Nephron sparing surgery in tumours greater than 7cm.

INTRODUCTION: Partial nephrectomy (PN) is the gold standard treatment for renal cell carcinomas under 4cm. No robust data exists to recommend PN for tumours>7cm (cT2). The objective of this work is to evaluate the results of PN for cT2 tumours. PATIENTS AND METHODS: All patients who underwent PN or radical nephrectomy (RN) for cT2 tumours between 2000 and 2013 at our institution have been included. Patient demographics, postoperative data including renal function, morbidity, mortality and oncologic outcomes were reviewed retrospectively and compared using χ2 test, Mann-Whitney test, Kaplan-Meier method and log rank test. RESULTS: We included 130 patients, 49 (38%) in the PN group and 81 (62%) in the RN group, with a median follow-up of 42 months [19-69]. Variation of postoperative renal function at day 5 and last recorded value was significantly different between the groups (P=0.03 and P<0.001). The PN group had a significantly higher complication rate as compared with RN group (37% versus 14%, P=0.002). There were no significant differences between the two groups for overall, recurrence free and specific survival (P=0.55, P=0.55, P=0.24, respectively). In univariate analysis, the type of surgery (PN versus RN) was not associated with a significant difference of oncologic outcome (margins, survival). CONCLUSION: PN can be offered for cT2 tumours with oncological outcomes similar to RN. Despite an increased morbidity, it remains acceptable with the demonstrated advantage of preservation of renal function. LEVEL OF EVIDENCE: 4.

Simple and complex renal cysts in adults: Classification system for renal cystic masses.

Ultrasound and slice imaging are currently the key modalities for diagnosing simple renal cysts. Benign simple renal cysts are defined by a set of strict criteria. Any cystic lesions that do not meet these criteria should be classified as "atypical" or "complex" and considered as suspicious. For over three decades, the Bosniak classification has been the central tool for diagnosing renal cystic masses larger than 1 cm. The Bosniak classification is based upon the results of a well-established pre- and post-contrast computed tomography (CT) protocol. Lesions that are difficult to classify or that remain indeterminate after CT can benefit from a multimodal diagnostic approach combining CT, non-contrast-enhanced and contrast-enhanced ultrasound, and magnetic resonance imaging.

[Sporadic kidney cancer of young subjects: Study of the clinical and pathological features of a bicentric cohort]. / Le cancer du rein sporadique du sujet jeune : étude des particularités cliniques et anatomopathologiques d'une cohorte bicentrique.

INTRODUCTION: The epidemiology of kidney cancer is evolving with a net increase in the incidence of renal tumors, globally, and in young people in particular. OBJECTIVE: To evaluate the incidence and clinical and pathological characteristics of sporadic renal tumors in young subjects and their risk factors. MATERIAL AND METHODS: A retrospective study aimed at collecting clinical, epidemiological and anatomopathological information from the 118 patients aged 18 to 40 treated for a sporadic kidney tumor in two Parisian university hospital centers between 2003 and 2013. RESULTS: Our study showed a very significant increase in the incidence of renal tumors in our 11 years of decline (P=6.10-15). The mode of discovery also seems to have evolved with a majority of tumors (67 %), due to the considerable growth of imaging in recent decades. We also showed a different pathological distribution compared to the literature with a significant increase in the number of papillary tumors (16.9 %) and chromophobes (15.2 %), in addition to a decrease in the number of carcinomas (43.2 %) as well as the appearance of a new pathological entity of particular clinical severity: renal carcinoma related to translocation Xp11.2 (15.3 %) (P<10-5). Among the risk factors, hypertension seems to be a definite risk factor while tobacco and obesity do not have a significant influence. CONCLUSION: Our study showed a marked increase in the incidence of renal tumors with specific clinical and epidemiological features in a population of young subjects. The role and importance of oncogenetic management as well as the study of environmental factors could lead to the identification of new risk factors and corollary to their prevention. LEVEL OF EVIDENCE: 4.

[Cancer genetic screening for patient with multiple renal tumors: What is the current practice for what results?]. / Dépistage oncogénétique des patients atteints de tumeurs rénales multiples : quelle pratique pour quels résultats ?

