The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett's Esophagus.

OBJECTIVES: Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created. RESULTS: There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95. CONCLUSIONS: ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.

Transjugular intrahepatic portosystemic shunt for treatment of intractable colonic ischemia associated with portal hypertension: a bridge to liver transplantation.

A 64-year-old man with portal hypertension secondary to hepatic nodular transformation was awaiting liver transplantation when he presented with severe, unrelenting abdominal pain, fever, and hypotension. Computed tomographyrevealed pneumatosis within the cecum and ascending colon. Because of his advanced liver disease and the perceived high likelihood of a poor outcome after colonic resection, he was managed medically. He improved initially but had a lengthy hospital course notable for intractable intestinal ischemia and gastrointestinal bleeding. Magnetic resonance angiography demonstrated patent mesenteric, portal, and hepatic vessels. His blood pressure was typically 90/55 mm Hg (mean arterial pressure, 65-70 mm Hg) despite intravenous fluids and blood product replacement. The hypothesis developed that the patient's level of portal hypertension was sufficiently severe (in the face of his low mean systemic arterial pressure) to compromise perfusion of the colonic mucosa. Were this hypothesis correct, then portal decompression might enhance the blood pressure gradient across the bowel and improve mucosal perfusion. With this in mind, a transjugular intrahepatic portosystemic shunt (TIPS) was placed. There was reduction of the portal vein to inferior vena cava gradient from 29 mm Hg to 9 mm Hg and his abdominal pain and gastrointestinal bleeding ceased. His prompt and sustained improvement following TIPS shunt placement is consistent with the hypothesis that high portal pressure was flow limiting, thus contributing to persisting intestinal ischemia. This case represents the first report of use of a TIPS shunt to address colonic ischemia associated with portal hypertension.

Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy affect endoscopic gastric biopsy interpretation?

Accurate diagnosis of gastrointestinal graft-versus-host disease (GvHD) is important, as it contributes significantly to postallogeneic stem cell transplant (SCT) morbidity and mortality. To test the hypothesis that proton pump inhibitor (PPI) therapy may interfere with histologic evaluation of gastric GvHD by inducing apoptosis, we evaluated epithelial apoptotic body counts in antral and fundic biopsies from SCT recipients and control patients, both taking and not taking PPIs at the time of endoscopic biopsy. Hematoxylin and eosin-stained slides of gastric biopsies from 130 patients (75 allogeneic SCT with GvHD on clinical and histologic grounds, and a comparison group of 55 age- and sex-matched nontransplant patients with histologically normal gastric biopsies) were reviewed. The groups were further stratified into patients taking (PPI+) and not taking PPIs (PPI-) at the time of biopsy. Apoptotic bodies (AB)/10 (400 x) high power fields (HPF) were quantified for each case. Mean apoptotic body counts were then calculated for each case group. Seventy antral cases (31 control and 39 transplant) were also evaluated via gastrin immunohistochemistry, and the mean number of gastrin positive cells/400 x HPF calculated. In the PPI- groups, apoptosis was increased in biopsies from transplant patients, compared with controls, both in antral and fundic mucosa. In PPI+ patients, there was significantly more apoptosis in the gastric body in transplant patients than in controls. However, comparing antral biopsies from control and transplant PPI+ patients, there was no significant difference in AB quantitation. More apoptosis was seen in antral biopsies from PPI+ control patients when compared with PPI- control patients (P = 0.009). Mean numbers of gastrin positive cells/400 x HPF were increased in both control and transplant patients taking PPIs (85 and 58, respectively) compared with samples from those patients not taking PPIs (48 and 51, respectively). PPI therapy is associated with increased apoptosis in antral biopsies and may interfere with the evaluation of GvHD in biopsies from this site. A similar increase in apoptosis was not seen in fundic biopsies; biopsy of the gastric fundus rather than antrum may be preferable for the diagnosis of upper gastrointestinal GvHD.

Resection of mesenteric inflammatory veno-occlusive disease causing ischemic colitis.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of mesenteric ischemia that is diagnosed by histologic examination of the operative specimen. Recurrence of symptoms occurs, but further resection of ischemic intestine is seldom required. We describe the case of MIVOD in a young patient with clinical findings of ischemic colitis. The patient experienced complete resolution of the process, thus confirming the relatively benign course of this disease following resection. This report substantiates resolution of the inflammatory process after resection, colostomy, and reanastomosis. We review the literature and make conclusions regarding the clinical management of this disease.

Miliary tuberculosis as a cause of acute empyema.

Adult respiratory distress syndrome (ARDS) and sepsis are known, life-threatening complications of miliary tuberculosis. This report describes a patient with miliary tuberculosis who rapidly developed an acute tuberculous empyema. She had a fulminant course culminating in ARDS, sepsis and subsequent death. This case highlights the rare association of acute empyema with miliary tuberculosis.