Expanding the clinical and genetic spectra of NKX6-2-related disorder.

Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole-exome or whole-genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation.

[Is initial success after Monarc(®) suburethral sling durable at mid-term evaluation?]. / Le succès thérapeutique après bandelette Monarc(®) est-il durable à moyen terme ?

OBJECTIVES: Suburethral sling is the gold standard treatment for stress urinary incontinence (SUI). Short-term cure rates are high, but only few studies are available for longer assessment after transobturator tape procedure. The objectives of this study were to assess mid-term functional outcome for Monarc(®) transobturator tape after initial success, and to identify risk factors for recurrence. MATERIAL AND METHODS: We conducted a single centre retrospective study (2004-2013) on consecutive women with SUI who underwent Monarc(®) transobturator tape procedure and were initially cured at the postoperative medical consultation. Pre- and postoperative data (age, weight, height, body mass index, hormonal status, surgical history, associated organ prolapse [Baden and Walker], associated urinary symptoms, postoperative complications [Clavien-Dindo]) were extracted from the electronic medical record. Subjective cure was defined by a score of zero from the ICIQ-SF questionnaire, no second intervention for recurrent SUI and no need for pads at latest news. Statistical analysis was performed using SAS(®) v9.3 (P<0.05). RESULTS: One hundred and thirty-three consecutive women underwent TOT Monarc(®) procedure, and 125 women were cured in the short-term. Among these women, 103 (82%) were available for mid-term evaluation. Sixty-four women (62%) had pure stress urinary incontinence. The mean follow-up period was 51 months [2-119]. At last follow-up, cure rate was 61%. Seventy-eight percent of women with recurrent urinary incontinence had SUI. Other women had mixed urinary incontinence (3/40), or de novo urgency (6/40). In univariate analysis, we could not identify pejorative prognostic factors for mid-term failure. CONCLUSION: In our experience, mid-term functional outcome after Monarc(®) transobturator tape procedure seems to deteriorate. After 4 years of follow-up, 61% of the women who were initially cured were still free from any leakage. LEVEL OF EVIDENCE: 4.

The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: HOX gene expression is altered in many cancers; previous microarray revealed changes in HOX gene expression in head and neck squamous cell carcinoma (HNSCC), particularly HOXD10. METHODS: HOXD10 expression was assessed by qPCR and immunoblotting in vitro and by immunohistochemistry (IHC) in tissues. Low-expressing cells were stably transfected with HOXD10 and the phenotype assessed with MTS, migration and adhesion assays and compared with the effects of siRNA knockdown in high-HOXD10-expressing cells. Novel HOXD10 targets were identified using expression microarrays, confirmed by reporter assay, and validated in tissues using IHC. RESULTS: HOXD10 expression was low in NOKs, high in most primary tumour cells, and low in lymph node metastasis cells, a pattern confirmed using IHC in tissues. Overexpression of HOXD10 decreased cell invasion but increased proliferation, adhesion and migration, with knockdown causing reciprocal effects. There was no consistent effect on apoptosis. Microarray analysis identified several putative HOXD10-responsive genes, including angiomotin (AMOT-p80) and miR-146a. These were confirmed as HOXD10 targets by reporter assay. Manipulation of AMOT-p80 expression resulted in phenotypic changes similar to those on manipulation of HOXD10 expression. CONCLUSIONS: HOXD10 expression varies by stage of disease and produces differential effects: high expression giving cancer cells a proliferative and migratory advantage, and low expression may support invasion/metastasis, in part, by modulating AMOT-p80 levels.

[Bladder tumor targeting by Hexvix(®) fluorescence: 4 years results after prospective monocentric evaluation]. / Ciblage diagnostique par Hexvix(®) des tumeurs urothéliales de vessie : résultats après quatre ans d'évaluation prospective monocentrique.

