J. J. Wendler

Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

PurposeThe nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE.MethodsResults of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys.ResultsIn the dedicated investigation, no acute vascular destruction of the renal parenchyma and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave.ConclusionThe NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.

A prospective Phase 2a pilot study investigating focal percutaneous irreversible electroporation (IRE) ablation by NanoKnife in patients with localised renal cell carcinoma (RCC) with delayed interval tumour resection (IRENE trial)

INTRODUCTION Focal ablation therapy is playing an increasing role in oncology and may reduce the toxicity of current surgical treatments while achieving adequate oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue-selective with potential advantages compared with current thermal-ablation technologies or radiotherapy. The aim of this pilot trial is to determine the effectiveness and feasibility of focal percutaneous IRE in patients with localised renal cell cancer as a uro-oncological tumour model. METHODS Prospective, monocentric Phase 2a pilot study following current recommendations, including those of the International Working Group on Image-Guided Tumor Ablation. Twenty patients with kidney tumour (T1aN0M0) will be recruited. This sample permits an appropriate evaluation of the feasibility and effectiveness of image-guided percutaneous IRE ablation of locally confined kidney tumours as well as functional outcomes. Percutaneous biopsy for histopathology will be performed before IRE, with magnetic-resonance imaging one day before and 2, 7, 27 and 112 days after IRE; at 28 days after IRE the tumour region will be completely resected and analysed by ultra-thin-layer histology. DISCUSSION The IRENE study will investigate over a short-term observation period (by magnetic-resonance imaging, post-resection histology and assessment of technical feasibility) whether focal IRE, as a new ablation procedure for soft tissue, is feasible as a percutaneous, tissue-sparing method for complete ablation and cure of localised kidney tumours. Results from the kidney-tumour model can provide guidance for designing an effectiveness and feasibility trial to assess this new ablative technology, particularly in uro-oncology.

Irreversible Electroporation (IRE): Standardization of Terminology and Reporting Criteria for Analysis and Comparison

Summary Background Irreversible electroporation (IRE) as newer ablation modality has been introduced and its clinical niche is under investigation. At present just one IRE system has been approved for clinical use and is currently commercially available (NanoKnife® system). In 2014, the International Working Group on Image-Guided Tumor Ablation updated the recommendation about standardization of terms and reporting criteria for image-guided tumor ablation. The IRE method is not covered in detail. But the non-thermal IRE method and the NanoKnife System differ fundamentally from established ablations techniques, especially thermal approaches, e.g. radio frequency ablation (RFA). Material/Methods As numerous publications on IRE with varying terminology exist so far – with numbers continuously increasing – standardized terms and reporting criteria of IRE are needed urgently. The use of standardized terminology may then allow for a better inter-study comparison of the methodology applied as well as results achieved. Results Thus, the main objective of this document is to supplement the updated recommendation for image-guided tumor ablation by outlining a standardized set of terminology for the IRE procedure with the NanoKnife Sytem as well as address essential clinical and technical informations that should be provided when reporting on IRE tumor ablation. Conclusions We emphasize that the usage of all above recommended reporting criteria and terms can make IRE ablation reports comparable and provide treatment transparency to assess the current value of IRE and provide further development.

A Randomised Phase II Trial Comparing Docetaxel Plus Prednisone with Docetaxel Plus Prednisone Plus Low-Dose Cyclophosphamide in Castration-Resistant Prostate Cancer.

Background: Docetaxel plus prednisone is a standard treatment for castration-resistant prostate cancer. Cyclophosphamide may be an effective combination partner. Methods: This randomised, multicentre, phase II trial compared the combination therapy of docetaxel plus prednisone plus cyclophosphamide with the standard therapy of docetaxel plus prednisone. Results: Thirty-three patients received six 3-week treatment cycles (in total 171 cycles). During treatment, an adequate decline in prostate-specific antigen was seen in both groups (p = 0.068) without between-group differences (p = 0.683). No relevant differences between within-group changes were observed for blood pressure, weight, pain score, laboratory variables or quality of life. There were no serious side effects apart from leucopenia requiring treatment (docetaxel + prednisone + cyclophosphamide arm) and no drug-related withdrawals; all three fatalities were considered to be cancer related. Conclusions: The oncological effectiveness and tolerability of docetaxel plus prednisone were supported; an additional effect of cyclophosphamide was not detected. However, the small number of patients and short observation period restrict the generalisability of the results.

