[Urinary tract infection caused by Candida while using an SGLT-2 inhibitor]. / Urineweginfectie door Candida bij gebruik SGLT2-remmer.

BACKGROUND: Sodium glucose transporter 2 (SGLT-2) inhibitors are a relatively new group of antidiabetic drugs. The renal glucose reabsorption is blocked resulting in higher glucose levels in the urine (glucosuria). Recently studies are being conducted into the medications nephrological and cardiovascular potential. As a result, we may expect that SGLT-2 inhibitors will be more and more frequently prescribed. Thus, physicians of any specialty may come into contact with patients that are using this drug. CASE DESCRIPTION: We describe a case of a male patient who developed a urinary tract infection with Candida glabrata while using a SGLT-2 inhibitor. After discontinuing the SGLT-2 inhibitor, the infection subsided. CONCLUSION: Urinary tract infections from Candida are rarely seen in healthy individuals. Glucosuria is a known risk factor for fungal genital infections. More research is needed to determine whether SGLT-2 inhibitors increase the risk of fungal urinary tract infections.

[A man with a palpable node on the prostate]. / Een palpabele nodus in de prostaat.

A 64-year-old man was referred to our urology outpatient clinic with lower urinary tract symptoms (LUTS). During rectal examination a smooth nodule was identified. MRI-images showed a prostatic cyst, originating from the utriculus. An utriculus cyst is a relatively rare finding and originates from a persistent remnant of the Müllerian duct.

Sexual Concerns after (Pelvic) Radiotherapy: Is There Any Role for the Radiation Oncologist?

INTRODUCTION: Sexual function is an important aspect of quality of life, and may be impaired after (pelvic) radiation. AIM: The aim of this study was to identify practice, responsibility attitudes, knowledge, and barriers of Dutch radiation oncologists regarding sexual counseling. METHODS: A cross-sectional survey was performed using a 28-item questionnaire sent to all members of the Dutch Society for Radiotherapy and Oncology. MAIN OUTCOME MEASURES: Self-reported practice, knowledge, barriers, need for training and responsibility attitudes in regard to demographic characteristics. RESULTS: Of the surveyed sample, 54.6% of the radiation oncologists completed the instrument (n = 119). Frequency of discussing sexual function was fluctuating, depending on the type of tumor. The majority of the responding radiation oncologists (75%) agreed that discussing sexual function is their responsibility, about one-third (33.6%) pointed at the involved specialist (surgeon, urologist, gynecologist, or oncologist), a fifth also considered the general practitioner responsible (21%). Additional training about discussing sexuality was required according to 44.4%, the majority agreed that sexual counseling should be a regular component of radiation oncology residency (n = 110, 94%). Barriers most mentioned included patient is too ill (36.2%), no angle or reason for asking (32.4%), advanced age of the patient (27%) and culture/religion (26.1%). For prostate cancer patients, phosphodiesterase 5 inhibitor information was supplied regularly (49.2%) and often (40.7%). CONCLUSIONS: Radiation oncologists generally perform sexual counseling in case of pelvic radiation therapy, but not consistently in case of gastrointestinal, breast, and other cancers. The majority of radiation oncologists considered counseling on sexual functioning as a part of their job, some also pointed at the referring specialist or general practitioner. The findings suggest that awareness about sexual dysfunction is present among radiation oncologists, but responsibility for active counseling is uncertain. Results emphasize the need for providing educational and practical training, as well as a list for specialized referral.

The ocular disease of Aristodemus and Eurytus 480 BC: diagnostic considerations.

OBJECTIVE: In the historic description of Herodotus on the battle of Thermopylae at 480 BC two formerly healthy warriors suffer from "ophthalmia". The purpose of this study is to assess the possible aetiologies of this disease. DESIGN: We studied Herodotus' description in translation and offer a differential diagnosis. RESULTS: From the text we deduced that the "ophthalmia" was a condition in two physically fit males with a bilateral decreased or distorted vision, lasting longer than an hour, with an acute or subacute onset in Ancient Greece. The condition ultimately went into remission in one of the two patients, whereas the other subject deceased in combat not long after the onset of the disease, still suffering from the disease. The differential diagnosis consists of (1) anticholinergic syndrome secondary to an intoxication with the berries of the plant Atropa belladonna, (2) automutilation and (3) psychogenic loss of visual acuity. CONCLUSION: It is impossible to assess the ultimate cause of the "opthalmia" after 2500 years, but we suggest the anticholinergic syndrome by intoxication with Atropa belladonna is the most likely.

