Acute heart failure in elderly patients admitted to the emergency department with acute dyspnea: a multimarker approach diagnostic study.

BACKGROUND AND IMPORTANCE: Diagnosing acute heart failure (AHF) is difficult in elderly patients presenting with acute dyspnea to the emergency department. OBJECTIVES: To assess the diagnostic accuracy of NT-proBNP, high-sensitivity cardiac troponin-I (Hs-cTnI), soluble ST2 (ST2), galectin-3 and CD146 alone and in combination for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency department. DESIGN, SETTINGS AND PARTICIPANTS: This was a prospective, multicenter study performed between September 2016 and January 2020, including elderly patients presenting with acute dyspnea to the emergency department of 6 French hospitals. INTERVENTION: Measurement of NT-proBNP, hs-cTnI, ST2, galectin-3 and CD146. OUTCOME MEASURE AND ANALYSIS: The reference standard, AHF, was adjudicated by two independent physicians based on ED and hospitalization clinical, biological (excluding biomarkers), radiological and echocardiography data (performed by a cardiologist in the cardiology department specifically for this study). Three exploratory methods (two using a cross-sectional approach with logistic regression and counting all biomarker combinations, and one using a sequential approach with gray zone optimizations) were applied to create comprehensive combinations of the 5 biomarkers for measuring diagnostic accuracy. MAIN RESULTS: Two hundred thirty-eight patients (median age of 85 years, IQR = 8) were analyzed, and 110 (46%) were diagnosed with AHF. The accuracies of NT-proBNP, CD146, hs-cTnI, galectin-3, and ST2 were 0.72 [95% confidence interval (CI) 0.66-0.77], 0.63 (95% CI 0.57-0.69), 0.59 (95% CI 0.53-0.65), 0.55 (95% CI 0.49-0.61) and 0.51 (95% CI 0.45-0.57), respectively. Regardless of the approach used or how the 5 biomarkers were combined, the best accuracy for diagnosing AHF (0.73, 95% CI 0.67-0.78) did not differ from that of NT-proBNP alone. CONCLUSION: In this study, NT-proBNP alone exhibited the best diagnostic accuracy for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency departments. None of the other biomarkers alone or combined improved the accuracy compared to NT-proBNP, which is the only biomarker to use in this setting.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Hyperendemicity of cysticercosis in Madagascar: Novel insights from school children population-based antigen prevalence study.

OBJECTIVE: Taenia solium (Ts) cysticercosis is a neglected zoonotic disease particularly prevalent in Madagascar. Few data are available for children, current data mainly rely on antibody prevalence. We sought to determine the Ts-antigen seroprevalence-determining active cysticercosis-amongst school children from various cities in Madagascar (excluding the capital) and evaluated associated risk factors. METHODS: In seven cities in Madagascar, the presence of cysticercosis in school children (n = 1751) was investigated in 2007 using the B158/B60 antigen (Ag)-ELISA. RESULTS: The overall prevalence based on Ag detection was 27.7% [95%CI: 10-37%]. Risk factors associated with Ag positivity were age, biotope, altitude and annual average rainfall. CONCLUSION: These results highlight the high prevalence of active cysticercosis in Madagascar among school children in an urban setting. This high prevalence as well as the risk factors unraveled point to the emergency to implement appropriate Public Health measure son a national scale.

To assess hemodynamic disturbances to the ostia of the renal arteries generated by the implantation of EVAR with a suprarenal fixation.

