Development and Validation of a Simple Index Based on Non-Enhanced CT and Clinical Factors for Prediction of Non-Alcoholic Fatty Liver Disease

OBJECTIVE: A widely applicable, non-invasive screening method for non-alcoholic fatty liver disease (NAFLD) is needed. We aimed to develop and validate an index combining computed tomography (CT) and routine clinical data for screening for NAFLD in a large cohort of adults with pathologically proven NAFLD.MATERIALS AND METHODS: This retrospective study included 2218 living liver donors who had undergone liver biopsy and CT within a span of 3 days. Donors were randomized 2:1 into development and test cohorts. CT(L-S) was measured by subtracting splenic attenuation from hepatic attenuation on non-enhanced CT. Multivariable logistic regression analysis of the development cohort was utilized to develop a clinical-CT index predicting pathologically proven NAFLD. The diagnostic performance was evaluated by analyzing the areas under the receiver operating characteristic curve (AUC). The cutoffs for the clinical-CT index were determined for 90% sensitivity and 90% specificity in the development cohort, and their diagnostic performance was evaluated in the test cohort.RESULTS: The clinical-CT index included CT(L-S), body mass index, and aspartate transaminase and triglyceride concentrations. In the test cohort, the clinical-CT index (AUC, 0.81) outperformed CT(L-S) (0.74; p < 0.001) and clinical indices (0.73–0.75; p < 0.001) in diagnosing NAFLD. A cutoff of ≥ 46 had a sensitivity of 89% and a specificity of 41%, whereas a cutoff of ≥ 56.5 had a sensitivity of 57% and a specificity of 89%.CONCLUSION: The clinical-CT index is more accurate than CT(L-S) and clinical indices alone for the diagnosis of NAFLD and may be clinically useful in screening for NAFLD.

Time-course changes in the expression levels of miR-122, -155, and -21 as markers of liver cell damage, inflammation, and regeneration in acetaminophen-induced liver injury in rats

Drug-induced liver injury (DILI) is a significant threat to patient health and a major concern during drug development. Recently, multiple circulating microRNAs (miRNAs) have been reported to be potential biomarkers for DILI. To adapt and validate miRNAs for clinical use, we investigated the time-course changes in miR-122 expression levels in an acetaminophen-induced liver injury model in rats. In addition, miR-155 and miR-21 were evaluated as makers of inflammation and regeneration, respectively, to characterize liver status. Our results revealed that miR-122 is an early and sensitive biomarker of hepatocellular injury at a stage when alanine transaminase, aspartate transaminase, and total bilirubin were not detectable. However, no significant differences in the expression levels of other miRNAs (miR-155 and -21) were observed between treatment and vehicle groups. Collectively, these time-course changes in the expression levels of miRNAs may be useful as markers for clinical decision-making, in the diagnosis and treatment of DILI.

Focal type of peliosis hepatis

No abstract available.

Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS: Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the HCCs and paired neighboring nonneoplastic liver tissue of 870 HCC patients who underwent hepatic resection. Of these, clinical data for 153 patients who underwent curative resection as a primary therapy were reviewed, and the relationship between FGFR isotype expression and overall survival was evaluated (development set). This association was also validated in 73 independent samples (validation set) by Western blot analysis. RESULTS: FGFR1, -2, -3, and -4 were expressed in 5.3%, 11.1%, 3.8%, and 52.7% of HCCs, respectively. Among the development set of 153 patients, FGFR2 positivity in HCC was associated with a significantly shorter overall survival (5-year survival rate, 35.3% vs. 61.8%; P=0.02). FGFR2 expression in HCC was an independent predictor of a poor postsurgical prognosis (hazard ratio, 2.10; P=0.02) in the development set. However, the corresponding findings were not statistically significant in the validation set. CONCLUSIONS: FGFR2 expression in HCC could be a prognostic indicator of postsurgical survival.

A case of primary hepatic actinomycosis: an enigmatic inflammatory lesion of the liver

Primary hepatic actinomycosis is one of the chronic abscess-forming infections of the liver. Accurate diagnosis is frequently delayed due to its indolent course and nonspecific clinical and radiological manifestations. We report a case of a 57-year-old man presenting with asymptomatic multiple hepatic masses on follow-up abdominal computed tomography performed 1 year after stomach cancer surgery. Although a percutaneous liver biopsy procedure was conducted twice in order to obtain confirmative pathology, only a nonspecific organizing abscess with plasma cell infiltration was revealed, without identification of any organism in the tissue cultures. Ultimately, actinomycosis was diagnosed following the detection of sulfur granules on open surgical biopsied tissue. This case suggests that primary hepatic actinomycosis should be considered as one of the possible causes for enigmatic inflammatory lesions of the liver.

