Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii, which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1ß (IL-1ß) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls (P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients (P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT (P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1ß gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT (P = 0.0494). The IL-10, IFN-γ, and IL-1ß polymorphisms influence the development of OT in the Colombian population.

Dysexecutive syndrome in amnesic mild cognitive impairment: a multicenter study.

BACKGROUND: Executive functions (EF) in Alzheimer's disease (AD), classically related to the prefrontal cortex, have been forgotten in mild stages, given more importance to temporal lobe associated disorders, such as memory. The study of disexecutive syndrome (DS) has been relegated to advanced stages of the disease. Our goal is to demonstrate that EF are already present in amnesic mild cognitive impairment (aMCI). Furthermore, we are interested in knowing whether poor scores in EF tests are related to the progression to AD or another kind of dementia. METHODS: We studied patients with aMCI (n = 81) and healthy controls (n = 142) from neurological departments of several centers of Basque Country with a cross-sectional design. Patients underwent a complete neuropsychological evaluation, neuroimaging testing APOE genotype and 3 year of prospective follow-up. RESULTS: In the first visit, patients with aMCI showed more alterations in tests that evaluate EF such as Stroop, trail-making and categorical verbal fluency. More alterations were also found in NPI scale (P <0.05). Stroop and Trail-Making test were not associated with the future development of AD, but fluency (p = 0.01) and apathy (p = 0.031) did. No patient developed a different kind of dementia different from AD. CONCLUSIONS: DS is a broad concept not confined to frontal lobes, and can be found in early stages of aMCI. DS impacts negatively on patient autonomy and may have prognostic value.

[Cryotherapy percutaneous for renal tumors: Our center's beginning experience]. / Cryothérapie pour les tumeurs rénales: le début d'expérience de notre centre.

OBJECTIVE: To evaluate oncologic and functional outcomes after percutaneous cryoablation (PCA) for renal masses based on our single center experience. PATIENTS AND METHODS: We retrospectively identified 26 patients who underwent PCA for 28 tumors between November 2006 and June 2011. Patient's demographics and baseline clinical characteristics, tumor features, perioperative information, and postoperative outcomes we rerecorded. A biopsy was performed systematically before each procedure. Control imaging was obtained at 1, 3, 6 and 12 months, and yearly thereafter. Oncological outcomes were determined by radiographic evidence of tumor recurrence, which was defined by contrast enhancement at the cryoablation site on control imaging at M3. RESULTS: Patients had mean age of 70.1 years, mean Charlson comorbidity index (CCI) and body mass index) were 6 and 29 kg/m(2) respectively. There were 11 kidney transplants, including 4 solitary. Mean tumor size was 29.5mm and was represented mainly by clear cell renal cell carcinomas (16/28), endophytic (17/28) and midkidney (14/28) (±9.8). Twenty-five cryoablations were performed percutaneously by two lumbotomy. Mean clearance preoperative MDRD was 66,1 mL/min. Mean length of stay was 3.3 days (±2.2). Intraoperative complications consisted of 2 pneumothorax and 6 minor complications postoperative (Clavien≤2). There were no major complications. Mean follow-up was 27.5 months (±15.7), MDRD clearance distance was 61.9 mL/min. Overall survival and disease-specific survival was 100%, while the recurrence-free survival was 78.6% (5 recurrences and 1 failure treatment). CONCLUSION: The percutaneous cryoablation provides a safe and oncologically to extirpative surgery for renal masses in patients with significant medical comorbidities. LEVEL OF EVIDENCE: 5.

[The W-shaped ileal neobladder: Long term functional outcomes and health-related quality of life]. / La néovessie iléale en W : résultats fonctionnels et qualité de vie à long terme.

PURPOSE: To evaluate functional outcomes and patients' health-related quality of life over ten years after a W-shaped ileal neobladder urinary diversion. PATIENTS AND METHODS: From 1994 to 2004, 87 patients with bladder cancer underwent a cystoprostatectomy with a W-shaped ileal neobladder. Among them, 31 patients (35.6%) were evaluated. The average follow-up was 158months, average age was 72years. We assessed functional outcomes (use of protections, USP score, uroflowmetry, postvoid residual volume), overall health-related quality of life (SF-36 score), and specific urinary-related quality of life (Ditrovie scale). RESULTS: Daytime continence was satisfactory in 29 patients (96.8%). Night-time continence was satisfactory in 27 patients (87.1%). Mean daytime continence, hyperactivity and dysuria scores of the USP were respectively 1.5/9, 3.2/21 and 2/9. Mean value of the maximum flow rate was 18mL/s for an average voiding volume of 324mL and an average postvoid residual volume of 70mL. The 8 dimensions of the SF-36 were all comparable with the French population's values. According to the Ditrovie scale whose average value was 1.83, the health-related quality of life was unchanged or little changed by urinary disorders in 28 patients (90.3%). CONCLUSIONS: Our results suggest that voiding status and health-related quality of life remain satisfactory over ten years after an orthotopic ileal neobladder derivation. LEVEL OF EVIDENCE: 5.

