Annemarie Uhlig

Treatment for Localized T1a Clear Cell Renal Cell Carcinoma: Survival Benefit for Cryosurgery and Thermal Ablation Compared to Deferred Therapy

AbstractPurposeTo evaluate survival of patients with localized T1a clear cell renal cell carcinoma (ccRCC) who received cryosurgery or thermal ablation compared to deferred therapy.nMaterials and MethodsnWe included 733 patients with histopathologically confirmed localized T1a ccRCC who either received cryosurgery (nxa0=xa0315) or thermal ablation (nxa0=xa0155), as well as patients who deferred therapy (nxa0=xa0263) from the 2000–2013 Surveillance, Epidemiology, and End Results Program urinary cancer file. Cox proportional hazard models were used to compare cancer-specific survival (CSS) across subgroups. Sensitivity analyses were conducted to assess potential unmeasured confounding by comorbidities.nResultsPatients treated with cryosurgery and thermal ablation had a statistically significant CSS benefit compared to those who deferred therapy (cryosurgery HR 0.25, 95% CI 0.14–0.45, pxa0<xa00.001; thermal ablation HR 0.27, 95% CI 0.13–0.55, pxa0<xa00.001, after adjustment for age at diagnosis, tumor grade, and size). There was no significant difference in CSS comparing cryosurgery to thermal ablation (HR 1.03, 95% CI 0.45–2.3, pxa0=xa00.95, after adjustment for age at diagnosis, tumor grade, and size). These results proved robust upon sensitivity analyses: After adjustment for comorbidities with varying prevalence assumptions, the corrected hazard ratio (cHR) of cryosurgery versus deferred therapy ranged between HR 0.09 and 0.68.ConclusionLocal ablative techniques provide relevant survival benefit and are preferable alternatives over deferred therapy. Cryosurgery and thermal ablation yield comparable outcomes.Level of Evidence2b according to the Oxford Centre for evidence-based medicine levels of evidence.

Primary bladder adenocarcinoma: Case report with long-term follow-up

Primary Bladder Adenocarcinoma is a rare malignancy that has been observed in a heterogeneous patient population. This case report presents a 51 year old female with muscle-invasive primary bladder adenocarcinoma diagnosed in 2008. After transurethral resection and cystectomy with ileum neobladder adjuvant radiochemotherapy was administered. Two years later, a symptomatic fistula between neobladder and ileoileal anastomosis was excised, resulting in urinary incontinency. In 2016, the patient shows no signs of disease relapse but suffers from reduction of bladder capacity. This case report presents classical symptoms of adenocarcinoma of the bladder and a possible treatment regimen with associated side effects.

Preventive Services Utilization Among Cancer Survivors Compared to Cancer-free Controls

RESEARCH ARTICLE Preventive Services Utilization Among Cancer Survivors Compared to Cancer-free Controls Annemarie Uhlig, Johannes Uhlig, Arne Strauss, Lutz Trojan, Joachim Lotz and Ali Seif Amir Hosseini Department of Urology, University Medical Center, University of Göttingen, Göttingen, Germany Department of Interventional and Diagnostic Radiology, University Medical Center, University of Göttingen, Göttingen, Germany Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States of America German CT for Cardiovascular Research, Partnersite Goettingen, Goettingen, Germany

Gender Specific Differences in Disease-Free, Cancer Specific and Overall Survival after Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose: We summarize the evidence on gender specific differences in disease‐free, cancer specific and overall survival after radical cystectomy for bladder cancer. Materials and Methods: We performed a systematic literature search of MEDLINE®, Embase® and the Cochrane Library in July 2017. Studies evaluating gender specific differences in disease‐free, cancer specific or overall survival after radical cystectomy for bladder cancer were included in study. Analyses included random effect meta‐analysis, subgroup analyses, meta‐influence and cumulative meta‐analyses. Funnel plots and the Egger test were used to assess publication bias. Results: Of the 3,868 studies identified during the literature search 59 published between 1998 and 2017 were included in analysis. Of the studies 30 in a total of 38,321 patients evaluated disease‐free survival, 44 in a total of 69,666 evaluated cancer specific survival and 26 in a total of 30,039 evaluated overall survival. Random effect meta‐analyses revealed decreased disease‐free, cancer specific survival and overall survival in female patients than in their male counterparts. Pooled estimates showed a HR of 1.16 (95% CI 1.06–1.27, p = 0.0018) for disease‐free survival, 1.23 (95% CI 1.15–1.31, p <0.001) for cancer specific survival and 1.08 (95% CI 1.03–1.12, p = 0.0004) for overall survival. Subgroup analyses confirmed impaired disease‐free, cancer specific and overall survival in female patients in all strata. Publication bias was evident only for studies of cancer specific survival (Egger test p = 0.0029). After adjusting for publication bias by the trim and fill method the corrected pooled estimated HR of cancer specific survival was 1.13 (95% CI 1.05–1.21, p = 0.0012). Conclusions: Female patients who underwent radical cystectomy for bladder cancer demonstrated worse disease‐free, cancer specific and overall survival than their male counterparts. The multifactorial etiology might include epidemiological differences, gender specific health care discrepancies and hormonal influences.

