18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (±6.3) to 8.1 (±2.9) after 1 week of chemoradiation (P = 0.070). In nonresponders (72%), the results were 9.7 (±5.4) and 7.1 (±3.8), respectively (P = 0.003). The MTV in responders fell from 36.6 (±22.7) to 22.3 (±10.4) cm3 (P = 0.180), while in nonresponders, this fell from 35.9 (±36.7) to 31.9 (±52.7) cm3 (P = 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer. © 2006 Cancer Research UK.

Differential pathologic variables and outcomes across the spectrum of adenocarcinoma of the esophagogastric junction

Background Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. Methods We adapted a large prospective database (n = 520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Results Compared with AEG type I tumors, type II and type III tumors had significantly (p\0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had[6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p = 0.03) improved for type I patients (38 months) compared with those with tumors classified as type II (28 months) and type III (24 months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. Conclusions In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study. © Société Internationale de Chirurgie 2010.

Chemotherapy for upper gastrointestinal tumours

The aim of this review is to identify current chemotherapy treatment for tumours of the oesophagus, stomach, pancreas, and liver. The role of both neoadjuvant, adjuvant, and palliative chemotherapy regimens will be discussed. This review will be of interest to oncologists in clarifying current issues regarding chemotherapy, and to physicians in other medical specialties, to increase their general understanding of benefits and drawbacks of chemotherapy in this patient group.

Toenail trace element status and risk of Barrett's oesophagus and oesophageal adenocarcinoma. Results from the FINBAR study

Trace elements have been cited as both inhibitory and causative agents of cancer but importantly exposure to them is potentially modifiable. Our study aimed to examine toenail trace element status and risk of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Toenail clippings from each hallux were obtained from 638 participants of the FINBAR (Factors Influencing the Barrett's Adenocarcinoma Relationship) study comprising 221 healthy controls, 98 reflux oesophagitis, 182 BO and 137 OAC cases. The concentrations of eight toenail trace elements were determined using instrumental neutron activation analysis. Using multivariable adjusted logistic regression analysis, odds ratios (OR) and 95% confidence intervals (CIs) were calculated within tertiles of trace element concentrations. A twofold increased risk of BO was observed, but not OAC, among individuals in the highest tertile of toenail zinc status OR 2.21 (95% CI, 1.11-4.40). A higher toenail selenium status was not associated with risk of OAC OR 0.94 (95% CI, 0.44-2.04) or BO OR 0.89 (95% CI, 0.37-2.12). A borderline significant increased risk of BO was detected with a higher toenail cobalt concentration, OR 1.97 (95% CI, 1.01-3.85). No association was found between toenail levels of chromium, cerium, mercury and OAC or BO risk. This is the first case-control study to investigate a variety of trace elements in relation to OAC and BO risk. Despite antioxidant and proapoptotic properties, no associations were found with selenium. Higher concentrations of toenail zinc and cobalt were associated with an increased BO risk, but not OAC. These findings need confirmation in prospective analysis.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study

Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

Dietary fiber and the risk of precancerous lesions and cancer of the esophagus:a systematic review and meta-analysis

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Sclérodermie et risques oncologiques [Systemic sclerosis and cancer]

The combination of skin induration with clinical features such as dyspnea, facial telangiectasia, digital infarctions and/or dysphagia supports the diagnosis of systemic sclerosis. The oesophageal dysmotility is associated with symptoms which may delay the diagnosis of gastro-oesophageal cancer. Herein we report a case of long standing systemic sclerosis with heartburn and dysphagia symptoms which were monitored closely. Unfortunately, these symptoms delayed the diagnosis of gastric adenocarcinoma. This case prompted us to review the evidence of the association of cancer and systemic sclerosis and if any oncologic evaluation is required during the follow-up of patients affected with systemic sclerosis.

Chirurgie

2007 was marked by a growing trend towards minimal invasive surgery and enhanced recovery, especially in visceral surgery. In comparison to the laparoscopic revolution in the eighties, Natural orifice transluminal endoscopic surgery (NOTES) must be watched on closely, and will probably have to be taken into account in a near future. Minimal invasive procedures in oesophageal cancer surgery have proved both efficient and oncologically safe. Implementation of Fast track protocols now permits a much faster patient's return to normal daily activity. In hepatobiliary and pancreatic surgery, multidisciplinary efforts have been done to better select patients, widen the indications and increase efficiency.