INTRODUCTION: The treatment of abdominal aortic aneurysm (AAA) is increasingly performed via endovascular aneurysm repair (EVAR). Different types of fixation are possible with EVAR, i.e., below (infrarenal fixation) or above (suprarenal fixation) the renal arteries. Hemodynamic alterations in renal arterial flow with suprarenal (SR) fixation remain to be demonstrated. The IFIXEAR (Impact of Supra-renal Fixation of EVAR on Hemodynamics of Renal Arteries) study is designed to assess the hemodynamic effects at the ostia of at least 1 renal artery, generated immediately post-surgery by the implantation of an aortic stent with SR fixation. METHODS: IFIXEAR is a prospective, 2 center study. Every patient undergoing elective EVAR with SR fixation is eligible for inclusion. Patients with previous hemodynamic disturbances to the ostia of 1 of the renal arteries are not eligible. All patients undergo echocardiography and renal arteries duplex ultrasound within a month before surgery, and at 1 and 12 months after surgery. The primary endpoint is hemodynamic disturbance, defined as a peak systolic velocity greater than 120 cm/second, at the ostia of 1 of the renal arteries in the immediate postoperative period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee "Comité de Protection des Personnes Ouest V" under the number 18/019-2 on April 20, 2018. All patients provide written informed consent before inclusion. The University Hospital of Besancon is the trial sponsor. Results of the study will be submitted for publication in a peer-reviewed international medical journal. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT03594786, principal investigator: Dr Patricia Costa, Registered on April 24, 2018).

Pregnancy vulnerability in urban areas: a pragmatic approach combining behavioral, medico-obstetrical, socio-economic and environmental factors.

Multiple risk factors are associated with adverse pregnancy outcomes (APO), but how all these different factors combine and accumulate remains unknown. The objective of this observational retrospective study was to describe the accumulation of multiple vulnerability markers in pregnant women living in an urban area. Women living in Besançon (France) who delivered between 2005 and 2009 were included. Individual data were collected from the obstetrical records while environmental exposures were collected using environmental prediction models. The accumulation of 15 vulnerability markers, grouped into six dimensions (maternal age, smoking, body mass index (BMI), socio-economic, medico-obstetrical and environmental vulnerabilities) was described and analyzed in comparison with four APO. Among the 3686 included women, 20.8% were aged under 20 or over 34 and 21.9% had an extreme pre-pregnancy BMI. 18.8% declared smoking during pregnancy. Women exposed to socio-economic, medico-obstetrical or environmental vulnerability were 14.2%, 31.6% and 42.4% respectively. While 20.6% were not exposed to any marker, 18.8% accumulated three or more dimensions. The risk of APO increased significantly with the cumulative number of vulnerabilities. Define and validate a vulnerability score could be useful to identify vulnerable women, adapt their pregnancy monitoring and help policy makers to implement appropriate education or health promotion programs.

Development and interlaboratory agreement of real-time PCR for HPV16 quantification in liquid-based cervical samples.

High risk HPV infection is the necessary cause for the development of precancerous and cancerous lesions of the cervix. Among HPV, HPV16 represents the most carcinogenic type. Since the determination of HPV16 DNA load could be clinically useful, we assessed quantitative real-time PCR targeting E6HPV16 and albumin genes on two different platforms. Series of SiHa cells diluted in PreservCyt were used to assess repeatability and reproducibility of two in-house real-time PCR techniques run in two different laboratories to determine HPV16 load. Furthermore, 97 HPV16 positive cervical samples were evaluated to estimate inter-center variability using Bland-Alman plots. As a whole, both techniques presented coefficients of variation for HPV16 load measurement similar to those established for other virus quantification with commercial kits. Moreover, the two real-time PCR techniques showed a very good agreement for HPV16 load calculation. Finally, we emphasize that robust HPV16 DNA quantification requires normalization of viral load by the cell number.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

BACKGROUND & AIMS: The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. METHODS: We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. RESULTS: We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. CONCLUSION: One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate screening.

Case-Finding for Persistent Airway Obstruction in Farmers: A Questionnaire With Optimal Diagnosis Criteria.

