Daniel Engeler

The 2013 EAU Guidelines on Chronic Pelvic Pain: Is Management of Chronic Pelvic Pain a Habit, a Philosophy, or a Science? 10 Years of Development

CONTEXTnProgress in the science of pain has led pain specialists to move away from an organ-centred understanding of pain located in the pelvis to an understanding based on the mechanism of pain and integrating, as far as possible, psychological, social, and sexual dimensions of the problem. This change is reflected in all areas, from taxonomy through treatment. However, deciding what is adequate investigation to rule out treatable disease before moving to this way of engaging with the patient experiencing pain is a complex process, informed by pain expertise as much as by organ-based medical knowledge.nnnOBJECTIVEnTo summarise the evolving changes in the management of patients with chronic pelvic pain by referring to the 2012 version of the European Association of Urology (EAU) guidelines on chronic pelvic pain.nnnEVIDENCE ACQUISITIONnThe working panel highlights some of the most important aspects of the management of patients with chronic pelvic pain emerging in recent years in the context of the EAU guidelines on chronic pelvic pain. The guidelines were completely updated in 2012 based on a systematic review of the literature from online databases from 1995 to 2011. According to this review, levels of evidence and grades of recommendation were added to the text. A full version of the guidelines is available at the EAU office or Web site (www.uroweb.org).nnnEVIDENCE SYNTHESISnThe previously mentioned issues are explored in this paper, which refers throughout to dilemmas for the physician and treatment team as well as to the need to inform and engage the patient in a collaborative empirical approach to pain relief and rehabilitation. These issues are exemplified in two case histories.nnnCONCLUSIONSnChronic pelvic pain persisting after appropriate treatment requires a different approach focussing on pain. This approach integrates the medical, psychosocial, and sexual elements of care to engage the patient in a collaborative journey towards self-management.

Management of von Hippel-Lindau Disease: An Interdisciplinary Review

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumour predisposition syndrome with an incidence of 1:36,000 newborns, the estimated prevalence in Europe is about 1-9/100,000. It is associated with an increased risk of developing various benign and malignant tumours, thus affecting multiple organs at different time points in the life of a patient. Disease severity and diversity as well as age at first symptoms vary considerably, and diagnostic delay due to failure of recognition is a relevant issue. The identification of a disease-causing VHL germline mutation subsequently allows family members at risk to undergo predictive genetic testing after genetic counselling. Clinical management of patients and families should optimally be offered as an interdisciplinary approach. Prophylactic screening programs are a cornerstone of care, and have markedly improved median overall survival of affected patients. The aim of this review is to give an overview of the heterogeneous manifestations of the VHL syndrome and to highlight the diagnostic and therapeutic challenges characteristic for this orphan disease. A comprehensive update of the underlying genetic and molecular principles is additionally provided. We also describe how the St. Gallen VHL multidisciplinary group is organised as an example of interdisciplinary cooperation in a tertiary hospital in Switzerland.

The ideal analgesic treatment for acute renal colic--theory and practice.

Objective. With an annual incidence of 0.1–0.4%, renal colic is certainly a frequent disorder. Thanks to recent findings, the approach to treatment is changing. This prompted us to conduct a survey amongst all urologists in Switzerland regarding the analgesic measures they use in patients suffering from acute renal colic. Material and methods. In March 2005, we sent a total of 170 questionnaires to all practising urologists who are also members of the Swiss Urology Society. The questions covered the types of drugs used for first- and second-line analgesic therapy in acute renal colic and the approach to acute and follow-up analgesic therapy. Dosage adjustments in patients with renal failure were also included. The responses were compared with recent literature findings and international guidelines. Results. The response rate was 58%. Non-opioid analgesics are used for first-line therapy by 81% of respondents, with metamizol being used in 64% of cases. First-line therapy is given intravenously in 65% of cases. An opioid (pethidine) is used most frequently as acute second-line therapy (74% of cases). In the presence of renal failure, half of the respondents make a dose adjustment to the analgesic. Follow-up therapy consists mainly of non-steroidal anti-inflammatory drugs (75%). This complies with the literature and with the recommendations of the European Association of Urology. Conclusion. First-line therapy for acute renal colic should consist of a non-opioid analgesic, and only if the response to this is inadequate should opioids then be used.

Prostate biopsy in Switzerland: a representative survey on how Swiss urologists do it.

