Efficacy and Safety of Rebamipide versus Its New Formulation, AD-203, in Patients with Erosive Gastritis: A Randomized, DoubleBlind, Active Control, Noninferiority, Multicenter, Phase 3 Study

Background/Aims@#The mucoprotective drug rebamipide is used to treat gastritis and peptic ulcers. We compared the efficacy of Mucosta Ⓡ (rebamipide 100 mg) and its new formulation, AD-203 (rebamipide 150 mg), in treating erosive gastritis. @*Methods@#This double-blind, active control, noninferiority, multicenter, phase 3 clinical trial randomly assigned 475 patients with endoscopically proven erosive gastritis to two groups: AD-203 twice daily or Mucosta Ⓡ thrice daily for 2 weeks. The intention-to-treat (ITT) analysis included 454 patients (AD-203, n=229; Mucosta Ⓡ , n=225), and the per-protocol (PP) analysis included 439 patients (AD-203, n=224; Mucosta Ⓡ , n=215). The posttreatment assessments included the primary (erosion improvement rate) and secondary endpoints (erosion and edema cure rates; improvement rates of redness, hemorrhage, and gastrointestinal symptoms). Drug-related adverse events were evaluated. @*Results@#According to the ITT analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.7% and 43.8%, respectively. According to the PP analysis, the erosion improvement rates (posttreatment) in AD-203-treated and Mucosta Ⓡ -treated patients were 39.3% and 43.7%, respectively. The one-sided 97.5% lower limit for the improvement rate difference between the study groups was −4.01% (95% confidence interval [CI], –13.09% to 5.06%) in the ITT analysis and −4.44% (95% CI, –13.65% to 4.78%) in the PP analysis. The groups did not significantly differ in the secondary endpoints in either analysis. Twenty-four AD-203-treated and 20 Mucosta Ⓡ -treated patients reported adverse events but no serious adverse drug reactions; both groups presented similar adverse event rates. @*Conclusions@#The new formulation of rebamipide 150 mg (AD-203) twice daily was not inferior to rebamipide 100 mg (Mucosta Ⓡ ) thrice daily. Both formulations showed a similar efficacy in treating erosive gastritis.

Helicobacter pylori Eradication Induced Constant Decrease in Interleukin-1B Expression over More Than 5 Years in Patients with Gastric Cancer and Dysplasia

Background/Aims@#Helicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+ -adenosine triphosphatase (H+, K+ -ATPase) and stimulat-ing interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+ -ATPase and IL-1β after Hp eradication. @*Methods@#Two hundred twentyone subjects were categorized as Hp-negative (n=84) or Hppositive (n=137) according to the results of Hp tests (histol-ogy, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+ -ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reac-tion. @*Results@#The Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hperadicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dys-plasia subgroup, the IL-1B mRNA levels at 1, 2, 3–4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant. @*Conclusions@#Infection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradica-tion contributes to the prevention of metachronous GC after Hp eradication.

A case of intra-abdominal abscess caused by unconsciously ingestion of fish bone in elderly patient / 고신대학교의과대학학술지

Cases showing complications such as esophageal injury, deep neck infection, and mediastinitis caused by accidental ingestion of fish bone are common. But ingestion of fish bone rarely causes perforation of the gastrointestinal tract or an intra-abdominal abscess. We report herein a case of a 78-year-old man with a periumbilical mesenteric abscess caused by fish bone which was ingested unconsciously. The fish bone was found in the terminal ileum and it was removed by colonoscopy. The patient improved and he was discharged after systemic antibiotic therapy. Occasionally, when patients swallow fish bone without a foreign body sensation, clinicians should suspect perforation caused by fish bone in case of an intra-abdominal abscess of unknown cause.

Outcomes of patients treated with Sengstaken-Blakemore tube for uncontrolled variceal hemorrhage

BACKGROUND/AIMS: The aim of this study was to investigate the mortality, bleeding control rate, and their associated predictors in patients treated with Sengstaken-Blakemore (SB) tube for uncontrolled variceal hemorrhage associated with hemodynamic instability or failure of endoscopic treatment. METHODS: The clinical data of 66 consecutive patients with uncontrolled variceal hemorrhage treated with SB tube at Gyeongsang National University Hospital from October 2010 to October 2015 were retrospectively analyzed. RESULTS: The overall success rate of initial hemostasis with SB tube was 75.8%, and the independent factors associated with hemostasis were non-intubated state before SB tube (odds ratio, 8.50; p = 0.007) and Child-Pugh score < 11 (odds ratio, 15.65; p = 0.022). Rebleeding rate after successful initial hemostasis with SB tube was 22.0%, and esophageal rupture occurred in 6.1%. Mortality within 30 days was 42.4%, and the related independent factors with mortality were failure of initial hemostasis with SB tube (hazard ratio, 6.24; p < 0.001) and endotracheal intubation before SB tube (hazard ratio, 2.81; p = 0.018). CONCLUSIONS: Since the era of endoscopic band ligation, SB tube might be a beneficial option as a temporary salvage treatment for uncontrolled variceal hemorrhage. However, rescue therapy had a high incidence of fatal complication and rebleeding.

