Long-term follow-up of colorectal carcinoma patients by repeated CEA radioimmunoassay.

One of the major practical applications of carcinoembryonic antigen (CEA) assay is the monitoring of colorectal carcinoma patients after complete tumor resection. During the last 5 years, we have followed by repeated CEA assays 66 patients with histologically confirmed colon or rectum adenocarcinoma. Among 19 patients who developed a tumor recurrence, 17 had increased CEA levels preceding the clinical diagnosis by 2 to 26 months. Among the 47 patients who did not show any clinical evidence of tumor recurrence, 35 had CEA values remaining below the limit of 5 ng/ml, whereas 12 had moderate elevations of CEA level fluctuating around this limit. The majority of patients in this last group were heavy smokers or had liver enlargement, but in a few of them we did not find a satisfactory explanation for their moderately increased CEA levels. While our results confirm that repeated CEA assays can predict tumor recurrence with a lead time of several months over clinical diagnosis, they also give a word of warning concerning the interpretation of moderate elevations of CEA level. A moderate increase of CEA level can be the result of early distant metastases, local recurrence or exacerbation of an inflammatory disease. We feel that the decision of second look operations based on CEA results should be made only if increasing CEA values have been observed on three different blood samples taken within a period of 3 months and if no nonmalignant diseases known to increase CEA level are present. Ultimately only randomized clinical studies will determine if second look operations motivated by elevated CEA levels can improve the quality and length of survival of patients with colorectal carcinoma.

Roux-en-y Gastric Bypass is Superior to Gastric Banding in Non-superobese Patients. a Matched-case Study with Five-year Follow-up

Background: Roux-en-Y gastric bypass (RYGBP) and gastric banding (GB) are the two most popular bariatric procedures. Only few studies have compared their results and follow-up duration is usually limited to <3 years. Patients and Methods: Using our prospective bariatric database, we matched non-superobese GB to RYGBP patients for sex, age and BMI to RYGBP. Follow-up considered up to five years. Results: 442 patients were matched in 221 pairs. Mean age (38,6) and mean BMI (43) were identical. Overall operative morbidity was higher after RYGBP (17,2 versus 5,4 %, p<0,001), but major morbidity was similar (3,6 versus 2,2 %, p=0,57). More patients developed long-term complications after GB (43,9 % versus 19 %, p<0,001), and more required reoperations (24,4 % versus 12 %, p=0,001). After RYGBP, reoperations were mainly due to internal hernias (87 %), with no reversal, whereas 18,5 % of the GB patients required band removal. Even including only patients who retained their band, weight loss after RYGBP was better throughout the study period, with 5-year EBMIL of 77,6 % and 61,7 % (p<0,001) after RYGBP and GB respectively. RYGBP was associated with better food tolerance and greater improvement of the lipid profile. Conclusions: GB is associated with a smaller overall operative morbidity and similar major morbidity, but with more long-term complications, more reoperations, a significant number of reversal or conversion procedures, and reduced weight loss when compared with RYGBP. Five-year results of RYGBP are superior to GB and patients should be informed accordingly.

Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.