[Long-term results for subcutaneous Detour® prosthesis for ureteral obstruction: experiences of implantation, aftercare and management of complications].

BACKGROUND We present the long-term results of implementation of the Detour® prosthesis as an alternative to established methods of surgical, percutaneous or internal urinary diversion. PATIENTS AND METHODS Between 2004 and 2012 a total of 40 prostheses were implanted in 31 patients (mean age 65 years) with ureteral strictures of various origins. In the follow-up the patients underwent examinations and completed questionnaires. RESULTS The average follow-up was 23 months (range 1-92 months). Sonographic examinations showed no urinary retention in 38 out of 40 implanted systems. The retention values were stable in 19 patients, improved in 7 and worse in 3. The quality of life (QoL) was high (EORTC QLQ-C30 90%). Intraoperative complications were 2 intestinal lesions and 3 bleeding of the renal-pelvic system. Postoperative urinary tract infections and wound complications were encountered. In the long-term course three infected hydronephroses occurred which were treated and cured with antibiotics and temporary nephrostomy and 4 systems were explanted, including 2 exchanges. CONCLUSIONS The system may be considered for patients with ureteral strictures with palliative and curative intent. There were no significant disadvantages in comparison with established methods. There were fewer risks in implantation and complications were manageable. The quality of life was significantly improved.

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.

[Irreversible electroporation : The new generation of local ablation techniques for renal cell carcinoma.]

ZusammenfassungHintergrundLokale Ablationsverfahren stehen in der Onkologie im Fokus aktueller Entwicklungen. Vorrangiges Ziel ist es, ohne Kompromittieren der onkologischen Ergebnisse, Organe und Organfunktionen zu erhalten.MethodeDie irreversible Elektroporation (IRE) ist ein neues Ablationsverfahren und beruht auf einer induzierten Zellapoptose nach Applikation von Starkstromimpulsen ohne thermische Schädigung des Zielgewebes und benachbarter Strukturen.Ziel2005 erstmals publiziert, wird die IRE aktuell in einigen onkologischen Fachgebieten präklinischen und klinischen Untersuchungen unterzogen, die Ergebnisse sind bisher vielversprechend. Die IRE könnte eine deutliche Entwicklung in der Ablationstherapie beim Nierenzellkarzinom (NZK) bedeuten, der entscheidende Wirknachweis für das lokale NZK steht jedoch bisher aus. In dieser Arbeit werden eigene präklinische und erste klinische Untersuchungen und Ergebnisse dargestellt, diskutiert und mit anderen Ablationstechniken verglichen, um die aktuelle Wertigkeit der IRE aufzuzeigen.AbstractBackgroundLocal ablation techniques are a major focus of current developments in oncology. The primary aim is to retain organs and preserve organ functions without compromising the oncological outcome.MethodIrreversible electroporation (IRE) is a novel ablation technique that involves the application of high-voltage pulses to induce cell apoptosis without causing thermal damage to the target tissue or adjacent structures.AimFirst published in 2005 IRE is currently undergoing preclinical and clinical trials in several areas of oncology and the initial results have been promising. The IRE technique could be a significant development in ablation treatment for renal cell carcinoma (RCC) but decisive proof of its effectiveness for local RCC has not yet been provided. This study presents the results of preclinical and initial clinical trials which are discussed and compared with those of other ablation techniques in order to demonstrate the current value of IRE.BACKGROUND Local ablation techniques are a major focus of current developments in oncology. The primary aim is to retain organs and preserve organ functions without compromising the oncological outcome. METHOD Irreversible electroporation (IRE) is a novel ablation technique that involves the application of high-voltage pulses to induce cell apoptosis without causing thermal damage to the target tissue or adjacent structures. AIM First published in 2005 IRE is currently undergoing preclinical and clinical trials in several areas of oncology and the initial results have been promising. The IRE technique could be a significant development in ablation treatment for renal cell carcinoma (RCC) but decisive proof of its effectiveness for local RCC has not yet been provided. This study presents the results of preclinical and initial clinical trials which are discussed and compared with those of other ablation techniques in order to demonstrate the current value of IRE.

