Arne Strauß

Laser-supported partial laparoscopic nephrectomy for renal cell carcinoma without ischaemia time

BackgroundTo date, elective nephron-sparing surgery is an established method for the exstirpation of renal tumors. While open partial nephrectomy remains the reference standard of the management of renal masses, laparoscopic partial nephrectomy (LPN) continues to evolve. Conventional techniques include clamping the renal vessels risking ischaemic damage of the clamped organ. Thus, new techniques are needed that combine a sufficient tissue incision for exstirpation of the tumor with an efficient coagulation to assure haemostasis and abandon renal vessel clamping in LPN. Laser-excision of renal tumors during laparoscopic surgery seems to be a logical solution.MethodsWe performed nephron-sparing surgery without clamping of the renal vessels in 11 patients with a renal tumor in exophytic position (mean size 32 mm, ranging 8–45 mm) by laser-supported LPN.ResultsRegular ultrasound monitoring and insertion of a temporary drainage showed no evidence of postoperative hemorrhage. All tumors were removed with a histopathologically confirmed surrounding margin of normal renal tissue (R0 resection). Serum creatinine, hemoglobin, and hematocrit were nearly unaltered before and after surgery.ConclusionsThe experience won in these patients have confirmed that laser-assisted LPN without clamping of the renal vessels could be a safe and gentle alternative to classic partial nephrectomy in patients with exophytic position of renal tumors.

Increased expression of CYP17A1 indicates an effective targeting of the androgen receptor axis in castration resistant prostate cancer (CRPC)

Recent breakthrough therapies targeting androgen receptor signalling in castration resistant prostate cancer (CRPC) involve multifunctional androgen receptor (AR) blockade and exhaustive androgen deprivation. Nevertheless, limitations to an enduring effectiveness of new drugs are anticipated in resistance mechanisms occurring under such treatments.In this study we used CRPC cell models VCaP and LNCaP as well as AR-negative PC-3- and non-neoplastic epithelial BPH-1-cells treated with 5, 10 or 25 μmol/L abiraterone hydrolyzed from abiraterone acetate (AA). The origin of CYP17A1 up-regulation under AA treatment was investigated in CRPC cell models by qRT-PCR and western-blot procedures.AA treatments of AR positive CRPC cell models led to decreased expression of androgen regulated genes such as PSA. In these cells diminished expression of androgen regulated genes was accompanied by an up-regulation of CYP17A1 expression within short-term treatments. No such effects became evident in AR-negative PC-3 cells. AR directed siRNA (siAR) used in VCaP cells significantly reduced mRNA expression and AR protein abundance. Such interference with AR signalling in the absence of abiraterone acetate also caused a marked up-regulation of CYP17A1 expression. Down-regulation of androgen regulated genes occurs in spite of an elevated expression of CYP17A1, the very target enzyme for this drug. CYP17A1 up-regulation already takes place within such short treatments with AA and does not require adaptation events over several cell cycles. CYP17A1 is also up-regulated in the absence of AA when AR signalling is physically eliminated by siAR.These results reveal an immediate counter-regulation of CYP17A1 expression whenever AR-signalling is inhibited adequately but not a persisting adaptation yielding drug resistance.

A three-step technique for umbilicoplasty in a patent urachus.

The concept of ‘ umbilicoplasty ’ emphasises the cosmetic function of the umbilicus as a central structure of the body beyond a simple foetal remnant and focuses on the aesthetic aspects of reconstructive surgery. A protruding umbilicus is considered ‘ unattractive and undesirable ’ by some patients [ 1 ] . Therefore, one aim is to form an inverted umbilicus by resection of the umbilical scarifi cation [ 1 ] . Another aim, especially in female patients, is to form a ‘ scarless ’ and ‘ natural-appearing umbilicus ’ with a ‘ longitudinal deep depression ’ [ 2 ] . Many attempts have been made to establish standardised criteria to defi ne the appearance of an aesthetically pleasing umbilicus. From a study of 147 female participants, it was concluded that the Tor vertically shaped umbilicus with superior hood or shelf is a desirable goal in umbilical reconstruction, as it scored highest in aesthetic appeal [ 2 ] . Beyond cosmetic aspects, the crucial function of the umbilicus to ‘ seal off ’ the abdominal wall from the outer environment has to be restored to avoid urinary discharge and recurrent infections.

