Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis

Eosinophilic cholangiopathy is a rare condition characterized by eosinophilic infiltration of the biliary tract and causes sclerosing cholangitis. We report a patient with secondary sclerosing cholangitis with eosinophilic cholecystitis. A 46-year-old Japanese man was admitted to our hospital with jaundice. Computed tomography revealed dilatation of both the intrahepatic and extrahepatic bile ducts, diffuse thickening of the wall of the extrahepatic bile duct, and thickening of the gallbladder wall. Under the diagnosis of lower bile duct carcinoma, he underwent pyloruspreserving pancreatoduodenectomy and liver biopsy. On histopathological examination, conspicuous fibrosis was seen in the lower bile duct wall. In the gallbladder wall, marked eosinophilic infiltration was seen. Liver biopsy revealed mild portal fibrosis. He was diagnosed as definite eosinophilic cholecystitis with sclerosing cholangitis with unknown etiology. The possible etiology of sderosing cholangitis was consequent fibrosis from previous eosinophilic infiltration in the bile duct. The clinicopathological findings of our case and a literature review indicated that eosinophilic cholangiopathy could cause a condition mimicking primary sclerosing cholangitis （PSC）. Bile duct wall thickening in patients with eosinophilic cholangitis might be due to fibrosis of the bile duct wall. Eosinophilic cholangiopathy might be confused as PSC with eosinophilia.     

Clinical prevention of gastric cancer by Helicobacter pylori eradication therapy: a systematic review

Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. We conducted a systematic review concerning gastric cancer development after H. pylori eradication therapy. In total 15 papers matched our criteria, the results were reviewed. The H. pylori eradication therapy statistically diminished the prevalence of clinical gastric cancer by approximately one-third. The studies from Japan supported this conclusion; however, studies from overseas reported conflicting results. The differences in these conclusions lie in the diagnostic ability of endoscopic examination, since the clinical stage was quite different between these studies. Gastric cancer that developed after eradication revealed a mainly intestinal type histology and depressed-type appearance. The following are possible reasons for reduced gastric cancer: (1) eradication therapy inhibits the new occurrence of gastric cancer, (2) eradication regresses or inhibits the growth of gastric cancer, and (3) eradication interferes with the discovery of gastric cancer. Considering the biological nature of cancer cell proliferation, a sufficiently long-term follow-up may clarify the effect of eradication therapy on inhibition of the development (not discovery) of gastric cancer and reduction of gastric cancer-related mortality.     

Autoimmune pancreatitis associated with a large pancreatic pseudocyst that disappeared after corticosteroid therapy: a case report and literature review

A 51-year-old woman was admitted to our department because of upper abdominal pain. The serum IgG4 concentration was elevated, and abdominal computed tomography revealed diffuse enlargement of the pancreas associated with a large cyst, measuring 8 cm in diameter. Endoscopic retrograde cholangiopancreatography revealed narrowing of the main pancreatic duct (from the body to the tail), narrowing of the intrapancreatic bile duct, and dilatation of the bile ducts. The patient was given a diagnosis of autoimmune pancreatitis (AIP) associated with a pancreatic pseudocyst and intrapancreatic bile duct stenosis. Oral steroid therapy resulted in reduced pancreatic swelling, complete disappearance of the pancreatic cyst, and an improvement in biliary stenosis. AIP is rarely associated with pancreatic cyst, and only 13 cases, including ours, have been reported to date. In our patient, intense inflammation apparently led to cyst formation in association with AIP, which responded remarkably to corticosteroid therapy. Correct diagnosis of AIP associated with a pancreatic pseudocyst might save patients from undergoing unnecessary endoscopic and surgical procedures.     

Experience of appendicular thermal therapy applied to a patient with a left ventricular assist device awaiting heart transplantation

Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0 °C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure.     

Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

BackgroundImmunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy.MethodsThis was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks.ResultsLTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy.ConclusionsST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients.     

Flow cytometric analysis of skin blister fluid induced by mosquito bites in a patient with chronic active Epstein–Barr virus infection

In chronic active Epstein–Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56⁺ NK cells in the fluid compared with a simple mosquito allergy, in which the majority of infiltrated cells were CD203c⁺ cells, indicating basophils and/or mast cells. His fluid also contained CD203c⁺ cells, and his circulating basophils were activated by mosquito extracts in vitro. These results suggest that CD203c⁺ cells as well as NK cells may play pathogenic roles in the severe skin reactions to mosquito bites in NK-CAEBV.     

