Publications by authors named "Tim Nestler"

33 Publications

Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors.

Urol Int 2021 Jun 15:1-7. Epub 2021 Jun 15.

Department of Urology, Uro-Oncology, Robot Assisted and Reconstructive Urologic Surgery, University Hospital Cologne, Cologne, Germany.

Introduction: The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear.

Methods: We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics.

Results: Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, p = 0.031), visceral metastases (58 vs. 32%, p = 0.015), and poor prognosis (p = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, p = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, p = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (p = 0.049) during a median follow-up of 36 months (10-115.5).

Conclusions: The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.
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http://dx.doi.org/10.1159/000515715DOI Listing
June 2021

The combination of microRNA-371a-3p and 375-5p can distinguish viable germ cell tumor and teratoma from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens.

Transl Androl Urol 2021 Apr;10(4):1647-1655

Department of Urology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.

Background: To identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic germ cell tumor (GCT) patients with residual masses ≥1 cm after chemotherapy. Biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N.

Methods: We selected 48 metastatic GCT patients who had undergone pcRPLND. V, pure T and N was shown in the resected tissue of 16 patients, respectively. Of these areas total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T . N.

Results: On comparing V . N miR-371a-3p achieved the highest fold change (FC) of 31.1 (P=0.023) while for T . N miR-375-5p performed best (FC 64.2; P<0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3.

Conclusions: By combining miR-371a-3p and miR-375-5p in pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient's serum are needed to confirm the clinical impact of these biomarkers.
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http://dx.doi.org/10.21037/tau-20-1349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100847PMC
April 2021

Non-invasive urine markers for the differentiation between RCCs and oncocytoma.

J Clin Lab Anal 2021 May 7;35(5):e23762. Epub 2021 May 7.

Department of Urology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Background: Recently, our group showed that Vim3 is overexpressed in tissue samples of renal oncocytomas and Mxi-2 in clear cell renal carcinoma (ccRCC). The mechanism leading to the truncation of both proteins is known and involves with two miRs, both detectable in urine. Since the analysis of miRs is time-consuming, our aim was to identify the truncated proteins in urine instead. Furthermore, urine samples from small renal masses (SRMs) (n = 45, <4 cm) were analyzed to get a pre-surgical differentiation of the cancer subtypes.

Methods: Urines were accessed from the urological biobank (n = 350). Proteins were isolated from urine samples, and Western blots were performed. Each sample was analyzed with ELISA for the expression of Vim3 and Mxi-2. A lateral flow assay was established. For the detection of SRMs, the miRs were isolated and qRT-PCR was performed.

Results: A significant increase of Vim3 in urines from patients with oncocytoma (n = 20) was detectable with ELISA compared to all other subtypes of RCCs (chromophobe (n = 50), papillary (n = 40), ccRCC (n = 200), and controls (n = 40) (***p < 0.0001)). Mxi-2 was predominantly overexpressed in ccRCCs (***p < 0.0001). Lateral flow assay of Vim3 and Mxi-2 shows two bands in the case of oncocytoma and ccRCC indicating the specificity of this test. For SRMs, an overexpression of miR-15a/Mxi2 was detectable in urine samples from ccRCC and chromoRCC patients. In contrast to that, miR-498/Vim3 were predominantly overexpressed in oncocytoma patients.

Conclusion: Both proteins (Vim3 and Mxi-2) were detectable in patients' urines and can be used for the non-invasive differentiation of kidney cancers.
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http://dx.doi.org/10.1002/jcla.23762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128285PMC
May 2021

Feasibility and Oncologic Outcome of Salvage Surgery in Isolated Seminal Vesicle Remnants after Radical Prostatectomy.

Urol Int 2021 Apr 7:1-7. Epub 2021 Apr 7.

Department of Urology, Uro-Oncology and Robot-assisted Surgery, University Hospital of Cologne, Cologne, Germany.

Background: To demonstrate the feasibility of resecting isolated locally relapsing seminal vesicle remnants after primary radical prostatectomy and radiotherapy. Early oncologic outcomes and prognostic risk factors for relapse are demonstrated.

Objectives And Methods: A total of 32 patients underwent open resection of locoregional prostate cancer recurrence in seminal vesicles, as documented on either MRI, 11C-choline, or 68Ga-PSMA PET/CT scans. Age, PSA-DT, PSA, and time to recurrence after primary treatment resection status were used in a uni- and multivariate Cox regression analysis for biochemical relapse after surgery.

Results: Median patient age at time of salvage surgery was 70 (57-77) years. Median PSA and PSA-DT was 2.79 (0.4-61.54) ng/mL and 5.4 (1.6-20.1) months, respectively. Median surgical time and hospital stay was 132 (75-313) min and 5.5 (4-13) days, respectively. After a mean follow-up of 29 (2-92) months, 3 patients died at 8, 14, and 40 months after salvage surgery, and 6 (18.75%) patients remain without biochemical relapse and further treatment. Median progression-free survival was 12 (1-81) months. In the univariable Cox regression analysis, age at time of surgery, preoperative PSA, and the time from primary treatment to salvage surgery were identified as significant parameters for biochemical relapse. Only the interval from primary to salvage surgery was significant in the multivariate analysis with a hazard ratio of 1.008 (95% CI: 1.001-1.015, p = 0.018). In the entire cohort, 4 adjunctive surgeries (3 ureteroneocystostomies and 1 nephrectomy) were needed due to local progressive disease.

Conclusion: Seminal vesicle resection is feasible with no significant intra- or postoperative complications. Almost all patients progressed to biochemical or systemic relapse. Salvage surgery must be seen as a preventive for local symptoms, in our experience most often postrenal ipsilateral obstruction.
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http://dx.doi.org/10.1159/000514054DOI Listing
April 2021

Targeted Therapy in Patients with Metastatic Male Germ Cell Tumors.

Urol Int 2021 17;105(7-8):720-723. Epub 2021 Mar 17.

Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany.