INTRODUCTION: Appropriate identification of subjects who are candidates for spirometry through case-finding questionnaires may help solve the problem of chronic obstructive pulmonary disease misdiagnosis. The performance of case-finding questionnaires depends at least partially on the characteristics of the population used for their development. The use of an accurate threshold for the forced expiratory volume in 1 second / forced vital capacity ratio to define persistent airway obstruction is also vital in ascertaining chronic obstructive pulmonary disease. METHODS: Using a population examined between October 2012 and May 2013 that included a large subset of agricultural workers both exposed and unexposed to tobacco smoking, the authors aimed to select a combination of items that would identify persons most likely to have persistent airway obstruction defined as forced expiratory volume in 1 second / forced vital capacity less than the lower limit of normal according to the Global Lung Initiative-2012 equations. Two thirds of the population (n=3,397) were randomly selected to develop a questionnaire, and one third (n=1,698) was reserved for questionnaire validation. Statistical analysis was performed in 2016. RESULTS: The selected items were sex, dyspnea, BMI, tobacco smoking habits, age, history of respiratory diseases, and history of occupation at risk. The C-index of the model was 0.84 (95% CI=0.80, 0.88) for the development population and 0.76 (95% CI=0.66, 0.86) for the validation population. Using the selected items in combination, the sensitivity and specificity in identifying persistent airway obstruction were 76% and 77%, respectively, in the development population (and 68% and 73%, respectively, in the validation population) for a threshold value of 2.50%. CONCLUSIONS: This seven-item questionnaire is the first developed from a population comprising a large subset of agricultural workers and using the Global Lung Initiative-2012 equations.

Clinical Effectiveness of Intravenous Exenatide Infusion in Perioperative Glycemic Control after Coronary Artery Bypass Graft Surgery: A Phase II/III Randomized Trial.

BACKGROUND: We aimed to assess the clinical effectiveness of intravenous exenatide compared to insulin in perioperative blood glucose control in coronary artery bypass grafting surgery patients. METHODS: Patients more than 18 yr old admitted for elective coronary artery bypass grafting were included in a phase II/III nonblinded randomized superiority trial. Current insulin use and creatinine clearance of less than 60 ml/min were exclusion criteria. Two groups were compared: the exenatide group, receiving exenatide (1-h bolus of 0.05 µg/min followed by a constant infusion of 0.025 µg/min), and the control group, receiving insulin therapy. The blood glucose target range was 100 to 139 mg/dl. The primary outcome was the proportion of patients who spent at least 50% of the study period within the target range. The consumption of insulin (Cinsulin) and the time to start insulin (Tinsulin) were compared between the two groups. RESULTS: In total, 53 and 51 patients were included and analyzed in the exenatide and control groups, respectively (age: 70 ± 9 vs. 68 ± 11 yr; diabetes mellitus: 12 [23%] vs. 10 [20%]). The primary outcome was observed in 38 (72%) patients in the exenatide group and in 41 (80%) patients in the control group (odds ratio [95% CI] = 0.85 [0.34 to 2.11]; P = 0.30). Cinsulin was significantly lower (60 [40 to 80] vs. 92 [63 to 121] U, P < 0.001), and Tinsulin was significantly longer (12 [7 to 16] vs. 7 [5 to 10] h, P = 0.02) in the exenatide group. CONCLUSIONS: Exenatide alone at the dose used was not enough to achieve adequate blood glucose control in coronary artery bypass grafting patients, but it reduces overall consumption of insulin and increases the time to initiation of insulin.

Obesity is Not an Independent Factor for Adverse Outcome after Abdominal Aortic Aneurysm Repair.

BACKGROUND: The prevalence of obesity is increasing, and its impact on the outcome of open and endovascular abdominal aortic aneurysm (AAA) repair remains unclear, particularly in the European population. We herein assessed the impact of obesity on the postoperative course for both techniques. METHODS: From a database that consecutively collects all patients undergoing AAA repair; we selected all patients undergoing elective surgery for open or endovascular AAA repair, between January 2003 and December 2011. We considered obese patients (body mass index >30 kg/m(2)), overweight (25.1-30 kg/m(2)), and normal-weight patients (18.7-25 kg/m(2)), and compared mortality and/or severe complications at 30 days between obese and nonobese patients (overweight and normal weight) separately for each type of surgery by logistic regression analysis. We analyzed wound complications in the 2 groups. RESULTS: We included 748 patients, 174 obese, and 574 nonobese patients. Obese patients were younger (P < 0.001) and were less likely to have renal failure (P < 0.001) in both techniques. Obese patients in the open repair (OR) group showed a trend toward lower mortality and/or complication rates than in nonobese patients (4.8% vs. 7.5%, P = 0.34). In contrast, in the endovascular aortic aneurysm repair (EVAR) group, obese patients showed a trend toward higher mortality and/or complication rates than nonobese patients (7.1% vs. 3.2%, P = 0.17). In multivariate analysis, obesity was not an independent predictor of outcomes in OR (P = 0.18) or in EVAR (P = 0.20). Wound complications were not higher in obese patients in OR and in EVAR. CONCLUSIONS: Obesity should not be considered an independent risk factor of death and severe complications at 30 days in either open or endovascular AAA repair. Therefore, obesity should not systematically lead to the decision to use EVAR.

