Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis

Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

A Case of Graves' Disease Accompanied with Acute Hepatitis A Virus Infection / 대한소화기학회지

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

Successful Treatment of Bleeding Duodenal Varix by Percutaneous Transsplenic Embolization / 대한소화기학회지

Variceal bleeding occurs primarily in the esophagus or stomach in patients with liver cirrhosis, but can also occur rarely in the duodenum. Duodenal variceal bleeding has a high mortality and poor prognosis due to heavy blood flow originating from the portal vein (PV) and the technical difficulty of hemostatic procedures. Treatments including endoscopic sclerotherapy, endoscopic ligations, endoscopic clipping and transjugular intrahepatic portosystemic shunt have been tried, with only moderate and variable success. A percutaneous transsplenic approach offers another way of accessing the PV. Here we report a case of successfully treated duodenal variceal bleeding by percutaneous transsplenic embolization.

Endoscopic Ultrasound-guided Drainage of Fluid Collection on Lesser Sac after Pancreaticoduodenectomy Not Accessible to Percutaneous Drainage / 대한췌담도학회지

Postoperative fluid collection is a major complication after pancreaticoduodenectomy and can lead to increased mortality and hospital length of stay. External drainage has widely been used for postoperative fluid collections. Recently, EUS-guided drainage has also been used successfully in treating postoperative fluid collections. A 60-year-old woman was admitted due to weight loss and jaundice. She underwent pancreaticoduodenectomy for cholangiocarcinoma of the common bile duct. After 2 weeks, she had fever with abdominal pain and leukocytosis. CT showed a increased fluid collection in superior recess of lesser sac and EUS-guided drainage was performed. The symptoms resolved without any complication after drainage. This is the first case report of EUS-guided drainage for lesser sac in Korea.

Diffuse Ganglioneuromatosis of the Colon Presenting as a Large Subepithelial Tumor in Adults: Report of Two Cases / 대한소화기학회지

Colonic diffuse ganglioneuromatosis is a benign neoplastic condition characterized by disseminated, intramural, or transmural proliferation of neural elements involving the enteric plexuses, sometimes associated with von Recklinghausen's disease and other multiple tumor syndromes. Colonic diffuse ganglioneuromatosis is usually large, ranging from 1 to 17 cm, and thus can distort the surrounding tissue architecture as well as infiltrate the adjacent bowel wall. However, colonic diffuse ganglioneuromatosis is an exceptional finding in adults and only individual cases are reported in the literature. Herein, we report two unusual cases of adult patients with colonic diffuse transmural ganglioneuromatosis presenting as a large subepithelial tumor.

Entecavir Resistance at rtS202, rtM250 May Cause Poor Viral Response to Tenofovir-based Rescue Therapy in Chronic Hepatitis B / 대한내과학회지

BACKGROUND/AIMS: Long-term use of nucleos(t)ide analogues (NA) may lead to genotypic and/or phenotypic resistance of the hepatitis B virus (HBV). We investigated the efficacy of tenofovir-based rescue therapy in chronic hepatitis B (CHB) patients with newly developed genotypic resistance to prior NAs or partial virologic response to sequential rescue therapies. METHODS: Fifty-four CHB patients were included retrospectively. The patients were treated with tenofovir alone or combined with lamivudine or entecavir. RESULTS: There were 26 forms of genotypic resistance at enrollment. The median amount of serum HBV-DNA was 18,438 IU/mL and 83% of samples were positive for hepatitis B e antigen (HBeAg). Serum HBV-DNA was undetectable in 50%, 61%, and 76% of the patients at 3, 6, and 12 months, respectively. In multivariate analysis, HBV-DNA < 20,000 IU/mL and negative HBeAg at baseline were independent predictors of negativity for serum HBV-DNA. Interestingly, the rtS202 mutation tended to be associated with an unfavorable response. Other clinical variables and viral resistance genotypes showed non-significant viral response. CONCLUSIONS: Lower serum HBV-DNA, negative HBeAg and lack of rtS202G mutations at baseline may predict a favorable response to tenofovir-based rescue therapies in CHB patients with newly developed genotypic resistance to prior NAs or a partial virologic response to sequential rescue therapies.

