Training potential in minimally invasive surgery in a tertiary care, paediatric urology centre.

BACKGROUND: Minimally invasive surgery (MIS) is being utilized more frequently as a surgical technique in general surgery and in paediatric urology. It is associated with a steep learning curve. Currently, the centre does not offer a MIS training programme. It is hypothesized that the number of MIS procedures performed in the low-volume specialty of paediatric urology will offer insufficient training potential for surgeons. OBJECTIVE: To assess the MIS training potential of a highly specialized, tertiary care, paediatric urology training centre that has been accredited by the Joint Committee of Paediatric Urology (JCPU). STUDY DESIGN: The clinical activity of the department was retrospectively reviewed by extracting the annual number of admissions, outpatient consultations and operative procedures. The operations were divided into open procedures and MIS. Major ablative procedures (nephrectomy) and reconstructive procedures (pyeloplasty) were analysed with reference to the patients' ages. The centre policy is not to perform major MIS in children who are under 2 years old or who weigh less than 12 kg. RESULTS: Every year, this institution provides approximately 4300 out-patient consultations, 600 admissions, and 1300 procedures under general anaesthesia for children with urological problems. In 2012, 35 patients underwent major intricate MIS: 16 pyeloplasties, eight nephrectomies and 11 operations for incontinence (seven Burch, and four bladder neck procedures). In children ≥2 years of age, 16/21 of the pyeloplasties and 8/12 of the nephrectomies were performed laparoscopically. The remaining MIS procedures included 25 orchidopexies and one intravesical ureteral reimplantation. DISCUSSION: There is no consensus on how to assess laparoscopic training. It would be valuable to reach a consensus on a standardized laparoscopic training programme in paediatric urology. Often training potential is based on operation numbers only. In paediatric urology no minimum requirement has been specified. The number of procedures quoted for proficiency in MIS remains controversial. The MIS numbers for this centre correspond to, or exceed, numbers mentioned in other literature. To provide high-quality MIS training, exposure to laparoscopic procedures should be expanded. This may be achieved by centralizing patients into a common centre, collaborating with other specialities, modular training and training outside the operating theatre. CONCLUSION: Even in a high-volume, paediatric urology educational centre, the number of major MIS procedures performed remains relatively low, leading to limited training potential.

Improving radiopeptide pharmacokinetics by adjusting experimental conditions for bombesin receptor-targeted imaging of prostate cancer.

AIM: Prostate cancer (PC) is a major health problem. The Gastrin-Releasing Peptide Receptor (GRPR) offers a promising target for staging and monitoring of PC since it is overexpressed in PC and not in normal prostatic tissue. To improve receptor-mediated imaging we investigated the impact of various experimental conditions on pharmacokinetics using the Indium-111 labelled bombesin (BN) analogue AMBA. Besides frequently used androgen-resistant PC-3 also the clinically more relevant androgen sensitive VCaP celline was used as human PC xenograft in nude mice. METHODS: Non-purified [111In]AMBA was compared with HPLC-purified [111In]AMBA. Effect of specific activity was studied administering 0.1MBq [111In]AMBA supplemented with different amounts of AMBA (1-3000pmol). GRPR was saturated with Tyr4-BN 1 and 4h prior to injection of [111In]AMBA. RESULTS: GRPR-positive tissue showed a significant 2 to 3-fold increase in absolute uptake after HPLC-purification while keeping a stable tumor-to-pancreas ratio. Lowering specific activity resulted in decline in uptake to 43% in tumor, 49% in kidney and 92% in pancreas between 10 and 3000 pmol. Tumor-to-pancreas ratio improved six-fold from 0.1±0 after 10 pmol up to 0.6±0.2 after 3000 pmol (P<0.01). When saturating GRPR 4h prior to [111In]AMBA injection tumor-to-pancreas ratio improved from 0.10±0.3 to 0.22±0.2 (P<0.01) and tumor-to-kidney ratio increased from 0.92±0.16 to 3.45±0.5 (P<0.01). CONCLUSION: Besides specific peptide characteristics also the experimental conditions, such as HPLC-purification, variations in specific activity and saturation of the GRPR prior to [111In]AMBA administration essentially affect radiopeptide pharmacokinetics. Experimental conditions therefore need to be carefully selected in order to compose ideal standardised protocols for optimal targeting.

Peptide receptor imaging of prostate cancer with radiolabelled bombesin analogues.

Prostate Cancer (PC) is a type of cancer that is often diagnosed at very early stages due to improved detection among man in the Western world. Current imaging techniques are not optimal to determine extent of minimal early stage PC even though this is of great clinical importance. Human PC and high-grade PIN have shown high Gastrin-Releasing Peptide Receptor (GRPR) expression, while normal prostate tissue and BPH revealed to be predominantly GRPR-negative. Radiolabelled Gastrin-Releasing Peptide (GRP) or bombesin (BN) analogues targeting the GRPR can be used as non-invasive tools to diagnose, monitor and potentially treat PC. These BN analogues have already proven to be able to image PC in both tumour-bearing mice and clinical patients showing no important side effects. It's desirable that new peptides require fast-track standardised comparative testing in relevant PC models to select the best performing BN analogues for further evaluation in patients. Although knowledge about GRPR expression and development of new BN analogues can be extended, it is time to study performance of BN analogues for peptide receptor based imaging in patients validating results of PC imaging using histopathology as a golden standard.