which is significantly more likely to have serious underlying causes. A diagnostic work-up should be initiated with caution.

Balancing treatment efficacy, toxicity and complication risk in elderly patients with metastatic renal cell carcinoma.

The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly.

GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/µmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN were -2.14 ± 0.14 and -2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled ɛ-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (µPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with (18)F. Both tracers may have potential for GRPR-positive tumor imaging.

Outcomes of extra corporeal shock wave lithotripsy in renal and ureteral calculi.

BACKGROUND: Since the introduction in early 1980s, Extracorporeal Shockwave Lithotripsy (ESWL) became the accepted first line treatment modality for renal and upper ureteric stones. It is simple, safe and effective noninvasive procedure which can be performed without anaesthesia in outpatient basis. The objective of this study was to determine the efficacy of ESWL to achieve complete stone clearance in the patients with different sizes of renal and upper ureteric stones. OBJECTIVE: The aim of this study was to assess the outcome, efficacy and complications of ESWL in the treatment for renal and ureteric stones in terms of the site and the size of the stone in the patients presented at Dhulikhel Hospital Kathmandu University Hospital. METHOD: In this prospective study a total of 430 (214 renal and 216 ureteric) cases of urinary stone disease in 257 male and 173 female patients treated by ESWL at Dhulikhel Hospital, Kathmandu University Teaching Hospital during time period of May 2010 to June 2012 were included. Data of patients with renal and ureteric stones were evaluated for stone site, size, and number of sessions. Data were analyzed using spss 13.0. RESULT: Out of 430 cases, the overall stone free rate in after 1st session was 341 (79.3%) at one month and in three months follow up (3 sessions) it was increased up to 414 (96.3%). In 16 (3.7%) patients treatment was failed. Average size of the stone was 12.24 (SD± 3.65) mm. Stone free rate was 154 (72%) in the case of renal and 187 (86.6%) in the case of ureteric stones in first session. In three months follow up (three sessions) it was 204 (95.4%) and 210 (97.2%) respectively for renal and ureteric stones. In relation to size the stone free rate in <10 mm, 10-15 mm and > 15 mm was 97%, 97% and 90%. CONCLUSION: ESWL is the first line preferred choice for renal and upper ureteric stones which provides the maximum stone free rate in the case of stone size smaller than 1.5 cm.

Chest X-ray in the follow-up of renal cell carcinoma.

PURPOSE: To evaluate the value of chest X-ray in the follow-up of surgically treated T1-3N0M0 renal cell carcinoma. METHODS: We performed retrospective analysis of patients that underwent surgical treatment of a localized renal cell carcinoma (T1-3N0M0) between January 1993 and July 2010. Data on frequency and results of performed chest X-rays were collected from patients' records. RESULTS: In 17.5 years, 249 patients with a T1-3N0M0 renal cell carcinoma underwent a radical or partial nephrectomy. In 221 patients, 823 chest X-rays were performed during a median follow-up of 3.3 years (range 0.5-17 years). In 19 patients, a pulmonary recurrence occurred, of which 10 were not detected by the regular follow-up. Of the 9 patients that were diagnosed with a pulmonary recurrence with a chest X-ray during follow-up, 7 were asymptomatic at the time of diagnosis, and the chest X-ray has led to the detection; 0.85 % of the performed chest X-rays (7/823) have led to the detection of asymptomatic lung metastases. CONCLUSIONS: Due to the low yield of chest X-ray for detection of asymptomatic pulmonary recurrences, it has very low clinical value in the follow-up after nephrectomy for T1-3N0M0 renal cell carcinoma.

Outcomes of transurethral resection of the prostate in benign prostatic hyperplasia comparing prostate size of more than 80 grams to prostate size less than 80 grams.