Corrosive Esophagitis Caused by Ingestion of Picosulfate

Corrosive esophagitis is characterized by caustic injury due to the ingestion of chemical agents, mainly alkaline substances such as detergents. Esophageal bleeding, perforation, or stricture can be worsened by high-degree corrosive esophagitis. Picosulfate is a commonly used laxative frequently administered for bowel preparation before colonoscopy or colon surgery. Picosulfate powder should be completely dissolved in water before ingestion because the powder itself may cause chemical burning of the esophagus and stomach. Here, we report a case of corrosive esophagitis due to the ingestion of picosulfate powder that was not completely dissolved in water.

Phylogenetic Analyses of HBV Pre-S/S Genes in Mother-Child Pairs with Long-Term Infection by Presumed Vertical Transmission

Vertical transmission from mother to child, the main route of chronic hepatitis B virus (HBV) infection in the East Asia, is considered one of the most important predictors for the response to antiviral therapies as well as its complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is critical in both etiologic and prognostic aspects to confirm whether or not chronic HBV infection is acquired vertically. This study investigated whether mother-to-child infection could be proved by the phylogenetic analyses of HBV pre-S/S genes ever since several decades have elapsed in mother-child pairs with presumed vertical transmission. The pre-S and S regions of HBVs were compared and analyzed phylogenetically in a total of 36 adults (18 mother-child pairs) with chronic HBV infection. All of the isolates of HBV were genotype C and serotype adr. The divergence between mothers and offsprings was 0 to 1.5%. Phylogenetic trees revealed that 17 of 18 pairs (94%) with presumed vertical transmission were grouped into the same cluster. Vertical transmission from mother to child could be strongly suggested even in adults with a history of several decades of HBV infection using the phylogenetic analyses of pre-S and S genes.

A Case of Hepatitis B Virus Reactivation in a HBsAg-Negative and Anti-HBs-Positive Patient with Diffuse Large B-Cell Lymphoma after Rituximab plus CHOP Chemotherapy

The reactivation of hepatitis B virus (HBV) is well known complication among lymphoma patient related with chemotherapy. Rituximab is monoclonal antibody that targets B-lymphocytes for treatment of lymphoma and it increases reactivation of HBV. Although most of reactivation occurs in HBV carrier, it can also rarely occur when hepatitis B surface antigen (HBsAg) is negative. Furthermore it is less frequently reported in lymphoma patient when HBV serology shows HBsAg is negative and anti-HBs is positive. We report a case of HBV reactivation following 6 cycle of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for diffuse large B-cell lymphoma in HBsAg negative/anti-HBs positive 58-year-old male, with a review of the literature.

A Case of Intraductal Papillary Mucinous Neoplasm of the Pancreas with Pancreatoduodenal Fistula Diagnosed by Pancreatoscopy Using a Standard Upper Endoscope / 대한췌담도학회지

Intraductal papillary mucinous neoplasm of the pancreas (IPMN) is characterized by the production of mucin and marked dilatation of pancreatic duct. There are only several cases reports about fistula formation with adjacent organs in IPMN. A 61-year-old man was admitted due to jaundice and weight loss. CT scans showed that multiloculated cystic mass had replaced the body and tail of the pancreas. Interestingly, a fistula was found between cystic mass and duodenal bulb. With a diagnosis of malignant IPMN and pancreatoduodenal fistula, endoscopic forcep-biopsy was performed at the orifice of the fistula and pancreatic duct, through the fistula, under a fluoroscopic guidance. Pathologic examination showed only inflammatory cells. Direct peroral pancreatoscopy was performed through the pancreatoduodenal fistula using a standard upper endoscope with saline irrigation. Endoscopic forcep-biopsy was performed on the papillary tumor. Pathologic examination revealed intestinal type IPMN and radical total pancreatectomy was performed. Pathologic examination of the surgical specimen showed tubular adenocarcinoma arising from 15 cm sized intestinal type IPMN.

