Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model : A treatment planning study.

BACKGROUND AND PURPOSE: Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT). MATERIALS AND METHODS: In an orthotopic pancreatic cancer model, MRI/CT-based radiation treatment planning was established. Three irradiation techniques (rotational, 3D multifield, stereotactic) were performed with the SARRP system (Small Animal Radiation Research Platform, Xstrahl Ltd., Camberley, UK). Dose distributions in gross tumor volume (GTV) and organs at risk (OAR) were analyzed for each treatment setting. RESULTS: MRI with high soft tissue contrast improved imaging of GTV and OARs. Therefore MRI-based treatment planning enables precise contouring of GTV and OARs, thus, providing a perfect basis for an improved dose distribution and coverage of the GTV for all advanced radiation techniques. CONCLUSION: An MRI/CT-based treatment planning for high-precision IGRT using different techniques was established in an orthotopic pancreatic tumor model. Advanced radiation techniques allow considering perfect coverage of GTV and sparing of OARs in the preclinical setting and reflect clinical treatment plans of pancreatic cancer patients.

Evaluation of radiation-related invasion in primary patient-derived glioma cells and validation with established cell lines: impact of different radiation qualities with differing LET.

PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor and has a very poor overall prognosis. Multimodal treatment is still inefficient and one main reason is the invasive nature of GBM cells, enabling the tumor cells to escape from the treatment area causing tumor progression. This experimental study describes the effect of low- and high-LET irradiation on the invasion of primary GBM cells with a validation in established cell systems. METHODS: Seven patient derived primary GBM as well as three established cell lines (LN229, LN18 and U87) were used in this study. Invasion was investigated using Matrigel® coated transwell chambers. Irradiation was performed with low- (X-ray) and high-LET (alpha particles) radiation. The colony formation assay was chosen to determine the corresponding alpha particle dose equivalent to the X-ray dose. RESULTS: 4 Gy X-ray irradiation increased the invasive potential of six patient derived GBM cells as well as two of the established lines. In contrast, alpha particle irradiation with an equivalent dose of 1.3 Gy did not show any effect on the invasive behavior. The findings were validated with established cell lines. CONCLUSION: Our results show that in contrast to low-LET irradiation high-LET irradiation does not enhance the invasion of established and primary glioblastoma cell lines. We therefore suggest that high-LET irradiation could become an alternative treatment option. To fully exploit the benefits of high-LET irradiation concerning the invasion of GBM further molecular studies should be performed.

BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model : Experiences with a liquid fiducial marker.

BACKGROUND AND PURPOSE: High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark). METHODS: In an animal-based cancer model, different volumes of BioXmark (10-50 µl), application forms, and imaging modalities-cone-beam computer tomography (CBCT) incorporated in either the Small Animal Radiation Research Platform (SARRP) or the small-animal micro-CT Scanner (SkyScan; Bruker, Brussels, Belgium)-as well as subsequent RT with the SARRP system were analyzed to derive recommendations for BioXmark. RESULTS: Even small volumes (10 µl) of BioXmark could be detected by CBCT (SARRP and Skyscan). Larger volumes (50 µl) led to hardening artefacts. The position of BioXmark was monitored at least weekly by CBCT and was stable over 4 months. BioXmark was shown to be well tolerated; no changes in physical condition or toxic side effects were observed in comparison to control mice. BioXmark enabled an exact fusion with the original treatment plan with less hardening artefacts, and minimized the application of contrast agent for fractionated RT. CONCLUSION: An orthotopic pancreatic tumor mouse model was established for high-precision IGRT using a fiducial marker. BioXmark was successfully tested and provides the perfect basis for improved imaging in high-precision RT. BioXmark enables a unique application method and optimal targeted precision in fractionated RT. Therefore, preclinical trials evaluating novel fractionation regimens and/or combination treatment with high-end RT can be performed.

The hydrodynamic basis of the vacuum cleaner effect in continuous-flow PCNL instruments: an empiric approach and mathematical model.

PURPOSE: Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. METHODS: In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. RESULTS: In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli's equation provided the explanation of these effects and confirmed our experimental results. CONCLUSIONS: We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

[Tract sealing techniques in percutaneous nephrolitholapaxy]. / Versiegelungstechniken bei der perkutanen Nephrolitholapaxie.

Since the introduction of the percutanous nephrolitholapaxy (PNL), the instruments as well as the technique have experienced a tremendous modification. The miniaturisation of the instruments has led to a decreased hospital stay, reduced analgetic use as well as an extension of the indication for PNL. A nephrostomy tube was normally inserted to prevent urinoma and to provoke renal haemostasis. In 1997, the necessity for the regular use of a nephrostomy tube was first questioned. In a prospective study, the nephrostomy tube was successfully omitted in 50 selected patients. Since then, increasingly, the nephrostomy tube is omitted. Alternatively, different haemostatic substances are used for renal tract closure. The necessity for the use of these agents is still unclear.

[Report on notifications according to section 8d of the German Transplantation Act (TPG) for the years 2009-2011]. / Bericht zur Meldung nach § 8d Transplantationsgesetz (TPG) für die Jahre 2009 bis 2011.

