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.

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.

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.

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.

Congenital Cytomegalovirus Infection Associated with Massive Periventricular Calcification and Probably in Burnt out Phase: An autopsy case report

We report an autopsy case of congenital cytomegalic inclusion disease that was associated with massive periventricular calcification and hydrocephalus. The male boy was bron by cesarian section at 38 weeks of gestational age to a 28 year old mother and was dead two hours after delivery because of respiratory difficulty. Radiologic findings showed characteristic linear periventricular calcification, being associated with marked dilatation of the lateral ventricles. At autopsy, the brain parenchyme became 0.4 cm in average thickness due to obstructive hydrocephalus at aqueductal level. The inner surface of the lateral ventricle showed grayish white granular appearance that could correspond to the calcification seen on plain skull X-ray films. Although active ependymitis, destruction of the brain parenchyma with dystrophic calcification and gliosis were noted, there was no intranuclear inclusion. After scrutinizing many sections of various organs and tissue, we could be able to demonstrate a few inclusion bodies, highly suggestive of cytomegalic inclusion disease. It was discussed that this case might suggest that intranuclear inclusions in cytomegalovirus infection could by very difficult to find particularly when the infection is in inactive phase despite the presence of tissue necrosis and calcification of the brain.

Nonalcoholic Steatohepatitis / 대한간학회지

No abstract available.

Biliary Papillomatosis / 대한간학회지

No abstract available.

Primary Neuroendocrine Carcinoma of the Liver / 대한간학회지

No abstract available.

Metaplastic Variant of the Gallbladder Adenoma: A report of a case

A case of papillary adenoma of the gallbladder in a sixty seven-year-old female with varietise of epithelial components in metaplastic nature is presented. This adenoma was bordered by hyperplastic epithelium with intervening Paneth cells and enterochromaffin cells, but goblet cells were rarely participated, as with focal epithelial change resembling gastric foveolar epithelium and aggregation of antral type mucous glands. Based on its morphologically distinct type of gallbladder adenoma and histogenetic point of view, we propose this neoplasm to be designated as a metaplastic adenoma or polyp, and the relationship of various metaplastic changes to adenoma or carcinoma is discussed.

Male Pseudohermaphroditism Associated with Bochdalek Diaphragmatic Hernia: An autopsy case report

An autopsy case of male pseudohermaphrodite associated with Bochdalek diaphragmatic hernia is reported. This newborn infant showed a large clitoris and hypospadic urethra which was the only opening in the perineum except for the anus. There were urethrovaginal fistula and uterus didelphys. The adrenals were slightly larger than normal, but microscopically did not show any features of cortical hyperplasia. Well formed testes were found and were histologically unremarkable. In addition, Bochdalek type of diaphragmatic hernia was present, associated with severe left lung hypoplasia and massively herniated abdominal organs into the chest cavity, shifting the mediastinum considerably and eventually led to death in a few minutes after birth. The pathogenesis of genital anomaly and diaphragmatic hernia is briefly discussed and it is suggested that this type of genital abnormality might be due to defect of testicular M llerian inhibitor factor and can be categorized as incomplete male pseudohermaphroditism.

Primary Carcinoma of the Gallbladder: An Analysis of 34 Cholecystectomy Cases with Special Reference to Metaplastic Changes

Primary gallbladder carcinoma is generally assumed as uncommon but dismal malignancy. Only sporadic studies about pathologic features of the gallbladder carcinoma have drawn pathologists attention especially in association with cholelithiasis. Currently, we have focused much on the role of metaplastic changes in diseased gallbladders including cholecystitis with or without cholelithiasis, and raised its implication in the development of benign or malignant neoplasm. The authors reviewed 34 cholecystectomy cases with primary gallbladder carcinoma, and their histologic findings were analyzed with reference to the association of metaplastic changes both in tumor and adjacent nonneoplastic mucosal epithelium. Association with gallstones and metaplastic changes in the surrounding nontumorous mucosa is more frequent in intestinal typen than in non-intestinal type (P<0.05). Gallstones may play a role of irritant stimuli to the gallbladder mucosa which can be eventually reconstructed with more resistant cell type. And the subsequent increase in absorptive capacity and accumulation of carcinogenic substance may result in malignant transformation of (reserve) cells in replication zone. At this time we can assume that association of cholelithiasis and presence of metaplastic changes are in parallel relationshop in intestinal type adenocarcinoma. Intestinal type adenocarcinomas are usually papillary (72.7%) especially in superficial portion, but deeper area also shows infiltrative growth focally. This finding is comparable to intestinal type gastric carcinoma which represents frequently a polypoid and papillary growth pattern. With these results, as in the gastric carcinoma it is strongly supported that intestinal metaplasia may play a major role as a precancerous lesion in a minor group of the gallbladder adenocarcinoma. Controlled prospective study on biological behavior of intestinal type adenocarcinoma should be followed with more cumulative cases.

Two Patterns of Gastric Carcinoma with Lymphoid Stroma

Various clinical and pathologic parameters in order to determine the prognosis of gastric carcinoma have been proposed. Among them "carcinoma with lymphoid stroma" has been proven to show good prognosis. But the criteria of lymphoid stroma in this condition remain vague and not clear. A total of 7 cases of gastric carcinoma with heavy lymphoid stromal response out of 947 surgically resected gastric carcinomas was reviwed with histotopographic analysis. They were all advanced carcinoma, Borrmann type I and II. Histologically, the lymphoid stromal response could be divided into three patterns; nodular (3 cases), diffuse (3 cases) and mixed (1 case). The nodular pattern was characterized by massive lymphoid cell infiltration with many follicle formation and little desmoplastic reaction, while the diffuse pattern showed diffuse permeative type of inflammatory cell infiltration with scarce lymphoid follicle formation and mild desmoplasia. Regional lymph node metastasis was found in 2 cases; one in diffused and another one in mixed pattern. The stromal reaction was not directly related with the depth of tumor invasion. We propoose that the term GCLS should be used in the cases of nodular pattern with complete follicle formation of lymphoid stroma.

