INTRODUÇÃO: No mundo ocidental, a prevalência de adenocarcinoma da junção esofagogástrica vem crescendo nas últimas décadas. Atualmente, é aceito que o adenocarcinoma do esôfago se desenvolve de uma lesão pré-maligna: esôfago de Barrett. Este carcinoma é de difícil diagnóstico nos seus estágios iniciais, o que resulta em uma mortalidade significativa. O estudo da biologia molecular tem demonstrado que grande parte dos tumores malignos tem origem na interação entre o componente hereditário e influências externas, que em indivíduos predispostos podem ocasionar alterações genéticas que influenciem o controle da diferenciação e crescimento celular. O p21 (WAF1/CIP1) tem um papel fundamental na regulação do ciclo celular, e sua expressão imunoistoquímica tem sido estudada em diversos tumores, mostrando influência no prognóstico de várias neoplasias. OBJETIVO: Verificar a prevalência da expressão da proteína p21 em pacientes com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre (GCEE/HCPA). METODOLOGIA: A população em estudo foi constituída de 42 pacientes com adenocarcinoma de esôfago diagnosticados no GCEE/HCPA entre janeiro de 1998 e dezembro de 2002. A expressão da proteína p21 foi realizada por meio de imunoistoquímica, com anticorpo primário, p21, clone SX118, código M7202 da DAKO, e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system – IRS). RESULTADOS: Foram estudados 42 pacientes. 83,3% eram do sexo masculino, com idade superior a 40 anos. Destes, 56,2% foram submetidos a procedimentos cirúrgicos com intenção curativa: Gastrectomia total e Esofagogastrectomia transiatal. Os demais foram submetidos à cirurgia paliativa ou não sofreram tratamento cirúrgico. Apenas cinco pacientes receberam tratamento adjuvante com quimioterapia e radioterapia, isoladas ou combinadas. Quanto ao estadiamento, 78,6% dos pacientes apresentavam doença avançada, estádios III e IV. Apenas 9 apresentaram positividade para o p21, quando considerado o Sistema de Escore de Imunorreatividade (em que p21+ é ³ 3). CONCLUSÃO: A proteína p21 esteve expressa em 9 dos 42 pacientes (21,4%) com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre. Nessa casuística, o acúmulo de p21 não se mostrou essencial no processo de carcinogênese do adenocarcinoma esofágico. / INTRODUCTION: In western societies, the prevalence of adenocarcinoma of the gastroesophageal junction has increased in recent years. It is commonly accepted today that esophageal adenocarcinoma develops from a premalignant lesion: Barrett’s esophagus. This type of carcinoma is hardly diagnosed at early stages, which results in significant mortality. Molecular biology studies have shown that most malignant tumors originate from the interaction between inherited characteristics and external factors, which may cause genetic changes that interfere with the control over the differentiation and growth of cells in susceptible individuals. p21 (WAF1/CIP1) has a key role in the regulation of the cell cycle, and its immunohistochemical expression has been investigated in several tumors, showing that it influences the prognosis of various neoplasms. OBJECTIVE: To check the prevalence of p21 protein expression in patients with esophageal adenocarcinoma diagnosed in the last five years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre (GCEE/HCPA). METHODS: The study population consisted of 42 patients with esophageal adenocarcinoma diagnosed by the GCEE/HCPA between January 1998 and December 2002. The expression of p21 protein was determined by immunohistochemistry using primary antibody, p21, clone SX118, code M7202 (Dako), and assessed according to the Immunoreactive scoring system (IRS). RESULTS: Of 42 analyzed patients, 83.3% were male and older than 40 years. Among these, 56.2% were submitted to curative resection: total gastrectomy and transhiatal esophagogastrectomy. The remaining patients were submitted to palliative surgery or did not undergo any surgical treatment. Only five patients received adjuvant chemotherapy and radiation therapy, either alone or combined. Advanced disease (stages III and IV) was detected in 78.6% of the patients. Only nine patients were positive for p21, according to the immunoreactive scoring system (p21+ ³ 3). CONCLUSION: p21 was expressed in 9 of 42 patients (21.4%) with esophageal adenocarcinoma diagnosed in the last five years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre. In our patient population, the accumulation of p21 did not play a key role in the carcinogenesis of esophageal adenocarcinoma.