In Germany, the Tissue Act came into effect on 1 August 2007. Since then, every tissue establishment is legally obligated to keep a record of its activities according to section 8d subsection 3 of the Transplantation Act (TPG). An annual report must be submitted to the Paul Ehrlich Institute once a year up to 1 March of the subsequent year. The report should include the types and quantities of tissues procured, conditioned, processed, stored, distributed or otherwise disposed of, imported, and exported. The report should be made on a TPG-based notification form published on the Internet by the Paul Ehrlich Institute. The present report according to section 8d subsection 3 of the TPG is based on data of the reporting years 2009-2011. Six years after implementation of the TPG's reporting obligation for tissue establishments, the number of tissue establishments known by the Paul Ehrlich Institute has increased from 349 in 2007 to 949 in 2011. In the course of continuous optimization of the notification forms, including tissue-specific glossaries, the reported data of most of the tissues and tissue preparations have become more conclusive.

Seminal vesicle invasion: accuracy and analysis of infiltration patterns with high-spatial resolution T2-weighted sequences on endorectal magnetic resonance imaging.

OBJECTIVE: To evaluate the accuracy of high-spatial resolution T2-weighted endorectal magnetic resonance imaging (eMRI) for detection and pattern depiction of seminal vesicle invasion (SVI) in patients with prostate cancer (PCa). METHODS: 376 patients were included who underwent eMRI for staging before radical open prostatectomy at 1.5 T with an endorectal coil. Statistical accuracy for detection of SVI was calculated. MR images of patients with SVI were further evaluated by two radiologists according to the classification by Wheeler and Ohori. RESULTS: In the cohort, 35 patients had SVI after histopathological evaluation of the prostatectomy specimen (stage pT3b). Sensitivity and specificity for detection of SVI were 48.6 and 97.7%, respectively. Negative and positive predictive values and overall accuracy were 94.9, 68.0, and 93.1%, respectively. Infiltration pattern analysis showed that type I invasion was most common with 48.6 followed by type IIa (31.4%) and IIb (20%). Type III was not present. There was no statistical significant difference between the three groups regarding Gleason score, age, and prostate-specific antigen level. CONCLUSIONS: eMRI with high-spatial resolution T2-weighted imaging is accurate for assessment of SVI. Depiction of different infiltration types of SVI is feasible. By adding information about the extent of SVI, diagnostic reporting and risk stratification could be improved.

Influence of body mass index, surgical approach and lymphadenectomy on the development of symptomatic lymphoceles after radical prostatectomy.

PURPOSE: Identification of factors influencing lymphocele formation requiring intervention after radical prostatectomy. METHODS: 302 patients undergoing radical retropubic prostatectomy (RRP, n = 174) or transperitoneal robot-assisted laparoscopic prostatectomy (RALP, n = 128) by the same surgeon were retrospectively reviewed. Incidence of symptomatic lymphoceles (SLC) was compared with clinical and pathological data (contingency analyses, Wilcoxon-Kruskal-Wallis test). RESULTS: Sixteen patients (5.3%) developed SLC. SLC occurred significantly more frequently after RRP compared to RALP (8.0 vs. 0.8%, p = 0.0008). Patients with SLC had more lymph nodes (LN) removed median (17 vs. 13, p = 0.009) and a significantly lower BMI (median 24.4 vs. 26.4, p = 0.0008). Presence of LN metastases (n = 18 patients, 6.0%) showed no statistical impact on SLC. In a multivariate analysis surgical method, the number of resected LN and the BMI remained independent predictors of SLC formation. CONCLUSIONS: The lower incidence of SLC after RALP compared to RRP probably results from peritoneal drainage of lymphatic fluid. The correlation of removed LN and SLC might be explained by increased injury of lymphatic vessels during more extended LN dissection. Why patients with lower BMI are more prone to develop SLC still remains unclear. However, early postoperative mobilization in nonobese patients might be a contributing factor.

Impact of S3 training courses "Sedation and Emergency Management in Endoscopy for Endoscopy Nurses and Assisting Personnel" on the process and structure quality in gastroenterological endoscopy in practices and clinics - results of a nationwide survey.

INTRODUCTION: After the S3 Guideline Sedation in Gastrointestinal Endoscopy was published, a training curriculum for a three-day course for endoscopy nurses was developed. The aim of this study was to investigate what effect the course participation had on the daily routine process and structure quality by implementing a German-wide survey in gastroenterology practices and clinics. METHODS: A questionnaire with a total of 44 individual questions on personnel, space, and equipment structure, sedation, peri- and post-interventional monitoring, as well as discharge and complication management in endoscopy departments was sent to a total of 2113 course participants (1056 Institutions). They had completed the seminar between December 2008/January 2009 and June 2010. RESULTS: The response rate was 21.2 % (224 /1056). Fifty-four percent were from clinic endoscopy departments, 46 % from practices. Overall, some form of structural change occurred in 86.8 % of the clinics and in 84.5 % of the practices. New staff was hired in 28.1 % of the clinics and 12.6 % of the practices. Rosters were changed in 11.6 % of the clinics and 7.8 % of the practices. Almost all issues improved after course participation. However, they did not reach statistic significance with the exception of the availability of peri-interventional ECG-monitoring in practices. The "performance of sedation in threesomes" increased in clinics by more than 20 % and in practices by more than 15 %. The use of the ASA-classification to assess risk increased significantly in clinics (before 24 %, after 50 %) as well as practices (before 40 %, after 60 %) by more than 20 % (p = 0.0007 and p = 0.0385, respectively). The documentation of the discharge status (e. g. using checklists) more than doubled in clinics (before 19 %, after 41.3 %) and practices (before 17.5 %, after 38.8 %) after course completion. CONCLUSION: The only nationwide endoscopy nurses' survey on structure and process quality in endoscopy so far, shows that since the publication of the S3 guideline in 2008 numerous processes and structures have improved with respect to patient safety.

