Jährlich werden in Deutschland 5190 Neuerkrankungen an einem Ösophaguskarzinom registriert. Diese Tumorentität steht bei Männern an 13. Stelle der Häufigkeiten der Krebserkrankungen und bei den Frauen an 17. Stelle. Die Fünfjahresüberlebensrate wird in der Literatur für männliche Patienten mit 11-22% und für Frauen mit 15-20% angegeben. Somit hat das Ösophaguskarzinom nach wie vor eine schlechte Prognose. Ziel der durchgeführten Studie war es, retrospektiv einen Überblick über die Patienten zu erstellen, welche im Zeitraum von 2007 bis 2011 aufgrund eines Ösophaguskarzinoms in der Klinik für Viszeral-, Transplantations-, Thorax-, und Gefäßchirurgie der Universitätsklinik Leipzig operativ behandelt wurden und die gewonnenen deskriptiven Statistiken und Überlebenszeitanalysen mit denen der Fachliteratur zu vergleichen, sowie gegebenenfalls Rückschlüsse zur Therapieoptimierung zu ziehen. Insgesamt lag die mediane Überlebenszeit der Patienten bei 23,7 Monaten (95%KI 13,7-33,6). Die 5-Jahres-Überlebensrate lag bei 30,3%. Zusammenfassend konnten signifikante Überlebensvorteile für das männliche Geschlecht, eine niedrigere lokale Infiltrationstiefe des Tumors (pT), das Fehlen von regionalen Lymphknotenmetastasen im Gesamtkollektiv und in der Gruppe der Adenokarzinome (pN), ein niedrigeres pUICC-Stadium ebenfalls im Gesamtkollektiv und in der Gruppe der Adenokarzinome, eine R0-Resektion und in der Subgruppe der Plattenepithelkarzinom die alleinige Operation ohne neoadjuvante Therapie festgestellt werden.

BACKGROUND:In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed.METHODS:A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70Gy (62.4-75Gy).RESULTS:At a median follow-up of 14months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications.CONCLUSIONS:IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

Class of 2010 Abstract / OBJECTIVES: To assess disease-related and resource consumption characteristics of esophageal cancer mortality within hospital inpatient settings in the United States from 2002 to 2006. METHODS: This retrospective investigation of adults aged 18 years or older with diagnoses of malignant neoplasms of the esophagus (ICD-9: 150.x) utilized nationally-representative hospital discharge records from the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample. Cases resulting in inpatient death were analyzed with respect to patient demographics, payer, hospital characteristics, number of procedures and diagnoses, Deyo-Charlson disease-based case-mix risk adjustor, and predominant comorbidities. RESULTS: Overall, 168,450 inpatient admissions for esophageal cancer were observed between 2002 and 2006, averaging 66.3 + or - 11.9 years, length of stay of 10.3 + or - 15.2 days, and charge of $51,600 + or _ 92,377. Predominant comorbidities within these persons included: secondary malignant neoplasms; disorders of fluid, electrolyte, and acid-base balance; pneumonia; respiratory failure/collapse or insufficiency; sepsis; anemia; hypertension; cardiac arrhythmias; obstructive pulmonary disease; acute or chronic renal disease; and heart failure. Significant predictors of increased charges included longer lengths of stay, higher numbers of diagnoses and procedures, median annual family income over $45k, urban hospital location, and presence of heart failure, chronic pulmonary disease, fluid and electrolyte disorders, or metastatic cancers (P< or = 0.05). Longer lengths of stay were associated with higher total charges, female sex, larger number of diagnoses and procedures, Medicaid, black race, increased case-mix severities, and fluid and electolyte disorders (P< or = 0.05). CONCLUSIONS: Patient mortality occurs in over one-tenth of esophageal cancer hospital admission cases. Further research is warranted to understand the impact of various comorbidities or treatment approaches and to assess potential disparities in lengths of stay.

The RAF-MEK-ERK is an important signaling pathway that controls cellular proliferation, differentiation and survival. Recent reports indicate that R-RAF is mutated at a high frequency in human cancer. The mutations are clustered in the glycine-rich loop and activation segment which are encoded by exon 11 and exon 15, respectively. Among these mutations, V600E is the most prevalent found in varieties of human cancers, include melanoma and thyroid carcinomas. In this thesis, we analyzed 86 human cancer specimens, including 62 lung cancers and 24 esophageal cancers, for the mutation of exons 11 and 15 by PCR and direct DNA sequencing. However, we can not detect any mutation in these two exons in these clinical samples, these results suggest indicating that BRAF mutation might be rare and analysis of larger sample size is needed to confirmed this conclusion.