PURPOSE: Prospective evaluation of bladder tumor targeting by Hexvix(®) fluorescence. PATIENTS AND METHODS: From September 2008 to April 2012, 107 patients have been evaluated using Hexvix(®) technique (blue light) for typically papillary bladder tumor or suspected bladder tumor. Clinical and pathological data have been collected prospectively and patients have been classified using EORTC score. RESULTS: From the 107 patients, 67 have been identified with bladder cancer and 328 samples have shown positive fluorescence in blue light. Compared to white light, 13 additional tumors have been diagnosed by Hexvix(®) for 11 patients: Cis (n=6), LMP (n=3), pTa low grade (n=3), pT1 low grade (n=1) (P=0.003). The false positive rate for Hexvix(®) was 53.4% versus 52% for white light. Previous TCC history, multifocality and EORTC score for recurrence and progression have been associated with better bladder cancer targeting by Hexvix(®) (P=0.007; P=0.01; P=0.03; P=0.04). CONCLUSION: In our experience, Hexvix(®) targeting was associated with better diagnosis for bladder cancer with 9% (13/144) of new positive samples (P=0.003). In our study, false positive rate is a critical point (53.4%). Multifocality, previous TCC, and EORTC score for recurrence and progression might allow selecting patients to be targeted by Hexvix(®).

[Results of nephrectomy for native kidney tumors in renal transplanted patients]. / Résultats des néphrectomies pour tumeurs des reins natifs chez les patients transplantés rénaux.

OBJECTIVE: Evaluate epidemiology, diagnosis and outcome of de novo renal cell carcinoma in renal transplanted patients. PATIENTS AND METHOD: From June 1989 to December 2007, 824 renal transplantations were carried out and followed in annual consultation by an urologist with abdominal echography or tomodensitometry. The suspect renal lesions were treated by a widened nephrectomy. Incidence, diagnosis, treatment, histological type, and outcome of all patients were analysed. RESULTS: Thirty-three patients had nephrectomy for suspect renal lesions. Twenty-two de novo tumours of native kidneys among 21 patients were diagnosed (15 renal clear cell carcinoma and seven papillary tumours) with mean time after transplantation of 25,6 months (2.3-105.5). All tumours were classified pT1aN0M0. Only one patient died at 8 months of metastatic dissemination of a papillary tumour classified initially pT1aN0M0. All the other patients are alive with mean follow-up of 34.8 months (2.8-113.9). Specific survival to 5 years was 93.3%. CONCLUSION: The increase risk of tumour at the renal transplanted patient led to propose in the event of suspect lesions of the native kidneys, a widened nephrectomy. In our series, 65% of the operated patients carried a cancer. The good forecast of these localized tumours justifies a regular radiological monitoring and an aggressive therapeutic attitude despite of absence of tumours in 35% of the transplanted patients.

De novo renal carcinoma in renal transplant recipients: effect of early treatment.

OBJECTIVE: To evaluate the epidemiology, diagnosis, and outcome of de novo renal cell carcinoma in renal transplant recipients. PATIENTS AND METHODS: From June 1989 to August 2006, 800 renal transplant recipients were followed up annually by a urologist using abdominal ultrasonography or computed tomography. Renal lesions considered suspect were treated using extended nephrectomy. Incidence, diagnosis, histologic type, treatment, and outcome were analyzed in all patients. RESULTS: Thirty-three patients underwent nephrectomy because of suspect renal lesions including 22 de novo tumors in 21 native kidneys (renal clear-cell carcinoma in 15 and papillary carcinoma in 7). All tumors were classified as pT1aN0M0. Mean (range) time after diagnosis was 25.6 (2.3-105.5) months. Only 1 patient died, at 8 months after diagnosis. All other patients were alive at follow-up of 34.8 (2.8-113.9) months. Five-year survival was 92%. CONCLUSION: The increased risk of tumor in renal transplant recipients leads us to propose extended nephrectomy in the case of suspect lesions in the native kidney. In our patients, 65% of patients had malignant lesions. Good prognosis for these localized tumors justified aggressive therapy even though 35% of transplant recipients were tumor-free.

Endoscopic management of urologic complications following renal transplantation: impact of ureteral anastomosis.

OBJECTIVE: To evaluate the success of ureteral stent placement to treat or prepare for surgical treatment of urologic complications after renal transplantation, according to a type of ureteral anastomosis. PATIENT AND METHODS: From May 1989 to December 2006, we performed 703 kidney transplantations including 412 extravesical ureteroneocystostomy (according to Lich-Gregoire technique) and 265 transvesical ureteroneocystostomy (according to Politano-Leadbetter technique). We retrospectively analyzed our endoscopic management of urinary leaks and ureteral strictures. The criteria of success were the feasibility to place a ureteral stent, permitting good drainage of the upper renal graft tract before further endoscopic or surgical treatment. RESULTS: Forty-three urinary leaks or ureteral strictures occurred after extravesical ureteroneocystostomy (n = 21) or after Politano-Leadbetter anastomosis (n = 22). The success rate of endoscopic management was 75% (n = 16) for Politano-Leadbetter anastomosis versus 53% (n = 11) for the Lich-Gregoire anastomosis. There was no statistical difference (P = .1). CONCLUSION: Ureteroneocystostomy according to Lich-Gregoire procedure were twice less complicated than those according to the Politano-Leadbetter technique, but were associated with a rate of failure of ureteral stent placement in urgency higher to 25%.