Combined carotid and transcranial color-coded sonography in acute ischemic stroke.

The objective of this study is to clarify whether the combination of carotid duplex sonography (CD) and transcranial color-coded sonography (TCCS) can accurately detect occlusive lesions in extra and intracranial brain arteries in acute stroke patients, using angiography as the standard. Just before angiography, we performed CD and TCCS in 40 consecutive patients within 24 h after stroke onset. We assessed 320 vessels in total, bilateral internal carotid arteries, vertebral arteries, M1 segments of middle cerebral arteries (MCAs), and P2 segments of posterior cerebral arteries (PCAs). Out of all vessels, 250 (78.1%) could be evaluated by neurosonography because 32 MCAs and 38 PCAs were excluded due to inadequate acoustic windows for TCCS. Significant occlusive lesions (>50%) were observed in 21 out of 250 vessels by neurosonography. Angiography confirmed 20 occlusive lesions as revealed by neurosonography. In the remaining 229 neurosonographically normal vessels, angiography showed no significant lesions except M2 occlusions. The accuracy, sensitivity, and specificity of neurosonography for the detection of occlusive vessels were 99.6, 100 and 99.6%, respectively. Occlusive lesions were observed in 20 of all patients by neurosonography. Nineteen of them were confirmed by angiography. The combination of CD and TCCS can make an accurate diagnosis for significant occlusive lesions in brain arteries in acute stroke patients.     

A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility

The collagen-gel droplet embedded-culture drug sensitivity test (CD-DST), a chemosensitivity test, evaluate the efficacy of anticancer drugs and to was used clinically to thus plan rational postoperative chemotherapy for patients with pancreatic and biliary tract carcinomas. The CD-DST solves some problems inherent in other conventional assays. This method: (1) allows evaluation of four chemotherapeutic agents, using small quantities of cells (1 × 10⁵ cells), (2) shows high primary culture success rates, (3) maintains the original growth characteristics of the cultured cells, (4) eliminates the effects of fibroblasts by employing image analysis, and (5) permits evaluation using physiologic drug concentrations. Primary cultures of tumor cell samples from all 25 patients with pancreatic or biliary tract carcinomas studied were successful. Against pancreatic carcinomas, the efficacy rates, assessed by CD-DST, of four anticancer drugs evaluated were: 25.0% for mitomycin (MMC), followed by 23.5% for adriamycin, 18.8% for 5-fluorouracil (5-FU), and 11.8% for cisplatin (CDDP). Against biliary tract carcinomas, the rates were highest for 5-FU and MMC (50.0%) and lowest for CDDP (25.0%). The efficacy rates for all four anticancer drugs evaluated were higher against biliary tract carcinomas than against pancreatic carcinomas. Tumor cultures from 10 of 17 patients with pancreatic cancer and 3 of 8 patients with biliary tract cancer showed no sensitivity to any of the drugs tested. The in-vitro results with CD-DST suggest the risk of administering non-selective postoperative chemotherapy to patients with pancreatic and biliary tract carcinomas, and emphasize the importance of carefully selecting effective chemotherapeutic agents based on adequate chemosensitivity testing.     

Enhanced exon 2 skipping caused by c.910G>A variant and alternative splicing of MEFV genes in two independent cases of familial Mediterranean fever

Most reported cases of familial Mediterranean fever (FMF) involve missense mutations of MEFV concentrated within exon 10. We experienced two independent pedigrees of a unique variant in the MEFV gene that might cause excessive exon 2 skipping due to enhanced alternative splicing. In this study, we tried to elucidate the molecular mechanism of the MEFV variant as a cause of the FMF phenotype. Peripheral blood was obtained from volunteers and two patients with homozygous c.910G>A variant of the MEFV gene. MEFV messenger RNA (mRNA) expression patterns in mononuclear cells and granulocytes were compared using forward and reverse primers from exons 1 and 3, respectively. Expression profiles of pyrin were examined by transfecting wild-type and variant MEFV genes into HEK293T cells. Expression of normal-sized mRNA was extremely reduced in these patients, whereas that of aberrant short mRNA, deleting exon 2 (Δex2), was significantly increased. Immunohistochemical and immunoblotting analyses revealed a truncated immunoreactive pyrin protein in cells transfected with Δex2 cDNA. The MEFV gene c.910G>A variant results in accelerated aberrant splicing with abnormal protein size, presumably leading to anomalous pyrin function. This is the first report to show that an MEFV variant other than missense mutation is responsible for the FMF phenotype.