Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies.

Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development.

Organ preservation technique without ischemia in patients with testicular tumor.

OBJECTIVE: To determine the safety and efficacy of organ-sparing surgery (OSS) without ischemia in patients with testicular tumor. METHODS: From January 2003 to October 2010, marker-negative clinical stage I testicular tumors ≤ 30 mm and marker-positive tumors in case of a tumor in a singular testis were managed by an organ-sparing approach. After localization of the tumor by ultrasound and accurate staging, OSS was performed without ischemia. Frozen section analyses of the tumor and tumor bed biopsies were obtained. In cases of malignant germ cell tumor with a normal contralateral testis, an orchiectomy of the tumor-bearing testis was performed. In all other cases, the organ-preserving procedure was completed. RESULTS: A total of 65 patients underwent this approach. In 35 patients with a germ cell tumor on frozen section report (mean tumor size 1.4 cm; standard deviation ± 8.54 mm) and presence of a normal contralateral testis, a radical orchiectomy of the tumor-bearing testis was performed. Thirty-three organ-preserving procedures were completed in 30 patients without any complications (mean tumor size 0.9 cm; range, 0.2-2.0). No local or systemic recurrence was observed in all the 65 patients, and serum testosterone levels remained within normal limits in all but 2 patients. All patients are currently free of disease at a median follow-up of 52.5 months (range, 3-107). CONCLUSION: Our findings suggest that a "no-clamping" OSS technique is safe and feasible in selected tumor patients.

Organ-sparing surgery is the treatment of choice in benign testicular tumors.

PURPOSE: Ablation of the testis has been the reference standard for malignant and benign testicular tumors in the past. Nowadays, an organ-sparing surgery (OSS) can be attempted in special cases. Removal of a testis for a benign lesion should be avoided. In this retrospective survey, we analyze the results and long-term follow-up of OSS in benign testicular tumors. METHODS: Charts of all patients that underwent OSS because of a benign testicular tumor between 1999 and 2011 at our department were searched and the data from patients were collected. Before surgery, all patients underwent ultrasound (US) and complete staging. Surgery was performed under US or palpation guidance. Frozen-section examination of the tumor and tumor bed biopsies was obtained. All patients underwent postoperative follow-up. We retrospectively reviewed surgical technique, histology, epidemiology, and outcome in all patients. RESULTS: In the study period, 40 benign testicular tumors were surgically removed in 37 consecutive patients. Definitive histology did not report of any malignant histopathologic features in all patients. All patients are free of disease after a mean follow-up of 63 months (range 10-120). During this period, two patients developed a second leydig cell tumor (LCT) on the contralateral side; another patient had a second LCT within the same testicle, but on the opposite pole. All patients underwent a subsequent organ-sparing tumor resection. CONCLUSIONS: An overtreatment for benign testicular tumors should be avoided. Our initial results indicate that OSS in benign tumors is a safe, feasible treatment for patients.

Stress-related and homeostatic cytokines regulate Vγ9Vδ2 T-cell surveillance of mevalonate metabolism.

The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vγ9Vδ2 T cells with antitumor potential. We show here that Vγ9Vδ2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues. Vγ9Vδ2 T cells induced this way effectively proliferated even under severe lymphopenic conditions and the antioxidant N-acetylcysteine significantly improved reconstitution of γδ T cells predominantly with a central memory phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector cells in an antigen-independent fashion, which rapidly produced abundant interferon γ (IFNγ) upon antigen re-encounter. IL-15 induced effector γδ T cells displayed increased levels of the cytotoxic lymphocyte-associated proteins CD56, CD96, CD161 and perforin. In response to stimulation with isoprenoid pyrophosphates, these effector cells upregulated surface expression of CD107a and exhibited strong cytotoxicity against tumor cells in vitro. Our data clarify understanding of innate immunosurveillance mechanisms and will facilitate the controlled generation of robust Vγ9Vδ2 T cell subsets for effective cancer immunotherapy.

The need for repeated urological evaluation in low-risk patients with microscopic hematuria after negative diagnostic work-up.

