First experiences and results after cryoablation of prostate cancer with histopathological evaluation and imaging-based follow-up.

Aim: To share our experience after 28 cryoablation treatments for prostate cancer (PCa) with histopathology, clinical data and MRI as the follow-up methods. Methods: Clinical follow-up comprised prostate-specific antigen (PSA)-measurements, PSA-density and quality of life-parameters. multi-parametric (mp)MRI pre- and post-cryoablation were retrospectively re-analyzed in 23 cases using Likert scores. Follow-up-histopathology was performed via MRI/ultrasound fusion-guided and/or systematic biopsy. Receiver operating characteristic curve analysis was performed. Results: 17 PCa (61%) were diagnosed within 12-month post-cryotherapy (infield and out-of-field disease). PSA levels and PSA density were not significantly different between patients with or without PCa recurrence. mpMRI can characterize the decrease in prostate volume and necrosis. Area under the curve for the detection of PCa was 81% (global Likert scores), 74-87% (T2), 78% (diffusion weighted imaging) and 57-78% (dynamic contrast enhanced imaging; Youden-selected cutoff ≥3). Conclusion: Besides histopathological evaluation and control biopsy, MRI might have the potential to accurately detect PCa after cryotherapy. Clinical data and interdisciplinary communication are required for efficient monitoring after cryoablation treatments for PCa.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

Applicability of readout-segmented echoplanar diffusion weighted imaging for prostate MRI.

To evaluate readout-segmented echoplanar (rsEPI) diffusion weighted imaging (DWI) for multiparametric (mp) magnetic resonance imaging (MRI) of the prostate compared to the established single-shot echoplanar imaging (ssEPI) sequence.One hundred ten consecutive patients with clinical suspicion of prostate cancer underwent mp prostate MRI using both, the ssEPI and the rsEPI DWI sequence. For an objective assessment, delineation of the prostate shape on both DWI sequences was compared to T2-weighted images by measuring organ diameters. Apparent diffusion coefficient (ADC) values, image contrast and contrast-to-noise ratio (CNR) were compared between the 2 sequences on a region-of-interest-based analysis. Diagnostic accuracy for quantitative ADC-values was calculated. Histopathology from MRI/ultrasound fusion-guided biopsy was used as reference standard. For a subjective assessment, 2 independent readers visually assessed image quality of both sequences using Likert-scales.Delineation of the prostate shape was more accurate with rsEPI compared to ssEPI. ADC values in target lesions were not significantly different but significantly higher in the surrounding normal prostatic tissue of the transition zone. CNR was comparable between ssEPI and rsEPI. Sensitivity and specificity were good for both sequences with 84/84% and 82/73% with a Youden selected cut-off of ADC = 0.971*10 mm/s for rsEPI and 1.017*10 mm/s for ssEPI. Anatomic artifacts were significantly less and SNR was lower on rsEPI compared to ssEPI in the subjective analysis.Delineation of the prostate shape was more accurate with rsEPI DWI than with ssEPI DWI with less anatomic artifacts and higher subjective SNR and image quality on rsEPI DW images. Diagnostic ability of quantitative ADC-values was not significantly different between the 2 sequences. Thus, rsEPI DWI might be more suitable for prostate MRI with regard to MRI-guided targeted biopsy and therapy planning.

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer.

PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Evaluation of MRI/Ultrasound Fusion-Guided Prostate Biopsy Using Transrectal and Transperineal Approaches.

PURPOSE: To evaluate transrectal (TR) and transperineal (TP) approaches for MRI/ultrasound (MRI/US) fusion-guided biopsy to detect prostate cancer (PCa). MATERIALS AND METHODS: 154 men underwent multiparametric MRI and MRI/US fusion-guided biopsy between July 2012 and October 2016. 79/154 patients were biopsied with a TR approach and 75/154 with a TP approach. MRI was retrospectively analyzed according to PI-RADS version 2. PI-RADS scores were compared with histopathological results. Descriptive statistics, accuracy, and negative and positive predictive values were calculated. Histopathological results of first, second, and third MRI targeted biopsy cores were compared to evaluate the impact of one verus multiple targeted cores. RESULTS: Detection rates of PCa were 39% for TR biopsy and 75% for TP biopsy. Sensitivity/specificity for tumor detection with PI-RADS ≥ 4 were 81/69% for TR biopsy and 86/84% for TP biopsy. In 31% for TR biopsy and 19% for TP biopsy, PCa was found in the second or third MRI targeted biopsy core only. CONCLUSION: MRI/US fusion-guided biopsy may be conducted with the TR as well as the TP approach with high accuracy, giving more flexibility for diagnosis and the option for focal treatment of PCa.

