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1.  Fate of Dyspeptic or Colonic Symptoms After Laparoscopic Cholecystectomy 
Gallbladder diseases can give rise to dyspeptic or colonic symptoms in addition to biliary pain. Although most biliary pain shows improvement after cholecystectomy, the fates of dyspeptic or colonic symptoms still remain controversial. This study assessed whether nonspecific gastrointestinal symptoms improved after laparoscopic cholecystectomy (LC) and identified the characteristics of patients who experienced continuing or exacerbated symptoms following surgery.
Sixty-five patients who underwent LC for uncomplicated gallbladder stones or gallbladder polyps were enrolled. The patients were surveyed on their dyspeptic or colonic symptoms before surgery and again at 3 and 6 months after surgery. Patients' mental sanity was also assessed using a psychological symptom score with the Symptom Checklist-90-Revised questionnaire.
Forty-four (67.7%) patients showed one or more dyspeptic or colonic symptoms before surgery. Among these, 31 (47.7%) and 36 (55.4%) patients showed improvement at 3 and 6 months after surgery, respectively. However, 18.5% of patients showed continuing or exacerbated symptoms at 6 months after surgery. These patients did not differ with respect to gallstone or gallbladder polyps, but differed in frequency of gastritis. These patients reported lower postoperative satisfaction. Patients with abdominal symptoms showed higher psychological symptom scores than others. However, poor mental sanity was not related to the symptom exacerbation.
Elective LC improves dyspeptic or colonic symptoms. Approximately 19% of patients reported continuing or exacerbated symptoms following LC. Detailed history-taking regarding gastritis before surgery can be helpful in predicting patients’ outcome after LC.
PMCID: PMC4015198  PMID: 24840378
Brief Psychiatric Rating Scale; Cholecystectomy, laparoscopic; Gastritis; Postcholecystectomy syndrome
2.  Metachronous bile duct cancer nine years after resection of gallbladder cancer 
We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a well-differentiated adenocarcinoma, with negative resection margins (T2N0M0, stage IB). Nine years later, during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type IIIa, and performed bile duct excision, right hepatic lobectomy and Roux-en-Y hepaticojejunostomy. The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis (T1N1M0, stage IIB). Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.
PMCID: PMC2712910  PMID: 19610150
Biliary tree; Metachronous double cancer; Gallbladder cancer; Hilar bile duct cancer
3.  Abdominal Compartment Syndrome in Severe Acute Pancreatitis Treated with Percutaneous Catheter Drainage 
Clinical Endoscopy  2014;47(5):469-472.
Acute pancreatitis is one of the main causes of intra-abdominal hypertension (IAH). IAH contributes to multiple physiologic alterations and leads to the development of abdominal compartment syndrome (ACS) that induces multiorgan failure. We report a case of ACS in a patient with severe acute pancreatitis. A 44-year-old man who was admitted in a drunk state was found to have severe acute pancreatitis. During management with fluid resuscitation in an intensive care unit, drowsy mentality, respiratory acidosis, shock requiring inotropes, and oliguria developed in the patient, with his abdomen tensely distended. With a presumptive diagnosis of ACS, abdominal decompression through percutaneous catheter drainage was performed immediately. The intraperitoneal pressure measured with a drainage catheter was 31 mm Hg. After abdominal decompression, the multiorgan failure was reversed. We present a case of ACS managed with percutaneous catheter decompression.
PMCID: PMC4198568  PMID: 25325011
Severe acute pancreatitis; Intra-abdominal hypertension; Percutaneous catheter drainage
4.  A Case of Choledocholithiasis and Intestinal Malrotation in an Adolescent with Repaired Gastroschisis 
Clinical Endoscopy  2014;47(2):201-204.
Most infants with repaired gastroschisis develop normally and remain in good health. About 10% of patients with gastroschisis have other malformations. We report a case of choledocholithiasis and intestinal malrotation in an adolescent with repaired gastroschisis. A 17-year-old girl presented with fever, jaundice, and abdominal pain. She had undergone an operation to repair gastroschisis at birth. Physical examination revealed icteric sclera, a tight abdominal wall, and a longitudinal surgical scar at the midline. An abdominal computed tomography scan revealed a round calcifying lesion near the pancreas and a midline-positioned liver and gallbladder. Absence of the retroperitoneal duodenum and the anterior and left-sided position of the superior mesenteric vein compared with the superior mesenteric artery were observed. Results of abarium examination revealed intestinal malrotation. Endoscopic retrograde cholangiopancreatography revealed diffuse dilatation of the biliary trees and a malpositioned gallbladder. A single stone was removed by using a basket. The clinical symptoms improved after the patient underwent endoscopic retrograde cholangiopancreatography.
