Introducció. El carcinoma colorectal (CCR) és una de les neoplàsies més freqüents als països desenvolupats, amb un índex de supervivència inferior al 50% als 5 anys. A l'estat espanyol es diagnostiquen més d'11.000 casos/any. A la demarcació de Tarragona presenta un increment anual del 3,5% als homes i un 2,7% a les dones. Un dels aspectes més importants per millorar la supervivència és l'establiment de programes de seguiment que intentin detectar el més precoçment possible les recidives i l'aparició de lesions preneoplàsiques o neoplàsiques en un estadi curable. Hipòtesi. El seguiment intensiu del CCR operat amb pretensió curativa pot contribuir a millorar la supervivència.Objectius. 1. Estudi de prevalença, incidència, tendència i mortalitat del CCR a les comarques del sud de Catalunya. 2. Analitzar i comparar els resultats de la supervivència dels malalts operats amb pretensió radical en funció de l'acompliment d'un programa de seguiment estricte (intensiu vs no intensiu). Material i Mètode. En base a la hipòtesi de treball i objectius, els pacients van quedar distribuïts en dos grups:-estudi de prevalença i incidència-estudi de supervivènciaEl primer inclou els malalts diagnosticats de CCR durant el període objecte de l'estudi (1982-2001). L'anàlisi és de tipus observacional i descriptiu. Pel segon estudi, es va efectuar un tall longitudinal que s'inicia l'1 de gener de 1989 i perllongant-se fins el 31 de desembre de 1996. El tall va establir una mostra de 334 pacients. D'aquests, 275 van ser intervinguts amb intenció radical. Es va dissenyar un programa empíric de seguiment intensiu, assignant-se els malalts al grup de seguiment intensiu o no intensiu (control) en funció de l'acompliment estricte del programa. Els valors d'odds ratio i de risc relatiu s'han aplicat per determinar l'eficàcia dels tractaments i tipus de seguiment. Corbes de supervivència de Kaplan-Meier. Anàlisis de regressió per avaluar l'impacte de les diverses variables sobre el risc d'aparició de recidives i sobre la supervivència a llarg termini.Resultats.Incidència i prevalença: 4697 CCR diagnosticats amb una mortalitat de 2591 pacients (55,2%). El càncer de colon presenta una taxa ajustada 21,9 als homes, i de 17,8 les dones. Per la neoplàsia de recte, 12,8 pels homes, i 6,5 les dones. L'anàlisi de la tendència sobre la incidència mostra un increment anual notable ambdós sexes, sobre tot pel respecte al càncer de colon, en que s'evidencia un augment de la taxa ajustada en un 11% als homes i un 9% en les dones. La neoplàsia de recte mostra un increment moderat al sexe masculí (3,1%), mentre que pel femení, hi ha una certa tendència a la baixa (-1,4%). L'edat mitjana del diagnòstic se situa en els 68 anys en els homes i 70 en les dones. S'observa una millora progressiva en la supervivència. Als 5 anys, la supervivència ha passat del 42% al 49% en els malalts diagnosticats entre els períodes 1985-89 i 1990-94.Estudi de supervivència. L'estadiatge (Dukes) dels 334 malalts era: estadi A: 4,5%, B1: 13,2%, B2: 308%, C1: 9,3%, C2: 25,5%, D: 14,1%. En 9 (2,7%) casos no es va poder determinar. Dels 275 intervinguts amb intenció radical s'ha pogut efectuar el seguiment de 256, que van ser distribuïts segons el tipus de seguiment efectuat. No hi havia diferències en quant a la homogeneitat (P=NS). S'observa una més baixa expressió de l'antígen carcinoembrionari (CEA) en les dones (P=0,018), diferències que es van traduir significativament en la supervivència. En el grup de malalts amb CEA basal elevat, la supervivència era significativament més alta en el sexe femení (P=0,043) mentre que no hi havien diferències si el CEA basal era normal (P=0,132). La normalització del CEA desprès de la cirurgia es relaciona amb un índex més baix de patir una recidiva local o locorregional (P=0,004, RR 3,1) o de desenvolupar metàstasi (P=0,005, RR 4,2). La supervivència dels que basalment tenien el CEA normal vers els que el tenien elevat es altament significativa (P=0,007). Entre un 23,2 i un 70% dels malalts van presentar una recidiva. La recaiguda a nivell local anastomòtic i l'aparició de metàstasi a distància van constituir les més freqüents. La comparació de l'aparició de