AIM: To evaluate the role of repeated urological evaluation after negative initial diagnostic work-up of asymptomatic microhematuria (AMH) in low-risk patients. PATIENTS AND METHODS: Criteria for patient inclusion were a complete negative initial diagnostic assessment including ultrasound (US), cystoscopy, upper urinary tract (UUT) imaging using intravenous urography (IVU) or multiphasic computed tomography (CT), absence of risk factors and a follow-up period of at least three years. Based on our institutional practice, urinalysis was repeated yearly; cystoscopy with US was repeated three years after initial work-up. The oncological outcome was evaluated across a mean follow-up of 8 (range: 3.7-10.2) years. RESULTS: A case series of 87 (32.2% of 270) low-risk patients, 56 women and 31 men, with a mean age of 52.4 (range: 19-87) years was studied. Three years after initial work-up, cystoscopy confirmed no bladder carcinoma in any of these 87 patients. Prostate cancer was diagnosed in one (1.1%) patient. In five (5.6%) patients, nephrological evaluation due to concomitant proteinuria on follow-up demonstrated chronic renal insufficiency (n=3), IgA nephropathy (n=1) and papillary necrosis of the kidney (n=1). CONCLUSION: Low-risk patients with persistent AMH after negative urological evaluation have a neglectable risk of developing bladder cancer on follow-up. Newly-discovered proteinuria on follow-up should be clarified by a nephrologist, as proteinuria could be a sign of significant glomerular disease.

Orthotopic bladder replacement in women: focus on functional results of a retrospective, single-centre study.

OBJECTIVE: The aim of this study was to investigate the functional and oncological outcomes of orthotopic neobladders in women with urothelial cancer. MATERIAL AND METHODS: From 1993 to 2007, 61 women underwent radical cystectomy and orthotopic ileal neobladder using the hemi-Kock pouch or Skinner T pouch. Sixteen of them were excluded owing to a lack of available follow-up data. Finally, 39 women with diagnosed TCC were included in this retrospective study. Demographic data, functional outcome including micturition characteristics such as voided volume, continence situation, use of clean intermittent catheterization (CIC), residual urine volume and recurrence rate were collected 3, 6 and >12 months after surgery. RESULTS: Tumours were non-muscle-invasive in 13 patients (pT1; 32.8%) with isolated carcinoma in situ (after failure of bacillus Calmette-Guérin) in five patients (13.0%) and muscle-invasive in 19 patients (pT2-3; 49.0%), extensive superficial bladder cancer was shown in one patient (2.6%), and remaining dysplasia after transurethral resection of the bladder for T1 G2 in one patient (2.6%). Median follow-up was 37 (range 3-165) months. Day-time (71.4%) and night-time (67.8%) continence (0-1 pad/24 h) 3 months postoperatively increased to 83.8% on long-term follow-up. Clean intermittent self-catheterization was required by 20%. At a mean follow-up of 39.5 (8-86) months, two women experienced local recurrence (septum rectovaginale, pelvic floor), urethral recurrence was seen in 5.2% and distant metastasis (pulmonary, peritoneal carcinosis) also in 5.2%. CONCLUSIONS: Orthotopic bladder replacement is an efficient option in appropriately selected women undergoing radical cystectomy, with encouraging functional outcome and low urethral recurrence rates, similar to published literature in men.

Postchemotherapy laparoscopic retroperitoneal lymph node dissection for low-volume, stage II, nonseminomatous germ cell tumor: first 100 patients.