Ten years follow-up after deep sclerectomy with collagen implant

RAPPORT DE SYNTHESE : BUT : Le but de ce sujet de recherche est d'évaluer le taux de succès et les complications à long terme de la sclérectomie profonde non pénétrante avec implant de collagène (SPIC) chez les patients atteints de glaucome à angle ouvert. METODES ET PATIENTS : Il s'agit d'une étude clinique, prospective, monocentrique, non-randomisée, effectuée sur 105 patients atteints d'un glaucome à angle ouvert médicalement non-contrôlé. Ces patients ont tous bénéficiés d'une SPIC, effectuée selon le geste chirurgicale standard (technique décrite dans l'article). Dans le cadre de cette étude, nous avons effectué un bilan ophtalmologique complet avant l'acte chirurgical puis un suivi postopératoire à 1 et 7 jours ; 1,2,3,6,9,12 mois et ensuite tous les 6 mois durant les dix années suivantes. RESULTATS : Le suivit moyen de cette étude s'étend sur 101.5 ± 43.1, [3-144] mois (moyenne ± écart type, [étendue]). La pression intraoculaire (PIO) préopératoire était élevée à 26.8 ± 7.7, (14-52] mmHg, et l'acuité visuelle corrigée à 0.71 ± 0.33, [0.02-1.5]. Au terme des dix années après le traitement chirurgical, le nombre de patients suivit était de 52 avec une pression intraoculaire abaissée à 12.2 ± 4.7, [6-20] mmHg et une acuité visuelle corrigée de 0.63 ± 0.34, [0.01-1.2]. Le nombre de médicaments par patient a diminué de 2.3 ± 0.7, [ 1-4] à 1.3 ± 1.1, [0-3]. Dix ans après la SPIC, une pression intraoculaire <_ 21 mmHg sans médicaments (succès complet) était obtenue chez 47.7 % des patients et 89 % avec ou sans traitement médicamenteux (succès relatif). Les gestes postopératoires additionnels par gonioponcture ont été effectués sur 61 yeux (59.8%) et les injections sous-conjonctival de 5-fluorouracil ont été pratiquées sur 25 yeux dont 5 incluant un needling. CONCLUSIONS : Le suivit à long terme sur une période de dix ans, démontre que la sclérectomie profonde avec implant de collagène (SPIC) est efficace dans le contrôle de la pression intraoculaire et présente peu de complications postopératoires.

A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up.

This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.

Persistence of Increased Eotaxin-1 (CCL11) Level in Tears of Patients Wearing Contact Lenses: A Long-Term Follow-Up Study.

BACKGROUND: Eotaxin-1 (CCL11) is a potent eosinophil chemotactic and activating peptide that may be implicated in the pathogenesis of chronic allergic eye disease and has been associated with the wearing of contact lenses (CL) in patients with contact lens papillary conjunctivitis (CLPC). The purpose of this study was to study eotaxin-1 expression in the tears of long-term CL wearers. PATIENTS AND METHODS: Tears were collected with glass capillaries from 15 patients (2 male, 13 female) with various degree of CLPC at 2-year intervals. CLPC severity was graded from 0 to 4 with reference to standard slit-lamp photographs of the superior tarsal conjunctiva. The eotaxin-1 level in the tears was measured by an ELISA, using mouse anti-human eotaxin monoclonal antibodies. RESULTS: The mean age was 32.5 ± 13.3 years (range: 17 - 69 years). The mean interval between the tear collections was 30 ± 4.8 months. The mean concentration of eotaxin was 2150 ± 477 pg/mL and 2486 ± 810 pg/mL for the first and second series, respectively. The difference was not statistically significant (paired Wilcoxon/Kruskal-Wallis, p = 0.803). The mean score of papilla grade was 1.26 ± 0.18 for the first sample and 1.40 ± 0.19 two years later. There was no significant difference of grading between the two time periods (paired Wilcoxon/Kruskal-Wallis, p = 0.751). CONCLUSIONS: the eotaxin-1 level remains up-regulated over a long time period in patients wearing CL, most of them with chronic CLPC. Eotaxin may play a role in the pathogenesis of contact lens intolerance.

