[Prospective evaluation of the direct costs of prostate enucleation by the HoLEP® laser during the learning curve period]. / Évaluation prospective des coûts directs de l'énucléation prostatique par le laser HoLEP® pendant la courbe d'apprentissage.

OBJECTIVE: Holmium laser enucleation of the prostate (HoLEP) has been shown to be effective in treating large prostates compared to prostate transurethral resection (TURP). There are no published data evaluating specifically the impact of the learning curve on the direct costs of HoLEP. The objective of this study was to evaluate the direct costs generated by the use of HoLEP laser during the learning curve period. METHOD: The costs of all medical devices (DM) and drugs used, pre- and post-operative parameters during surgery have been prospectively collected between March and October 2016. RESULTS: A total of 32 patients were included in the study with a mean age of 70.8 years and a mean prostate volume of 68.6 cm3. The mean cost of anesthesia was 39.0 € and that of drugs and DM used for surgery was 257.95 € but could reach 470.76 € in case of conversion to bipolar resection. The mean duration of enucleation and morcellation was 150minutes with a mean weight of enucleated specimens of 40.4g. The total mean duration of patient care was 197minutes at an estimated hourly cost of € 636. CONCLUSIONS: Despite some limitations, this study makes it possible to analyze the direct costs of the management of benign prostatic hypertrophy using HoLEP, an innovative surgical technique, and to specify that these costs are more related to bipolar conversion and voluminous adenomas especially during the learning curve. LEVEL OF EVIDENCE: 5.

Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study.

BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

From individual to collective displacements in heterogeneous environments.

Animal displacement plays a central role in many ecological questions. It can be interpreted as a combination of components that only depend on the animal (for example a random walk) and external influences given by the heterogeneity of the environment. Here we treat the case where animals switch between random walks in a homogeneous 2D environment and its 1D boundary, combined with a tendency for wall-following behaviour (thigmotactism) that is treated as a Markovian process. In the first part we use mesoscopic techniques to derive from these assumptions a set of partial differential equations (PDE) with specific boundary conditions and parameters that are directly given by the individual displacement parameters. All assumptions and approximations made during this derivation are rigorously validated for the case of exploratory behaviour of the ant Messor sanctus. These PDE predict that the stationary density ratio between the 2D (centre) and 1D (border) environment only depends on the thigmotactic component, not on the size of the centre or border areas. In the second part we test this prediction with the same exploratory behaviour of M. sanctus, in particular when many ants move around simultaneously and may interact directly or indirectly. The prediction holds when there is a low degree of heterogeneity (simple square arena with straight borders), the collective behaviour is "simply" the sum of the individual behaviours. But this prediction breaks down when heterogeneity increases (obstacles inside the arena) due to the emergence of pheromone trails. Our approach may be applied to study the effects of animal displacement in any environment where the animals are confronted with an alternation of 2D space and 1D borders as for example in fragmented landscapes.

Second-line chemotherapy with pegylated liposomal doxorubicin and carboplatin is highly effective in patients with advanced ovarian cancer in late relapse: a GINECO phase II trial.

BACKGROUND: Platinum-based chemotherapy is standard second-line treatment of patients with advanced ovarian cancer (AOC) in late relapse. Pegylated liposomal doxorubicin (PLD) has significant single-agent activity in this setting. Therefore, we evaluated the use of PLD plus carboplatin in this patient population. PATIENTS AND METHODS: PLD 30 mg/m(2) followed by carboplatin at area under the curve (AUC) 5 mg.min/ml, repeated every 28 days for a maximum of nine cycles, was administered to 104 women with AOC relapsing >or=6 months after completion of first- or second-line therapy with platinum-taxane-based regimens. RESULTS: Overall response was 63%, with a 38% complete response, median progression-free survival of 9.4 months, and median overall survival (OS) of 32 months. Grade 3 or 4 neutropenia occurred in 51% of patients, but febrile neutropenia in only 3%. Nonhematologic toxic effects were primarily grades 1 and 2, with low rates of alopecia and neurotoxicity. CONCLUSIONS: PLD plus carboplatin is highly effective, prolongs OS, and is well tolerated in women with AOC in late relapse previously treated with both platinum and taxanes. Evaluation of this regimen in phase III trials is warranted.

[CDKN2A gene mutation and loss of p16 protein activity in a patient on levodopa presenting sporadic multiple primary melanoma]. / Mutation du gène CDKN2A et perte d'activité de la protéine p16 chez un malade traité par L-Dopa et atteint de mélanomes sporadiques multiples.