BACKGROUND: Benign prostatic hyperplasia is a condition occurring in elderly men in which the prostate gland is enlarged, hence the condition also known as benign enlargement of prostate. Benign hyperplasia can lead to both obstructive and irritative symptoms. Transurethral resection of prostate (TURP) still remains the gold standard modality of surgical treatment of obstructive lower urinary tract symptoms due to Benign hyperplasia. OBJECTIVES: The objective of this study was to evaluate the outcomes of TURP in large prostate (>80 grams) in comparison to small prostate (<80 grams) in terms of efficacy, safety and complications. METHODS: A total of 65 cases included in this prospective study, which were operated by a single surgeon with conventional monopolar TURP using standard technique. Intra -operative and post-operative complications, pre and post- operative quality of life (QoL) and international prostate symptom score (IPSS), operative time, time to removal of catheter and hospital stay were evaluated between small and large prostate gland volumes. RESULTS: Out of 65 cases, 30 were with large prostate size i.e. 80 grams or more (group 1), and 35 cases were with small prostate size than 80 grams size (group 2). Mean age was 71.8 SD ± 6.9 years in group 1 and 68.2 SD ± 12.7 years in group 2. The mean preoperative volume of prostate was 88.8 grams (range 80-115 grams) in group 1 and 40.3 (range 20-65 grams) in group 2. The mean preoperative post void residual volume of urine (PVRU) was 244 ml SD ± 190.8 ml in group 1 and 117 ml ± 70.3 ml in group 2. Mean resection time in group 1 was 110 (range 90-130) minutes and in group 2 it was 90 minutes (range 55-115) minutes. There were quite satisfactory improvements in IPSS and QoL. No significant complications were observed except TUR syndrome in 2 cases from group 2, which were managed well in postoperative period. CONCLUSION: With meticulous resection and intra-operative haemostasis using continuous out flow resectoscope, conventional monopolar TURP is equally safe and effective in large size prostate as compare in small size.

Preclinical evaluation of a novel ¹¹¹In-labeled bombesin homodimer for improved imaging of GRPR-positive prostate cancer.

Rational-designed multimerization of targeting ligands can be used to improve kinetic and thermodynamic properties. Multimeric targeting ligands may be produced by tethering multiple identical or two or more monomeric ligands of different binding specificities. Consequently, multimeric ligands may simultaneously bind to multiple receptor molecules. Previously, multimerization has been successfully applied on radiolabeled RGD peptides, which resulted in an improved tumor targeting activity in animal models. Multimerization of peptide-based ligands may improve the binding characteristics by increasing local ligand concentration and by improving dissociation kinetics. Here, we present a preclinical study on a novel radiolabeled bombesin (BN) homodimer, designated (111)In-DOTA-[(Aca-BN(7-14)]2, that was designed for enhanced targeting of gastrin-releasing peptide receptor (GRPR)-positive prostate cancer cells. A BN homodimer was conjugated with DOTA-NHS and labeled with (111)In. After HPLC purification, the GRPR targeting ability of (111)In-DOTA-[Aca-BN(7-14)]2 was assessed by microSPECT imaging in SCID mice xenografted with the human prostate cancer cell line PC-3. (111)In labeling of DOTA-[(Aca-BN(7-14)]2 was achieved within 30 min at 85 °C with a labeling yield of >40%. High radiochemical purity (>95%) was achieved by HPLC purification. (111)InDOTA-[Aca-BN(7-14)]2 specifically bound to GRPR-positive PC-3 prostate cancer cells with favorable binding characteristics because uptake of 111In-DOTA-[Aca-BN(7-14)]2 in GRPR-positive PC-3 cells increased over time. A maximum peak with 30% radioactivity was observed after 2 h of incubation. The log D value was -1.8 ± 0.1. (111)In-DOTA-[Aca-BN(7-14)]2 was stable in vitro both in PBS and human serum for at least 4 days. In vivo biodistribution analysis and microSPECT/CT scans performed after 1, 4, and 24 h of injection showed favorable binding characteristics and tumor-to-normal tissue ratios. This study identifies (111)In-DOTA-[(Aca-BN(7-14)]2 as a promising radiotracer for nuclear imaging of GRPR in prostate cancer.

Complement mediated renal inflammation induced by donor brain death: role of renal C5a-C5aR interaction.

