Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

[Low-grade serous ovarian carcinoma: A retrospective study on 34 complete cytoreductive surgeries]. / Carcinome séreux de bas grade ovarien à un stade avancé : étude rétrospective sur 34 patientes en résection complète.

AIM OF THE STUDY: Low-grade serous ovarian cancer is a distinct, slow-growing entity that affects mainly young women. The objective of this study was to describe the clinical characterisitics and survival outcomes of a population of patients suffering from advanced stage CSBG. PATIENTS AND METHODS: A retrospective study was carried out in patients with advanced stage ovarian CSBG (FIGO IIIb-IV) who had complete macroscopic cytoreductive surgery, at Gustave Roussy Institut, Villejuif, between 2004 and 2017. RESULTS: Thirty-four patients were included, who were mainly young women (mean age 41.3 years), diagnosed at FIGO stage IIIC (91 %). The median follow-up was 41 months. Neoadjuvant chemotherapy was administered in 16 patients (47.1 %), and complete response never occurred. Upper abdominal surgical procedures were necessary in 90 % of cases and a bowel resection was performed in more than 80 % of cases. Over 90 % of patients received adjuvant chemotherapy followed by maintenance treatment with bevacizumab in over 40 % of cases. During follow-up, 9 (26 %) deaths occurred. Five-year overall survival was 70 % and disease-free survival was 20 %. CONCLUSION: CSBG of the ovary has a low chemosensitivity and requires maximum surgical management, which should be performed in expert centers.

Medium-term Follow-up of Vascular-targeted Photodynamic Therapy of Localized Prostate Cancer Using TOOKAD Soluble WST-11 (Phase II Trials).

BACKGROUND AND OBJECTIVE: To assess the medium-term tumor control in patients with localized prostate cancer (PCa) treated with vascular-targeted photodynamic (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term tolerability of the treatment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: During the clinical phase II studies, 68 patients were treated with VTP under optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a light density index ≥1) and have been included in a 3.5-yr follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-interventional visits were scheduled every 6 mo and conducted as per local standard practice in each study center. Cancer-free status was assessed by means of prostate-specific antigen kinetics, multiparametric magnetic resonance imaging and/or prostate biopsies. RESULTS AND LIMITATIONS: At the end of the 3.5-yr follow-up, overall successful focal ablation was achieved for 51 patients (75%). Cancer was identified in the untreated lobe in 17 patients (25%). In total, 34 patients (50%) were cancer-free in both the prostate lobes. In case of recurrent/persistent malignancy, the Gleason score remained consistent or changed at the maximum by one point (upgrading by 1 Gleason point to 3+4 for eight patients and 4+3 for two patients). There were 64 related adverse events (AEs): 48% were Clavien grade I, 47% were grade II, and 5% were grade III. There were no Clavien grade IV and V AEs. Limitations included small sample size and heterogeneity in the follow-up for some centers. CONCLUSIONS: VTP is a safe and efficient treatment and represents an alternative option for localized low-risk PCa management over the medium term. Precise diagnostic methods and imaging tools are thereby essential requirements to ensure safe and complete targeted therapy. PATIENT SUMMARY: In this report, we looked at the medium-term outcomes of focal photodynamic therapy for early-stage prostate cancer. We found that this form of treatment is efficient and might have the potential to become a therapeutic option for low-risk cancer. Effectiveness depends on precise diagnostic methods, such as magnetic resonance imaging and accurate biopsy.

Functional Outcome of Completely Intracorporeal Robotic Ileal Ureteric Replacement.