PMCID: PMC3994266  PMID: 24765606
Gastroschisis; Intestinal malrotation; Choledocholithiasis
5.  Differential Expression of E-Cadherin, β-Catenin, and S100A4 in Intestinal Type and Nonintestinal Type Ampulla of Vater Cancers 
Gut and Liver  2013;8(1):94-101.
Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, β-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival.
A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, β-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed.
Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and β-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous β-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs.
Dysregulation of E-cadherin, β-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.
PMCID: PMC3916694  PMID: 24516707
Ampullary adenocarcinoma; Intestinal type; Pancreatobiliary type; Epithelial-mesenchymal transition
6.  Podoplanin, α-Smooth Muscle Actin or S100A4 Expressing Cancer-Associated Fibroblasts Are Associated with Different Prognosis in Colorectal Cancers 
Journal of Korean Medical Science  2013;28(9):1293-1301.
The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), α-smooth muscle actin (α-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or α-SMA CAFs were detected in all the cases. PDPN/S100A4 and α-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/α-SMAhigh CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4high CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the α-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/α-SMAhigh or PDPN-/S100A4high CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.
PMCID: PMC3763102  PMID: 24015033
Cancer-Associated Fibroblast; Podoplanin; α-Smooth Muscle Actin; S100A4; Colorectal Neoplasms
7.  Efficacy of cap-assisted endoscopy for routine examining the ampulla of Vater 
AIM: To determine the efficacy of a cap-assisted endoscopy (CAE) to completely visualize the ampulla of Vater (AV) in patients failed by conventional endoscopy.
METHODS: A prospective study was conducted on 120 patients > 20 years of ages who visited the Health Promotion Center of Chungbuk National University Hospital for conscious sedation esophagogastroduodenoscopy (EGD) as a screening test from July to October, 2011. First, forward-viewing endoscopy was performed with reasonable effort using a push and pull method. We considered complete visualization of the AV when we could observe the entire AV including the orifice clearly, and reported the observation as complete or incomplete (partial or not found at all). Second, in cases of complete failure of the observation, an additional AV examination was conducted by attaching a short cap (D-201-10704, Olympus Medical Systems, Tokyo, Japan) to the tip of a forward-viewing endoscope. Third, if the second method failed, we replaced the short cap with a long cap (MH-593, Olympus Medical Systems) and performed a re-examination of the AV.
RESULTS: Conventional endoscopy achieved complete visualization of the AV in 97 of the 120 patients (80.8%) but was not achieved in 23 patients (19.2%). Age (mean ± SD) and gender [male (%)] were not significantly different between the complete observation and the incomplete observation groups. Additional short CAE was performed in patients in whom we could not completely visualize the AV. This group included 13 patients (10.9%) with partial observation of the AV and 10 (8.3%) in which the AV was not found. Short CAE permitted a complete observation of the AV in 21 of the 23 patients (91.3%). Patients in whom visualization of the AV failed with short CAE had satisfactory outcomes by replacing the short cap with a long cap. The additional time for CAE took an average of 141 ± 88 s. There were no complications and no significant mucosal trauma.
CONCLUSION: CAE is safe to use as a salvage method to achieve complete visualization of the AV when a regular EGD examination fails.
PMCID: PMC3623980  PMID: 23599622
Ampulla of Vater; Conventional endoscopy; Cap-assisted endoscopy; Screening test; Complete observation
8.  Rescue endoscopic band ligation of iatrogenic gastric perforations following failed endoclip closure 
Iatrogenic gastric perforation is one of the most serious complications during therapeutic endoscopy, despite significant advances in endoscopic techniques and devices. This case study evaluated the clinical efficacy and safety of the rescue endoscopic band ligation (EBL) technique in iatrogenic gastric wall perforation following the failure of primary endoclip closure. Five patients were enrolled in this study. These patients underwent emergency endoscopy following the onset of acute gastric wall perforation during endoscopic procedures. The outcome measurements were primary technical success and immediate or delayed procedure-related complications. Successful endoscopic closure using band ligation was reported in all patients, with no complication occurring. We conclude that EBL may be a feasible and safe alternate technique for the management of acute gastric perforation, especially in cases where closure is difficult with endoclips.
PMCID: PMC3574896  PMID: 23429885
Gastric perforation; Endoscopy; Band ligation
9.  Extended Spectrum-β-Lactamase or Carbapenemase Producing Bacteria Isolated from Patients with Acute Cholangitis 
Clinical Endoscopy  2012;45(2):155-160.
