Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer.

BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors involved in genetic control of many cellular processes. PPAR and PPAR have been implicated in colonic malignancy. Here we provide three lines of evidence suggesting an inhibitory role for PPAR in colorectal cancer development. METHODS: Levels of PPAR mRNA and protein in human colorectal cancers were compared with matched non-malignant mucosa using RNAse protection and western blotting. APC(Min)/+ mice were randomised to receive the PPAR activator methylclofenapate 25 mg/kg or vehicle for up to 16 weeks, and small and large intestinal polyps were quantified by image analysis. The effect of methylclofenapate on serum stimulated mitogenesis (thymidine incorporation), linear cell growth, and annexin V and propidium iodide staining were assessed in human colonic epithelial cells. RESULTS: PPAR (mRNA and protein) expression levels were significantly depressed in colorectal cancer compared with matched non-malignant tissue. Methylclofenapate reduced polyp area in the small intestine from 18.7 mm(2) (median (interquartile range 11.1, 26.8)) to 9.90 (4.88, 13.21) mm(2) (p=0.003) and in the colon from 9.15 (6.31, 10.5) mm(2) to 3.71 (2.71, 5.99) mm(2) (p=0.009). Methylclofenapate significantly reduced thymidine incorporation and linear cell growth with no effect on annexin V or propidium iodide staining. CONCLUSIONS: PPAR may inhibit colorectal tumour progression, possibly via inhibition of proliferation, and may be an important therapeutic target.

Peripheral exudative hemorrhagic chorioretinopathy: polypoidal choroidal vasculopathy and hemodynamic modifications.

PURPOSE: To investigate choroidal vascular abnormalities in peripheral exudative hemorrhagic chorioretinopathy, using dynamic ultrawide-field fluorescein angiography (FA) and indocyanine green angiography (ICGA).¦DESIGN: Prospective observational case series.¦METHODS: This institutional study comprised a consecutive series of 40 patients (48 eyes) with peripheral exudative hemorrhagic chorioretinopathy. Choroidal vascular abnormalities were assessed with dynamic ultrawide-field (150-degree) FA and ICGA, using the Staurenghi 230 SLO Retina Lens and the Heidelberg scanning laser ophthalmoscope. The main outcome measures were morphologic descriptions of structural vascular abnormalities and choroidal hemodynamics (comparison with 30 normal eyes).¦RESULTS: The peripheral mass lesions were highly exudative and hemorrhagic, and usually associated with a pigment epithelium detachment. FA revealed nonspecific alterations corresponding to the visible fundoscopic changes (window defects, blockage, staining), but no neovascular membrane. However, despite frequent masking, ICGA showed hyperfluorescent polyp-like structures in the choroid of the lesion area in 33 eyes (69%) and an abnormal choroidal vascular network in 24 eyes (50%). The abnormal choroidal vascular network filled in the arterial or early venous phase, while the polyp-like structures filled some seconds later. Optical coherence tomography revealed the typical dome-shaped elevation of the pigment epithelium over the vascular polyps. Peripheral choriocapillaris closure was observed as well as dilated shunting vessels.¦CONCLUSION: Peripheral exudative hemorrhagic chorioretinopathy shares many characteristics (polyp-like choroidal telangiectases, abnormal choroidal vascular networks, exudative and hemorrhagic presentation) with polypoidal choroidal vasculopathy. Clarification of the precise role of these abnormalities requires further studies.

Discovery of a 29-gene panel in peripheral blood mononuclear cells for the detection of colorectal cancer and adenomas using high throughput real-time PCR.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in developed countries. Early detection of CRC leads to decreased CRC mortality. A blood-based CRC screening test is highly desirable due to limited invasiveness and high acceptance rate among patients compared to currently used fecal occult blood testing and colonoscopy. Here we describe the discovery and validation of a 29-gene panel in peripheral blood mononuclear cells (PBMC) for the detection of CRC and adenomatous polyps (AP). Blood samples were prospectively collected from a multicenter, case-control clinical study. First, we profiled 93 samples with 667 candidate and 3 reference genes by high throughput real-time PCR (OpenArray system). After analysis, 160 genes were retained and tested again on 51 additional samples. Low expressed and unstable genes were discarded resulting in a final dataset of 144 samples profiled with 140 genes. To define which genes, alone or in combinations had the highest potential to discriminate AP and/or CRC from controls, data were analyzed by a combination of univariate and multivariate methods. A list of 29 potentially discriminant genes was compiled and evaluated for its predictive accuracy by penalized logistic regression and bootstrap. This method discriminated AP >1cm and CRC from controls with a sensitivity of 59% and 75%, respectively, with 91% specificity. The behavior of the 29-gene panel was validated with a LightCycler 480 real-time PCR platform, commonly adopted by clinical laboratories. In this work we identified a 29-gene panel expressed in PBMC that can be used for developing a novel minimally-invasive test for accurate detection of AP and CRC using a standard real-time PCR platform.