Vaginal pelvic repair. Always with mesh or not

ZusammenfassungFür die anatomiegerechte Rekonstruktion des weiblichen Beckenbodens konkurrieren verschiedene operative Verfahren. Der erfahrene Operateur schöpft aus dem Erfahrungsschatz der offenen, laparoskopischen und vaginalen Techniken, welche durch eine unterschiedliche Erfolgs- und Rezidivrate sowie operationsspezifische Komplikationsrisiken gekennzeichnet sind. Im Zuge der Zunahme der Morbidität der Patientinnen besteht der Bedarf nach einer sicheren minimal-invasiven Operationstechnik. Durch die rasante Entwicklung der synthetischen Netze hat sich bei der primären Rekonstruktion des weiblichen Beckenbodens ein unkritischer Einsatz von Fremdmaterial beim vaginalen „Repair“ verbreitet. Dabei ist der vaginale Zugangsweg gegenüber den anderen Operationsverfahren eine weniger invasive Technik mit einer schnellen Rekonvaleszenz, der auch ohne Verwendung von synthetischen Netzen sehr gute Ergebnisse mit einer geringen Komplikations- und Rezidivrate erreicht.AbstractSeveral surgical methods are possible when aiming at reconstruction of pelvic organ prolapse in women, and the experienced surgeon implements the knowledge gained from open, laparoscopic, and vaginal techniques. These feature different rates of success and relapse as well as different complication risks. Because of the accumulating morbidity of aging patients, there is a search for a safe minimally invasive technique. With the advent of synthetic meshes, surgeons have used them frequently and often uncritically for reconstruction of the female pelvic floor. In these cases the vaginal approach is preferred as opposed to alternative techniques, as it is less invasive and allows for better convalescence. Furthermore, this approach leads to low complication and relapse rates even when synthetic meshes are omitted.Several surgical methods are possible when aiming at reconstruction of pelvic organ prolapse in women, and the experienced surgeon implements the knowledge gained from open, laparoscopic, and vaginal techniques. These feature different rates of success and relapse as well as different complication risks. Because of the accumulating morbidity of aging patients, there is a search for a safe minimally invasive technique. With the advent of synthetic meshes, surgeons have used them frequently and often uncritically for reconstruction of the female pelvic floor. In these cases the vaginal approach is preferred as opposed to alternative techniques, as it is less invasive and allows for better convalescence. Furthermore, this approach leads to low complication and relapse rates even when synthetic meshes are omitted.

Role of N-cadherin in proliferation, migration, and invasion of germ cell tumours

Germ cell tumors (GCTs) are the most common malignancies in young men. Most patients with GCT can be cured with cisplatin-based combination chemotherapy, even in metastatic disease. In case of therapy resistance, prognosis is usually poor. We investigated the potential of N-cadherin inhibition as a therapeutic strategy. We analyzed the GCT cell lines NCCIT, NTERA-2, TCam-2, and the cisplatin-resistant sublines NCCIT-R and NTERA-2R. Effects of a blocking antibody or siRNA against N-cadherin on proliferation, migration, and invasion were investigated. Mouse xenografts of GCT cell lines were analyzed by immunohistochemistry for N-cadherin expression. All investigated GCT cell lines were found to express N-cadherin protein in vitro and in vivo. Downregulation of N-cadherin in vitro leads to a significant inhibition of proliferation, migration, and invasion. N-cadherin-downregulation leads to a significantly higher level of pERK. N-cadherin-inhibition resulted in significantly higher rates of apoptotic cells in caspase-3 staining. Expression of N-cadherin is preserved in cisplatin-resistant GCT cells, pointing to an important physiological role in cell survival. N-cadherin-downregulation results in a significant decrease of proliferation, migration, and invasion and stimulates apoptosis in cisplatin-naive and resistant GCT cell lines. Therefore, targeting N-cadherin may be a promising therapeutic approach, particularly in cisplatin-resistant, therapy refractory and metastatic GCT.

