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Midesophageal biopsies from normal-appearing mucosa should be obtained in all patients with unexplained solid food dysphagia; this may diagnose EE in about one in 10 cases.

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0 100); histologic remission was defined as a peak count of <20 eosinophils/ mm2 in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

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Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.

known to induce hepatocellular injury. 5,6 Although ceramides Although ceramide signaling pathways have been imare well known to cause cell death by inducing apoptosis, plicated in cell death, neither their role in hepatocellular they can also cause cell death by necrosis. [3][4][5]7 Based on these death nor the cellular mechanisms mediating ceramidedata, we generated the hypothesis that the ceramide signalinduced cell death are known. The mitochondrial meming pathway induces cell death in hepatocytes, either by causbrane permeability transition (MMPT) has been proing apoptosis or necrosis. posed as a common final pathway in cell death. Thus the Induction of the mitochondrial membrane permeability aims of our study were to determine if ceramides cause transition (MMPT), an abrupt increase in the permeability of hepatocellular death by inducing the MMPT. Ceramides the inner mitochondrial membrane to small molecular weight induce hepatocellular death by necrosis and not solutes, has been implicated as a final common pathway causapoptosis as confirmed by morphology and the absence ing hepatocellular injury. 1,[8][9][10] The MMPT is characterized by of internucleosomal DNA cleavage. Ceramide-mediated mitochondrial depolarization, failure of oxidative phosphoryhepatocyte necrosis was acyl chain-length, concentralation with ATP depletion, and ultimately cell death. 1 The tion, and time-dependent. Ceramide induced cell necroincreased permeability of the inner mitochondrial membrane sis was associated with adenosine triphosphate (ATP) is thought to be facilitated by a specific proteinaceous ''megadepletion and mitochondrial depolarization suggesting pore'' located on the inner mitochondrial membrane. The that ceramides caused mitochondrial dysfunction. In opening of this pore is partially inhibited by cyclosporine A isolated mitochondria, ceramides induced the cycloplus trifluoperazine (CyA/TFP). 8-11sporine A-sensitive MMPT in an acyl chain-length and The overall objective of our study was to determine if ceraconcentration dependent manner. Ceramide toxicity mide causes hepatocyte necrosis by inducing the MMPT. Our was specific as the less potent dihydro form did not inspecific aims were to answer the following questions: 1) Do duce cell necrosis, significant ATP depletion, mitochonceramides induce cell death, and if so, does cell death occur by drial depolarization nor the MMPT. 1 However, we have suggested that signaling ley rats (200-300 g) as previously described.12 For those experiments cascades may induce cell death. 2 For example, we have pro-employing multiparameter digitized video microscopy, the hepatoposed that phospholipase-mediated calpain activation contri-cytes were cultured on collagen-coated glass coverslips. [13][14][15] butes to hepatocellular death during anoxia.2 Another potenDetermination of Cell Viability and ATP. In cells suspensions, cell tial signaling mechanism for hepatocellular death maybe the viability was determined by propidium iodide fluorometry.12 ATP was quantified using the luciferin...

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