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is indicated after chemotherapy in case of radiologic incomplete remission or teratomatous elements in orchiectomy specimens. Open RPLND is associated with considerable morbidity, but technical difficulty of postchemotherapy laparoscopic RPLND (L-RPLND) can be significant; therefore, literature concerning pc L-RPLND is sparse. OBJECTIVE: To evaluate feasibility and long-term oncologic outcome of postchemotherapy L-RPLND for clinical stage II disease at a single institution. DESIGN, SETTING, AND PARTICIPANTS: Records of patients with nonseminomatous germ cell tumor who underwent postchemotherapy L-RPLND between 1993 and 2010 were retrospectively reviewed. Unilateral template resection was used until a bilateral nerve-sparing approach was introduced in 2004. Follow-up investigations were performed at 3-mo intervals for the first 3 yr, every 6 mo for the next 2 yr, and annually thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: This was a descriptive analysis. RESULTS AND LIMITATIONS: The study cohort comprised 100 patients with stage II retroperitoneal disease (stage IIC: n=16; IIB: n=68; IIA with persisting tumor marker: n=16). Mean diameter of retroperitoneal masses before and after chemotherapy was 3.5 cm and 1.4 cm, respectively. Unilateral and bilateral templates were resected in 71 and 29 patients, respectively. Surgery was successfully completed in all but one patient, whose procedure was converted to open surgery due to bleeding. Mean operation time for unilateral and bilateral resection was 241 and 343 min, respectively. Mean blood loss was 84 ml. Postoperative complications were a large lymphocele in one patient and chylous ascites in another. Mean postoperative hospital stay was 3.9 d. L-RPLND specimens showed teratoma in 38 patients and active tumor in 2 patients. During a mean follow-up of 74 mo, one patient recurred. No recurrence was observed inside the applied surgical field. No patient died of tumor progression. After bilateral nerve-sparing postchemotherapy L-RPLND, 95.2% of patients reported antegrade ejaculation. CONCLUSIONS: Postchemotherapy L-RPLND performed by experienced hands is feasible and associated with low morbidity and high oncologic efficacy.

Influence of achieved paternity on quality of life in testicular cancer survivors.

OBJECTIVE: To investigate the influence of achieved/non-achieved paternity on quality of life (QoL) in testicular cancer (TC) survivors. PATIENTS AND METHODS: We invited TC survivors treated at our department between 1989 and 2006 to complete a QoL assessment, including the European Organisation for the Research and Treatment of Cancer QoL questionnaire, EORTC QLQ-C30 (version 3.0©)/+ TC26, and follow-up questions. A total of 311 TC survivors answered the questionnaire, of whom 207 patients who did not desire paternity were excluded. The remaining 104 patients who stated a desire for paternity after TC treatment were further divided in group A (TC survivors who achieved paternity; n = 51) and group B (TC survivors who did not achieve paternity; n = 53). The data obtained were statistically analysed. RESULTS: Significant differences between groups regarding QoL were detected for social functioning (P = 0.002), emotional functioning (P = 0.001), general QoL (P = 0.018), fatigue (P = 0.025), pain (P = 0.01), sleeping problems (P = 0.024), treatment satisfaction (P = 0.039), financial aspects (P = 0.006), sexual problems (P = 0.017), body image problems (P < 0.001), dyspnoea (P = 0.005) and cognitive functioning (P = 0.019). For all scales except 'sexual enjoyment', patients in group A were found to have a better long-term QoL than those in group B. CONCLUSIONS: Whilst acknowledging the shortcomings in retrospective analyses, we believe our data clearly underline the important impact on QoL for TC survivors of achieved paternity. Counselling patients early at diagnosis as well as using cryopreservation of semen in all potential patients before treatment (only excluding patients definitely claiming they do not wish to achieve paternity) should therefore be regarded as the standard of care.

Real-time sonoelastography for the evaluation of testicular lesions.

PURPOSE: To evaluate the feasibility of using real-time sonoelastography (RTE) for the differentiation and characterization of testicular lesions. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and the requirement to obtain informed consent was waived. Fifty patients (mean age, 42 years; age range, 18-81 years) with testicular lesions detected with gray-scale ultrasonography (US) and color and/or power Doppler US were evaluated with RTE between December 2004 and August 2010 to assess tissue elasticity of the testes. Stiff or "hard" lesions were suspected of being malignant. Testicular lesions with normal or decreased tissue stiffness ("soft" lesions) were considered benign. Findings from surgery and histopathologic examination were used as the reference standard in 34 cases, and findings from clinical and US follow-up were used as the reference standard in 16 cases. Sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic accuracy were calculated. RESULTS: Thirty-four of the 50 lesions (68%) were testicular tumors and 16 (32%) were of nontumorous origin. RTE showed the presence of hard lesions in all cases of testicular tumors and three cases of nontumorous lesions. Four lesions with an uncertain diagnosis when tested with gray-scale US and color and/or power Doppler US alone were soft at RTE and showed nontumorous character at follow-up. RTE showed a sensitivity of 100%, a specificity of 81%, a negative predictive value of 100%, a positive predictive value of 92%, and an accuracy of 94% in the diagnosis of testicular tumors. CONCLUSION: RTE demonstrated all testicular tumors as lesions with increased tissue stiffness. Because of its higher specificity, RTE can provide additional information in cases with indeterminate US findings.

