Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study.

AIM: To assess the clinical characteristics of patients with complicated erosive esophagitis (EE) and their associated factors. METHODS: This prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios (aOR) and 95%CI for the association with complicated EE. RESULTS: During the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors (PPIs) were included. Of them, 143 (8.2%) had EE complications. Esophageal bleeding occurred in 84 (4.8%) patients, esophageal strictures in 45 (2.6%) patients, and 14 (0.8%) patients experienced both. Multivariate analysis showed that increased age (aOR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents (aOR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B (aOR: 2.69; 95%CI: 1.48-4.96), C (aOR: 15.38; 95%CI: 8.62-28.37), and D (aOR: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated (aOR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age (aOR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B (aOR: 3.60; 95%CI: 1.52-8.50), C (aOR: 27.61; 95%CI: 12.34-61.80), and D (aOR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age (aOR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom (aOR: 2.51; 95%CI: 1.39-4.51), concomitant use of psychotropic agents (aOR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C (aOR: 7.35; 95%CI: 3.32-16.25), and D (aOR: 20.34; 95%CI: 8.36-49.53) and long-segment Barrett's esophagus (aOR: 4.63; 95%CI: 1.64-13.05). CONCLUSION: Aging and severe EE were common associated factors, although there were more associated factors in esophageal strictures than esophageal ulcer bleeding. Despite the availability and widespread use of PPIs, EE complications are likely to remain a problem in Japan owing to the aging population and high-stress society.

Effect of obstructive jaundice on hepatic hemodynamics: use of Sonazoid-enhanced ultrasonography in a prospective study of the blood flow balance between the hepatic portal vein and hepatic artery.

PURPOSE: To prospectively clarify the effects of obstructive jaundice (OJ) on hepatic hemodynamics using contrast-enhanced ultrasonography (US). METHODS: Subjects comprised 14 patients admitted to our hospital for OJ between April 2013 and March 2014. Contrast-enhanced US was performed using the LOGIQ E9 ultrasound device during the jaundice phase, before biliary drainage, and again after improvement of jaundice. After injecting the Sonazoid contrast agent, contrast dynamics were recorded in the right kidney and liver segments 5 or 6. Prototype software was used to calculate mean arrival time (AT) of the contrast agent in the liver parenchyma. Statistical analysis was performed to compare the mean AT in the jaundice and improved jaundice phases. RESULTS: We were unable to follow up three of the 14 patients after biliary drainage; thus, we included 11 patients for further analysis. The mean AT of the contrast agent was 2.0 ± 1.8 and 6.1 ± 2.3 s in the jaundice and improved jaundice phases, respectively, showing significantly shorter AT in the jaundice phase (p = 0.0033). CONCLUSION: Our findings indicate that OJ may influence the blood flow balance between the hepatic portal vein and hepatic artery.

Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature.

The present study reports the case of a 68-year-old male patient who presented to Tokyo Rosai Hospital for the treatment of alcoholic liver disease. A high density was observed in liver segment S2, while a tumor, 30 mm in size, exhibiting a low density was observed in the delayed phase upon contrast-enhanced computed tomography (CT), which was performed prior to admission. The tumor appeared slightly poorly defined upon abdominal ultrasound and was observed as a 30 mm low-echoic nodule that was internally heterogeneous. A 5-mm thick contrast enhancement effect was observed in the tumor border in the vascular phase on Sonazoid contrast-enhanced ultrasonography, while a defect in the entire tumor was observed in the post-vascular phase. Dysphagia had commenced three months prior to presentation and a weight loss of ~3 kg was observed. Therefore, the patient was admitted to Tokyo Rosai Hospital due to the presence of a hepatic tumor, and to undergo a close inspection of the cause of the tumor. Upon close inspection, it was determined that the weight loss and aphagia were caused by progressive bulbar paralysis. A contrast-enhanced CT was performed on post-admission day 29 as a follow-up regarding the hepatic tumor. As a result, although no change in the tumor size was observed, the contrast enhancement in the tumor borderline had disappeared. Necrosis of the tumor was considered. However, as viable persistence of the malignant tumor could not be excluded, a hepatic left lobe excision was performed. The patient was diagnosed with hepatocellular carcinoma (HCC) based on the morphology of the cellular necrosis. In addition, occlusion due to thrombus was observed within the blood vessels passing inside the fibrous capsule. It was hypothesized that the formation of a thick fibrous capsule and occlusion due to thrombus in the feeding vessel were possibly involved as the cause of complete spontaneous necrosis. Written informed consent was obtained from the patient.