Ten to fifteen percent of patients with metastatic testis cancer (mGCT) will develop chemorefractory disease of which about 50% will die. We report on the integration of next generation sequencing in daily clinical practice to identify druggable mutations in metastatic lesions of 3 patients with mGCT. Mutational analysis revealed KIT D820G, TP53, and NPM1 mutations as well as mismatch repair deficiency with loss of MSH2 and MSH6 proteins so that targeted therapy with sunitinib (n = 2) or pembrolizumab (n = 1) was initiated resulting in remarkable partial remissions for 9, 12+, and 15 months.
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http://dx.doi.org/10.1159/000510717DOI Listing
March 2021

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

World J Urol 2021 Mar 8. Epub 2021 Mar 8.

SWENOTECA, Trondheim, Norway.

Purpose: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients.

Methods: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR).

Results: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p  ≤  0.001), respectively.

Conclusions: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.
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http://dx.doi.org/10.1007/s00345-021-03635-3DOI Listing
March 2021

[Using preorchiectomy tumor marker serum concentrations for International Germ Cell Consensus Classification (IGCCCG) risk group assignment results in significant numbers of up- and downstaging].

Urologe A 2021 Mar 11;60(3):337-343. Epub 2021 Jan 11.

Klinik für Urologie, Uro-Onkologie, spezielle urologische und roboter-assistierte Chirurgie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland.

Background: The prognostic classification system of the International Germ Cell Cancer Cooperative Group (IGCCCG) for testicular germ cell tumors is based on the histological subtype, location of the primary tumor, extent of metastatic spread and prechemotherapy tumor marker serum concentrations.

Objectives: In this study, we aim to identify whether the use of preorchiectomy instead of prechemotherapy tumor marker serum concentration has an impact on IGCCCG risk group assignment.

Materials And Methods: We performed a retrospective analysis including 135 patients with metastasized testicular germ cell tumors. Analysis of the clinical information with a focus on the tumor marker serum concentration preorchiectomy and prechemotherapy was performed, thus leading to the grouping of patients according to IGCCCG risk group assignment.

Results: Using preorchiectomy instead of prechemotherapy tumor markers led to an incorrect IGCCCG risk group classification in 8% (11/135) of all patients, and consequently to a non-guideline concordant treatment. Up-staging was observed in 8 of 11 patients, representing 6% (8/135) of the total patient cohort. Three of the 11 misclassified patients showed a down-staging and thus describe 2% (3/135) of the total patient cohort.

Conclusions: Using preorchiectomy tumor markers instead of prechemotherapy serum concentration might lead to an incorrect IGCCCG risk group assignment as well as non-guideline concordant treatment. Consequently, prechemotherapy tumor marker serum concentration should be applied for guideline concordant staging of patients.
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http://dx.doi.org/10.1007/s00120-020-01432-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979643PMC
March 2021

Major complications of post-chemotherapy retroperitoneal lymph node dissection in a contemporary cohort of patients with testicular cancer and a review of the literature.

World J Surg Oncol 2020 Sep 24;18(1):253. Epub 2020 Sep 24.

Department of Urology, Albertinen Krankenhaus Hamburg, Suentelstrasse 11a, 22457, Hamburg, Germany.

Background: Post-chemotherapy retroperitoneal lymph node dissection (pc-RPLND) is one cornerstone in the clinical management of patients with nonseminomatous testicular germ cell tumours (GCT). A wide range of complication rates in this type of surgery is reported so far. We retrospectively evaluated the frequency of major complications by using the Clavien-Dindo classification and analysed the influence of various clinical factors on complication rates in pc-RPLND.

Methods: We retrospectively analysed 146 GCT patients undergoing pc-RPLND. Complications of grade III-V according to the Clavien-Dindo classification occurring within 30 days after surgery were registered along with the following clinical factors: age, body mass index (BMI), duration of surgery, number of anatomic fields resected, side of primary tumour, histology of surgical specimen, histology of primary tumour, and total dose of cisplatin applied prior to surgery. For comparison, we also evaluated 35 chemotherapy-naïve patients with primary RPLND and 19 with laparoscopic RPLND. We analysed types and frequencies of the various complications as well as associations with clinical factors using descriptive statistical methods.

Results: A total of 14.4% grade III-IV complications were observed in pc-RPLND, and 8.6% and 5.3% in primary and in laparoscopic RPLND, respectively. There was no perioperative mortality. Lymphocele was the most frequent adverse event (16% of grade III-IV complications). Operation time > 270 min (p = 0.001) and vital cancer in the resected specimen (p = 0.02) were significantly associated with higher complication rates. Left-sided resection fields involved two-fold higher complication rates, barely missing statistical significance (p = 0.06).

Conclusions: Pc-RPLND involves a grade III-V complication rate of 14.4%. Prolonged operation time and vital cancer in the residual mass are significantly associated with higher complication rates. The Clavien-Dindo classification system may allow inter-observer variation in rating complication grades, which may represent one reason for the wide range of reported RPLND complication rates. RPLND represents major surgery and surgeons active in this field must be competent to manage adverse events.
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http://dx.doi.org/10.1186/s12957-020-02032-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517823PMC
September 2020

Prediction of Radioresistant Prostate Cancer Based on Differentially Expressed Proteins.

Urol Int 2021 13;105(3-4):316-327. Epub 2020 Aug 13.

Department of Urology, University Hospital of Cologne, Cologne, Germany.

Introduction: Although relapses after radiotherapy are common in prostate cancer (PCA) patients, those with a high risk for radioresistance cannot be identified prior to treatment yet. Therefore, this proof-of-concept study was performed to compare protein expression profiles of patients with radio-recurrent PCA to patients treated with primary radical prostatectomy separated by Gleason risk groups. We hypothesized that radio-recurrent PCA have a similar protein expression as high-risk Gleason PCA.

Methods: Patient cohorts consisted of (i) 31 patients treated with salvage prostatectomy for locally recurrent PCA after primary radiotherapy and (ii) 94 patients treated with primary prostatectomy split into a Gleason high-risk (≥4 + 3; n = 42 [44.7%]) versus a low-risk group (≤3 + 4; n = 52 [55.3%]). Immunohistochemistry was performed using 15 antibodies with known association to radioresistance in PCA in vitro. ELISA was used for validation of selected markers in serum.