Prevalence and risk factors for COPD in farmers: a cross-sectional controlled study.

There are conflicting data regarding the magnitude and determinants of chronic obstructive pulmonary disease (COPD) risk in farmers.In a cross-sectional study of 917 nonfarming working controls and 3787 farmers aged 40-75 years, we assessed respiratory symptoms, tobacco exposure, job history (without direct exposure measurement) and lung function. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70) and by the Quanjer reference equation (post-bronchodilator FEV1/FVC

The impact of hospital and surgeon volume on the 30-day mortality of lung cancer surgery: A nation-based reappraisal.

OBJECTIVE: Our objective was to analyze the time trend variation of 30-day mortality after lung cancer surgery, and to quantify the impact of surgeon and hospital volumes over a 5-year period in France. METHODS: We used Epithor, the French national thoracic database and benchmark tool, which catalogues more than 180,000 procedures of 89 private and public hospitals in France. From January 2005 to December 2010, 19,556 patients who underwent major lung resection (lobectomy, bilobectomy, pneumonectomy) were included in our study. Multilevel logistic models were designed to investigate the relationship between 30-day mortality and surgeon (model 1) or hospital (model 2) volumes. The 3 levels considered were the patient, the surgeon, and the hospital. RESULTS: From 2005 to 2007, the 30-day mortality of patients who underwent major lung resection averaged 10%, and then decreased until it reached 3.8% in 2010 (P < .0001). A significant decrease in 30-day mortality was observed over time (P = .0046). During the study period, the mean annual number of procedures per surgeon was 46.1 (standard deviation [SD] = 23.6) and per hospital was 97.9 (SD = 50.8). Model 1 showed that surgeon volume had a significant impact on 30-day mortality (P = .03), whereas model 2 failed to show that hospital volume influenced 30-day mortality (P = .75). CONCLUSIONS: Since 2007, when France's first National Cancer Plan became effective, 30-day mortality of primary lung cancer surgery has decreased and currently measures 3.8%. Low mortality was correlated with higher surgeon volume but was not influenced by hospital volume, which cannot be considered a proxy measure for determining the safety of lung cancer surgery.

Real-time duplex PCR for simultaneous HPV 16 and HPV 18 DNA quantitation.

HPV 16 and HPV 18 are responsible for more than 75% of cervical cancers and high HPV 16 loads are associated with both prevalent and incident lesions. The objective of the present study was to develop a method allowing the detection and quantitation of HPV 16 and 18 DNA to improve future strategies for cervical cancer screening. A duplex real-time PCR allowing the simultaneous quantitation of both HPV 16 and HPV 18 was carried out. Mixes of HPV 16 and HPV 18 whole genome plasmids were prepared to test a wide range of viral DNA concentrations. The values obtained for each mix of plasmids with the simplex and the duplex PCR were very close to the theoretical values except when a HPV type represented only 1:1000 genome equivalent or lower than the concurrent type. Cervical samples harboring HPV 16, HPV 18 or both types were tested by comparing the results with simplex and duplex real-time PCR assays. HPV 16 and HPV 18 genome titers were similar with the two assays. In conclusion, the real-time duplex PCR proved to be robust for HPV 16 and HPV 18 DNA quantitation.

Evaluation of the number of opportunities for hand hygiene in hospital: a new methodological approach.