OBJECTIVE: To assess perioperative, clinical, and functional outcomes following completely robotic ileal ureter. METHODS: We retrospectively reviewed 7 consecutive patients undergoing completely intracorporeal ileal ureteric replacement between November 2015 and May 2017. One patient had a solitary kidney. A 4-arm technique was used. In 5 patients, additional psoas hitch procedure was performed. Patients had retrograde filling and removal of the ileal stent and transurethral catheter at an average of 14 days postoperatively. Renal ultrasonography, serum analysis, and diuretic renography were performed at follow-up 3 months postoperatively. RESULTS: Mean operative time was 328 ± 66.3 minutes and median estimated blood loss was 100 mL (range 50-200); mean length of the ileal substitute was 20.4 cm (range 18-24). No case was converted to open surgery. In 1 patient, there was a prolonged insufficiency of the pyeloileal anastomosis, requiring prolonged stenting. Apart from that, there were no major complications and no open surgical or endoscopic reinterventions. On 3-month follow-up, all patients presented symptom-free, with no signs of obstruction on ultrasound and significantly improved glomerular filtration rate, creatinine levels, and differential renal function (P = .02, 0.03, and 0.046, respectively). Five patients had a diuretic halftime <10 minutes, 2 had a halftime between 10 and 20 minutes. CONCLUSION: Completely intracorporeal robotic ileal ureteric replacement results in full functional restoration of the upper tract in cases of long defects of the mid and upper ureter.

[Minimally invasive vs. open partial nephrectomy : Perioperative success and complication rates]. / Minimal-invasive vs. offene Nierenteilresektionen : Perioperative Erfolgs- und Komplikationsraten.

BACKGROUND: Solid renal masses are increasingly treated with nephron-sparing surgery. As in other uro-oncological surgical techniques, minimally invasive and robotic-assisted techniques are becoming increasingly popular. OBJECTIVES: The perioperative results from minimally invasive nephron-sparing surgery versus open surgery were retrospectively compared. MATERIALS AND METHODS: In our single center retrospective study, all patients who underwent nephron-sparing tumor excision between 2006 and 2016 were divided into two groups (group O = open approach and group M = minimally invasive approach). The (pre-)operative data, complications, and change in renal function were compared. Trifecta criteria (R0, no perioperative complications, ischemia ≤25 min) were used to determine success rates. RESULTS: Of 329 patients, 310 were included for analysis (group O 123, group M 187). Patients in group O had significantly worse ASA score but comparable Charlson Index and significantly more pT3/4 tumors but equal PADUA-score when compared with group M. Otherwise, preoperative patient and tumor characteristics were comparable. Patients in group M had significantly shorter hospital stays (p < 0.001) and lower transfusion rates (p < 0.05). Trifecta criteria were more frequently met in group M than in O (M: 66.8% vs. 0: 49.6%; p < 0.001). Both major and minor complications were lower in group M (major: 10.7% vs 17.1%; minor: 13.9% vs. 26.0%; p < 0.05). Preservation of renal function was comparable in both groups. R0 rates did not differ significantly between groups (M: 97.8% vs O: 97.5%). Surgical procedure times were significantly longer in group M (p < 0.001; mean 30 min). CONCLUSIONS: Minimally invasive, robotic assisted partial nephrectomy also proved to be successful in complex cases. In all aspects studied, the minimally invasive approach was shown to be at least equivalent to the open approach.

Performance comparison of protein A affinity resins for the purification of monoclonal antibodies.

During the selection of protein A affinity resin for the purification of monoclonal antibodies, dynamic binding capacity (Q(dyn10%)), volumetric production rate (Pr(vol)) and 'process robustness' are essential parameters to be evaluated. In this article, empirical mathematical models describe these parameters as a function of antibody concentration in load (C0), load flow rate (u(load)) and bed height (L). These models allow us to select optimal process conditions for each of the evaluated protein A affinity resins. C0, u(load) and L largely affect dynamic binding capacity (Q(dyn10%)) and volumetric production rate (Pr(vol)). Maximum Q(dyn10%) is generally obtained at high C0 and at low u(load). Maximum Pr(vol) is obtained at high C0 and at lowest L, run at high u(load). All evaluated resins have a relatively high robustness against variations in C0. |DeltaQ(dyn10%)/deltaC0| ranges from 0.0 to 7.8. It is clear that Q(dyn10%), Pr(vol) and 'process robustness' cannot be maximized all at the same time. Furthermore, some other aspects like IgG recovery, protein A leaching, easiness to pack, easiness to clean, number of re-uses and cost of production might be important to be taken into the equation. Certain evaluation parameters may be more important than others, depending on the specific situation. Therefore, a case-by-case evaluation is recommended.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

[Focal therapy for small renal masses : Observation, ablation or surgery]. / Fokale Therapie von kleinen Nierentumoren : Beobachtung, Ablation oder Operation.

BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.

Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation.

Neurotrophin-4 (NT-4) is perhaps the still most enigmatic member of the neurotrophin family. We show here that NT-4 is expressed in neurons of paravertebral and prevertebral sympathetic ganglia, i.e., the superior cervical (SCG), stellate (SG), and celiac (CG) ganglion. Mice deficient for NT-4 showed a significant reduction (20-30%) of preganglionic sympathetic neurons in the intermediolateral column (IML) of the thoracic spinal cord. In contrast, neuron numbers in the SCG, SG, and CG were unchanged. Numbers of axons in the thoracic sympathetic trunk (TST) connecting the SG with lower paravertebral ganglia were also reduced, whereas axon numbers in the cervical sympathetic trunk (CST) were unaltered. Axon losses in the TST were paralleled by losses of synaptic terminals on SG neurons visualized by electron microscopy. Furthermore, immunoreactivity for the synaptic vesicle antigen SV2 was clearly reduced in the SG and CG. Levels of catecholamines and tyrosine hydroxylase immunoreactivity were dramatically reduced in the SG and the CG but not in the SCG. Despite this severe phenotype in the sympathetic system, blood pressure levels were not reduced and displayed a pattern more typical of deficits in baroreceptor afferents. Numbers of IML neurons were unaltered at postnatal day 4, suggesting a postnatal requirement for their maintenance. In light of these and previous data, we hypothesize that NT-4 provided by postganglionic sympathetic neurons is required for establishing and/or maintaining synapses of IML neurons on postganglionic cells. Impairment of synaptic connectivity may consequently reduce impulse flow, causing a reduction in transmitter synthesis in postganglionic neurons.

[Cancer control in focus insights and future perspectives for the focal treatment of prostate cancer]. / Krebskontrolle im Fokus - Einblicke und Ausblicke rund um die fokale Therapie des Prostatakrebses.

Faced with the dilemma of choosing between the extremes of standard whole gland therapy and active surveillance, those affected by prostate cancer have recently been on the lookout for less invasive alternatives. Particularly the question of whether it would be possible in low risk cancer to treat only the tumour itself while sparing the organ has long been considered. This article discusses the pros and cons of focal treatment and elucidates the latest innovative technologies. High overtreatment rates in low-risk patients submitted to standard therapy and considerable technological advances in diagnosis (particularly multiparametric MRI) and therapy are regarded by the authors as key arguments for abandoning complete tumour eradication with its side effects in favour of sufficient local cancer control by focal treatment with better preserved quality of life in suitable cases.

[Irreversible electroporation. Current value for focal treatment of prostate cancer]. / Irreversible Elektroporation. Aktueller Stellenwert in der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy (FT) with its postulated features, especially the absence of a thermal ablative effect. Thus far, there is no adequate tumor-entity-specific proof of its effectiveness, and its clinical application has hitherto been confined to very small patient cohorts. This also holds true for prostate cancer (PCA). Nevertheless, it is now being increasingly applied outside clinical trials-to a certain extent due to active advertising in the lay press. AIM OF THE STUDY: In this study, current discrepancies between the clinical application and study situation and the approval and market implementation of the procedure are described. The media portrayal of IRE is discussed from different perspectives, particularly with reference to the FT of PCA. This is followed by a final clinical assessment of IRE using the NanoKnife® system. DISCUSSION: Strict requirements govern new drug approvals. According to the German Drug Act (AMG), evidence of additional benefit over existing therapy must be provided through comparative clinical trials. For medicotechnical treatment procedures, on the other hand, such trial-based proof is not required according to the Medical Devices Act (MPG). The use of IRE even outside clinical trials has been actively promoted since the NanoKnife® system was put on the market. This has led to an increase in the number of uncontrolled IRE treatments of PCA in the last 2 years. The patients have to cover the high treatment costs themselves in these cases. If articles in the lay press advertise the procedure with promising but unverified contents, false hopes are raised in those concerned. This is disastrous if it delays the use of truly effective treatment options. CONCLUSION: IRE basically still has high potential for the treatment of malignancies; however, whether it can really be used for FT remains unclear due to the lack of data. This also holds true for the treatment of PCA. Only carefully conducted scientific research studies can clarify the unresolved issues regarding IRE of PCA. The urgently needed development of universally valid treatment standards for IRE is unnecessarily hampered by the flow commercially driven patients.