Quality of life during dendritic cell vaccination against metastatic renal cell carcinoma.

Patients with metastatic renal cell carcinoma (RCC) undergoing cytokine or targeted therapies may show a remarkable decline in quality of life (QoL). We wanted to evaluate QoL in patients with metastatic RCC undergoing therapeutic vaccination with dendritic cells (DCs). In a cross-sectional analysis, QoL was therefore assessed in RCC patients participating in three consecutive clinical trials of DC vaccination. Before the first and after the third vaccination with DCs, patients completed a QoL questionnaire (EORTC QLQ-C30, version 3). Data were transformed into scale scores and analysed using SPSS 12.0 software. Mean values of the resulting scores obtained before and after DC vaccination were compared using students t test and Wilcoxon rank-sum test. P < 0.05 was considered statistically significant. The questionnaire was completed by 55 of 71 patients (compliance rate, 77.5%) who had a median age of 58.7 years (from 30 to 75 years). No significant reductions in functioning scales including physical, emotional and social criteria as well as symptom scores, which assess typical symptoms of tumour therapies, were observed indicating that QoL remained high during DC vaccination. Significant correlations were found between overall survival and functional as well as symptom scores. Our data indicate that DC vaccination, which is a personalised treatment modality, maintains QoL and thus represents an attractive nontoxic treatment option for patients with metastatic RCC. It will be important to identify the most effective conditions of DC vaccination including combinations with other therapeutics to maximise clinical efficacy while still preserving QoL.

In young adults with a low body mass index ultrasonography is sufficient as a diagnostic tool for ureteric stones.

OBJECTIVE: • To identify additional factors that might improve the diagnosis of ureteric stones using ultrasonography (US) as the primary diagnostic method. PATIENTS AND METHODS: • We performed a retrospective study of 228 patients who underwent rigid ureterorenoscopy (URS) for obstructive ureteric stones. • Patient age, sex, body mass index (BMI) and stone location and size were recorded. • All patients underwent US for stone detection before surgery. • If no cause of the flank pain was found by US, computer tomography (CT) was performed to confirm the absence of ureteric stones. RESULTS: • In 57 (25%), 15 (6.6%) and 156 (68.4%) patients a stone was localized on the proximal, mid- and distal ureter, respectively. • In 96 (42.1%), 122 (53.5%) and 10 (4.4%) patients the stone measured 0-5, 6-10 and >10 mm, respectively. • The mean (range) BMI of the patients was 24.7 (17.3-37.2) kg/m(2). • The overall stone detection rate using US was 86.4% overall, and 96.4% in adults ≤ 35 years. In 72/197 patients (36.5%) the stones found using US measured ≤ 5 mm and in 24/31 patients (77.4%) the stones found using CT measured ≤ 5 mm. • Age (P= 0.008), stone size (P < 0.001) and BMI (P= 0.013) were factors that independently affected ureteric stone diagnosis using US. CONCLUSION: • Although CT has served as the 'gold standard' for stone detection, its high costs and radiation dose, together with the high detection rate of US in the hands of experienced radiologists, lead us to conclude that US should be the first choice for primary diagnostic purposes, especially in young slim adults as no patient ≤ 35 years with a BMI ≤ 24 kg/m(2) needed unenhanced CT for ureteric stone diagnosis.

Two cycles of cisplatin-based chemotherapy for low-volume stage II seminoma: results of a retrospective, single-center case series.