INTRODUÇÃO: No mundo ocidental, a prevalência de adenocarcinoma da junção esofagogástrica vem crescendo nas últimas décadas. Atualmente, é aceito que o adenocarcinoma do esôfago se desenvolve de uma lesão pré-maligna: esôfago de Barrett. Este carcinoma é de difícil diagnóstico nos seus estágios iniciais, o que resulta em uma mortalidade significativa. O estudo da biologia molecular tem demonstrado que grande parte dos tumores malignos tem origem na interação entre o componente hereditário e influências externas, que em indivíduos predispostos podem ocasionar alterações genéticas que influenciem o controle da diferenciação e crescimento celular. O p21 (WAF1/CIP1) tem um papel fundamental na regulação do ciclo celular, e sua expressão imunoistoquímica tem sido estudada em diversos tumores, mostrando influência no prognóstico de várias neoplasias. OBJETIVO: Verificar a prevalência da expressão da proteína p21 em pacientes com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre (GCEE/HCPA). METODOLOGIA: A população em estudo foi constituída de 42 pacientes com adenocarcinoma de esôfago diagnosticados no GCEE/HCPA entre janeiro de 1998 e dezembro de 2002. A expressão da proteína p21 foi realizada por meio de imunoistoquímica, com anticorpo primário, p21, clone SX118, código M7202 da DAKO, e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system – IRS). RESULTADOS: Foram estudados 42 pacientes. 83,3% eram do sexo masculino, com idade superior a 40 anos. Destes, 56,2% foram submetidos a procedimentos cirúrgicos com intenção curativa: Gastrectomia total e Esofagogastrectomia transiatal. Os demais foram submetidos à cirurgia paliativa ou não sofreram tratamento cirúrgico. Apenas cinco pacientes receberam tratamento adjuvante com quimioterapia e radioterapia, isoladas ou combinadas. Quanto ao estadiamento, 78,6% dos pacientes apresentavam doença avançada, estádios III e IV. Apenas 9 apresentaram positividade para o p21, quando considerado o Sistema de Escore de Imunorreatividade (em que p21+ é ³ 3). CONCLUSÃO: A proteína p21 esteve expressa em 9 dos 42 pacientes (21,4%) com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre. Nessa casuística, o acúmulo de p21 não se mostrou essencial no processo de carcinogênese do adenocarcinoma esofágico. / INTRODUCTION: In western societies, the prevalence of adenocarcinoma of the gastroesophageal junction has increased in recent years. It is commonly accepted today that esophageal adenocarcinoma develops from a premalignant lesion: Barrett’s esophagus. This type of carcinoma is hardly diagnosed at early stages, which results in significant mortality. Molecular biology studies have shown that most malignant tumors originate from the interaction between inherited characteristics and external factors, which may cause genetic changes that interfere with the control over the differentiation and growth of cells in susceptible individuals. p21 (WAF1/CIP1) has a key role in the regulation of the cell cycle, and its immunohistochemical expression has been investigated in several tumors, showing that it influences the prognosis of various neoplasms. OBJECTIVE: To check the prevalence of p21 protein expression in patients with esophageal adenocarcinoma diagnosed in the last five years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre (GCEE/HCPA). METHODS: The study population consisted of 42 patients with esophageal adenocarcinoma diagnosed by the GCEE/HCPA between January 1998 and December 2002. The expression of p21 protein was determined by immunohistochemistry using primary antibody, p21, clone SX118, code M7202 (Dako), and assessed according to the Immunoreactive scoring system (IRS). RESULTS: Of 42 analyzed patients, 83.3% were male and older than 40 years. Among these, 56.2% were submitted to curative resection: total gastrectomy and transhiatal esophagogastrectomy. The remaining patients were submitted to palliative surgery or did not undergo any surgical treatment. Only five patients received adjuvant chemotherapy and radiation therapy, either alone or combined. Advanced disease (stages III and IV) was detected in 78.6% of the patients. Only nine patients were positive for p21, according to the immunoreactive scoring system (p21+ ³ 3). CONCLUSION: p21 was expressed in 9 of 42 patients (21.4%) with esophageal adenocarcinoma diagnosed in the last five years by the Group for Surgeries of the Esophagus and Stomach of Hospital de Clínicas de Porto Alegre. In our patient population, the accumulation of p21 did not play a key role in the carcinogenesis of esophageal adenocarcinoma.