[Focal HIFU vs robot-assisted total prostatectomy: Functionnal and oncologic outcomes at one year]. / Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an.

OBJECTIVE: To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). PATIENTS AND METHODS: Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). RESULTS: The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). CONCLUSION: In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. LEVEL OF EVIDENCE: 3.

Genotyping of high-risk human papillomaviruses in p16/Ki-67-positive urothelial carcinoma cells: even a worm will turn.

OBJECTIVE: Co-expression of p16INK4a protein and Ki-67 (p16/Ki-67) is noted in almost all high-grade urothelial lesions. However, the aetiological role or, conversely, the absence of causative effect of high-risk human papillomaviruses (hr-HPVs) has not been documented. The purpose of this study is to evaluate HPV DNA in p16/Ki-67-positive, high-grade urothelial tumour cells. METHODS: Fifty-seven urine samples collected from 50 patients, including 55 histologically proven high-grade proliferations and two cases with clinical evidence of malignancy, were analysed for p16/Ki-67. Immunolabelling was performed in destained Papanicolaou-stained slides after ThinPrep(®) processing. HPV genotyping was performed by polymerase chain reaction (PCR) using a DNA microarray for 35 HPV types. Confirmation of the presence (or absence) of HPV in tissue samples was verified using a reasoned approach combining PCR and in situ hybridization (ISH) for hr-HPVs. RESULTS: Co-expression of p16/Ki-67 was noted in 43 of 57 (75.4%) cases. In these, hr-HPVs 16, 31 and 70, and low risk HPV 84, were detected in the urine in four patients (8%). Upregulation of p16INK4a protein was confirmed on bladder biopsy or transurethral resection specimens, but PCR and ISH for hr-HPVs were both negative on the tissue sections. CONCLUSION: Our results show a low prevalence of HPV infection in the urinary tract of patients with p16/Ki-67-positive urothelial malignancy. The study confirms that the deregulated cell cycle, as demonstrated by p16/Ki-67 dual labelling, is independent of the oncogenic action of hr-HPVs in high-grade urothelial proliferations.

Value of prostate multiparametric magnetic resonance imaging for predicting biopsy results in first or repeat biopsy.

AIM: To assess multiparametric magnetic resonance imaging (mp-MRI) in predicting prostate biopsy results. MATERIALS AND METHODS: Patients who underwent mp-MRI prior to prostate biopsy were prospectively included. The prostate was subdivided into 14 sectors and mp-MRI findings assessed using a five-level subjective suspicion score (SSS). Biopsy included targeted samples of abnormal sectors and systematic samples of normal peripheral zone sectors. RESULTS: Two hundred and eighty-eight patients were included [153 biopsy naïve, 135 with negative (n = 51) or positive (n = 84) prior biopsy]. Biopsy was positive in 168 patients. mp-MRI area under the receiver operating characteristic (ROC) curve (AUC) was 69.1% (95% CI: 67.1-70.9%), 72.5% (95% CI: 69.5-76%), and 73.8% (95% CI: 68.3-79.3%) at per sector, per lobe, and per patient analysis, respectively. At the per sector level, the AUC was significantly larger if detection was limited to cancers with a Gleason score of ≥7 (72.6%; 95% CI: 69.8-75.8%; p < 0.01) or ≥8 (87.1%; 95% CI: 78.3-95.7%; p < 0.01). mp-MRI performance was significantly influenced by prostate volume (p = 0.02), the presence of a concordant hypoechoic area (p < 0.001), but not by prostate-specific antigen (PSA) value, status of prior biopsy, or radiologists' experience. SSS was significantly associated with the Gleason score in true-positive lobes and patients (p < 0.0001). Using a SSS threshold of ≥3, cancer was missed in 13/102 lobes and 4/72 patients with cancers of Gleason score ≥7. CONCLUSION: mp-MRI provides a good detection of cancers with a Gleason score of ≥7 in candidates suitable for prostate biopsy.

Diagnostic terminology for urinary cytology reports including the new subcategories 'atypical urothelial cells of undetermined significance' (AUC-US) and 'cannot exclude high grade' (AUC-H).

