Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable.

Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma

We report the first use of endoscopic submucosal dissection(ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus(EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution,and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor,primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion,an 8 mm submucosal tumor. Immunohistologically,tumor cells differentiating into ductal epithelium and myoepithelium were observed,and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall,vertical stump or horizontal margin invasion with p T1 b-SM2 staining(1800 μm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD)patients.Denosumab has been shown to increase bone mineral density(BMD)and decrease the risk of osteoporotic fracture in the general population.However,there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo.The study period for evaluating efficacy and safety was 12 mo.Changes from baseline in BMD at the lumbar spine,femoral neck,and total hip were evaluated at 12 mo of denosumab treatment.Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5b(bone resorption marker),serum total procollagen type I N-terminal propeptide(bone formation maker),and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients,138(34.1%)patients were diagnosed with osteoporosis;among these,78 patients met the exclusion criteria and thus 60 patients were finally included in the present study.The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine,femoral neck,and total hip were+4.44%,+3.71%,and+4.03%,respectively.Denosumab significantly improved BMD,regardless of sex,patient age,and presence of liver cirrhosis.Serum tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P<0.001).Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P=0.010).No patients experienced fractures and moderate-to-severe adverse events,except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD,suppressed bone turnover,and improved bone quality marker levels in CLD patients with osteoporosis,irrespective of differences in baseline characteristics.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis

AIM To evaluate the therapeutic effects of ursodeoxycholic acid(UDCA) on autoimmune hepatitis(AIH).METHODS A total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy(Group U, n = 48) and prednisolone(PSL) monotherapy(Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse(Subgroup U1, n = 34) and patients who additionally received PSL during follow-up(Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factorscontributing to the response to UDCA monotherapy.RESULTS In Group U, 34 patients(71%) achieved and maintained remission over 49(range: 8-90) mo(Subgroup U1) and 14 patients(29%) additionally received PSL(Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse(15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7(range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase(ALT) levels at onset(124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation(A1) on histological examination(70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference(P = 0.013).CONCLUSION To prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower.

Mouse models for investigating the underlying mechanisms of nonalcoholic steatohepatitis-derived hepatocellular carcinoma

As the incidence of hepatocellular carcinoma(HCC) caused by infection with the hepatotropic viruses hepatitis B and hepatitis C decreases, greater attention has become focused on HCC caused by nonalcoholic steatohepatitis(NASH), an advanced form of nonalcoholic fatty liver disease which has shown increasing prevalence in correspondence with the overall increase in metabolic syndrome over the recent decades. Several clinical population studies have shown a positive relationship between NASH and HCC, while also providing initial insights into the underlying mechanisms of HCC development from NASH. Research into the pathological progression of NASH to HCC has advanced by use of several beneficial rodent models. In this review, we summarize the established mouse models for preclinical research of NASH-associated HCC and discuss the underlying hepatic mechanisms of NASH-related tumorigenesis identified to date that could lead to new targets for treatment and prevention.

The Efficacy of the Consumption of n-3 Polyunsaturated Fatty Acids for the Maintenance of Remission in Patients with Inflammatory Bowel Disease

The aim of the present study was to investigate the efficacy of the actual consuming n-3 PUFA for remission-maintenance in IBD patients. A questionnaire on the dietary habits of patients one month before hospitalization (Q1) was completed by 24 patients with IBD (10 ulcerative colitis (UC) subjects and 14 Crohn’s disease (CD) subjects) treated at our hospital. We educated the study subjects about an n-3 PUFA diet, and a follow-up survey (Q2) was conducted 6 to 12 months after discharge. Disease activity was evaluated using the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score and/or the Crohn’s Disease Activity Index (CDAI) score for CD and the partial UCDAI score without endoscopic evaluation for UC. Q1 showed that the average n-3 and n-6 PUFA intakes were 1673 ± 1651 mg and 9146 ± 5217 mg, respectively, and the average n-3/n-6 ratio was 0.27 ± 0.31. In Q2, the intake of n-3 PUFA was significantly higher (3671 ± 1684 mg, p < 0.001), whereas the n-6 PUFA intake decreased significantly (5217 ± 1973 mg, p < 0.001) compared to those in Q1. As a consequence, the dietary n-3/ n-6 ratio was significantly increased (0.87 ± 0.60, p < 0.001). Maintenance of the remission rate was significantly higher in IBD patients who complied with the n-3 diet, and these patients maintained a dietary n-3/n-6 ratio of 0.432 or higher (17 of 23 cases;70.8%, p < 0.03) compared to that observed for IBD patients who did not comply with the diet. These results emphasize the importance of adjusting dietary PUFA and suggest that the n-3 diet may be effective in maintaining the remission of IBD.

Pancreatic cancer screening in patients with presumed branch-duct intraductal papillary mucinous neoplasms

Because delayed diagnosis is one of the causes of poor prognosis in pancreatic ductal adenocarcinoma(PDAC), early detection is a key for overall improvement of prognosis. Towards this end, periodic screening is recommended for individuals considered high-risk for PDAC. Advances in diagnostic imaging modalities have increased the frequency of incidental findings of pancreatic cysts,including the intraductal papillary mucinous neoplasm(IPMN)-a major risk factor of PDAC, having 1% annual prevalence of concomitance with IPMN.Proper retainment of patients with IPMN and regular follow-up by routine imaging examination will likely improve early detection and better prognosis of PDAC. Unfortunately, current guidelines only address management of PDAC derived from IPMN and overlook PDAC concomitant with IPMN. Screening of patients with IPMN, by endoscopic ultrasonography(currently the most reliable modality for detecting small PDAC), may facilitate early detection of both IPMNderived and-concomitant PDAC. Prospective studies to evaluate the usefulness of endoscopic ultrasonography in screening of IPMN-concomitant PDAC will also help in determining the optimal surveillance strategy for more widespread applications.