AIM: To evaluate in a high volume center the practice and the performance of cancer genetic screening for patients with multiple renal tumors without a predisposition to kidney tumors known at the time of surgery. METHOD: All patients treated for multiple renal tumors from January 2000 to December 2013 in our center were included. Patients with a family history of renal cell carcinoma, a kidney disease or a genetic predisposition to renal cancer known at the time of surgery were excluded from the analysis. Our list of patients was retrospectively compared to the records from PREDIR (PREDisposition to Kidney Tumors) center of Île-de-France, which regionally centralizes the care of patients with kidney tumors associated with a genetic predisposition. RESULTS: One hundred and thirty-six patients were included. Twenty-six patients of 136 (19%) were referred to PREDIR center: 23 followed the screening and 3 did not show up in consultation. Of the 23 patients screened, three genetic predispositions to kidney tumors were identified (13%). Of the 95 patients with synchronous tumors, 48% with more than 3 tumors benefited from cancer genetics investigation against 13% of those presenting only two tumors. CONCLUSION: Our study shows that cancer genetic investigations are not routinely offered to patients with multiple kidney tumors, conversely to existing guidelines. Urologists must be aware of this screening. LEVEL OF EVIDENCE: 4.

Multimodal management of primary adenocarcinoma of the female urethra: About four cases.

PURPOSE: To retrospectively analyse female patients treated for urethral adenocarcinoma, modalities of treatment and long-term outcomes. PATIENTS: Four cases of primary female urethral adenocarcinoma were treated in the departments of urology and radiation-oncology at Georges-Pompidou and Necker hospitals (France) over a 7-year period. RESULTS: All of them underwent surgery, with three presenting stage pT3-pT4 and one a positive cytology on inguinal node. Three patients received adjuvant cisplatin-based chemoradiotherapy up to 60Gy, and one preoperative chemoradiotherapy at 45Gy. Two recurrences were observed: one local relapse occurred at 9months from the diagnosis and was treated by anterior pelvic exenteration followed by chemoradiotherapy, with no recurrence. One tumour relapsed both at the local level and on distant metastatic sites at 9months from the diagnosis, and died 21months after this progression. Median survival and progression-free survival are respectively 4.2years and 13months. Three patients are alive at 7, 4.5 and 3years from diagnosis. CONCLUSION: Female urethral adenocarcinoma is a very rare entity and often present in locally advanced stages. Initial extensive surgery with pelvic exenteration should be considered, followed by chemoradiotherapy according to the surgical margins and lymph nodes involvement.

Tubulocystic renal cell carcinoma: a new radiological entity.

UNLABELLED: Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. KEY POINTS: • Tubulocystic renal cell carcinoma is a new entity with typical imaging features • Diagnosis of tubulocystic renal cell carcinoma can be suggested preoperatively by imaging • Cystic renal lesions with high echogenicity may correspond to tubulocystic carcinoma.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs.

BACKGROUND: Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs. METHODS: Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression. RESULTS: We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001). CONCLUSIONS: RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.

Double-echo gradient chemical shift MR imaging fails to differentiate minimal fat renal angiomyolipomas from other homogeneous solid renal tumors.

OBJECTIVES: The purpose of this retrospective study was to evaluate the diagnostic performance of double-echo gradient chemical shift (GRE) magnetic resonance (MR) imaging for the differentiation of angiomyolipomas with minimal fat (mfAML) from other homogeneous solid renal tumors. METHODS: Between 2005 and 2010 in two institutions, all histologically proven homogenous solid renal tumors imaged with computed tomography and MR imaging, including GRE sequences, have been retrospectively selected. A total of 118 patients (mean age: 61 years; range: 20-87) with 119 tumors were included. Two readers measured independently the signal intensity (SI) on GRE images and calculated SI index (SII) and tumor-to-spleen ratio (TSR) on in-phase and opposed-phase images. Intra- and interreader agreement was obtained. Cut-off values were derived from the receiver operating characteristic (ROC) curve analysis. RESULTS: Twelve mfAMLs in 11 patients were identified (mean size: 2.8cm; range: 1.2-3.5), and 107 non-AML tumors (3.2cm; 1-7.8) in 107 patients. The intraobserver reproducibility of SII and TSR was excellent with an intraclass correlation coefficient equal to 0.99 [0.98-0.99]. The coefficient of correlation between the readers was 0.99. The mean values of TSR for mfAMLs and non-mfAMLs were -7.0±22.8 versus -8.2±21.2 for reader 1 and -6.7±22.8 versus -8.4±20.9 for reader 2 respectively. No significant difference was noticed between the two groups for SII (p=0.98) and TSR (p=0.86). Only 1 out of 12 mfAMLs and 11 of 107 non-AML tumors presented with a TSR inferior to -30% (p=0.83). CONCLUSION: In a routine practice, GRE sequences cannot be a confident tool to differentiate renal mfAMLs from other homogeneous solid renal tumors.