OBJECTIVE: We studied whether atypical, non-superficial urothelial cells (AUC) could be separated into new subcategories including AUC 'of undetermined significance' (AUC-US) and 'cannot exclude high grade'' (AUC-H) in order to help to standardize urine cytopathology reports, as it is widely accepted in the Bethesda system for gynaecological cytopathology. METHODS: We investigated whether AUC-US and AUC-H, defined by distinctive cytological criteria, might be separated with statistical significance according to actual diagnosis and follow-up data. A series of 534 cyto-histological comparisons taken in 139 patients, including 221 AUC at various steps of their clinical history was studied. There were 513 (96.1%) postcystoscopy and 469 (87.8%) ThinPrep® liquid-based specimens (95.9% and 89.1% of AUC cases, respectively). Patients viewed between 1999 and 2011 had histological control in a 0- to 6-months delay and were followed-up during an additional 5.9 ± 9.2 (0- to 56-) months period. RESULTS: The 221 AUC represented 0.8-2% of the specimens viewed during the study period. Among AUC-H cases, 70 out of 185 (37.8%) matched with high-grade lesions, compared with 3 of 38 (8.3%) of AUC-US cases (P = 0.0003). Conservatively treated patients with AUC-H more frequently developed high-grade lesions than those with AUC-US (54.1% versus 16.7%, P = 0.0007) with a 17.6-months mean delay. Nuclear hyperchromasia, a nuclear to cytoplasm (N/C) ratio > 0.7 and the combination of both were the more informative diagnostic criteria, all with P < 0.01. CONCLUSION: We conclude that the new subcategories could help to standardize urine cytopathology reports and contribute to the patient's management, provided it is validated by multicentric studies.

Differentiation of transitional zone prostate cancer from benign hyperplasia nodules: evaluation of discriminant criteria at multiparametric MRI.

AIM: To assess topographical and magnetic resonance imaging (MRI) features in characterizing prostate transitional zone (TZ) nodules. MATERIALS AND METHODS: Two radiologists evaluated all TZ nodules visible at multiparametric MRI in 52 consecutive patients who underwent radical prostatectomy. The radiologists assessed topographical (anteroposterior and superior-inferior location, crossing of the sagittal midline) and T2-weighted (shape, presence and distinctness of capsule, distinctness of contours, presence of cysts) features, the apparent diffusion coefficient (ADC), and eight semi-quantitative and quantitative enhancement parameters derived from dynamic contrast-enhanced (DCE) imaging. The nature of the nodules was assessed using prostatectomy specimens. Five statistical methods taking into account multiple testing were used. RESULTS: One hundred and thirty-seven nodules (117 benign, 20 malignant) were evaluated. Mean ADC, all topographical, and all T2-weighted features were significant predictors of malignancy according to at least four out of the five statistical methods. Particularly, 20/20 and 18/20 cancers involved the anterior and apical third of the TZ, respectively. None of the enhancement parameters was significantly different between cancers and benign nodules. By assessing the presence of cysts, the nodules' capsule, and their anteroposterior and superior-inferior location, 111/117 benign nodules were correctly diagnosed, without misclassifying any cancer. CONCLUSION: Topographical, T2-weighted, and diffusion-weighted features can be used to characterize TZ nodules. DCE imaging does not seem to provide additional information.

p16(INK4a) /Ki-67 dual labelling as a marker for the presence of high-grade cancer cells or disease progression in urinary cytopathology.

OBJECTIVE: Overexpression of p16(INK4a) independent of the presence of E6-E7 oncoproteins of high-risk papillomaviruses has been identified in bladder carcinoma in situ lesions with or without concurrent papillary or invasive high-grade (HG) urothelial carcinoma. As p16(INK4a) and Ki-67 co-expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16(INK4a) /Ki-67 dual labelling in urinary cytology samples. METHODS: Immunolabelling was performed in demounted, destained Papanicolaou slides after ThinPrep(®) processing. A total of 84 urinary cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37 high grade) were analysed for p16(INK4a) /Ki-67 co-expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow-up data in every case. RESULTS: Compared with raw histopathological results, p16 (INK4a) /Ki-67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant potential or low-grade carcinomas (P = 0.05). All cases with high-grade/malignant cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG lesions were dual labelled. Extended follow-up allowed three cases of progression to be diagnosed in dual-labelled cases with negative/low-grade cytology results after a 9- to 11-months delay. CONCLUSIONS: The data show that p16(INK4a) /Ki-67 co-expression allows most HG cancer cells to be detected initially and in the follow-up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine.

[HIFU for prostate cancer in patients with a history of severe colorectal disease]. / Cancer de prostate associé à une pathologie rectale sévère. Résultats préliminaires carcinologiques et fonctionnels du traitement par HIFU (Ablatherm).