Results: Androgen receptor (AR) was overexpressed in most radio-recurrent PCA (89.7%) and in most primary high-risk Gleason PCA (87.8%; p = 0.851), while only 67.3% of the low-risk group showed an expression (p = 0.017). Considering the highest Gleason pattern in primary PCA, aldo-keto reductase family 1 member C3 (AKR1C3) was most similarly expressed by patients with radio-recurrent PCA and patients with Gleason patterns 4 and 5 (p = 0.827 and p = 0.893) compared to Gleason pattern 3 (p = 0.20). These findings were supported by ELISA.

Conclusion: This is the first study to evaluate protein markers in order to predict radioresistance in PCA. Our results point to AR and AKR1C3 as the most promising markers that might help stratify patients for radiotherapy.
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http://dx.doi.org/10.1159/000509447DOI Listing
July 2021

Ga-PSMA-PET/CT helps to select patients for salvage radical prostatectomy with local recurrence after primary radiotherapy for prostate cancer.

BJU Int 2020 12 4;126(6):679-683. Epub 2020 Aug 4.

Department of Urology, Uro-Oncology and Robot Assisted Surgery, University Hospital of Cologne, Cologne, Germany.

Objective: To investigate the diagnostic performance of gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography ( Ga-PSMA PET/CT) in patients with recurrent prostate cancer with regard to the presence of lymph node metastases (LNM) and local recurrences after primary radiotherapy.

Patients And Methods: We retrospectively reviewed 142 patients following salvage radical prostatectomy (sRP), 50 of which had a Ga-PSMA PET/CT performed as a preoperative staging module. Predictive clinical parameters were analysed in a multivariate Cox regression analysis. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and the accuracy of Ga-PSMA PET/CT were analysed with regard to LNM and local recurrence.

Results: In all, 613 lymph nodes were resected in 40 patients and 23 lymph nodes had metastatic deposits in 14 patients. In all patients local recurrence could have been found with Ga-PSMA PET/CT. Sensitivity, specificity, PPV and NPV and accuracy on a per lymph node basis were 34.78% (16.38-57.2%), 100% (99.38-100%), 100%, 97.52% (96.69-98.15%) and 97.55% (96.00-98.62%). For detecting local recurrence, the sensitivity and PPV were both 100% with an accuracy of 100% (92.89-100%).

Conclusion: Ga-PSMA PET/CT should be the standard imaging in biochemical recurrent prostate cancer. With this imaging module one detects first local recurrence and can detect locoregional and distant metastases more precisely than standard CT and bone scan.
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http://dx.doi.org/10.1111/bju.15135DOI Listing
December 2020

Human chorionic gonadotropin-positive seminoma patients: A registry compiled by the global germ cell tumor collaborative group (G3).

Eur J Cancer 2020 06 29;132:127-135. Epub 2020 Apr 29.

Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: The prognostic role of human chorionic gonadotropin (hCG) and lactate dehydrogenase (LDH) serum levels in seminoma patients remains uncertain. This observational study evaluates the prognostic impact of tumour marker levels, and other clinicopathological findings, in hCG-positive seminoma patients.

Methods: Seminoma patients with serum hCG levels above normal at first diagnosis were eligible for recruitment. Statistical analysis, including multivariate regression, was performed to identify risk factors. Primary end-points were overall survival (OS) and recurrence-free survival (RFS).

Results: We recruited 1031 hCG-positive patients (stage I: n = 586; stage II + III: n = 427) diagnosed between 1981 and 2018. In metastatic disease, LDH levels ≥3 above upper normal limit (UNL) pre- (n = 109) or post-orchiectomy (n = 73) and patients aged ≥40 years (n = 187) were associated with poor prognosis: 5-year OS rates of 84% (LDH ≥3 UNL pre-orchiectomy) versus 92% (<3 UNL pre-orchiectomy) (hazard ratio [HR]: 3.155, [95% confidence interval {CI}: 1.28-7.75], P = 0.012), 82% (≥3 UNL post-orchiectomy) versus 92% (<3 UNL post-orchiectomy) (HR: 6.877, [95% CI: 1.61-29.34]; P = 0.009) and 86% (≥40 years) versus 91% (<40 years) (HR: 6.870, [95% CI: 1.45-13.37], P = 0.009), respectively. A subset of patients with hCG levels ≥2000 IU/l pre-orchiectomy (n = 17) exhibited a poor prognosis, with 5-year OS rates of 73% (≥2000 IU/l) versus 94% (<2000 IU/l) (HR: 3.936, [95% CI: 1.02-12.61], P = 0.047).

Conclusions: Age and LDH levels are significantly associated with poor prognosis in hCG-positive seminoma patients. A small number of patients, with levels of hCG ≥2000 IU/l, may represent a separate prognostic subgroup associated with impaired survival rates.
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http://dx.doi.org/10.1016/j.ejca.2020.03.022DOI Listing
June 2020

Pelvic exenteration surgery in patients with locally advanced castration-naïve and castration-resistant, symptomatic prostate cancer.

BJU Int 2020 09 16;126(3):342-349. Epub 2020 May 16.

Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urological Surgery, University Hospital Cologne, Cologne, Germany.

Objectives: To evaluate retrospectively the surgical, symptomatic and oncological outcomes of pelvic exenteration surgery (PES) in men with significant intrapelvic complications of locally advanced castration-sensitive (CSPC) and castration-resistant prostate cancer (CRPC).

Patients And Methods: A total of 103 patients with locally advanced progressive and symptomatic CSPC or CRPC underwent PES (radical cystoprostatectomy, n = 71 [68.9%]; radical prostatectomy with continent vesicostomy, n = 9 [8.7%]; total exenteration, n = 23 [22.3%]). All patients underwent local staging via magnetic resonance imaging, cystoscopy and rectoscopy. Systemic staging was carried out with chest, abdominal and pelvic computed tomography scans and bone scans. Peri-operative complications were assessed according to Clavien-Dindo classification. Symptom-free and overall survival were evaluated using the Kaplan-Meier method. Statistical tests were two-tailed with a P value <0.05 taken to indicate statistical significance.

Results: After a median (range) follow-up of 36.5 (3-123) months, the symptom-free survival rate at 1 and 3 years was 89.2% (n = 89) and 64.1% (n = 66), respectively. The median symptom-free survival was 27.9 months. A total of 78.6% of the patients were symptom-free during their remaining lifetime. The overall survival rate at 1 and 3 years was 92.2% and 43.7%, respectively, and the median overall survival was 33.6 months. Clavien-Dindo grades 2, 3 and 4 complications developed in 31 (30.6%), 12 (11.6%) and eight patients (8.1%), respectively.

