RESUMEN
OBJECTIVES: The insulin-like growth factor (IGF) pathway and visceral obesity have been independently linked with esophageal cancer. This study aimed to delineate the differential and interlinked role of visceral obesity and the IGF-1 system in esophageal adenocarcinoma and esophageal squamous-cell carcinoma (SCC). METHODS: IGF-1 receptor (IGF-1R) mRNA and protein were examined in esophageal SCC (KYSE 410, OE21) and esophageal adenocarcinoma (OE19, OE33) cell lines by western blotting. Tumor cell proliferation in response to IGF-1 was assessed by bromodeoxyuridine incorporation assay. In esophageal tumor sections, expression of IGF-1R and CD68(+) cell numbers were assessed by immunohistochemistry. IGF-1 was measured in serum from esophageal cancer patients, Barrett's esophagus patients, and healthy controls by enzyme-linked immunosorbent assay. RESULTS: Higher IGF-1R protein expressions were observed in SCC cells compared with esophageal adenocarcinoma cells however only adenocarcinoma cell lines significantly increased proliferation in response to IGF-1 (P<0.01). Serum IGF-1 levels were highest in esophageal adenocarcinoma patients (P<0.01) and higher in viscerally obese vs. nonobese (P<0.05) patients. In resected esophageal cancer, increased expression of IGF-1R was observed in the tumor and invasive edge compared with tumor-associated stroma (P<0.05), which coincided with increased CD68(+) cells in stromal tissue surrounding invasive tumor edge (P<0.01). CONCLUSIONS: This novel study examined the differential role of the IGF system in esophageal adenocarcinoma and SCC, and its association with visceral obesity. These results indicate that the IGF-1 axis has a key role in malignant progression of esophageal cancer, and represents a plausible mechanism through which visceral obesity impacts on esophageal adenocarcinoma risk and tumor biology.
Asunto(s)
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Obesidad/metabolismo , Receptor IGF Tipo 1/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Proliferación Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Esófago/metabolismo , Esófago/patología , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Masculino , Persona de Mediana Edad , Obesidad/genética , Obesidad/patología , Receptor IGF Tipo 1/genéticaRESUMEN
Excess visceral adiposity is associated with increased gastrointestinal cancer risk. Evidence suggests that the systemic inflammation and dysmetabolism observed in visceral obesity underpins this association. Along with magnetic resonance imaging, computed tomography is a gold standard for abdominal fat quantification and is routinely available for gastrointestinal cancer research. However, no gender-specific cutoff values are currently available for classifying visceral obesity in white populations. Using the metabolic syndrome (MetSyn) as an indicator of obesity-associated dysmetabolism, this study aimed to establish pathologically relevant, gender-specific cut-off values for use in obesity-associated cancer research. Total, visceral and subcutaneous fat areas were calculated between the L3 and L4 invertebral space from computed tomography scans in a cohort of 170 males and 66 females undergoing gastrointestinal resection. Receiver operating characteristics analysis was used to determine cut-off values for total, visceral and subcutaneous fat areas associated with MetSyn. Linear regression was used to correlate these values with waist circumference. Visceral fat area (VFA) strongly correlated with the presence of MetSyn (P < .0001). The cut-off value for VFA associated with the presence of MetSyn was 163.8 cm(2) in males (83.6% sensitivity, 62.5% specificity) and 80.1 cm(2) for females (96% sensitivity, 73.2% specificity). The waist circumference corresponding to these VFA values was 96.1 cm in males and 83.2 cm in females. This study is the first to generate gender-specific and pathologically relevant cut-off values for VFA in patients with gastrointestinal cancer. In the field of obesity-associated research, this new anthropometric measure is of paramount importance for determining the accurate pathological obesity status of cancer patients.
Asunto(s)
Neoplasias Gastrointestinales/etiología , Grasa Intraabdominal/diagnóstico por imagen , Síndrome Metabólico/diagnóstico por imagen , Obesidad/complicaciones , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Grasa Intraabdominal/patología , Masculino , Síndrome Metabólico/patología , Persona de Mediana Edad , Obesidad/patología , Curva ROC , Valores de Referencia , Factores de Riesgo , Sensibilidad y Especificidad , Factores Sexuales , Circunferencia de la CinturaRESUMEN
Achalasia is an oesophageal motility disorder characterised by aperistalsis and failure of relaxation of a hypertensive lower oesophageal sphincter. Treatment intent targets the sphincter, and either Heller's myotomy or pneumatic dilatation successfully relieves dysphagia in the majority of cases. End-stage achalasia, typified by a massively dilated and tortuous oesophagus, may occur in patients previously treated but where further dilatation or myotomy fails to relieve dysphagia or prevent nutritional deterioration, and oesophagectomy may be the only option. We describe two patients with end-stage achalasia and nutritional failure despite exhaustive conventional therapy including pneumatic dilatation and surgical myotomy. Both patients were successfully managed with transhiatal oesophagectomy and cervical gastro-esophageal anastomosis, with excellent symptomatic control and improved quality of life. These cases are discussed and the literature reviewed.