OBJECTIVE: To assess the number of alcohol-based hand rubbing (ABHR) opportunities in different wards of a university hospital. MATERIALS AND METHODS: The amount of care procedures was measured in nine wards (4 medical wards, 4 surgical wards, 1 intensive care unit) over a two-year period. We converted the number of care procedures into a number of ABHR opportunities using the definition provided by the World Health Organization that takes in account the nature of the care procedure and the number of healthcare workers involved in. We compared these data with those obtained by other authors and the theoretical minimal number of ABHR opportunities defined by the French Ministry of Health. RESULTS: 1,252,671 care procedures (with a mean period of 734 days/department, 122,866 days of hospitalization and 21,905 patients) were converted into ABHR opportunities. The mean number of care procedures and ABHR per day and per patient was 6.1 and 35 for the medical departments, 7.6 and 49 for the surgery departments, 14.8 and 237 for the intensive care unit, respectively. CONCLUSION: Our methodological approach strengthens the results of previous observational studies. Here, we showed that the number of ABHR opportunities is far higher than that defined by the French Ministry of Health to measure the hand hygiene hospital endeavour.

Analysis of human papillomavirus type 16 (HPV16) DNA load and physical state for identification of HPV16-infected women with high-grade lesions or cervical carcinoma.

Integration of human papillomavirus (HPV) DNA into the host cell genome is a frequent event in cervical carcinogenesis, even though this phenomenon does not seem to be mandatory for cervical cancer development. Our objective was to describe the load and physical state of HPV type 16 (HPV16) DNA in a series of cervical samples representative of the natural history of cervical cancer. We used a combination of three real-time PCR assays targeting E6, E2, and albumin genes to calculate HPV16 load (E6 and albumin) and the E2/E6 ratio as a surrogate of integration. This method was applied to 173 HPV16-positive cervical samples. Results show that viral load increases with the lesion grade (from 102 HPV16 DNA copies per 10(3) cells in normal samples up to 56,354 copies per 10(3) cells in cancers), while E2/E6 ratio decreases (from 1 in normal samples down to 0.36 in cancers). We propose that, according to this technique, an HPV16 viral load of higher than 22,000 copies/10(3) cells or an E2/E6 ratio of lower than 0.50 allows the identification of women with prevalent high-grade lesions or worse with a high specificity. In conclusion, both viral load and E2/E6 ratio, used in combination with an appropriate cutoff value, are suitable to screen women with prevalent cervical intraepithelial neoplasia grade 2 or 3 or cancer. Therefore, these assays would be useful in addition to routine HPV testing to more accurately identify women with (pre)cancerous lesions.

A municipal solid waste incinerator as the single dominant point source of PCDD/Fs in an area of increased non-Hodgkin's lymphoma incidence.

Since 1971, a municipal solid waste incinerator (MSWI) with high dioxin emission levels has been in operation in Besançon, France. We recently found a 2.3-fold risk of non-Hodgkin's lymphoma in the highest exposure zone using a Gaussian-type dispersion model as a proxy for dioxin exposure. However, the sources of PCDD/Fs in this area are a matter of controversy. The aim of this survey was therefore to examine the nature of the PCDD/F soil contamination in the surroundings of the MSWI to characterize whether more than one potential emission source could explain the presence of the PCDD/Fs. PCDD/F congener profiles were determined in 75 soil samples collected in the vicinity of the MSWI. They were compared according to the most environmentally impacted zones and to various spatial contrasts. PCDD/F concentrations ranged from 0.25 to 28.06 pg WHO-TEQ g(-1). Two different clustering algorithms identified the same main cluster (consisting of 73 samples). The remaining two soil samples composed either one, or two clusters. All clusters showed similar congener profiles. Moreover, no contrast was observed for congener distributions between complex and simple topographies, inside and outside the city boundary, the two most and the two least exposed areas, reflecting a common fingerprint. Congener profiles indicate that the area under influence of the MSWI is not subject to other point sources of PCDD/Fs. Since, the most polluting combustion chambers were recently shut down and replaced by a new one with up-to-date pollution control, slowly decreasing dioxin concentrations in the soils are to be expected.