recidives en funció de l'afectació ganglionar i/o el grau de penetració tumoral no va demostrar significació estadística (P=0,319). Vint-i-un malalts sotmesos a seguiment intensiu van fer una recidiva local endoscòpica i van poder ser reintervinguts radicalment un 61,9%, mentre que dels no seguits intensivament només ho van ser un 25%, (P<0,05). Pel que fa a la relació entre l'aparició d'una recidiva locorregional com a primera recidiva entre els sotmesos a seguiment intensiu enfront dels que no, les diferències són significatives (P=0,001). La supervivència dels malalts operats amb intenció radical i estratificada en funció del seguiment efectuat és altament significativa a favor dels malalts que han complert un seguiment intensiu (P=0,018). L'anàlisi de regressió posa de manifest que el factor pronòstic més important per a la supervivència (descartades les metàstasi) es la recidiva locorregional (P=0,002). No són significatives la situació de la neoplàsia (P=0,790) ni tampoc l'elevació postoperatòria del CEA (P=0,086).Conclusions. 1.La supervivència per CCR a la demarcació augmenta progressivament, passant del 42 al 49%.2. La neoplàsia més freqüent és la de sigma (37,7%), seguida de la rectal (34,1%).3. El símptoma de debut de la malaltia que es relaciona amb un millor resultat referit a la supervivència és el canvi de ritme deposicional.4. El CEA va tenir valor estadístic en relació a la supervivència. (P=0,018)5. En la sèrie analitzada hi ha un elevat índex de pacients intervinguts amb pretensió radical (82,3%).6. L'estadi més freqüent va ser el B2, fet que es relaciona amb un diagnòstic en estadis menys avançats.7. El seguiment endoscòpic intensiu va permetre detectar recidives que es van poder beneficiar d'una resecció amb pretensió curativa en un 61,9%, mentre que els no seguits intensivament només ho van ser un 25% (P<0,05).8. El seguiment intensiu es relaciona significativament amb una millor supervivència (P<0,001). / Introduction. Colorectal cancer (CR) is one of the most frequent neoplasms in developed countries with a survival index lower than 50% in 5 years. In the whole of Spain more than 11.000 cases per year are diagnosed. In Tarragona province it presents a yearly increase of 3.5% in men and of 2.7% in women.. One of the most important aspects in order to improve survival is to set follow-up programs that attempt to detect the most precociously possible relapses and showing up of pre-neoplasic and neoplasic injuries at a curable stage. Hipothesis. From the set out data, we can establish as a work hipothesis that intensive follow-up of CR operated with curative pretense can contribute to improve survival.Objectives. 1.Study of prevalence, incidence and CR tendency analysis in southern Catalonia districts. 2. Analyse and compare monitoring results on survival of those patients who undergone major CR surgery with a radical purpose, as a result of the fullfilment of a strict follow up program (intensive vs. non intensive).3. Relate patient's progress in terms of the state of progress of neoplasm by the moment the diagnosis is done.4. Investigate which are the predictive factors related to CR prognosis, and that, consequently must be included in follow up programes.Material and Methode. In line with the work's hipothesis, objectives and carried out research, patients were distributed into two groups:-Study of prevalence and incidence.-Study of survival.Which have been the object of different analysis according to the objectives.The first group includes those patients diagnosed of CR during the period of the study (1982 - 2001) and that are living in Tarragona province. The analysis is an observative and descriptive type, so that it allows knowledge of the impact of the disease and its incidence, as well as to evaluate possible changes in tendency and progress of the disease. As for the second group a cross section was made, begining 01-01-1989 and going on to 31-12-1996. The section set up a sample of 334 patients. From those, 275 were operated with a radical purpose. It was designed an empiric program of intensive follow up, in which patients were attached to the intensive or non intensive (control) follow up groups