[Can MRI be used to distinguish between superficial and invasive transitional cell bladder cancer?]. / L'IRM permet-elle de distinguer les tumeurs urothéliales vésicales superficielles et infiltrantes ?

OBJECTIVE: To determine the sensitivity and specificity of MRI to distinguish between superficial and invasive transitional cell bladder cancer. MATERIAL AND METHODS: Sixty patients (52 men and eight women) with a mean age of 66.8 years were assessed by bladder MRI between May 2002 and November 2005 for a primary bladder cancer diagnosed by endoscopy, followed by transurethral resection and histological examination of the bladder cancer. Patients presenting a discordance between MRI findings and histological examination were analysed. RESULTS: Imaging and pathology staging was concordant for 49 bladder cancers (40 superficial and nine invasive). Ten tumours considered to be invasive on MRI were superficial on histological examination and six of them relapsed at the resection scar at one or three months. The sensitivity of MRI was 80% for a specificity of 90% and a positive predictive value of 97.5%. CONCLUSION: MRI is a reliable examination to confirm the superficial nature of bladder cancer. When MRI and histological examination of a bladder cancer resection specimen are discordant, second look surgery is recommended to treat residual disease, which was present in 60% of cases in the present series.

[Report of 2 cases of arterio-ureteral fistula]. / A propos de deux cas de fistule artério-urétérale.

Uretero-arterial fistulas are exceptional complications: only about forty cases have been reported in the literature. The authors report new two cases of fistula between the common iliac artery and the ureter. One fistula occurred in a context of prolonged ureteric stenting after radiotherapy and pelvic surgery for cancer of the uterus, and the other occurred after an aorto-bifemoral allograft. These fistulas generally occur in a particular clinical context, associating several aetiological factors. The clinical presentation is dominated by often massive and intermittent haematuria. The most useful diagnostic examinations are retrograde ureteropyelography and arteriography. The proposed treatment options (nephrectomy, vascular bypass graft and even embolization) depend on the urgency of the situation and involve both the blood vessel and the urinary tract. The prognosis depends on early diagnosis, but preventive measures can be envisaged to decrease the risk of appearance of these fistulas in high-risk patients.

[Renal transitional carcinoma and caval tumor thrombus]. / Carcinome transitionnel rénal et thrombus tumoral cave.

Transitional cell carcinoma of the kidney with caval tumour thrombus is extremely rare. The authors describe the radiological signs suggesting the preoperative diagnosis and guiding the therapeutic approach. They present the case of a 51-year-old patient with excluded caliceal stones, and review 17 cases published over a period of 24 years during which considerable progress has been made in radiological investigations. Only CT appears to be able to indicate this aetiology and allows retrograde ureteropyelography looking for a tumour of the urinary tract. MRI provides the best assessment of tumour involvement of the inferior vena cava. Nephroureterectomy with excision of a perimeatal bladder cuff and cavotomy is the only oncological surgical procedure, despite the extremely poor prognosis.

[Stenosis of the vesico-urethral anastomosis. Our experience with 114 radical prostatectomies]. / Sténose de l'anastomose vésico-uréthrale. Notre expérience sur 114 prostatectomies radicales.

The authors report a retrospective series of 114 radical prostatectomies performed over a ten-year period. This study was designed to investigate the factors likely to cause complications in order to prevent them. Stenosis of the vesicourethral anastomosis was observed in 22 patients and represented the commonest complication (19.2%). It generally occurred before the 12th month, while late stenoses. An anastomotic leak after removal of the bladder catheter appears to be the most significant factor. The decreasing incidence of these stenoses over the ten-year study period illustrates the role of operator experience. The most effective treatment for these stenoses is mono-incision which, completed by dilatation sessions, prevents recurrence without compromising continence.

[Transurethral incision of the prostate. 5 years of follow-up. Apropos of 57 patients]. / Incision transuréthrale de la prostate. Cinq années de recul. A propos de 57 patients.