Subclonal analysis in a lobular breast cancer with classical and solid growth pattern mimicking a solid-papillary carcinoma.

Recently, a new variant of invasive lobular breast cancer (ILBC) with solid-papillary-like growth pattern has been described. We present a case of ILBC with solid-papillary-like growth pattern in the main tumour mass and classical invasive lobular growth pattern in adjacent satellite foci. The two tumour components were subjected to comprehensive molecular analyses. Both components were ER/PR-positive, HER2-negative, and showed a complete loss of E-cadherin and beta-catenin protein expression, as determined by immunohistochemistry. Gene expression profiling classified the main tumour and a satellite focus as luminal-B and luminal-A subtypes, respectively. Whole-genome copy number profiles were highly similar in both tumour components. Shared copy number alterations (CNAs) included gains of chromosome 1q21.1-q43 and losses of chromosome 16q11.2-q24.3, the locus of the CDH1/E-cadherin tumour suppressor gene. CNAs detected only in the main tumour included a gain of chromosome 20q12-q13.33 and a loss of chromosome 1p36.33-p34.3, which has recently been associated with the solid variant of ILBC. Next generation sequencing revealed an identical, truncating CDH1 mutation (p.G169fs*5) in both tumour components confirming a common clonal ancestry. In conclusion, we confirm the recently described variant of ILBC with solid-papillary-like growth pattern and provide evidence that it evolves from classical ILBC by subclonal evolution.

Standardized Reporting of Prostate MRI: Comparison of the Prostate Imaging Reporting and Data System (PI-RADS) Version 1 and Version 2.

INTRODUCTION: Objective of our study was to determine the agreement between version 1 (v1) and v2 of the Prostate Imaging Reporting and Data System (PI-RADS) for evaluation of multiparametric prostate MRI (mpMRI) and to compare their diagnostic accuracy, their inter-observer agreement and practicability. MATERIAL AND METHODS: mpMRI including T2-weighted imaging, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced imaging (DCE) of 54 consecutive patients, who subsequently underwent MRI-guided in-bore biopsy were re-analyzed according to PI-RADS v1 and v2 by two independent readers. Diagnostic accuracy for detection of prostate cancer (PCa) was assessed using ROC-curve analysis. Agreement between PI-RADS versions and observers was calculated and the time needed for scoring was determined. RESULTS: MRI-guided biopsy revealed PCa in 31 patients. Diagnostic accuracy for detection of PCa was equivalent with both PI-RADS versions for reader 1 with sensitivities and specificities of 84%/91% (AUC = 0.91 95%CI[0.8-1]) for PI-RADS v1 and 100%/74% (AUC = 0.92 95% CI[0.8-1]) for PI-RADS v2. Reader 2 achieved similar diagnostic accuracy with sensitivity and specificity of 74%/91% (AUC = 0.88 95%CI[0.8-1]) for PI-RADS v1 and 81%/91% (AUC = 0.91 95%CI[0.8-1]) for PI-RADS v2. Agreement between scores determined with different PI-RADS versions was good (reader 1: κ = 0.62, reader 2: κ = 0.64). Inter-observer agreement was moderate with PI-RADS v2 (κ = 0.56) and fair with v1 (κ = 0.39). The time required for building the PI-RADS score was significantly lower with PI-RADS v2 compared to v1 (24.7±2.3 s vs. 41.9±2.6 s, p<0.001). CONCLUSION: Agreement between PI-RADS versions was high and both versions revealed high diagnostic accuracy for detection of PCa. Due to better inter-observer agreement for malignant lesions and less time demand, the new PI-RADS version could be more practicable for clinical routine.

Chest wall resection and reconstruction for locally advanced primary breast cancer.

OBJECTIVE: We sought to evaluate clinical and oncologic outcomes of selected patients with locally advanced breast cancer undergoing full thickness chest wall resection (FTCWR) and reconstruction in a multidisciplinary setting. PATIENTS AND METHODS: Between 2008 and 2010, five women underwent FTCWR followed by chest wall repair for locally advanced primary breast cancer. In all cases, chest wall repair was performed with a Peri-Guard Repair Patch (Synovis, St. Paul, MN, USA). At follow-up (7-12 months) quality of life, respiratory function and oncologic status were assessed. RESULTS: Successful chest wall resection and repair were achieved in all patients. Plastic reconstruction of post-mastectomy tissue defects was necessary in one case. One patient was treated by breast conserving therapy. Chest ultrasound imaging confirmed absence of adhesions, haematoma or seroma and normal expansion and respiratory movement of the underlying lung in all patients. On follow-up all patients reported good quality of life. CONCLUSION: Multidisciplinary surgical approaches to chest wall resection and reconstruction in selected patients with locally advanced primary breast cancer are feasible, safe, associated with short operation time and hospital stay and negligible morbidity.

