Avaliação dos danos do DNA na mucosa esofágica e sangue periférico de portadores da doença do refluxo gastroesofágico

RACIONAL: A doença do refluxo gastroesofágico é a afecção digestiva de maior prevalência. Os portadores podem apresentar na evolução algumas complicações, sendo o esôfago de Barrett a de maior importância, tendo em vista seu potencial de malignidade. Todavia os processos inflamatórios do trato gastrointestinal podem apresentar degeneração maligna. OBJETIVOS: Avaliar os possíveis danos do DNA em portadores de esofagite de refluxo gastroesofágico de vários graus e verificar a aplicação do ensaio Cometa na detecção dos mesmos. MÉTODOS: Foram estudados 25 pacientes distribuídos em quatro grupos: controle (n=5), esofagite leve (n=8), esofagite severa (n=5) e câncer (n=7). O ensaio Cometa foi realizado no sangue periférico (linfócitos) e biópsia do terço distal do esôfago. RESULTADOS: O ensaio Cometa detectou danos no DNA nos pacientes com esofagite leve e severa (sangue periférico e biópsia), sendo que na esofagite severa a intensidade dos danos foi maior (p<0,05). Os danos do DNA dos pacientes com esofagite severa e câncer não mostraram diferença significativa e a intensidade dos mesmos corresponde ao ensaio Cometa classe 4 (maior que 95% de danos). CONCLUSÕES: 1) As frequências de quebras do DNA da mucosa esofágica e linfócitos estão diretamente relacionadas ao grau de inflamação; 2) a esofagite severa apresenta praticamente a mesma frequência de danos no DNA do câncer esofágico; 3) o ensaio Cometa mostrou-se muito sensível para a detecção dos danos do DNA.

Outcome of superficial squamous cell carcinoma of the esophagus: a clinicopathological study

PURPOSE: To analyze the clinicopathological features and outcome of patients with pathologically proven superficial squamous cell carcinoma of the esophagus. METHODS: A total of 234 consecutive cases of esophageal carcinoma in a 15-year period were reviewed. RESULTS: Superficial esophageal cancer was found in five patients (2.1%). They were four men and one woman and the mean age was 52.5 years. Smoking and alcohol were the main risk factors. Achalasia due to Chagas disease occurred in one patient and a second primary tumor developed in the larynx in another patient. Four patients underwent esophagectomy and one patient received chemoradiotherapy. The histopathologic diagnosis was of squamous cell carcinoma in all cases. Intramucosal tumor (Tis) was identified in three cases and superficially invasive carcinoma in two cases. Four patients are free of disease with survival times of two, four, six and nine years. The patient who developed laryngeal cancer died six years after esophagectomy. CONCLUSION: Long-term survival in patients with esophageal cancer is related to early diagnosis. Therefore, a less aggressive surgical approach, such as endoscopic resection, may be a good option for these patients, if depth of tumor invasion can be accurately predicted by the new imaging tools.

High-risk human papillomaviruses in two different primary tumors in the same patient

Abstract

Avaliação da qualidade de vida em pacientes portadores de câncer de esôfago submetidos à inserção de stent esofágico auto-expansível

Pós-graduação em Bases Gerais da Cirurgia - FMB

Estudos imuno-histoquímico das proteínas p53, p16, Fhit, caspase 3 e antígeno Ki67 ; e citogenético molecular em lesões benignas e carcinoma de esôfago

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos da intervenção nutricional pós-operatória com vitaminas do complexo B sobre os indicadores metabólicos da via sulfurada e a sobrevida de pacientes com câncer de esôfago

Pós-graduação em Bases Gerais da Cirurgia - FMB

Molecular epidemiological studies on genetic predispositions to squamous cell carcinoma of the head and neck

Two molecular epidemiological studies were conducted to examine associations between genetic variation and risk of squamous cell carcinoma of the head and neck (SCCHN). In the first study, we hypothesized that genetic variation in p53 response elements (REs) may play roles in the etiology of SCCHN. We selected and genotyped five polymorphic p53 REs as well as a most frequently studied p53 codon 72 (Arg72Pro, rs1042522) polymorphism in 1,100 non-Hispanic White SCCHN patients and 1,122 age-and sex-matched cancer-free controls recruited at The University of Texas M. D. Anderson Cancer Center. In multivariate logistic regression analysis with adjustment for age, sex, smoking and drinking status, marital status and education level, we observed that the EOMES rs3806624 CC genotype had a significant effect of protection against SCCHN risk (adjusted odds ratio= 0.79, 95% confidence interval =0.64–0.98), compared with the -838TT+CT genotypes. Moreover, a significantly increased risk associated with the combined genotypes of p53 codon 72CC and EOMES -838TT+CT was observed, especially in the subgroup of non-oropharyneal cancer patients. The values of false-positive report probability were also calculated for significant findings. In the second study, we assessed the association between SCCHN risk and four potential regulatory single nucleotide polymorphisms (SNPs) of DEC1 (deleted in esophageal cancer 1) gene, a candidate tumor suppressor gene for esophageal cancer. After adjustment for age, sex, and smoking and drinking status, the variant -606CC (i.e., -249CC) homozygotes had a significantly reduced SCCHN risk (adjusted odds ratio = 0.71, 95% confidence interval = 0.52–0.99), compared with the -606TT homozygotes. Stratification analyses showed that a reduced risk associated with the -606CC genotype was more pronounced in subgroups of non-smokers, non-drinkers, younger subjects (defined as ≤ 57 years), carriers of TP53 Arg/Arg (rs1042522) genotype, patients with oropharyngeal cancer or late-stage SCCHN. Further in silico analysis revealed that the -249 T-to-C change led to a gain of a transcription factor binding site. Additional functional analysis showed that the -249T-to-C change significantly enhanced transcriptional activity of the DEC1 promoter and the DNA-protein binding activity. We conclude that the DEC1 promoter -249 T>C (rs2012775) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites. Additional large-scale, preferably population-based studies are needed to validate our findings.^

