Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Endoscopic Full-Thickness Resection for Gastric Subepithelial Lesions Arising from the Muscularis Propria

Most cases of gastric subepithelial lesions follow a good clinical course; however, some lesions progress to malignant tumors, and treatment of tumors with a high risk of malignancy is essential. Surgical excision has been the primary treatment for tumors originating from the propria muscle layer, but it has the disadvantages of being invasive and causing postoperative functional abnormalities. With the development of endoscopic techniques and instruments, the role of endoscopic resection, which is a less invasive method for the removal of gastric subepithelial lesions, has been attracting attention. We performed an endoscopic full-thickness resection for 8 patients with gastric subepithelial lesions originating from the muscularis propria. No fatal complications occurred. Our findings suggest the need to develop various devices for resection and closure and to accumulate further experience through additional studies to prevent complications and specimen loss.

Primary Signet Ring Cell Carcinoma of the Gallbladder Mimicking Calculous Cholecystitis / 대한췌담도학회지

Signet ring cell carcinoma is a rare form of gallbladder cancer and has a worse prognosis. Since few cases have been reported, information regarding the behavior and prognosis of the gallbladder carcinoma is limited. About twenty four cases of gallbladder signet ring cell carcinoma have been reported so far. We present a rare case of primary signet ring cell carcinoma of the gallbladder. A 58-year-old male presented with epigastric pain. Abdominal computed tomography showed diffuse gallbladder wall thickening with enhancement, gallstones, and choledocholithiasis. After endoscopic treatment of choledocholithiasis, laparoscopic cholecystectomy was performed. Pathologic examination of the resected gallbladder revealed adenocarcinoma of signet ring cell type in the epithelium. Immunohistochemical stain for cytokeratin 7 was positive for tumor cells. The final pathologic diagnosis was primary signet ring cell carcinoma of the gallbladder. Lymph node metastasis was detected and he received chemotherapy and radiotherapy. After one year of follow-up, bone metastasis in the lumbar spine and malignant ascites were found. The patient is being provided with palliative care.

A Case of Endoscopically Treated Laryngopharyngitis Resulting from Clinostomum complanatum Infection / 대한소화기학회지

A 46-year-old woman visited our hospital presenting throat pain and globus sensation. The symptoms occurred seven days after eating raw perch and mullet. An endoscopy under sedation showed a fluke―with an approximate length of 4.8 mm and width of 1.5 mm―on the left aryepiglottic fold, with active motility on the mucosa. It was extracted from the larynx using biopsy forceps and was identified as Clinostomum complanatum. To the best of our knowledge, this is the second reported case of human infection with Clinostomum complanatum diagnosed and treated by an endoscopy in Korea. Endoscopy is a useful tool in the diagnosis and treatment of patients at risk for parasitic infections complaining of throat pain.

A Case of Endoscopic Removal of a Giant Appendicolith Combined with Stump Appendicitis

Stump appendicitis is an acute inflammation of the residual appendix and is a rare complication after appendectomy. The physician should be aware of the possibility of stump appendicitis in patients with right lower abdominal pain after appendectomy so that delayed diagnosis and treatment can be prevented. Stump appendicitis is usually treated by surgical resection, and endoscopic treatment has not been reported previously. A 48-year-old man who had undergone appendectomy 35 years earlier presented to the hospital because of right lower quadrant discomfort. A computed tomography scan showed a large stone in the residual appendix. Colonoscopic findings revealed a large, smooth, protruding lesion at the cecum with a stone inside the appendiceal orifice. Endoscopic removal after incision of the appendiceal orifice was performed successfully.

A Case of Enteritis Cystica Profunda in the Ampulla of Vater Mimicking Choledochocele

Enteritis cystica profunda is a very rare disease in which a mucin-filled cystic space is surrounded partially with nonneoplastic columnar epithelium in the submucosa of the small intestine. Most of the cases are accompanied by intestinal diseases, and the disease usually occurs in the jejunum and the ileum and there has been no report of a case that occurred in the ampulla of Vater. A 58-year-old healthy female patient without any particular symptom visited the hospital to get additional examination for a mass found on the ampulla of Vater by accident. In esophagogastroduodenoscopy, a cystic mass showing a positive pillow sign was found on the ampulla of Vater. Endoscopic retrogradecholangiopancreatography was conducted as choledochocele was suspected, but no abnormality was found in the biliary system. In endoscopic ultrasonography, multiseptated cystic structures were detected in the submucosal layer of the duodenum. The lesion was resected completely through endoscopic snare polypectomy and the case was histologically diagnosed as enteritis cystica profunda.