BACKGROUND: Cutaneous melanoma is a complex disease involving genetic and environmental factors. Levodopa has been incriminated in the development and/or progression of melanoma. OBSERVATION: We report the case of a man treated with levodopa and a dopadecarboxylase inhibitor for Parkinson's disease and presenting 22 cutaneous melanomas over a 4-year period. The patient is of phototype II and presents multiple nevi. Genetic analysis of predisposing genes demonstrated a CDKN2A mutation with loss of p16 activity. DISCUSSION: Multiple melanomas may be associated with genetic predisposition, and screening for the latter should be performed. The exceptionally high number of melanomas developed by our patient raised suspicions about levodopa, a precursor in melanin synthesis, as a potential inducer. Increased dermatologic controls and screening for predisposing genetic factors appear to us to be warranted in the event of melanoma development in patients on levodopa.

Ant navigation en route to the goal: signature routes facilitate way-finding of Gigantiops destructor.

We investigated in laboratory conditions how foragers of the tropical ant Gigantiops destructor develop individually distinctive landmark routes. Way-finding along a familiar route involved the recognition of at least two locations, nest and feeding site, and the representation of spatial relations between these places. Familiar visual landmarks were important both at the beginning and at the end of the foraging journey. A motor routine guided the ants at the start of their foraging path towards the first landmarks, which they learnt to pass consistently on the same side, before taking the next direction. At the last stage of the route, landmark recognition allowed them to pinpoint their preferred feeding site without using distant cues or odometric information. By contrast, ants en route to the goal were not systematically guided by a stereotyped sequence of snapshots recalled at each corresponding stage of the route. Each ant slalomed in an idiosyncratic distinctive way around different midway landmarks from a foraging excursion to the next, which induced a variability of the path shapes in their intermediate parts. By reducing the number of landmark recognition-triggered responses, this economical visuomotor strategy may be helpful in the Amazonian forest where many prominent landmarks are alike.

Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: This study was conducted to assess the antitumour activity of docetaxel in combination with doxorubicin for neoadjuvant therapy of patients with breast cancer. PATIENTS AND METHODS: Forty-eight women were treated with intravenous doxorubicin 50 mg/m(2) over 15 min followed by a 1-h infusion of docetaxel 75 mg/m(2) every 3 weeks for six cycles. Dexamethasone or prednisolone premedication was allowed. Granulocyte colony-stimulating factor was not allowed as primary prophylaxis. The primary end point was the pathologically documented complete response rate (pathological response). RESULTS: The mean relative dose intensity calculated for four or more cycles was 0.99 for doxorubicin and 0.99 for docetaxel. Overall, the pathological response rate was 13%. There were 11 complete and 29 partial clinical responses for an overall response rate of 85% [95% confidence interval (CI) 75% to 95%] in the evaluable population (n = 47). Disease-free and overall survival rates were 85% (95% CI 71% to 94%) and 96% (95% CI 85% to 99%), respectively, after a median follow-up of 36.6 months. Grade 3/4 neutropenia was observed in 65% of patients and 17% reported grade 4 febrile neutropenia. CONCLUSIONS: Docetaxel and doxorubicin is an effective and well-tolerated combination in the neoadjuvant therapy of breast cancer. Future controlled trials are warranted to investigate the best schedules and to correlate response with biological factors.

[Palpable mantel cell lymphoma in the breast]. / Localisation mammaire et palpébrale d'un lymphome du manteau.

BACKGROUND: Extranodal involvement is not unusual in mantle cell lymphoma (MCL) which accounts for 6% of non-Hodgkin's lymphomas. Simultaneous localization in the eyelid and in the breast, as observed in our case, is however exceptional. CASE REPORT: Chronic lymphoid leukemia (CLL) was suspected in a 71-year-old woman with asthenia, a cervical and axillary nodal enlargement and elevated lymphocyte count. Blood immunoflow cytometry analysis, occurrence of rapidly growing tumors involving the two breasts and eyelids and cytogenetic and molecular features led to the diagnosis of MCL. A very good partial remission was obtained with second-line polychemotherapy composed of cytarabin, cisplatin and dexamethasone, but lasted only 3 months after the end of 6 cycles. DISCUSSION: Primary breast and eyelid lymphomas are rare. Such localizations are exceptional in MCL and are signs of aggressive disease. Before extra-nodal involvement, MCL may simulate banal CLL. Therefore, systematic immunohistochemistry and if necessary molecular analysis are useful for early diagnosis of MCL. Prognosis is particularly poor. Conventional chemotherapy cannot provide cure of MCL and median survival is 48 months. For this reason, high-dose chemotherapy with stem cell graft has to be discussed in young patients. MCL is currently characterized by Bcl1 rearrangement, t(11-14) translocation and cyclin D1 overexpression among small B-cell lymphomas in recent REAL- and WHO-classifications.

