Detection and size measurements of kidney stones on virtual non-contrast reconstructions derived from dual-layer computed tomography in an ex vivo phantom setup.

OBJECTIVES: To systematically investigate the usability of virtual non-contrast reconstructions (VNC) derived from dual-layer CT (DLCT) for detection and size measurements of kidney stones with regards to different degrees of surrounding iodine-induced attenuation and radiation dose. METHODS: Ninety-two kidney stones of varying size (3-14 mm) and composition were placed in a phantom filled with different contrast media/water mixtures exhibiting specific iodine-induced attenuation (0-1500 HU). DLCT-scans were acquired using CTDIvol of 2 mGy and 10 mGy. Conventional images (CI) and VNC0H-1500HU were reconstructed. Reference stone size was determined using a digital caliper (Man-M). Visibility and stone size were assessed. Statistical analysis was performed using the McNemar test, Wilcoxon test, and the coefficient of determination. RESULTS: All stones were visible on CI0HU and VNC200HU. Starting at VNC400 HU, the detection rate decreased with increasing HU and was significantly lower as compared to CI0HU on VNC≥ 600HU (100.0 vs. 94.0%, p < 0.05). The overall detection rate was higher using 10 mGy as compared to 2 mGy protocol (87.9 vs. 81.8%; p < 0.001). Stone size was significantly overestimated on all VNC compared to Man-M (7.0 ± 3.5 vs. 6.6 ± 2.8 mm, p < 0.001). Again, the 10 mGy protocol tended to show a better correlation with Man-M as compared to 2 mGy protocol (R2 = 0.39-0.68 vs. R2 = 0.31-0.57). CONCLUSIONS: Detection and size measurements of kidney stones surrounded by contrast media on VNC are feasible. The detection rate of kidney stones decreases with increasing iodine-induced attenuation and with decreasing radiation dose as well as stone size, while remaining comparable to CI0HU on VNC ≤ 400 HU. KEY POINTS: • The detection rate of kidney stones on VNC depends on the surrounding iodine-induced attenuation, the used radiation dose, and the stone size. • The detection rate of kidney stones on VNC decreases with greater iodine-induced attenuation and with lower radiation dose, particularly in small stones. • The visibility of kidney stones on VNC ≤ 400 HU remains comparable to true-non-contrast scans even when using a low-dose technique.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

[Perception of the COVID-19 Pandemic among Pneumology Professionals in Germany]. / Wahrnehmung der COVID-19-Pandemie unter pneumologischen Fachkräften in Deutschland.

The COVID-19 pandemic represents a huge burden on global health systems. Although far-reaching prevention measures such as the increase of intensive care capacities and drastic restrictions of public life have so far been able to avert an overload of the German health care system, the current situation implies an exceptionally high burden on medical professionals. The current study presents the results of an opinion evaluation among 513 pneumology specialists in Germany in the period from March 27th to April 11th, 2020. While the majority of respondents stated that Germany was "well" prepared for the pandemic, this assessment was significantly worse among participants from the outpatient sector compared to the hospital sector (p < 0.001). Furthermore, a lack of medical protective equipment was reported significantly more frequently by respondents from the outpatient sector (p < 0.001). The importance of telemedicine approaches during the COVID-19 pandemic was rated "high" (35.2 %) or "very high" (17.2 %) by most pneumology professionals, with participants from the hospital sector giving a higher rating (p < 0.001). Finally, 45.8 % of the respondents expressed a "negative" influence of the COVID-19 pandemic on their personal mood and 58.3 % expressed "strong" or "very strong" concerns about the health of their fellow human beings. This assessment was significantly stronger among female participants and participants from the nursing sector (p < 0.001). In summary, the current study analyses for the first time the professional and personal impact of the COVID-19 pandemic on pneumology professionals in Germany. The results could help to identify first starting points to better support health professionals during the current and future challenges.

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

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

Efficacy of galcanezumab in patients with episodic migraine and a history of preventive treatment failure: results from two global randomized clinical trials.

BACKGROUND AND PURPOSE: The efficacy of galcanezumab, a monoclonal antibody for migraine prevention, has been demonstrated in two pivotal trials in patients with episodic migraine. METHODS: EVOLVE-1 and EVOLVE-2 were identical phase 3, randomized, double-blind, placebo-controlled studies in patients with episodic migraine. Mean migraine headache days per month at baseline was 9. Patients were randomized 2:1:1 to monthly injections of placebo, galcanezumab 120 mg/240 mg during the 6-month double-blind treatment period. Key efficacy outcomes were assessed in subgroups amongst patients for whom, previously, for efficacy and/or safety/tolerability reasons (i) one or more (≥1) preventives failed, (ii) two or more (≥2) preventives failed and (iii) preventives were never used, or used but not failed (no prior failure). RESULTS: In an integrated analysis of EVOLVE studies, galcanezumab 120 mg/240 mg versus placebo led to larger overall mean (SE) reductions in monthly migraine headache days across 6 months in patients with prior preventive failures (P < 0.001): ≥1 failure: 120 mg: -4.0 (0.4); 240 mg: -4.2 (0.5); placebo: -1.3 (0.4); ≥2 failures: 120 mg: -3.1 (0.7); 240 mg: -3.8 (0.8); placebo: -0.5 (0.6). Similar results were observed amongst patients with no prior failure, but the placebo response was larger: 120 mg: -4.7 (0.2); 240 mg: -4.5 (0.2); placebo: -3.0 (0.2) (P < 0.001 versus placebo). Significant improvements were observed with galcanezumab versus placebo for ≥50% and ≥75% reduction in monthly migraine headache days. CONCLUSION: In patients with episodic migraine treated with galcanezumab, those with ≥1 or ≥2 prior preventive failures had significantly larger improvements, versus placebo, in efficacy outcomes. Similar results were observed in patients with no prior failure, with a larger placebo response.