Contribution of congenital malformations to perinatal mortality. A 10 years prospective regional study in The Netherlands.

OBJECTIVE: : To determine the precise contribution of congenital malformations to perinatal mortality in a region. DESIGN: Prospective, descriptive. SETTING: Region, Delft-Westland-Oostland (DWO) in the Netherlands. MATERIAL AND METHODS: The registration was based on data concerning all deliveries of women domiciled in the health region DWO of the Netherlands. The incidence and contribution of congenital malformations to perinatal death was evaluated by a team consisting of a gynaecologist. a paediatrician and a paediatric pathologist. Malformations were classified as lethal or nonlethal and recorded separately for stillbirth (from 28 weeks gestation) and liveborn infants with 7-day follow-up. RESULTS: In 10 years (1993-1992) 28983 children were born in the region DWO. The perinatal mortality was calculated as 247 cases (0.85%). The overall incidence of congenital malformations in the perinatal death-group was 33%. Lethal congenital malformations were found in 51% of the cases in the stillbirth-group and 70% of the cases in the neonatal death-group. Congenital malformations of the central nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular- and pulmonary-defects were more prominent in the neonatal period (27% and 33% respectively of the neonatal deaths). Uro-genital and minor malformations (miscellaneous) are more often seen in perinatal deaths without being a contributor to the cause of death. CONCLUSIONS: As most congenital malformations are multifactorial in origin, it is in the understanding and control of such conditions that efforts and resources should now be turned. Through a detailed postmortem fetal and placental examination and clinical-pathological correlations lethal congenital malformations were found in 51% in stillbirths (mainly central nervous system) and 70% in neonates (mainly cardiovascular and pulmonary defects).

Evaluation of 239 cases of perinatal death using a fundamental classification system.

OBJECTIVE: To classify 239 cases of perinatal death in a newly introduced classification system for underlying causes of perinatal death. DESIGN: Prospective, descriptive. SETTING: Dutch healthcare region Delft-Westland-Oostland (DWO). MATERIALS AND METHODS: In 10 years (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. We used a classification model based upon the underlying cause of death using simple principles of obstetrical and neonatal pathology. A team consisting of a gynaecologist, neonatologist and pathologist classified all cases of perinatal death into seven groups to determine the "most-probable" cause of death. RESULTS: Birth trauma was seen in two cases (0.8%). Infections were seen in 16 cases (6.8%). Acute/subacute placental pathology in 77 cases (32.2%) and chronic placental pathology in 50 cases (21%). Bloodtype antagonism was seen in two cases (0.8%). Lethal congenital malformations in 55 cases (23%). Complications of pre-viable delivery in 20 cases (8.4%). Unclassifiable were 17 cases (7%): two cases could not be classified despite thorough investigation (1%) and 15 cases were lost for follow-up (6%). CONCLUSIONS: Classification of perinatal death causes by using our fundamental classification system gives insight in the possible underlying causes of death. The results of such a classification can be used as guidelines for preventive measures in the future.

Fundamental classification of perinatal death. Validation of a new classification system of perinatal death.

