Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.

The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.

[Entero-urinary fistula]. / Les fistules uro-digestives.

AIM: To present the results of the diagnostic and the management of entero-urinary fistulae. METHODS: we performed a retrospective study on 18 patients with entero-urinary fistulas that had been diagnosed and treated at the Hospital Ibn Sina Rabat during the period spanning 1989-2006 RESULTS: The surgery was the main etiology of fistulas. The location was colo-vesical in 2 cases, prostato-rectal in 7 cases, vesico-rectal in 2 cases, uretero-colic in 3 cases, uretro-rectal in 3 cases and uretero-ileal in 1 case. The clinical manifestations were principally urological in the form of recurrent urinary infection, pneumaturia and fecaluria. The most useful diagnostic techniques were voiding retrograde cystourethrography and abdominal CT scan showing the fistulae in 12 cases. Treatment was by surgery in 15 cases. The transperitoneal way was adopted for the upper tract fistulas and the way of York Mason preferred for the lower urinary tract fistulas. No complications have been reported in the follow-up of these patients. CONCLUSION: Although the diagnosis of entero-urinary fistulae seems easy, the management remains difficult. It depends on its location and on the general state of the patient. He must be appropriate to avoid a recurrence which the management would be more complicated.

[Ureterocele in adults based on a series of 14 cases]. / Urétérocèle de l'adulte. A propos de 14 cas.

OBJECTIVE: To evaluate the efficacy of endoscopic meatotomy in the treatment of ureterocele in adults and to determine the incidence of its main complication, vesico-ureteric reflux. MATERIAL AND METHOD: Retrospective study of 14 cases of ureterocele in adults observed between March 1989 and August 2004, corresponding to 7 males and 7 females with a mean age of 39 years (range: 17-73 years). The ureterocele was observed in a context of single ureter in 13 cases (94%) and duplicated ureter arising from the superior renal unit in one patient (7%). The ureterocele was complicated by stones in 9 cases (64%). Endoscopic meatotomy was performed in 13 patients, while immediate resection of the ureterocele followed by Hendren ureterovesical reimplantation was performed in one patient with major proximal repercussions. RESULTS: The postoperative course was uneventful in all patients including the patient treated by conventional surgery. Postoperative follow-up consisted of clinical and radiological assessment at 3 months and 6 months. Endoscopic treatment was effective in every case with resolution of low back pain and absence of residual stones when the ureterocele was initially complicated by stones. In contrast, de novo vesicoureteric reflux appeared secondarily in 5 patients (38.5%) but persisted at 6 months in only one patient, who required re-operation: resection of the ureterocele and Hendren ureteric reimplantation. CONCLUSION: Endoscopic meatotomy can be considered to be the firstline treatment for ureterocele in adults in the absence of severe dilatation of the proximal urinary tract. Its main complication remains vesico-ureteric reflux. Radiological surveillance by urethrocystography therefore appears to be essential.

Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery.

UNLABELLED: Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). All patients with metastatic melanoma treated with ipilimumab from June 2010 to September 2012 were identified and stratified by presence (A) or absence (B) of brain metastases at the time of ipilimumab administration. All patients with brain metastases received SRS. Overall survival (OS) was defined as time from the date of stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and Cox proportional hazards model was employed to compute the hazard ratios (HR). RESULTS: Five out of 10 patients in Cohort A and 10 out of 21 patients in Cohort B died as of last follow-up. In Cohort A, median number of lesions treated with SRS was 3. Median survivals from date of stage IV for Cohorts A and B were 29.3 and 33.1 months, respectively (HR = 0.93, P = 0.896). Median survival from cycle 1 ipilimumab was 16.5 and 24.5 months for Cohort A and B, respectively (HR = 1.05, P = 0.931). The 3-year survival rates from the date of cycle one of ipilimumab administration for Cohort A and B were 50% (95% CI: 27-93%) and 39% (95% CI: 19-81%), respectively. Eight of 10 patients in Cohort A maintained a good PS. Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases.

[Endoscopic realignment for post-traumatic rupture of posterior urethra]. / Le réalignement endoscopique dans la rupture post-traumatique de l'urètre postérieur.