Margin evaluation in the presence of deformation, rotation, and translation in prostate and entire seminal vesicle irradiation with daily marker-based setup corrections.

PURPOSE: To develop a method for margin evaluation accounting for all measured displacements during treatment of prostate cancer. METHODS AND MATERIALS: For 21 patients treated with stereographic targeting marker-based online translation corrections, dose distributions with varying margins and gradients were created. Sets of possible cumulative delivered dose distributions were simulated by moving voxels and accumulating dose per voxel. Voxel motion was simulated consistent with measured distributions of systematic and random displacements due to stereographic targeting inaccuracies, deformation, rotation, and intrafraction motion. The method of simulation maintained measured correlation of voxel motions due to organ deformation. RESULTS: For the clinical target volume including prostate and seminal vesicles (SV), the probability that some part receives <95% of the prescribed dose, the changes in minimum dose, and volume receiving 95% of prescription dose compared with planning were 80.5% ± 19.2%, 9.0 ± 6.8 Gy, and 3.0% ± 3.7%, respectively, for the smallest studied margins (3 mm prostate, 5 mm SV) and steepest dose gradients. Corresponding values for largest margins (5 mm prostate, 8 mm SV) with a clinical intensity-modulated radiotherapy dose distribution were 46.5% ± 34.7%, 6.7 ± 5.8 Gy, and 1.6% ± 2.3%. For prostate-only clinical target volume, the values were 51.8% ± 17.7%, 3.3 ± 1.6 Gy, and 0.6% ± 0.5% with the smallest margins and 5.2% ± 7.4%, 1.8 ± 0.9 Gy, and 0.1% ± 0.1% for the largest margins. Addition of three-dimensional rotation corrections only improved these values slightly. All rectal planning constraints were met in the actual reconstructed doses for all studied margins. CONCLUSION: We developed a system for margin validation in the presence of deformations. In our population, a 5-mm margin provided sufficient dosimetric coverage for the prostate. In contrast, an 8-mm SV margin was still insufficient owing to deformations. Addition of three-dimensional rotation corrections was of minor influence.

Dose escalation and quality of life in patients with localized prostate cancer treated with radiotherapy: long-term results of the Dutch randomized dose-escalation trial (CKTO 96-10 trial).

PURPOSE: To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients. PATIENTS AND METHODS: Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of ≥10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates. RESULTS: At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores. CONCLUSION: Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant.

Changes in the penile arteries of the rat after fractionated irradiation of the prostate: a pilot study.

INTRODUCTION: External beam radiotherapy for prostate cancer leads to erectile dysfunction in 36%-43% of patients. The underlying mechanism is largely unknown, although some clinical studies suggest that the arterial supply to the corpora cavernosa is responsible. Two animal experimental studies reported on the effects of a single fraction of prostate irradiation on the penile structures. However, irradiation in multiple fractions is more representative of the actual clinical treatment. AIM: The present prospective, controlled study was initiated to investigate the effect of fractionated prostate irradiation on the arteries of the corpora cavernosa. MAIN OUTCOME MEASURES: Histological evaluation of the penile tissue in comparison with control rats at 2, 4, and 9 weeks after irradiation. METHODS: The prostate of twelve rats was treated with external beam radiation in 5 daily fractions of 7.4 gray. Three control rats were treated with sham irradiation. Prostatic and penile tissue was evaluated for general histology (hematoxylin-eosin). The penile tissue was further evaluated after combined staining for collagen (resorcin fuchsin) and alpha-smooth muscle actin (SMA) (Biogenex). RESULTS: The prostate showed adequate irradiation with fibrosis occurring at 9 weeks after irradiation. The corpora cavernosa showed arteries that had developed loss of smooth muscle cells expressing SMA, thickening of the intima, and occlusions. All the control rats maintained normal anatomy. CONCLUSION: This is the first animal experimental study that demonstrates changes in the arteries of the corpora cavernosa after fractionated irradiation to the prostatic area. The preliminary data suggests that erectile dysfunction after radiotherapy might be caused by radiation damage to the arterial supply of the corpora cavernosa.

Deformation of prostate and seminal vesicles relative to intraprostatic fiducial markers.