Câncer do esôfago em paciente com megaesôfago chagásico

RACIONAL: O megaesôfago constitui problema de saúde pública em nosso país, pois acomete indivíduos em sua fase de maior produtividade. Os doentes com essa afecção podem apresentar em sua evolução associação com câncer do esôfago. OBJETIVO: Analisar os aspectos clínicos e epidemiológicos de pacientes com megaesôfago e câncer do esôfago. MÉTODOS: Foram avaliados de maneira retrospectiva 20 pacientes com megaesôfago e câncer (grupo 1) e 20 com câncer do esôfago (grupo 2). Estudaram-se os dados demográficos, hábitos (etilismo e tabagismo), tipo histológico do tumor, localização da lesão, diferenciação celular, estádio, tratamento e sobrevida. RESULTADOS: Não foi observada diferença entre os grupos, com relação à idade, sexo, localização da lesão, tipo histológico do tumor, diferenciação celular, estádio e sobrevida. Com relação aos hábitos de vida, a associação de etilismo e tabagismo foi observada em maior número de pacientes com câncer do esôfago sem o antecedente de megaesôfago. CONCLUSÃO: As características clínicas dos pacientes com megaesôfago e câncer não diferem daqueles com neoplasia maligna esofágica não associada ao megaesôfago, principalmente no que se refere ao prognóstico desfavorável frente ao tratamento instituído. Nos pacientes com megaesôfago o tumor pode se localizar em qualquer porção do órgão.

Níveis plasmáticos de taurina e de seus precursores em pacientes com câncer de esôfago

RACIONAL: O câncer de esôfago tem impacto relevante no metabolismo protéico do hospedeiro, mas pouco se conhece sobre as implicações no metabolismo protéico sulfurado. Deste, destaca-se a taurina, composto participante de várias funções fisiológicas importantes como a manutenção do sistema de defesa celular e possível sobrevida do paciente. OBJETIVO: Estudar as variações plasmáticas da taurina e de seus precursores em pacientes com câncer de esôfago. MÉTODO: em estudo transversal foram triados 16 pacientes (43-73 anos) com câncer de esôfago e 20 voluntários (27-65 anos) controles sadios que preencheram os critérios clínicos e éticos da pesquisa. Para caracterização do estado geral de saúde efetuou-se avaliação antropométrica, hematimétrica (Hb, Ht, glóbulos brancos, linfócitos) e bioquímica (albumina, glicose, lipídios, aminotransferases). Adicionalmente, foram realizadas, no plasma, análises cromatográficas de taurina e seus precursores cisteína e homocisteína. Foi registrado o tempo de sobrevivência dos pacientes, a partir do diagnóstico histopatológico. RESULTADOS: Os pacientes com câncer de esôfago foram predominantemente do sexo masculino, raça branca, classe socioeconômica baixa, tipo carcinoma espinocelular de localização no terço superior, em estádio IV, sobrevida de 7,8 ± 5,5 anos, referindo perda de peso em 16,4% e apresentando hipoalbuminemia em 50%, com massa muscular e adiposa semelhante ao controle. Os pacientes apresentaram valores estatisticamente menores do que os controles para Hb, Ht, colesterol total, HDL-colesterol e cisteína e maiores de AST, ALT, taurina e homocisteína. Dentre os pacientes houve correlação positiva da taurina tanto com a contagem total de linfócitos, como com a sobrevida dos pacientes. CONCLUSÃO: Os níveis reduzidos de cisteína e elevados de homocisteína, taurina e as associações positivas da taurina com os indicadores da imunocompetência celular e da mortalidade sugerem participação efetiva da taurina na sobrevida dos pacientes e, portanto, os cuidados nutricionais específicos com a sua via geradora (cisteína, metionina e vitaminas do complexo B).

Carcinoma basalóide escamoso: uma forma rara e agressiva de câncer do esôfago e revisão da literatura

RACIONAL: O carcinoma basalóide escamoso ocorre com maior freqüência no trato aerodigestivo superior e raramente acomete o esôfago. OBJETIVO: Apresentar os aspectos clínico-patológicos e os atributos imunoistoquímicos de um paciente com carcinoma basalóide escamoso do esôfago. RELATO do CASO: Dos 134 pacientes com câncer do esôfago atendidos no Hospital Universitário de Botucatu-Unesp, São Paulo, de 1990 a 1999, somente um paciente (0,74%) apresentou carcinoma basalóide escamoso do esôfago. Tratava-se de paciente masculino, 41 anos, branco, lavrador com disfagia, regurgitação e emagrecimento há três meses. Referia tabagismo e etilismo há muitos anos. O esofagograma e o exame endoscópico revelaram lesão vegetante no terço distal do esôfago. A biópsia demonstrou neoplasia intraepitelial de alto grau associada a blocos de células basalóides que infiltravam o cório da mucosa, caracterizando o carcinoma basalóide escamoso. Os marcadores imunoistoquímicos foram positivos para o antígeno carcinoembriônico e para citoceratinas de alto peso molecular. A tomografia computadorizada revelou múltiplas metástases nos pulmões, fígado, e nódulos linfáticos regionais, documentando a fase avançada de evolução da doença. O tratamento consistiu apenas na realização de gastrostomia. O paciente apresentou queda acentuada do estado geral e evoluiu para óbito com quadro de melena quatro meses após o diagnóstico. CONCLUSÃO: O carcinoma basalóide escamoso é uma forma rara e agressiva de câncer do esôfago e o prognóstico depende do estadiamento da lesão e das condições clínicas do paciente no momento do diagnóstico.

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.