Viral persistence in surface and drinking water: Suitability of PCR pre-treatment with intercalating dyes.

After many outbreaks of enteric virus associated with consumption of drinking water, the study of enteric viruses in water has increased significantly in recent years. In order to better understand the dynamics of enteric viruses in environmental water and the associated viral risk, it is necessary to estimate viral persistence in different conditions. In this study, two representative models of human enteric viruses, adenovirus 41 (AdV 41) and coxsackievirus B2 (CV-B2), were used to evaluate the persistence of enteric viruses in environmental water. The persistence of infectious particles, encapsidated genomes and free nucleic acids of AdV 41 and CV-B2 was evaluated in drinking water and surface water at different temperatures (4 °C, 20 °C and 37 °C). The infectivity of AdV 41 and CV-B2 persisted for at least 25 days, whatever the water temperature, and for more than 70 days at 4 °C and 20 °C, in both drinking and surface water. Encapsidated genomes persisted beyond 70 days, whatever the water temperature. Free nucleic acids (i.e. without capsid) also were able to persist for at least 16 days in drinking and surface water. The usefulness of a detection method based on an intercalating dye pre-treatment, which specifically targets preserved particles, was investigated for the discrimination of free and encapsidated genomes and it was compared to virus infectivity. Further, the resistance of AdV 41 and CV-B2 against two major disinfection treatments applied in drinking water plants (UV and chlorination) was evaluated. Even after the application of UV rays and chlorine at high doses (400 mJ/cm(2) and 10 mg.min/L, respectively), viral genomes were still detected with molecular biology methods. Although the intercalating dye pre-treatment had little use for the detection of the effects of UV treatment, it was useful in the case of treatment by chlorination and less than 1 log10 difference in the results was found as compared to the infectivity measurements. Finally, for the first time, the suitability of intercalating dye pre-treatment for the estimation of the quality of the water produced by treatment plants was demonstrated using samples from four drinking-water plants and two rivers. Although 55% (27/49) of drinking water samples were positive for enteric viruses using molecular detection, none of the samples were positive when the intercalating dye pre-treatment method was used. This could indicate that the viruses that were detected are not infectious.

Deciphering the Diversities of Astroviruses and Noroviruses in Wastewater Treatment Plant Effluents by a High-Throughput Sequencing Method.

Although clinical epidemiology lists human enteric viruses to be among the primary causes of acute gastroenteritis in the human population, their circulation in the environment remains poorly investigated. These viruses are excreted by the human population into sewers and may be released into rivers through the effluents of wastewater treatment plants (WWTPs). In order to evaluate the viral diversity and loads in WWTP effluents of the Paris, France, urban area, which includes about 9 million inhabitants (approximately 15% of the French population), the seasonal occurrence of astroviruses and noroviruses in 100 WWTP effluent samples was investigated over 1 year. The coupling of these measurements with a high-throughput sequencing approach allowed the specific estimation of the diversity of human astroviruses (human astrovirus genotype 1 [HAstV-1], HAstV-2, HAstV-5, and HAstV-6), 7 genotypes of noroviruses (NoVs) of genogroup I (NoV GI.1 to NoV GI.6 and NoV GI.8), and 16 genotypes of NoVs of genogroup II (NoV GII.1 to NoV GII.7, NoV GII.9, NoV GII.12 to NoV GII.17, NoV GII.20, and NoV GII.21) in effluent samples. Comparison of the viral diversity in WWTP effluents to the viral diversity found by analysis of clinical data obtained throughout France underlined the consistency between the identified genotypes. However, some genotypes were locally present in effluents and were not found in the analysis of the clinical data. These findings could highlight an underestimation of the diversity of enteric viruses circulating in the human population. Consequently, analysis of WWTP effluents could allow the exploration of viral diversity not only in environmental waters but also in a human population linked to a sewerage network in order to better comprehend viral epidemiology and to forecast seasonal outbreaks.

Large scale survey of enteric viruses in river and waste water underlines the health status of the local population.