Incidence des cancers et polypes colorectaux dans le canton de Vaud, 1983-2007: tendances et déterminants

Le cancer colorectal atteint, chaque année, plus d'un million de personnes dans le monde et plus de 500'000 en meurent [1]. Il affecte de manière très inégalitaire les différentes parties du monde. En effet, s'il constitue un problème de santé publique majeur dans des régions telles que l'Amérique du Nord, l'Europe ou l'Océanie (incidence supérieure à 50 pour 100'000), il est nettement plus rare dans certains pays d'Asie, d'Afrique ou d'Amérique du Sud (incidence inférieure à 10 pour 100'000) [2]. Aux Etats-Unis, on estime que 5 à 6% de la population générale présentera un cancer colorectal au cours de sa vie [3]. En Suisse, le cancer colorectal est le deuxième cancer le plus mortel, avec quelque 1'600 décès par an, après le cancer du poumon [4]. Avec 4'000 nouveaux cas annuels, il représente 11% de tous les cancers chez l'homme et chez la femme [5]. Le cancer colorectal est le troisième cancer le plus fréquent après celui du poumon et de la prostate chez l'homme, alors qu'il n'est précédé chez la femme que par le cancer du sein. Pour la période 2003-07, l'incidence en Suisse est estimée à 50 cas/100'000 hommes et 32 cas/100'000 femmes (taux standardisés selon la population européenne) [5] et son taux de survie relative à 5 ans est de 60%, ce qui en fait le taux le plus élevé d'Europe [6]. Le fait que l'incidence chez les migrants ait tendance à rattraper celle des indigènes en moins d'une génération suggère que les facteurs environnementaux jouent un rôle prédominant dans la carcinogénèse des tumeurs colorectales [7]. Cependant, d'autres facteurs, notamment génétiques, interviennent dans la survenue des cancers colorectaux. En effet, dans des conditions de vie similaires, on observe une incidence de cancers colorectaux différente entre différentes ethnies. Des études américaines ont par exemple montré une incidence plus élevée chez les noirs (48 pour 100'000) que chez les blancs (40/100'000) ou les hispaniques (26/100'000) [8]. Les hommes sont plus fréquemment touchés par le cancer colorectal que les femmes, avec un sexe ratio de 1,5 [9]. Les premiers cas de cancers colorectaux apparaissent à partir de 25 ans et l'incidence augmente de manière quasi exponentielle jusqu'à un âge de 75-80 ans, puis se stabilise [10]. L'âge moyen au diagnostic se situe entre 65 et 70 ans. Environ 66% des cancers colorectaux sont localisés dans le côlon (dans l'ordre décroissant: au niveau du sigmoïde, du côlon ascendant, descendant et transverse), 27% dans le rectum, 4% dans l'anus tandis qu'environ 4% restent multiples et indéfinis [10]. Notons encore, qu'à des fins de comparaisons épidémiologiques, les cancers du côlon, du rectum et de l'anus sont souvent regroupés dans l'unique groupe des tumeurs colorectales.

Long-term outcomes following functional endoscopic sinus surgery in Samter's triad.

OBJECTIVE: This study aimed to assess the long-term outcome of functional endoscopic sinus surgery for Samter's triad patients using an objective visual analogue scale and nasal endoscopy. METHOD: Using a retrospective database, 33 Samter's triad patients who underwent functional endoscopic sinus surgery were evaluated pre- and post-operatively between 1987 and 2007 in Hospital of La Chaux-de-Fonds, Switzerland. RESULTS: A total of 33 patients participated in the study, and the mean follow-up period was 11.6 years (range 1.2-20 years). Patients were divided into two groups based on visual analogue scale scores of the five parameters with the greatest difference in intensity of symptoms between the beginning and end of follow up. Group 1 included patients with a mean visual analogue scale score of 6 and below at the end of follow up and group 2 included patients with a mean visual analogue scale score of more than 6. The only statistically significant difference noted between the two groups was the endonasal findings: stage III-IV polyposis was present in 1 out of 24 patients (4 per cent) in group 1 and in 5 out of 9 patients (56 per cent) in group 2. CONCLUSION: The results of our study indicate that functional endoscopic sinus surgery helps stabilise disease progression. Stage III-IV polyposis had a significant adverse effect on long-term outcome.

Peutz-Jeghers syndrome: a systematic review and recommendations for management

Peutz¿Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype¿phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.

