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.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Radiation Oncology Johannesburg, 2016 / Purpose: To assess the improvement in swallowing status, overall survival and treatment related complications in patients with Carcinoma of the Oesophagus treated with palliative radiotherapy. Methods: A retrospective analysis of patients with advanced squamous cell carcinoma of the oesophagus who were treated for palliation from May 2007 to June 2012 at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) was done. Ninety- nine patients received palliative radiation therapy during this period, 63% were male and 37% female with a mean age of 60, 6 years. The predominant site of lesion was middle 3rd (56%) and 86, 9% of patients had lesions more than 5cm in length. Patients received palliative External beam irradiation (EBRT) with or without High dose rate brachytherapy (HDRBT) as per the CMJAH, Department of Radiation Oncology protocol. Results: There was an overall significant improvement in swallowing status (p<0,001). Eighty –four patients (85%) had an improvement in swallowing score after treatment. The effect of treatment was not significant in the relationship between the change in swallowing status and treatment group. Overall mean time to progression was 3, 7 months. The median overall survival was 7, 7 months. The type of treatment did not affect survival significantly, unadjusted (p=0, 31) or adjusted for prognostic parameters (age, sex, length of lesion, site of lesion, and pre-treatment swallowing status) (p=0.29). There were treatment related complications in 32% of cases, consisting of ulcerations (24%), tracheo- oesophageal fistula (5%) and strictures (3%). Conclusion: In patients with advanced squamous cell oesophageal carcinoma, palliative radiotherapy is an effective modality in improving a patient’s dysphagia and thus quality of life. / MT2016

by Chan Chi Wai, Angus. / "Submitted in Jan 1999, revised in Jan 2000." / Thesis (M.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 262-294). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A Atresia de esÃfago (AE) à uma anomalia estrutural que acontece em fetos quando nÃo ocorre a septaÃÃo completa do septo esofagotraqueal. Estudou-se a repercussÃo da AE induzida por Doxorrubicina (Doxo) na contratilidade in vitro do esÃfago distal e fundo de estÃmago. 26 Ratas wistar (267 g), com acasalamento controlado, nos dias 8 e 9 de gestaÃÃo receberam 2,2 mg/Kg de Doxo intraperitonealmente, enquanto 13 ratas controle receberam o mesmo volume de NaCl 0,9%. No dia 21,5 as ratas foram submetidas a cesariana, anÃlise dos fetos para confirmaÃÃo da AE e divisÃo em 3 grupos: controle, cujas mÃes receberam apenas NaCl 0,9%; Doxo sem AE, cujas mÃes receberam Doxo, mas nÃo desenvolveram AE; e Doxo com AE, os que desenvolveram AE. Foram montados em sistema para banho de ÃrgÃo isolado os anÃis de fundo de estÃmago dos fetos e em sistema miÃgrafo de agulha os segmentos de esÃfago distal, ambos contendo soluÃÃo fisiolÃgica Tyrode a 37 ÂC, pH 7,4 e oxigenaÃÃo constante, tensÃo basal de 1 g para estÃmago e 8 mN para esÃfago. Realizou-se curva concentraÃÃo-efeito ao agonista colinÃrgico Carbacol (CCh) (0,01 â 300 &#956;M) em ambos os tecidos nos 3 grupos. Em seguida, agora apenas nos segmentos de esÃfago isolado, foi construÃda uma curva concentraÃÃo-efeito ao KCl (10 â 100 mM), em que a contraÃÃo se deve prioritariamente à entrada de cÃlcio do meio extracelular por meio de canais operados por voltagem (VOC). A anÃlise estatÃstica foi determinada utilizando two-way anÃlise de variÃncia (ANOVA) e a significÃncia foi testada pelo Student-Newman-Keuls test. No fundo de estÃmago nÃo houve diferenÃa estatÃstica entre os grupos na resposta contrÃtil ao CCh (p>0,05, ANOVA), os valores da CE50 dos animais controle foram 2,17 [1,03 â 4,58] &#956;M e Emax 0,084  0,016 g/mg de tecido (n=7); Doxo sem AE 1,47 [0,83 â 2,61] &#956;M e 0,068  0,006 g/mg de tecido (n=12); Doxo com AE 3,26 [1,90 â 5,60] &#956;M e 0,070  0,022 g/mg de tecido (n=6). No esÃfago, animais controle com Emax 5,97  0,58 mN (n=11) foram estatisticamente diferentes (p<0,05, ANOVA) dos