PURPOSE: To analyse the long-term results of treatment of posterior urethral disruptions with endoscopic realignment, and to assess the efficacy, simplicity and benefit of this technique. MATERIAL AND METHODS: Between 1989 and 2001, thirty six patients were treated by endoscopic realignment for traumatic rupture of the posterior urethra. The analysis of the results took in consideration the quality of urinary stream, the continence and the erectile function. RESULTS: With a mean follow-up of thirty four months (12 to 72 months), the 36 patients treated by endoscopic realignment are continent and urinate with a satisfactory urine output. This result was obtained after internal urethrotomy in 13 patients (36.1%), and after transperineal urethroplasty in two patients. Only 7 patients (19.4%) developed an impotence. CONCLUSION: The endoscopic realignment can be considered like initial treatment of all post-traumatic rupture of the posterior urethra. This simple and little aggressive technique doesn't compromise the recourse to another type of ulterior treatment and resulted in negligible morbidity. The secondary urethral strictures are short and accessible to an endoscopic urethrotomy.

[Urinary bladder mesonephric clear cell adenocarcinoma]. / Adénocarcinome à cellules claires de type mésonéphrique de la vessie.

Mesonephric adenocarcinoma of the urinary bladder is a rare tumour, whose origin is still uncertain. The authors report the case of a 19-year old woman hospitalized for a huge pelvic mass revealed by hematuria. Trans-urethral biopsy showed the mesonephric nature of this mass. The treatment consisted of an anterior pelvectomy with total colpectomy, associated to complementary radiotherapy. With a follow-up of 30 months, the patient is still alive without recurrence or metastasis. The etiopathogenic, histologic and therapeutic aspects of this tumour are reviewed.

A huge renal cyst mimicking ascites: a case report.

BACKGROUND: Renal cysts are common in old patients, and usually remain untreated. Giant renal cyst measuring more than 15 cm in diameter and containing more than 1500 mls of serous fluid are rarely seen. We report a case of a 75-year-old man with a giant right renal cyst. CASE PRESENTATION: A 75-year-old man presented with a five years history of suprapubic pain, abdominal distension. He had no urological symptoms. Physical examination revealed a distended abdomen with shifting dullness. Routine hematology, biochemistry, and serum tumor markers were within normal limits. Erroneously diagnosed as ascites on ultrasonographic examination. Abdominal paracentesis of supposed ascites was performed. The diagnosis of giant renal cyst was finally made by Computed tomography (CT) and patient underwent continuous percutaneous catheter drainage with negative pressure, whereby 8 liters of fluid were removed with negative cytology. Subsequent Computed tomography after 6 months revealed disparition of the cysts, and the patient remained asymptomatic. CONCLUSION: Giant renal cysts are uncommon; we conclude that the CT remains the best exam in patients evaluated for giant renal cyst. This to the best of our knowledge is the largest renal cyst in the medical literature. Studies are needed with particular attention to the factors associated with renal cyst enlargement.

Ultra-low flow liquid chromatography assay with ultraviolet (UV) detection for piperine quantitation in human plasma.

A robust and sensitive ultra-low flow liquid chromatography (UFLC) method that can reproducibly, at reasonable cost, detect low concentrations of piperine from human plasma is necessary. Piperine in plasma was separated and quantified by a gradient method using ultraviolet detection at a maximal absorbance wavelength of 340 nm. An aliquot was injected onto a reversed-phase column Waters SymmetryShield, 2.1 x 100 mm, 3.5 microm, C(18) column, attached to a Waters absorbosphere, 4.6 x 30 mm, C(18) guard column and eluted with a mobile phase containing a mixture of acetonitrile/water/acetic acid (25:74.9:0.1, v/v/v) on line A and acetonitrile/acetic acid (99.9:0.1, v/v) on line B. The flow rate was 0.3 mL/min. The gradient method consisted of an opening condition of 20% pump B, with a linear increase to 37% pump B over 8 min, then a linear increase to 100% pump B at 11 min, 2 min at 100% pump B, and then a return to the opening condition (20% pump B) via a linear gradient over 2 min, followed by 5 min re-equilibration at opening conditions. The total run time was 20 min for each sample. All samples were processed protected from ambient light to avoid isomerization of piperine. The plasma assay was linear with R = 0.9995, with a lower limit of detection [signal-to-noise (S/N) > 5:1] of 100 pg of piperine loaded into the analytical system with acceptable accuracy and precision. Extraction recoveries of piperine from human plasma were 88% for quality control high (QCH), 93% for quality control medium (QCM), and 90% for quality control low (QCL), and the matrix effect was <12%. Piperine was quantifiable from a 50 mg oral dose given to human volunteers. A UFLC method for the rapid assay of human plasma with sensitivity to detect as low as 5 ng/mL piperine was developed. The method sensitivity equals that of liquid chromatography/tandem mass spectrometry (LC/MSMS) methods with much less cost.