Digital health information on surgical treatment options for overactive bladder is underrepresented.

PURPOSE: Digital health information gains growing importance in the medical landscape. Despite its opportunities, there is a risk of patient misinformation which may adversely influence the patient-physician relationship. This investigation aimed to identify and compare differences in the content and quality of online health information on overactive bladder (OAB) between different digital platforms. METHODS: The platforms Google search, Facebook, Instagram, LinkedIn, and YouTube were searched for the keyword OAB. The search result links were classified as useful or misleading, advertisement and personal experience. Information regarding the organization of the source and available content on treatment modalities was collected. Descriptive analysis was applied. Univariate and multivariate analyses were performed to evaluate heterogeneity regarding the distribution of information depending on the source. A p value < 0.05 was considered statistically significant. RESULTS: The source with the highest quantity of useful content was YouTube (100%) and Google (100%), whereas LinkedIn included mostly misleading content (73%). YouTube and Google provided the greatest variety of health information and were dominated by professional associations. Surgical procedures for treating OAB were only described in 32% and 48% of Google and YouTube results, respectively. On Google, sacral neuromodulation and OnabotulinumtoxinA were described in 26% and bladder augmentation in only 16% of the search results. In contrast, alternative medicine was present in 76%. CONCLUSIONS: A large gap in the information on surgical treatments of OAB could be identified independently from the utilized source. In contrast, conservative treatments and alternative medicine dominate the current informational sources.

Shikonin Inhibits Cell Growth of Sunitinib-Resistant Renal Cell Carcinoma by Activating the Necrosome Complex and Inhibiting the AKT/mTOR Signaling Pathway.

Therapy resistance remains a major challenge in treating advanced renal cell carcinoma (RCC), making more effective treatment strategies crucial. Shikonin (SHI) from traditional Chinese medicine has exhibited antitumor properties in several tumor entities. We, therefore, currently investigated SHI's impact on progressive growth and metastatic behavior in therapy-sensitive (parental) and therapy-resistant Caki-1, 786-O, KTCTL-26, and A498 RCC cells. Tumor cell growth, proliferation, clonogenic capacity, cell cycle phase distribution, induction of cell death (apoptosis and necroptosis), and the expression and activity of regulating and signaling proteins were evaluated. Moreover, the adhesion and chemotactic activity of the RCC cells after exposure to SHI were investigated. SHI significantly inhibited the growth, proliferation, and clone formation in parental and sunitinib-resistant RCC cells by G2/M phase arrest through down-regulation of cell cycle activating proteins. Furthermore, SHI induced apoptosis and necroptosis by activating necrosome complex proteins. Concomitantly, SHI impaired the AKT/mTOR pathway. Adhesion and motility were cell line specifically affected by SHI. Thus, SHI may hold promise as an additive option in treating patients with advanced and therapy-resistant RCC.

High-Normal Preoperative Potassium Level Is Associated with Reduced 30-Day Morbidity and Shorter Hospital Stay after Radical Cystectomy.

BACKGROUND: Radical cystectomy has high complication rates and, consequently, a high socioeconomic burden. The association between preoperative electrolyte levels and postoperative outcomes after radical cystectomy has not been investigated. Therefore, we aimed to investigate the association between preoperative potassium level and clinical (30-day morbidity) and economical (length of hospital stay) postoperative outcomes of patients undergoing radical cystectomy. MATERIALS AND METHODS: We retrospectively evaluated clinical data of 317 patients who had undergone radical cystectomy for bladder cancer. Univariate and multivariate logistic regression analyses were performed to determine whether preoperative patient clinical factors influence clinical (30-day morbidity according to the Clavien-Dindo classification) and economical (length of hospital stay) postoperative outcomes. RESULTS: In univariate analysis, low Charlson comorbidity score (p = 0.011), low ASA score (p = 0.015), no aspirin intake (p = 0.048) and high-normal preoperative potassium level (p = 0.034) were associated with reduced 30-day morbidity. In multivariate analysis, only high preoperative potassium remained an independent predictive factor for a reduced risk of postoperative complications (odds ratio 0.67, 95% confidence interval (0.48, 0.92), p = 0.014). Furthermore, high-normal preoperative potassium was the only preoperative factor associated with a shorter hospital stay ≤21 days (p = 0.007). CONCLUSIONS: High-normal preoperative potassium level was associated with better clinical (lower 30-day morbidity) and economical (shorter hospital stay) outcomes in patients undergoing radical cystectomy. We recommend that a randomized controlled trial be performed to investigate whether there is a causal relationship between preoperative potassium supplementation and postoperative complications and length of hospital stay.

Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells.

Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and 'non-cancerous' cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of 'normal, non-cancerous' cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.

Shikonin Reduces Growth of Docetaxel-Resistant Prostate Cancer Cells Mainly through Necroptosis.

The prognosis for advanced prostate carcinoma (PCa) remains poor due to development of therapy resistance, and new treatment options are needed. Shikonin (SHI) from Traditional Chinese Medicine has induced antitumor effects in diverse tumor entities, but data related to PCa are scarce. Therefore, the parental (=sensitive) and docetaxel (DX)-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1-1.5 µM], and tumor cell growth, proliferation, cell cycling, cell death (apoptosis, necrosis, and necroptosis), and metabolic activity were evaluated. Correspondingly, the expression of regulating proteins was assessed. Exposure to SHI time- and dose-dependently inhibited tumor cell growth and proliferation in parental and DX-resistant PCa cells, accompanied by cell cycle arrest in the G2/M or S phase and modulation of cell cycle regulating proteins. SHI induced apoptosis and more dominantly necroptosis in both parental and DX-resistant PCa cells. This was shown by enhanced pRIP1 and pRIP3 expression and returned growth if applying the necroptosis inhibitor necrostatin-1. No SHI-induced alteration in metabolic activity of the PCa cells was detected. The significant antitumor effects induced by SHI to parental and DX-resistant PCa cells make the addition of SHI to standard therapy a promising treatment strategy for patients with advanced PCa.

Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction.

Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1-100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.

Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis.

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1-100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART's impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.

Persistent storage symptoms after TURP can be predicted with a nomogram derived from the ice water test.

PURPOSE: To predict the persistence of storage symptoms after transurethral resection of the prostate (TURP) using a nomogram derived from the ice water test (IWT). METHODS: The IWTs of 73 men with lower urinary tract symptoms and prostatic bladder outlet obstruction were retrospectively analyzed. The strength of the detrusor contraction was approximated by using the detrusor gradient of Δpdet /Δt at maximum detrusor pressure and the area under the curve. The parameters were utilized in a nomogram, which facilitated a severity categorization from 1 to 10. Patients with a positive IWT in the categories 1 to 2 were assigned to group A, categories 3 to 4 to group B and categories 5 and higher to group C. After TURP, patients with persisting storage symptoms were offered a botulinum toxin injection. RESULTS: There were 32 patients (44%) with negative and 41 patients (56%) with positive IWTs. Patients with negative IWTs were classified in category 1. Regarding patients with positive IWTs, 14 (34%) were correlated to group A, 14 (34%) to group B, and 13 (32%) to group C. The necessity of a subsequent botulinum toxin injection correlated significantly with a higher nomogram category (P < .001) as well as higher severity categorization (P < .001). In multivariate analysis, the nomogram category was an independent predictor for botulinum toxin injection (P = .002, OR, 6.9, CI, 2.0-23.9). CONCLUSION: The quantification of the detrusor contraction during the IWT allowed stratification of patients in risk categories for persistent storage symptoms after TURP and the potential need for later botulinum toxin injections.

CT-guided nephrostomy-An expedient tool for complex clinical scenarios.

