Photodynamic cystoscopy for bladder cancer diagnosis and for NMIBC follow-up: An overview of systematic reviews and meta-analyses.

INTRODUCTION: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up. MATERIAL AND METHODS: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC. RESULTS: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear. CONCLUSIONS: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed.

Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

STUDY QUESTION: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION: In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE: Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA: Data available on request. LIMITATIONS, REASONS FOR CAUTION: More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene-confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Qualitative and quantitative contrast-enhanced ultrasonography for the characterisation of non-palpable testicular tumours.

AIM: To assess the diagnostic performance of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of non-palpable intratesticular tumours. MATERIALS AND METHODS: The local ethics review board approved the protocol, and all of the patients provided written informed consent. Between December 2011 and February 2014, men with non-palpable testicular tumours and normal tumour markers who were referred for surgery were included. The tumours were analysed by conventional US, including B-mode and colour Doppler US (CDUS) as well as by CEUS. Morphological aspects and qualitative and quantitative CEUS criteria, based on visual enhancement and time-intensity curves, were assessed for each lesion. RESULTS: Forty patients were ultimately included. Based on histopathological results, the tumours were classified into three groups: benign tumours (n=16), malignant tumours (n=15), and burned-out tumours (n=9). In B-mode, the morphological aspects were significantly different between benign and malignant tumours (p-values from 0.0002 to 0.008). Qualitative and quantitative analyses of the CEUS images revealed that burned-out tumours exhibited significantly less enhancement than malignant and benign tumours: in burned-out tumours, time-intensity curves were flat, whereas in both benign and malignant tumours the curves had a bell-shaped pattern. All intensity parameters were lower for burned-out tumours compared to benign and malignant tumours (p-value from 0.0001 to 0.026). Both benign and malignant tumours enhanced strongly, however, and no significant difference between the two was noted (p-value from 0.0721 to 0.0953). CONCLUSION: Unlike conventional US, which enable benign lesions to be differentiated from malignant or burned-out tumours, CEUS failed to enabled differentiation between benign lesions and malignant vascularised testicular tumours. CEUS appears to have the potential, however, to differentiate burned-out tumours from vascularised testicular tumours.

Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers.

We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families. Thirty-seven RCC were diagnosed in 34 carriers (19%) at a median age of 40. Among the 23 RCC with pathology review, 13 were papillary type 2. There were 4 papillary RCC of unspecified type, 3 unclassified, 2 tubulocystic, and 1 collecting duct (CD) RCC, all 2SC+ and most (8/10) FH-. Of the remaining 14, papillary type 2, papillary unspecified, CD, and clear cell histologies were reported. The vast majority of RCC (82%) were metastatic at diagnosis or rapidly became metastatic. Median survival for metastatic disease was 18 months (95%CI: 11-29). 133 cases (73%) had a history of cutaneous leiomyomas, 3 developed skin leiomyosarcoma. Uterine leiomyomas were frequent in women (77%), but no sarcomas were observed. Only 2 cases had pheochromocytomas/paraganglioma. CONCLUSION: Our findings have direct implications regarding the identification and management of HLRCC patients.

CT and MR imaging features of mucinous tubular and spindle cell carcinoma of the kidneys. A multi-institutional review.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently identified renal malignancy. Diagnosis of this rare subtype of renal tumour can be challenging for pathologists, and as such, any additional data would be helpful to improve diagnostic reliability. As imaging features of this new and rare sub-type have not yet been clearly described, the purpose of this study was to describe the main radiologic features on computed tomography (CT) and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective review of pathology and imaging databases. Using a combination of CT/MRI features, diagnosis of MTSCC could be suggested in many cases. A combination of slow enhancement with plateau on dynamic contrast-enhanced CT/MRI, intermediate to high T2 signal intensity contrasting with low apparent diffusion coefficient values on MRI appeared evocative of this diagnosis. KEY POINTS: • A slow enhancement with plateau is observed either on CT or MRI. • High T2 signal components but low apparent coefficient diffusion are evocative. • T2-weighted imaging features depend on the mucin components of the tumour.

[New anti-angiogenic strategies in the management of kidney cancer]. / Nouvelles stratégies anti-angiogéniques dans la prise en charge du cancer du rein.

INTRODUCTION: The aim of this study was to clarify the current role of adjuvant and neo-adjuvant in the treatment of kidney cancer. MATERIALS AND METHODS: The data were explored in Medline (http://www.ncbi.nlm.nih.gov) using the following MeSH terms or combinations of these keywords: "cancer", "rein", "kidney", "adjuvant", "neoadjuvant", "antiangiogenique", "antiangiogenic" and selecting the items produced in their methodology, their relevance to the theme explored and their date of publication. RESULTS: Thirty-two English and French items published between 2001 and 2011 were selected: five studies of evidence level 1, nine level 2 studies, nine level 4 studies, five studies at level 5 and four literature reviews. The cytoreductive nephrectomy as first-line treatment of locally advanced or metastatic kidney cancer is now controversial with the advent of new targeted anti-angiogenic therapies. In neoadjuvant setting, these treatments showed a moderate decrease in tumor volume and rarely improved resectability. In adjuvant setting, their place has yet to be specified and several trials are currently underway. CONCLUSION: Recent years have seen the anti-angiogenic therapeutic strategies upset in locally advanced and metastatic renal cancer. The development of clinical trials and research protocols will allow us to determine in the near future the optimal therapeutic sequences.