Comparison of adjustable male slings and artificial urinary sphincter in the treatment of male urinary incontinence: a retrospective analysis of patient selection and postoperative continence status.

PURPOSE: To analyze and compare preoperative patient characteristics and postoperative results in men with stress urinary incontinence (SUI) selected for an adjustable male sling system or an artificial urinary sphincter (AUS) in a large, contemporary, multi-institutional patient cohort. METHODS: 658 male patients who underwent implantation between 2010 and 2012 in 13 participating institutions were included in this study (n = 176 adjustable male sling; n = 482 AUS). Preoperative patient characteristics and postoperative outcomes were analyzed. For statistical analysis, the independent T test and Mann-Whitney U test were used. RESULTS: Patients undergoing adjustable male sling implantation were less likely to have a neurological disease (4.5% vs. 8.9%, p = 0.021), a history of urethral stricture (21.6% vs. 33.8%, p = 0.024) or a radiation therapy (22.7% vs. 29.9%, p = 0.020) compared to patients that underwent AUS implantation. Mean pad usage per day (6.87 vs. 5.82; p < 0.00) and the ratio of patients with a prior incontinence surgery were higher in patients selected for an AUS implantation (36.7% vs. 22.7%; p < 0.001). At maximum follow-up, patients that underwent an AUS implantation had a significantly lower mean pad usage during daytime (p < 0.001) and nighttime (p = 0.018). Furthermore, the patients' perception of their continence status was better with a subjective complete dry rate of 57.3% vs. 22.0% (p < 0.001). CONCLUSIONS: Patients selected for an AUS implantation showed a more complex prior history and pathogenesis of urinary incontinence as well as a more severe grade of SUI. Postoperative results reflect a better continence status after AUS implantation, favoring the AUS despite the more complicated patient cohort.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

Comprehensive pharmaceutical care to prevent drug-related readmissions of dependent-living elderly patients: a randomized controlled trial.

BACKGROUND: Elderly patients are vulnerable to adverse drug reactions (ADRs). Drug-related readmissions (DRRs) can be a major consequence of ADR. Therefore, this study aimed to investigate the effects of a ward-based, comprehensive pharmaceutical care service on the occurrence of DRRs as the endpoint in dependent-living elderly patients. METHODS: A randomized, controlled trial was performed at a German University Hospital. Patients fulfilling the following criteria were eligible: admission to a cooperating ward, existing drug therapy at admission, 65 years of age and older, home-care or nursing home residents in ambulatory care, and a minimum hospital stay of three days. Patients received either standard care (control group) or pharmaceutical care (intervention group). Follow-up consultations were conducted for each patient at 1, 8, 26, and 52 weeks after discharge. The time to DRR was defined as the primary outcome measure and was analysed using the log-rank test. The Cox-proportional hazard model was used for risk factor analysis. RESULTS: Sixty patients (n = 31 intervention group, n = 29 control group) participated in the study. For patients in the intervention group, the median time to DRR was prolonged; however, the level of statistical significance was not reached (log-rank test P = 0.068; HR = 3.28, P = 0.086). When the risk factors 'age' or 'length of stay on the ward' were added to the Cox proportional hazard model, patients in the control group exhibited a significantly higher risk of experiencing a DRR than patients of the intervention group (HR = 4.62; P = 0.028 including age and HR = 5.76; P = 0.033 including length of stay on the ward). CONCLUSIONS: Our findings demonstrate the successful implementation of ward-based, comprehensive pharmaceutical care for dependent-living elderly. Despite a low participation rate, which led to an underpowered study, the results provide a preliminary efficacy signal and effect size estimates to power a definitive trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01578525 , prospectively registered April 13, 2012.

Surgical management of complex residual masses following systemic chemotherapy for metastatic testicular germ cell tumours.