Conclusion: Pelvic exenteration surgery is technically feasible in well-selected patients, resulting in symptom relief in >90% of patients, covering 80% of their remaining lifetime.
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http://dx.doi.org/10.1111/bju.15088DOI Listing
September 2020

Role of primary retroperitoneal lymph node dissection in stage I and low-volume metastatic germ cell tumors.

Curr Opin Urol 2020 03;30(2):251-257

Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.

Purpose Of Review: Early-stage testicular cancers are highly curable. Following orchidectomy, management options for stage I disease include active surveillance, nerve-sparing retroperitoneal lymph node dissection (nsRPLND) and primary chemotherapy as recommended by the current guidelines. Primary RPLND has for decades played an integral part of treatment in patients with early-stage testicular germ cell tumors (TGCT), particularly in nonseminomatous germ cell tumors (NSGCT) with focus on reducing the long-term morbidity. We review the role of RPLND in stage I NSCGT as well as stage II A/B NSGCT and as seminoma.

Recent Findings: Radiation therapy and systemic chemotherapy are established treatments for seminoma; however, long-term data has demonstrated the association of such therapies with late toxicity including secondary malignancies, hearing loss, cardiovascular disease as well as metabolic syndromes. Given the well established role of RPLND in NSGCTs, clinicians have developed an interest in utilization of surgery for low-volume retroperitoneal metastatic disease. Two prospective clinical trials (SEMS and PRIMETEST) are underway to determine the role of RPLND alone in low volume metastatic seminoma.

Summary: RPLND is a highly effective treatment for early-stage germ cell tumors but represents overtreatment in low-volume stage I disease where active surveillance is recommended. RPLND has shown a promising role in low-volume stage II seminomas. Two phase II clinical trials are underway to further determine the curative potential of this approach.
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http://dx.doi.org/10.1097/MOU.0000000000000736DOI Listing
March 2020

Vimentin 3 Allows Differentiation between Normozoospermia and Oligoasthenoteratozoospermia.

Dis Markers 2019 10;2019:9803498. Epub 2019 Dec 10.

Department of Urology, University Hospital of Cologne, Germany.

Vimentin is a structural protein predominantly located in the head of sperms. The function and localization of the previously identified truncated version, Vimentin 3 (Vim3), are still unknown. To investigate whether the expression of Vim3 can be used as a reliable marker for the differentiation of sperm quality, we analyzed ejaculates from patients with oligoasthenoteratozoospermia (OAT) syndrome and normozoospermia. We identified sperms with head, neck, and tail changes, which were less positive for Vim3 in OAT syndrome compared to normozoospermia. The expression of Vim3 was significantly downregulated in patients with OAT syndrome compared to sperms from patients with normozoospermia ( < 0.01). The ELISA analysis showed similar results as ejaculates from normozoospermic patients showed a significantly higher Vim3 concentration than patients with OAT syndrome ( < 0.001). This study demonstrates that Vim3 is more highly expressed in ejaculates from patients with normozoospermia compared to ejaculates from patients with OAT syndrome. Therefore, we postulate that Vim3 can be used to determine ejaculate quality. Furthermore, we identified the marker, Vim3, to differentiate between mature sperms with no morphological changes and sperms with head, neck, and tail changes. A lateral flow assay that allows quick analysis is currently under development.
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http://dx.doi.org/10.1155/2019/9803498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925920PMC
May 2020

Radiomics allows for detection of benign and malignant histopathology in patients with metastatic testicular germ cell tumors prior to post-chemotherapy retroperitoneal lymph node dissection.

Eur Radiol 2020 Apr 11;30(4):2334-2345. Epub 2019 Dec 11.

Department of Urology, University Hospital of Cologne, Cologne, Germany.

Objectives: To evaluate whether a computed tomography (CT) radiomics-based machine learning classifier can predict histopathology of lymph nodes (LNs) after post-chemotherapy LN dissection (pcRPLND) in patients with metastatic non-seminomatous testicular germ cell tumors (NSTGCTs).

Methods: Eighty patients with retroperitoneal LN metastases and contrast-enhanced CT were included into this retrospective study. Resected LNs were histopathologically classified into "benign" (necrosis/fibrosis) or "malignant" (viable tumor/teratoma). On CT imaging, 204 corresponding LNs were segmented and 97 radiomic features per LN were extracted after standardized image processing. The dataset was split into training, test, and validation sets. After stepwise feature reduction based on reproducibility, variable importance, and correlation analyses, a gradient-boosted tree was trained and tuned on the selected most important features using the training and test datasets. Model validation was performed on the independent validation dataset.

Results: The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a misclassification of 8 of 36 benign LNs as malignant and 4 of 25 malignant LNs as benign (sensitivity 88%, specificity 72%, negative predictive value 88%). In contrast, a model containing only the LN volume resulted in a classification accuracy of 0.68 with 64% sensitivity and 68% specificity.

Conclusions: CT radiomics represents an exciting new tool for improved prediction of the presence of malignant histopathology in retroperitoneal LN metastases from NSTGCTs, aiming at reducing overtreatment in this group of young patients. Thus, the presented approach should be combined with established clinical biomarkers and further validated in larger, prospective clinical trials.

Key Points: • Patients with metastatic non-seminomatous testicular germ cell tumors undergoing post-chemotherapy retroperitoneal lymph node dissection of residual lesions show overtreatment in up to 50%. • We assessed whether a CT radiomics-based machine learning classifier can predict histopathology of lymph nodes after post-chemotherapy lymph node dissection. • The trained machine learning classifier achieved a classification accuracy of 0.81 in the validation dataset with a sensitivity of 88% and a specificity of 78%, thus allowing for prediction of the presence of viable tumor or teratoma in retroperitoneal lymph node metastases.
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http://dx.doi.org/10.1007/s00330-019-06495-zDOI Listing
April 2020

Centralization tendencies of retroperitoneal lymph node dissection for testicular cancer in Germany? A total population-based analysis from 2006 to 2015.