Objective. The procedure of prostate biopsy is often performed but has not been standardized. Therefore, a survey of all urologists in Switzerland was carried out to investigate indications, patient preparation and technique with regard to transrectal prostate biopsy. Material and methods. A questionnaire was mailed to all 178 urologists working in Switzerland, either as self-employed urologists (SEUs) or as employed urologists at a hospital (EUHs), i.e. a teaching centre. Results. The questionnaire was returned by 133 urologists (75%). Eighty-seven of the respondents (65%) are SEUs and 46 (35%) work as EUHs. If digital rectal examination (DRE) raises suspicion of cancer, 129 urologists perform a biopsy. A serum prostate-specific antigen (PSA) level of 4 ng/ml is used as a cut-off value by 84% of respondents (SEUs 83%, EUHs 87%). A fluoroquinolone antibiotic is prescribed by 126 of the respondents. Fifty-nine percent of respondents (SEUs 52%, EUHs 72%) are offering periprostatic injection of a local anaesthetic drug. At the initial biopsy, 24% of respondents (SEUs 30%, EUHs 13%) obtain six cores, 45% (SEUs 37%, EUHs 61%) 8–10 and 17% (SEUs 18%, EUHs 15%) ≥12. The subsequent procedure performed after two negative biopsy sessions varies considerably. Conclusions. This survey provides an insight into the practice pattern of urologists in Switzerland concerning prostate biopsy. For almost all urologists, a positive DRE is an indication for prostate biopsy. The majority use a serum PSA level of 4 ng/ml as a cut-off value. A fluoroquinolone is the antibiotic of choice. Periprostatic nerve block is the commonest form of anaesthesia. Most urologists take 8–10 cores per biopsy.

Erectile function following brachytherapy, external beam radiotherapy, or radical prostatectomy in prostate cancer patients

Background and purposeFor localized prostate cancer, treatment options include external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT). Erectile dysfunction (ED) is a common side-effect. Our aim was to evaluate penile erectile function (EF) before and after BT, EBRT, or RP using a validated self-administered quality-of-life survey from a prospective registry.Material and methodsAnalysis included 478 patients undergoing RP (nu2009=u2009252), EBRT (nu2009=u200991), and BT (nu2009=u2009135) with at least 1 year of follow-up and EF documented using IIEF-5 scores at baseline, 6 weeks, 6 months, 1 year, and annually thereafter.ResultsDifferences among treatments were most pronounced among patients with no or mild initial ED (IIEF-5u2009≥u200917). Overall, corrected for baseline EF and age, BT was associated with higher IIEF-5 scores than RP (+u20097.8 IIEF-5 score) or EBRT (+u20093.1 IIEF-5 score). EBRT was associated with better IIEF-5 scores than RP (+u20094.7 IIEF-5 score). In patients undergoing EBRT or RP with bilateral nerve sparing (NS), recovery of EF was observed and during follow-up, the differences to BT were not statistically significant. Overall age had a negative impact on EF preservation (corrected for baseline IIEF).ConclusionIn our series, EF was adversely affected by each treatment modality. Considered overall, BT provided the best EF preservation in comparison to EBRT or RP.ZusammenfassungHintergrund und ZielDie externe Radiotherapie (EBRT), die radikale Prostatektomie (RP) sowie die Brachytherapie (BT) stellen Behandlungsoptionen für das lokalisierte Prostatakarzinom dar. Die erektile Dysfunktion (ED) ist eine häufige Nebenwirkung dieser Therapien. Unser Ziel war es, die penile erektile Funktion (EF) vor und nach BT, EBRT und RP mit Hilfe eines validierten, vom Patienten ausgefüllten Lebensqualitätsfragebogens aus einer prospektiven Datenbank zu beurteilen.Material und MethodenMit einer minimalen Nachbeobachtungszeit von einem Jahr wurden 478 Patienten analysiert, die eine RP (nu2009=u2009252), EBRT (nu2009=u200991) oder BT (nu2009=u2009135) erhalten hatten und deren EF mit dem IIEF-5-Score vor Therapie sowie nach 6 Wochen, 6 Monaten, nach einem Jahr und danach jährlich ermittelt worden sind.ErgebnisDie größten therapiebedingten Unterschiede wurden bei Patienten ohne oder nur mit milder initialer ED beobachtet (IIEF-5u2009≥u200917). Korrigiert für die EF und das Alter bei Therapie, war die BT mit höherem IIEF-5-Score assoziiert als die RP (+u20097,8 IIEF-5-Score) oder die EBRT (+u20093,1 IIEF-5-Score). Die EBRT war mit einem besseren IIEF-5-Score assoziiert als die RP (+u20094,7 IIEF-5-Score). Bei Patienten mit bilateraler nervenschonender RP oder einer EBRT wurde eine Erholung der EF beobachtet; im Verlauf war der Unterschied zur BT nicht mehr statistisch signifikant. Insgesamt hatte ein höheres Alter einen negativen Einfluss auf die Erhaltung der EF (korrigiert für Ausgangs-EF).SchlussfolgerungIn unserer Serie verschlechterte sich die EF durch alle Therapieformen. Insgesamt bot die BT die beste EF-Erhaltung verglichen mit der EBRT oder RP.