Diagnostic accuracy of cone-beam breast computed tomography: a systematic review and diagnostic meta-analysis

PurposeTo review the published evidence on cone-beam breast computed tomography (CBBCT) and summarize its diagnostic accuracy for breast lesion assessment.Materials and MethodsA systematic literature search was conducted using the EMBASE, MEDLINE and CENTRAL libraries. Studies were included if reporting sensitivity and specificity for discrimination of benign and malignant breast lesions via breast CT. Sensitivity and specificity were jointly modeled using a bivariate approach calculating summary areas under the receiver-operating characteristics curve (AUC). All analyses were separately performed for non-contrast and contrast-enhanced CBBCT (NC-CBBCT, CE-CBBCT).ResultsA total of 362 studies were screened, of which 6 with 559 patients were included. All studies were conducted between 2015 and 2018 and evaluated female participants. Four of six studies included dense and very dense breasts with a high proportion of microcalcifications. For NC-CBBCT, pooled sensitivity was 0.789 (95% CI: 0.66–0.89) and pooled specificity was 0.697 (95% CI: 0.471–0.851), both showing considerable significant between-study heterogeneity (I2 = 89.4%, I2 = 94.7%, both p < 0.001). Partial AUC for NC-CBBCT was 0.817. For CE-CBBCT, pooled sensitivity was 0.899 (95% CI: 0.785–0.956) and pooled specificity was 0.788 (95% CI: 0.709–0.85), both exhibiting non-significant moderate between-study heterogeneity (I2 = 57.3%, p = 0.0527; I2 = 53.1%, p = 0.0738). Partial AUC for CE-CBBCT was 0.869.ConclusionThe evidence available for CBBCT tends to show superior diagnostic performance for CE-CBBCT over NC-CBBCT regarding sensitivity, specificity and partial AUC. Diagnostic accuracy of CE-CBBCT was numerically comparable to that of breast MRI with meta-analyses reporting sensitivity of 0.9 and specificity of 0.72.Key Points• CE-CBBCT rather than NC-CBBCT should be used for assessment of breast lesions for its higher diagnostic accuracy.• CE-CBBCT diagnostic performance was comparable to published results on breast MRI, thus qualifying CE-CBBCT as a potential imaging alternative for patients with MRI contraindications.

Partial nephrectomy versus ablative techniques for small renal masses: a systematic review and network meta-analysis

PurposeTo compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes.Material and methodsThe MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed.ResultsForty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively).ConclusionHigher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation.Key Points• Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy.• Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival.• The decline of renal function is smallest after radiofrequency ablation for small renal masses.

Intra- and interobserver variability in the diagnosis of GERD by real-time MRI

The purpose of this study was to assess the reproducibility of functional and anatomical parameters of swallowing events as determined by real-time MRI at 40u202fms temporal resolution (25 frames per second). Twenty-three consecutive patients with gastroesophageal reflux disease (GERD) underwent real-time MRI of the gastroesophageal junction at 3.0u202fT. Real-time MRI was based on highly undersampled radial fast low angle shot (FLASH) acquisitions with iterative image reconstruction by regularized nonlinear inversion (NLINV). MRI movies visualized the esophageal transport of a pineapple juice bolus, its passage through the gastroesophageal junction and functional responses during a Valsalva maneuver. His-angle, sphincter position, sphincter length and sphincter transit time were assessed by two radiologists. Interobserver and intraobserver intraclass correlation coefficients (ICC) were evaluated and Bland-Altman plots were constructed to assess the observer agreement. Interobserver agreement was excellent for sphincter transit time (ICCu202f=u202f0.92), His-angle (ICCu202f=u202f0.93), His-angle during Valsalva maneuver (ICCu202f=u202f0.91) and sphincter-to-diaphragm distance (ICCu202f=u202f0.98). Sphincter length and oesophageal diameter showed good interobserver agreement (ICCu202f=u202f0.62 and ICCu202f=u202f0.70). Intraobserver agreement was good for sphincter length (ICCu202f=u202f0.80) and excellent for sphincter transit time, His-angle and His-angle during Valsalva maneuver, sphincter-to-diaphragm distance, and esophageal diameter (ICCu202f=u202f0.91; ICCu202f=u202f0.97; ICCu202f=u202f0.97; ICCu202f=u202f0.998; ICCu202f=u202f0.93). All functional parameters of the gastroesophageal junction had good to excellent reproducibility. Visual assessment of Bland Altman plots did not reveal any systematic interobserver bias. In conclusion, the visualization of swallowing events by real-time MRI has a high potential for clinical application in gastroesophageal reflux disease.