OBJECTIVES: To report the functional and oncological outcomes of HIFU for prostate cancer in patients with a history of severe colorectal disease. METHODS: Between 2002 and 2009, 14 patients with a history of severe colorectal disease (cancer, lymphoma, inflammatory bowel diseases [IBD]) were treated with HIFU as a primary care option for localized prostate cancer. RESULTS: Mean age was 65.8 ± 6.1 years. Mean time between colorectal disease treatment and HIFU was 10.6 ± 6.8 years. The mean Prostate Specific Antigen (PSA) before HIFU was 12.1 ng/mL (4.5-55). Gleason score was inferior or equal to 6 in four patients (28.6%), equal to 7 in nine patients (64.3%) and superior or equal to 8 in one patient (7.1%). The mean prostate volume before HIFU was 22.1 ± 11.7 mL. The number of HIFU sessions per patient was 1.35. The mean nadir PSA was 0.61 ± 0.82 ng/mL. Systematic control biopsies were negative in seven patients (50%). Mean follow-up was 22 months with a 35.7% complication rate (three erectile dysfunctions, two urinary stress incontinences). No recto-urethral fistula occurred. CONCLUSION: HIFU was an interesting therapy for patients with a history of colorectal disease for whom regular treatment was challenging or non feasible.

[Outcomes of HIFU for localised prostate cancer using the Ablatherm Integrate Imaging® device]. / Traitement du cancer localisé de la prostate avec l'appareil Ablatherm Imagerie Intégrée® : résultats carcinologiques et fonctionnels.

OBJECTIVES: To report the functional and oncological outcomes of HIFU for prostate cancer using the Ablatherm Integrate Imaging(®) device. METHODS: Between January 2005 and June 2009, all patients treated with HIFU as a primary care option for localized prostate cancer and fulfilling the French Urological Association (AFU) guideline were included in this study. Validated questionnaires were used to assess continence, potencies and quality of life. RESULTS: A total of 297 patients met the inclusion criteria: 149 were low risk and 148 were intermediate risk according to d'Amico's risk group. The median prostate specific antigen (PSA) nadir was 0.12ng/ml with 65% of patients reaching a nadir less than 0.3 ng/ml. Systematic control biopsies were performed on 175 patients with 89% of negative biopsies. The disease free survival rate at 40 months was 79% for low risk group and 62% for intermediate risk group. The pre and post-HIFU treatment International Prostate Symptoms Score (IPSS) score and quality of life questionnaire were not statistically different. In the opposite, the pre and post-HIFU erection function and continence status were significantly different. CONCLUSION: Local control and Biochemical Free Survival Rate achieved with HIFU were similar to those expected with conformal external radiation beam therapy. Among the functional outcomes, potency was the most impacted by the treatment.

[MR detection of local prostate cancer recurrence after transrectal high-intensity focused US treatment: preliminary results]. / Détection par IRM des récidives locales du cancer de prostate après traitement par ultrasons focalisés de haute intensité (HIFU) transrectaux: étude préliminaire.

PURPOSE: To assess T2W and dynamic: contrast-enhanced (DCE) MR imaging in the detection of local tumor recurrence after transrectal high-intensity focused US (HIFU) treatment. MATERIALS AND METHODS: Fifteen patients treated by HIFU for prostate cancer were referred for MR due to biological evidence of tumor recurrence. Axial, sagittal and coronal T2W images and DCE images (12 3-mm thick axial images, temporal resolution: 15 seconds) were obtained first. Transrectal biopsies were then obtained under US guidance. MR findings were compared to biopsy results for 10 prostate sectors. RESULTS: Biopsies demonstrated tumor recurrence in 13/15 patients (23/108 sectors). On T2W images, the treated prostate tissue was diffusely hypointense which interfered with interpretation. Three patients (5 sectors) had suspicious areas of T2W signal abnormality and 15 patients (29 sectors) had suspicious areas on DCE scans. An analysis per sector for T2W and DCE imaging showed sensitivity, specificity, positive predictive and negative predictive values respectively of 0.13, 0.98, 0.6 and 0.81 and 0.70, 0.85, 0.55 and 0.91. DCE MR was strongly predictive of positive biopsy results (Odds ratio: 12.8 (95% confidence interval: 4.4-37.3)) whereas T2W imaging was not (Odds ratio: 4.0 (95% confidence interval: 0.5-30)). CONCLUSION: MR, especially DCE MR, is promising for the detection and localization of local prostate cancer recurrence after transrectal HIFU treatment.

Variability induced by the MR imager in dynamic contrast-enhanced imaging of the prostate.