Re-implantation after insufficient primary 125-i permanent prostate brachytherapy

IntroductionWe describe five patients receiving a re-implantation (RI) after post-operative dosimetry of the primary 125-I permanent prostate brachytherapy (BT) for prostate cancer revealed an insufficient dose coverage.Materials and methodsFive out of 222 consecutive patients treated (from March, 2001 to August, 2012) with 125-I BT, received a RI after dosimetric verification by CT and MRI fusion four to eight weeks after implantation displayed an insufficient dose coverage. RIs were performed with 10 to 19 seeds, three to four months after primary intervention. Dosimetry after RI showed an improved and sufficient total dose coverage in all patients.ResultsAt last follow-up (18 to 99xa0months, median 57xa0months), none of the patients had relevant implant associated side-effects. Functional outcome was comparable to patients after one-time implantation. PSA levels post intervention showed a decreasing tendency in 4 patients. One patient had a local recurrence after 12xa0months.ConclusionIn our series, approximately 2% of the patients treated with permanent prostate BT required a RI due to insufficient dose coverage. None of the patients who underwent RI experienced complications. Our series, although only with 5 cases and limited follow-up, along with other published reports, demonstrates good tolerability.

Development and clinical testing of individual immunoassays for the quantification of serum glycoproteins to diagnose prostate cancer.

Prostate Cancer (PCa) diagnosis is currently hampered by the high false-positive rate of PSA evaluations, which consequently may lead to overtreatment. Non-invasive methods with increased specificity and sensitivity are needed to improve diagnosis of significant PCa. We developed and technically validated four individual immunoassays for cathepsin D (CTSD), intercellular adhesion molecule 1 (ICAM1), olfactomedin 4 (OLFM4), and thrombospondin 1 (THBS1). These glycoproteins, previously identified by mass spectrometry using a Pten mouse model, were measured in clinical serum samples for testing the capability of discriminating PCa positive and negative samples. The development yielded 4 individual immunoassays with inter and intra-variability (CV) <15% and linearity on dilution of the analytes. In serum, ex vivo protein stability (<15% loss of analyte) was achieved for a duration of at least 24 hours at room temperature and 2 days at 4°C. The measurement of 359 serum samples from PCa positive (n = 167) and negative (n = 192) patients with elevated PSA (2–10 ng/ml) revealed a significantly improved accuracy (P <0.001) when two of the glycoproteins (CTSD and THBS1) were combined with %fPSA and age (AUC = 0.8109; P <0.0001; 95% CI = 0.7673–0.8545). Conclusively, the use of CTSD and THBS1 together with commonly used parameters for PCa diagnosis such as %fPSA and age has the potential to improve the diagnosis of PCa.

Salvage radiotherapy for macroscopic local recurrences after radical prostatectomy