A Case of Perforated Gastrointestinal Stromal Tumor in the Jejunum as a Rare Cause of Acute Abdomen

Preoperative diagnosis of Gastrointestinal Stromal Tumors (GISTs) in the small intestine is often delayed until complications such as hemorrhage, bowel obstruction or perforation develop. Such GISTs are usually asymptomatic and tumor perforation is an uncommon clinical presentation. In this report, we review the diagnosis, pathology and treatment of a 32-year-old male with a perforated GIST in the jejunum who presented with symptoms of acute abdomen. Abdominal computed tomography (CT) showed a ruptured huge tumor with inhomogeneous density in the small intestine. The patient underwent a complete tumor excision and jejunal segmental resection. A histopathological examination of the tumor confirmed that it was a GIST. Postoperatively, the patient received medical treatment, using oral Imatinib 400 mg daily for 10 months without any signs of disease recurrence. Prognosis is worse in ruptured GISTs and in these cases, complete surgical resection of the tumor must be followed by adjuvant therapy with Imatinib.

A Case of Acute Colonic Diverticulitis as a Complication of Colonoscopy

Colonoscopy is a good diagnostic tool and facilitates treatment of various colonic diseases. Nevertheless, it can induce many serious complications such as perforation and hemorrhage. Diverticulitis has also been reported as a serious complication of colonoscopy, with an incidence ranging from 0.04% to 0.08%. A 44-year-old male with chronic hepatitis B was presented with general weakness, myalgia, and febrile sensation. After admission for evaluation, pneumonia detected in the left upper and lower lobe and treated. We performed colonoscopy for screening and found multiple colonic diverticula in the right side of the colon. After 48 hours, the patient complained of abdominal pain and febrile sensation. Physical examination revealed tenderness in the right side of the abdomen. Abdomen-pelvis computed tomography showed bowel wall thickening of the cecum and ascending colon and multiple inflamed diverticula at the cecum with pericolic fat infiltration and fluid collection. We diagnosed the patient with acute diverticulitis after colonoscopy. Thereafter, he was treated with bowel rest and broad-spectrum intravenous antibiotics, and recovered. With a review of the relevant literature, we report a case of acute colonic diverticulitis as a complication of colonoscopy.

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

BACKGROUND/AIMS: We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. METHODS: We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. RESULTS: Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was > or =6x10(5) IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). CONCLUSIONS: Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.

Safety and Efficacy of Deep Sedation with Propofol Alone or Combined with Midazolam Administrated by Nonanesthesiologist for Gastric Endoscopic Submucosal Dissection

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a treatment for gastric neoplasms and usually requires deep sedation. The aim of this study was to evaluate the safety and efficacy profiles of deep sedation induced by continuous propofol infusion with or without midazolam during ESD. METHODS: A total of 135 patients scheduled for ESDs between December 2008 and June 2010 were included in this prospective study and were randomly assigned to one of two groups: the propofol group or the combination group (propofol plus midazolam). RESULTS: The propofol group reported only one case of severe hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases of mild hypotension were observed in the propofol group, and 11 cases were observed in the combination group. The combination group had a lower mean total propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5 minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events (32.8% vs 17.6%, p=0.042). CONCLUSIONS: Deep sedation induced by continuous propofol infusion was shown to be safe during ESD. The combination of continuous propofol infusion and intermittent midazolam injection can decrease the total dose and infusion rate of propofol and the overall occurrence of adverse events.