Dispersion modeling as a dioxin exposure indicator in the vicinity of a municipal solid waste incinerator: a validation study.

Whether low environmental doses of dioxin affect the general population is the matter of intense debate and controversy. In a previous study, we found a 2.3-fold risk for non-Hodgkin lymphoma associated with residence in areas classified as highly exposed to dioxin emitted from a municipal solid waste incinerator (MSWI) (Besançon, France). The main limitation lay within the use of a first-generation Gaussian-type dispersion model as a proxy for dioxin exposure, since its accuracy had not been assessed before. The aim of this study was to validate this geographic-based exposure through PCDD/F measurements from soil samples. PCDD/F concentration, pH, organic carbon concentration, cation exchange capacity, and geomorphology and ecology features were assessed for 75 sampling points. In simple terrain (i.e. northeast of the MSWI), a significant association was highlighted between modeled dioxin ground-level air concentrations and log-transformed measured dioxin soil concentrations with a strong gradient across exposure categories. Conversely, in a complex topography situation (i.e. southwest of the MSWI), the model overpredicted ground-level air concentrations, particularly in the high exposure zone. First-generation modeling provided a reliable proxy for dioxin exposure in simple terrain, reinforcing the results of our case-control study. However, a more advanced atmospheric diffusion model should have been used for refined assessment in complex terrain.

Expression of E-cadherin and alpha-, beta-, gamma-catenins in patients with bladder cancer: identification of gamma-catenin as a new prognostic marker of neoplastic progression in T1 superficial urothelial tumors.

Loss of intercellular adhesion facilitates tumor invasion. To clarify the relation between altered expression of cell adhesion molecules and progression of T1 superficial bladder tumors, 101 cases (71 T1 tumors, 30 T2/T3 tumors) were examined immunohistochemically for E-cadherin and alpha-, beta-, and gamma-catenins. A highly significant correlation was observed between the decreased expression of all molecules and increased TNM stage (P < .001). Univariate analysis, performed in cases of T1 tumors, revealed association of abnormal E-cadherin with beta-catenin diminution. Survival curves were established with the Kaplan-Meier method and analyzed according to clinical and histopathologic parameters using the log-rank test. Cox multivariate analysis revealed only gamma-catenin as an independent predictor of progression-free survival in patients with stage T1 bladder urothelial tumors. The characterization of T1 tumors that will progress could lead to the identification of patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.

Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix.

OBJECTIVES: Humoral and cellular immune responses are likely to play a key role for the clearance or persistence and progression of high risk (HR) HPV-associated cervical lesions. Although there are many studies describing the systemic T-cell responses to HPV16 and 18 proteins, few data are available regarding the cellular mucosal immune responses. We used immunohistochemistry to characterize populations of T-immune cells (CD4+, CD8+, CD45RO+) in HR-HPV-infected precancerous and cancerous lesions of the uterine cervix. METHODS: Four biopsies from normal cervix, 9 CIN1 which have regressed (rCIN), 5 CIN1 which have progressed (pCIN) to high grade lesions, 13 CIN3 and 11 invasive carcinomas were included. All dysplasias and carcinomas were HR-HPV-positive and low-risk-HPV-negative. They were stained with monoclonal antibodies specific for CD4, CD8 and CD45RO and examined by microscopy. STATISTICAL ANALYSIS: The Kruskal-Wallis test and the Siegel's and Castelan's method were used. RESULTS.: CD4+ cells predominated in regressing CIN1 both within the stroma and the epithelium with the highest CD4+/CD8+ ratio compared with pCIN1, CIN3 and invasive carcinoma. At the exception of CD45RO+ cells, T cells were detected with similar frequencies in both pCIN1 and CIN3. However, in 7 out of 10 CIN3, CD4+ and CD8+ cells were visible as organized lymphoid follicle structure. The CD8+ and CD45RO+ cells far exceeded the CD4+ cells in invasive cancers. CONCLUSIONS: Density and distribution of immune T cells depend on the malignant potential of HR-HPV lesions. These results suggest that the studied lymphocyte subsets have an important role to fulfil during the natural history of HR-HPV-associated lesions.