according to the strict fulfilment of the program. Values of odds ratio and relative risk have been applied to determine the effectiveness of treatments and follow up systems. Kaplan-Meier survival curves. In order to evaluate the impact of those different variables over the risk of relapses turn up, and over long term survival, logistic regression analysis were fulfilled.Results.Incidence and prevalence. From those 4697 diagnosed CR's, global mortality in that period was of 2591 patients (55.2%). Colorectal cancer shows a fitted tax of 21,9% with males, while in women it is of 17.8%. As for rectum neoplasm, they are of 12,8 and 6,5% respectively. The analysis on the incidence shows us a remarkable annual increase on both sexes, particularly about cancer of the colon, in wich we notice an increase in gross tax of 11% on men and 9% on women. Rectum neoplasm gives us a more moderate increase in relation to male sex (3.1%) whilst to feminine there is some tendency to its decrease (-1.4%). The average age of colon neoplasm diagnosis is placed in 68 for men and 70 for women; As for rectum neoplasm is quite similar (69 and 70 years old respectively). Despite in our province the incidence of survival is lower than in some others, a progressive improvement is noticed. After 5 years survival has increased from 42% to 49% among patients diagnosed between the periods 1985-89.Study of survival. The stage (Dukes) of those 334 patients was: stage A:4.5%; B1: 13.2%; B2: 30.8%; C1: 9.3%; C2: 25.5%; D:14.1%). In 2.7% cases Duke's stage couldn't be determined. From those 275 patients operated with a radical purpose 256 could be followed up, being distributed according to the follow-up method used on them: intensive or non intensive. There were no differences related to homogeneity (P=NS). A lower expression of carcinoembryonic antigen (CEA) was detected in women (P=0.018), differences that were significantly translated in terms of survival. In that group of patients with an increase basal CEA, survival is meaningfuly higher on women (P=0.043) while there were no difference when basal CEA was normal (P=0.132). Settling down of CEA levels after surgery is related to a lower index of suffering a local or loco-regional relapse (RR 3.1) or developing a metastasis (RR 4.2). Survival of those patients with standard CEA in front of those with raised levels is highly significant (P=0.007). Between 23.2% and 70% of patients had a relapse. Relapse at a local anastomotic level and distant metastasis turn up as the most frequent ones. Comparison of relapses in terms of ganglionar damage and/or tumoral penetration degree didn't show a statistic meaning (P=0.319). Twenty-one patients under an intensive follow-up suffered from a local endoscopic relapse and 61.9% of them could be re-operated with a radical purpose, whilst from those patients non-intensively followed-up only 25% (P<0.05) of them were re-operated with differences as to following life. With regard to the relationship between a loco-regional relapse show up as a first relapse on patiens subdued to an intensive follow up in front of those who were not, differences are highly significant (P=0.001). Survival on patients radical-purpose operated and stratified according to the following-up used method, is highly meaningful for those patients object of an intensive follow up (P=0.018). Regression analysis shows us that the most important prognosis factor is the loco-regional relapse (P=0.002). Neoplasm situation (P=0.790) nor post-surgery CEA increasing (P=0.086) are meaningless.Conclusions.1. Survival to CRR at the province increases progressively, from 42% to 49%.2. Sigma neoplasm is the most frequent one (37.7%), followed by rectum neoplasm (34.1%).3. The first symptom of the disease conected to a better result with regard to survival is the change of defecating rate.4. CEA had a statistic value as for survival (P=0.018).5. In the analysed section there is a high index of radical purpose operated patients.6. The most frequent stage was B2 (30.8%), a fact which is connected to a diagnosis in less developed stages.7. Intensive endoscopic follow-up is connected significantly to a higher survival (P<0.001).