Renal papillary carcinoma: CT and MRI features.

PURPOSE: To describe the CT and MRI appearances of papillary renal cell carcinoma. MATERIALS AND METHODS: Retrospective study of 102 papillary carcinomas in 79 patients, 81 tumors examined by CT and 56 by MRI. Tumor size, homogeneity and contrast enhancement were recorded. RESULTS: The most common presentation of papillary renal cell carcinoma was a small homogeneous hypovascular tumor both on CT and MRI. Eighty-nine percent of lesions were hypointense on T2 weighted images compared to the renal parenchyma. Seventeen percent of the lesions did not significantly enhance with contrast on CT. All of the lesions examined on MRI had a significant enhancement percentage. Calcifications were rare and only seen in 7% of cases (CT). The second most common presentation was a bulky necrotic tumor. In addition, atypical types of disease were found which were difficult to diagnose, including infiltrating tumors and tumors with a fatty component. CONCLUSION: A homogeneous hypovascular renal tumor which is hypointense on T2 weighted images should suggest a diagnosis of papillary carcinoma. Some papillary carcinomas do not enhance significantly on CT. MRI is then required to diagnose the renal tumor.

Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients. METHODS: We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates. RESULTS: In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013). CONCLUSION: Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.

[Histopathology of coeliac disease]. / Le diagnostic histologique de la maladie cœliaque.

Coeliac disease is a common disease, affecting 1% of the population. Clinical manifestations are multiple. The diagnosis requires serologic testing and a duodenal biopsy that shows the characteristic findings of intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy, and a positive response to a gluten-free diet. In most patients, the histological diagnosis is easily established. Pitfalls in the pathological diagnosis include a poorly orientated biopsy specimen, either an inadequate biopsy sampling in patients with patchy villous atrophy and the other causes of villous atrophy. A non-response to the gluten-free diet needs to reassess first, the initial diagnosis, second to be sure of the gluten-free diet adherence, and third, to exclude malignant complications such as refractory celiac disease or enteropathy-associated T-cell lymphoma.

Outcome of continence procedures after failed endoscopic treatment with dextranomer-based implants (DEFLUX®).

PURPOSE: To evaluate outcome of further continence procedures after failure of endoscopic injections of dextranomer-based bulking agent. MATERIALS AND METHODS: From 1997, 89 children (3-18 years) and one young adult were treated for incontinence with 145 endoscopic injections of dextranomer. On evaluation, each patient was classified as: dry, significantly improved, or treatment failure. Eighty-five patients had at least 12 months of follow up. Out of 34 (40%) treatment failures, 24 patients had a subsequent bladder neck procedure: artificial urinary sphincter (7), bladder neck plasty (9), bladder neck closure (1), fascial sling (3). Six patients had further endoscopic treatment (including 2 after bladder neck plasty). RESULTS: At surgery, Deflux(®) paste was easily identified with minimal surrounding tissue inflammatory reaction. Artificial urinary sphincter: all 7 dry; bladder neck plasty: 7 dry, 1 improved and 1 still incontinent; 1 bladder neck closure patient dry; fascial sling: 1 significantly improved and 2 dry. Repeated endoscopic treatment: 1 dry, 1 improved and 4 failed. Eleven of the 21 (52%) patients who are either dry or improved have voiding abilities. CONCLUSION: Endoscopic injections with dextranomer do not adversely affect the outcome of further surgical procedures. Repeated injections after a previous endoscopic treatment failure have a low success rate.

Morphological mosaicism of the pancreatic islets: a novel anatomopathological form of persistent hyperinsulinemic hypoglycemia of infancy.

BACKGROUND: Morphological studies of the pancreas in persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have focused on the diagnosis of focal vs. diffuse forms, a distinction that determines the optimal surgical management. ABCC8 or KCNJ11 genomic mutations are present in most of them. AIM: Our aim was to report a new form of PHHI with peculiar morphological and clinical characteristics. RESEARCH DESIGN AND METHODS: Histopathological review of 217 pancreatic PHHI specimens revealed 16 cases morphologically different from diffuse and focal forms. They were analyzed by conventional microscopy, quantitative morphometry, immunohistochemistry, and in situ hybridization. RESULTS: Their morphological peculiarity was the coexistence of two types of islet: large islets with cytoplasm-rich ß-cells and occasional enlarged nuclei and shrunken islets with ß-cells exhibiting little cytoplasm and small nuclei. In small islets, ß-cells had abundant insulin content but limited amount of Golgi proinsulin. Large islets had low insulin storage and high proinsulin production and were mostly confined to a few lobules. No evidence for K(ATP) channels involvement or 11p15 deletion was found. Genomic mutations for ABCC8, KCNJ11, and GCK were absent. Patients had normal birth weight and late hypoglycemia onset and improved with diazoxide. Ten were cured by limited pancreatectomy. Six recurred after surgery and were medically controlled. CONCLUSION: This new form of PHHI is characterized by a morphological mosaicism. Pathologists should recognize this mosaicism on intraoperative frozen sections because it is often curable by partial pancreatectomy. The currently unknown genetic background does not involve the classical genomic mutations responsible for diffuse and focal PHHI.