[Inverted papilloma of the pyelo-ureteral junction, current literature data]. / Papillome inversé de la jonction pyélo-urétérale, données actuelles de la littérature.

The authors report the fourth case of inverted papilloma of the ureteropelvic junction since the first description of this lesion in 1963 by Potts and Hirst. In view of the rarity of this lesion and its unusual presentation, they conducted an exhaustive review of the literature concerning inverted papillomas of the upper urinary tract. This proliferative lesion of the urothelium can precede, accompany or follow superficial or invasive urothelial tumours. Rigorous treatment and surveillance are therefore justified to detect an associated tumour. The controversy concerning the benign nature of inverted papilloma has still not been clarified.

Multilocus enzyme analysis in aerobic and anaerobic bacteria using gel electrophoresis-nitrocellulose blotting.

An optimized multilocus enzyme electrophoresis method, which involves polyacrylamide-agarose gel electrophoresis followed by electrophoretic transfers on nitrocellulose sheets, was developed for the analysis of enzyme polymorphism in several aerobic and anaerobic bacterial species including Staphylococcus aureus, Streptococcus pneumoniae, S. agalactiae, Klebsiella pneumoniae and K. oxytoca, Clostridium bifermentans and C. sordellii, and Prevotella bivia. Serial electrophoretic transfers (during 5-15 min each) from a single polyacrylamide gel could be achieved for most enzymes studied, and allowed an increased definition of enzyme bands on nitrocellulose as compared to migration gels. Four enzymes, which could not be blotted in such conditions, could still be stained in gels after blotting. Thus, the method allowed the combined analysis of several enzymes after a single gel electrophoresis separation. The analysis of enzyme polymorphism in the various species studied raised the interest of polymorphic loci such as esterase or glutamic-oxaloacetic transaminase for epidemiologic studies. The method characterized a genetic diversity of enzyme loci of S. pneumoniae higher than previously reported, and is thus convenient for the analysis of genetic relationships between related isolates. Since the present method reduces the tediousness of multilocus enzyme electrophoresis and requires experimental conditions that are not specific for the bacterial population studied, it may be proposed for rapid population genetics analysis of a wide variety of bacteria.

[Carotid surgery under loco-regional anesthesia. Early results of 100 recent cases]. / Chirurgie carotidienne sous anesthésie loco-régionale. Résultats précoces de 100 cas récents.

A prospective single-centre study was performed to evaluate the safety and efficacy of carotid revascularisation under local anesthesia. Between November 1, 1996 and March 30, 1998, 92 patients underwent surgery for 100 carotid artery stenoses under local cervical block anesthesia. Fifty-eight stenoses were asymptomatic and 42 were symptomatic. Duplex ultrasound scanning showed a tight (n = 17) or very tight carotid artery stenosis (n = 83); angiography showed 19 contralateral carotid artery stenosis and 30 hemodynamically significant stenosis of vertebral and/or subclavian arteries. Cerebral Magnetic Resonance Imaging (MRI) (N = 87) with circle of Willis Magnetic Resonance Angiogram (MRA) (n = 83) detected 29 ischemic defects (33%). Fifteen ischemic defects were found in 58 asymptomatic patients (26%). Circle of Willis was incomplete in 41%. Anesthesia was performed using superficial cervical block (n = 100). Endarterectomy was the most commonly used revascularisation technique in 86 cases with 5 eversion endarterectomies; carotid vein or prosthetic graft was used in 14%. In this study, there was no mortality, and no cardiac or neurologic complications, during the first postoperative month. Twelve patients experienced neurologic intolerance to carotid clamping. This clamping-related ischemia required 4 shunts. All patients with clamping intolerance had a good clinical outcome after revascularisation with no objective or MRI sequelae. Incomplete circle of Willis on MRA was a significant predictive test of clamping intolerance (p < 0.0001). Carotid artery surgery under local anesthesia reduces the cumulative mortality and morbidity rate (TCMM) to a very low level: 0% in this study. These recent results are the modern reference for current carotid artery surgery evaluation.