Although enteric viruses constitute a major cause of acute waterborne diseases worldwide, environmental data about occurrence and viral load of enteric viruses in water are not often available. In this study, enteric viruses (i.e., adenovirus, aichivirus, astrovirus, cosavirus, enterovirus, hepatitis A and E viruses, norovirus of genogroups I and II, rotavirus A and salivirus) were monitored in the Seine River and the origin of contamination was untangled. A total of 275 water samples were collected, twice a month for one year, from the river Seine, its tributaries and the major WWTP effluents in the Paris agglomeration. All water samples were negative for hepatitis A and E viruses. AdV, NVGI, NVGII and RV-A were the most prevalent and abundant populations in all water samples. The viral load and the detection frequency increased significantly between the samples collected the most upstream and the most downstream of the Paris urban area. The calculated viral fluxes demonstrated clearly the measurable impact of WWTP effluents on the viral contamination of the Seine River. The viral load was seasonal for almost all enteric viruses, in accordance with the gastroenteritis recordings provided by the French medical authorities. These results implied the existence of a close relationship between the health status of inhabitants and the viral contamination of WWTP effluents and consequently surface water contamination. Subsequently, the regular analysis of wastewater could serve as a proxy for the monitoring of the human viruses circulating in both a population and surface water.

CT appearance of pulmonary carcinomas after stereotactic radiation therapy.

Stereotactic radiation therapy (SRT) is becoming more and more important in the treatment of inoperable patients with early stages of pulmonary carcinomas (T1-T2 N0M0). In certain cases, evaluation of the response is still problematical and it can be difficult to differentiate response from progression. The aim of this paper is to set out these various changes and to produce a protocol for optimal monitoring. By comparing our clinical experience with data from the literature, the main visual aspects on a CT scan are set out and illustrated for each clinical situation: radiation pneumonitis, radiation fibrosis, therapeutic response and progression. The literature was reviewed by querying the main databases and selecting papers concerning pulmonary SRT and post-therapeutic radiological appearance. CT appearance induced by SRT differs significantly from images after classic conformal radiation therapy, both morphologically and chronologically. In particular, the modifications induced by stereotactic radiation therapy are only seen in a limited volume surrounding the volume treated. Knowledge of the radiological criteria necessary to differentiate between a therapeutic response and recurrence is of major importance in the present context of increase in use of this technique.

Results and special considerations when treating elderly patients with CyberKnife®: a review of 345 cases.

The relatively recent introduction of CyberKnife® in the field of radiotherapy has prompted the question of accessibility and usefulness of this technique for seniors. From June 2007 to June 2009, we treated 345 patients of all ages with CyberKnife as part of a single-center study. Median age was 61 years (range, 8-86 years). Ninety-eight patients were over 70 and 17 were older than 80. The treatment could not be completed with 2% (2/98) patients over 70 vs. 3.6% (9/247) among the younger (ns). Physiologic or psychologic problems in maintaining position for a long time were not more frequent among those over 70. The same was true with those over 80. Patients over 70 years old are able to tolerate CyberKnife treatment as efficiently as their younger counterparts. Elderly patients should not be restricted from access to CyberKnife radiosurgery with curative intent.

[Stereotactic radiotherapy for lung cancer: Non-invasive real-time tumor tracking]. / Radiothérapie stéréotaxique de carcinomes bronchiques primitifs: suivi non invasif de la cible en temps réel.

PURPOSE: Stereotactic radiation therapy using the CyberKnife(®) has been introduced in France in 2006. Two treatment modalities are currently available: the first one (Synchrony(®)) is a real-time fiducial-based target tracking system, while the other (Xsight Lung Tracking [XLT] System(®)) is completely fiducial-free. PATIENTS AND METHODS: Sixty-eight patients were treated for a pulmonary tumor between June 2007 and November 2009. Since august 2008, the XLT System(®) was used for 26 patients. We report the necessary conditions for the XLT System (position, laterality and size of the tumor), the toxicity and outcome of this treatment. RESULTS: Twenty-two patients were analyzed. Median follow-up was 6 months (min=3; max=16). Local control rate was 100%. The main toxicity was grade grade 1 pulmonary alveolitis (27%). No grade 3 or 4 toxicities were reported. CONCLUSION: The high local control rate and low toxicity obtained with the CyberKnife(®) XLT System(®) suggest that such treatment is an alternative for inoperable patients.

Sistemas de contención de órganos en movimiento: Radioterapia Adaptada a la Respiración (RAR) / Content systems of moving organs: radiotherapy adapted to respiration (RAR)

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Pronostic factors of synchronous brain metastases from lung cancer.