grupos Doxo sem AE 4,48  0,34 mN (n=11) e Doxo com AE 4,42  0,68 mN (n=8), enquanto a CE50 nÃo apresentou diferenÃa estatÃstica significativa entre os grupos (p>0,05, ANOVA) controle 190 [96 â 379] nM, Doxo sem AE 228 [125 â 418] nM e Doxo com AE 439 [206 â 936] nM, quanto a resposta contrÃtil ao CCh. Na resposta ao KCl houve incremento de tensÃo inferior ao observado com CCh sem diferenÃa entre os trÃs grupos (p>0,05, ANOVA), 8 valores de Emax foram no controle 1,31  0,14 mN (n=5), Doxo sem AE 1,27  0,42 mN (n=7) e Doxo com AE 1,21  0,20 mN (n=7). Concluiu-se que o tratamento de ratas com Doxo durante o perÃodo gestacional leva a uma diminuiÃÃo da contratilidade de esÃfago isolado de seus fetos, independente do desenvolvimento de AE. Aparentemente, essa diminuiÃÃo nÃo se deve a uma menor funcionalidade dos canais VOC. O fundo de estÃmago isolado nÃo apresentou alteraÃÃes da resposta contrÃtil. / Esophageal atresia (EA) is a structural anomaly that results from an incomplete esophago-traqueal septation in the fetus during intrauterine development. The in vitro contractility of the distal esophagus and gastric fundus of fetuses with esophageal atresia induced by Doxorubicin (Doxo) was studied. 26 Female Wistar rats (267 g), were subjected to date-controlled mating, subsequently receiving 2.2 mg/kg Doxo intraperitoneally on days 8 and 9 of pregnancy, while a controlled group of 13 rats received the same volume of 0.9% NaCl. On day 21.5 the pregnant rats were submitted to a cesarean surgery, with the fetuses analysed to confirm EA and thereafter divided into 3 groups: control, whose mothers received only 0.9% NaCl; Doxo without EA, whose mothers received Doxo but not developed EA; Doxo with EA, who developed EA. After being sacrificed, ring-strips of the gastric fundus were obtained from the fetuses and mounted in isolated organ bath, while the distal esophageal strips were mounted in wire myograph system; both strips contained a standard Tyrode solution maintained at 37 ÂC, pH 7.4, in addition to constant oxygenation and a basal tension of 1 g for the fundic strips and 8 mN for the esophagus. For each set up, we carried out a cholinergic-agonist concentration- effect curve with Carbachol (CCh) (0.01 â 300 &#956;M) in both tissue in the three groups. The participation of voltage-operated channels (VOCs) was studied; a KCl- concentration-effect curve (10 â 100 mM) was conducted on isolated esophageal strips. Collected data was subjected to two-way analysis of variance (ANOVA) and the significance was tested using Student-Newman-Keuls test. There was not significant statistical difference in fundic stripsâ contractility in response to CCh (p>0.05, ANOVA), the EC50 values of the control animals were 2.17 [1.03 â 4.58] &#956;M and Emax 0.084  0.016 g/mg tissue (n=7); Doxo without EA 1.47 [0.83 â 2.61] &#956;M and 0.068  0.006 g/mg tissue (n=12); Doxo with EA 3.26 [1.90 â 5.60] &#956;M and 0.070  0.022 g/mg tissue (n=6). However, significant statistical difference was noted (p<0.05, ANOVA), in esophageal stripsâ contractility in response to CCh in the Emax value of control 5.97  0.58 mN (n=11), vs Doxo without EA 4.48  0.34 mN (n=11) and Doxo with EA 4.42  0.68 mN (n=8), while there was not significant statistical difference (p>0.05, ANOVA) in the EC50 value of control 190 [96 â 379] nM, Doxo without EA 228 [125 â 418] nM and Doxo with EA 439 [206 â 936] nM. Tensional response to KCl were present in all groups, though lower than that seen in response &#65532;to CCh, however not statistically different when comparing all the three groups (p>0.05, ANOVA), Emax of control was 1.31  0.14 mN (n=5), Doxo without EA 1.27  0.42 mN (n=7) and Doxo with EA 1.21  0.20 mN (n=7). It is possible to conclude that the treatment of rats with Doxo during pregnancy leads to decrease contractility of isolated esophagus of their fetuses, independent of the development of EA. Apparently, such a decrease is not due to a lower functionality of VOC channels. The isolated gastric fundus strips showed no change in contractile response.

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.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 6 uppsatser.