CK19 is a sensitive marker for yolk sac tumours of the testis

BackgroundMalignant germ cell tumours are the most common malignant tumours in young men. They are histologically divided into seminomas and non-seminomas. Non-seminomas are further subdivided into embryonic carcinomas, yolk sac tumours, chorionic carcinomas, and teratomas. For the therapeutic management it is essential to differentiate between these histological subtypes.MethodsInvestigated cases included normal testis (n = 50), intratubular germ cell neoplasia (n = 25), seminomas (n = 67), embryonic carcinomas (n = 56), yolk sac tumours (n = 29), chorionic carcinomas (n = 2), teratomas (n = 7) and four metastases of YST’s for their CK19 expression. In addition Leydig cell- (n = 10) and Sertoli cell- tumours (n = 4) were included in this study.ResultsAll investigated seminomas, embryonic carcinomas as well as normal testis and intratubular germ cell neoplasias did not express CK19. In contrast, all investigated yolk sac tumours strongly expressed CK19 protein. These findings became also evident in mixed germ cell tumours consisting of embryonic carcinomas and yolk sac tumours, although CK19-expression could also be observed in analysed chorionic carcinomas and epithelial components of teratomas.ConclusionCK19 proved to be a sensitive marker to identify yolk sac tumours of the testis and to distinguish them from other germ cell tumours, especially seminomas and embryonic carcinomas.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4075546891400979.

Prolapse surgery. With abdominal or vaginal meshes

In prolapse surgery several surgical techniques are available. The different open, laparoscopic and vaginal approaches are distinguished by distinct success and relapse rates and operation-specific complications. A safe and optimal therapeutic pelvic floor surgery should be based on the three support levels according to DeLancy and be individually adjusted for every patient. The vaginal approach may be used for all kinds of female genital prolapse and is a comparatively less invasive technique with a short time of convalescence. Apart from stress incontinence there is no need for synthetic meshes in primary approaches and excellent results with low complication and relapse rates can be achieved. An uncritical application of synthetic material is to be avoided in vaginal repair at all times. Abdominal surgical techniques, both open and laparoscopic, present their strengths in the therapeutic approach to level 1 defects or stress incontinence. They provide excellent functional and anatomical corrections and low relapse rates. Abdominally inserted meshes have lower complication rates than vaginal ones.

Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors

BackgroundTesticular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes.MethodsImmunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software.ResultsIn tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis.ConclusionsIn conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15 expression in the preinvasive precursor cells, which may provide diagnostic value to distinguish between benign and pre-malignant testicular specimen, and may indicate a role for MED15 in carcinogenesis in TGCT.

[Laser now also to be used in organ-preserving kidney surgery?].

Kidney surgery is subject to continuous change. Partial nephrectomy is the prevailing method for small and medium-sized tumours and proven to be superior to radical nephrectomy. The conventional technique usually includes clamping the renal vessels. The duration of the ischaemia caused determines the outcome of the remaining renal function. The shorter the ischaemic time the more likely the renal function will be preserved. Thus, new techniques are needed to abandon renal vessel clamping. Essential is a combination of good cutting abilities and assured haemostasis. To date, the commonly used techniques for cutting in partial nephrectomy only partially fulfil these requirements. Establishment of laser in urology offers a new surgical technique that combines both. In spite of the still limited data on laser use in kidney surgery, this method can be assessed favourably. Laser offers a possibility of both open and laparoscopic partial nephrectomy avoiding renal vessel clamping without additional risks or complications.ZusammenfassungDie Nierentumorchirurgie unterliegt einem ständigen Wandel. Als ein Fortschritt in der Therapie von kleineren und mittleren Tumoren der Niere wird heute statt der radikalen Tumornephrektomie, die noch vor einigen Jahren als Standard bei allen Tumoren galt, eine organerhaltende Tumorresektion empfohlen. Die Resektion der Tumoren wird häufig noch unter Ausklemmen der Nierengefäße durchgeführt. Hierbei nimmt man eine warme Ischämie in Kauf. Die Dauer der dabei entstehenden Ischämie ist entscheidend für das Outcome der Nierenrestfunktion. Je kürzer die Ischämiezeit, desto wahrscheinlicher ist eine gute Restfunktion der verbleibende Niere. Daher bedarf es neuer Techniken, die es ermöglichen gänzlich auf ein Ausklemmen der Niere zu verzichten. Diese sollten eine gute Schnittleistung mit einer sicheren Hämostase vereinen. Die bis dato gebräuchlichen Verfahren konnten diese Anforderungen noch nicht hinlänglich erfüllen. Die Etablierung der Lasertechnik in der Urologie ermöglicht nun ein operativ-technisches Verfahren, das eine gute Koagulations- und Schnittleistung in einem verbindet. Die noch spärliche Datenlage zum Einsatz von Laser in der Nierenchirurgie verleiht diesem einen experimentellen Charakter; die bisherigen Ergebnisse sind jedoch durchweg als positiv zu werten. Der Laser bietet sowohl bei der offenen als auch bei der laparoskopischen Nierenteilresektion die Möglichkeit einer sicheren Schnittführung und Hämostase ohne Inkaufnahme zusätzlicher oder vermehrter Komplikationen.AbstractKidney surgery is subject to continuous change. Partial nephrectomy is the prevailing method for small and medium-sized tumours and proven to be superior to radical nephrectomy. The conventional technique usually includes clamping the renal vessels. The duration of the ischaemia caused determines the outcome of the remaining renal function. The shorter the ischaemic time the more likely the renal function will be preserved. Thus, new techniques are needed to abandon renal vessel clamping. Essential is a combination of good cutting abilities and assured haemostasis. To date, the commonly used techniques for cutting in partial nephrectomy only partially fulfil these requirements. Establishment of laser in urology offers a new surgical technique that combines both. In spite of the still limited data on laser use in kidney surgery, this method can be assessed favourably. Laser offers a possibility of both open and laparoscopic partial nephrectomy avoiding renal vessel clamping without additional risks or complications.