To understand the mechanisms of transcriptional regulation of PXR, we performed yeast two-hybrid screenings to search for PXR-interacting proteins in a human liver cDNA library using the PXR ligand binding domain as the bait. More than one million independent clones were screened. One positive clone was a partial cDNA of CNOT2 (amino acid 183-540). CNOT2 is a component of CCR4-NOT that is a multi-subunit protein complex highly conserved from yeast to humans. Using a mammalian two-hybrid system in CV-1 cells and GST-pull down assays, we confirmed the direct interaction between PXR and CNOT2 and mapped the specific domains of association. In HepG2 cells, over expression of CNOT2 suppressed the PXR-regulated luciferase reporter gene activity. siRNA knockdown of CNOT2 potentiated PXR-transcriptional activity. These results strongly suggest that the CCR4-NOT complex is significantly involved in transcriptional regulation of PXR. The immuno-precipitated CNOT2 complex contained deadenylase activity as determined by an in vitro RNA decay assay. The presence of transfected PXR inhibited the cNOT2-associated deadenylase activity, as demonstrated by poly(A) tail PCR. Cellular localization of PXR and cNOT2 by immuno-fluorescence microscopy indicates that the interaction might occur within Cajal Bodies. Taken together, these results suggest that PXR regulates the mRNA turnover through direct interaction with the NOT2 component of the CCR4-NOT complex. PXR is also involved in colon cancer progression. Our results indicate that the evolutionarily conserved PXR protects organisms from carcinogenesis by inhibiting tumor growth as well as eliminating carcinogenic substances. Our laboratory proposes that pregnane X receptor has an important role in maintaining the balance of cells progressing through the cell cycle. In vitro and in vivo experiments demonstrate expression of PXR in colon cancer cells slows the progression of tumor formation. Colony growth of the PXR-transfected HT29 cells was suppressed in soft agar assay. In the xenograft assay, the tumor size formed in nude mice was significantly suppressed in HT29 cells stably transfected with PXR (310 mg /- 6.2 vs. 120 mg±6, p<0.01). The number of Ki-67 positive cells were significantly decreased in PXR-transfected HT29 xenograft tumor tissue compared vector-transfected HT29 controls (p<0.01) as determined by immuno-histochemistry suggesting that PXR inhibits proliferation of colon cancer cells. Results of flow cytometry analysis indicated that PXR-transfection in HT29 cells caused G0/G1 arrest. The growth inhibitory effects of PXR are likely mediated through the E2F/Rb-regulated check point since E2F1 nuclear expression was significantly inhibited by PXR over expression.

Many Americans are afflicted with inflammation of the colon. They are also at a higher risk of developing colon cancer. Confocal microscopy of bulk epithelial tissue has the potential to provide information on tissue structural properties that may be lost in the fixation and slicing procedures required for histopathology. Optical sectioning provides images in three dimensions capturing the organizational structure of cells and colon crypts throughout the entire colon. I have constructed a custom built fluorescence and reflectance confocal microscope for imaging molecular and morphological changes associated with development of inflammation in a mouse model. A confocal microscope is a point scanning system that removes out of focus light by placing a pinhole aperture in the conjugate image plane located in front of the detector. We have two sources, 488 nm and 811 nm, for fluorescence and reflectance imaging, respectively. A polygon scanning mirror and a galvanometer scanning mirror allow for a variable scan rate between 8 and 15 fps. The lateral resolution of the system is approximately 3 μm with an axial resolution of 6 μm and 4 μm for reflectance and fluorescence mode, respectively. As colon tissue becomes inflamed, there is a distinct change in the structure and architecture of the tissue. The colon crypts are no longer uniform in size or distribution throughout the tissue. Having a large field of view of 1mm2 allows for many colon crypts to be visualized within a single frame. Histology was performed on the same tissue imaged for the inflammatory study confirming the constructed confocal microscope’s ability to characterize inflamed tissue and the potential use for guided biopsy. Mosaicing, or image tiling, is an imaging technique that stitches single frames together to produce a much larger field of view. An extended frame with 1 mm x 2 cm field of view is achieved within seconds. This extended frame would allow mosaicing of the entire mouse colon much faster than conventional methods without loss of resolution. The acquired confocal images of colon tissue demonstrate the microscope’s ability to resolve cell nuclei lining the colon crypts within a relatively large field of view.