[Urological complications after kidney transplantation from extended criteria donors: Ureteroneocystostomy versus pyelo-ureterostomy]. / Complications urologiques après transplantation de reins issus de donneurs à critères étendus : anastomoses urétéro-vésicales versus anastomoses pyélo-urétérales.

INTRODUCTION: The use of transplants from extended criteria donors increases the number of urological complications after renal transplantation. Two different anastomosis techniques used to restore urinary continuity are compared in this study. PATIENTS AND METHODS: Retrospective study, bi-center over a period of 5 years. One hundred and seventy six patients operated at Hospices Civils de Lyon benefited from ureteroneocystostomy according to De Campos-Freire (group 1) and 167 patients operated at the Necker Hospital in Paris had a pyelo-ureterostomy (group 2). The various urological complications (fistulas, strictures, seromas, haematomas and vesico-ureteric reflux) and their care were compared. Risk factors were sought. RESULTS: The waiting time before transplantation was longer in group 2 than in group 1 (51 and 33.84 months) as the percentage of anuric patients (52.9 % against 32.9 %) (P<0.001). The cold ischemic time was shorter in group 1 (939.3minutes on average against 1325.3minutes for group 2) (P<0.001). A double J stent was put in place in 97.6 % of cases in group 2 against 84.2 % for group 1 (P<0.001). We did not find any significant difference in the occurrence of stenosis and fistulas (major complications) between the 2 groups. There were more minor complications (hematoma, seroma and vesico-ureteric reflux) in group 1 (P=0.033). There was a difference in the treatment of these complications, especially stenosis (P=0.024) with a significantly more conservative approach in group 2. Multivariate analysis found anuria, sex of recipients and donor age as independent risk factors in the onset of complications and the double J stent as a protective factor. CONCLUSION: This study does not demonstrate the superiority of a urinary anastomosis technique. The establishment of a double J stent reduces the risk of complications. Analysis of risk factors allows to propose a decision tree to guide the surgical strategy, particularly in the population of anuric recipients. LEVEL OF EVIDENCE: 5.

[Impact of neoadjuvant chemotherapy on therapeutic management of muscle-invasive bladder cancer]. / Impact de la chimiothérapie néoadjuvante sur la prise en charge des tumeurs de vessie infiltrant le muscle.

OBJECTIVE: Assess the toxicity of neoadjuvant chemotherapy (NAC), its impact on surgical schedule and postoperative morbidity of cystectomy for muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Retrospective multicentric study of 78 patients who underwent a cystectomy from January 2009 to March 2012 for MIBC. The following criteria have been studied: toxicity of NC (WHO classification), precystectomy interval, postoperative morbidity (Clavien), duration of stay, downsizing on CT-scan before cystectomy, and free of cancer pathology (pT0). RESULTS: Seventy-eight patients had been included, thirty-nine had a NAC. Thirty-three percent had a incomplete chemotherapy because of toxicity. Forty-eight percent had a significant toxicity and grade ≥ 3 toxicity was 33%. Median time between diagnosis and cystectomy was 12.6 weeks (0.7-38), 18 weeks with NAC (group 1) versus eight weeks without NAC (group 2) (P=0.01). In case of toxicity, the delay was 3.5 weeks longer (P=0.12). After cystectomy, 60% of patients had at least one postoperative complication; including 23% had major morbidity. NAC did not increase neither postoperative morbidity (P=0.15) nor duration of stay (18 vs 20 days; P=0.2). Radiological response rate to NC was 38%. pT0 rate was 79 vs 7.7%. The increase of precystectomy interval after NC did not worsen the pathological stage (P=0.5). CONCLUSION: NC had a high toxicity, but without impact on postoperative morbidity, and precystectomy interval did not have any impact on the prognosis. LEVEL OF EVIDENCE: 5.

[Effectiveness of flexible ureteroscopy versus extracorporeal shock wave lithotripsy for kidney stones treatment]. / Efficacité de l'urétéroscopie souple versus lithotritie extracorporelle dans le traitement des calculs du rein.

