[Assessment of the optimization of the conditions of mitomycin C intravesical instillation completion in the setting of non-muscle invasive bladder cancer treatment]. / Évaluation de l'optimisation des conditions de réalisation des instillations endo-vésicales de mitomycine C dans le traitement des tumeurs de vessie non infiltrant le muscle.

OBJECTIVE: The efficacy of intravesical instillation of mitomycin C (MMC) requires alkalinisation and concentration of urine before each instillation. The objective of the study was to assess compliance and effectiveness of urine alkalinazation and fluid restriction protocols in patients treated with intravesical instillations of MMC for TVNIM. MATERIAL ET METHOD: Descriptive prospective epidemiological study in all patients consecutively treated with intravesical instillations of MMC for non-muscle invasive bladder cancer (NMIBC). Patients should be advised to drink 2 liters of water from Vichy and to perform fluid restriction the day before the instillations. Before each instillation, a questionnaire on the implementation of these measures was filled, density and pH were determined by urinalysis strips. RESULTS: On 126 questionnaires fulfilled, 117 patients (93%) and 106 patients (84%) reported having made alkalinization and fluid restriction, respectively. Ninety-one of patients (78%) reported having performed alkalinization had a pH greater than or equal to 6.5 and the mean urinary pH was 6.94 vs. 5.94 in patients stating not to have made alkalizing (P=0.0001). No significant differences in urine density according to fluid restriction was found. CONCLUSION: The observance of the instructions regarding urine alkalinization before MMC instillations was satisfactory and has achieved a sufficiently high urinary pH to prevent degradation of the product in 91% of cases. Conversely, the fluid restriction was not followed closely and has not shown its effectiveness on the concentration of urine.

Pterygium recurrence following preoperative topical Mitomycin C and 5-Fluorouracil eyedrops.

INTRODUCTION: Various adjuvant therapies have been used to prevent recurrence after pterygium excision. However, no single agent has been proven to be a gold standard for completely preventing recurrence with no associated complications. PURPOSE: This study aims to compare the recurrence rate following preoperative topical mitomycin C (MMC) and 5-fluorouracil (5-FU) eye drops in pterygium excision surgery. METHODS: In this interventional longitudinal comparative study, 90 patients with primary pterygium attending the Ophthalmology Clinic were enrolled and randomized into three equal groups of 30 each. Groups A, B, and C received preoperative 0.02% MMC eye drops, 1% 5-FU eyedrops, and placebo treatment respectively for one week before surgery followed by pterygium excision with conjunctival autograft and histopathological analysis. Patients were followed for 6months to identify recurrence. RESULTS: At the end of the 6months, the recurrence rate in the preoperative MMC group (6.7%) was less than the 5-FU (13.3%) and placebo (20%) groups. The histopathological findings were consistent with pterygium tissues. There were high grades of inflammation, degeneration, and vascularization in both the MMC and 5-FU groups in the specimens which recurred within a period of 6months. Five patients had a novel finding of smooth muscle choristoma tissue with bundles of smooth muscle cells and fat cells clustered among the conjunctival tissue. CONCLUSION: Based on our study results, we demonstrate that preoperative topical MMC and 5-FU eyedrops have efficacy in reducing recurrence in pterygium surgeries. The eyedrop route of administration has been proven to be an effective and easier alternative, enabling us to monitor for adverse effects of adjuvant drugs. Histopathological evaluation provides indices to predict features of future recurrence in pterygium specimens. This is the first study in which the efficacy of preoperative MMC and 5-FU is studied in eyedrop formulation along with histopathological correlation with recurrence.

[CCAFU Recommendations 2013: Bladder carcinoma]. / Recommandations en onco-urologie 2013 du CCAFU : Tumeurs de la vessie.

INTRODUCTION: The objective was to update the guidelines of the French Urological Association Cancer Committee for non invasive (NMIBC) and invasive bladder cancer (MIBC). METHODS: A Medline search was performed between 2010 and 2013, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. RESULTS: Diagnosis of NMIBC (Ta, T1, CIS) depends on cystoscopy and complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan, MRI and FDGPET remain optional. Cystectomy associated with extensive lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples, otherwise trans-ileal ureterostomy is recommended as urinary diversion. The interest of neoadjuvant chemotherapy is well known for advanced MIBC as T3-T4 and/or N1-3. As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when status (PS<1) and renal function (creatinine clearance > 60 ml/min) permits (only in 50% of cases). In second line treatment, only chemotherapy using vinfluvine has been validated to date. Conclusion.-These new guidelines will hopefully contribute not only to improve patient management, but also diagnosis and treatment for NMIBC and MIBC.

Haze prevention following photorefractive keratectomy in brown eyes.