Gallstone Ileus following Endoscopic Stone Extraction.

An 85-year-old woman was an outpatient treated at Tokyo Rosai Hospital for cirrhosis caused by hepatitis B. She had previously been diagnosed as having common bile duct stones, for which she underwent endoscopic retrograde cholangiopancreatography (ERCP). However, as stone removal was unsuccessful, a plastic stent was placed after endoscopic sphincterotomy. In October 2012, the stent was replaced endoscopically because she developed cholangitis due to stent occlusion. Seven days later, we performed ERCP to treat recurring cholangitis. During the procedure, the stone was successfully removed by a balloon catheter when cleaning the common bile duct. The next day, the patient developed abdominal pain, abdominal distension, and nausea and was diagnosed as having gallstone ileus based on abdominal computed tomography (CT) and abdominal ultrasonography findings of an incarcerated stone in the terminal ileum. Although colonoscopy was performed after inserting an ileus tube, no stone was visible. Subsequent CT imaging verified the disappearance of the incarcerated stone from the ileum, suggesting that the stone had been evacuated naturally via the transanal route. Although it is extremely rare for gallstone ileus to develop as a complication of ERCP, physicians should be aware of gallstone ileus and follow patients carefully, especially after removing huge stones.

Mucinous cystadenocarcinoma of the appendix in which contrast-enhanced ultrasonography was useful for assessing blood flow in a focal nodular lesion in the tumor cavity: A case report.

A 63-year-old woman was admitted to hospital with pain in the right lower quadrant. Abdominal computed tomography (CT) revealed a 60-mm cystic mass at a site corresponding to the appendix. The mass wall on the appendicular ostium was thickened and enhanced by contrast, while calcification was observed in the mass wall on the appendicular tip. No projection was observed in the mass cavity. On abdominal ultrasonography (US), the mass wall on the appendicular ostium was thickened and projections were observed at two sites in the mass cavity. On contrast-enhanced US (CEUS), only one of these projections was enhanced. Based on the thickened and contrast-enhanced wall of the mass on the appendicular ostium on CT and US, as well as the contrast enhancement of a projection on US, the mass was diagnosed as mucinous cystadenocarcinoma of the appendix. Ileocecal resection was subsequently performed on day 10. A detailed examination of the surgical specimen revealed carcinoma cells in the mass wall on the appendicular ostium. The contrast-enhanced projection was identified as granulation tissue that had grown to come into contact with the tumor, while the non-contrast-enhanced projection was identified as solidified mucus. US enabled successful visualization of projections in the mass cavity that were not visible on abdominal CT. CEUS also proved useful for assessing blood flow in these projections.

Endoscopic nasobiliary drainage improves jaundice attack symptoms in benign recurrent intrahepatic cholestasis: A case report.