This study examines the carcinogenic effect of HZE radiation and protective effects of different types of diets against colon carcinogenesis in a rat model. The effect of HZE radiation on health state and colon cancer development was evaluated. HZE radiation was found to suppress food consumption (P<0.0001) leading to lower body weight gain of irradiated rats when compared to the non-irradiated rats (P<0.05). The animals exposed to HZE radiation were found to start dying and/or getting pathologies 11 weeks earlier and at the end of the study had morbidity/mortality rate 14.2% higher (P=0.0005) than non-irradiated rats. There was no significant effect of HZE radiation on colon cancer incidence. The effects of dietary fibers and oils on health state and colon carcinogenesis were evaluated. Morbidity/mortality was found to be delayed in rats fed with pectinbased diets when compared to cellulose-based diet, regardless of radiation treatment. Similarly, fish oil was found to beneficially affect health of the experimental animals when compared to corn oil. Ten- and twenty-week delayed morbidity/mortality for irradiated and non-irradiated groups, respectively, was observed for rats fed with fish oil-based diets when compared to corn oil-based diets. Fish oil was also found to significantly reduce colon tumor incidence and multiplicity in non-irradiated rats (P<0.05). A similar trend was observed for the irradiated animals. No significant effect of fiber on colon cancer incidence was found. Finally, the effect of diets on general health and colon cancer development was investigated. Rats fed with corn oil/cellulose diet started dying and/or getting a disease earlier than rats fed with other diets, regardless of radiation treatment. The effect of diet on colon cancer development was found to depend on radiation treatment. Thus, in the absence of radiation treatment fish oil/cellulose was found to significantly reduce tumor incidence and multiplicity when compared to corn oil/pectin diet (P<0.05). In the presence of radiation treatment fish oil/pectin was found to lower the values of tumor incidence and tumor multiplicity, though the data obtained were not significant.

Introducción: El SII se caracteriza por la presencia de dolor abdominal, diarrea, estreñimiento, o la alternancia de ambas, la causa de esta patología tiene que ver con muchos factores: alimentación, antecedentes de enfermedades, estilo de vida, etc. En el Hospital Guillermo Almenara Irigoyen (HGAI), se desconoce la prevalencia del SII. Objetivos: Determinar la prevalencia del SII en la consulta ambulatoria del servicio de Gastroenterología del HGAI, así como también describir los subtipos de SII que se presentan. Material y Métodos: El presente estudio es de tipo descriptivo y de corte transversal. La muestra consta de 1365 pacientes, se utilizo el muestreo por conveniencia. Se confecciono una encuesta ad hoc, con dos partes: una ficha de recolección de datos (clínicos y sociodemográficos) y otra con los criterios de ROMA II para el diagnostico de SII. Los pacientes fueron encuestados en la sala de espera de los dos (02) consultorios ambulatorios del Servicio de Gastroenterología (SG) del HGAI, del 06 de Abril del 2003 al 06 de Junio del 2003. Se realizo el análisis estadístico con el programa SPSS v11, para la descripción de los resultados. Resultados: La prevalencia del SII en el SG del HGAI fue de 38.8%. De los pacientes con SII de acuerdo a los criterios de Roma II tenemos; el 44% presento SII tipo diarrea, el 32% fue tipo estreñimiento, el 19% fue tipo mixto y el 5% no se pudo determinar. De la prevalencia general de 38.8 %, el sexo femenino aportó una prevalencia del 26.5%, y el sexo masculino aporto una prevalencia del 12.2 %. La variable Sexo fue significativa, por lo que la probabilidad de que el diagnostico de SII se relaciona mas con el sexo femenino. Por lo que existiría un riesgo de 1.8 veces en el sexo femenino de tener el SII en relación al sexo masculino. El grupo etareo de 60 a 69 años es el que presenta la mayor prevalencia en el diagnostico de SII (10.2%). El grupo de edad de 50 años hacia delante presenta una prevalencia acumulada de 28.8%. Asimismo se encontraron hallazgos secundarios con las variables que tuvieron significancia estadística las cuales fueron: Sexo, Grupo etareo, Diabetes Mellitus (DM), Antecedente de Cirugía Pélvica y Antecedente personal de Cáncer gastrointestinal, Conclusión: Existe una alta prevalencia del SII (38.8%) en la población estudiada, siendo el SII de tipo Diarrea el más frecuente. El grupo de edad de 50 años hacia delante presenta una prevalencia acumulada de 28.8%.