IntroductionAlthough salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy.Material and methodsA total of 14 Swiss radiation oncology centers were asked to complete axa0survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology.ResultsThe majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66u2009Gy (range 65–72u2009Gy) with axa0boost to the macroscopic lesion used by 79% of the centers with axa0median total dose of 72u2009Gy (range 70–80u2009Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined.ConclusionWe observed axa0high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.ZusammenfassungEinleitungObwohl die Evidenz für eine frühzeitige Salvage-Radiotherapie (SRT) bei einem PSA-Rezidiv nach radikaler Prostatektomie spricht, werden viele Patienten erst bei einem makroskopischen Lokalrezidiv behandelt. Hier scheint es jedoch aufgrund der fehlenden Daten aus prospektiven Studien eine Variabilität der Behandlungskonzepte zu geben. Das Ziel der Studie war es, die aktuelle Behandlungspraxis in der SRT des makroskopischen Rezidivs eines Prostatakarzinoms zu untersuchen.Material und MethodenInsgesamt 14 Schweizer Strahlentherapiezentren wurden für eine Umfrage zu den Behandlungsparametern beim makroskopischen Lokalrezidiv eines Prostatakarzinoms kontaktiert und nach diagnostischen Maßnahmen, Dosisverschreibung, Strahlentherapietechniken und antihormoneller Therapie (ADT) befragt. Die variierenden Indikationen zur ADT wurden mittels der Objective-konsensus-Methodologie ausgewertet.ErgebnisseDie Mehrheit der Zentren empfahl vor der Therapie eine Magnetresonanztomographie (MRT) des Beckens und eine Cholin-Positronenemissionstomographie (PET). Die mediane verschriebene Dosis für die Prostataloge war 66u2009Gy (65–72u2009Gy) mit einem Boost auf das makroskopische Lokalrezidiv in 79u2009% der Zentren bis zu einer medianen Dosis von 72u2009Gy (70–80u2009Gy). Alle Zentren verwendeten intensitätsmodulierte Rotationstechniken, ein tägliches Cone-beam-CT wurde in 43u2009% der Zentren empfohlen. Eine begleitende ADT wurde von 43u2009% für jedes makroskopische Lokalrezidiv empfohlen, während die übrigen Zentren dies nur bei Hochrisikogruppen (mit unterschiedlichen Definitionen) durchführten.SchlussfolgerungEs wurde eine hohe Variabilität der Behandlungskonzepte für die SRT des makroskopischen Lokalrezidivs nach Prostatektomie beobachtet. Dies zeigt den Bedarf an standardisierten Behandlungskonzepten und weiteren Studien in diesem Bereich auf.

Therapie und Nachsorge bei malignen Blasentumoren

SummaryTreatment and follow up of bladder cancer strongly depends on stage and differentiation of the tumour. Superficial bladder tumours can mostly be controlled by transurethral resection followed by early intravesical application of a chemotherapeutic agent and a further close meshed follow-up. Generally, for muscle-invasive tumours radical cystectomy is indicated, whereas organ-spearing treatment due to combined therapeutic concepts can be offered in selected cases. For advanced and metastatic tumours, despite good response of bladder cancer to chemotherapy, prognosis is still poor. However, implementation of new chemotherapeutic agents indicate a trend towards improved survival rates.ZusammenfassungDie Therapie und Nachsorge des Blasenkarzinoms richtet sich stark nach dessen Stadium und Differenzierung. Die oberflächlichen Blasentumoren lassen sich grösstenteils organerhaltend durch eine transurethrale Resektion, ergänzt durch eine intravesikal applizierte Frühinstillation eines Chemotherapeutikums und gefolgt von einer engmaschigen Nachsorge beherrschen. Bei den muskelinvasiven Tumoren ist in der Regel die radikale Zystekomie indiziert, wobei mit neuen kombinierten Behandlungskonzepten in ausgewählten Fällen auch organerhaltend therapiert werden kann. Die lokal fortgeschrittenen und metastasierten Blasenkarzinome haben trotz guter Ansprechraten der Chemotherapeutika weiterhin eine sehr ungünstige Prognose, aber auch hier zeigt sich durch neu eingesetzte Substanzen eine tendenzielle Verbesserung des Gesamtüberlebens.

Advanced non-contrasted computed tomography post-processing by CT-Calculometry (CT-CM) outperforms established predictors for the outcome of shock wave lithotripsy

ObjectivesTo evaluate the predictive value of advanced non-contrasted computed tomography (NCCT) post-processing using novel CT-calculometry (CT-CM) parameters compared to established predictors of success of shock wave lithotripsy (SWL) for urinary calculi.Materials and MethodsNCCT post-processing was retrospectively performed in 312 patients suffering from upper tract urinary calculi who were treated by SWL. Established predictors such as skin to stone distance, body mass index, stone diameter or mean stone attenuation values were assessed. Precise stone size and shape metrics, 3-D greyscale measurements and homogeneity parameters such as skewness and kurtosis, were analysed using CT-CM. Predictive values for SWL outcome were analysed using logistic regression and receiver operating characteristics (ROC) statistics.ResultsOverall success rate (stone disintegration and no re-intervention needed) of SWL was 59% (184 patients). CT-CM metrics mainly outperformed established predictors. According to ROC analyses, stone volume and surface area performed better than established stone diameter, mean 3D attenuation value was a stronger predictor than established mean attenuation value, and parameters skewness and kurtosis performed better than recently emerged variation coefficient of stone density. Moreover, prediction of SWL outcome with 80% probability to be correct would be possible in a clearly higher number of patients (up to fivefold) using CT-CM-derived parameters.ConclusionsAdvanced NCCT post-processing by CT-CM provides novel parameters that seem to outperform established predictors of SWL response. Implementation of these parameters into clinical routine might reduce SWL failure rates.