Laser nun auch in der organerhaltenden Nierenchirurgie

Kidney surgery is subject to continuous change. Partial nephrectomy is the prevailing method for small and medium-sized tumours and proven to be superior to radical nephrectomy. The conventional technique usually includes clamping the renal vessels. The duration of the ischaemia caused determines the outcome of the remaining renal function. The shorter the ischaemic time the more likely the renal function will be preserved. Thus, new techniques are needed to abandon renal vessel clamping. Essential is a combination of good cutting abilities and assured haemostasis. To date, the commonly used techniques for cutting in partial nephrectomy only partially fulfil these requirements. Establishment of laser in urology offers a new surgical technique that combines both. In spite of the still limited data on laser use in kidney surgery, this method can be assessed favourably. Laser offers a possibility of both open and laparoscopic partial nephrectomy avoiding renal vessel clamping without additional risks or complications.ZusammenfassungDie Nierentumorchirurgie unterliegt einem ständigen Wandel. Als ein Fortschritt in der Therapie von kleineren und mittleren Tumoren der Niere wird heute statt der radikalen Tumornephrektomie, die noch vor einigen Jahren als Standard bei allen Tumoren galt, eine organerhaltende Tumorresektion empfohlen. Die Resektion der Tumoren wird häufig noch unter Ausklemmen der Nierengefäße durchgeführt. Hierbei nimmt man eine warme Ischämie in Kauf. Die Dauer der dabei entstehenden Ischämie ist entscheidend für das Outcome der Nierenrestfunktion. Je kürzer die Ischämiezeit, desto wahrscheinlicher ist eine gute Restfunktion der verbleibende Niere. Daher bedarf es neuer Techniken, die es ermöglichen gänzlich auf ein Ausklemmen der Niere zu verzichten. Diese sollten eine gute Schnittleistung mit einer sicheren Hämostase vereinen. Die bis dato gebräuchlichen Verfahren konnten diese Anforderungen noch nicht hinlänglich erfüllen. Die Etablierung der Lasertechnik in der Urologie ermöglicht nun ein operativ-technisches Verfahren, das eine gute Koagulations- und Schnittleistung in einem verbindet. Die noch spärliche Datenlage zum Einsatz von Laser in der Nierenchirurgie verleiht diesem einen experimentellen Charakter; die bisherigen Ergebnisse sind jedoch durchweg als positiv zu werten. Der Laser bietet sowohl bei der offenen als auch bei der laparoskopischen Nierenteilresektion die Möglichkeit einer sicheren Schnittführung und Hämostase ohne Inkaufnahme zusätzlicher oder vermehrter Komplikationen.AbstractKidney surgery is subject to continuous change. Partial nephrectomy is the prevailing method for small and medium-sized tumours and proven to be superior to radical nephrectomy. The conventional technique usually includes clamping the renal vessels. The duration of the ischaemia caused determines the outcome of the remaining renal function. The shorter the ischaemic time the more likely the renal function will be preserved. Thus, new techniques are needed to abandon renal vessel clamping. Essential is a combination of good cutting abilities and assured haemostasis. To date, the commonly used techniques for cutting in partial nephrectomy only partially fulfil these requirements. Establishment of laser in urology offers a new surgical technique that combines both. In spite of the still limited data on laser use in kidney surgery, this method can be assessed favourably. Laser offers a possibility of both open and laparoscopic partial nephrectomy avoiding renal vessel clamping without additional risks or complications.