INTRODUCTION & OBJECTIVES: Percutaneous nephrostomy [1] has emerged as a pivotal approach in the therapeutic management of the obstructed urinary tract. A consecutive incorporation of ultrasonic and radiographic guidance, the approach experienced an almost ubiquitious distribution while most centers currently applying either one or both of these tools jointly. However, success of ultrasound-guidance is limited in obese patients and non-dilated uropathy. In turn, fluoroscopy usually requires an opacification of the urinary collecting system by intravenous or antegrade contrast media injection, which might be harmful for already impaired renal function, raise intrapelvic pressure and augment the risk of sepsis and hemorrhage. CT-guided PCN aids in overcoming these limitations. In the current study, we present the experience of a tertiary referral center with this technique. MATERIALS & METHODS: Epidemiological and clinical data of all patients treated with a CT-guided PCN of native kidneys at the University Hospital Frankfurt between October 2003 and October 2013 were retrospectively collected from the patient charts. Procedural parameters including radiological aspects, technical and therapeutic success, complication and mortality rate have been analyzed statistically. RESULTS: In total, 140 PCN procedures have been performed in 77 patients with a median age of 69 (± 13). The median body mass index was 27 with 66.6% of patients being overweight or obese. Charlson comorbidity index was 7 ranging 0-16. Indications for PCNs were obstructive uropathy (62.9), urine extravasation (22.9%), urinary tract fistulas (11.4%) and technical reasons (2.8%). In 68.8% of patients, initial diagnosis was malignancy. 56.4% of kidneys were non-dilated before puncture. In 78.4% prone position, otherwise supine oblique position (17.3%) or supine position (4.3%) was used. 71.4% of PCNs were carried out solely under local anesthesia. Technical success has been achieved in 90% with a complication rate of 3.6% (all grade minor B) and was not significantly different between dilated and non-dilated kidneys. 42.9% of fistulas and 64.3% of urinary tract leakages, healed after PCN placement. 30 days mortality rate was 5.2% without being directly associated with the PCN procedure itself. CONCLUSION: CT-guided PCN is a feasible approach associated with low morbidity. It is particularly useful in complex clinical scenarios e.g. critically ill, newly operated or obese patients as well as non-dilated kidneys. Moreover, it represents a minimally-invasive option for treating leakages and fistulas of the urinary tract.

The TiLOOP® Male Sling: Did We Forejudge.

INTRODUCTION: To evaluate the safety and efficacy of the TiLOOP® male sling (pfm medical, Cologne, Germany) used in the treatment for male stress urinary incontinence (SUI). MATERIAL AND METHODS: We retrospectively evaluated a total of 34 patients with a TiLOOP® male sling. Perioperative complication rates were assessed and validated questionnaires were prospectively evaluated to assess quality of life and satisfaction rate. Outcome and complication rates were analysed by using descriptive statistics. Correlation of continence outcome and risk factors was performed with the chi-square test. A p value below 0.05 was considered statistically significant. RESULTS: The majority of patients (70.6%) were diagnosed with mild or moderate male SUI. During surgery, one instance (2.9%) of intraoperative urethral injury was observed. There were no immediate postoperative complications. The mean follow-up time was 44.6 months. An improvement of male SUI was reported by 61.9% of the patients and 38.1% reported no change according the Patient Global Impression of Improvement. The mean perineal pain score was 0.5 according to the international index of pain. CONCLUSIONS: The TiLOOP® is a safe treatment option for male SUI in our cohort with a low complication rate. However, the functional outcome of the TiLOOP® was inferior when compared to the outcome of the AdVance® male sling.

[Bipolar stimulation may improve the efficacy of the percutaneous nerve evaluation test of sacral neuromodulation]. / Die bipolare Stimulation kann die Erfolgsrate des Peripheren Nervenevaluationstests der sakralen Neuromodulation verbessern.

Purpose This study evaluates the hypothesis that bipolar stimulation of the S3 and S4 sacral roots may enhance the efficacy of the percutaneous nerve evaluation (PNE) test. Material and Methods In this case-control-study, we enrolled 43 patients undergoing bipolar PNE and 57 controls undergoing unipolar PNE. For bipolar PNE, four test electrodes were placed at the bilateral S3 and S4 roots. The electrodes at the S3 and S4 roots of each side were connected to obtain bipolar stimulation. The test protocol over eight days included unilateral and bilateral stimulation of the S3 and S4 sacral roots. Eight days after implantation, the electrodes were removed and test results from bladder diaries were collected. Results The unipolar test procedure was successful in 47 % (27/57) of cases. The bipolar test procedure was successful in 58 % (25/43). In the bipolar group, 63 % (12/19) of patients with neurogenic tract dysfunction profited from treatment, vs. 57 % (13/23) in the unipolar group. Patients without a neurologic disease had a successful test in 58 % (14/24) of cases treated with bipolar PNE vs. 41 % (14/24) treated with unipolar PNE. Multivariate analysis did not reveal a statistically significant difference between groups. Conclusion Although not significant in this population, bipolar PNE may improve efficacy compared to the unipolar test procedure. Similar observations were made in subgroups of neurogenic and non-neurogenic bladder dysfunctions.

Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells in vitro.

Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro. RCC cells were exposed to different concentrations of SFN and cell growth, cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized collagen, chemotactic activity, and influence on surface integrin receptor expression were investigated. SFN caused a significant reduction in both RCCres and RCCpar cell growth and proliferation, which correlated with an elevation in G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B resulted in significantly diminished RCC cell growth. SFN also modulated adhesion and chemotaxis, which was associated with reduced expression of the integrin subtypes α5, α6, and ß4. Distinct differences were seen in RCCres adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN) and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes demonstrated divergent action on RCC binding and invasion, depending on RCC cell sensitivity to everolimus. Therefore, SFN administration could hold potential for treating RCC patients with established resistance towards everolimus.

Evaluation of TKTL1 as a biomarker in serum of prostate cancer patients.

INTRODUCTION: Monocyte associated transketolase-like 1 (TKTL1) as a cancer biomarker has become popular with alternative practitioners, but plays no role in conventional medicine. This investigation evaluates the potential of serum TKTL1 as a biomarker for prostate cancer. MATERIAL AND METHODS: Patients (n = 66) undergoing curative radical prostatectomy (RPE) for biopsy-pro-ven PCa were included in the study. Controls (n = 10) were healthy, age-matched, male volunteers. 10 ml of peripheral blood was drawn from patients several days before surgery and from controls. Serum TKTL1 was measured using the ELISA method. RESULTS: The median age at tumor diagnosis was 66 years and median serum PSA was 8.0 ng/ml. Nearly 96% of PCas submitted to surgery were clinically significant. Compared to healthy controls, serum TKTL1 was significantly lower in PCa patients (p = 0.0001, effect size indicator r = Z/sqr(n) = 0.4179). No correlation was apparent between serum TKTL1 and serum PSA, Gleason sum, tumor stage or further clinical and pathologic parameters. CONCLUSIONS: Reduced serum TKTL1 in PCa patients stands in opposition to TKTL1 epitope detection in monocytes (EDIM) based studies, whereby increased TKTL1 in monocytes of tumor patients has been reported. Since serum TKTL1 does not correlate with clinical parameters in the current investigation, further research is needed to clarify whether serum TKTL1 has potential as a biomarker for PCa.

Amygdalin, quackery or cure?

BACKGROUND: The cyanogenic diglucoside, amygdalin, has gained high popularity among cancer patients together with, or in place of, conventional therapy. Still, evidence based research on amygdalin is sparse and its benefit controversial. PURPOSE: Since so many cancer patients consume amygdalin, and many clinicians administer it without clear knowledge of its mode of action, current knowledge has been summarized and the pros and cons of its use weighed. METHODS: A retrospective analysis was conducted for amygdalin relevant reports using the PubMed database with the main search term "Amygdalin" or "laetrile", at times combined with "cancer", "patient", "cyanide" or "toxic". We did not exclude any "unwanted" articles. Additionally, internet sources authorized by governmental or national institutions have also been included. SECTIONS: Individual chapters summarize pharmacokinetics, preclinical and clinical studies and toxicity. CONCLUSION: No convincing evidence showing that amygdalin induces rapid, distinct tumor regression in cancer patients, particularly in those with late-stage disease, is apparent. However, there is also no evidence that purified amygdalin, administered in "therapeutic" dosage, causes toxicity. Multiple aspects of amygdalin administration have not yet been adequately explored, making further investigation necessary to evaluate its actual therapeutic potential.

Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.

AIMS: Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed. MAIN METHODS: LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting. KEY FINDINGS: Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks. SIGNIFICANCE: Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.

Use of complementary and alternative medicine before and after organ removal due to urologic cancer.