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Approximately 25% of patients with locoregional esophageal adenocarcinoma (EC) are resistant (marked by minimal tumor regression; TRG 3) to preoperative chemoradiation, including 5FU‐based and CROSS regimens. Previously, an immunohistochemistry (IHC) test that accurately identifies patients as responders (TRG 0‐2) or non‐responders (TRG 3) to neoadjuvant CTRT was developed and validated. The current study was designed to identify gene expression profile (GEP) signatures able to predict response to preoperative treatment. Methods: Formalin‐fixed, paraffin‐embedded (FFPE) tumor tissue from 24 diagnostic biopsies (14 responders, 10 non‐responders) was collected. RNA was isolated, and RT‐PCR performed to assess the expression of 96 candidate genes chosen from in silicoanalysis. Genetic signatures incorporating genes with significant expression differences in pathologically determined responders versus non‐responders were identified, and linear and non‐linear predictive modeling methods were used to assess the accuracy of the signatures for predicting treatment response. Cross validation was performed to attain corrected accuracy values. Ten‐, 18‐, and 24‐gene signatures were identified with significantly different gene expression levels in responders compared to non‐responders (p < 0.05). Functional groups represented by the signatures included DNA damage repair, extracellular matrix remodeling, and 5FU metabolism. Partial Least Squares (PLS) prediction of treatment response was compared to pathologic TRG determined by blinded pathologic reading, and resulted in an area under the curve (AUC) of 0.99 and overall accuracy of 100% for the 24‐gene signature. Corrected AUC of 0.99 and accuracy of 95% resulted from five‐fold cross validation with 20 iterations. Heatmap analysis of the 24‐gene signature separated the EC cases into two distinct clusters, the first with 93% responders and the second with 90% non‐responders. The current study identifies novel gene signatures able to accurately predict EC patient response to preoperative treatment. The GEP may allow non‐responders to avoid unnecessary toxicities associated with chemoradiation therapy.

Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. Methods: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Results: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. Conclusions: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.

Song, Qingkun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 144-157). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Yam Hin-Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 138-157. / ABSTRACT --- p.2 / ACKNOWLEDGEMENT --- p.5 / CONTENT --- p.6 / Chapter I. --- INTRODUCTION --- p.8 / Chapter II. --- LITERATURE REVIEWS / Chapter 1. --- Esophagus and Esophageal Carcinoma --- p.11 / Chapter 2. --- Characterization of Cell Line --- p.23 / Chapter 3. --- Membrane Surface --- p.26 / Chapter 4. --- Differentiation and Cancer --- p.36 / Chapter 5. --- Calcium Ion --- p.42 / Chapter III. --- MATERIALS AND METHODS / Chapter 1. --- Characterizations of EC/CUHK2 Cell Line --- p.48 / Chapter 2. --- SQM1 Localization on EC/CUHK2 Cells --- p.57 / Chapter 3. --- SQM1 Localization on Other Cells and Cell Lines --- p.62 / Chapter 4. --- Characterizations of EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.65 / Chapter 5. --- SQM1 Localization on EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.71 / Chapter 6. --- SQM1 Localization on EC/CUHK2 Cells with Changes of Extracellular Calcium Ion Concentrations --- p.73 / Chapter IV. --- RESULTS / Chapter 1. --- Characterizations of EC/CUHK2 Cell Line --- p.74 / Chapter 2. --- SQM1 Localization on EC/CUHK2 Cells --- p.81 / Chapter 3. --- SQM1 Localization on