World J Urol 2020 Jul 11;38(7):1765-1772. Epub 2019 Oct 11.

Department of Urology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.

Introduction: Retroperitoneal lymph node dissection (RPLND) is a standard treatment in the management of metastatic testicular cancer. Due to modified treatment algorithms, it is becoming less frequent.

Materials And Methods: We analyzed data from the nationwide German hospital billing database covering 2006-2015. Cases with a testicular cancer diagnosis combined with RPLND were included. We assessed the length of hospital stay (LOS), blood transfusion, and in-hospital mortality stratified for surgical approach, hospital characteristics, and annual caseload. Annual hospital caseload categories were defined as low (< 4), medium (4-10), and high (> 10). We supplemented tumor incidence and staging data from the German cancer registry (60% of population).

Results: 4926 cases were included with decreasing annual caseload numbers from 623 in 2006 to 382 in 2015. The incidence of testicular cancer and higher tumor stages remained stable. High-volume hospitals performed 19.4%, medium-volume hospitals 43.7%, and low-volume hospitals 36.8% RPLNDs. Low- abd medium-volume hospitals declined, while high-volume hospitals (n = 5) maintained their annual caseload. Overall in-hospital mortality was 0.47%. Blood transfusion rates were higher in high-volume centers assumedly due to selection of more complex cases. However, high-volume hospitals showed a shorter LOS with 10.5 vs. 11.2 (medium volume), and 12.7 days (low volume).

Conclusion: Total numbers of RPLND have declined from 2006 to 2015, while tumor incidences and stages remained fairly stable. Constant reduction of indication in guidelines contributes to this finding. High-volume hospitals achieve shorter hospital stays in spite of assumedly more complex and extensive cases. There is a modest trend towards unregulated centralization.
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http://dx.doi.org/10.1007/s00345-019-02972-8DOI Listing
July 2020

External validation of 2 models to predict necrosis/fibrosis in postchemotherapy residual retroperitoneal masses of patients with advanced testicular cancer.

Urol Oncol 2019 11 17;37(11):809.e9-809.e18. Epub 2019 Sep 17.

Department of Urology, University Hospital Cologne, Cologne, Germany; Department of Urology, Medical University Vienna, Austria. Electronic address:

Objectives: Nonseminomatous testicular germ cell tumors with residual retroperitoneal lesions >1 cm are treated with postchemotherapy retroperitoneal lymph node dissection (pcRPLND). However, up to 50% of patients are overtreated since the histology shows only residual necrosis/fibrosis. We aim to validate the 2 currently best performing prediction models (Vergouwe and Leao) for postchemotherapy residual mass histology.

Methods And Materials: We performed a retrospective analysis including 402 patients who underwent a pcRPLND from 2008 to 2015. The study cohort was used to validate the 2 prediction models by Vergouwe and Leao using the published formulas and thresholds.

Results: Using our validation cohort, the Vergouwe model reached a significantly better area under the curve compared to the Leao model (0.760 (confidence interval 0.713-0.807) vs. 0.692 (0.640-0.744), P = 0.002) in the prediction of benign histology. At a threshold of >70% for the predicted probability of benign disease, the Leao model revealed that pcRPLND would be avoided in 10.2% of patients with benign disease with an error rate of 3.8% for viable tumor, while the Vergouwe model would avoid pcRPLND in 27.4% of all patients with benign disease with an error rate of 10.1% for viable tumor and 2.9% for teratoma. Adjusting the models to our data had no significant improvement. Limitations include the retrospective design.

Conclusions: The discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of pcRPLND. Therefore, further studies including new biomarkers are needed to optimize the accuracy of potential prediction models and to minimize pcRPLND overtreatment.
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http://dx.doi.org/10.1016/j.urolonc.2019.07.021DOI Listing
November 2019

[Personalised medicine in prostate cancer].

Aktuelle Urol 2019 Sep 29;50(5):509-512. Epub 2019 Aug 29.

Universitätsklinikum Köln, Urologie, Köln.

Prostate cancer is the most common cancer in men. Its incidence increases with age. New treatment options have been introduced and there is a clear trend to more aggressive treatment in newly diagnosed metastatic disease. While prolonged survival of patients has been achieved, the new expensive drugs are associated with an increased burden on the healthcare system. Meanwhile, similarly to other tumour entities, there is a pool of different drugs available with comparable oncologic efficacy, but different side-effects. Effective diagnostic investigation and treatment decisions require additional factors, above and beyond clinical parameters, for a more individual treatment approach. In castration-resistant prostate cancer (CRPCA), there are promising molecular markers for treatment decisions. In metastatic disease, liquid biopsies and next generation sequencing of metastatic biopsies allow for genetic analysis. These will provide more insight into tumour dynamics and allow for patient selection. This review concentrates on molecular markers in CRPCA.
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http://dx.doi.org/10.1055/a-0972-0824DOI Listing
September 2019

European Association of Urology Guidelines on Testis Cancer: Important Take Home Messages.

Eur Urol Focus 2019 Sep 16;5(5):742-744. Epub 2019 Aug 16.

Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany.

Testicular germ-cell tumors represent the most common solid neoplasms among young men aged 20-40 yr. Owing to interdisciplinary management and high chemosensitivity, cure rates are high even among patients with poor risk. Although the diagnostic and therapeutic approaches for organ-confined disease and low-volume and high-volume metastatic disease are well standardized and reported in numerous national and international guidelines, guidelines, high frequency of guideline noncompliance has recently been observed, resulting in poorer long-term outcomes. This article underlines the clinically most important messages that should be adhered to in the management of testis cancer patients to avoid patient harm and achieve the best therapeutic outcomes. These recommendations include: (1) a detailed pathology report by an experienced uropathologist; (2) organ-sparing surgery or frozen section analysis for patients with bilateral testis cancer or testicular masses of uncertain identity; (3) risk-adapted therapy for clinical stage I seminomas and nonseminomas; and (4) interdisciplinary management of patients with advanced testis cancer in high-volume centers. PATIENT SUMMARY: Management of testis cancer has been standardized but lack of compliance with guidelines is increasing, resulting in inferior oncological outcomes. Close adherence to guidelines and early referral of complex cases are of utmost importance for high cure rates.
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http://dx.doi.org/10.1016/j.euf.2019.08.002DOI Listing
September 2019

Adjuvant carboplatin therapy in patients with clinical stage 1 testicular seminoma: is long-term morbidity increased?