New aspects in shear-wave elastography of prostate cancer.

Aim This study was designed to evaluate the performance of shear-wave elastography as a diagnostic tool for prostate cancer in a larger cohort of patients than previously reported. Patients and methods Seventy-three patients with suspected prostate carcinoma were investigated by ultrasound elastography followed by directed biopsy. The elastographic and histological results for all biopsies were compared. Results After exclusion of invalid and non-assessable results, 794 samples were obtained for which both a histological assessment and an elastometric result (tissue stiffness in kPa) were available: according to the histology 589 were benign and 205 were malignant. Tissue elasticity was found to be weakly correlated with patients age, PSA level and gland volume. ROC analysis showed that, for the set of results acquired, elastometry did not fulfil literature claims that it could identify malignant neoplasia with high sensitivity and specificity. However, it did show promise in distinguishing between Gleason scores ≤6 and >6 when malignancy had already been identified. Unexpected observations were the finding of a smaller proportion of tumours in the lateral regions of the prostate than generally expected, and also the observation that the elasticity of benign prostate tissue is region-sensitive, the tissue being stiffest in the basal region and more elastic at the apex. Conclusions Shear-wave elastography was found to be a poor predictor of malignancy, but for malignant lesions an elasticity cut-off of 80 kPa allowed a fairly reliable distinction between lesions with Gleason ≤6 and those with Gleason >6. We demonstrate an increase in elasticity of benign prostate tissue from the basal to the apical region.

Langzeitergebnisse zur subkutanen Detour ®-Harnleiterprothese bei Ureterobstruktion

BACKGROUND We present the long-term results of implementation of the Detour® prosthesis as an alternative to established methods of surgical, percutaneous or internal urinary diversion. PATIENTS AND METHODS Between 2004 and 2012 a total of 40 prostheses were implanted in 31 patients (mean age 65 years) with ureteral strictures of various origins. In the follow-up the patients underwent examinations and completed questionnaires. RESULTS The average follow-up was 23 months (range 1-92 months). Sonographic examinations showed no urinary retention in 38 out of 40 implanted systems. The retention values were stable in 19 patients, improved in 7 and worse in 3. The quality of life (QoL) was high (EORTC QLQ-C30 90%). Intraoperative complications were 2 intestinal lesions and 3 bleeding of the renal-pelvic system. Postoperative urinary tract infections and wound complications were encountered. In the long-term course three infected hydronephroses occurred which were treated and cured with antibiotics and temporary nephrostomy and 4 systems were explanted, including 2 exchanges. CONCLUSIONS The system may be considered for patients with ureteral strictures with palliative and curative intent. There were no significant disadvantages in comparison with established methods. There were fewer risks in implantation and complications were manageable. The quality of life was significantly improved.

Circular Abscess Formation of the Inner Preputial Leaf as a Complication of a Penile Mondor's Disease: The First Case Report

Introduction. Mondors disease of the penis is an uncommon condition characterized by thrombosis or thrombophlebitis involving the superficial dorsal veins. An accompanied lymphangitis is discussed. There is typical self-limiting clinical course. Case Presentation. This paper firstly reports a secondary abscess formation of the preputial leaf two weeks after penile Mondors disease and subcutaneous lymphangitis as complication of excessive sexual intercourse of a 44-year-old man. Sexual transmitted diseases could be excluded. Lesions healed up completely under abscess drainage, antibiotic, and anti-inflammatory medication. Conclusion. Previous reports in the literature include several entities of the penile Mondors disease. Our patient is very unusual in that he presented with a secondary preputial abscess formation due to superficial thrombophlebitis, subcutaneous lymphangitis, and local bacterial colonisation. Abscess drainage plus antiphlogistic and antibiotic medication is the treatment of choice.