Other Cells and Cell Lines --- p.83 / Chapter 4. --- Characterization of EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.87 / Chapter 5. --- SQM1 Localization on EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.96 / Chapter 6. --- SQM1 Localization on EC/CUHK2 Cells with Changes of Extracellular Calcium Ion Concentrations --- p.105 / Chapter V. --- DISCUSSIONS / Chapter 1. --- Characterizations of Carcinoma Cell Line --- p.107 / Chapter 2. --- SQM1 Distribution on Esophageal Cancer Cells --- p.118 / Chapter 3. --- SQM1 Distribution on Other Cells --- p.122 / Chapter 4. --- Calcium-Induced Differentiation of Esophageal Carcinoma Cells --- p.125 / Chapter 5. --- SQM1 Distribution on Calcium-Induced Esophageal Carcinoma Cells 6 --- p.132 / Chapter VI. --- CONCLUSION --- p.136 / Chapter VII. --- REFERENCES --- p.138 / Chapter VIII. --- ILLUSTRATIONS --- p.158

Resumo: A perfuração esofágica é uma entidade clínica rara, difícil e desafiadora. Seu manejo adequado, ainda nos dias de hoje, permanece controverso e, apesar dos avanços nas técnicas cirúrgicas, reanimação, cuidados intensivos e antibioticoterapia, a mortalidade permanece elevada. Avaliar qual tratamento é mais eficaz para a perfuração esofágica: o tratamento reparador ou o tratamento conservador. Revisão sistemática de ensaios clínicos randomizados, quaserrandomizados e estudos controlados. As seguintes bases de dados foram pesquisadas: Pubmed, CENTRAL (the Cochrane Library), Embase e Lilacs. A data da última busca foi em abril de 2011. Foi planejado considerar ensaios clínicos que avaliassem o tratamento reparador versus conservador em pacientes com perfuração esofágica. Dois revisores, independentemente, selecionaram os estudos em potencial. 3.311 referências foram identificadas pelas principais bases de dados eletrônicas. Deste total, 62 artigos foram selecionados para potencial inclusão na revisão. Entretanto, estes estudos foram classificados, em sua maioria, como série de casos retrospectivos e, desta forma, nenhum estudo preencheu os critérios de inclusão da revisão. Não há evidências de nível Ib, de acordo com a classificação do Centro para Medicina Baseada em Evidências de Oxford (CEBM), para definir a eficácia dos tratamentos reparador e conservador na perfuração esofágica. Há urgência da realização de ensaios clínicos para responder a esta questão clínica de relevância baseando-se no protocolo de revisão sistemática apresentado neste capítulo e, no momento, a tomada de decisões deve ser norteada em níveis de evidências inferiores, neste caso, série de casos retrospectivos / Abstract: Esophageal perforation is a rare, difficult and challenging clinical issue. Management strategies even these days remain controversial and in despite of technological advances in surgical techniques, resuscitation, intensive care and antibiotic therapy, mortality remains high. To assess which treatment is most effective for esophageal perforation cases, repair or conservative treatment. Systematic review of randomized controlled trials, quasi-random method and controlled studies. She following databases were searched: PubMed, CENTRAL (the Cochrane Library), Embase and Lilacs. The date of the last search was in April, 2011. It has been planned to consider clinical trials to analyze the repair versus conservative treatment in patients with esophageal perforation. Two reviewers selected potential studies independently. 3,311 references were identified by the major electronic databases. From the total, 62 articles were selected as potential for the inclusion in the review. However, these studies were classified mostly as a retrospective cases series and, thus, no studies met the criteria to be included in the review. No evidences of level Ib according to the the Center for Evidence Based Medicine in Oxford (EMBC) classification to define the efficacy of the repair and conservative treatments in esophageal perforation. It is urgent to carry out clinical trials to respond to this clinical relevant issue, based on the systematic review protocol presented in this chapter and, at the moment, decisions should be guided in lower levels of evidence, in this case, retrospective case series / Orientador: José Guilherme Minossi / Coorientador: Daniele Cristina Cataneo / Banca: Maria Aparecida Coelho de Arruda Henry / Banca: Ricardo Mingarini Terra / Mestre