Synchronous Malignant Intraductal Papillary Mucinous Neoplasms of the Bile Duct and Pancreas Requiring Left Hepatectomy and Total Pancreatectomy / 대한소화기학회지

Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) and intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) have striking similarities and are recognized as counterparts. However, simultaneous occurrence of IPMN-B and IPMN-P is extremely rare. A 66 year-old female presented with recurrent epigastric pain and fever. During the past 9 years, she had three clinical episodes related to intrahepatic duct stones and IPMN-P in the pancreas head and was managed by medical treatment. Laboratory test results at admission revealed leukocytosis (12,600/mm3) and elevated CA 19-9 level (1,200 U/mL). Imaging study demonstrated liver abscess in the Couinaud's segment 4, IPMN-B in the left lobe, and IPMN-P in the whole pancreas with suspicious malignant change. Liver abscess was drained preoperatively, followed by left lobectomy with bile duct resection and total pancreatectomy with splenectomy. On histologic examination, non-invasive intraductal papillary mucinous carcinoma arising from various degree of dysplastic mucosa of the liver and pancreas could be observed. However, there was no continuity between the hepatic and pancreatic lesions. This finding in our case supports the theory that double primary lesions are more likely explained by a diffuse IPMN leading to synchronous tumors arising from both biliary and pancreatic ducts rather than by a metastatic process. Herein we present a case of simultaneous IPMN of the bile duct and pancreas which was successfully treated by surgical management.

Positioning During CT Gastrography in Patients with Gastric Cancer: the Effect on Gastric Distension and Lesion Conspicuity

OBJECTIVE: We wanted to prospectively evaluate the effect of various positions of the patient on gastric distension and lesion conspicuity during performance of CT gastrography (CTG). MATERIALS AND METHODS: One hundred thirteen consecutive patients with gastric cancer underwent CTG in the 30degrees left posterior oblique (LPO), supine, and prone positions. Two radiologists scored (a grade from 1-4) the degree of gastric distension and the lesion conspicuity according to the three scanning positions and the three gastric portions. Two- (2D) and three-dimensional (3D) images were used for analysis. Finally, these data were compared with the endoscopic findings and surgical results. RESULTS: The mean scores of gastric distension and lesion conspicuity for the LPO and supine positions were higher than those for the prone position (p or = 0.21). As for the gastric upper portion, the mean scores of gastric distension in the prone position were higher than those in the two other positions (p < 0.001). The prone position showed better lesion conspicuity than the two other positions for only one of two cases of gastric cancer in the upper portion of the stomach. CONCLUSION: CTG performed in the LPO position or the supine position combined with CTG performed in the prone position is optimal for achieving good gastric distension and evaluating the lesion conspicuity of gastric cancer.

Surgical Treatment of Primary Neuroendocrine Tumors of the Liver

PURPOSE: Primary neuroendocrine tumor (PNET) of the liver is a very rare neoplasm. This study was conducted to analyze the clinical experience of 8 hepatic PNET cases. METHODS: Four male and 4 female patients with a mean age of 50.4 +/- 9.5 years (range 37-64 years) underwent liver resection for hepatic PNET between January 1997 and December 2006. The diagnosis was confirmed histologically using light microscopy and immunohistochemistry in the absence of an alternative primary site RESULTS: Curative resection was achieved in 6 of the 8 patients, and 5 of the patients were alive and disease free after a mean follow-up period of 47.6 months. However, 3 patients died 3, 5 and 26 months after surgery due to multiple liver metastasis. A proliferative index of Ki67 appeared to indicate a significant risk factor for tumor recurrence. Additionally, recurrence occurred in 1 of the 6 patients that underwent curative resection during the follow-up period. Overall, both the 5-year recurrence rate and the 5-year survival rate were 50%. CONCLUSIONS: Active exclusion of an extrahepatic primary site is essential for diagnosis of hepatic PNET. The primary treatment for PNET is curative liver resection, and a proliferative index of Ki67 appears to be a prognostic factor for tumor recurrence.

A Case of Vanishing Bile Duct Syndrome Associated with Hypersensitivity to Allopurinol / 대한간학회지

Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome.

Clinical Characteristics of 17 Cases of Autoimmune Chronic Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. METHODS: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. RESULTS: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjogren's syndrome were present in 1 case, respectively. CONCLUSIONS: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid.