This study assessed the antibiotic resistance organisms isolated from the blood and bile of acute cholangitis and evaluated risk factors associated with them and their impact on clinical outcomes.
The identities and antibiotic resistance profiles of bacteria isolated from 433 cases of acute cholangitis from 346 patients were analyzed. Risk factors and the outcomes of patients infected with them were assessed.
Microorganisms were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures. Isolates from bile and blood were identical in 71% of the cases. A total of 20 extended spectrum-β-lactamase (ESBL)-producers and 4 carbapenemase-producing organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase-producers were isolated from bile. Sixty-four (14.8%) cases were infected with any one of these bacteria isolated from blood or bile. Risk factors associated with them in blood were nosocomial infection and prior biliary intervention. In bile, indwelling biliary device was a risk factor associated with them. Antibiotic-resistant bacteria were associated with mortality, independent of other prognostic factors.
ESBL or carbapenemase-producing bacteria were frequently isolated in acute cholangitis patients especially with prior biliary intervention and nosocomial infection. Isolation of antibiotic-resistant bacteria was an independent risk factor of mortality.
PMCID: PMC3401620  PMID: 22866257
Acute cholangitis; Bile culture; Blood culture; Microbial drug resistance
10.  Comparison of Midazolam Alone versus Midazolam Plus Propofol during Endoscopic Submucosal Dissection 
Clinical Endoscopy  2011;44(1):22-26.
For proper sedation during endoscopic submucosal dissection (ESD), propofol has been widely used. This study aimed to compare the levels of sedation and tolerance of patients treated with midazolam (M group) and a combination of midazolam and propofol (MP group) during ESD.
A total of 44 consecutive patients undergoing ESD were randomly assigned to the two groups. In the M group, 2 mg of midazolam was given repeatedly to maintain after a loading dose of 5 mg. The MP group initially received 5 mg of midazolam and 20 mg of propofol. Then, we increased the dosage of propofol by 20 mg gradually.
The average amount of midazolam was 12 mg in the M group. In the M group, 10 patients were given propofol additionally, since they failed to achieve proper sedation. The average amount of propofol was 181 mg in the MP group. Procedure time, vital signs and rates of complications were not significantly different between two groups. Movement of patients and discomfort were lower in the MP group.
During ESD, treatment with propofol and a low dose of midazolam for sedation provides greater satisfaction for endoscopists compared to midazolam alone.
PMCID: PMC3363047  PMID: 22741108
Endoscopic submucosal dissection; Sedation; Midazolam; Propofol
11.  Primary endoscopic approximation suture under cap-assisted endoscopy of an ERCP-induced duodenal perforation 
Duodenal perforation during endoscopic retrograde cholangiopancreatography (ERCP) is a rare complication, but it has a relatively high mortality risk. Early diagnosis and prompt management are key factors for the successful treatment of ERCP-related perforation. The management of perforation can initially be conservative in cases resulting from sphincterotomy or guide wire trauma. However, the current standard treatment for duodenal free wall perforation is surgical repair. Recently, several case reports of endoscopic closure techniques using endoclips, endoloops, or fully covered metal stents have been described. We describe four cases of iatrogenic duodenal bulb or lateral wall perforation caused by the scope tip that occurred during ERCP in tertiary referral centers. All the cases were simply managed by endoclips under transparent cap-assisted endoscopy. Based on the available evidence and our experience, endoscopic closure was a safe and feasible method even for duodenoscope-induced perforations. Our results suggest that endoscopists may be more willing to use this treatment.
PMCID: PMC2868227  PMID: 20458771
Duodenal perforation; Endoscopic retrograde cholangiopancreatography; Endoscopic therapy; Endoclip
12.  A Case of Idiopathic Adulthood Ductopenia 
Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.