The Adequate Induction Dose of Propofol for Conscious Sedation During Esophagogastroduodenoscopy in Persons 60 Years or Older / 대한소화기내시경학회지

BACKGROUND/AIMS: Propofol is an effective sedative drug in endoscopic procedures, but it has potentially serious adverse effects, so close monitoring of the vital signs should be performed during endoscopy. This study was undertaken to determine the adequate induction dose of propofol for safe and effective sedation during esophagogastrodudenoscopy (EGD) in persons 60 years or older. METHODS: Three hundred patients who visited our hospital for EGD were randomly assigned to three groups (A,B and C). An initial induction dose of 0.5 mg/kg, 0.75 mg/kg and 1.0 mg/kg of propofol was allocated to groups A, B and C, respectively. RESULTS: The 0.5 mg/kg, 0.75 mg/kg and, 1 mg/kg dose of propofol were all safe as an initial dose of propofol for achieving sedation during EGD in persons 60 years or older. There was no difference in the total amount of propofol among the three groups. Group C had a significantly shorter induction time and a lower dose was required for an additional injection of propofol without increasing adverse events, as compared to the two other groups. CONCLUSIONS: We suggest that 1 mg/kg of propofol is an effective induction dose for sedation during EGD in persons 60 years or older.

A Case of Signet-ring Cell Carcinoma of the Ampulla of Vater / 대한소화기내시경학회지

Signet-ring cell carcinoma of the ampulla of Vater is so rare that only 16 cases have been reported. Here we report a case of a 47-year-old man with signet-ring cell carcinoma in the ampulla of Vater. The patient was hospitalized for right upper quadrant abdominal pain and jaundice which had developed 10 days prior. Computed tomography (CT) and ultrasonography (US) revealed dilatation of the common bile duct and the intrahepatic bile duct. On duodenoscopy, a bulging mass with an irregular margin in the major papilla was noted. Histologic findings showed a signet-ring cell carcinoma. Surgical resection was not done because lymph node metastasis was noted during the operation. Hence, conservative treatment including chemotherapy and bile drainage was done.

Clinical Characteristics and Gestational Complications Associated with Acute Hepatitis A in Pregnancy / 대한소화기학회지

BACKGROUND/AIMS: Acute hepatitis A was recently significant increased among women with gestational age in Korea. However, the clinical course and gestational complications have not been fully elucidated in pregnant patients with acute hepatitis A. We evaluated the clinical impact of acute HAV infection in pregnancy. METHODS: Twelve pregnant women out of 85 female patients with acute hepatitis A during 6 years were retrospectively reviewed. RESULTS: The median age of the pregnant group was 26.5 years old. The number of patient with acute hepatitis A were 5 cases in the 1st trimester, 3 cases in the 2nd and 4 cases in the 3rd. 4 cases had significant gestational complications. One case experienced the abortion in 1st trimester and one fetal distress was noted in 3rd trimester. The latter case was delivered of a low birth weight infant (2,390 g) caused by premature rupture of membrane in 36 weeks of gestational age. Other two cases experienced premature contraction and they had been required tocolytic treatment. But, all mothers featured full recovery from HAV infection. Except one aborted fetus and one premature birth, Newborn babies were not affected by maternal hepatitis A. CONCLUSIONS: Acute HAV infection during pregnancy may be associated with the risk of gestational complications. HAV serology and vaccination for women with gestation age should be considered at high prevalence area of acute hepatitis A.

The Adequate Dose of Propofol for Inducing Sedation during Performance of Upper Gastrointestinal Endoscopy in Koreans / 대한소화기내시경학회지

BACKGROUND/AIMS: Propofol sedation is increasingly being used when performing upper gastrointestinal endoscopy because of its rapid onset and good recovery profile. For achieving safe sedation during endoscopy, close monitoring of the vital signs is necessary because of the sedation's potentially serious adverse effects. There are only a few studies on the induction of sedation with using propofol for endoscopy in Korea. The present study was undertaken to evaluate the adequate initial injected dose of propofol for achieving safe and effective sedation when performing upper gastrointestinal endoscopy in Koreans. METHODS: From March 2008 to July 2008, 150 subjects who visited Kwangju Christian Hospital were randomized into 3 groups. An initial bolus dose of 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg of propofol was allocated to groups A, B and C, respectively. The effectiveness and safety profiles of each injected dose of propofol were prospectively assessed by measuring various parameters of the vital signs and the adverse events. RESULTS: Group C had a significantly shorter induction time and the patients in group C did not require additional injections of propofol without increasing adverse events, as compared to that of the other 2 groups. CONCLUSIONS: 1.5 mg/kg of propofol was found to be more appropriate than 0.5 mg/kg or 1.0 mg/kg of propofol as the initial injected dose for induction of sedation during performance of upper gastrointestinal endoscopy in Koreans.