Hydrozoa e Scyphozoa existentes no instituto paulista de oceanografia

Continuing the inventory of the Coelenterate Fauna of the Brazilian coast, 23 species of Hydrozoa and a Scyphomedusa are recorded from different points of the coast aproximately between 22º and 24º lat. S. Of these, 14 species were already known from other points of the coast and the remaining 10 were unknown from this latitude. Two species are here listed as new, they are: Halocordyle fragHis and Calicella gabriellae. 1. - Halocordyle fragilis, Stechow's (1923) correction of the generic name Pennaria has been followed, shows remarkable distinctive specific characters such as: alternate distribution of the cladii which do not lie all in the same plane, they are inserted at random on the hydrocaulus with a tendency towards a spiral dexiotropic distribution, sparse distribution of the pedicels which are alternate and not all located on the same side of the hydrocladium, and, finally, the long, wiry aspect of the colony which is as brittle as light glass. This characteristics are not sufficient, to my belief, to establish a new genus, since the polyps and the gonophores are entirely of the Halocordyle type, but they confer upon the species a very peculiar habitus. 2. - Calicella gabriellae forms erect hydrocauli which are extremely soft and flexuose, with hydrothecate and intermediate internodes. The thecae are deep, cylindrical, with a conical base, there are 10-12 long and narrow opercular valves. The gonangia are small, conical, with a short distal digitiform process. The included sporosac exhibits maturing ova. Dynamena heteroclonta described by Jarvis (1922) as a new species, is here considered as a new form of the very variable species Dynamena quadridentata. Schizotricha billardi nom. nov., is specifically separated from Sch. diaphana (Heller) to which it had been identified up to know. The Brazilian colonies agree with the French Somaliland specimens described by Billard (1904) and they are reunited in a new species named after the French worker. The main difference, between the two mentioned species are: shape and size of the gonothecae, of the thecae and of the nematophores. A description is given of all the species not previously recorded from the Brazilian coast as well as biological observations on Olindias sambaquiensis whose shoals during winter months are very large and may entangle partially the fishermen's nets. Its feeding and swimming habits are described and the species proves to be an excellent laboratory animal both for class and research purposes, for it easily endures long transportation (even up to 12 hours during summer months) as well as unoxygenized acquaria and nevertheless greadily feeds on any animal food.

Síndrome de Peutz-Jeghers: relato de caso

Peutz-Jeghers syndrome (PJS) is a dominant autosomal inherited disorder characterized by intestinal hamartomatous polyps in association with mucocutaneous melanocytic maculae. This syndrome is rare, and the frequency reaches from 1 in 60,000 to 1 in 300,000 people in the USA. The symptom presentations vary greatly in this disease. Some patients require minor clinical treatment while others undergo many hospitalizations and surgical treatments. In addition, patients with PJS have an increased risk for developing a variety of malignant tumors. The aim of the present study was to report one case studied of Peutz-Jeghers syndrome.

Hiperplasia nodular focal múltipla do fígado: subtipo misto hiperplásico/adenomatoso

Focal Nodular Hyperplasia is a benign lesion of the liver, which usually presents with one or two localizations. We report the uncommon case of a 51-year-old female who presents with right upper quadrant pain that worsened in the previous month, without association with feeding. Four hepatic lesions were evidenced at Computerized tomography, the largest being of 8 cm in diameter, of atypical behavior. She was submitted to hepatic segmentectomy of the segment III. The pathologic diagnosis returned focal nodular hyperplasia mixed hyperplastic and adenomatous sub-type. The patient had a good postoperative evolution and is in ambulatory follow-up.

Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

Análisis de polimorfismos del receptor Beta 2 adrenérgico en pacientes colombianos afectados por fibrosis quística

El gen ADRB2 y sus polimorfismos se han asociado al cuadro clínico de los pacientes con Fibrosis Quística. En nuestra población existe asociación de los haplotipos G16E27I164 y R16Q27I164 y la enfermedad, así como la presencia de Pólipos y genotipo E27E y el haplotipo R16E27T164.

Asociacion entre resultados de histeroscopia y el exito de reproduccion asistida en mujeres con problemas de fertilidad