A Clinical Review of the Intussusception in Adult

BACKGROUND/AIMS: Intussusception is uncommon in adults compared with children. The present study aimed to review our experience of adult intussusceptions and discuss the preoperative diagnosis and management. METHODS: A retrospective review was performed for 25 patients, at least 18 years old. These patients were diagnosed as intestinal intussusceptions at Hallym University Sacred Heart Hospital from January 1999 to October 2010. RESULTS: There were 14 male and 11 female with a mean age of 55 years. The most common symptom was abdominal pain. The preoperative diagnostic rate was 92% because of the use of an abdominal computed tomography (CT) and an ultrasound. A total of 9 (36%) patients had enteroenteric intussusception, 8 had ileocolic, 1 had ileocecal and 7 patients had colocolic intussusception. A discrete pathologic process was present in 22 (88%) patients and the remaining 3 (12%) patients were idiopathic. There were 12 small bowel lesions and 10 colonic lesions. Neoplasms were the most common etiology of intussusceptions. Of the cases with a defined colonic cause, 8 (80%) were malignant. Overall, 12 (48%) patients underwent primary resection of the intussusception without prior reduction, 11 (44%) patients had reduction of their intussusception followed by resection. CONCLUSIONS: Adult colonic intussusception is usually associated with malignancy. All patients with obstruction of unknown cause or lead point on CT should consider surgical exploration.

A Case of Multiple Gastrointestinal Stromal Tumor of the Jejunum Which Was Diagnosed by Capsule Endoscopy / 대한소화기학회지

More than 90% cases of chronic gastrointestinal bleeding can be diagnosed by upper endoscopy and/or colonoscopy, and therefore, obscure gastrointestinal bleeding has been defined as bleeding of unknown origin that persists after these conventional endoscopic evaluation. Gastrointestinal stromal tumors (GISTs) are rare tumors, but the most common form of mesenchymal tumors of the gastrointestinal tract. Small bowel is the second most common primary site for GISTs, and accounts for 2-10% of chronic bleeding sites. GISTs usually present as a sporadic and solitary tumor, and a minority of the cases of multiple GISTs are discovered as forms of hereditary or idiopathic tumor syndromes. Small bowel tumor has been difficult to diagnose because of absence of accurate and proper diagnostic tools. Recently developed wireless capsule endoscopy helps in the diagnostic work-up of small bowel diseases. We report a case of multiple jejunal GISTs presenting melena in a 39-year-old male, which was diagnosed with wireless capsule endoscopy.

A Case of Henoch-Schonlein Purpura with Suspicious Focal Bowel Necrosis in an Adult

Henoch-Schonlein purpura (HSP) is a vasculitis of the small vessels of the skin, joints, gastrointestinal tract, and kidneys characterized by immunoglobulin A deposits in the involved organs. HSP is typified by the classic tetrad of purpura, arthralgia, abdominal pain, and renal involvement. It is common in childhood, but may also occur in adults and can be accompanied by severe complications. Gastrointestinal symptoms occur in up to 85% of patients, and gastrointestinal involvement can manifest as severe problems including intussusception, obstruction, and perforation. The disease course is often self-limited, but severe manifestations occasionally require surgical intervention. We report the case of a 24-year-old man with HSP who presented with abdominal pain and vomiting. Computerized tomography revealed thickening of the ileal wall and multifocal disrupted prominent mucosal enhancement. These findings suggested hemorrhagic enteritis and mucosal necrosis. After treatment with high dose corticosteroids, the lesion improved and surgical intervention was avoided. Our experience suggests that corticosteroid therapy may help in controlling HSP with suspicious small bowel necrosis.

A Case of Gastric Lymphoepithelioma-like Carcinoma with Lymph Node Metastasis

Gastric lymphoepithelioma-like carcinoma is a very rare cancer of the stomach. It has undifferentiated malignant cells with rich lymphoid stroma histologically and its prognosis has known to be relatively fair. Recently, there were some reports on the successful removal of the lesion by endoscopic submucosal dissection technique. We present a case of 70 years old man who had 2 cm sized early gastric cancer of lymphoepithelioma-like carcinoma with perigastric lymph node metastasis, and also review the relevant medical literature.

Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic hepatitis C patients coinfected with hepatitis B virus / 대한간학회지

BACKGROUND/AIMS: Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV. METHODS: Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained. RESULTS: HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL. CONCLUSIONS: The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.