A Case of Jejunogastric Intussusception that was Diagnosed by Gastroscopy in a Patient who had Undergone Subtotal Gastrectomy / 대한소화기내시경학회지

Jejunogastric intussusception is a rare, but potentially lethal complication after gastrectomy or gastrojejunostomy. In the acute condition, early diagnosis and prompt surgical treatment are mandatory to reduce the incidence of mortality. We present here a case of jejunogastric intussusception that was diagnosed by gastroscopy in a patient with a history of subtotal gastrectomy, and she had experienced increasing epigastric pain and vomiting for 1 day.

A Case of an Eosinophilic Granuloma Mimicking a Submucosal Tumor in the Ascending Colon Probably Caused by Anisakis / 대한소화기내시경학회지

Anisakiasis in the gastrointestinal tract is caused by the ingestion of raw marine fish that contain Anisakis lavae. In rare cases, Anisakiasis is found as an eosinophilic granuloma that mimics a submucosal tumor. The diagnosis is usually made after surgical resection. Several cases of gastric anisakiasis imitating a submucosal lesion have been reported. However, colonic anisakiasis forming a submucosal lesion is very rare and only a few cases have been reported. All of the cases were confirmed after surgery. Recently, we encountered a male patient with a submucosal lesion on the ascending colon during a health screening. Several biopsies were performed on the same site as the lesion. The pathological finding was eosinophilic granuloma. We tentatively diagnosed the patient with eosinophilic granuloma due to Anisakis as the patient consumed raw seafood and eosinophilia was detected on a laboratory test. We decided not to perform any procedure. One month later, the eosinophilic granuloma disappeared as seen on a follow-up colonoscopy.

A Case of Duodenal Fistula Caused by Intra-abdominal Tuberculous Lymphadenopathy during Anti-tuberculous Medication / 대한소화기내시경학회지

Recently, the proportion of extrapulmonary tuberculosis in patients has increased in Korea. Though intestinal tuberculosis in not infrequent, a duodenal fistula caused by tuberculosis is a rare condition. A 29-year-old man was admitted to the Department of Internal Medicine because of fever and weight loss. The patient was a doctor participating in a resident fellowship. The patient was diagnosed with intra-abdominal tuberculous lymphadenopathy and was given anti-tuberculous medication. One month after the administration of medication, the patient showed symptoms and signs of duodenal obstruction because of marked duodenal wall edema and a deep ulcer on the second portion of the duodenum. A computerized tomogram and duodenography revealed the formation of a fistula at the second portion of the duodenum and the presence of abscess-forming tuberculous lymphadenopathy. The use of continuous anti- tuberculous medication resulted in the improvement of the clinical symptoms, with complete healing of the duodenal fistula and tuberculous lymphadenitis. This case suggests that transient clinical worsening in intra-abdominal tuberculous lymphadenitis may occur during an early period of anti- tuberculous medication.

A Case of Refractory Esophageal Stricture Induced by Lye Ingestion and Treated by Temporary Placement of Newly Designed Self-Expanding Metal Stent and Wetting with Mitomycin C / 대한소화기내시경학회지

Ingestion of strong acids or strong alkalies may produces severe inflammation on the mucosa of the esophagus and this may also causes esophageal stricture. Several forms of non-operative dilatations have been utilized for the treatment of esophageal stricture and they have shown good results. Yet some patients do not achieve acceptable symptom relief despite of intensive dilatation. Temporary placement of esophageal stent has recently been used in some of these patients. Furthermore, mitomycin C has been used as a conservative treatment for refractive esophageal stricture in children, yet its efficacy has not been well established. We experienced a case of a 64-year old man with severe, recurrent esophageal stricture, and this was successfully managed by temporary placement of an esophageal stent, together with a spray of mitomycin C. We report on this case along with the review of the literature.

A Case of Pneumoperitoneum, Pneumoretroperitoneum, Pneumomediastinum, and Subcutaneous Emphysema after Endoscopic Submucosal Resection / 대한소화기내시경학회지

Flexible fiberoptic colonoscopy is extensively used for the diagnosis and management of colorectal disease. Many possible complications can occur. The most common and most serious complications are hemorrhage, perforation and respiratory problems. Colonic perforation usually results in a fatal and emergent condition. However, management of iatrogenic colonic perforation has been controversial. The choice between the medical versus the surgical approach has been dependent on the mechanism of the perforation, bowel preparation, location, size of the defect and severity of symptoms. We report here a case where colonic perforation emerged during endoscopic submucosal resection of a rectal tumor. The rectal perforation was accompanied with pneumoperitoneum, subcutaneous emphysema, pneumoretroperitoneum and pneumomediastinum. As the bowel preparation was excellent, intravenous antibiotics and total parenteral nutirition were administered. The patient was treated successfully without any complications.