J Cancer Res Clin Oncol 2019 Sep 8;145(9):2335-2342. Epub 2019 Jul 8.

Klinik für Urologie, Albertinen-Krankenhaus Hamburg, Suentelstr. 11a, 22457, Hamburg, Germany.

Purpose: Clinical stage (CS) 1 testicular seminoma is cured in almost 100% of cases following either retroperitoneal radiotherapy, carboplatin monotherapy, or surveillance strategies. Little is known about potential long-term effects of carboplatin. We, therefore, examined late sequelae of this drug in seminoma patients.

Patients And Methods: We retrospectively identified 451 patients with CS1 testicular seminoma treated between 1994 and 2014, of whom 243 underwent carboplatin therapy [median follow-up (F/U) 96 months], 81 received radiotherapy (median F/U 142 months), and 127 underwent surveillance (median F/U 40 months). Satisfaction regarding management, as well as the following events during F/U, were analysed by questionnaire: subsequent malignant neoplasms (SMNs), cardiovascular events, arterial hypertension, peptic ulcer, tinnitus, peripheral neuropathy, hypogonadism, and infertility. The relative frequencies of the events were analysed using descriptive statistics. The frequency of observed SMNs was compared with the expected number.

Results: Patients receiving carboplatin tolerated the treatment less well (71.2%) than those under surveillance (81.9%). After carboplatin, 12 SMNs (5.0%) were noted vis-a-vis 5.0 expected. There were three cases of prostatic cancer and 3 melanomas among the SMNs. Half of these SMNs occurred early after treatment. Among the other health events, only reported hypogonadism (13.2%) appeared to be marginally increased in frequency.

Conclusions: This study found a 2.4-fold higher than expected rate of SMN-and a slightly increased rate of hypogonadism-in the long-term period following carboplatin treatment. Although further studies are needed to confirm these preliminary findings, these results are probably informative for clinicians caring for seminoma patients.
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http://dx.doi.org/10.1007/s00432-019-02965-5DOI Listing
September 2019

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia.

Urol Int 2019 8;103(1):108-115. Epub 2019 May 8.

Department of Urology, PAN-Clinic, Cologne, Germany.

Background: The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT).

Objectives: To analyse the use of tamoxifen in iOAT.

Method: Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment.

Results: After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7-4.8] vs. 5.3 [3.1-7.1]; p = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9-11.5] vs. 15.9 mIU/mL [8.4-19.9]; p = 0.003) and luteinizing hormone (4.5 [3.3-6.6] vs. 7.6 mIU/mL [4.8-10.7]; p = 0.007) significantly increased. At a cut-off of >8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068-0.773]; p  = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of <82 ng/L (OR 18.0 [95% CI 1.267-255.744]; p = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events.

Conclusions: Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.
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http://dx.doi.org/10.1159/000500301DOI Listing
February 2020

Management of residual masses in testicular germ cell tumors.

Expert Rev Anticancer Ther 2019 04 22;19(4):291-300. Epub 2019 Feb 22.

a Department of Urology, Urologic Oncology, Robot-assisted and Specialized Urologic Surgery , University Hospital Cologne , Köln , Germany.

Introduction: About 50% of all patients with advanced testicular cancer demonstrate residual retroperitoneal or extraretroperitoneal masses. About two thirds of the masses harbour necrosis/fibrosis only whereas as about 10% and 40% harbour vital cancer or teratoma. Appropriate therapy will result in a high cure rate if performed properly. Areas covered: This review article covers the indication, the surgical technique and the oncological outcome of PC-RPLND and resection of extraretroperitoneal residual masses following chemotherapy in patients with advanced testis cancer. Expert commentary: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays an integral part of the multimodality treatment in patients with advanced testicular germ cell tumours. Patients with nonseminomas, residual masses < 1cm and good prognosis can undergo active surveillance. In all other cases, PC-RPLND with or without resection of adjacent organs needs to be performed for curative intent. PC-RPLND requires a complex surgical approach and should be performed in experienced, tertiary referral centres only.
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http://dx.doi.org/10.1080/14737140.2019.1580146DOI Listing
April 2019

Predictors of thrombosis in testicular cancer during platinum-based chemotherapy.

World J Urol 2019 Sep 13;37(9):1907-1916. Epub 2018 Dec 13.

Department of Urology, Uro-Oncology, Robot Assisted and Reconstructive Urologic Surgery, University Hospital Cologne, Kerpener Straße 62, 50937, Cologne, Germany.

Purpose: To identify potential risk factors for the development of venous thromboembolic events in testicular cancer patients receiving platinum-based chemotherapy.

Methods: We performed a retrospective analysis including 255 patients with testicular germ cell tumors who received platinum-based chemotherapy from 2003 to 2018 as a multi-center observational cohort study. Patient and tumor characteristics of patients with and without a thromboembolic event were analyzed.

Results: 49 (19%) patients experienced a venous thromboembolic event, with the majority representing pulmonary embolism and deep venous thrombosis (47%). There were no significant differences regarding the development of a venous thromboembolic event between first- and second-line regimes. Multivariate analysis showed an increased risk for a venous thromboembolic event in patients with clinical stage ≥ IIC disease (OR 2.259 [95% CI 1.105-4.618], p = 0.026), elevated serum LDH (OR 2.162 [95% CI 1.018-4.593], p = 0.045), febrile neutropenia (OR 2.973 [95% CI 1.363-6.487], p = 0.006) and central venous access (OR 3.465 [95% CI 1.068-11.243], p = 0.039). Patients suffering from a venous thromboembolic event revealed a significantly reduced overall survival (p = 0.033) during a median follow-up of 8 months [IQR 2-18].

Conclusions: 19% of all patients treated by platinum-based chemotherapy due to testicular cancer suffered from a venous thromboembolic event, associated with reduced overall survival. As a result, monitoring of cancer patients at risk as well as the improvement of patients' awareness of a thromboembolic event should thus be the main goal of their treating physicians.
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http://dx.doi.org/10.1007/s00345-018-2598-7DOI Listing
September 2019

Modern imaging techniques in urinary stone disease.