Primary endpoint was to objective a better effectiveness of flexible ureteroscopy (fURS) compared to extracorporeal shock wave lithotripsy (ESWL) 3 months after treatment of a unique kidney stone from 5 to 20mm. Secondary endpoints were to evaluate effectiveness in subgroup and tolerance. We conducted a prospective comparative randomised trial between May 2012 and February 2014. A computerised tomography was done before treatment and another 3 months after treatment. Of the 30 randomised patients, 8 dropped out from the study and 4 were lost to follow-up. Median time of follow-up was 3.82 months. In per-protocol analysis, success rate was 60% for fURS group versus 28.6% for ESWL group (P=0.29). In intention to treat analysis, success rate was 77.8% in fURS group versus 53.8% in ESWL group (P=0.38). In ESWL group, 5 patients (41.7%) needed a second treatment versus none in fURS group but it was not significant. During follow-up, 1 patient in each group presented a complication. Results of this feasibility study did not allowed to conclude on superiority of a technic. A multicenter study with more important enrollment is necessary considering economic side and tolerance of these treatments.

[Management of rectourethral fistulas with the York Mason procedure: surgical techniques and outcomes]. / Traitement des fistules uréthro-rectales par voie trans-anorectale de York Mason: technique et résultats.

OBJECTIVE: To report our experience for the management of urethro-rectal fistula by the York Mason technique. PATIENTS AND METHODS: We retrospectively analyzed the data of patients treated surgically for FUR by the technique of York Mason, between 2000 and 2012. RESULTS: Seventeen patients were included in the study. All patients had a bowel diversion before surgery. We observed four recurrences of FUR (23.5%). Recurrences occurred in a radiation field for two patients and in a oncologic recurrence for 1 patient. The fourth recurrence was treated by a second procedure of York Mason successfully. CONCLUSION: In our study, the York Mason technique was safe and reproducible for the treatment of FUR. The main factor of failure was a history of pelvic radiotherapy.

[A mini-invasive approach to renal autotransplantation in the management of loin pain hematuria syndrome]. / Approche mini-invasive de l'autotransplantation rénale dans la prise en charge du loin pain hematuria syndrome.

OBJECTIVE: To review retrospectively our experience with laparoscopic approach to renal autotransplantation in four patients using a single iliac incision in the management of loin pain hematuria (LPH) syndrome. METHODS: Four patients with LPH (all women, mean age 29.5 years, range 23-36 years) underwent four technically successful laparoscopic nephrectomies with renal autotransplantation, using a single iliac incision to both harvest and transplant the kidney. Hand assistance was used in two patients immediately before clamping the renal pedicle. All patients required narcotic analgesics preoperatively. RESULTS: Mean total surgical time was 4.1 hours. For laparoscopic donor nephrectomy phase, mean operative time was 1.9 hours. The warm ischemia time was 5 minutes. The cold ischemia time was 58 minutes. The hospital stay was 6 days. None of the patients had abnormal renal function postoperatively. Three of four patients had episodes of iliac fossa pain with effort at the level of the transplantation incision. Two of four patients became Morphine-free. The other two required a significantly reduced dose of oral narcotics. None of these patients required nephrectomy. (Median follow-up 9 months). CONCLUSION: Laparoscopic approach to renal autotransplantaion using a single extended iliac incision in the management of LPH syndrome can be considered as a less invasive treatment compared to open renal autotransplantation in selected patients. This technique may be extended to patients having other conditions requiring autotransplantation.

[New ultrasound navigational system in extracorporeal lithotripsy: decreased fluoroscopy and radiation]. / Nouveau repérage échographique en lithotritie extracorporelle: diminution des temps de scopie et de l'irradiation.

PURPOSE: Extracorporeal shock wave lithotripsy is the most common method of treatment for kidney stones. Both fluoroscopy and ultrasound imaging can be used to locate stones, but fluoroscopy is more frequently employed. Evaluation of a new stereotaxic navigational system: the stone was located using an ultrasound probe, and its 3D location was saved. The table automatically moved to position the stone at the focal point. A real-time follow-up was possible during treatment. Our objective was to demonstrate a decrease in the use of fluoroscopy to locate kidney stones for extracorporeal shock wave lithotripsy through the use of a 3D ultrasound stone locking system. PATIENTS AND METHODS: Prospective analysis of the case records of the 20 patients preceding and the 20 patients succeeding the arrival of the ultrasound stone locking system Visio-Track (EDAP-TMS). We used a Student test to compare age, BMI, kidney stone size, number of shock waves and administered energy. RESULTS: Patient characteristics were comparable. The average age was 55 years old and the average kidney stone size was 10.7 mm. Radiation duration was 174.8 seconds in the group without Visio-Track versus 57.1 seconds in the group with it (P<0.0001). A similar result was observed for radiation doses: 5197.25 mGy x cm2 for the group without versus 1987.6 mGy x cm2 for the group with Visio-Track (P=0.0033). CONCLUSION: The stone locking system Visio-Track reduced fluoroscopy in our first group of patients, which decreased the patient's individual absorbed irradiation dose.