BACKGROUND: The prognosis of brain metastases (BM) from lung cancer is poor. The management of lung cancer with BM is not clear. This retrospective study attempts to determine their prognostic factors, and to better define the role of different treatments. METHODS: We reviewed the clinical characteristics of 271 consecutive patients with synchronous brain metastases (SBM) from lung cancer (small-cell lung cancers and non-small-cell lung cancers), collected between January 1985 and May 1993. Data were available for all patients as well as follow-up information on all patients through to death. Patients had all undergone heterogeneous treatments. Each physician had chosen the appropriate treatment after collegiate discussion. Survival curves were compared using the log-rank test in univariate analysis, and Cox's Regression model in multivariate analysis. Statistical significance was defined as P<0.05. RESULTS: 249 patients were assessable. Treatments included: neurosurgical resection in 56 cases, brain irradiation in 87 cases, and chemotherapy in 126 cases. Median overall survival time from the date of histological diagnosis of SBM was 103 days (range, 1-1699). In multivariate analysis, prognostic factors for longer overall survival times were: absence of adrenal metastases (P=0.007), neurosurgical resection (P=0.028), chemotherapy (P=0.032) and brain irradiation (P=0.008). Moreover, risk factors of intracranial hypertension as cause of death were number of SBM and absence of neurosurgical resection. CONCLUSIONS: These results and others suggest that patients with SBM from lung cancer be considered for carcinologic treatment, and not only for best supportive care. However, further studies are necessary to evaluate quality of life with or without carcinologic treatment.

Microwave thermochemotherapy in the treatment of the bladder carcinoma--electromagnetic and dielectric studies--clinical protocol.

Microwave thermotherapy is currently used in clinical routines for benign prostatic hyperplasia treatments. The temperature increase is obtained using an endocavitary microwave applicator placed in the prostatic urethra. This urethral applicator after a technical modification can be placed inside the bladder in order to potentiate the effects of the treatment by chemotherapy of vesical carcinoma. This paper deals with electromagnetic studies of this new endocavitary applicator. First of all, the experimental determination of the dielectric permittivities for the propagation domain characterization is achieved in order to be used in the electromagnetic model. Compared to experimental results, these simulations obtained by the finite-difference time-domain formalism allow us to determine the electromagnetic performance of this applicator. Finally, the in vivo study realized on anesthetized dogs to determine the therapeutic protocol associating chemotherapy and thermotherapy in the treatment of the bladder cancer is presented.

New 434 MHz interstitial hyperthermia system monitored by microwave radiometry: theoretical and experimental results.

A new complete microwave interstitial hyperthermia system monitored automatically by microwave radiometry and working at 434 MHz is described in this paper. This system, which includes a new radiometer with two internal temperature references, is detailed. All its characteristics for microwave heating and radiometry are presented. The new possibilities are shown through numerous experiments on acrylamide phantom and excised tissues, which have been carried out for different antennae implantation corresponding to the clinical situation. The clinic protocol, associate to the brachytherapy, imposes the use of semi-loop catheters. Coaxial antennae, inserted in these catheters, are not, therefore, positioned in a rectilinear manner but undergo a curve. So, models based on the FDTD formalism are developed to determine the theoretical power deposition. Owing to these models, the effects of this physical motive on radiation diagrams can be taken into account. The results of the power deposition are presented for two antennae. Thermal patterns can then be determined by the solution of the bioheat-transfer equation in the steady state. Also, the comparison of the results given by the new interstitial hyperthermia system with those obtained with the previous 915 MHz one shows an improvement of the thermal performances.

[Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder]. / Etude de la synergie hyperthermie micro-onde/chimiothérapie intravésicale dans la prévention des récidives des tumeurs superficielles de vessie.

OBJECTIVES: Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment. MATERIAL AND METHODS: An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method. RESULTS: In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, regardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively. CONCLUSION: A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.

Concomitant b.i.d. radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in unresectable squamous-cell carcinoma of the pharynx: clinical and pharmacological data of a French multicenter phase II study.

