Multiple lesions of adenocarcinoma with extensive dysplasia in long-segment Barrett’s esophagus treated with thoracoscopic surgery: a case report

In contrast to Western countries, in Japan esophageal adenocarcinoma and classic Barrett’s esophagus (long-segment Barrett’s esophagus) have been considered extremely uncommon. Although alternative therapeutic techniques such as endoscopic ablation, photodynamic therapy, and endoscopic mucosal resection have been improved, esophagectomy remains the gold standard treatment for high-grade dysplasia and/or early adenocarcinoma of the esophagus. Recently, minimally invasive operational procedures have been developed as a safe and feasible alternative technique to traditional open techniques, which has enabled us to expand the indication. In this report, we describe a Japanese case of multiple lesions of adenocarcinoma in long-segment Barrett’s esophagus, resected by thoracoscopic surgery. Our experience indicates that thoracoscopic esophagectomy could be one of the treatment options for multiple malignant or extensive precancerous lesions in long-segment Barrett’s esophagus.     

Endoscopic ultrasound-guided fine-needle aspiration in patients with lymphadenopathy suspected of recurrent malignancy after curative treatment

Background  The diagnosis of lymphadenopathy after treatment of malignancy is sometimes difficult, especially in patients whose treatment was deemed curative and without local recurrence or those who have increased serum levels of related tumor markers. We aimed to evaluate the effectiveness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a diagnostic tool in patients with lymphadenopathy after curative treatment of malignancy. Methods  Consecutive patients with mediastinal, intraabdominal, or pelvic lymphadenopathy after curative treatment of malignancy who were referred to our hospital between October 2003 and September 2007 were enrolled in this study. Results  A total of 62 patients were included. The lymph nodes were located at the mediastinum in 22 patients, intraabdomen in 38 patients, and intrapelvis in 2 patients. From the pathological findings of the FNA sample, 31 patients (50%) were confirmed to have recurrence of the prior malignancy, and 9 patients (15%) were diagnosed as having a different new malignancy. The remaining 22 patients (35%) were shown to have no recurrence or no other malignancies. However, 1 of them was later diagnosed with recurrence by open laparotomy. The overall sensitivity, specificity, accuracy, and positive and negative predictive values of the EUS-FNA were 97%, 100%, 98%, 100%, and 97%, respectively. Conclusions  Lymphadenopathy after treatment of malignancy is not a definitive sign of recurrence. Therefore, pathological sampling and diagnosis are essential for determining the appropriate treatment. For this purpose, EUS-FNA is a safe, convenient, and minimally invasive procedure with high diagnostic value.     

Diagnostic utility of biopsy specimens for autoimmune pancreatitis

Background and aims  Infiltration of IgG4-positive plasma cells in the pancreas and other organs is characteristic of autoimmune pancreatitis (AIP). However, it is undetermined whether needle or forceps biopsy of pancreas or other organs is indeed useful for the diagnosis of AIP. We aimed to clarify this point. Methods  Among 39 AIP patients, tissue sampling without laparotomy was performed in 27. Biopsy of pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was performed in 15, 17, 11, 5 and 7, respectively. The obtained specimens were examined for IgG4-positive plasma cells. We also examined gastric mucosa of 18 patients with pancreatic cancer as controls. When the number of IgG4-positive plasma cells was more than 10 per high-power field, we regarded it as diagnostic. Results  Diagnostic sensitivity in pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was 47% (7/15), 47% (8/17), 36% (4/11), 0% (0/5), and 57% (4/7), respectively. Conclusions  Sensitivity of IgG4 immunostaining was unsatisfactory when tissue sampling was performed by needle or forceps biopsy. Biopsy of gastric mucosa might be a good subsidiary diagnostic tool.     

Bioconversion of AS1387392: bioconversion studies involving Amycolatopsis azurea JCM 3275

We screened actinomycetes capable of converting AS1387392 to AS1429716 and identified those strains capable of hydroxylation. Amycolatopsis azurea JCM 3275 was found to be a particularly efficient strain, capable of converting AS1387392 to AS1429716, with a yield of 44% after 9?h. This strain can metabolize not only the hydroxylation of phenylalanine at the meta and para positions but also the reduction of hydroxyketones, as shown by the isolation of bioconversion products. Examination of more suitable conversion conditions showed that pH 7.8 and 25?°C were the optimum pH and temperature for bioconversion, respectively. We also demonstrated the effect of carbon and nitrogen sources in the culture media on hydroxylation. Using this strain, we were able to efficiently produce AS1429716 as a chemical template. Further derivatization studies may provide more effective, safer immunosuppressants than those that are currently on-market.     

MRP transporters as membrane machinery in the bradykinin-inducible export of ATP

Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18α-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl^? channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3⁺ and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 μM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2⁺-activated Cl^? channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2⁺-activated Cl^? channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl^? channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.     

Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein

BACKGROUND & AIMS: Despite the evidence of hepatic iron overload in patients with chronic hepatitis C, it remains unknown if iron overload is related to hepatocarcinogenesis in this condition. The aim of this study was to determine whether iron overload contributes to development of hepatocellular carcinoma (HCC) in transgenic mice expressing the hepatitis C virus (HCV) polyprotein. METHODS: Male C57BL/6 transgenic mice expressing the HCV polyprotein and nontransgenic littermates were fed an excess-iron diet or control diet. Mice in each group were assessed for altered liver morphology and function and the development of liver tumors. RESULTS: Hepatic iron concentrations in mice fed the excess-iron diet were comparable to those of patients with chronic hepatitis C. There was no inflammation in transgenic and nontransgenic livers. Compared with mice in 3 other groups, transgenic mice fed the excess-iron diet showed marked hepatic steatosis including the centrilobular microvesicular type, ultrastructural alterations of the mitochondria and decreased degradation activity of fatty acid at 6 months, and greater hepatic content of lipid peroxidation products and 8-hydroxy-2'-deoxyguanosine at 12 months after initiation of feeding. The number of proliferating hepatocytes was significantly increased in mice fed the excess-iron diet but was not different between transgenic and nontransgenic mice. Hepatic tumors including HCC developed in 5 of 11 (45%) transgenic mice fed the excess-iron diet but not in mice in other groups at 12 months after initiation of feeding. CONCLUSIONS: Iron overload induces mitochondrial injury and increases the risk of HCC development in transgenic mice expressing the HCV polyprotein.