Mario W. Kramer

Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer

BackgroundFibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.Methods212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of FN1 mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.ResultsMean tissue specific FN1 mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean FN1 expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10-5; Wilcoxon rank sum test). Patients with advanced disease had higher FN1 expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher FN1 mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).ConclusionsTo our knowledge, this is the first study to show that FN1 mRNA expression is higher in RCC compared to normal renal tissue. FN1 mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.

Obesity is associated with improved survival in patients with organ-confined clear-cell kidney cancer

ObjectivesObesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on long-term prognosis of RCC patients.MethodsWe evaluated 1,338 clear-cell RCC patients with complete information about their BMI, who had undergone surgery for renal cell cancer at the University Hospitals in Hannover and Marburg between 1991 and 2005. The mean follow-up was 5.1xa0years.ResultsUnderweight, normal weight, pre-obesity, and obesity were diagnosed in 14 (1.0%), 444 (33.2%), 593 (44.3%), and 287 (21.4%) RCC patients, respectively. A lower BMI was significantly associated with higher age, tumor grade, and the rate of metastasis at diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 70.9% (pre-obese), 74.0% (obese grad I), and 85.6% (obese grad ≥II) as opposed to 63.8% for patients with a BMI below 25 (pxa0<xa00.001). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was found in organ-confined RCC only.ConclusionWe identified overweight as an independent prognostic marker of improved cancer specific survival in patients with organ-confined but not advanced RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.

Current evidence for transurethral laser therapy of non-muscle invasive bladder cancer

IntroductionBladder cancer is the second most common malignancy of urologic tumors. Back in 1976, lasers were added to the endourological armetarium for bladder tumor treatment. Despite nowadays’ standard procedure for staging and treating non-muscle invasive bladder tumor by transurethral resection of bladder tumors (TURB) via a wire loop, laser resection techniques for bladder tumor came back in focus with the introduction of Ho:YAG and not to mention recently Tm:YAG lasers. This review aims to display the current evidence for these techniques.Materials and methodsThroughout April 2010, MEDLINE and the Cochrane central register of controlled trials were searched previously for the following terms: “Laser, resection, ablation, coagulation, Nd:YAG Neodym, HoYAG: Holmium, Tm:YAG Thulium and transitional carcinoma, bladder, intravesical.”ResultsEleven articles on Ho:YAG and 7 on Tm:YAG were identified. Searches by Cochrane online library resulted in no available manuscripts.ConclusionToday, Nd:YAG does not play any role in treatment of lower urinary tract transitional cell carcinoma. Ho:YAG and Tm:YAG seem to offer alternatives in the treatment of bladder cancer, but still to prove their potential in larger prospective randomized controlled studies with long-term follow-up. Future expectations will show whether en bloc resection of tumors are preferable to the traditional “incise and scatter” resection technique, in which is contrary to all oncological surgical principles. For the primary targets, here are within first-time clearance of disease, in addition to low in-fields and out-of-fields recurrence rates.

Tm:YAG laser en bloc mucosectomy for accurate staging of primary bladder cancer: early experience

IntroductionExact pathological staging of bladder cancer is crucial for determination of further treatment. One limiting factor is the surgical ‘incise and scatter’ technique that might contribute to tumour recurrence. En bloc resection techniques are en emerging issue. We present initial results with Thulium:YAG (Tm:YAG) en bloc resection of bladder tumours for treatment and accurate staging of solitary transitional cell carcinoma of the bladder.Materials and methodsFrom June through October 2010, six patients were treated by TmLRBT (Thulium laser resection of bladder tumour). Inclusion criteria were solitary lesions, treatment naive patients and tumour localisation of the lower bladder wall and trigonum. En bloc resection was applied on all of the tumours. Two cold-cut biopsies from the tumour base were extracted. On five of the six patients, a re-resection was performed after 6xa0weeks.ResultsPathological evaluation revealed 1 patient with pTa G1, 2 patients with pTa G2 and 3 patients with pT1 G3. All of the resected specimens provided detrusor muscle, and all biopsies were positive for muscle cells. No intra-, peri- or post-operative complications were observed. Bladder irrigation was mandatory in only 50% of the patients. All patients were negative for residual TCC in re-resection 6xa0weeks after initial treatment.ConclusionTmLRBT has been proven safe and effective for both, treatment and pathological staging of primary TCC of the bladder. Tm:YAG en bloc resection therefore could be an appropriate tool for accurate staging with possibly lower scattering potential for the assessment and treatment of patients with TCC.