BACKGROUND: To report on the oncological outcome and toxicity of patients treated with 2 cycles of cisplatin-based chemotherapy for low-volume metastatic stage II seminoma. METHODS: We retrospectively identified a case series of 15 patients with seminoma stage IIA (26.7%) and IIB (73.3%) who underwent chemotherapy consisting of 2 cycles of cisplatin, etoposide and bleomycin (PEB) (cisplatin 20 mg/m(2) on days 1-5, etoposide 100 mg/m(2) on days 1-5, bleomycin 30 mg on days 1, 8 and 15) according to patient preference (refusing a 3rd cycle of PEB) or institutional practice in the last decades. Complete staging before chemotherapy was available in all patients. Patient age, the side and diameter of the primary tumor, the size of the lymph nodes before and after chemotherapy, acute and late toxicity of chemotherapy, the incidence of second malignancies, the relapse-free rate and cancer-specific mortality were recorded. RESULTS: Chemotherapy was well tolerated and no episode of febrile neutropenia occurred. Thrombocytopenia grade 4 was not seen in any patient, while leukopenia grade 4 was observed in 4 (26.6%) patients. The mean (range) lymph node size decreased significantly from 2.54 cm (1.1-4.0) before chemotherapy to 0.75 cm (0.4-2.2) after chemotherapy (p < 0.001). After a median (range) follow-up of 60 (13-185) months, no patient had relapsed, no patient had died as a result of seminoma and second malignancy was seen in only 1 (6.6%) patient. CONCLUSIONS: These excellent long-term results from a retrospective case series of 2 cycles of PEB in stage IIA/IIB seminoma patients represent a hint for further research with a view to reducing treatment burden. However, these incidental findings should be studied in prospective trials prior to drawing any conclusions.

Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques.

OBJECTIVE: To report an observed high frequency of Leydig cell tumours (LCTs) diagnosed at our centre. PATIENTS AND METHODS: Charts of all patients who underwent surgery for a testicular tumour between 1999 and 2008 at our department were searched and data from patients with LCT were collected. Before surgery all patients underwent ultrasound and complete staging. In all but two patients with LCT an organ-sparing surgery was performed. Surgery was performed under ultrasound or palpation guidance. All patients underwent postoperative follow-up. We retrospectively reviewed surgical technique, histology, epidemiology and outcome in all LCT patients. RESULTS: In the study period, 197 testicular tumours were surgically removed of which 29 were diagnosed as LCT (14.7% of 197; further study group) in 25 patients. Mean age of patients with LCT was 45 years (range 21-68 years). Tumour size ranged from 1.2 to 80 mm (mean 10.23 mm). In two patients (8%) the lesion was palpable whereas incidental diagnosis was made in seven patients (28%). In the remaining patients diagnosis was made by ultrasound performed for testicular pain (six patients, 24%) or during infertility or erectile dysfunction evaluation (10 patients, 40%). Definitive histology reported no malignant histopathological features in all but one patient; this particular patient experienced tumour progression after 2 months and died from advanced disease 1 year later. All other patients are free of disease after a mean follow up of 56 months (range 7-93 months). During this period one patient developed a second LCT on the contralateral side; another patient had a recurrence within the same testicle, but on the opposite pole. Both underwent a subsequent organ-sparing tumour resection. CONCLUSION: The percentage of LCT (14.7% of all testicular tumours removed) was significantly higher than expected from the literature. One possible explanation for this phenomenon is the increasing use of better ultrasound technology and the subsequent increased detection of small nodules that have not been found in historical series. Use of 'observation-only' for very small lesions detected at infertility clinics is under debate.

C-reactive protein is a strong predictor for anaemia in renal cell carcinoma: role of IL-6 in overall survival.