Made available in DSpace on 2014-06-11T19:22:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-05-07Bitstream added on 2014-06-13T20:48:32Z : No. of bitstreams: 1 fresca_a_me_botfm.pdf: 331178 bytes, checksum: 1089a9ca98c48ae16944fa75faebc949 (MD5) / Universidade Estadual Paulista (UNESP) / Objetivo: Avaliação da qualidade de vida dos pacientes portadores de câncer de esôfago inoperável submetidos à inserção de stents esofágicos auto-expansíveis como opção no tratamento paliativo da neoplasia avançada. Pacientes e métodos: Avaliação prospectiva de 50 pacientes admitidos no Departamento de Endoscopia do Hospital de Câncer de Barretos com câncer de esôfago inoperável, em estágio avançado e com indicação de tratamento paliativo no período de agosto de 2007 a setembro de 2009. Os pacientes foram encaminhados para o Departamento de Endoscopia após serem estadiados pela classificação TNM e realizados exames. Após definido o tratamento paliativo com stent, os pacientes foram avaliados nas primeiras 24 horas (M0) ainda em ambiente hospitalar, 7dias (M1), 8 (M2) e 16 (M3) semanas após a colocação do stent, aplicando o questionário EORTC QLQ-C30 (versão 3), Escala do Índice de Karnofsky, classificação do grau disfagia, sintoma de dor retroesternal através escala numérico-verbal, avaliação nutricional e tempo de sobrevida. As perguntas foram respondidas pelos pacientes e nos casos de dificuldade de entendimento ou leitura os mesmos foram orientados por uma equipe de enfermagem treinada. Resultados: dos 50 pacientes que participaram do estudo, 41 eram homens (82%) e 9 eram mulheres (18%). Os stents utilizados, todos autoexpansíveis, de tecnologia totalmente brasileira, foram 32 recobertos e 18 descobertos e o local mais comum da neoplasia maligna foi o terço médio do esôfago e o tipo histológico carcinoma de células escamosas em todos os pacientes. A disfagia melhorou significativamente... / Objectives: Evaluation of quality of life in patients with inoperable esophageal cancer submitted to insertion of self expandable stent as an option on the palliative treatment of advanced neoplasia. Patients and methods: Prospective evaluation of 50 patients admitted at the endoscopy department of Barretos Cancer Hospital with inoperable esophageal cancer in an advanced state with indication of palliative treatment during the period from August 2007 to September 2009. The patients were forwarded to the endoscopy department after being staged by the TNM classification. After have defined the palliative treatment with stent, patients were evaluated during on the first 24 hours (M0) still at the hospital, 7 days (M1), 8(M2) and 16(M3) weeks, after stent placement applying the EORTC QLQ-C30 (version 3) questionnaire, scale of the Karnofsky index, dysphagia, retrosternal pain symptoms, through verbal numeric scale, nutritional evaluation, and survival time. The questions were answered by the patients and in cases of difficulty in understanding or reading they were guided by a trained nursing staff. They followed exclusion and inclusion criteria for the stent insertion. Results: of 50 patients that participated on the study, 41 were men (82 %) and 9 women (18%). The stents used were all self expandable stent of totally Brazilian technology , 32 were covered and 18 uncovered and the most common places for malignant neoplasia were the third medium of the esophagus and the histological type were squamous cells carcinoma in all patients... (Complete abstract click electronic access below)