En bloc resection of urothelium carcinoma of the bladder (EBRUC): a European multicenter study to compare safety, efficacy, and outcome of laser and electrical en bloc transurethral resection of bladder tumor

PurposeEn bloc resection of bladder tumors (ERBT) may improve staging quality and perioperative morbidity and influence tumor recurrence. This study was designed to evaluate the safety, efficacy, and recurrence rates of electrical versus laser en bloc resection of bladder tumors.MethodsThis European multicenter study included 221 patients at six academic hospitals. Transurethral ERBT was performed with monopolar/bipolar current or holmium/thulium laser energy. Staging quality measured by detrusor muscle involvement, various perioperative parameters, and 12-month follow-up data was analyzed.ResultsElectrical and laser ERBT were used to treat 156 and 65 patients, respectively. Median tumor size was 2.1xa0cm; largest tumor was 5xa0cm. Detrusor muscle was present in 97.3xa0%. A switch to conventional TURBT was significantly more frequent in the electrical ERBT group (26.3 vs. 1.5xa0%, pxa0<xa00.001). Median operation duration (25xa0min), postoperative irrigation (1xa0day), catheterization time (2xa0days), and hospitalization (3xa0days) were similar. Overall complication rate was low (Clavienxa0≥xa03, nxa0=xa06 [2.7xa0%]). Hemoglobin was significantly lower after electrical ERBT (pxa0=xa00.0013); however, overall hemoglobin loss was not clinically relevant (0.38xa0g/dl). Patients (nxa0=xa0148) were followed for 12xa0months; 33 (22.3xa0%) had recurrences. In total, 63.6xa0% recurrences occurred outside the ERBT resection field. No difference was noted between ERBT groups.ConclusionsERBT is safe and reliable regardless of the energy source and provides high-quality resections of tumors >1xa0cm. Recurrence rates did not differ between groups, and the majority of recurrences occurred outside the ERBT resection field.

Current evidence for transurethral en bloc resection of non-muscle-invasive bladder cancer

Abstract Introduction : Despite todays standard procedure for staging and treating non-muscle-invasive bladder cancer by transurethral resection via a wire loop (TURBT), several other publications have dealt with a different concept of en bloc resection of bladder tumors using different energy sources. Material and methods : MEDLINE and the Cochrane central register were searched for the following terms: en bloc, mucosectomy, laser, resection, ablation, Neodym, Holmium, Thulium, transitional cell carcinoma. Results : Fourteen research articles dealing with en bloc resection of non-muscle-invasive bladder cancer could be identified (modified resection loops: six, laser: six, waterjet hydrodissection: two). Conclusion : En bloc resection of bladder tumors >1 cm can be performed safely with very low complication rates independent of the power source. By using laser, complication rates might even be decreased, based on their good hemostatic effect and by avoiding the obturator nerve reflex. A further advantage seems to be accurate pathologic staging of en bloc tumors. Randomized controlled trials are still needed to support the assumed advantages of en bloc resection over the standard TURBT with regard to primary targets: First-time clearance of disease, accurate staging and recurrence rates.

Neoadjuvant targeted therapy in a primary metastasized renal cell cancer patient leads to down-staging of inferior vena cava thrombus (IVC) enabling a cardiopulmonary bypass-free tumor nephrectomy: a case report

BackgroundWe report on a 62-year-old gentleman presenting at our urological department with an advanced renal cell cancer of the right kidney (10xa0cm in diameter), with an extensive caval vein thrombus (level IV) and bilateral pulmonary metastases. Another suspicious lesion at the left hemithorax was radiologically described.MethodA presurgical, neoadjuvant systemic therapy with sunitinib, a tyrosine kinase inhibitor, was initiated for 4 cycles in total (50xa0mg/day; 4xa0weeks on/2xa0weeks off). The cytoreductive nephrectomy was performed following the fourth cycle of sunitinib and after a 14-day break. Transesophageal echocardiography was used for intraoperative monitoring of the caval vein thrombus. Systemic treatment with sunitinib was continued 4xa0weeks after surgery.ResultsA significant reduction in tumor size, metastatic sites and down-staging of IVC from level IV to level III according to Novick classification was achieved.ConclusionSignificant down-staging of the tumor caval vein thrombus which initially reached the right atrium enabled us to perform surgery limited to the abdominal cavity without extracorporeal circulation nor hypothermia.