Histopathologic Analysis of Helicobacter Pylori Associated Gastritis

Gastric mucosa shows continuous changes in surface epithelium as well as inflammatory reaction by various substances from the outside and their metabolic products. Gastric mucosal lesions are proven to be associated with bacterial infection by the discovery of Heliobacter pylori(H. pylori) and many studies about histopathologic changes of gastric mucosa associated H. pylori infection has been advanced. It is known that H. pylori associated gastritis displays surface foveolar epithelial changes, such as cytoplasmic vacuolation, mucin loss, juxtaluminal cytoplasm erosion, epithelial denudation, and mucosal irregularity. There have been many studies that H. pylori infection is associated with intestinal metaplasia, gastric dysplasia, and carcinoma. Also chronic H. pylori infection with its induction of gastric lymphoid follicle has been implicated as a precursor of gastric lymphoma of the unique B-cell type that arises from mucosa-associated lymphoid tissue(MALT). However, these gastric mucosal changes are also observed in gastritis with other causes. In this study, we aimed to define specific histopathiologic findings associated with H. pylori infection. A total of 463 gastric biopsy specimens were reviewed. They were Helicobacter-associated gastritis and were divided as many (MH), a few (AH), and no (NH), according to the number of H. pylori. 210 (MH), 131 (AH), and 122 (NH) biopsy specimens were included. Lymphocytes, plasma cells in lamina propria, eosinophils and neutrophils in surface epithelium and crypt as well as lamina propria were graded from 0 to 3. Surface epithelial changes including cytoplasmic vacuolation, mucin loss, juxtaluminal erosion, epithelial denudation and mucosal irregrarity were observed in 200 of 210 cases(95%) in MH group, 34 of 131 cases(26%) in AH group, and 6 of 122 cases(5%) in NH group. This result indicates there is significant difference in surface epithelial changes according to the number of H. pylori(p<0.001). Severity of eosinophil, neutrophil, lymphocyte, and plasma cell infiltration is increased in proportion to the number of H. pylori. Especially, neutrophilic infiltration is not identified in 95 of 122 cases(78%) in NH group, whereas MH group shows severe infitration (grade 3) in 127 of 210 cases(61%), and no (grade 0) in 11 of 210 cases(5%). This data well explains that the severity of neutrophil infiltration is associated with, the degree of H. pylori infection in chronic active gastritis, with statistical significance. The prevalence of lymphoid follicle formation was 17 of 120 cases(14%) in NH group, 24 of 131 cases(18%) in AH group, and 52 of 210 cases(25%) in MH group. This shows that lymphoid follicle formation correlates with the number of H. pylori, but without statistical significance. The prevalence of intestinal metaplasia in NH, AH, and MH was 43 of 122 cases(35%), 46 of 131 cases(35%), and 69 of 210 cases(33%), showing no association between intestinal metaplasia and H. pylori. In summary, H. pylori associated gastritis dispays characteristic histopathological changes in gastric mucosa, in which surface epithelial changes and various inflammatory infiltrates are increased in proportion to the number of H. pylori. Especially vacuolization of surface foveolar epithelium, cryptitis, and crypt abscess are specific findings of H. pylori associated gastritis.

Sclerosing Stromal Tumor of the Ovary: A report of 3 cases

Three cases of sclerosing stromal tumor of the ovary are presented. All three patients were nulliparous young wemen of 23~25 years of age, presenting with menstrual irregularity for 6 months to 4 years. Grossly the tumors ranged in size from 8 to 22cm in greatest diameter, showing gray white to yellow solid or predominantly cystic tissue with serous fluid. The common microscopic finding was that of cellular areas admixed with densel fibrous and/or edematous tissue, presenting pseudolobular appearance. Two types of tumor cells were rounded cells with clear vacuolated cytoplasm and less numerous spindle shaped cells. Postoperative course was uneventful and menstrual irregularity disappeared postoperatively. In case 2, the patient got pregnant after 1 year and 4 months. This clinical course suggests that sclerosing stromal tumor of the ovary may be endocrinologically active.

Primary Sclerosing Cholangitis: A Report of Two Liver Explants

Primary sclerosing cholangitis (PSC) is usually progressive to the end stage liver disease and a common indication for liver transplantation (LT). We report two cases of liver explants with PSC. Case 1 was that of a 35-year-old male who was admitted for 4 weeks because he had jaundice. He had been treated several times without receiving a definite diagnosis during the last 7 years because he was excreting dark urine. Case 2 was that of a 30-year-old female who had taken a prednisolone for 6 years for treatment of ulcerative colitis. She also had stones and underwent a cholecystectomy and choledocholithotomy 2 years ago. She had complained of epigastric pain and febrile sensation for 2 months. In both cases, serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phospatase, gamma glutamyl transpeptidase, and direct builirubin were elevated. Autoantibodies were not detected. Computerized tomography scan and endoscopic retrograde cholangiopancreatography revealed hepato-splenomegaly, stricture of intra- and extra-hepatic bile ducts, and beaded dilatation of the intrahepatic bile ducts. Despite stent insertions and medication, another episode of jaundice occurred in case 1 and cirrhosis finally developed in case 2. The histopathologic features of liver needle biopsy specimens were nonspecific, while explant livers displayed periductal fibrosis, ductopenia, and/or ductular proliferation, which are characteristic features for PSC.