OBJECTIVE: • To elucidate the association of progression of advanced renal cell carcinoma with anaemia and investigate factors influencing tumor-associated anaemia. PATIENTS AND METHODS: • We analyzed different clinical variables to study associations with anaemia in 86 metastatic renal cell carcinoma patients. • 45 (52%) of patients had already developed anaemia prior to therapy. RESULTS: • Anaemic patients had an increase in the serum markers C-reactive protein (CRP), IL-6 and erythropoietin (EPO). In addition we observed substantial correlation between IL-6 and CRP serum levels (R = 0.639, P < 0.0001). • Univariate logistic regression analysis revealed that patients with IL-6 >10 pg/mL had a considerable increase in risk for anaemia (odds ratio 3.86, P= 0.003). • In addition, patients with CRP >0.7 mg/dL had a very strong increase in risk for anaemia (OR = 14.08, P < 0.0001). • Stepwise multivariate logistic regression analysis confirmed CRP >0.7 mg/mL as the only independent predictor for anaemia. Cox-regression modeling selected serum IL-6 as the strongest independent prognostic indicator (hazard ratio 3.58, P < 0.0001). CONCLUSION: • Anaemia depends on serum IL-6, which is a strong inductor of CRP and regulator of the iron-transport. Serum IL-6 may be considered as a target to treat cancer-related anaemia.

Serum IgG against Candida predict survival in patients with metastatic renal cell carcinoma.

BACKGROUND AND AIM: In contrast to hematologic malignancies, little is known about the role of fungi in the development and progression of solid tumors. This prompted us to analyze and correlate serum levels of different fungal IgG with survival of patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Serum IgG to Candida sp., Saccharomyces cerevisiae and Aspergillus fumigatus were measured in a cross-sectional study in 64 patients with advanced disease. Univariate and multivariate analyses were chosen to study serum IgG as prognostic indicators. RESULTS: Median follow-up was 29.0 months (range 0.3-122). Median overall survival of patients, which tested negative for Candida IgG, was significantly increased (median not reached, >29 months) compared with Candida IgG positive patients (17.8 months, P = 0.002). Median survival of Saccharomyces IgG negative patients was 33.1 months as opposed to 19.4 months in Saccharomyces IgG positive patients, although this difference was not significant (P = 0.281). No difference in overall survival was found between Aspergillus IgG positive patients (28.0 months) and Aspergillus IgG negative patients (29.1 months) (P = 0.181). Cox backward-stepwise regression confirmed Candida IgG as the strongest predictor of survival in metastatic renal cell carcinoma patients (risk ratio 3.27, P = 0.001, [95% CI 1.86-5.73]). CONCLUSION: Our findings suggest that IgG antibodies directed against yeast fungi and particularly against Candida but not against mold fungi have prognostic relevance.

Routine scrotal ultrasonography during the follow-up of patients with testicular cancer leads to earlier detection of asynchronous tumours and a high rate of organ preservation.

OBJECTIVE: To compare outcomes of patients with asynchronous tumours detected before and after the introduction of scrotal ultrasonography (SUS) during routine follow-up examinations. PATIENTS AND METHODS: Since January 2001 SUS was also used during the follow-up of patients with testicular cancer. A series of 16 consecutive patients with asynchronous bilateral testicular tumours diagnosed while still complying with routine follow up investigations were identified and divided into two groups; group A was diagnosed by palpation only, before 2001, and group B was diagnosed after 2000. The groups were compared statistically for the interval between asynchronous tumours, clinical stage, tumour diameter at the time of diagnosis and rate of testis-sparing surgery. RESULTS: All tumours in group A were diagnosed by palpation, but only two in group B were palpable at the time of diagnosis. The mean tumour diameter was statistically significantly smaller in group B (1.2 cm) than in group A (2.68 cm); testis-sparing surgery was used in all of group B and only three patients in group A. After organ-sparing surgery all patients had normal testosterone levels. All patients after organ-sparing surgery had adjuvant scrotal radiotherapy because of germ cell tumour, and no patient had a local recurrence. CONCLUSION: Our data indicate that using SUS for the remaining testicle in routine follow-up visits of patients with testicular cancer leads to the earlier detection of smaller tumours and, consequently, a higher rate of organ preservation. The maintenance of physiological endocrine function might finally result in a better quality of life.

Metastasizing renal cell carcinoma developing in a congenital ectopic and dysplastic kidney.

UNLABELLED: We present the first case of a metastasizing renal cell carcinoma arising within a partially regressed multicystic dysplastic and ectopic left kidney in a 34-year-old patient. Despite nephrectomy and adjuvant immunotherapy, the patient died 4 months after diagnosis. Even though a recent systematic review found no evidence to support any of the different modalities for following up children with MCKD by ultrasound (Oxford Centre for Evidence-Based Medicine, LEVEL OF EVIDENCE: 3a), our case supports the contrary and we emphasize that an annual control could be an important diagnostic choice ( LEVEL OF EVIDENCE: 4).