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Minimally invasive esophagectomy

Background: We aimed to assess the outcomes including the effect on quality of life (QoL) of a group of patients having a minimally invasive esophagectomy (MIE). Methods: Patients with esophageal cancer were offered MIE over a 22-month period. Data on outcomes were collected prospectively, including formal quality-of-assessments. Results: There were 25 patients offered MIE. Two patients were converted to a laparotomy to improve the lymphadenectomy. There were no deaths. Respiratory problems (pneumonia, 28%) were the most common in the 64% of patients who had a complication. The median blood loss was 300 ml, time of surgery 330 min, and time to discharge 11 days. There was a decrease in the measured QoL both in general and specifically for the esophageal patients, taking 18-24 months to return to baseline. Conclusion: MIE was performed with morbidity similar to other approaches. There were no clear benefits shown in this group of patients with respect to postoperative recovery or short- to medium-term QoL.

Development of a learning resource manual for nurses new to thoracic surgery

Background: Patients with lung and esophageal cancer often have surgery as a means of treatment. In Newfoundland and Labrador, patients with lung and esophageal issues are cared for on Six East, the General/Thoracic Surgery unit at St. Clare’s Mercy Hospital. These patients frequently require chest tubes, which are managed and assessed by Registered Nurses (RNs) on the unit. For nurses new to thoracic surgery, fulfilling their new role and caring for chest tube systems can be daunting. Purpose: The purpose of this practicum project was to develop a learning resource manual for nurses who are new to thoracic surgery. Via self-directed learning, the manual can increase the knowledge and self-efficacy of nurses who are caring for thoracic surgery clients and assessing chest tube systems. Methods: An informal needs assessment, integrated literature review, and several consultations via in-person interviews were conducted. Results: Based on the findings from these methodologies, Knowles’ Adult Learning Theory, and Benner’s Novice to Expert Model, a learning resource manual was created. The manual was divided into chapters covering various aspects of patient and chest tube system care and assessment. Conclusion: For the purpose of this practicum project, no evaluation was conducted. However, a plan for future evaluation of the learning resource manual has been developed to determine if the manual assisted with increasing the knowledge and self-efficacy of nurses new to thoracic surgery. “Test Your Knowledge” questions were included at the end of each chapter in the manual as well as case study scenarios to allow for participant self-evaluation.

Ideación suicida y desesperanza en pacientes con cáncer

El objetivo de la presente investigación fue identificar la relación entre ideación suicida y desesperanza en 160 pacientes con cáncer. La ideación suicida se midió a través de dos ítems de una entrevista semiestructurada, la escala de ideación suicida (ISS), el ítem 9 del inventario de depresión de Beck (BDI-IA). La desesperanza se midió con la escala de desesperanza de Beck (BHS). Los resultados obtenidos indicaron una relación significativa (p=.000) entre ideación suicida y desesperanza; una prevalencia de ideación suicida en los pacientes con cáncer entre 4.4% y 13.8% y de riesgo de suicidio entre 5.6% y 30.6%; y algún grado de desesperanza en 31.9 % de los participantes. De acuerdo con lo anterior, se confirma que existe relación entre la desesperanza y la ideación suicida en pacientes oncológicos adultos. Adicionalmente, que estas variables están presentes en los pacientes y que ameritan atención en la intervención interdisciplinaria.

Esophageal and head and neck cancer

Clinical Nutrition for Oncology Patients provides clinicians with the information they need to help cancer survivors and patients make informed choices about their nutrition and improve their short-term and long-term health. This comprehensive resource outlines nutritional management recommendations for care prior to, during, and after treatment and addresses specific nutritional needs and complementary therapies that may be of help to a patient. This book is written by a variety of clinicians who not only care for cancer survivors and their caregivers but are also experts in the field of nutritional oncology.

Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995–1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27–2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84–1.64) p for trend 5 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37–2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91–1.78) p for trend 5 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5–<25 kg/m2) [HR (95% CI) 0.76 (0.63–0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96–1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90–1.05)]. p for interaction 5 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.