PURPOSE: The aim of this phase II study conducted on unresectable squamous cell carcinoma (USCC) of the oro- and hypopharynx was to associate twice-a-day (b.i.d.) continuous nonaccelerated radiotherapy with concomitant cisplatin (CP)-5-fluorouracil (5-FU) chemotherapy, both given at full dose. Feasibility, efficacy, survival, and pharmacokinetic-pharmacodynamic relationships were analyzed. METHODS AND MATERIALS: Fifty-four consecutive patients with strictly USCC of oro- and/or hypopharynx received continuous b.i.d. radiotherapy (RT) (2 daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total RT dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Three chemotherapy (CT) courses of CP-5-FU were given during RT at 21-day intervals (third not delivered after the end of RT). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (day 2-day 6: 750 mg/m2/day cycle 1, 750 mg total dose/day cycle 2 and 3). Pharmacokinetics was performed for 5-FU (105 h follow-up) and CP (single sample at 16 h). Special attention was paid to supportive care. RESULTS: Good feasibility of RT was observed (85.2% of patients with total dose > 75 Gy). Five patients received 1 CT cycle, 34: 2 cycles, and 15: 3 cycles. The most frequent and severe acute toxicities were mucositis with grade 3-4 occurring in 28% at cycle 1 and 86% at cycle 2, as well as neutropenia (43% at cycle 2). Locoregional control at 6 months was observed in 66.7% of patients. No late toxicity above grade 2 RTOG was noticed. CP dose and 5-FU AUC(0-105h) were significantly linked to grade 3-4 neutropenia (cycle 2). Cumulative total platinum (Pt) concentration and Karnofsky index were the only independent predictors of locoregional control at 6 months. Finally, total RT dose and total Pt concentration were the only independent predictors of specific survival. CONCLUSION: This protocol showed good locoregional response with an acceptable toxicity profile. Pharmacokinetic survey is probably an effective approach to further reduce toxicity and improve efficacy. A multicentric randomized phase III study, now underway, should confirm these encouraging results.

[Iris metastases. Apropos of 4 cases]. / Les métastases iriennes. A propos de 4 observations.

Metastatic tumors of the iris are rare. They most commonly arise from a primary breast or lung neoplasm and are associated with widespread carcinomatosis. They appear as white pink masses; anterior uveitis and hypertony can be seen. They are most often associated with short life expectancy. We report four cases and we show the interest of radiotherapy.

Study of the effects of thermotherapy in benign prostatic hypertrophy.

UNLABELLED: Prostatic transurethral thermotherapy was evaluated clinically using the Prostcare microwave system of the Bruker Company, which uses a microwave radiometer to measure and control intraprostatic temperature. OBJECTIVES: The aim of our study was to evaluate the immediate histological lesions induced in the prostatic tissue depending on the temperatures delivered to the prostate; the histological changes when adenectomy is carried out after thermotherapy, and the endoscopic appearance of the prostatic fossa 48 h, and 1, 2, 3 and 6 months after thermotherapy. METHODS: Our study was divided into three stages: in the first stage, we conducted thermotherapy in 10 patients in whom suprapubic adenectomy was indicated. During thermotherapy, a multipoint fiber-optic receptor and two thermocouples were implanted into the prostage gland at a distance of 5-15 mm from the urethra. Adenectomy was carried out 10 min after thermotherapy; the second stage of our study concerned the changes seen over time. We heated adenomas using the same protocol and carried out adenectomy 24, 48, 72 h, and 1 week, 6 weeks and 3 months after thermotherapy, and lastly, we studied the endoscopic appearance after a single heating-session of 30 min by endoscopic controls at different times after thermotherapy (48 h, 1, 2, 3 and 6 months after thermotherapy). RESULTS: Macroscopic appearance: necrotic lesions measured 30 mm in length on average. Necrosis was roughly circumferential. Immediate histological aspect: in all cases, histological examination showed coagulation necrosis with periurethral thromboses. Histological changes: at 8 days, necrosis intensity was maximal and histological structures were difficult to identify. Endoscopic appearance: 3 months after thermotherapy, the typical endoscopic appearance was a large periurethral cavity. There was a sharp demarcation between untreated areas and cicatricial tissue. CONCLUSION: The efficacy of thermotherapy depends on the radiometric temperature, which should reach 47 degrees C (i.e. a temperature of 55-65 degrees C delivered to the prostate), and a rapid increase in temperature, i.e. in the power applied, which should reach the thermal radiometric level of 47 degrees C in 5 min. As soon as necrosis is obtained, the power is automatically reduced. Using this protocol, heating proves effective in 30 min.

[Use of real-time system of portal imaging in the daily monitoring of patients treated by radiotherapy for thoracic cancer]. / Utilisation d'un système d'imagerie en temps réel dans le contrôle quotidien de patients traités par irradiation pour un cancer thoracique.