PURPOSE: To evaluate the variability induced by the imager in discriminating high-grade (Gleason≥7) prostate cancers (HGC) using dynamic contrast-enhanced MRI. MATERIAL AND METHODS: We retrospectively selected 3T MRIs with temporal resolution<10 seconds and comprising T1 mapping from a prospective radiologic-pathologic database of patients treated by prostatectomy. Ktrans, Kep, Ve and Vp were calculated for each lesion seen on MRI using the Weinmann arterial input function (AIF) and three patient-specific AIFs measured in the right and left iliac arteries in pixels in the center of the lumen (psAIF-ST) or manually selected by two independent readers (psAIF-R1 and psAIF-R2). RESULTS: A total of 43 patients (mean age, 63.6±4.9 [SD]; range: 48-72 years) with 100 lesions on MRI (55 HGC) were selected. MRIs were performed on imager A (22 patients, 49 lesions) or B (21 patients, 51 lesions) from two different manufacturers. Using the Weinmann AIF, Kep (P=0.005), Ve (P=0.04) and Vp (P=0.01) significantly discriminated HCG. After adjusting on tissue classes, the imager significantly influenced the values of Kep (P=0.049) and Ve (P=0.007). Using patient-specific AIFs, Vp with psAIF-ST (P=0.008) and psAIF-R2 (P=0.04), and Kep with psAIF-R1 (P=0.03) significantly discriminated HGC. After adjusting on tissue classes, types of patient-specific AIF and side of measurement, the imager significantly influenced the values of Ktrans (P=0.0002), Ve (P=0.0072) and Vp (P=0.0003). For all AIFs, the diagnostic value of pharmacokinetic parameters remained unchanged after adjustment on the imager, with stable odds ratios. CONCLUSION: The imager induced variability in the absolute values of pharmacokinetic parameters but did not change their diagnostic performance.

Characterization of prostate cancer using T2 mapping at 3T: a multi-scanner study.

RATIONALE AND OBJECTIVES: To assess the prostate T2 value as a predictor of malignancy on two different 3T scanners. PATIENTS AND METHODS: Eighty-three pre-prostatectomy multiparametric MRIs were retrospectively evaluated [67 obtained on a General Electric MRI (scanner 1) and 16 on a Philips MRI (scanner 2)]. After correlation with prostatectomy specimens, readers measured the T2 value of regions-of-interest categorized as "cancers", "false positive lesions", or "normal tissue". RESULTS: On scanner 1, in PZ, cancers had significantly lower T2 values than false positive lesions (P=0.02) and normal tissue (P=2×10(-9)). Gleason≥6 cancers had similar T2 values than false positive lesions and significantly higher T2 values than Gleason≥7 cancers (P=0.009). T2 values corresponding to a 25% and 75% risk of Gleason≥7 malignancy were respectively 132 ms (95% CI: 129-135 ms) and 77 ms (95% CI: 74-81 ms). In TZ, cancers had significantly lower T2 values than normal tissue (P=0.008), but not than false positive findings. Mean T2 values measured on scanner 2 were not significantly different than those measured on scanner 1 for all tissue classes. CONCLUSION: All tested tissue classes had similar mean T2 values on both scanners. In PZ, the T2 value was a significant predictor of Gleason≥7 cancers.

Diagnosis of Xp11 translocation renal cell carcinomas in adult patients under 50 years: interest and pitfalls of automated immunohistochemical detection of TFE3 protein.

Renal cell carcinomas associated with Xp11.2 translocations form a new and little known entity of the WHO 2004 classification. An immunohistochemical (IHC) test aiming at demonstrating the nuclear expression of the protein TFE3, product of a gene frequently involved in translocation, has been proposed as a diagnostic tool. The aims of this work were to define our evaluation criteria of the immunohistochemical test with the antibody anti-TFE3 and to describe new cases of renal cell carcinomas with TFE3 translocations. Using immunohistochemistry with antibody anti-TFE3, we retrospectively studied 83 renal cell carcinomas diagnosed at Edouard Herriot Hospital and Biomnis Laboratory, Lyon, between 2003 and 2009. The patients were 50 years old or younger. We detail our experience of the IHC test using the anti-body anti-TFE3 and the interpretation criteria. This work has enabled two new cases of renal cell carcinomas associated with TFE3 translocations to be detailed, confirmed by molecular biology. The TFE3 immunohistochemical test is a useful tool that demands strict interpretation criteria. In our experience, more than 80% of nuclei stained with an intensity of ++ to +++ is necessary to suspect the diagnosis of Xp11 translocation renal cell carcinoma.

[Conjunctival epidermoid carcinoma revealed by a chronic limbic corneal ulceration]. / Un carcinome épidermoïde de la conjonctive révélé par une ulcération chronique du limbe cornéen.

PURPOSE: Conjunctival epidermoid carcinoma (CEC) is a rare tumor affecting mainly the perilimbal region of the bulbar conjunctiva. We report an atypical presentation of a CEC mimicking a Mooren pseudo-ulcer. CASE REPORT: A 78-year-old man presented a limbic corneal ulcer of the left eye that had appeared a few months before. Ophthalmologic examination showed a thinning limbic corneal ulceration, associated with substantial conjunctival thickening. The diagnosis of Mooren pseudo-ulcer was first suspected. Etiological investigations were negative. The worsening of the corneal ulcer led us to perform surgical excision on the conjunctiva around the ulcer. Histologic examination concluded in an invasive conjunctival carcinoma. Adjuvant radiotherapy was required because of incomplete surgical excision and chorion tumoral invasion.