Fifty-seven bladder neck incisions were studied with a minimum follow-up of 5 years. The results published after one year were very satisfactory, but became more disappointing after 5 years, with a 38.7 reoperation rate. The weight of the prostate appears to be the determining factor. The indications, 5 years ago, were much wider than they are today, with prostate weights of up to 45 g on digital rectal examination. This type of operation should now be reserved for young subjects wishing to retain antegrade ejaculation with a prostate not exceeding 20 to 30 g and in high surgical risk patients unsuitable for transurethral resection.

[Bilateral ureteral stenosis after pancreatitis]. / Sténose urétérale bilatérale après pancréatite.

The authors report a rare case of bilateral ureteric stenosis associated with necrotic infiltration due to acute alcoholic pancreatitis. The obstruction was caused by bilateral ureteric fibrosis with calcified incrustations on the right side and massive obstructive calculi on the left side. Only one faintly similar case has been reported in the literature out of 17 cases of unilateral or bilateral ureteric stenosis complicating acute or chronic pancreatitis.

[Late renal and hypertensive complications of extracorporeal lithotripsy. Myth or reality?]. / Complications rénales et hypertensives tardives de la lithotritie extracorporelle. Mythe ou réalité?

Extracorporeal shock wave lithotripsy (ESWL) has produced dramatic advances in the surgical management of urinary calculi. However this new procedure could induce deleterious effects as loss of renal function and hypertension. Animal studies show that ESWL induces focal areas of necrosis and subsequent fibrosis in renal tissue. In humans, imaging technics demonstrate renal alterations in 80% of the patients. Acute renal hemodynamic and functional changes is frequent but transient in most of the cases. Some studies have shown a tendancy to an increase in blood pressure related to a decrease in renal plasma flow in one study. However most of these results are based on retrospective surveys of blood pressure and renal function. Therefore prospective clinical trials are needed to investigate the important questions of ESWL-induced hypertension and decrease renal function.

[Hydatid cyst of the kidney. Contribution of imaging techniques]. / Kyste hydatique du rein. Apport de l'imagerie.

The authors report a case of renal hydatid disease, a rare disease in France. After reviewing the recent data of the literature, they stress the value of computed tomography and especially MRI in the presumptive diagnosis.

[Internal urethrotomy in the treatment of stenosis of the urethra. Late results and a review of the literature]. / L'urétrotomie interne dans le traitement des sténoses de l'urètre. Résultats à distance et revue de la littérature.

The authors report their experience with 37 patients treated by internal urethrotomy for urethral strictures. The results were appreciated on urethral calibration and flow rate after a median follow-up of 33,5 months and a minimal follow-up of one year. The rate of satisfying results was 78,3%. The authors emphasize the need of dilatations associated to low-doses of cortico-steroids in the post-operative period during the first three months, to improve the results.

[Intra-diverticular tumors of the bladder. Natural history and management perspectives]. / Tumeurs intra-diverticulaires de la vessie. Histoire naturelle et perspectives d'approche.

The review of the literature and our study of 15 tumors in bladder diverticula (IDT) show us that these tumors are rare and mainly observed in elderly adult males. Bleeding is the major symptom. Diagnosis is difficult and treatment is not well defined. Prognosis is good for low stage tumors and catastrophic in the short term for high stage tumors. Nearly half of IDT were primary tumors, and one third of them stay primary until death of the patients. Most of the high stage tumors contained a squamous cell differentiation and all the tumors with these features were deeply invasive. The bad prognosis is mainly related to the difficult and delayed diagnosis, with a long symptomatic period, regardless of treatment. This emphasizes the need for further investigations (biopsies, sonography, computer tomography) when the diagnosis is not evident. The treatment of these tumors depends on the general status of patients and the volume and stage of tumors. Low stage tumors (Ta) and diverticula could be treated either by transurethral resection or by open surgery with good results. In (T1) tumors, only open surgery is recommended to avoid loco-regional relapse. High stage tumors (greater than or equal to P T3) were treated by either TUR or open palliative surgery with the same bad prognosis. No radical treatment was indicated since patients have a bad performance status and most of the tumors extended beyond the diverticulum. Adjuvant treatments were not helpful. While preventive diverticulectomy is to be discussed case by case, we think that an important step in improving the prognosis of these tumors is to make the diagnosis at an earlier stage.