PURPOSE: Retrospective analysis of the results obtained with daily interactive use of portal imaging for monitoring thoracic cancer radiotherapy. MATERIALS AND METHODS: A Siemens electronic portal imaging system called Beamviewplus was used daily in 15 lung cancer patients for each X-ray field. Out of the 714 expected portal images, 585 (82%), were obtained and printed. RESULTS: We counted 94 errors in the 585 successful controls (16%). Four main classes of errors were identified: irradiation field placement (47 cases, 50%), shielding placement (30 cases, 32%) patient's position on the till examining table (14 cases, 15%), and selection of the energy (3 cases, 3%). Forty percent of these errors were potentially serious in terms of treatment volume and vital organ protection. CONCLUSION: Only portal imaging control could easily detect errors because they occurred randomly. We thus consider the use of this daily system helpful for patient management.

Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study.

BACKGROUND: Stage I nonirradiated T2 N0 non-small cell lung carcinoma has a postoperative prognosis not very different from stage II irradiated T1 N1 carcinoma. The hypothesis was that more locoregional malignant sites are overlooked in T2 N0 M0 than in T1 N0 M0 tumors, considering the better prognosis of this last group, and that T2 N0 cancer might benefit from postresection irradiation. METHODS: From 1985 to 1991, 163 non-small cell lung carcinomas were classified T2 N0 M0 and randomized for irradiation or nonirradiation after operation. After revision of all the cases, 132 were included in this study: 60 were irradiated and 72 were not irradiated. All were followed up. The study was closed in October 1995. Statistical analysis was then performed considering volume, location, cell type, survival, and recurrence in the two groups. RESULTS: One hundred thirteen patients were followed up during a minimum of 5 years: the survival was 44.2%. There was no significant difference considering cell type or irradiation. There was no recurrence-free survivor beyond 5 years with a tumor invading the visceral pleura. At the close of the study (follow up, 4 years 3 months to 10 years 1 month), 49 of 132 patients were alive. The median survival was 3 years 11 months. Fifty-nine patients had died of local (21) or distant (40) recurrences (2 patients had both local and distant recurrence). There was again no significant difference considering cell type or irradiation, either in the survival or in the mode of recurrence. CONCLUSIONS: Stage I T2 N0 M0 non-small cell lung carcinoma tends to manifest distant metastasis. Prospective studies of stratified systemic adjuvant therapy should improve the present moderate result of radical resection in this group of tumors.

[Results of postoperative cervical node irradiation in carcinoma of the pharyngo-larynx. A study of the cooperative group of radiotherapists]. / Résultats de l'irradiation ganglionnaire cervicale postopératoire dans les carcinomes du pharyngolarynx. Etude du groupe coopérateur des radiothérapeutes de centre.

From 1981 to 1985, 428 patients presenting with an epidermoid carcinoma of the hypopharynx and/or larynx were treated with a curative intent by surgical resection and postoperative irradiation. Two-thirds of the tumours were T3 and 60% of patients presented with a clinical node involvement. The rates of local failure were 8%, 18% and 13%, respectively, for cancers of the larynx, of the piriform sinus and of the posterior wall; the rates of regional failure were 8%, 23% and 13%, respectively. There is no head and neck site with either a high or low risk of recurrence after resection, but the capsular rupture remains a factor of poor prognosis. The survival rate at 5 years of the whole series is 38%, for laryngeal localisation it reaches 62%. The risk of metastases is related to the node involvement and the interval between surgery and irradiation.

Epilarynx: pharynx or larynx?

BACKGROUND: As a general rule, epilarynx is studied as a part of supraglottis. On the contrary, in France, due to its particular natural history, it is often studied separately. METHODS: To assess the value of this French classification, we compared from an epidemiologic point of view, in one study, 86 cases of epilarynx squamous cell carcinoma (SCC) with 431 oropharynx, 339 hypopharynx, and 89 vestibule SCC. In another study, we compared, from a clinical point of view, 232 epilarynx SCC with 1351 oropharynx, 652 hypopharynx, and 372 vestibule SCC. RESULTS: Epilarynx patients appeared to be much heavier drinkers than larynx patients and similar to pharynx patients but tobacco consumption did not differ. The patterns of nodal involvement were similar for pharynx and epilarynx SCC. For stages I and II, patterns of failures were similar, but for stages III and IV, there were fewer locoregional failures in vestibule patients; distant metastases were equally frequent for these tumors. From the standpoint of multiple primaries, epilarynx SCC appeared to be more akin to pharynx than to larynx SCC with a much lower incidence of lung cancers. Finally, the outcome after treatment was different for vestibule, epilarynx, and pharynx SCC, with a 5-year survival of 43%, 27%, and 13%, respectively. CONCLUSIONS: These data support the identification of epilarynx as a real entity that should be taken into account for stratification in clinical trials.