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.

Preretinal neovascularisation associated with choroidal melanoma.

BACKGROUND: The rare occurrence of iris neovascularisation and choroidal (subretinal) neovascularisation in patients with choroidal melanoma has been reported. However, the occurrence of preretinal neovascularisation (NVE) fed from the retinal circulation in eyes with choroidal melanoma is far less frequently reported. METHODS: Three case reports of choroidal melanoma with the very rare finding of overlying NVE. RESULTS: The three patients had choroidal melanomas, localised serous retinal detachment, and NVE. Two cases showed definite retinal capillary non-perfusion, and one of these two cases demonstrated retinal telangiectasis. One patient's melanoma responded quickly to iodine-125 plaque radiotherapy; however, the retinal neovascularisation persisted and caused vitreous haemorrhage. Localised scatter photocoagulation was successful in causing the complete regression of the neovascularisation. The other two patients had their eyes enucleated (one with planned pre-enucleation external beam radiotherapy). Demonstration of preretinal vessels in one of the cases was possible in histological sections. CONCLUSION: Preretinal neovascularisation may occur as a complication of choroidal melanoma. Possible aetiologies include the release of tumour angiogenic factors, inflammation, chronic retinal detachment with secondary retinal ischaemia, retinal vascular occlusion secondary to retinal vessel invasion by the tumour, or following radiation therapy. Optimal management of the neovascularisation is not known at this time. Supplemental localised scatter photocoagulation may be of benefit in some cases.

Retinoblastoma manifesting as orbital cellulitis.

Five children with previously undiagnosed retinoblastoma had signs of unilateral orbital cellulitis and were treated with systemic antibiotics, corticosteroids, or both. When retinoblastoma was finally diagnosed clinically, radiologists believed in every case that, on the basis of the soft-tissue swelling seen with computed tomography, there was orbital extension of the tumor. However, intraoperative and histopathologic observations disclosed no demonstrable orbital tumor involvement. The affected eyes all had neovascular glaucoma, and all harbored highly necrotic tumors that were contained within the eye. We concluded that orbital inflammation can occur with retinoblastoma confined to the eye and that signs of orbital cellulitis do not necessarily imply orbital extension of the tumor.

Clinical parameters predictive of enlargement of melanocytic choroidal lesions.

The authors followed up 197 melanotic choroidal lesions (62 categorised as benign naevi, 76 classified as suspicious naevi, 41 diagnosed as dormant melanomas, and 18 categorised as active melanomas) left untreated after their initial clinical documentation. Thirty-nine of these lesions enlarged during a five-year follow-up interval (cumulative proportion of lesions that enlarged = 26.2% by Kaplan-Meier method). Individual clinical parameters predictive of lesion enlargement (p less than 0.01) included larger size of the lesion, especially lesion thickness, presence of retinal detachment, location of the lesion's posterior margin within 2 disc diameters of the optic disc, presence of symptoms, and presence of orange pigment clumps on the lesion's surface. The best combination of these parameters for prediction of lesion enlargement, as identified by multivariate Cox regression analysis, consisted of thickness of the lesion, retinal detachment, and symptoms. The five-year incidence of lesion enlargement for patients with none of these prognostic parameters was 5.8%, while that for patients with all three unfavourable parameters simultaneously was 90.6%.

Clinicopathologic study of organic dye. Laser in the human fundus.

One day before enucleation for choroidal melanoma, four patients consented to experimental laser photocoagulation for the purpose of comparing the histopathologic appearance of acute chorioretinal lesions produced by various dye laser wavelengths with krypton red and argon green laser controls. Three patients had simulated "light" and "heavy" treatment of an extrafoveal choroidal neovascular membrane (CNVM) with wavelengths 577 nm (yellow), 595 nm (orange), and 600 nm (orange). One patient had simulated panretinal photocoagulation (PRP) with four different dye laser wavelengths. Extrafoveal "light" treatment with the three dye wavelengths and both controls spared the inner retina and produced similar effects in the outer retina, pigment epithelium, and choriocapillaris. Choroidal penetration was deepest with the longer wavelengths (590-647 nm) in both "light" and "heavy" treatment groups. "Heavy" treatment gave varying degrees of full-thickness retinal uptake for all dye and both control wavelengths. Both ends of the orange spectrum (590-600 nm) produced the most severe inner retinal uptake. Panretinal photocoagulation produced similar full-thickness retinal uptake for all four dye wavelengths tested. These results indicate that caution should be used when treating "heavily" with 590 and 600 nm in the extrafoveal area.

Natural course of melanocytic tumors of the iris.

The authors received the charts and photographs of 175 patients who had suspicious melanocytic lesions of the iris and who were followed without treatment. Only eight (4.6%) of these lesions showed clinical evidence of enlargement during follow-up intervals of 1 to 12 years (mean, 4.7 years). Features that were associated with enlargement of the lesion included medial location of the mass on the iris and presence of pigment dispersion onto the adjacent iris and anterior chamber angle structures. Features that were unassociated with growth of the lesion included patient age and sex, intraocular pressure, iris color, tumor size and vascularity, and presence of pupillary distortion, ectropion iridis, and sector cataract. From these results, recommendations are made which can assist the ophthalmologist in the management of pigmented iris lesions.

Acanthamoeba keratitis and infectious crystalline keratopathy.

Two cases of Acanthamoeba keratitis and infectious crystalline keratopathy, occurring simultaneously, are presented. Three and 12 months after initiating topical corticosteroid therapy in cases 1 and 2, respectively, alpha-hemolytic Streptococcus viridans was cultured from each cornea. Topical corticosteroid therapy was initiated for the treatment of an annular stromal opacity, presumably secondary to herpes simplex keratitis. Acanthamoeba was identified in culture following penetrating keratoplasty in case 1, and Acanthamoeba polyphaga, Acanthamoeba rhysodes, and Acanthamoeba castellanii were identified using indirect fluorescent antibody staining in case 2. Histopathologic examination and electron microscopy demonstrated sheets of cocci within stromal lamellae characteristic of infectious crystalline keratopathy and double-walled encysted organisms typical of Acanthamoeba. These case reports alert one to the possibility of developing bacterial keratitis, such as infectious crystalline keratopathy, following the use of topical corticosteroids for the treatment of Acanthamoeba keratitis.

Enlargement of melanocytic iris lesions.

We evaluated the natural history of 175 melanocytic lesions (nevus or melanoma) of the iris which were managed initially by observation without surgical intervention. Only eight of the 175 lesions (4.6%) enlarged during a median follow-up interval of 3.9 years. Univariate Cox regression analysis revealed that tumor location in the medical portion of the iris (P = 0.047) and pigment dispersion from the lesion onto the adjacent iris and trabecular meshwork (P = 0.056) were the only significant clinical conditions predictive of tumor enlargement. Based on these findings, we recommend conservative management of most melanocytic lesions of the iris.