La infertilidad es definida como la incapacidad para concebir después de un año de relaciones sexuales frecuentes es sin método anticonceptivo. Su incidencia está en 10% y 20% de las parejas a nivel mundial.Aunque las causas de infertilidad pueden ser múltiples entre ellas las endocrinológicas, la edad por disminución de la capacidad función ovárica. La evidencia científica establece que una de las principales causas es la presencia de alteraciones estructurales e inflamatorias a nivel uterino (30% ,40%) por lo cual muchos autores recomiendan la realización de histerosocopia previa a tratamiento de reproducción asistida. Se realizó un estudio de cohorte retrospectiva donde se incluyeron 205 mujeres con problemas de fertilidad que fueron llevadas a histeroscopia antes de iniciar algún tipo de tratamiento de reproducción asistida. En mujeres con infertilidad secundaria, la presencia de histeroscopia anormal aumenta la posibilidad de embarazo entre un 61% y un 74% comparado con mujeres con histeroscopia normal, siendo estadísticamente significativo. Los pólipos evidenciados en la histeroscopia y por patología fue mayor en mujeres en quien el tratamiento no fue exitoso. Respecto a los resultados de patología, se evidenció una diferencia estadísticamente significativa respecto a la presencia de endometritis crónica (p=0,0035) siendo más frecuente el grupo de mujeres que no quedaron embarazadas. La presencia de resultados anormales en la histeroscopia se asoció como factor protector para el éxito en la reproducción asistida en mujeres con problemas de fertilidad, y se asocian al éxito de la reproducción asistida en mujeres con infertilidad secundaria.

Caracterización de pólipos colorectales en pacientes sometidos a colonoscopia en el Hospital Universitario de la Samaritana durante el periodo 2009 a 2011

Los pólipos del colon son un importante factor de riesgo para el desarrollo de neoplasia, su identificación precoz, remoción y clasificación histológica es fundamental para determinar curación y sobrevida. OBJETIVO: Describir las características de los pólipos del colon resecados en un hospital de tercer nivel de Cundinamarca. METODOS: Estudio descriptivo retrospectivo tipo serie de casos, de pacientes mayores de 18 años sometidos a colonoscopía en quienes se resecaron pólipos de colon, durante el periodo 2009 a 2011. RESULTADOS: Durante el periodo de estudio de realizaron 3267 colonoscopías, se excluyeron los pacientes que no tenían pólipos, sin reporte de patología o en quienes no se recupero la pieza para histología. Se analizaron 381 pacientes con pólipos los cuales fueron incluidos en el análisis final. La localización principal de los pólipos fueron recto y sigmoide 66%, poliposis múltiple se identifico en el 2,9%. Los pólipos hiperplásicos fueron los mas frecuentemente diagnosticado, seguido por adenomas tubulares. En los pacientes que se le realizó resección de múltiples pólipos se diagnosticó cáncer en 2. Las indicaciones de realización de colonoscopía que no están claramente aprobadas pero en las cuales se identificaron y resecaron pólipos son mas del 30%. CONCLUSIONES: La mayoría de pacientes eran mujeres, sigue siendo el sangrado digestivo la principal indicación de realización de colonoscopía. Los pólipos hiperplásicos seguido de los adenomas son el principal hallazgo de patología.

Experiencia en el manejo de cancer colorrectal en el hospital universitario mayor - Mederi

Introducción: El cáncer colorrectal es el tercer cáncer más diagnosticado en los hombres y el segundo en las mujeres a nivel mundial. Hasta 1.000 casos nuevos se diagnostican en Colombia cada año, por lo que es importante conocer la experiencia con esta patología en un centro de experiencia recientemente creado en el “Méderi, Hospital Universitario Mayor”. Materiales y métodos: Se realizó un estudio de corte transversal de la población con diagnóstico de cáncer colorrectal atendida entre agosto 2012 y diciembre 2014 que corresponde al tiempo de funcionamiento del servicio de Coloproctología. Resultados: Se atendieron un total de 152 pacientes con cáncer colorrectal en la institución. Se operó el 91% de los pacientes. El estadío más frecuente fue el IV. Solo el 4.9% presentó dehiscencia de anastomosis, datos concordantes con la literatura cuando el manejo es a cargo de expertos. El subtipo histológico más frecuente fue adenocarcinoma moderadamente diferenciado y la mortalidad perioperatoria de 2.63%. Discusión: El cáncer colorrectal es una entidad con alta morbimortalidad lo cual puede cambiar si se realizan pruebas de tamizaje, para realizar un manejo temprano y oportuno. Además juega un papel importante la experiencia del cirujano y la discusión de los pacientes en juntas multidisciplinarias. Palabras clave: cáncer de colon, cáncer de recto, epidemiología, estadificación

PASSCLAIM: diet-related cancer

The strongest markers presently available are precancerous lesions (e. g. polyps or aberrant crypt foci) in humans and precancerous lesions and tumours in animal models. The only marker that presently can be used for a 'reduction of disease risk' claim (type B) for food components is 'polyp recurrence'. Type B claims cannot be made on the basis of results in animal models. All of the other biomarkers examined presently lack validation against the 'true endpoint', the tumour, and thus cannot be used for type B claims. 'Reduction of disease risk' claims in the area of 'diet-related cancer' should be based primarily on human intervention studies using relevant/acceptable endpoints. An important area for future research will be the validation of these surrogate endpoints.