PMCID: PMC2732788  PMID: 19721865
Idiopathic adulthood ductopenia; Cholestasis
13.  A case of idiopathic colonic varices: A rare cause of hematochezia misconceived as tumor 
Colonic varices are a very rare cause of lower gastrointestinal bleeding. Fewer than 100 cases of colonic varices, and 30 cases of idiopathic colonic varices (ICV) have been reported in the English literature. Among these 30 cases of ICV, 19 cases were diagnosed by angiography, and 7 operated cases were diagnosed later as ileocecal vein deficit, hemangioma, and idiopathic in 1, 1, 5 cases, respectively. We report the case of a 24-year-old man who suffered from multiple episodes of hematochezia of varying degree at the age of 11 years. He had severe anemia with hemoglobin of 21 g/L. On colonoscopy, tortuously dilated submucosal vein and friable ulceration covered with dark necrotic tissues especially at the rectosigmoid region were seen from the rectum up to the distal descending colon. It initially appeared to be carcinoma with varices. Mesenteric angiographic study suggested a colonic hemangioma. Low anterior resection was done due to medically intractable and recurrent hematochezia. Other bowel and mesenteric vascular structures appeared normal. Microscopic examination revealed normal colonic mucosa with dilated veins throughout the submucosa and serosa without representing new vessel growth. Taken all of these findings together, the patient was diagnosed as ICV. His postoperative course was uneventful.
PMCID: PMC4088003  PMID: 16688816
Idiopathic colonic varices; Hematochezia; Colon cancer; Hemangioma
14.  Hemobilia from Ruptured Hepatic Artery Aneurysm in Polyarteritis Nodosa 
Hemobilia, in patients with the diagnosis of polyarteritis nodosa, is rare at clinical presentation and has a grave prognosis. We describe a case of massive hemobilia, due to aneurysmal rupture, in a patient with polyarteritis nodosa. A 39-year-old man was admitted to the hospital with upper abdominal pain. The patient had a history of partial small bowel resection, for intestinal infarction, about 5 years prior to this presentation. Abdominal computed tomography demonstrated multiple high attenuation areas in the bile duct and gallbladder. Hemobilia with blood seepage was visualized on endoscopic retrograde cholangiopancreatography; this bleeding stopped spontaneously. The following day, the patient developed a massive gastrointestinal bleed with resultant hypovolemic shock. Emergent hepatic angiogram revealed multiple microaneurysms; a communication was identified between a branch of the left hepatic artery and the bile duct. Hepatic arterial embolization was successfully performed. The underlying disease, polyarteritis nodosa, was managed with prednisolone and cyclophosphamide.
PMCID: PMC3891070  PMID: 16646571
Hemobilia; Polyarteritis nodosa
15.  H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO) 
This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, NG-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.
PMCID: PMC4211127  PMID: 25352763
Circular smooth muscle; Corpus; H2 receptors; Histamine; Human stomach; Nitric Oxide (NO); Relaxation
16.  A Novel Germline Mutation in Exon 10 of the SMAD4 Gene in a Familial Juvenile Polyposis 
Gut and Liver  2013;7(6):747-751.
Familial juvenile polyposis (FJP) is a rare autosomal dominant hereditary disorder that is characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of cancer. Recently, germline mutations, including mutations in the SMAD4, BMPR1A, PTEN and, possibly, ENG genes, have been found in patients with juvenile polyps. We herein report a family with juvenile polyposis syndrome (JPS) with a novel germline mutation in the SMAD4 gene. A 21-year-old man presented with rectal bleeding and was found to have multiple polyps in his stomach, small bowel, and colon. His mother had a history of gastrectomy for multiple gastric polyps with anemia and a history of colectomy for colon cancer. A review of the histology of the polyps revealed juvenile polyps in both patients. Subsequently, mutation screening in DNA samples from the patients revealed a germline mutation in the SMAD4 gene. The pair had a novel mutation in exon 10 (stop codon at tyrosine 413). To our knowledge, this mutation has not been previously described. Careful family history collection and genetic screening in JPS patients are needed to identify FJP, and regular surveillance is recommended.
PMCID: PMC3848546  PMID: 24312718
Familial juvenile polyposis; Mutation; SMAD4; Exon 10
17.  Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients 
Diagnostic Pathology  2013;8:99.
Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients.
We evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR.
Loss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation.
The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.
Virtual slides
The virtual slides for this article can be found here:
PMCID: PMC3728147  PMID: 23783026
Epithelial to mesenchymal transition; E-cadherin; β-catenin; S100A4; Tumor budding; Colorectal cancer
18.  Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives 
The Scientific World Journal  2013;2013:704912.
Currently, two direct-acting antivirals (DAAs) show well-established efficacy against hepatitis C virus (HCV), namely, first-wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC) regimens. Future therapeutic drugs were divided into three categories. They are second-wave protease inhibitors, second-generation protease inhibitors, and polymerase inhibitors. Second-wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN) not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR). But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug-resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%). Oral drug combinations will be standard of care in the near future.