Kidneys retrieved from brain-dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complement contributes to allograft injury remains to be elucidated. The aim of this study was to investigate systemic C5a release after BD in human donors and direct effects of C5a on human renal tissue. C5a levels were measured in plasma from living and brain-dead donors. Renal C5aR gene and protein expression in living and brain-dead donors was investigated in renal pretransplantation biopsies. The direct effect of C5a on human renal tissue was investigated by stimulating human kidney slices with C5a using a newly developed precision-cut method. Elevated C5a levels were found in plasma from brain-dead donors in concert with induced C5aR expression in donor kidney biopsies. Exposure of precision-cut human kidney slices to C5a induced gene expression of pro-inflammatory cytokines IL-1 beta, IL-6 and IL-8. In conclusion, these findings suggest that systemic generation of C5a mediates renal inflammation in brain-dead donor grafts via tubular C5a-C5aR interaction. This study also introduces a novel in vitro technique to analyze renal cells in their biological environment.

Urinary bladder carcinoma: impact of smoking, age and its clinico-pathological spectrum.

BACKGROUND: Urinary bladder carcinoma is common urological malignancy. Although epidemiological evidence favors role of occupational exposure to chemical carcinogen as the aetiological factor of bladder carcinoma, many cases arise with no obvious occupational exposure to chemical carcinogen. Tobacco and cigarette smoking is common in both rural and urban areas of Nepal. OBJECTIVE: The objective of this study was to determine the impact of smoking and age in urinary bladder carcinoma with related clinicopathological correlations. METHOD: A total of 56 (44 males and 12 females) cases of urinary bladder cancer treated at Dhulikhel Hospital, Kathmandu University Teaching Hospital during time period of January 2004 to December 2013 were included in the study. Data of patients with Urinary bladder cancer were obtained from hospital records and evaluated for age, sex, history of smoking, clinical presentations, cystoscopic findings and histopathological characteristics. RESULTS: Out of 56 cases, 51 (91.1%) of the patients had hematuria. History of smoking was found in 44 patients. Smoking was found much higher in males (88%) than females (41.66%). Transitional cell carcinoma (TCC) was the most common histological variety, which was seen in 51 (91.07%) patients. The significant impact of smoking was found in terms of grade of TCC. CONCLUSION: The incidence of bladder carcinoma is higher in male and TCC is the most common variety of Urinary bladder malignancy. History of smoking correlated with grade.

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.

[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.

The association between Peyronie's and Dupuytren's disease.

Peyronie's disease (PD) is known to be associated with Dupuytren's disease (DD) since 1828. The aim of this study was to investigate the coexistence of DD in a consecutive series of patients with PD and their clinical characteristics. From January 1988 to December 2009 all patients, presenting at our outpatient urological clinic, with PD were also examined for DD. The sample consisted of 415 male subjects with PD, 89 (22.1%) also had DD. A total of 28 men (6.7%) reported to have one or more first or second degree relatives with DD.

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.

Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors.

BACKGROUND: Patients with elevated human chorionic gonadotrophin (HCG) can have hyperthyroidism. We assessed the prevalence of hyperthyroidism in patients presenting with disseminated non-seminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: In all patients with metastatic NSGCT who started chemotherapy at our center from April 2001 to April 2007, thyroid function was analyzed. The association between thyroid function and HCG level was examined and the frequency of hyperthyroidism in patients with low (<5000 IU/l), intermediate (> or = 5000 but <50 000 IU/l) and high (> or = 50 000 IU/l) serum HCG was assessed. RESULTS: For 144 of 148 eligible patients, thyroid function tests were available. Five patients with hyperthyroidism (3.5%) were identified, who all had high-serum HCG (mean 1 325 147 IU/l). Fifty percent of the patients with high HCG levels had hyperthyroidism versus 0% of the patients with HCG <50 000 IU/l (P < 0.001). Free thyroxin levels normalized within 26 days after starting chemotherapy in all patients. CONCLUSIONS: Hyperthyroidism frequently accompanies NSGCT with highly elevated HCG. Since its symptoms overlap with those of extensive metastatic disease, it may not be recognized. Thyroid function should be assessed in patients with high HCG levels and symptomatic hyperthyroidism should be treated temporarily with beta-blockade or antithyroidal medication.