Bilateral renal lymphangiomatosis: imaging and histopathologic findings.

Renal lymphangiomatosis is an extremely rare disease characterized by developmental malformation of the lymphatic system surrounding the kidneys. We present the case of a 22-year-old pregnant female discovered because of worsening. Ultrasound, computed tomography, and magnetic resonance imaging studies were performed. An 18 × 11 × 10 cm voluminous cystic subcapsular lesion compressing the left kidney and subcapsular cysts of the right kidney were found. After the delivery, marsupialization was performed and the pathological analysis confirmed the diagnosis of lymphangiomatosis. A review of the literature is proposed.

[Metastatic melanoma in upper urinary tract: three cases and literature review]. / Mélanome métastatique aux voies excrétrices supérieures. À propos de trois cas et revue de la littérature.

Melanoma is a slowly growing malignancy, with potential distant metastasis at various sites. In this article, we reported three original cases of melanoma metastases in the upper urinary tract, and we achieved a literature review. Symptoms are inconstant and non-specific (pain or haematuria). Nephroureterectomy is performed in the majority of cases. Even if this metastatic location remains uncommon, it should be timely detected in order to allow an appropriate management and to improve the prognostic of melanoma.

[Non-obstructive azoospermia: option of the testicular sperm extraction performed on the day of oocyte retrieval]. / Azoospermie non obstructive: intérêt du prélèvement testiculaire synchrone du recueil ovocytaire.

OBJECTIVE: Analyzing the results and validating the procedure of testicular sperm extraction (TESE) performed on the day of oocyte retrieval in non obstructive azoospermia (NOA) patients. PATIENTS AND METHODS: Sixty TESE were performed on the day of oocyte retrieval (dOR), in 52 NOA men. Patients were sorted into three groups according to the results of the surgical procedure: 1: sperm recovery with possible sperm freezing (n=20); 2: sperm recovery without freezing (n=27); 3: "negative" biopsy (n=13). ICSI outcomes in the two groups with sperm recovery were compared to those of ICSI performed with frozen-thawed sperm obtained from TESE performed (n=13). RESULTS: The rate of positive sperm retrieval was 78%. While the overall clinical pregnancy rate was 50%, no difference in the fertilization, implantation and clinical pregnancy rates was found in the two groups with positive sperm retrieval as compared to frozen-thawed sperm group. Twelve pregnancies were obtained in patients without further sperm cryopreservation. CONCLUSION: After TESE in NOA men, cryopreserved sperm produced comparable results with freshly obtained sperm. However, TESE performed on dOR can offer the opportunity, in patients with rare sperm that might not survive freeze-thaw, to have a possible fresh embryo transfer. Couples should be counselled regarding the possibility of oocyte retrieval without sperm for ICSI.

[Renal oncocytosis: case report]. / Oncocytose rénale : à propos d'un cas.

Renal oncocytoma represent 5% of kidney tumors. Oncocytoma is a benign tumor, usually asymptomatic and fortuitous discovery. Standard treatment is tumorectomy when technically feasible. Surgery is indicated when oncocytoma becomes symptomatic, large or grows quickly. In a small proportion of cases, oncocytomas are bilateral and/or multifocal. These forms are most often sporadic or are integrated in the Birt-Hogg-Dube syndrome. We report here the case of a patient suffering from renal oncocytosis responsible for a diffuse renal involvement by numerous oncocytic nodules.

Recurrence of HUS due to CD46/MCP mutation after renal transplantation: a role for endothelial microchimerism.

Mutations in the gene of the membrane cofactor protein (MCP/CD46), a complement regulatory protein, were recently described as a cause of hemolytic uremic syndrome (HUS). MCP is a transmembrane glycoprotein expressed in kidneys; therefore, the transplantation of a normal kidney should not be complicated by HUS recurrence. However, we report the case of a 32-year-old woman with an MCP mutation who developed a recurrence of HUS after renal transplantation. We found that she had vascular microchimerism of endothelial cells. We suggest that recurrence may be favored by vascular microchimerism, in which the mutated protein is produced in the in the kidney graft by endothelial cells originating from recipient.

Successful organ transplantation after treatment of fatal cyanide poisoning with hydroxocobalamin.

