Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study.

OBJECTIVES: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS: We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS: After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS: In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

A pro-inflammatory genotype predisposes to Barrett's esophagus.

INTRODUCTION: Severity of mucosal inflammation is shown to be associated with Barrett's esophagus (BE) development in animals. It has therefore been postulated that a strong pro-inflammatory host response predisposes to BE. AIM: To determine the impact of cytokine gene polymorphisms on the development of BE. METHODS: The multiplex SNaPshot method was used to determine interleukin (IL)-12B (A+1188C), IL-10 (C-592A, C-819T, A-1082G), IL-8 (A-251T), IL-6 (G-174C) and IL-2 (G-330T) gene polymorphisms in 255 patients with BE and 247 patients with reflux esophagitis (RE). RESULTS: The presence of the IL-12B C-allele, which is associated with increased IL-12p70 expression, was more frequently observed in BE than in RE patients [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.2-2.7; P = 0.007). The risk of BE was increased in patients in whom the IL-12B C-allele coincided with a hiatal hernia (OR 2.9; 95% CI 1.32-6.58; P = 0.008). The IL-10(-1082) GG genotype, which is associated with higher IL-10 levels, was also associated with a decreased risk of BE when it was associated with the IL-12B C-allele, indicating IL-10-dependent down-regulation of IL-12p70 expression. A combination of the IL-12B AA genotype and the IL-10 AA or AG genotypes was associated with RE (OR 1.4; 95% CI 1.05-1.85; P = 0.011). CONCLUSION: A genetic profile predisposing to a strong pro-inflammatory host response, mediated by IL-12p70 and partially dependent on IL-10, is associated with BE. This risk further increases when this genotype coincides with a hiatal hernia, suggesting that exposure to gastroesophageal reflux in the presence of a pro-inflammatory genetic background is a driving force in the development of BE.

The role of endorectal ultrasound in therapeutic decision-making for local vs. transabdominal resection of rectal tumors.

INTRODUCTION: In rectal tumors, preoperative biopsies frequently fail to diagnose an invasive carcinoma. Endorectal ultrasound is considered a useful adjunct in preoperative staging of rectal tumors. However, feasibility of endorectal ultrasound and its role in therapeutic decision-making in presumed rectal adenomas is sparsely studied. METHODS: Endorectal ultrasound was performed in 268 tumors referred for local excision because biopsies showed tubulovillous adenoma. Feasibility of endorectal ultrasound was studied and ultrasound staging was compared with definite histopathologic findings. RESULTS: In 231 tumors, endorectal ultrasound was technically feasible (86 percent). Median distance from the dentate line was 11 cm in nonassessable tumors and 7 cm in assessable tumors (P < 0.001). In 21 tumors, endorectal ultrasound was not conclusive, mainly in tumors being recurrent or after recent endoscopic manipulation (P < 0.001). With endorectal ultrasound the rate of preoperative missed carcinomas could be reduced from 21 to 3 percent (P < 0.01). In diagnosing tubulovillous adenomas, sensitivity and specificity of endorectal ultrasound was 89 and 86 percent, respectively. CONCLUSIONS: Endorectal ultrasound is technically feasible in almost all presumed rectal adenomas, referred for local excision. Proper endorectal ultrasound interpretation is possible in 78 percent of all presumed rectal adenomas. Endorectal ultrasound is very reliable in diagnosing tubulovillous adenomas, and therapeutic decision-making regarding local excision vs. radical surgery based on endorectal ultrasound is valid.

A patient with gastric fundal varices and colonic varices due to splenic vein thrombosis.

We report a patient presenting with melena. Endoscopic examination showed gastric fundal varices as well as colonic varices. The latter is rarely encountered and is usually associated with portal hypertension. On angiography there appeared to be a splenic vein thrombosis which is only reported once earlier as a cause of colonic varices. A short review of the literature concerning colonic varices is added.

Renography in diagnosis and follow-up of renal vein thrombosis.

The case of a patient in whom the diagnosis of renal vein thrombosis was supported by renographic and scintigraphic patterns that disappeared several days after the initiation of heparin therapy is reported. This observation suggests that renal investigation with radionuclides can be an important aid in the diagnosis and follow-up of patients with acute renal vein thrombosis.