Two unusual sites of metastases of esophageal adenocarcinoma.

The most common sites of metastasis for esophageal cancers include the liver, lungs, and bones. We report a rare case of esophageal adenocarcinoma with metastasis to the subcutaneous perianal region as well as to the small bowel. Physicians should consider the possibility of metastasis in a patient with esophageal adenocarcinoma even after the onset of remission. It is essential to examine these patients and maintain a high index of suspicion for possible metastases. Early recognition helps in the accurate staging of the disease and enables the initiation of life-prolonging therapy and achieving meaningful palliation.

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target.

Diagnostic yield of malignancy during EUS-guided FNA of solid lesions with and without a stylet: a prospective, single blind, randomized, controlled trial.

BACKGROUND: Use of a stylet during EUS-guided FNA (EUS-FNA) is believed to improve the quality and diagnostic yield of specimens. OBJECTIVE: To compare samples obtained by EUS-FNA with (S+) and without (S-) a stylet for diagnostic yield of malignancy and cytological characteristics. DESIGN: Randomized, controlled trial. SETTING: Tertiary referral center. PATIENTS: Consecutive patients referred for EUS-FNA of solid lesions. INTERVENTION: EUS-FNA; the number of passes was determined by lesion site (6 pancreas/others and 4 lymph nodes). MAIN OUTCOME MEASUREMENTS: Diagnostic yield of malignancy and degree of cellularity, specimen adequacy, contamination, and amount of blood. RESULTS: One hundred patients were prospectively enrolled in this randomized, controlled trial and the sites of EUS-FNA were the pancreas, 58; lymph node, 25; and other, 17. The overall diagnosis was malignancy in 56, benign in 30, suspicious/atypical in 7, and inadequate specimen in 7 lesions. There were 550 passes made (275 with a stylet and 275 without a stylet). Interim analysis demonstrated no difference in the diagnostic yield of malignancy (94 passes with a stylet [34.2%] vs 110 without a stylet [40%], P = .2) and in the proportion of inadequate specimens (57 with a stylet [20.7%] vs 64 without a stylet [23.3%], P = .2). There was no difference with regard to cellularity (P = .83), contamination (P = .31), number of cells (P = .25), and amount of blood (P = .6). Similar results were noted in a subgroup analysis based on lesion site. Applying the rules of futility, the study was terminated. LIMITATIONS: Subjectivity in cytopathologists' assessment, endosonographer not blinded. CONCLUSIONS: There was no difference in the diagnostic yield of malignancy or proportion of inadequate specimens between passes with and without a stylet. These results suggest that the use of a stylet does not confer any advantage during EUS-FNA.

Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report.

INTRODUCTION: Pheochromocytoma is a rare cause of hypertension but it could have severe consequences if not recognized and treated appropriately. The association of pheochromocytoma and thrombosis is even rarer but significantly increases management complexity, morbidity and mortality. To the best of our knowledge, this is the first report of a patient with pheochromocytoma presenting with left axillary arterial and intracardiac thrombus. CASE PRESENTATION: A 47-year-old Caucasian woman with a past medical history of hypertension presented for medical attention with left arm numbness. Doppler ultrasound showed an obstructing thrombus in her left axillary artery. She had symptom resolution after stent placement in her left axillary artery. A subsequent echocardiogram demonstrated a large intracardiac mass and abdominal computed tomography revealed a 7 cm mass between her spleen and left kidney. Labile blood pressure was noted during admission and she had very high levels of plasma and 24-hour urine catecholamines and metanephrines tests. A (123)I- metaiodobenzylguanidine scan showed intense uptake in the left abdominal mass. After adequate alpha blockage with phenoxybenzamine, laparoscopic tumor resection was performed without complications. She had normal metanephrines and complete symptom resolution afterwards. The intracardiac mass also disappeared with anticoagulation. All other endocrine laboratory abnormalities returned to normal after surgery. CONCLUSION: Arterial and ventricular thrombosis occurring in patients with pheochromocytoma is rare. A multi-disciplinary approach is necessary in caring for this type of patient. Catecholamines likely contributed to the development of thrombosis in our patient. Early recognition of pheochromocytoma is the key to improving outcome.

Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine.

Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

OBJECTIVE: Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. DESIGN: Prospective, randomized controlled study. SETTING: Animal laboratory in a university medical center. SUBJECTS: C57Bl/6 mice. INTERVENTIONS: Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. MEASUREMENTS AND MAIN RESULTS: Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. CONCLUSIONS: When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may help explain this differential response.