Background: Post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) represents the treatment of choice in patients with residual masses following chemotherapy for metastatic germ cell tumours. Involvement of major retroperitoneal vessels or thoracic/lumbar spine is rare and challenging but needs complete resection for curative intent. We report on our experience in the management of such complex cases. Patients and methods: A total of 185 patients underwent PC-RPLND and we identified 25 (13.5%) patients who needed complex adjunctive vascular (n = 16, 8.6%), skeletal (n = 5, 2.7%) and pancreaticoduodenal (n = 4, 2.2%) surgeries. We performed a retrospective analysis of treatment-associated complications according to the Clavien-Dindo classification. Progression-free, cancer-specific and overall survival was calculated. Results: All patients were of intermediate/poor prognosis according to IGCCCG. Median tumour diameter at time of surgery was 18.6 (9.0-35) cm. Sixteen (8.6%) underwent vascular surgery including aortic resection and replacement, complete or partial resection of the inferior vena cava with thrombectomy, and resection and replacement of the iliac vessels. In five patients, 1-2 metastatic lumbar vertebral bodies were resected, stabilized and replaced. Four patients underwent en-bloc resection of a suprahilar mass with pancreas and duodenum. Pathohistology revealed vital cancer in five patients; teratoma and malignant somatic transformation was identified in 12 and 6 patients, respectively. Complications occurred more often in the group of complex RPLND (41.7 versus 7.2%, P = 0.02) with the majority representing grade I-IIa. After a median follow-up of 28.5 months, four patients developed recurrent disease and one patient died of the disease. Conclusions: Few patients with advanced GCT need complex vascular, skeletal or intestinal surgery in an interdisciplinary setting with good functional and oncological outcome. Due to the complexity, treatment should be performed at specialized centres.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

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

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

[Importance of pathology for therapy planning of testicular germ cell tumors]. / Bedeutung der Pathologie für die Therapieplanung testikulärer Keimzelltumoren.

Testicular tumors can be divided into germ cell tumors and sex cord stromal tumors. Malignant testicular germ cell tumors (TGCT) represent about 90-95 % of all testicular tumors and are the most common solid neoplasms in young men aged 20-40 years with an increasing incidence in industrialized countries. Treatment of TGCT is performed by an individual and risk-adapted approach taking primary tumor histology, histopathlogical and molecular prognostic risk factors, tumor stage and for metastasized tumors the response to systemic chemotherapy into consideration. Knowledge of the specific histopathology of the primary tumor and the prognostic factors is of utmost importance for the treating urologist and oncologist in order to avoid undertreatment or overtreatment. Established risk factors which have been validated in retrospective and prospective studies for clinical stage I non-seminomatous TGCT are the presence of vascular invasion and the percentage of embryonal carcinoma. In clinical stage I seminomas tumor size (> 4 cm) and presence of rete testis infiltration have been identified as risk factors in retrospective but not in prospective studies. Quantitative histopathology of the primary tumor is also important for the management of small residual masses following chemotherapy: if the masses are ≤ 1 cm, postchemotherapy retroperitoneal lymph node dissection is only indicated if the primary tumor contains ≥ 50 % teratoma. Quantitative pathohistology of the resected residual masses is of importance for the decision-making process of a consolidating chemotherapy which is only of benefit if the amount of vital cancer tissue is > 10 %. Resection of residual hepatic and thoracic masses is indispensable. For gonadal stromal tumors knowledge of atypical nuclear forms, increased rate of mitosis and increased growth fractions are important for therapy planning.

A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Intetumumab is a fully human mAb with antiangiogenic, antitumor properties which has shown potential therapeutic effect in castration-resistant prostate cancer (CRPC) patients. PATIENTS AND METHODS: In a phase 2, randomized, double-blind, multicenter study, men with metastatic CRPC without prior systemic nonhormonal therapy were randomly assigned to 75-mg/m(2) docetaxel (Taxotere) and 5-mg prednisone plus placebo (N = 65) or 10-mg/kg intetumumab (N = 66) q3w. Placebo patients with progressive disease (PD) could cross over to 10-mg/kg intetumumab alone or with docetaxel. The primary end-point was progression-free survival (PFS). The secondary end-points included tumor response (complete response + partial response, CR + PR), prostate-specific antigen (PSA) response, and overall survival (OS). RESULTS: All efficacy end-points favored placebo over intetumumab, including PFS (median 11.0 versus 7.6 months, P = 0.014), tumor response (20% versus 16%, P = 0.795), PSA response (68% versus 47%, P = 0.018), OS (median 20.6 versus 17.2 months, P = 0.163). Common all-grade adverse events (AEs) with placebo and intetumumab were alopecia (43% versus 26%); diarrhea, leukopenia (both 34% versus 27%); neutropenia (35% versus 23%). Grade ≥ 3 leukopenia (28% versus 17%) and neutropenia (26% versus 18%) occurred more often with placebo than with intetumumab. Intetumumab serum concentrations increased with repeated dosing and did not reach steady-state. Greater decreases in N-telopeptide of type I collagen (NTx), C-telopeptide (CTx) and CTCs occurred with intetumumab than with placebo. CONCLUSION: The addition of intetumumab to docetaxel resulted in shorter PFS without additional toxicity among CRPC patients.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Metastatic castration-resistant prostate cancer: integrating new learnings to optimise treatment outcomes.

The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy significantly. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to: (1) summarize the data of established treatment options in mCRPC; (2) highlight new developments of medical treatment; (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.