Palliation therapy for dysphagia using esophageal stents is the current treatment of choice for those patients with inoperable esophageal malignancies. However, the stents currently used in the clinical setting, regardless of the type of metal mesh or plastic mesh stents (covered/uncovered), may cause complications, such as tumor ingrowth and stent migration into the stomach. Furthermore, metal mesh stents have limited capacities for loading anti-cancer drugs. To effectively reduce/overcome those complications and enhance the efficacy of drug release, we designed and 3D-printed a tubular, flexible polymer stent with spirals, and then load anti-cancer drug, paclitaxel, on the stent for drug release. Non- spiral 3D-printed tubular and mesh polymer stents served as controls. The self-expansion and anti migration properties, cytotoxicity, drug release profile, and cancer cell inhibition of the 3D-printed stent were fully characterized. Results showed the self-expansion force of the 3D-printed polymer stent with spirals was slightly higher than the stent without spirals. The anti-migration force of the 3D-printed stent with spirals was significantly higher than the anti-migration force of a non-spiral stent. Furthermore, the stent with spirals significantly decreased the migration distance compared to the migration distance of the non-spiral 3D-printed polymer stent. The in vitro cytotoxicity of the new stent was examined through the viability test of human esophagus epithelial cells, and results indicated that the polymer stent does not have any cytotoxicity. The results of in vitro cell viability of esophageal cancer cells further indicated that the paclitaxel in the spiral stent treated esophageal cancer cells much more efficiently than that in the mesh stent. Furthermore, the results of the in vitro drug release profile and drug permeation showed that the dense tubular drug-loaded stent could efficiently be delivered more paclitaxel through the esophageal mucosa/submucosa layers in a unidirectional way than mesh stent that delivered less paclitaxel to the esophageal mucosa/submucosa but more to the lumen. In summary, these results showed that the 3D-printed dense polymer stent with spirals has promising potential to treat esophageal malignancies. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

Rationale/Objective: Excess lung cancer risks associated with exposure to inhaled radon decay products among uranium miners has well been established. Although ingestion is also a potentially important route of exposure, the relationship between ingested radon decay products and gastrointestinal cancer risks are not well examined. The objective of this study is to determine the relationship between exposure to radon decay products and the incidence and mortality of gastrointestinal (esophagus, stomach, and colorectal) cancer among men employed as uranium miners in Ontario. Secondly, to determine whether the duration of exposure (dose rate), years since last exposure and age at first exposure modify these associations. Methods: A cohort of miners who had ever worked in an Ontario uranium mine between 1954 and 1996 was created using the Mining Master File and the National Dose Registry. Cumulative radon exposures measured in Working Level Months (WLM) were previously estimated for each miner. Cancer diagnoses (1964-2004) and cancer deaths (1954-2004) occurring in Ontario were determined by probabilistic record linkage with the Ontario Cancer Registry. To calculate person-years at risk, non-cancer deaths were also ascertained from the Ontario mortality file for the period between 1954 and 2004. Poisson regression methods for grouped data were used to estimate the relative risks (RR) and 95% Confidence Intervals (CI) by exposure level. Results/Conclusions: The final cohort consisted of 28,273 Ontario uranium miners. By the end of 2004, 34 miners had been diagnosed with esophageal cancer, 86 with stomach cancer, and 359 with colorectal cancer. There were 40 deaths due to esophageal cancer, 69 from stomach cancer, and 176 from colorectal cancer. When comparing the highest cumulative exposure category (>40 WLM) to the referent group (0 WLM), significant increases in both stomach (RRIncidence= 2.30, 95% CI;1.02-5.17 and RRMortality=2.90, 95% CI;1.11-7.63) and colorectal cancers (RRIncidence =1.56, 95% CI;1.07-2.27 and RRMortality =1.74, 95% CI;1.01-2.99) after adjusting for age at risk and period effects. However, no relationships were observed for esophageal cancer. Suggestive evidence of modifying effects of these associations by duration of employment (dose rate) and years since last exposure for colorectal cancer was also observed.