PURPOSE: To quantify the residual geometric uncertainties after on-line corrections with intraprostatic fiducial markers, this study analyzed the deformation of the prostate and, in particular, the seminal vesicles relative to such markers. PATIENTS AND METHODS: A planning computed tomography (CT) scan and three repeat CT scans were obtained for 21 prostate cancer patients who had had three to four cylindrical gold markers placed. The prostate and whole seminal vesicles (clinical target volume [CTV]) were delineated on each scan at a slice thickness of 1.5 mm. Rigid body transformations (translation and rotation) mapping the markers onto the planning scan positions were obtained. The translation only (T(only)) or both translation and rotation were applied to the delineated CTVs. Next, the residue CTV surface displacements were determined using nonrigid registration of the delineated contours. For translation and rotation of the CTV, the residues represented deformation; for T(only), the residues stemmed from deformation and rotation. T(only) represented the residues for most currently applied on-line protocols. The patient and population statistics of the CTV surface displacements were calculated. The intraobserver delineation variation was similarly quantified using repeat delineations for all patients and corrected for. RESULTS: The largest CTV deformations were observed at the anterior and posterior side of the seminal vesicles (population average standard deviation

Dose-volume parameters of the corpora cavernosa do not correlate with erectile dysfunction after external beam radiotherapy for prostate cancer: results from a dose-escalation trial.

PURPOSE: To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer. METHODS AND MATERIALS: Between June 1997 and February 2003, a randomized dose-escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose-volume parameters were calculated. RESULTS: Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose-volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED. CONCLUSION: No correlation was found between ED after EBRT for prostate cancer and radiation dose to the crura or penile bulb. The present study is the largest study evaluating the correlation between ED and radiation dose to the corpora cavernosa after EBRT for prostate cancer. Until there is clear evidence that sparing the penile bulb or crura will reduce ED after EBRT, we advise to be careful in sparing these structures, especially when this involves reducing treatment margins.

Stereographic targeting in prostate radiotherapy: speed and precision by daily automatic positioning corrections using kilovoltage/megavoltage image pairs.

PURPOSE: A fully automated, fast, on-line prostate repositioning scheme using implanted markers, kilovoltage/megavoltage imaging, and remote couch movements has been developed and clinically applied. The initial clinical results of this stereographic targeting (SGT) method, as well as phantom evaluations, are presented. METHODS AND MATERIALS: Using the SGT method, portal megavoltage images are acquired with the first two to six monitor units of a treatment beam, immediately followed by acquisition of an orthogonal kilovoltage image without gantry motion. The image pair is automatically analyzed to obtain the marker positions and three-dimensional prostate displacement and rotation. Remote control couch shifts are applied to correct for the displacement. The SGT performance was measured using both phantom images and images from 10 prostate cancer patients treated using SGT. RESULTS: With phantom measurements, the accuracy of SGT was 0.5, 0.2, and 0.3 mm (standard deviation [SD]) for the left-right, craniocaudal, and anteroposterior directions, respectively, for translations and 0.5 degrees (SD) for the rotations around all axes. Clinically, the success rate for automatic marker detection was 99.5%, and the accuracy was 0.3, 0.5 and 0.8 mm (SD) in the left-right, craniocaudal, and anteroposterior axes. The SDs of the systematic center-of-mass positioning errors (Sigma) were reduced from 4.0 mm to <0.5 mm for all axes. The corresponding SD of the random (sigma) errors was reduced from 3.0 to <0.8 mm. These small residual errors were achieved with a treatment time extension of <1 min. CONCLUSION: Stereographic targeting yields systematic and random prostate positioning errors of <1 mm with <1 min of added treatment time.

Erectile dysfunction after radiotherapy for prostate cancer and radiation dose to the penile structures: a critical review.

Erectile dysfunction (ED) is a common sequela after external beam radiotherapy and brachytherapy for prostate cancer. There are several structures in the vicinity of the prostate that are critical to erectile function and that receive a substantial radiation dose: neurovascular bundles (NVBs), internal pudendal arteries (IPAs), accessory pudendal arteries, corpora cavernosa and the penile bulb. Most reports analyzing the correlation between radiation dose to these structures and radiation-induced ED are limited by the small number of patients analyzed in each study. So far, there is no evidence for a role of the NVBs in radiation-induced ED. There are no reports on the IPAs, based on reduced arterial flow in the penis. Several studies show contradicting results on the corpora cavernosa, which house the erectile tissue required for erection. There are contradicting reports on the penile bulb, although studies with more patients tend not to find any correlation. Sparing of the penile bulb to improve potency-preservation is not sufficiently supported by the current literature. If sparing of the penile bulb is achieved by reducing the margin for the apex, an oncological risk is taken, while it is uncertain whether this will improve potency-preservation.

Sexual function after three-dimensional conformal radiotherapy for prostate cancer: results from a dose-escalation trial.

PURPOSE: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. METHODS AND MATERIALS: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. RESULTS: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%. After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. CONCLUSION: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.