Intrinsic endometriosis of ureter and bladder in young women without gynecological symptoms.

Urological endometriosis as the primary and sole form of presentation is rare. With ultrasound being available at routine examinations by the urologist and gynecologist, asymptomatic and incidental hydronephrosis is picked up far more than before. The behavior of endometriosis may be very aggressive in terms of ingrowth and fibrosis of the ureter, the periureteral structures and the bladder. It is important to get to an accurate and timely diagnosis to prevent loss of renal function. We report 2 cases who presented with asymptomatic hydronephrosis. Because of severe ureteric obstruction and infiltration of the ureters and/or bladder, surgery was selected as treatment option. Ureteric stenting was not possible because of severe fibrosis and stricture formation of the distal ureter. Primary surgery gave satisfactory results at more than 1 year of follow-up.

Serum antibodies against Saccharomyces cerevisiae: a new prognostic indicator in metastatic renal-cell carcinoma.

PURPOSE: A recent study reported that a diet rich in bread and refined cereals might have an unfavorable role in the development of renal cell carcinoma (RCC). To test whether an underlying intolerance of bread ingredients is responsible for the unfavorable influence of bread on RCC, we examined patient sera for the presence of food-specific IgG. EXPERIMENTAL DESIGN: A commercial test was used to detect food-specific IgG directed against a panel of 113 food antigens in sera of 54 patients with metastatic RCC. Kaplan-Meier estimates were used for univariate survival analysis, and differences in survival curves were assessed with the log-rank test. Multivariate survival analysis was done using a Cox regression model. RESULTS: We found that RCC patients with elevated serum levels of IgG antibodies against S. cerevisiae, commonly known as baker's yeast and yet another bread component, have an unfavorable clinical course. Median survival of patients with high levels of S. cerevisiae IgG was only 17.8 months, whereas median survival of patients with low S. cerevisiae IgG was 43.8 months (P = 0.0022; log-rank). Multivariate survival analysis identified high levels of S. cerevisiae IgG as a strong and independent prognostic risk factor (risk ratio 4.6, P = 0.001; 95% CI 1.61-13.08). CONCLUSIONS: Our findings indicate that serum levels of IgG against S. cerevisiae may predict survival in patients with metastatic RCC. The data suggest not cereals but baker's yeast being the critical component of bread that may cause immune deviation and impaired immunosurveillance in predisposed RCC patients.

Influence of intravesical potassium on pelvic floor activity in women with recurrent urinary tract infections: comparative urodynamics might lead to enhanced detection of dysfunctional voiding.

OBJECTIVES: To investigate the influence of intravesical potassium on pelvic floor activity (PFA) during voiding in women with recurrent urinary tract infections (rUTIs) by using comparative urodynamics (CUD). PATIENTS AND METHODS: CUD was conducted in 49 women (mean age 34.6 years, range 15-82) with rUTI. Every patient had two sessions of pressure-flow studies with simultaneous measurement of PFA by perineal surface electromyography (EMG); the first was with 0.9% saline and in the second the bladder was filled with 0.2 m KCl solution. All patients had voiding cysto-urethrography, and dysfunctional voiding (DV) was diagnosed when significant PFA was measured by EMG during voiding. RESULTS: Overall, DV was diagnosed in 37 patients (76%) using CUD; 16 (32%) had DV with saline on the pelvic floor EMG. In all these patients there were significantly greater EMG signals in the presence of KCL. In 21 patients (43%) DV was only detected using KCL; this improvement in the detection rate of DV was statistically significant (P = 0.006). Filling with KCl also prompted a statistically significant difference (P < 0.05) in maximum bladder capacity, maximum and average flow rates and in postvoid residual urine volume. CONCLUSION: The present data show that DV is present in most women with rUTI but cannot sufficiently be diagnosed by conventional urodynamics with standard 0.9% saline. The present study suggests that CUD might enhance the detection rates of DV.