The Effects of Tamoxifen on Human Hepatocelluar Carcinoma Cell Proliferation and Transforming Growth Factor-beta1 Expression / 대한간학회지

BACKGROUND/AIMS: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-beta1 (TGF-beta1) which had been known as an important cytokine in growth of HCC. METHODS: Hep 3B cells were cultivated in estrogen free media with 0.1 micro M, 0.5 micro M, 1 micro M, 5 micro M, and 10 micro M of tamoxifen for 6 days. Viable cells were counted daily and the TGF-beta1 concentrations in supernatant were measured by ELISA method. RESULTS: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1 micro M) compared with that of the control (2.59x10(7) vs. 1.97x10(7); p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10 micro M) compared with that of the control (1.40x10(7) vs. 1.97x10(7); p<0.05). TGF-beta1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. CONCLUSIONS: These results suggest that tamoxifen may suppress TGF-beta1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-beta1 expression may inhibit the growth and progression of HCCs over-expressing TGF-beta1 in vivo.

Prevalence and Clinicopathologic Features of Mucinous Cystic Tumor and Intraductal Papillary Mucinous Tumor of Pancreas in Korea

BACKGROUND: Mucin producing cystic neoplasms, such as mucinous cystic tumor (MCT) and intraductal papillary mucinous tumor (IPMT) of the pancreas, are uncommon but become increasing in their incidences. The pathologic classification and biologic potential of these neoplasmsremain the subject of controversy. METHODS: The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists analyzed the clinicopathologic characteristics of 85 casesof MCT and 72 cases of IPMT and examined the expression patterns of p53, CEA and MUC1. RESULTS: IPMT was located largely in the head, and showed connection with the main pancreatic duct (MPD, 68.1%), no ovarian-like stroma (0/72), and presence of intervening intratumoralnormal or atrophic parenchyma. On the other hand, MCT was located largely in thetail (73%), and showed common ovarian-like stroma (66/80), rare connection with the MPD(7/85) and no intervening pancreatic parenchyma. CEA and p53 immunoexpressions weresignificantly increased from adenoma through borderline to carcinoma, but MUC 1 was expressedonly in the invasive carcinoma among cases of MCT and IPMT. CONCLUSIONS: The tumorlocation, ovarian-like stroma, connection with the MPD and intratumoral intervening nonneoplastictissue were helpful in the differential diagnosis between IPMT and MCT. CEA and p53expressions can be indicators of malignancy, while MUC 1 expression can indicate invasion.

Clinical manifestations of autoimmune liver diseases in Korea / 대한내과학회지

BACKGROUND: Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), and autoimmune cholangiopathy (AIC) are major classes of liver diseases currently considered autoimmune. We investigated the clinical, biochemical, and immunologic findings in Korean patients with these disease entities. METHODS: We retrospectively analyzed 47 patients with AIH, 27 with PBC, 3 with Overlap syndrome, 15 with AIC, and 5 with PSC. RESULTS: About 90% of the patients were women, while 40% in PSC. The mean age of onset ranged from 47 to 57 years, while it was 28 years in PSC. Fatigue and jaundice were the most frequent manifestations at diagnosis. In AIH, 13% of patients had an acute onset and 1 died of fulminant hepatic failure. The serum level of IgG was elevated in 67.5%, and antinuclear antibody and anti-smooth muscle antibody were detected in 95.7% and 43.2%. Fifty eight per cent of the patients who received immunosuppressive therapy showed a complete response. In patients with PBC, the level of IgM was elevated in 75% and all of the patients were positive for anti-mitochondrial antibody. Biochemical remission was observed in 37% on ursodeoxycholic acid therapy. Except for the negative anti-mitochondrial antibody, the clinical and biochemical features in AIC were not different from those in PBC. CONCLUSION: Autoimmune liver diseases are not rare in Korea. Considering that these entities are potentially treatable diseases, a high index of suspicion is needed, especially in patients negative for the serologic markers of viral hepatitis.

Nonalcoholic Steatohepatitis / 대한간학회지

No abstract available.

Papillary Stenosis and Cholangitis Caused by Endoscopic Mucosal Resection of Ampullary Adenoma / 대한소화기내시경학회지

Adenomas of the major duodenal papilla are rare but clinically important since they are a premalignant condition. Endoscopic mucosal resection has emerged as the first line therary for ampullary adenoma. However, various complications such as pancreatitis, bleeding or duodenal perforation have been reported after endoscopic mucosal resection. To our knowledge, cholangitis has not been reported as a complication of the procedure in the literature. We report a case of papillary stenosis and cholangitis caused by endoscopic mucosal resection of ampullary adenoma. We performed the endoscopic biliary spincterotomy followed by biliary stenting and cholangitis was successfully controlled.