A 66-year-old male with unbearable pruritus and jaundice was admitted for detailed examination. Blood tests on admission showed increased bilirubin with a dominant direct fraction. Ultrasonography and computed tomography performed subsequent to admission showed no narrowing or distension of the bile ducts. As the jaundice symptoms were not improved by the oral administration of ursodeoxycholic acid (300 mg/day) that had been started immediately after admission, endoscopic retrograde cholangiopancreatography (ERCP) was performed on hospital day 14. This also showed no abnormalities of the bile ducts. After considerating its potential effects for improving jaundice, endoscopic nasobiliary drainage (ENBD) was performed on the same day and was followed by immediate improvements in pruritus and jaundice. Detailed examinations were performed to identify the cause of the jaundice, which was suspected to be viral hepatitis, autoimmune hepatitis or drug-induced liver injury, however, there were no findings suggestive of any of these conditions. Following a further increase in bilirubin levels, confirmed by additional blood tests, a liver biopsy was performed. Histological findings were consistent with the histological features of benign recurrent intrahepatic cholestasis (BRIC). Although ursodeoxycholic acid is used as a first-line treatment in most cases of BRIC, ENBD should also be considered for patients not responding to this treatment.

A case of branch duct type intraductal papillary neoplasm of the bile duct treated by open surgery after 11 years of follow-up.

The intraductal papillary neoplasm of the bile duct (IPNB) is a novel disease concept that was recently classified as a biliary cystic tumor by the revised World Health Organization classification. This is the case report of a 70-year-old female patient who experienced repeated episodes of obstructive jaundice and cholangitis since 2000, attributed to a mucus-producing hepatic tumor. Surgery was advised due to the repeated episodes; however, the patient refused. In May, 2011, the patient developed jaundice and fever and was treated with antibiotics. Since there was no improvement, the patient was admitted to the Tokyo Rosai Hospital. Abdominal computed tomography (CT) revealed a 50-mm cystic mass with an internal septum in the left hepatic lobe. Although the tumor size had remained almost unchanged compared to the initial CT scan performed in 2000, intra- and extra-hepatic bile duct dilation was more prominent on the second CT scan. Following admission, endoscopic retrograde cholangiopancreatography was performed and revealed an expanded papilla of Vater due to a mucous plug. A balloon catheter was inserted into the bile duct to remove the mucous plug, resulting in the drainage of copious amounts of mucus and infected bile. The patient finally consented to surgery and left hepatic lobectomy was performed. Consequently, the diagnosis of low-grade IPNB was made. Branch duct type IPNB, which is characterized by imaging appearance of a cystic mass and slow progression, is attracting increasing attention. In the present case, a cystic mass was identified in the left hepatic lobe, with no significant change in size after 11 years of follow-up, leading to the diagnosis of branch duct type IPNB. Considering the fact that IPNB is usually treated surgically at the time of diagnosis, the present case, due to the long-term follow-up, provides valuable insight into the natural history of the tumor.

Retinoid storage in the egg of reptiles and birds.

Storage of retinal has been confirmed in eggs from a range of anamniotic vertebrates (teleosts and amphibians) and an ascidian, but the retinoid-storage state in eggs of oviparous amniotic vertebrates (reptiles and birds) has yet to be clarified in detail. We studied four reptilian and five avian species and found that retinal was commonly stored in their egg yolk. Furthermore, retinal was the major retinoid in reptilian eggs, with only low levels of retinol, whereas significant amounts of retinol as well as retinal were stored in avian eggs. In both reptilian and avian eggs, retinal was commonly bound to proteins, which were assumed to be homologous to the proteins that bind retinal in the eggs of anamniotic vertebrates. Despite the common storage state of retinal, retinol would be bound to different proteins. In the reptilian eggs, retinol was found in the yolk-granule fraction, which also contained retinal. However, retinol in avian eggs was found largely in the yolk-plasma fraction, separate from retinal. These results suggest that retinol storage in avian eggs acquired after the divergence of birds from the reptiles, while retinal storage was acquired before the appearance of the vertebrates, and has subsequently been conserved during evolution of oviparous vertebrates.

Involvement of NF-kappa B pathway in TL1A gene expression induced by lipopolysaccharide.