Kidney graft outcome and quality (after transplantation) from uncontrolled deceased donors after cardiac arrest.

The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been developed in France to compensate for organ shortage. The quality of these kidneys remains unclear. We analyzed kidney graft function and histology from 27 uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal deceased donors. Kidneys from ECD and SPK donors were preserved by static cold storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA graft function at 3 years posttransplantation (estimated with MDRD and measured with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs. 37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07 in the uDDCA and ECD groups, respectively). The histological assessment of 3-month and 1-year protocol biopsies did not show differences for interstitial lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys and encourage continuation of this program and development of similar programs.

Uptake, efficacy, and systemic distribution of naked, inhaled short interfering RNA (siRNA) and locked nucleic acid (LNA) antisense.

Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) promise specific correction of disease-causing gene expression. Therapeutic implementation, however, has been forestalled by poor delivery to the appropriate tissue, cell type, and subcellular compartment. Topical administration is considered to circumvent these issues. The availability of inhalation devices and unmet medical need in lung disease has focused efforts in this tissue. We report the development of a novel cell sorting method for quantitative, cell type-specific analysis of siRNA, and locked nucleic acid (LNA) ASO uptake and efficacy after intratracheal (i.t.) administration in mice. Through fluorescent dye labeling, we compare the utility of this approach to whole animal and whole tissue analysis, and examine the extent of tissue distribution. We detail rapid systemic access and renal clearance for both therapeutic classes and lack of efficacy at the protein level in lung macrophages, epithelia, or other cell types. We nevertheless observe efficient redirection of i.t. administered phosphorothioate (PS) LNA ASO to the liver and kidney leading to targeted gene knockdown. These data suggest delivery remains a key obstacle to topically administered, naked oligonucleotide efficacy in the lung and introduce inhalation as a potentially viable alternative to injection for antisense administration to the liver and kidneys.

[Treatment of stress urinary incontinence after prostate surgery: results of the artificial urinary sphincter after suburethral sling failure]. / Traitement de l'incontinence urinaire d'effort après prostatectomie : résultats du sphincter urinaire artificiel après échec de bandelette sous-urétrale.

OBJECTIVE: To determine whether the presence of a previously implanted suburethral sling for post-prostatic surgery incontinence influences the outcomes of subsequent AUS implantation. PATIENTS AND METHODS: A retrospective study comparing 15 patients who underwent AUS placement after suburethral sling failure between November 2004 and December 2009 to 15 patients who underwent AUS placement as first-line treatment during the same period. Demographic characteristics, preoperative assessment of urinary incontinence and technique of implantation of the AUS were similar in the both arms. A USP(®) continence questionnaire was sent to patients by mail. Success was defined as a subjective improvement of the incontinence in patients using less than one pad per day. RESULTS: No perioperative incidents were noted in either arm. Mean operative time, the size of implanted cuffs, duration of catheterisation, length of hospital stay and postoperative complication rate, as well as the rate of surgical revision, were similar in both arms. The follow-up was slightly lower in the first arm (21 vs. 28.8 months, P=0.83). Stress incontinence and bladder overactivity scores of the USP(®) questionnaire, as well as success rates (73.3 vs. 80%, P=0.67), were equivalent in both arms. CONCLUSION: The results associated with the AUS procedure were not significantly different between men who had a suburethral male sling implanted before and those who had the AUS implanted as a first-line treatment.

[Partial versus radical nephrectomy for renal cell carcinoma involving peri renal fat. Oncological and functional outcomes]. / Néphrectomie partielle versus élargie en cas d'envahissement de la graisse périrénale. Résultats oncologiques et fonctionnels.

PURPOSE: In the latest guidelines of the European Association of Urology, partial nephrectomy was a reference standard in tumors less than 7cm confined to the kidney. The invasion of the perirenal fat and therefore dissection in a potentially tumor tissue with an increased risk of recurrence. MATERIAL: From 1995 to 2009, we retrospectively evaluated the oncological outcomes of partial versus radical nephrectomy in tumors with local extension beyond the boundaries of the kidney, without adrenal involvement or metastatic lymph node extension. We evaluated the histological factors influencing the prognostic. RESULTS: A total of 43patients have been included (ten partial and 33radical nephrectomy). We did not found any significant difference in terms of specific and recurrence-free survival between partial and radical nephrectomy in tumor invading the perirenal fat (P=0.739 and P=0.683 respectively). Factors influencing the prognosis were the Fuhrman grade (P=0.010), the invasion of the urinary tract (P=0.017) and the presence of a positive surgical margin (P=0.041). The renal function was better after partial nephrectomy. The complication rate was similar between partial and radical nephrectomy. CONCLUSION: The perirenal fat invasion by kidney tumor did not impact the oncological outcomes of partial versus radical nephrectomy with better functional outcomes for partial nephrectomy.