Severe Upper Gastrointestinal Bleeding in Patients on Antithrombotic Therapy

BACKGROUND/AIMS: As the elderly population taking antithrombotic therapy (ATT) increases, gastrointestinal (GI) bleeding risk during ATT may likely increase. This study was conducted to evaluate the clinical characteristics of severe upper GI bleeding (UGIB) during ATT. MATERIALS AND METHODS: Among patients on ATT at Gyeongsang National University Hospital between March 2005 and February 2010, those with severe UGIB requiring endoscopic hemostasis were selected for the study. Their medical records were retrospectively reviewed for clinical variables. RESULTS: Among 59,773 patients taking ATT, 125 (0.21%) developed severe UGIB and comprised 12.8% of the overall endoscopic hemostasis cases (125/978) during the same period. The patients with severe UGIB on ATT were older than the ones not on ATT (68.3 vs. 59.9 years, P<0.001). The common indications for ATT were cardiovascular (60.8%, 76/125) and cerebrovascular diseases (25.6%, 32/125). Fifty-nine patients (47.2%) were taking two or more agents, 36 (28.8%) were on aspirin monotherapy, while 22 (17.6%) were taking warfarin alone. Aspirin was involved in 68.8% (86/125) of severe UGIB. According to ATT type, the incidence of severe UGIB was 0.48% with warfarin, 0.38% with aspirin, and 0.33% with clopidogrel. The main causes of severe UGIB were gastric (78, 62.4%) and duodenal ulcers (15, 12.0%). UGIB recurred in 11 cases (8.8%), but all were successfully controlled with repeated hemostasis and there was no mortality. CONCLUSIONS: The frequency of severe UGIB during ATT was 0.21%. Aspirin was the most common agent leading to severe UGIB, but its incidence was highest with warfarin. Gastric ulcer was the most common focus. Endoscopic hemostasis was effective and safe for UGIB during ATT.

Incidence of Gastric Cancer in Patients with Laryngeal Cancer

BACKGROUND/AIMS: Gastric cancer (GC) is the second most common cancer in Korea and the most common in men in the south of the country. We investigated the incidence of synchronous GC in patients with head and neck squamous cell carcinoma (HNSCC) in the southern part of Korea. MATERIALS AND METHODS: We retrospectively reviewed the medical records of HNSCC patients treated between 2011 and 2014. In patients with synchronous GC, evaluation included a history of smoking and alcohol consumption, endoscopic findings, Campylobacter-like organism (CLO) test, and immunohistochemical analysis of preserved HNSCC tissues. RESULTS: Analysis of the records of 153 HNSCC patients revealed tumors of the larynx in 56 patients (36.6%), of the pharynx in 74 patients (48.4%), and tumors at other locations in 23 patients (15.0%). The mean age of patients was 66.0 years, and the men:women ratio was 8:1. Synchronous cancers were detected in 12 patients. We observed esophageal squamous cell carcinoma (SCC) in five patients (3.3%), and gastric adenocarcinoma in seven patients (4.6%). Synchronous GC was detected in patients with laryngeal SCC. All cases of GC were classified as early GC. CONCLUSIONS: Synchronous GC was as frequent as esophageal SCC in patients with HNSCC, and all cases of GC were observed to be early stage cancers in this study. Thorough endoscopic examination should be performed in patients with laryngeal cancer to detect the presence of synchronous GC.

A Case of Composite Hepatocellular Carcinoma and Neuroendocrine Carcinoma in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis B / 대한소화기학회지

Primary hepatic neuroendocrine carcinoma (PHNEC) is rare and its origin is not clearly understood. The coexistence of PHNEC and hepaotcellular carcinoma has been reported in only a few cases. We report a rare case of combined PHNEC and hepaotcellular carcinoma in a patient with liver cirrhosis caused by chronic hepatitis B that resulted in aggressive behavior and poor prognosis.

Early monitoring for detection of antituberculous drug-induced hepatotoxicity

BACKGROUND/AIMS: We investigated the time of onset of antituberculous drug-induced hepatotoxicity (ADIH) and related characteristics. METHODS: Adult patients (n = 1,031) treated with first-line antituberculous drugs between February 2009 and January 2013 were enrolled. RESULTS: Of the 1,031 patients, 108 patients (10.5%) developed ADIH a mean of 39.6 +/- 43.7 days after treatment initiation. Twenty-eight patients (25.9%) developed ADIH within 7 days, 73 (67.6%) within 30 days, and the rest after 30 days. The 30-day group. In subgroup analysis, the 40 IU/L (odds ratio [OR], 2.995; 95% confidence interval [CI], 1.580 to 5.680; p = 0.001) and presence of anti-hepatitis C virus (OR, 4.204; 95% CI, 1.822 to 9.700, p = 0.001) were independent risk factors for development of ADIH. CONCLUSIONS: Approximately 70% of the cases of ADIH occurred in the first month of antituberculous treatment, and were associated with continuation of the first-line drug regimen.