BACKGROUND: Cyanide-poisoned patients are potential organ donors provided that organs are not damaged by the poison or by antidotal treatment. CASE STUDY: A patient with third-degree burns and smoke inhalation-associated cyanide poisoning confirmed by measurements of whole blood cyanide was found in cardiac arrest and administered epinephrine and hydroxocobalamin (5 g + 5 g). Cardiac activity resumed, but the patient was declared brain dead on the third day of hospitalization when coma deteriorated to a shock state with refractory hypoxemia. Kidneys, heart, and liver were removed and transplanted into four patients. Gross pre-transplantation inspection of the donor organs and renal histology showed no evidence that hydroxocobalamin caused organ toxicity. Donor organs functioned normally through follow-up periods of several months. CONCLUSION: Anoxic cardiac arrest following acute cyanide poisoning treated with hydroxocobalamin (5 g + 5 g) was not a contraindication to organ transplantation after confirmed encephalic death in this patient.

Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma.

BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.

Failure of rituximab to treat a lupus flare-up with nephritis.

The autoantibodies secreted by B lymphocytes have recently been shown to play an important role in autoimmune disease. B lymphocyte depletion by rituximab, a monoclonal anti-CD20 antibody, has been introduced for the treatment of several autoimmune disorders. Few reports have underlined its potential use for the treatment of systemic lupus erythematosus (SLE). We report here the occurrence of extracapillary glomerulonephritis associated with a thrombotic event shortly after rituximab treatment for a lupus flare-up in a patient with anticardiolipin antibodies. This observation suggests that rituximab alone may be insufficient to control severe SLE with glomerulonephritis and should therefore be used with caution in patients with this condition.

Cytogenetic, molecular and testicular tissue studies in an infertile 45,X male carrying an unbalanced (Y;22) translocation: case report.

(Y;autosome) translocations have been reported in association with male infertility. Different mechanisms have been suggested to explain the male infertility, such as deletion of the azoospermic factor (AZF) on the long arm of the Y chromosome, or meiosis impairment. We describe a new case with a de novo unbalanced translocation t(Y;22) and discuss the genotype-phenotype correlation. A 36 year old male with azoospermia was found to have a mosaic 45,X/46,X, + mar karyotype. Fluorescence in situ hybridization (FISH) showed the presence of a derivative Y chromosome containing the short arm, the centromere and a small proximal part of the long-arm euchromatin of the Y chromosome and the long arm of chromosome 22. The unstable small marker chromosome included the short arm and the centromere of chromosome 22. This unbalanced translocation t(Y;22)(q11.2;q11.1) generated the loss of the long arm of the Y chromosome involving a large part of AZFb, AZFc and Yq heterochromatin regions. Testicular tissue analyses showed sperm in the wet preparation. Our case shows the importance of documenting (Y;autosome) translocations with molecular and testicular tissue analyses.

Wide metastatic spreading in infiltrating lobular carcinoma of the breast.

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.

A histopathologic investigation of PGE(2) pathways as predictors of proliferation and invasion in urothelial carcinomas of the bladder.

INTRODUCTION AND OBJECTIVES: The pattern of arachidonate acid (AA) transformation in tumor cells has been shown to play a role in determining tumor cell invasiveness. AA is released from membrane phospholipids by cPLA(2). Then it is metabolized into prostaglandins and PGE(2) especially via cyclooxygenase pathways. PGE(2) production seems to be necessary for rendering the cells invasive. We aimed to characterize cPLA(2), cyclooxygenase 2 (COX2) and prostaglandine E synthase (PGES) expression in human transitional carcinoma (TCC) of the urinary bladder and correlate with the Ki-67 proliferating marker. METHODS: Formalin-fixed human TCC tissues (n=54) obtained from TURB or cystectomies were evaluated for cPLA(2), COX2, PGES and Ki-67 expression using specific antibodies. There were 6 CIS, 9 pTaG1, 9 pTaG3, 10 pT1G3 and 10 pT2G3. 10 normal bladder tissues were also evaluated. Control slides were incubated without primary antibodies and treated in a similar way. RESULTS: cPLA(2), COX2 and PGES were not expressed in the 10 normal tissues. In the same normal tissues, Ki-67 expression was observed only in 1% of the cells. However, cPLA(2) was expressed in 1/6 CIS, 1/9 pTaG1, 3/9 pTaG3, 6/10 pT1G3 and 2/10 pT2G3. COX2 was expressed in 0/6 CIS, 0/10 pTaG1, 2/9 pTaG3, 3/10 pT1G3 and 1/10 pT2G3. PGES was expressed in 4/6 CIS, 0/9 pTaG1, 4/9 pTaG3, 2/10 pT1G3 and 5/10 pT2G3. Ki-67 expression was 39.5% for CIS, 6.5% in pTaG1, 37% in pTaG3, 34.5% in pT1G3 and 55% in pT2G3. If we consider it a positive result when at least one enzyme was expressed, there were 5/6 CIS positive, 1/9 pTaG1 positive, 9/9 pTaG3 positive, 10/10 pT1G3 positive and 10/10 pT2G3 positive. Also the Ki-67 is more often expressed in cells with high grade tumor. CONCLUSIONS: These results suggest that (i). not only COX2 is involved in the tumorogenesis of the TCC but also cPLA(2) and PGES, (ii). there is relationship between the AA metabolic PGE(2) pathway expression and the aggressiveness of the TCC of the urinary bladder.