Thesis (Ph. D. in Cell Biology)--Vanderbilt University, May 2004. / Title from PDF title screen. Includes bibliographical references.

published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Master / Master of Medical Sciences

In Hong Kong, the number of colon cancer patients has increased over the years. But at the same time, early detection of colon cancer has also become more readily available due to the recent technological advancement and increased accessibility to medical care. In recent years, more patients have become eligible for having curative sphincter saving operation and one of the objectives of this operation is to preserve continence function without stoma formation. However, colon cancer patients’ journeys do not finish after their operation. For instance, they may have bowel disorder after the operation, namely ‘Anterior Resection Syndrome’. This debilitating condition may not be amenable by surgical technique or medical therapy and it affects the bio-psycho-social wellbeing of the patient. One of the responsibilities of nurses is to promote the general wellbeing of the clients. Therefore, in this study, the possible methods of alleviating the condition of Anterior Resection Syndrome among colon cancer patients were inspected. By using strategic search of current evidences, this study found that several primary studies support the use of biofeedback to alleviate the condition. After conducting a comprehensive review of the selected studies, the biofeedback treatment was considered as an appropriate recommendation for the current clinical setting. After assessing the implementation potential of the current practice, an evidence-based protocol with considerations of local factors was established. In addition, in order to minimize resistance on the change of current practice, plans on communicating with stakeholders, pilot study and evaluation were carefully established. The purpose of this study is to provide professional nursing care by using evidence based practice for those in need. / published_or_final_version / Nursing Studies / Master / Master of Nursing

Background Colorectal cancer (CRC) is one of the most common cancers with high morbidity and mortality among both genders and yet it carries a better prognosis when detected early. Colorectal cancer screening using faecal occult blood test (FOBT) is proven to be cost-effective, however worldwide FOBT uptake rate is suboptimal which directly affects the cost-effectiveness of the screening program. Identifying those factors that influence the uptake of colorectal cancer screening using FOBT will allow implementation of relevant measures when planning a population based screening program. Methods A structured electronic search using PubMed and Medline was conducted in order to identify studies that included factors influencing the uptake of CRC screening by using FOBT. Qualities of included studies were assessed by quality assessment checklist STROBE. Results Factors that contributed to the low uptake rate of CRC screening by FOBT were identified and summarized. They were broadly divided into 3 groups. Demographic factors: age, gender, social economic status, insurance status and education, for ethnicity, employment status and obesity further studies in the future may be needed. Subject factors: subject’s attitudes and knowledge towards CRC screening, type of FOBT screening, health concerned behavior, frequency of clinical visit and physiciancomment. Provider factors: health care system factor and physicians’ factors. Conclusion Different factors, in particular those factors that were associated with low FOBT uptake rate in CRC screening, were reviewed and summarized in this paper. With the continuous effort from worldwide as well as local investigators, timely measures can be implemented to tackle this deathly disease and to ensure cost effectiveness of a screening program. / published_or_final_version / Public Health / Master / Master of Public Health