BACKGROUNDS: Recent studies have shown that TL1A (TNFSF15) is one of the definitive susceptibility genes to Crohn's disease (CD). To determine the immunological contribution of TL1A to CD, it is essential to investigate the transcriptional regulation of TL1A. METHODS/RESULTS: We analyzed the transcriptional mechanisms of TL1A induced by lipopolysaccharide (LPS) using the human monocytic cell line U937. RT-PCR revealed that LPS induced TL1A mRNA expression. Transient transfection assays using the promoter-reporter construct which contained 5' flanking region of TL1A revealed that LPS induce transcription of TL1A. Serial deletion constructs revealed that the positive regulatory elements involved with LPS-induced transcriptional activation were located between -247 and -135 in TL1A, in which one putative NF-kappa B binding site was predicted. Overexpressions of I-kappa Balpha inhibited LPS-induced transcriptional activation. Mutation of the predicted NF-kappa B binding site abolished the LPS-induced transcriptional activation. The binding of NF-kappa B to the predicted NF-kappa B motif was demonstrated by electrophoretic mobility shift assays. CONCLUSION: (1) LPS induces TL1A expression through the transcriptional activation via a NF-kappa B pathway. (2) The NF-kappa B binding site in the 5' flanking region of TL1A was identified.

TNFSF15 transcripts from risk haplotype for Crohn's disease are overexpressed in stimulated T cells.

TNFSF15 is a susceptibility gene for Crohn's disease (CD). It remains to be elucidated how the associated single nucleotide polymorphisms (SNPs) in TNFSF15 affect the susceptibility to CD. Because there are no non-synonymous SNPs in TNFSF15, we speculated that one or more of the SNPs associated with CD may act as cis-regulatory SNPs. To reveal the effects of the SNPs on the transcriptional activity of TNFSF15, we first examined the allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells (PBMCs). When PBMCs stimulated by phytohemagglutinin (PHA) were examined, the allelic ratio of mRNA transcribed from the risk haplotype to the non-risk haplotype increased, compared with the ratio without stimulation. When peripheral blood T cells and Jurkat cells stimulated by phorbol 12-myristate 13-acetate + ionomycin were examined, an allelic expression imbalance similar to that observed in PBMCs stimulated by PHA was confirmed. The promoter assay in stimulated Jurkat cells showed that the luciferase activity of the promoter region (-979 to +35) of the risk haplotype was significantly higher than that of the non-risk haplotype, and deletion and mutagenesis analysis demonstrated that this difference resulted from the -358T/C SNP. The promoter activity of -358C (risk allele) was higher than that of -358T (non-risk allele) in stimulated T cells. This effect of -358T/C on the transcriptional activity in stimulated T cells may confer susceptibility to CD.

Identification of 3,4-didehydroretinal isomers in the Xenopus tadpole tail fin containing photosensitive melanophores.

It is well characterized that melanophores in the tail fin of Xenopus laevis tadpoles are directly photosensitive. In order to better understand the mechanism underlying this direct photosensitivity, we performed a retinal analysis of the tail fins and eyes of Xenopus tadpoles at stages 51-56 using high performance liquid chromatography (HPLC). Following the extraction of retinoids by the formaldehyde method, a fraction containing retinal and/or 3,4-didehydroretinal isomers from the first HPLC analysis were collected. These isomers were then reduced by sodium borohydride to convert retinal and/or 3,4-didehydroretinal isomers into the corresponding retinol isomers to prepare for a second HPLC analysis. Peaks of 11-cis and all-trans 3,4-didehydroretinol were detected in the eyes and tail fins containing melanophores, but they were not detected in the tail fins without melanophores. The amounts of 11-cis and all-trans 3,4-didehydroretinol were 27.5 and 5.7 fmol/fin, respectively, and the total quantity of 3,4-didehydroretinal was calculated at approximately 5 x 10(6) molecules/melanophore. These results strongly suggest the presence of 11-cis and all-trans 3,4-didehydroretinal in melanophores of the tadpole tail fin, which probably function as the chromophore of photoreceptive molecules.