Clinical follow-up of women infected with human papillomavirus-16, either alone or with other human papillomavirus types : identification of different risk groups

Rapport de synthèse Objectifs : Évaluer l'impact clinique de femmes infectées par de multiples papillomavirus human (HPV) à haut risque dont le HPV 16 en comparaison de l'évolution de femmes infectées par du HPV 16 seul. Méthode : 169 femmes ont été classifiées en trois groupes, dépendant de leur profile HPV: HPV-16 seul, HPV-16 et un HPV de type bas risque, HPV-16 et un autre HPV à haut risque. Le HPV-DNA des frottis cervicaux a été analysé par polymerase chain reaction (PCR) et reverse line blot hybridization (RLBH). Toutes les femmes ont été suivies à la consultation de colposcopie pour une durée de 24 mois ou plus. La prise en charge s'est faite selon les recommandations de Bethesda. Résultats : Les femmes infectées par du HPV 16 et un autre HPV à haut risque n'ont présenté aucun changement voire une progression de leur dysplasie en comparaison des femmes des autres groupes (RR: 1.39; 95%CI: 1.07 à 1.82; p value: 0.02 à 6 mois; RR: 2.10; 95%CI: 1.46 à 3.02; p value: <0.001 à 12 mois; RR: 1.82; 95%CI: 1.21 à 2.72; p value: 0.004 à 24 mois). Conclusions : Les femmes présentant une co-infection par du HPV 16 ainsi qu'un autre HPV de haut risque voient leur risque d'évolution défavorable augmenter.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes.

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.

Total hip replacement with a collarless polished cemented anatomic stem: clinical and gait analysis results at ten years follow-up.

PURPOSE: The aim of this study was to determine outcomes of total hip replacement (THR) with the Lemania cemented femoral stem. METHODS: A total of 78 THR patients were followed and compared to 17 "fit", healthy, elderly and 72 "frail" elderly subjects without THR, using clinical outcome measures and a portable, in-field gait analysis device at five and ten years follow-up. RESULTS: Forty-one patients (53%), mean age 83.4 years, available at ten years follow-up, reported very good to excellent satisfaction. Mean Harris Hip and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were 81.2 and 10.5 points, respectively, with excellent radiological preservation of proximal femur bone stock. Spatial and temporal gait parameters were close to the fit group and better than the frail group. CONCLUSIONS: Lemania THR demonstrated very good, stable clinical and radiological results at ten years in an older patient group, comparable to other cemented systems for primary THR. Gait analysis confirmed good walking performance in a real-life environment.

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Développement de l'interprétation quantitative de la sismique réflexion lacustre : application de l'AVO aux sédiments quaternaires dans le lac Léman