Galectin-3 expression in prostate cancer and benign prostate tissues: correlation with biochemical recurrence

BackgroundGalactin-3 is a cell adhesion molecule involved in tumor progression. Our aim was to examine Gal-3 expression in tumor, benign tissue adjacent to the tumor (adjacent-benign) and benign prostate specimens and correlated it with biochemical recurrence.Materials and methodsTissue microarrays were prepared from 83 tumor, 78 adjacent-benign and 75 benign tissues obtained from 83 patients undergoing prostatectomy for clinically localized prostate cancer. Tissues were stained using a Gal-3 antibody and immunohistochemistry. The staining was graded between 0 and 300 depending upon staining intensity and the area of staining. In 37 patients on whom there was follow-up (Mean: 57.8xa0months; Median: 68xa0months), staining intensity was correlated with biochemical recurrence.ResultsGal-3 showed both nuclear and cytoplasmic localization in benign, adjacent-benign and tumor tissues. Median Gal-3 staining scores significantly decreased from benign (192.5) to adjacent-benign (148.8 pxa0=xa00.007) and to tumor (108.8; pxa0<xa00.0001) tissues. In univariate analysis, age (pxa0=xa00.028), Gleason sum (pxa0=xa00.007), T stage (pxa0=xa00.011), seminal vesicle invasion (pxa0=xa00.009), pre-operative prostate-specific antigen (pxa0=xa00.045) and Gal-3 staining in tumor tissues (0.018) significantly correlated with biochemical recurrence. In multivariate analysis, Gal-3 expression in tumor (pxa0=xa00.04), adjacent-benign (pxa0=xa00.037) and benign (pxa0=xa00.005) tissues significantly correlated with biochemical recurrence. Gal-3 staining in tumor tissues had 91.7xa0% sensitivity, 64xa0% specificity and 73xa0% accuracy in predicting biochemical recurrence.ConclusionsThis is the first study that showed a decreasing gradient of Gal-3 expression in benign, adjacent-benign and tumor tissues. Gal-3 expression may be useful in predicting biochemical recurrence.

Is there an anti-androgen withdrawal syndrome for enzalutamide?

AbstractBackgroundnThe anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495–503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.MethodsIn total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.ResultsMean withdrawal follow-up was 6.5xa0weeks (range 1–26.1xa0weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9xa0% (range 0.5–440.7xa0%) with a median of 44.9xa0%.ConclusionsIf existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.

Long-term bowel disorders following radial cystectomy: an underestimated issue?

PurposePatients after radical cystectomy (RC) frequently complain about bowel disorders (BDs). Reports addressing related long-term complications are sparse. This cross-sectional study assessed changes in bowel habits (BH) after RC.MethodsA total of 89 patients with a minimum follow-up ≥1xa0year after surgery were evaluated with a questionnaire. Patients with BD prior to surgery were excluded. Symptoms such as diarrhea, constipation, bloating/flatulence, incomplete defecation, uncontrolled stool loss, and impact on quality of life (QoL) were assessed.ResultsA total of 46.1xa0% of patients reported changes in BH; however, only 25.8xa0% reported experiencing related dissatisfaction. Primary causes of dissatisfaction were diarrhea and uncontrolled stool loss. The most common complaints were bloating/flatulence and the feeling of incomplete defecation, but these symptoms did not necessarily lead to dissatisfaction or impairment in quality of life. No difference was identified between an orthotopic neobladder and ileal conduit, and even patients without bowel surgery were affected. QoL, health status, and energy level were significantly decreased in unsatisfied patients.ConclusionsAbout 25xa0% of patients complain about BDs after RC. More prospective studies assessing symptoms, comorbidities, and dietary habits are necessary to address this issue and to identify strategies for follow-up recommendations.