Genetic relationships within the genus Prevotella analyzed by multilocus enzyme electrophoresis and DNA-DNA hybridization.

The genetic diversity and relationships within the genus Prevotella were studied by analyzing twenty-five strains by multilocus enzyme electrophoresis (MLEE) at nine metabolic enzyme loci and DNA-DNA hybridization. MLEE revealed a high genetic diversity with 25 electrophoretic types (ETs) for the 25 strains studied, a mean number of alleles per enzyme locus of 6.8 and a mean genetic diversity per locus of 0.786. The index of association described by Maynard Smith et al. (1993) revealed a clonal structure within the genus Prevotella. A dendrogram generated by cluster analysis of a matrix of ETs showed that species like P. bivia, P. buccae, P. oris, P. oralis, P. nigrescens, and P. denticola form clusters that are consistent with DNA homologies. However, strains identified as P. melaninogenica or P. loescheii by DNA-DNA hybridization did not constitute distinct subpopulations in MLEE. MLEE analysis demonstrated its high power in differentiating closely related strains. It provides an alternative to 16S rRNA analysis for the study of phylogenetic relationships within the genus Prevotella, especially for differentiating strains with high DNA homology or high rRNA homology.

Endopyelotomy with the Acucise cutting balloon device. Early clinical experience.

OBJECTIVES: To evaluate the efficacy of the Acucise balloon cutting device in the treatment of ureteropelvic junction (UPJ) stenosis. METHODS: Forty-four patients with primary (21) or secondary (23) UPJ stenosis underwent Acucise endopyelotomy between July 1992 and February 1995. RESULTS: The average operating time was 53 min and the average hospital stay was 6 +/- 4 days. The follow-up schedule included a symptom questionnaire, intravenous urography and diuretic renal scan. Of the 44 patients, 38 have been followed for a minimum of 3 months postoperatively (mean: 12 months, range: 3-39 months). Overall success was achieved in 29 (76%). The procedure was successful in 16 out of 19 cases (84%) with secondary strictures. When the technique was used for the treatment of primary UPJ strictures, the success rate was only 68% (13 out 19). The presence of a large periureteric urinoma was identified as the cause of failure in 2 cases of primary strictures. CONCLUSION: We recommend the use of the Acucise device as the first-line therapy for treatment of secondary UPJ stenosis (except in the presence of large enclosed stones). We do not approve the use of the Acucise device for treatment of primary UPJ strictures. In primary hydronephrosis, the negative role of periureteric extravasation probably explains the low success rate of 68% (as opposed to 85% for a large series of percutaneous endopyelotomies.

Ureteropelvic invagination procedure for endopyelotomy (Gelet technique): review of 51 consecutive cases.

Between 1990 and 1995, we performed 51 endopyelotomies on 38 cases of primary and 13 of secondary obstruction of the ureteropelvic junction (UPJ) using the ureteropelvic invagination technique. Of the 51 patients in the series, 49 have been followed for a minimum of 3 months postoperatively (mean follow-up 16 months). Overall, success was achieved in 38 (77.5%). Endoscopic endopyelotomy was successful in 11 of 13 cases (84.5%) with secondary strictures. When the technique was used for the treatment of primary UPJ stricture, the success rate was only 75% (27 of 36). The presence of a crossing vessel was identified as the cause of failure in five cases of primary strictures; hence, we advocate the use of angiography to identify crossing vessels preoperatively. We recommend the use of the ureteropelvic invagination technique as the first-line therapy for primary hydronephrosis in adults in the absence of a crossing vessel.

VAD-PECC regimen in the treatment of advanced-stage multiple myeloma.