Résumé Des développements antérieurs, au sein de l'Institut de Géophysique de Lausanne, ont permis de développer des techniques d'acquisition sismique et de réaliser l'interprétation des données sismique 2D et 3D pour étudier la géologie de la région et notamment les différentes séquences sédimentaires du Lac Léman. Pour permettre un interprétation quantitative de la sismique en déterminant des paramètres physiques des sédiments la méthode AVO (Amplitude Versus Offset) a été appliquée. Deux campagnes sismiques lacustres, 2D et 3D, ont été acquises afin de tester la méthode AVO dans le Grand Lac sur les deltas des rivières. La géométrie d'acquisition a été repensée afin de pouvoir enregistrer les données à grands déports. Les flûtes sismiques, mises bout à bout, ont permis d'atteindre des angles d'incidence d'environ 40˚ . Des récepteurs GPS spécialement développés à cet effet, et disposés le long de la flûte, ont permis, après post-traitement des données, de déterminer la position de la flûte avec précision (± 0.5 m). L'étalonnage de nos hydrophones, réalisé dans une chambre anéchoïque, a permis de connaître leur réponse en amplitude en fonction de la fréquence. Une variation maximale de 10 dB a été mis en évidence entre les capteurs des flûtes et le signal de référence. Un traitement sismique dont l'amplitude a été conservée a été appliqué sur les données du lac. L'utilisation de l'algorithme en surface en consistante a permis de corriger les variations d'amplitude des tirs du canon à air. Les sections interceptes et gradients obtenues sur les deltas de l'Aubonne et de la Dranse ont permis de produire des cross-plots. Cette représentation permet de classer les anomalies d'amplitude en fonction du type de sédiments et de leur contenu potentiel en gaz. L'un des attributs qui peut être extrait des données 3D, est l'amplitude de la réflectivité d'une interface sismique. Ceci ajoute une composante quantitative à l'interprétation géologique d'une interface. Le fond d'eau sur le delta de l'Aubonne présente des anomalies en amplitude qui caractérisent les chenaux. L'inversion de l'équation de Zoeppritz par l'algorithme de Levenberg-Marquardt a été programmée afin d'extraire les paramètres physiques des sédiments sur ce delta. Une étude statistique des résultats de l'inversion permet de simuler la variation de l'amplitude en fonction du déport. On a obtenu un modèle dont la première couche est l'eau et dont la seconde est une couche pour laquelle V P = 1461 m∕s, ρ = 1182 kg∕m3 et V S = 383 m∕s. Abstract A system to record very high resolution (VHR) seismic data on lakes in 2D and 3D was developed at the Institute of Geophysics, University of Lausanne. Several seismic surveys carried out on Lake Geneva helped us to better understand the geology of the area and to identify sedimentary sequences. However, more sophisticated analysis of the data such as the AVO (Amplitude Versus Offset) method provides means of deciphering the detailed structure of the complex Quaternary sedimentary fill of the Lake Geneva trough. To study the physical parameters we applied the AVO method at some selected places of sediments. These areas are the Aubonne and Dranse River deltas where the configurations of the strata are relatively smooth and the discontinuities between them easy to pick. A specific layout was developed to acquire large incidence angle. 2D and 3D seismic data were acquired with streamers, deployed end to end, providing incidence angle up to 40˚ . One or more GPS antennas attached to the streamer enabled us to calculate individual hydrophone positions with an accuracy of 50 cm after post-processing of the navigation data. To ensure that our system provides correct amplitude information, our streamer sensors were calibrated in an anechoic chamber using a loudspeaker as a source. Amplitude variations between the each hydrophone were of the order of 10 dB. An amplitude correction for each hydrophone was computed and applied before processing. Amplitude preserving processing was then carried out. Intercept vs. gradient cross-plots enable us to determine that both geological discontinuities (lacustrine sediments/moraine and moraine/molasse) have well defined trends. A 3D volume collected on the Aubonne river delta was processed in order ro obtain AVO attributes. Quantitative interpretation using amplitude maps were produced and amplitude maps revealed high reflectivity in channels. Inversion of the water bottom of the Zoeppritz equation using the Levenberg-Marquadt algorithm was carried out to estimate V P , V S and ρ of sediments immediately under the lake bottom. Real-data inversion gave, under the water layer, a mud layer with V P = 1461 m∕s, ρ = 1182 kg∕m3 et V S = 383 m∕s.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: Ten-year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

PURPOSE/OBJECTIVE(S): To analyze the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer compared with hyperfractionated radiotherapy alone. MATERIALS/METHODS: From July 1994 to July 2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiotherapy (median dose 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20mg/m2 for 5 consecutive days of weeks 1 and 5). The primary endpoint was time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to RTOG criteria. The trial was registered at the National Institutes of Health (www.clinicaltrials.gov; identifier number: NCT00002654). RESULTS: Median follow-up was 9.5 years (range, 0.1 - 15.4 years). Median time to any treatment failure was not significantly different between treatment arms (p = 0.19). Locoregional control (p\0.05), distant metastasis-free survival (p = 0.02) and cancer specific survival (p = 0.03) were significantly improved in the combined treatment arm, with no difference in late toxicity between treatment arms. However, overall survival was not significantly different (p = 0.19). CONCLUSIONS: After long-term follow-up combined treatment with cisplatin and hyperfractionated, radiotherapy maintained an improved locoregional control, distant metastasis-free survival, and cancer specific survival as compared to hyperfractionated radiotherapy alone with no difference in late toxicity.

Sporadic late-onset nemaline myopathy with MGUS: Long-term follow-up after melphalan and SCT.

OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS: We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS: Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS: This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.