A Case of Pneumoperitoneum, Pneumoretroperitoneum, Pneumomediastinum, and Subcutaneous Emphysema after Endoscopic Submucosal Resection / 대한소화기내시경학회지

Flexible fiberoptic colonoscopy is extensively used for the diagnosis and management of colorectal disease. Many possible complications can occur. The most common and most serious complications are hemorrhage, perforation and respiratory problems. Colonic perforation usually results in a fatal and emergent condition. However, management of iatrogenic colonic perforation has been controversial. The choice between the medical versus the surgical approach has been dependent on the mechanism of the perforation, bowel preparation, location, size of the defect and severity of symptoms. We report here a case where colonic perforation emerged during endoscopic submucosal resection of a rectal tumor. The rectal perforation was accompanied with pneumoperitoneum, subcutaneous emphysema, pneumoretroperitoneum and pneumomediastinum. As the bowel preparation was excellent, intravenous antibiotics and total parenteral nutirition were administered. The patient was treated successfully without any complications.

Three Cases Of Gas-Forming Liver Abscesses Successfully Treated By Early Pigtail Catheter Drainage / 대한내과학회지

Many advances, including the development of antibiotics, the advent of diagnostic techniques and the use of nonsurgical drainage have decreased the mortality rate of pyogenic liver abscess. But, early prompt diagnosis and proper treatment is mandatory in gas-forming pyogenic liver abscess because it may run a fulminating course to death. Gas-forming pyogenic liver abscess mostly occurred to old diabetics. Symptoms of duration are shorter and the prognosis is poorer in the gas-forming than in the non-gas-forming liver abscess. We report three cases of gas-forming pyogenic liver abscess which occurred in old diabetic patients. They were successfully managed by parenteral antibiotics and early percutaneous drainage under sonographic guidance. Early and adequate drainage of pus by pigtail catheter may play a crucial role on the treatment of gas-forming liver abscess.

A Study on the Usefulness of ERCP in Patients with Pyogenic Liver Abscess / 대한소화기내시경학회지

BACKGROUND/AIMS: This study was undertaken to evaluate the usefulness of ERCP in patients with pyogenic liver abscess. METHODS: An endoscopic retrograde cholangiographic study of 70 consecutive cases of pyogenic liver abscess was conducted during the period from January, 1993 to December, 1997. Among 70 cases of pyogenic liver abscess, the male to female ratio was 1.69 :1, and the peak incidence was in the sixth decade. RESULTS: The common associated diseases were liver cirrhosis (11.4%), diabetes mellitus (8.5%), and malignancy (5.7%). The most common origins of the abscess in decreasing order of frequency were, transbiliary infection (51%), hematogenous spread, and trauma-associated causes. The ascending infection through the biliary tract as the etiology of liver abscess, has been common since the 1970's. The positive rate of abdominal US, CT, and ERCP in the diagnosis of the etiology of the liver abscess was 68, 82, 84% respectively. The treatments of the pyogenic liver abscess were, surgical drainage in 15 cases (21%) and percutaneous drainage in 51 cases (73%). Among 70 patients treated for pyogenic liver abscess, 12 patients had CBD stones and 11 patients were cured by EST. CONCLUSIONS: The most common origin of liver abscess is ascending infection through the biliary tract and ERCP may be a effective tool in the assessment and management of the etiology of pyogenic liver abscess.

A Case of Squamous Cell Carcinoma of the Common Bile Duct / 대한소화기내시경학회지

A 57-year-old female with jaundice and right upper quadrant abdominal pain, was found on exploration to have squamous cell carcinoma of the common bile duct. Squamous cell carcinoma of the common bile duct is a very rare tumor, simulating adenocarcinoma in its clinical presentation and aggressiveness. Although no consistent causative factors for this tumor has been demonstrated, it has been theorized that the normal columnar epithelium of the bile duct under the influence of an inflammatory stimulus, can develop into squamous epithelium with the ongoing process leading to squamous metaplasia, and eventually carcinoma. Cholelithiasis has been implicated as a cause for bile duct cancer, which was manifested in this patient. The prognosis of this carcinoma was grave, despite all forms of surgical and medical management. A case of squamous cell carcinoma of the common bile duct is reported with a review of relevant literature.