OBJECTIVE: To validate a newly introduced classification system for the registration of perinatal mortality. DESIGN: Descriptive. SETTING: Dutch Healthcare region Delft-Westland-Oostland (DWO). MATERIAL AND METHODS: In a 10-years period (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. Six assessors: four gynaecologists and two paediatricians were asked to classify all cases using a classification model proposed by the authors. This model is based on the underlying cause of death using simple principles of obstetrical and neonatal pathology: birth trauma, infection, placenta or cord pathology, pathology of immune tolerance of mother and fetus, congenital malformation of the fetus and complications of a pre-viable delivery. Therefore, we used the term fundamental classification. The six assessors worked independently of each other in classifying all cases of perinatal death, were not involved in the original development of the system and were unaware of the results of the classification of their colleagues. Agreement beyond chance between assessors was calculated using kappa's coefficient for multiple observers and multiple test results. RESULTS: Overall kappa was 0.70 (95% confidence interval (C.I.) 0.68-0.72). Reproducibility was poor for the categories trauma and unclassifiable, fair for the categories infections and placental/cord pathology, and very good to excellent for the categories maternal immune system pathology, congenital malformations and complications of prematurity. CONCLUSIONS: The proposed system showed a good level of agreement and appeared to be simply applicable. It offers a good insight in the underlying cause of death with the possibility for recognising preventive factors in future pregnancies and will enable (inter)national comparisons in causes of perinatal death. A reliable uniform registration of perinatal death based on the underlying causes should be the basis for improvement of the quality of perinatal care.

[Perinatal mortality in Delft and surrounds, 1983-1992: further reduction is possible by targeting lethal congenital abnormalities and placental insufficiency]. / Perinatale sterfte in Delft en omstreken, 1983-1992: verdere reductie mogelijk door gerichte aandacht voor letale congenitale afwijkingen en placenta-insufficiëntie.

OBJECTIVE: To establish the distribution of perinatal mortality over the various levels of obstetrical care, taking into account the various causes of perinatal mortality. DESIGN: Prospective, descriptive. METHODS: Data were collected on all parturitions of women living in the region Delft-Westland-Oostland (DWO), the Netherlands, during the period 1983-1992, regardless of the ultimate setting of the parturition. A prospective regional registration system for perinatal mortality in the region was matched with the registration by the Central Statistics Office (CBS). With anonymous linking, duplicatures could be excluded. The causes of death were assessed by a gynaecologist, a paediatrician and a child pathologist. It was determined for all cases of perinatal mortality whether the antenatal care had been under the final responsibility of a midwife or a general practitioner (primary care), either at home or in the outpatient clinic, or under the final responsibility of a gynaecologist (secondary care). RESULTS: In the decade studied, 28,983 children were born in the DWO region; 51% under primary care management. The actual perinatal mortality of the region was calculated as amounting to at least 247 cases (0.85%). In 26% (n = 64) of these, the childbirth was managed under primary care responsibility, in 43% (n = 106) after risk selection from primary to secondary care, in 14% (n = 34) under the exclusive responsibility of secondary care and in 17% (n = 43) after risk selection from secondary to tertiary care. The most frequent causes of death were progressive placental insufficiency and lethal congenital anomalies. CONCLUSIONS: The results show that further decrease of perinatal mortality may be achieved by risk selection (in primary care) with regard to lethal congenital anomalies and acute or progressive placental abnormalities. The perinatal mortality is so low (0.85%) that further medicalization of childbirth may be expected to contribute only little to a further decrease of the perinatal mortality figures.

[Discrepancy between results of registration of perinatal cause of death by the CBS (Central Bureau of Statistics) and by personal studies in the Delft-Westland-Oostland region]. / Discrepantie tussen resultaten van registratie van perinatale doodsoorzaken door CBS en door eigen onderzoek in de regio Delft-Westland-Oostland.