Cartilage calcification of the ankle joint is associated with osteoarthritis in the general population

BackgroundCartilage calcification (CC) is associated with osteoarthritis (OA) in weight-bearing joints, such as the hip and the knee. However, little is known about the impact of CC and degeneration on other weight-bearing joints, especially as it relates to the occurrence of OA in the ankles. The goal of this study is to analyse the prevalence of ankle joint cartilage calcification (AJ CC) and to determine its correlation with factors such as histological OA grade, age and BMI in the general population.MethodsCC of the distal tibia and talus in 160 ankle joints obtained from 80 donors (mean age 62.4xa0years, 34 females, 46 males) was qualitatively and quantitatively analysed using high-resolution digital contact radiography (DCR). Correlations with factors, such as the joint’s histological OA grade (OARSI score), donor’s age and BMI, were investigated.ResultsThe prevalence of AJ CC was 51.3% (95% CI [0.40, 0.63]), independent of gender (pu2009=u20090.18) and/or the joint’s side (pu2009=u20090.82). CC of the distal tibia was detected in 35.0% (28/80) (95% CI [0.25, 0.47]) and talar CC in 47.5% (38/80) (95% CI [0.36, 0.59]) of all cases. Significant correlations were noted between the mean amount of tibial and talar CC (ru2009=u20090.59, pu2009=u20090.002), as well as between the mean amount of CC observed in one ankle joint with that of the contralateral side (ru2009=u20090.52, pu2009=u20090.02). Furthermore, although the amount of AJ CC observed in the distal tibia and talus correlated with the histological OA-grade of the joint (ru2009=u20090.70, pu2009<u20090.001 and ru2009=u20090.72, pu2009<u20090.001, respectively), no such correlation was seen in the general population with relation to age (pu2009=u20090.32 and pu2009=u20090.49) or BMI (pu2009=u20090.51 and pu2009=u20090.87).ConclusionThe prevalence of AJ CC in the general population is much higher than expected. The relationship between the amount of AJ CC and OA, independent of the donors’ age and BMI, indicates that CC may play a causative role in the development of OA in ankles.

Novel Breast Imaging and Machine Learning: Predicting Breast Lesion Malignancy at Cone-Beam CT Using Machine Learning Techniques

OBJECTIVEnThe purpose of this study is to evaluate the diagnostic performance of machine learning techniques for malignancy prediction at breast cone-beam CT (CBCT) and to compare them to human readers.nnnSUBJECTS AND METHODSnFive machine learning techniques, including random forests, back propagation neural networks (BPN), extreme learning machines, support vector machines, and K-nearest neighbors, were used to train diagnostic models on a clinical breast CBCT dataset with internal validation by repeated 10-fold cross-validation. Two independent blinded human readers with profound experience in breast imaging and breast CBCT analyzed the same CBCT dataset. Diagnostic performance was compared using AUC, sensitivity, and specificity.nnnRESULTSnThe clinical dataset comprised 35 patients (American College of Radiology density type C and D breasts) with 81 suspicious breast lesions examined with contrast-enhanced breast CBCT. Forty-five lesions were histopathologically proven to be malignant. Among the machine learning techniques, BPNs provided the best diagnostic performance, with AUC of 0.91, sensitivity of 0.85, and specificity of 0.82. The diagnostic performance of the human readers was AUC of 0.84, sensitivity of 0.89, and specificity of 0.72 for reader 1 and AUC of 0.72, sensitivity of 0.71, and specificity of 0.67 for reader 2. AUC was significantly higher for BPN when compared with both reader 1 (p = 0.01) and reader 2 (p < 0.001).nnnCONCLUSIONnMachine learning techniques provide a high and robust diagnostic performance in the prediction of malignancy in breast lesions identified at CBCT. BPNs showed the best diagnostic performance, surpassing human readers in terms of AUC and specificity.

Gender-specific Differences in Recurrence of Non–muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

CONTEXTnThe incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB.nnnOBJECTIVEnTo conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC).nnnEVIDENCE ACQUISITIONnAn unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test.nnnEVIDENCE SYNTHESISnOf 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence.nnnCONCLUSIONSnWomen are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses.nnnPATIENT SUMMARYnIn this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men.