Curr Opin Urol 2019 03;29(2):81-88

Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany.

Purpose Of Review: Radiological imaging techniques are a fast developing field in medicine. Therefore, the purpose of this review was to identify and discuss the latest changes of modern imaging techniques in the management of urinary stone disease.

Recent Findings: The introduction of iterative image reconstruction enables low-dose and ultra-low-dose (ULD) protocols. Although current guidelines recommend their utilization in nonobese patients recent studies indicate that low-dose imaging may be feasible in obese (<30 kg/m) but not in bariatric patients. Use of dual energy computed tomography (CT) technologies should balance between additional information and radiation dose aspects. If available on a dose neutral basis, dual energy imaging and analysis should be performed. Current guidelines recommend measuring the largest diameter for clinical decision making; however, recent studies suggest a benefit from measuring the volume based on multiplanar reformation. Quantitative imaging is still an experimental approach.

Summary: The use of low-dose and even ULD CT protocols should be diagnostic standard, even in obese patients. If dual energy imaging is available, it should be limited to specific clinical questions. The stone volume should be reported in addition to the largest diameter for treatment decision and a more valid comparability of upcoming studies.
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http://dx.doi.org/10.1097/MOU.0000000000000572DOI Listing
March 2019

Testicular cancer guideline adherence and patterns of care in Germany: A nationwide survey.

Eur J Cancer Care (Engl) 2019 Jan 25;28(1):e12917. Epub 2018 Sep 25.

Department of Urology, University Hospital Dresden, Dresden, Germany.

Testicular cancer has excellent cure rates; however, poor guideline adherence can lead to inappropriate management, with a detrimental effect on outcomes. Therefore, we aimed to investigate the current patterns of care for testicular cancer patients and to evaluate guideline adherence. A 19-item survey was distributed among German urologists between September 2015 and September 2016. The response rate was 45% (411/920). Staging imaging of the chest was performed by computed tomography (CT) in 85.5% and X-ray in 17.7%, and for the abdomen, by CT in 83.7% and by magnetic resonance imaging (MRI) in 21.1%. Areas of discrepancy with respect to guideline recommendations included underuse of MRI and infrequent follow-up examinations for changes in the cardiovascular, endocrine, neurological, and pulmonary systems, in addition to psychological burden. Further deviations of reported routine procedures from guideline recommendations were identified in the fields of active surveillance in Stage I seminoma, contralateral biopsies (63.1% overuse) and cryopreservation (19.2% underuse). Moreover, we found that hospital-based clinicians and younger specialists, with ≤5 years of practice following board certification, perform a more accurate and thorough follow-up. German urologists show relatively strong guideline adherence in staging patterns. Significant improvements are necessary in the following areas: recommending cryopreservation, imaging modalities and accurate follow-up examinations with a focus on late toxicities.
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http://dx.doi.org/10.1111/ecc.12917DOI Listing
January 2019

Diagnostic accuracy of third-generation dual-source dual-energy CT: a prospective trial and protocol for clinical implementation.

World J Urol 2019 Apr 3;37(4):735-741. Epub 2018 Aug 3.

Department of Urology, Federal Armed Services Hospital Koblenz, Rübenacher Str. 170, 56072, Koblenz, Germany.

Purpose: Uric acid (UA) calculi can be referred to chemolitholysis rather than invasive treatment. Dual-energy computed tomography (DECT) may be able to distinguish between UA and non-UA (NUA) calculi. The aim of this study was to evaluate the validity of third-generation DECT for the first time and to investigate whether combining DECT with clinical parameters can increase its predictive accuracy.

Materials And Methods: All patients who presented to our emergency department between January 2015 and March 2017 with urinary stones were prospectively included in this observational study and underwent DECT with subsequent interventional stone removal. Stone composition was analyzed using infrared spectrometry as the gold standard. Predictive accuracy of DECT and clinical covariates was computed by assessing univariate and multivariate areas under the curve (AUCs).

Results: Of 84 patients with 144 urinary stones, 10 (11.9%) patients had UA stones according to infrared spectrometry, and the remaining stones were NUA or mixed stones. DECT had a positive predictive value of 100% and a negative predictive value of 98.5% for UA stones. The AUC for urine pH alone was 0.71 and 0.97 for DECT plus urine pH. No UA stones were found in patients with a urine pH above > 5.5. Mean DLP was 225.15 ± 128.60 mGy*cm and mean effective dose was 3.38 ± 1.93 mSv.

Conclusions: DECT is a safe method for assigning patients to oral chemolitholysis. Clinical preselection of patients based on urinary pH (< 6.0) leads to a more liable use of DECT. Third-generation DECT needs significant lower radiation doses compared to previous generations.
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http://dx.doi.org/10.1007/s00345-018-2430-4DOI Listing
April 2019

Liquid Biopsy Using Whole Blood from Testis Tumor and Colon Cancer Patients-A New and Simple Way?

Health Phys 2018 07;115(1):114-120

Bundeswehr Institute of Radiobiology affiliated to the University Ulm, Neuherbergstraße 11, 80804, Munich, Germany.

Tumor cells shed exosomes, which are released to the blood. Detecting tumor-derived exosomes containing RNA in plasma (liquid biopsy) is currently being investigated for early identification of occult metastases or relapses. Isolation of exosomes is laborious, resulting in low RNA yields. As a more robust (but less sensitive) alternative, the authors examined whether whole blood can be used as well. Tumor samples from nonmetastasized seminoma (n = 5) and colon cancer patients (n = 6) were taken during surgery. Whole-blood samples were taken before and 5-7 d after surgery. A whole genome mRNA microarray screening was performed. Candidate genes were selected based on two criteria: (1) gene expression in the presurgical whole-blood sample/tumor biopsy; and (2) a two-fold decrease in the copy number of candidate genes was expected in the postsurgical whole-blood sample 5-7 d after intervention, relative to the presurgical blood sample. The rationale behind this is the loss of tumor material in the body and the decline in the release of tumor-derived RNA in exosomes. For both tumor entities and for each patient, several hundred candidate genes could be identified. In a group-wise comparison, 20 candidate genes could be identified in the seminoma and 32 in the colon cancer group. These findings indicate that whole blood might be suitable for a liquid biopsy. However, this study identified the short period after surgery (5-7 d) as a possible confounder. The authors plan to add an additional time point several weeks after the operation to discriminate tumor candidate genes from genes induced by the surgery.
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http://dx.doi.org/10.1097/HP.0000000000000867DOI Listing
July 2018

Primary and Postchemotherapy Retroperitoneal Lymphadenectomy for Testicular Cancer.