OBJECTIVE: Many patients use complementary and alternative medicine (CAM) as primary treatment or symptom relief for a variety of illnesses. This study was designed to investigate the influence of surgical removal of a tumor-bearing urogenital organ on CAM use. METHODS: From 2007 to 2011, 350 patients underwent major urological surgery for kidney, prostate, or bladder cancer at the Goethe-University Hospital, Frankfurt, Germany. Data from 172 patients (49%), who returned a questionnaire, were retrospectively evaluated using the hospital information system along with the questionnaire to objectify CAM use 2 years before and after surgery. RESULTS: From the 172 patients returning questionnaires, 56 (33%) used CAM before and/or after surgery and 116 (67%) never used CAM. Of the 56 CAM users, 30 (54%) used CAM presurgery and 53 (95%) used CAM postsurgery, indicating a significant change of mind about CAM use. Patients of German nationality used CAM significantly more than patients of other nationalities. Higher educational status (high-school diploma or higher) was a significant factor in favor of CAM use. The most common type of CAM used before/after surgery was an alternative medical system (63/49%), a manipulative and body-based method (50/19%), and a biological-based therapy (37/32%). Information about CAM, either provided by medical professionals or by other sources, was the main reason determining whether patients used CAM or not. CONCLUSION: The number of patients using CAM almost doubled after surgical removal of a cancer-bearing organ. Better awareness and understanding of CAM use by medical professionals could improve patient counseling.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Molecular analysis of sunitinib resistant renal cell carcinoma cells after sequential treatment with RAD001 (everolimus) or sorafenib.

Sequential application of target drugs is standard procedure after renal cell carcinoma (RCC) patients develop resistance. To optimize the sequence, antitumour effects of the mTOR inhibitor RAD001 or the tyrosine kinase inhibitor (TKI) sorafenib on RCC cells with acquired resistance to the TKI sunitinib was evaluated. RCC cells were exposed to 1 µM sunitinib for 24 hrs (as control) and for 8 weeks (to induce resistance) and then switched to RAD001 (5 nM) or sorafenib (5 µM) for a further 8 weeks. Tumour cell growth, cell cycle progression, cell cycle regulating proteins and intracellular signalling were then investigated. Short-term application of sunitinib (24 hrs) induced cell growth blockade with accumulation in the G2/M phase. RCC cells became resistant to sunitinib after 8 weeks, demonstrated by accelerated cell growth along with enhanced cdk1, cdk2, loss of p27, activation of Akt, Rictor and Raptor. Switching to sorafenib only slightly reduced growth of the sunitinib resistant RCC cells and molecular analysis indicated distinct cross-resistance. In contrast, full response was achieved when the cancer cells were treated with RAD001. p19 and p27 strongly increased, phosphorylated Akt, Rictor and Raptor decreased and the tumour cells accumulated in G0/G1. It is concluded that an mTOR-inhibitor for second-line therapy could be the strategy of choice after first-line sunitinib failure.

MR-guided laser-induced thermotherapy in ex vivo porcine kidney: comparison of four different imaging sequences.

PURPOSE: To evaluate the clinical value of different magnetic resonance imaging (MRI) sequences for a real-time thermo-monitoring during laser-induced thermotherapy (LITT) in kidneys. METHODS: Twenty-eight ex vivo pig kidneys were treated with laser ablation under MR guidance in a high-field MR scanner (Magnetom Espree or Avanto Fit, Siemens, Germany). For the thermal ablation of the kidney, a neodymium yttrium-aluminum-garnet (Nd:YAG) laser was used in combination with a special protective catheter (length 43 cm, 4 French) which is sealed at the distal end. First, ablation was performed for 7, 10, and 13 minutes using FLASH sequences for investigation of time-dependent growth of lesion size. In the second step, we evaluated the optimal imaging sequence during a 7 minutes ablation of the kidney and after cooling using four different MR sequences (Haste, FLASH, radial VIBE, and Caipirinha DIXON). RESULTS: Macroscopic lesion volume increased from 3,784 ± 1,525 mm(3) to 7,683 ± 5,756 mm(3) after the ablation from 7 to 13 minutes and MR volume ranged from 2,107 ± 1,674 mm(3) to 2,934 ± 1,549 mm(3) after the ablation from 7 to 13 minutes. During ablation, FLASH (132 ± 34%) and radial VIBE (120 ± 43%) sequences displayed lesion volumes most efficiently with a trend to overestimation. The Caipirinha DIXON (323 ± 24%) sequence overestimated the volumes significantly during real-time monitoring. The volumes measured by MRI with FLASH (61 ± 30%), Haste (67 ± 28%), or radial VIBE (48 ± 14%) sequences after cooling of the kidney after ablation were always underestimated. The Caipirinha DIXON (142 ± 2%) sequence still overestimated the lesion volume after cooling of the kidney. CONCLUSION: LITT is a feasible ablation modality in kidney tissue. Moreover, macroscopic and MR lesion volume increases time-dependently. For online monitoring, radial VIBE and FLASH sequences seem to be most efficient.