OBJECTIVES: To study corneal haze following myopic photorefractive keratectomy (PRK) in a high-risk population and to assess methods for minimizing the risk. METHODS: The medical records of 150 patients who underwent PRK were reviewed. A total of 300 eyes were included. All patients underwent myopic PRK using the Allegretto Wave Concerto 500Hz (Wavelight AG, Erlangen, Germany)excimer laser platform with intraoperative mitomycin-C (MMC) application. Demographic data including age, gender and ethnicity in addition to preoperative and postoperative subjective manifest refraction, spherical equivalent, best-corrected distance visual acuity, uncorrected distance visual acuity (UDVA), postoperative corneal haze grade and other possible postoperative complications were retrieved. Hanna grading (0-4+) was used to evaluate corneal haze. RESULTS: The patients were comprised of 74 men (49.3%) and 76 women (50.7%). The mean age at the time of surgery was 26.5±6.0 (range, 17-46) years. All patients were Saudis with brown irides. UDVA improved to 20/25 in 93.8% at 3 months. The mean and standard deviation of preoperative spherical equivalent was -3.02±1.63 (range, -7.63 - -0.13). At 3 months, postoperative spherical equivalent improved to 0.05±0.50 (-1.00 - +1.00). At 6 months, 13.6% exhibited corneal haze of grade 1, and none exhibited grades 2 or 3. CONCLUSIONS: The results of this study confirmed that patients with brown irides can achieve favorable outcomes after PRK. MMC, postoperative topical steroids and ultraviolet protection evidently play a major role in preventing corneal haze in high-risk populations.

Corneal haze post photorefractive keratectomy.

Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.

[Fanconi anemia at the University Hospital (CHU) Hassan II of Fez: about 6 cases]. / Anémie de fanconi au CHU Hassan II Fès: à propos de 6 observations.

Fanconi anemia is a recessive disorder associated with chromosomal instability. It is marked by phenotypical heterogeneity which includes medullary deficiency, a variable malformation syndrome, a predisposition to develop acute leukaemias myéloïdes (ALM) and a cellular over-sensitiveness with the agents bridging the ADN. The diagnosis is based on the abnormal increase in the rate of spontaneous breaks chromosomal but especially and in a specific way, on a clear increase in these chromosomal breaks in the presence of bifunctional alkylating agents, which is the case in our six patients. Genetic counseling is that available for autosomal recessive diseases. We report our initial observations conducted at the University Hospital (CHU) Hassan II of Fez confirmed by the detection of a large chromosomal instability after culture with Mitomycin C compared to a normal control group. The purpose of this study was to update our knowledge of Fanconi anemia genes and to highlight the role of cytogenetics in its diagnosis and the genetic counseling for better management of affected children and their families.

[Thrombotic microangiopathy and cancer]. / Microangiopathie thrombotique et cancer.

Thrombotic microangiopathy (TMA) is a group of disorders characterized by mechanical hemolytic anemia with thrombocytopenia and an ischemic organic lesion of variable and potentially fatal importance affecting mostly the kidneys and the brain with histologically a disseminated and occlusive microvasculopathy. The incidence of TMA represents 15% of acute kidney failure in oncological setting, largely due to the introduction of anti-angiogenic agents over the past decade. It may be more rarely related to cancer itself. The iatrogenic TMA can be classified into 2 types: The type I, secondary to chemotherapy (mitomycinC, gemcitabine), exposes to a chronic dose-dependent renal injury as well as an increase in morbidity and mortality; iatrogenic type II, secondary to anti-angiogenic agents', results in a dose-independent renal involvement and renal functional recovery is usual when the drug is discontinued. There is no randomized controlled trial to establish EBM-type management in TMA support. However, complement activation pathways and regulatory factors analyses allowed us to understand the mechanisms of endothelial lesions. As a result, the current trend includes the use of immunosuppressive agents in recurrent or plasmapheresis-refractory MAT.

Cytomorphological effects of mitomycin C on urothelial cells: eosinophils may be clue to the drug-induced changes.

Cytomorphological changes of mitomycin C on urothelial cells may be misinterpreted as a neoplastic process. A 60-year old male patient who was given an eight-week course of intravesical mitomycin C due to non-invasive low grade transitional cell carcinoma. During his follow-up care, the findings of a urine cytology exam were as follows: nuclear enlargement of cells, wrinkled nuclear membranes, little hyperchromasia, pleomorphism, abnormal nuclear morphology and disordered orientation of the urothelium. Furthermore, there were eosinophils nearby the atypical cells. This report aimed at reminding the cytomorphologic changes of mitomycin C may be misinterpreted as carcinoma, so the presence of eosinophils is required to predict the drug-induced changes.