PMCID: PMC3687480  PMID: 23844410
20.  High K+-Induced Relaxation by Nitric Oxide in Human Gastric Fundus 
This study was designed to elucidate high K+-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K+ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K+-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 µM) and KT 5720 (1 µM) which block protein kinases (PKG and PKA) had no effect on high K+-induced relaxation. K+ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K+ channel (KV) blocker, did not affect high K+-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K+-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K+-induced relaxation that was activated by the nitric oxide/sGC pathway through a KV channel-dependent mechanism.
PMCID: PMC3484514  PMID: 23118553
Fundus; High K+; Human stomach; Longitudinal smooth muscle; Nitric oxide; Relaxation
21.  Common bile duct dilatation after cholecystectomy: a one-year prospective study 
Bile duct dilatation after cholecystectomy continues to be a matter of controversy. We aimed determine the magnitude of common bile duct (CBD) dilatation after cholecystectomy followed up to 1 year.
Sixty-four cases (age, 47.3 ± 11.7 years; men, 28; women, 36) enrolled in this study. They received laparoscopic cholecystectomy in Chungbuk National University Hospital for symptomatic cholelithiasis or gallbladder polyps with normal bile duct, less than 7 mm. The CBD diameter was measured by one radiologist using ultrasonography at the maximum point after full length evaluation of extrahepatic bile duct. Forty-five and thirty-one cases were followed at 6 months and 1 year, respectively.
The CBD was dilated slightly from 4.1 mm at baseline to 5.1 mm at 6 months and 6.1 mm at 12 months after cholecystectomy. The number of cases of CBD dilatation of more than 7 mm at 6 months and at 12 months after cholecystectomy were 11 (24.4%) and 9 (29.0%), respectively. Seven cases at 6 months and 5 cases at 12 months showed bile duct dilation of more than 3 mm compared to baseline. There were no cases having bile duct dilation of more than 10 mm.
Postcholecystectomy dilatation of the bile duct occured slightly in most cases. But some cases showed more than 3 mm dilatation over baseline. Asymptomatic bile duct dilatation of up to 10 mm can be considered as normal range in patients after cholecystectomy.
PMCID: PMC3412191  PMID: 22880184
Cholecystectomy; Common bile duct; Dilatation; Ultrasound
22.  High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B 
Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.
Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy.
The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).
ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.
PMCID: PMC3326991  PMID: 22511906
Adefovir; Entecavir; Combination drug therapy; Drug resistance; Treatment efficacy
24.  Nitric Oxide-mediated Relaxation by High K+ in Human Gastric Longitudinal Smooth Muscle 
This study was designed to elucidate high-K+induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K+ (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K+ (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K+-induced relaxation. K+ channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba2+) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K+ channel (KV) blocker, inhibited high K+-induced relaxation, hence reversing to tonic contraction. High K+-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and KV channel blocker sensitive high K+-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K+-induced relaxation which was activated by NO/sGC pathway and by KV channel dependent mechanism.
PMCID: PMC3282229  PMID: 22359479
Human stomach; Relaxation; Nitric oxide (NO); Longitudinal smooth muscle; High K+
25.  Mechanism of Action of Cholecystokinin on Colonic Motility in Isolated, Vascularly Perfused Rat Colon 
It is generally believed that cholecystokinin (CCK) stimulates colonic motility, although there are controversial reports. It has also been suggested that postprandial peptide YY (PYY) release is CCK-dependent. Using a totally isolated, vascularly perfused rat colon, we investigated: (1) the roles of CCK and PYY on colonic motility, (2) to determine if CCK modulates PYY release from the colon to influence the motility and (3) to clarify whether the action of CCK and PYY on colonic motility is mediated via the influence of cholinergic input.
An isolated whole rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers from proximal and distal colon. After a control period, CCK-8 or PYY was administerd intraarterially with or without an anti-PYY serum, loxiglumide or atropine at 12, 60 and 240 pM. Each dose was given for a period of 15-minute and the contractile response was expressed as % changes over basal. PYY concentration in the portal effluent was determined by radioimmunoassay.
Exogenous CCK-8 increased colonic motility which paralleled the increase in PYY release in the portal effluent. Exogenous PYY also significantly increased colonic motility although it was less potent than CCK. The stimulating effect of CCK-8 was significantly inhibited by an anti-PYY serum, and was completely abolished by loxiglumide, and almost completely abolished by atropine.
CCK increases colonic motility via CCK1 receptor and it is mediated partly by PYY. Cholinergic input is required for the increased motility by either PYY or CCK.
PMCID: PMC3042223  PMID: 21369495
Cholecystokinin; Colon; Peptide YY

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