Oncol Res Treat 2018 17;41(6):370-378. Epub 2018 May 17.

Clinical stage I (CS I) testicular non-seminomatous germ cell tumours (NSGCT) are highly curable. Following orchidectomy, a risk-adapted approach using active surveillance, nerve-sparing retroperitoneal lymph node dissection (RPLND) and primary chemotherapy is recommended by the current guidelines. CS I is defined as showing negative values for tumour markers (or values declining to their half-life following orchidectomy) and negative imaging studies of the chest, abdomen and retroperitoneum. Active surveillance can be performed in low- and high-risk NSGCT with an anticipated relapse rate of about 15% and 50%, respectively. The majority of patients will relapse with good and intermediate prognosis tumours, which have to be treated with 3 to 4 cycles of chemotherapy. About 25-30% of these patients will have to undergo postchemotherapy (PC) RPLND for residual masses. Primary chemotherapy with 1-2 cycles of cisplatin, etoposide, bleomycin (PEB) is a therapeutic option for high-risk CS I NSGCT associated with a recurrence rate of only 2-3% and a minimal acute and long-term toxicity rate. Nerve-sparing RPLND, if performed properly, will cure about 85% of all high-risk patients with CS I NSGCT without the need for chemotherapy. PC-RPLND plays an integral part of the multimodality treatment in patients with advanced testicular germ cell tumours (TGCT). According to current guidelines and recommendations, PC-RPLND in advanced seminomas with residual tumours is only indicated if a positron emission tomography scan performed 6-8 weeks after chemotherapy is positive. In non-seminomatous TGCT, PC-RPLND is indicated for all residual radiographical lesions with negative or plateauing markers. Loss of antegrade ejaculation represents the most common long-term complication, which can be prevented by a nerve-sparing or modified template resection. The relapse rate after PC-RPLND is around 12%; however, it increases significantly to about 45% in cases with redo RPLND and late relapses. Patients with increasing markers should undergo salvage chemotherapy. Only select patients with elevated markers who are thought to be chemo-refractory might undergo desperation PC-RPLND if all radiographically visible lesions are completely resectable. PC-RPLND requires a complex surgical approach and should only be performed in experienced, tertiary referral centres.
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http://dx.doi.org/10.1159/000489508DOI Listing
August 2019

Thromboprophylaxis and the route of administration of chemotherapy in testicular cancer patients in German-speaking countries.

World J Urol 2018 Jun 7;36(6):913-920. Epub 2018 Feb 7.

Department of Urology, Federal Armed Services Hospital Koblenz, Koblenz, Germany.

Purpose: Due to the excellent cure rates for testicular cancer (TC), focus has shifted towards decreasing therapy-related morbidities. Thrombosis is a frequent complication of cisplatin chemotherapy. Furthermore, the optimal route of administration for chemotherapy is still under debate. The purpose of this study was to assess the patterns of care concerning dosing and duration of thromboprophylaxis currently utilized in TC patients in German-speaking countries as well as the route of chemotherapy administration.

Methods: A standardized questionnaire was sent to all members of the German TC Study Group (GTCSG) and to all the urological university hospitals in Germany. The questionnaire was also sent to the oncologic clinics at those universities where urologists do not administer chemotherapy.

Results: The response rate was 87% (55/63). Prophylactic anticoagulation with low-molecular-weight heparin (LMWH) was administered in 94% of the clinics. The dosing of LMWH was prophylactic (85%), high prophylactic (adjusted to bodyweight) (7%), or risk adapted (9%). After completion of chemotherapy, anticoagulation was continued in 15 clinics (33%) for 2 to 24 weeks, while the remainder stopped the LMWH upon cessation of chemotherapy. Chemotherapy was administered via central venous access in 59%, peripheral IV in 27%, or both in 14% of the clinics.

Conclusions: Most of the institutions performed some form of thromboprophylaxis, although the modes of application varied by institution type and amongst the urologists and oncologists. Prospective studies are needed to evaluate the incidence, date of occurrence, and risk factors of venous thrombosis during TC chemotherapy to provide a recommendation concerning prophylactic anticoagulation.
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http://dx.doi.org/10.1007/s00345-018-2222-xDOI Listing
June 2018

Widespread use of internet, applications, and social media in the professional life of urology residents.

Can Urol Assoc J 2017 Sep;11(9):E355-E366

Department of Urology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.

Introduction: Digital media have revolutionized communication and information dissemination in healthcare. We aimed to quantify and evaluate professional digital media use among urology residents.

Methods: We designed a 17-item survey to assess usage and perceived usefulness of digital media, as well as communication type and device type and distributed it via email to 143 Canadian and 721 German urology residents.

Results: In total, 58 (41% response rate) residents from Canada and 170 (24% response rate) from Germany reported professional usage rates of 100% on the internet, 89% on apps, and 46% on social media (SoMe). For professional use, residents spent a median of 30 minutes per day on the internet, 10 minutes on apps, and 15 minutes on SoMe. 100% rated the internet, 89% apps, and 31% SoMe as useful for clinical practice. Most (94%) used digital media for communication with colleagues and 23% for communication with patients. Digital media use was allocated to desktop computers (55%) and mobile devices (45%). Canadian residents had higher usage rates of apps (96% vs. 86%; p=0.042) and SoMe (65% vs. 39%; p=0.002) and longer daily usage times for the internet, apps, and SoMe than German residents (p<0.001 each).

Conclusions: Digital media are an integral part of the daily professional practice of urology residents, reflected by high usage rates and perceived usefulness of the internet and apps, and the growing importance of SoMe. Urologists should strive to progressively exhaust the vast potential of digital media for academic and clinical practice.
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http://dx.doi.org/10.5489/cuaj.4267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798440PMC
September 2017
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