Long-term follow-up in composite tissue allotransplantation: in-depth study of five (hand and face) recipients.

Composite tissue allotransplantations (CTAs) have clinically shown little, if any, evidence of chronic rejection. Consequently, the effect of chronic rejection on bones, joints, nerves, muscles, tendons and vessels may still have undescribed implications. We thoroughly assessed all allograft structures by histology, magnetic resonance imaging, ultrasonography and high resolution peripheral quantitative computed tomography scan in four bilateral hand-grafted patients (10, 7, 3 and 2 years of follow-up, respectively) and in one facial allotransplantation (5 years of follow-up). All the recipients presented normal skin structure without dermal fibrosis. Vessels were patent, without thrombosis, stenosis or intimal hyperplasia. Tendons and nerves were also normal; muscles showed some changes, such as a variable degree of muscular hypotrophy, particularly of intrinsic muscles, accompanied by fatty degeneration that might be related to denervation. In the majority of hand-grafted patients graft radius and recipient tibia showed a decrease in trabecular density, although in the graft radius the alterations also involved the cortices. No deterioration of graft function was noted. In these cases of CTA no signs of chronic graft rejection have been detected. However, the possibility that chronic rejection may develop in CTA exists, highlighting the necessity of close continuous follow-up of the patients.

Progression from amnesic mild cognitive impairment to Alzheimer's disease: ESR1 and ESR2 polymorphisms and APOE gene.

BACKGROUND: Many genes have been studied to determine how they might be involved in Alzheimer's disease (AD). Estrogens have a protective effect in the central nervous system. The mechanisms of action of estrogens are mediated by two estrogen receptors (ERs), ERα and ERß. Thus, these genes could also play a role in the progression of amnesic mild cognitive impairment (MCIa) to AD. The aim of this study was to examine the role of ER single nucleotide polymorphisms (SNPs) as a risk factor for MCIa, as well as the interaction with apolipoprotein E (APOE) ε4 in the progression to AD. METHODS: 79 MCIa patients and 138 healthy controls were analyzed. SNPs were genotyped via restriction fragment length polymorphisms and real-time PCR, RT-PCR or RT-PCR (TaqMan) assays. RESULTS: There is a lack of association between MCIa patients who converted to AD and ER SNPs. APOE ε4 allele is an independent risk factor of MCIa (OR=1.86; 95% CI=1.02-3.38, p=0.042) with a high prevalence in converted subjects. APOE ε4 is able to predict the progression from MCIa patients to AD (OR=2.55; 95% CI=1.20-5.42, p=0.015). CONCLUSIONS: The presence of the APOE ε4 allele, and not the alleles of ER SNPs, is a risk factor for MCIa. Furthermore, APOE genotype seems to predict the conversion from MCIa to AD.

Intra-operative 3.0 T magnetic resonance imaging using a dual-independent room: long-term evaluation of time-cost, problems, and learning-curve effect.

We present a short and comprehensive report of our 39-month experience using a 3.0 T intra-operative magnetic resonance imaging (ioMRI) neurosurgical-MR twin room, including a description of the problems encountered and the associated time-delays. Forty-seven problems were experienced during the 189 ioMRI procedures (two ioMRI were performed in five of the 184 surgical procedures) performed in the 39-month period, including a blocked transfer table, failure of anesthetic monitoring material, and specific MRI-related problems, such as head and coil positioning difficulties, artefacts, coil malfunctions and other technical difficulties. None of these problems prevented the ioMRI procedure from taking place or affected image interpretation, but they sometimes caused a significant delay. Fifteen (32%) of these problems occurred during the initial learning curve period. The mean duration of the ioMRI procedure was 75 min, which decreased slightly with experience, although an average waiting-for-access time of 24 min could not be avoided. These results illustrate that although performing ioMRI at 3.0 T with the dual room is a challenging procedure, it remains safe and feasible and associated with only minor dysfunctions while offering optimal image quality and standard surgical conditions.

[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.

[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.

Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study.

BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). METHODS: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed. RESULTS: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%). CONCLUSION: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov reference NCT00563953.