Factors associated with partial and complete regression of fetal lung lesions.

OBJECTIVE: A decrease in the volume of congenital pulmonary malformations (CPM) can be observed on prenatal ultrasonography, but the underlying mechanism for this phenomenon is unknown. Our objective was to identify factors associated with the prenatal reduction in size of cystic and/or hyperechoic lung lesions. METHODS: This was a retrospective study of cases with a prenatal diagnosis of hyperechoic and/or cystic lung lesion. The extent of reduction in lesion size was calculated from ultrasound measurements. Clinical, ultrasound, radiological and histological data were tested for their relationship with prenatal CPM reduction. RESULTS: In a 4-year period, 36 patients were referred with a cystic and/or hyperechoic fetal lung lesion diagnosed at a mean gestational age of 23.4 weeks. The lesions were cystic in 16 cases (44%), hyperechoic in 12 (33%) and both in eight (22%). The malformation was no longer visible before birth (apparent disappearance) in nine cases (25%), shrank by 18-90% in 15 (42%) and did not reduce in 12 (33%). Findings on postnatal computed tomography were always abnormal. Isolated hyperechoic lesions were significantly more likely to shrink in utero. The mean reductions were 79%, 35% and 19%, for isolated hyperechoic, cystic and mixed lesions, respectively (P=0.001). Only 8% of hyperechoic lesions demonstrated no volume reduction, as compared to 50% and 42% of cystic and mixed lesions, respectively (P=0.03). Greater gestational age at birth was also associated with a decrease in the incidence of malformations (P=0.02). In cases that underwent surgery, hyperechoic lesions were linked to a variety of pathological diagnoses, whereas cystic lesions were all described histologically as congenital cystic adenomatoid malformations. CONCLUSIONS: Prenatal size reduction of fetal lung malformations is associated with isolated hyperechogenicity and greater gestational age at birth. This might result from the resumption of normal lung development after local disruption of lung growth.

Enteropathy-associated T-cell lymphoma: a review on clinical presentation, diagnosis, therapeutic strategies and perspectives.

INTRODUCTION: Enteropathy-associated T-cell lymphoma (EATL) is a rare complication of celiac disease (<1% of lymphomas) and has a poor prognosis. METHODS: International literature review with PubMed search (up to January 2009) of pathophysiological, clinical and therapeutic data. RESULTS: EATL is found in patients with a mean age of 59 years, often with a complication that signals its diagnosis. Refractory celiac disease (RCD), equivalent to low-grade intraepithelial T-cell lymphoma, could be an intermediary between celiac disease and high-grade invasive T-cell lymphoma. The median survival is 7 months, with no significant difference between stages; the cumulative 5-year survival is less than 20%. The poor prognosis is determined by disease that has often spread before it is diagnosed (50%), multifocal involvement of the small bowel (50%), poor general health status and undernutrition, and recurrence of complications (infections, perforations, gastrointestinal haemorrhages, occlusions), thus delaying the chemotherapy and contributing to frequent chemotherapy resistance. There is currently no effective and consensual treatment: preventive surgery for complications is controversial, and the results of chemotherapy are disappointing. The classic CHOP protocol (combination of doxorubicin-cyclophosphamide-vincristine-prednisone) does not have satisfactory results and survival remains poor, especially in patients with underlying RCD. High-dose chemotherapy with autotransplantion seems to only improve the prognosis in localised forms. Allogeneic bone marrow transplantation was not evaluated. In all, 1/3 of patients, being unfit for treatment, die before 3 months and half of treated patients stop chemotherapy prematurely due to inefficacy, intolerance and/or complications. CONCLUSION: Improvement of the prognosis requires collaboration in order to compose a national cohort, to evaluate new diagnostic and therapeutic strategies and to define prognostic factors.