Papillary Stenosis and Cholangitis Caused by Endoscopic Mucosal Resection of Ampullary Adenoma / 대한소화기내시경학회지

Adenomas of the major duodenal papilla are rare but clinically important since they are a premalignant condition. Endoscopic mucosal resection has emerged as the first line therary for ampullary adenoma. However, various complications such as pancreatitis, bleeding or duodenal perforation have been reported after endoscopic mucosal resection. To our knowledge, cholangitis has not been reported as a complication of the procedure in the literature. We report a case of papillary stenosis and cholangitis caused by endoscopic mucosal resection of ampullary adenoma. We performed the endoscopic biliary spincterotomy followed by biliary stenting and cholangitis was successfully controlled.

Membranous Glomerulopathy as a Manifestation of Chronic Graft-versus-Host-Disease After Non-myeloablative Stem Cell Transplantation in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Allogeneic stem cell transplantation (allo-SCT) using related or unrelated donor could eradicate paroxysmal nocturnal hemoglobinuria (PNH) clones and may cure the disease. Chronic graft-versus host disease (GVHD) is a major complication of patients who have undergone allo-SCT. Nephrotic syndrome has been described as one of the rare manifestations of chronic GVHD following the usual myeloablative allo-SCT. We report a case of nephrotic syndrome that developed 25 months after non-myeloablative allo-SCT for PNH. The patient had grade II acute GVHD and extensive chronic GVHD after non-myeloablative allo-SCT. Typically the patient presented with preserved renal function and full nephrotic syndrome including generalized edema, proteinuria, hypoalbuminemia, and hypercholesterolemia. Renal biopsy revealed findings of membranous glomerulopathy (MG). The patient is alive with a stable engraftment and full donor chimerism under the administration of tacrolimus for control of chronic GVHD and MG without refractory hemolysis and cytopenia.

A Case of Liver Transplantation for Primary Sclerosing Cholangitis / 대한소화기학회지

Primary sclerosing cholangitis (PSC) is a rare disease entity. The medical therapy for PSC has not been reasonably beneficial. Thus liver transplantation is known to be the ultimate therapy. Because liver transplantation for PSC has been performed rarely in Korea, we report a case of liver transplantation for PSC with a review of the literature. A 35-year-old male was admitted to our hospital with recurrent jaundice for seven years. ERCP showed multiple strictures of intrahepatic duct and an irregularity of the extrahepatic duct wall. Despite medication and endoscopic treatment, liver functions did not imporve and clinical status got worsened. Thus liver transplantation was performed for the correction of hepatic failure. Two months after transplantation, liver functions and general weakness gradually improved and now, one year after liver transplantation, the patient is in normal life.

A Case of Eosinophilic Pancreatitis / 대한소화기학회지

Eosinophilic pancreatitis is a rare disorder that may only be diagnosed after pancreatic resection under the suspection of a pancreatic tumor. We experienced a 65-year-old female patient whose initial presentation suggested pancreatic cancer. Radiologic evaluation revealed a pancreatic mass-like lesion which was obstructing the main pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) showed double duct strictures involving the distal common bile duct and the main pancreatic duct. Serum IgE level was elevated. Percutaneous core needle biopsy with an 18-gauge needle was performed targeting the pancreatic lesion. The biopsy specimen revealed fibrotic interlobular septum and intralobular fibrosis with prominent eosinophilic infiltration. The patient was treated with oral prednisolone (40 mg/day). A plastic stent was inserted into the narrowed common bile duct. After three months of oral steroid therapy, symptoms and signs improved rapidly and serum IgE level was decreased. Abdominal computed tomography and ERCP revealed remission of pancreatic mass-like lesion.

A Case of Mucin-hypersecreting Biliary Papillomatosis: Including Review of Korean Literatures / 대한소화기내시경학회지

The mucin-hypersecreting bile duct tumor is rare and its clinical, radiologic, and pathologic features are not well known. We report the case of mucin-hypersecreting biliary papillomatosis with malignant transformation including review of 11 korean literatures. A 65-year-old female was admitted to our hospital with fever, chills, and right upper quadrant pain. A CT scan showed marked dilatation of left intrahepatic duct with intraductal filling defects. During endoscopic retrograde cholangiograpy, mucin from the ampulla was observed and dilated common bile duct with multiple amorphous filling defects was noted. Cholangioscopy revealed muliple coral-like mucosal papillary projections with large amount of mucin in the left intrahepatic ducts. The patient underwent left lobectomy, and the biopsy revealed intraductal papillary adenocarcinoma in the background of papillary adenoma.