[Active surveillance: concept for renal cell carcinoma?]. / Active Surveillance: Strategie beim Nierenzellkarzinom?

More than 80% of renal cell carcinomas are currently being detected incidentally by ultrasonic imaging and often affect elderly patients with substantial comorbidities. Surgical options cannot be applied in this cohort as routinely as in younger patients, as in some cases the perioperative risk factors may outweigh the risk of tumor-related death. In this context the concept of active surveillance for localized renal cell cancer in elderly patients is becoming increasingly important. The aim of active surveillance is to avoid surgery-related adverse effects and to achieve a controlled observation of tumor behavior with an option of delayed intervention in cases of aggressive clinical tumor features. This review sheds light on the current status of this strategy.

[Fusion imaging in urology: combination of MRI and TRUS for detection of prostate cancer]. / Fusionsbildgebung in der Urologie: Die Kombination von MRT und TRUS zur Detektion des Prostatakarzinoms.

Multiparametric magnetic resonance imaging (MRI) represents the most accurate imaging modality for prostate cancer imaging to date. Transrectal ultrasound (TRUS) is easily applied and therefore remains the gold standard for systematic prostate biopsies. However, the advantages of both modalities can be combined by image fusion. Currently, several image fusion devices are being implemented into clinical routine. First data show an increased detection rate of prostate cancer compared to systematic TRUS biopsies. At present prostatic deformation and intracorporeal movement represent technical challenges yet to be overcome. The present article gives an overview about the status of MRI-based biopsy techniques and highlights the current studies on the topic.

Prostatic peripheral nerve distribution may impact the functional outcome of nerve-sparing prostatectomy.

PURPOSE: To study microscopic patterns of remaining peripheral nerves (PN) after nerve-sparing (NS) radical prostatectomy (RP) and possible consequences for nerve preparation. METHODS: Specimens from 27 patients (7 = non-NSRP, 20 = unilateral NS) were examined. Sections were investigated for PN content by immunoassaying. 120 whole-mounted slides were divided into four sectors, and extracapsular nerves were counted; the mean posterior/anterior ratio was calculated. Calculated ratios were correlated with the respective volumes of prostatic tissue (PV). After dividing the patient cohort into two subgroups, shared by the median value of the posterior/anterior nerve ratios, the absolute PN contents on the anterior surface of the NS sides were compared. RESULTS: Anatomical posterior nerve percentage in non-NS aspects ranged from 0.0-100.0 to 26.7-94.6% with a mean of 66.60 ± 25.4% and 68.83 ± 16.0% (>/<200 µm, respectively). Individual ratios from two nerve categories showed significant correlation (P < 0.008). Mean posterior ratios were 83.04/79.68 and 39.21/56.00, respectively. After unilateral NS, 3.17-fold (2.25 vs. 0.71 nerves, P = 0.05) and 2.26-fold (21.54 vs. 9.53, P = 0.08) nerve fibers were resected in the anterior area in comparison with type A. After unilateral NS, the variation impact on the anterior nerve content of the NS side could be demonstrated. CONCLUSIONS: The amounts of nerves localized on the anterior prostate after RP vary interindividually. Saving only a minor part of the anterior areas may have an impact on the quantity of excised nerves adjacent to the specimen and impair postoperative functional results. Especially for those patients without a major posterolateral bundle distribution, surgeons should adapt the procedure and start nerve preservation more anteriorly to maximize the probability of satisfactory postoperative functional results.

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer.

BACKGROUND AND PURPOSE: This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0). PATIENTS AND METHODS: Pelvic IMRT to 45-50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. RESULTS: Acute radiation-related toxicity higher than grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1-2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5 years. CONCLUSION: Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.

Basal HIF-1α expression levels are not predictive for radiosensitivity of human cancer cell lines.

BACKGROUND AND PURPOSE: High levels of hypoxia inducible factor (HIF)-1α in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1α on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1α levels. MATERIAL AND METHODS: HIF-1α levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1α, HIF-2α, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1α siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. RESULTS: According to their basal HIF-1α status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1α expressors. The functionality of the high basal HIF-1α expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1α. Linear regression analysis revealed no correlation between basal HIF-1α levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. CONCLUSION: Our data suggest that basal HIF-1α levels in human tumor cell lines do not predict their radiosensitivity under normoxia.