OBJECTIVE: To determine the reliability of the Dutch registration of causes of perinatal death by the Centraal Bureau voor de Statistiek (CBS, Central Statistics Office). DESIGN: Prospective, descriptive. SETTING: Region Delft-Westland-Oostland, the Netherlands. MATERIAL AND METHODS: The registration was based on data concerning all deliveries of women domiciled in the region, irrespective of the ultimate place of delivery, during 1983-1992. By linking, in retrospect, a prospective regional registration system for perinatal mortality within the region anonymously to the CBS registration, the reliability of the latter registration with regard to the causes of death was determined. To establish the causes of death, all available data were judged by a team consisting of a gynaecologist, a paediatrician and a paediatric pathologist. The diagnoses were classified with the aid of the International Classification of Diseases 9 (ICD-9). RESULTS: In 10 years, 28983 children were born in the region. Over this period, the CBS recorded 227 cases of perinatal mortality. The actual perinatal mortality was calculated as at least 247 cases. In 32% of the cases of stillbirth, the cause of death was not known at the CBS. Of the 82 cases in which the CBS had recorded a diagnosis, the causes of death were in agreement with those found in the regional study in 46%. Of the first-week mortality, the diagnosis was unknown at the CBS in one case and of the remaining 76 cases, the registration of the cause of death was the same in 68% of the cases. CONCLUSIONS: Registration of the causes of death regarding perinatal mortality and particularly stillbirth by the CBS shows gaps, mostly due to incorrect reporting of the cause of death by the treating physician or autopsist, due to the fact that at the time of notification the morbid-anatomical diagnosis and/or laboratory data were not complete. For the study of the backgrounds of perinatal mortality the current CBS registration of causes of death appears unsuitable.

[Castration-resistant prostate cancer (CRPC)]. / Kastrationsrefraktäres Prostatakarzinom (CRPC).

In merely a short period of time the comprehension of castration-resistant prostate cancer has evolved. It is now possible to clearly outline the exact definition and variance of the disease pattern. A wealth of new effective agents can be applied to extend the patient's life span and improve the quality of life. An understanding of the pharmacodynamics and side effects of each substance is of utmost importance for the practical application. In order to use these new medicines in a differentiated manner urologists require continuous education. The evaluation of response to treatment has yet to be satisfyingly verified. Molecular markers still need to be developed and evaluated.

[Organ and function preservation in urethral cancer]. / Organ- und Funktionserhalt beim Urethralkarzinom.

Primary urethral carcinomas are rare tumors that can occur both in men and women. Histological patterns of these tumors are mixed, urothelial tumors occur as well as squamous cell tumors or adenocarcinomas.There are different clinical factors that define clinical prognosis, and the 1- and 5-year cancer-free survival is 75% and 54%. Therapy of locally limited disease is surgical resection, and organ-preserving treatment is possible if negative frozen sections prove complete surgical resection. However, in men a perineal urethrostomy might be necessary, and in women there is a high risk of urinary incontinence if more than 2 cm of the distal urethra is resected.In case of locally advanced tumors or tumors of the proximal urethra, a radical urethrectomy with supravesical urinrary diversion is necessary. In some cases neoadjuvant (radio-)chemotherapy may be an option.

[Prostate biopsy. Update for indication, procedure, and future developments]. / Biopsie der Prostata. Update zu Indikation, Durchführung und zukünftiger Entwicklung.

Transrectal ultrasound-guided prostate biopsy is considered the gold standard in the primary investigation of a suspicious prostate-related finding. The procedure can be carried out with ten probes or more on the lateral side of the prostate, after administering antibiotic prophylaxis and applying local anesthesia. The indication for a biopsy depends on the results of the digitorectal examination, on the serum prostate-specific antigen level, on the individual patient's wish and on his comorbidities. Whether multiparametric imaging should be used before or during the course of a primary or repeated biopsy in order to identify suspicious prostate lesions is the subject of current investigations. Extended biopsy protocols require further clinical investigations before they can become the new standard in the diagnostic work-up. This review delivers an update on the indication for, and technique of, prostate biopsies.