Although there had been some improvement of treatment results by the combination of concurrent chemoradiotherapy with esophagectomy, the overall prognosis for patients with esophageal cancer remained poor. Selection of optimal treatment strategy for individual patients would be improved by an objective biomarker that can predict prognosis accurately. The aim of this prospective study was to evaluate whether serum concentration of C-reactive protein (CRP) can be used as a prognostic factor to predict the survival of esophageal cancer patients treated with radiotherapy. Between Nov 2002 and July 2007, patients undergoing radiotherapy for newly diagnosed esophageal cancer were eligible for inclusion into this study. Serum CRP concentration was measured prospectively before the initiation of treatment. The relationship between the serum CRP levels and clinicopathological parameters were analyzed retrospectively. The prognosis factors of esophageal cancer were statistically determined. A total of 123 patients consisting of 120 males and 3 females were enrolled in this study. 81 patients (65.9%) had high CRP levels (greater than 5 mg/L). Patients with CRP levels higher than 5 mg/L had a shorter overall survival (P < 0.001). The 2-year survival was 78.4% for patients with CRP < 5 mg/L compared with 7.8% with CRP¡Ù5 mg/L. Hypoalbuminemia (albumin< 3.5g/dL) was significantly related to shorter survival in univariate analysis. Multivariate analysis demonstrated that higher serum CRP concentration and hypoalbuminemia were both independent prognostic factors for esophageal cancer. Pretreatment serum CRP and albumin levels are easily measurable biomarkers and are significant prognostic factors for esophageal cancer. They can be used in combination with the conventional staging system to predict survival and stratify patients with esophageal cancer treated with radiotherapy more accurately.

Le cancer de l’œsophage est un cancer particulièrement agressif, avec 450 000 nouveaux cas par an dans le monde. Malgré les récentes innovations thérapeutiques en oncologie, la radiochimiothérapie reste le traitement standard dans ce cancer. Ce traitement lourd est pourtant peu efficace, puisque la survie des patients 5 ans après le diagnostic atteint seulement 20%. Une meilleure connaissance des mécanismes moléculaires ainsi que de nouveaux marqueurs pronostics sont nécessaires afin de réaliser une avancée significative dans la compréhension du cancer de l’œsophage. L’objectif de ce travail concerne l’investigation de nouveaux paramètres pronostiques, macro- ou microenvironnementaux.Dans ce cadre, nous avons investigué l’impact de la composition corporelle et, plus particulièrement, de la qualité du tissu adipeux des patients sur leur survie générale. Les patients souffrant d’un cancer de l’œsophage présentent en général un statut nutritionnel complexe :l’obésité est un facteur de risque de développement d’un adénocarcinome de l’œsophage, tandis que les carcinomes épidermoïdes se développent fréquemment chez des patients malnutris. Nous avons montré que l’atténuation du tissu graisseux au CT-scan a un impact pronostique important. Spécifiquement, une faible densité de la graisse sous-cutanée et viscérale sont des facteurs pronostiques bénéfiques majeurs. Des résultats similaires ont été publiés pour d’autres cancers digestifs, notamment par notre équipe pour le cancer colorectal métastatique. Cependant, les mécanismes biologiques sous-tendant les variations de densité de ces tissus graisseux restent encore incertains. Un tissu graisseux de haute densité refléterait des adipocytes beiges, pauvres en triglycérides et métaboliquement plus actifs. Alors que des phénomènes extrinsèques à la tumeur pourraient amorcer ce phénomène, les facteurs sécrétés par la tumeur pourraient empirer ce processus et impacter l’état de santé général du patient. Nos résultats suggèrent que les traitements pourraient également aggraver ce mécanisme. L’analyse d’échantillons sanguins et de biopsies graisseuses de patients souffrant de cancers gastro-intestinaux nous permettra de dévoiler des marqueurs associés à la variation de densité graisseuse et de faire la lumière sur les mécanismes biologiques impliqués.Depuis quelques années, les motifs histopathologiques de croissance tumorale ont été l’objet de plusieurs études. Associés aux mutations génétiques de la tumeur mais aussi à son microenvironnement, ces motifs de croissance constituent le reflet de processus oncogéniques complexes. Nous avons d’abord exploré l’impact pronostique des motifs histopathologiques de croissance tumorale œsophagienne sur deux cohortes de patients. Nous avons confirmé l’impact pronostique négatif des tumeurs infiltrantes par rapport aux tumeurs expansives. Les tumeurs infiltrantes étaient également plus fréquemment associées à un Stade T et N plus avancés, ainsi qu’à la présence d’emboles lymphovasculaires et d’infiltrations péri-nerveuses. Nous avons ensuite exploré les voies de signalisation classiquement dérégulées dans la carcinogenèse sur la cohorte composée de données publiques ;ces analyses nous ont permis d’identifier l’angiogenèse, la transition épithélio-mésenchymateuse et l’inflammation comme étant surexprimées dans les tumeurs infiltrantes. Nous avons pu identifier OLR1, SFRP4 et CXCL9 comme étant trois gènes intéressants à investiguer pour chacune de ces voies, respectivement.Ces résultats n’ont pas été confirmés par qPCR dans la cohorte de validation. La qualité de l’ARN et le traitement pré- opératoire de ces patients ont réduit le nombre de patients analysables et vraisemblablement contribué à un biais important d’expression des mécanismes biologiques. Une analyse plus extensive de ces trois voies de signalisation pourrait distinguer des acteurs importants du développement de ces motifs de croissance tumorale.En conclusion, ce travail exploratoire a permis de définir plusieurs acteurs du pronostic des patients atteints d’un cancer de l’œsophage. Des analyses moléculaires supplémentaires permettront d’aborder les voies biologiques sous- tendant le développement des motifs histopathologiques de croissance tumorale, d’une part et de variation de densité du tissu graisseux, d’autre part. Ce travail permettra de dévoiler des aspects complexes et encore peu étudiés de l’agressivité des tumeurs œsophagiennes. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23375号 / 医博第4744号 / 新制||医||1051(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中本 裕士, 教授 松田 秀一, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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.

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)