PURPOSE: This prospective study was undertaken to evaluate the efficacy of combination chemotherapy with alternating cycles of vincristine, doxorubicin, and dexamethasone (VAD) and prednisone, vindesine, carmustine, and cyclophosphamide (PECC) in poor-risk multiple myeloma (MM). PATIENTS AND METHODS: Forty-four patients were previously untreated; 36 had been pretreated with an alkylating agent-containing regimen and had refractory or relapsed MM. All previously untreated patients had a high tumor burden at inclusion (stage III according to the Durie and Salmon classification). Logistic regression and the Cox proportional hazards models were used to assess the association between patient characteristics and response rate and survival, respectively. RESULTS: The overall response rate was 68% for previously untreated patients, compared with 54% for previously treated patients (P = .16). The median survival time for all patients was 28 months: 53 months in previously untreated patients, and 18 months in previously treated patients. Univariate analysis showed that the predictive factors that had a significant affect on survival in the newly diagnosed patients were age, therapeutic response to VAD-PECC, low pretreatment Karnofsky score, high baseline serum beta 2-microglobulin (beta 2M) level, bone marrow impairment, and renal insufficiency at the start of treatment. When these parameters were used as continuous variables in multivariate analysis, three were found to correlate with survival: serum beta 2M, followed by therapeutic response and Karnofsky score. In the previously treated group, only Karnofsky score entered the Cox model. CONCLUSION: These results indicate that combination VAD-PECC chemotherapy is an effective treatment that results in high response rates and long-term survival in advanced MM.

Clonal outbreaks of extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae demonstrated by antibiotic susceptibility testing, beta-lactamase typing, and multilocus enzyme electrophoresis.

Nineteen extended-spectrum beta-lactamase (ESBla)-producing Klebsiella pneumoniae isolates from Rouen Hospital were investigated for their implication in nosocomial outbreaks: in addition to antibiotic susceptibility testing, the ESBlas were characterized by isoelectric focusing, and the genetic relationships between the strains were analyzed by multilocus enzyme electrophoresis using a combined polyacrylamide electrophoresis-electrophoretic transfer technique. Four isoelectric focusing beta-lactamase patterns and 11 enzyme electrophoretic types (ETs) among the strains tested were described. Three strains isolated in the same neurological unit over a 7-day period exhibited an SHV 3 beta-lactamase (pI 7.0) and were assigned to a common ET. Three of five strains isolated from patients in a rehabilitation center over a 6-week period harbored an SHV 4 beta-lactamase (pI 7.8) and exhibited the same ET. These results differentiate nosocomial transmission from sporadic cases and provide evidence that multilocus enzyme electrophoresis is a potential tool for studying genetic relationships between strains harboring a common ESBla.

Multilocus enzyme typing of human and animal strains of Clostridium perfringens.

Multilocus enzyme electrophoresis was developed to evaluate the genetic diversity of 71 human strains and 17 animal strains of Clostridium perfringens. Crude protein extracts, obtained by sonication of washed bacteria, were analyzed by polyacrylamide-agarose gel electrophoresis to characterize electrophoretic mobility variants of seven enzymes (esterase, glutamate dehydrogenase, glutamic-oxaloacetic transaminase, nucleoside phosphorylase, phosphoglucose isomerase, phosphoglucomutase, threonine dehydrogenase). Genetic diversity of the enzyme loci ranged from 0.340 to 0.813. Sixty-nine electrophoretic types were described among the 88 strains tested and the index of discrimination was 0.994. All strains were typable, and epidemiological relationships between isolates could be established. This method showed a fair correlation with esterase electrophoretic typing based on hydrolytic and electrophoretic polymorphism of esterases. This work demonstrates that multilocus enzyme polymorphism is a reliable and discriminant marker of genetic diversity of strains of C. perfringens.

Electrophoretic transfer from polyacrylamide gel to nitrocellulose sheets, a new method to characterize multilocus enzyme genotypes of Klebsiella strains.

A new method for multilocus enzyme electrophoresis, based on electrophoretic transfers to nitrocellulose after polyacrylamide-agarose gel electrophoresis was explored. Electrophoretic separation was performed on 1-mm-thick slab gels with 6-mul samples of bacterial extracts and was followed by serial 5-min consecutive transfers. The transferability of 19 metabolic enzymes of Klebsiella strains was studied and allowed the simultaneous examination of one enzyme in the separation gel and at least five enzymes on nitrocellulose sheets. The resolution of enzyme bands was increased on nitrocellulose; thus, well-separated bands were recorded for nucleoside phosphorylase, peptidase, and phosphoglucose isomerase whereas their mobility variants could not be clearly distinguished in the separation gel because of stain diffusion. The study of genetic relationships of 42 strains of Klebsiella pneumoniae and 24 strains of Klebsiella oxytoca demonstrated the reliability of the method, since clustering analysis of electrophoretic types, based on electrophoretic polymorphism of 10 metabolic enzymes, showed two main clusters well correlated with the two species. The 57 electrophoretic types described confirm the usefulness of the method for the study of genetic relationships between closely related strains.