Clear-cell variant urothelial carcinoma of the bladder: a case report and review of the literature.

Clear cell variants of transitional cell carcinomas (TCC) of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

Pulmonary valve replacement in chronic pulmonary regurgitation in adults with congenital heart disease: impact of preoperative QRS-duration and NT-proBNP levels on postoperative right ventricular function.

BACKGROUND: Chronic severe pulmonary regurgitation (PR) causes progressive right ventricular (RV) dysfunction and heart failure. Parameters defining the optimal time point for surgery of chronic PR are lacking. The present study prospectively evaluated the impact of preoperative clinical parameters, cardiorespiratory function, QRS duration and NT-proBNP levels on post operative RV function and volumes assessed by cardiac magnetic resonance imaging (CMR) in patients with chronic severe PR undergoing pulmonary valve replacement. METHODS AND RESULTS: CMR was performed pre- and 6 months postoperatively in 27 patients (23.6 ± 2.9 years, 15 women) with severe PR. Postoperatively, RV endsystolic (RVESVI) and enddiastolic volume indices (RVEDVI) decreased significantly (RVESVI pre 78.2 ± 20.4 ml/m² BSA vs. RVESVI post 52.2 ± 16.8 ml/m²BSA, p<0.001; RVEDVI pre 150.7 ± 27.7 ml/m²BSA vs. RVEDVI post 105.7 ± 26.7 ml/m²BSA; p<0,001). With increasing preoperative QRS-duration, postoperative RVEF decreased significantly (r=-0.57; p<0.005). Preoperative QRS-duration smaller than the median (156 ms) predicted an improved RVEF compared to QRS-duration≥ 156 ms (54.9% vs 46.8%, p<0.05). Multivariate analysis identified preoperative QRS duration as an independent predictor of postoperative RVEF (p<0.005). NT-proBNP levels correlated with changes in RVEDI (r=0.58 p<0,005) and RVESVI (r=0.63; p<0,0001). Multivariate analysis identified NT-proBNP levels prior to PVR as an independent predictor of volume changes (p<0.05). CONCLUSION: Valve replacement in severe pulmonary regurgitation causes significant reduction of RV volumes. Both, preoperative NT-proBNP level elevation and QRS prolongation indicate patients with poorer outcome regarding RV function and volumes.

Unilateral fasciitis of the lower leg: a paraneoplastic manifestation of an occult pancreatic tumor.

We report an elderly woman with a 3-month history of abdominal pain and painful swelling of her right lower leg. Magnetic resonance imaging revealed extensive fasciitis of the right superficial and deep crural fasciae. Endoscopic ultrasonography identified a tumor in the tail region of the pancreas with regional lymphatic nodal disease and suspicion of liver metastasis. The temporal relationship between the fasciitis and the pancreatic tumor suggests cancer-associated fasciitis-panniculitis syndrome. We report for the first time the incidence of the fasciitis-panniculitis syndrome in a patient with a previously undiagnosed solid pancreatic tumor.

Accidental transplantation of a kidney with a cystic renal cell carcinoma following living donation: management and 1 yr follow-up.

Transmission of cancer is a fatal risk in organ transplantation. We present a case of incidental renal carcinoma in a kidney obtained from a living donor. A 56-yr-old father was evaluated for donation for his 28-yr-old daughter. An MRT scan revealed two cysts in the right kidney. Right-sided donor nephrectomy and subsequent transplantation was performed. The wall of the prominent cyst was partially excised prior to transplantation. Histology revealed a high-grade renal clear cell carcinoma 10 d after transplantation. Following careful evaluation the recipient underwent partial nephrectomy. Immunosuppression was switched to rapamune. The graft function remained stable. Donor and recipient are without evidence of tumor recurrence 1 yr after transplantation. Our policy to obtain the kidney presenting anatomical variations proved to be beneficial for the donor. In case of transmission of cancer partial resection preserving graft function might be justified.