A Korean patient with Guillain-Barré syndrome following acute hepatitis E whose cholestasis resolved with steroid therapy

Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.

A Case of Solid Variant of Serous Cystadenoma Misdiagnosed as a Neuroendocrine Tumor of the Pancreas / 대한내과학회지

Rapid advancements, access to and use of imaging techniques have increased the frequency of identification of pancreatic cystic neoplasms in clinical practice. However, a diagnostic dilemma among pancreatic cystic neoplasms remains. Solid variant serous cystadenoma is extremely rare and difficult to accurately diagnose preoperatively, as they are commonly mistaken for malignant solid tumors of other types. Here, we present a case of a solid variant serous cystadenoma preoperatively misdiagnosed as a neuroendocrine tumor of the pancreas with a review of the relevant literature.

Ectopic Opening of the Common Bile Duct into the Duodenal Bulb Accompanied with Cholangitis and Gallbladder Cancer: A Report of Two Cases

An ectopic opening of the common bile duct (CBD) into the duodenal bulb is a very rare congenital anomaly of the biliary system, which may cause recurrent duodenal ulcer or biliary diseases such as choledocholithiasis and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of this anomaly. We report two such cases: one in a 61-year-old man and the other in a 57-year-old man. In the first case, this anomaly caused acute cholangitis with multiple CBD stones, which were successfully treated by ERCP. In the second case, abdominal computed tomography showed pneumobilia, which was further evaluated using ERCP. Besides, this patient was diagnosed with an ectopic opening of the CBD associated with gallbladder cancer. We report these unusual cases and review the relevant medical literature.

Primary Non-ampullary Duodenal Adenocarcinoma: A Single-center Experience for 15 Years / 대한소화기학회지

BACKGROUND/AIMS: Primary non-ampullary duodenal adenocarcinomas (PNADAs) comprise or =2 mg/dL (OR, 85.28; 95% CI, 3.77-1,938.79; p=0.005) and distant metastasis (OR, 26.74; 95% CI, 3.13-2,328.14; p=0.003) at the time of diagnosis were independent poor prognostic factors. CONCLUSIONS: The majority of patients were diagnosed at an advanced stage. Presence of distant metastasis was independent prognostic factor of PNADA together with elevated total bilirubin.

Three Cases of Spontaneous Muscle Hematoma in Alcoholic Liver Cirrhosis / 대한내과학회지

Liver cirrhosis is commonly associated with bleeding complications due to portal hypertension or coagulopathy. Spontaneous muscle hematoma is a rare but potentially lethal complication of liver cirrhosis. Here we report three cases of spontaneous muscle hematoma diagnosed in patients with alcoholic liver cirrhosis. All three patients died due to recurrent bleeding and liver failure although they had undergone repeated transcatheter arterial embolization of the actively bleeding vessels. We reviewed 14 cases of spontaneous muscle hematoma that were associated with liver cirrhosis, including our cases, and found that the mortality rate was 86%, despite early diagnosis and treatment. Cirrhosis-associated spontaneous muscle hematoma occurred more frequently in patients with alcoholic liver cirrhosis, who accounted for -93% of cases. Thus, spontaneous muscle hematoma should be considered a life-threatening complication in patients with alcoholic liver cirrhosis, and abstinence from alcohol may help to prevent the occurrence of this deadly condition.

A Case of Splenic Hamartoma Diagnosed by Contrast-enhanced Ultrasonography and Magnetic Resonance Imaging / 대한소화기학회지

Splenic hamartoma is a very rare benign tumor, which is usually found incidentally after splenectomy or autopsy. Although percutaneous needle biopsy can be performed, it carries a high risk of bleeding after the procedure. Therefore, diagnosis is usually made by surgical resection. Herein, we report a case of splenic hamartoma diagnosed by magnetic resonance imaging and contrast-enhanced ultrasonography, which enables visualization of the unique signals of microbubbles in the vessels in real time. Relevant literature is also reviewed.

A Case of Malignant Perivascular Epithelioid Cell Tumor of the Retroperitoneum with Multiple Metastases / 대한소화기학회지

Perivascular epithelioid cell tumors (PEComas) are unusual mesenchymal neoplasms composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Although PEComas have the potential to behave in a malignant fashion, malignant PEComas arising from the retroperitoneum are extremely rare. A 68-year-old woman presented with a painful palpable mass in her left upper abdomen. Computed tomography of the abdomen showed a 9 cm sized heterogeneous mass in left para-aortic space and multiple hypervascular nodules in the liver. 18F-fludeoxyglucose-PET/CT showed multifocal hypermetabolic lesions in retroperitoneum, liver, and skeletal bones. Percutaneous needle biopsies were done on the retroperitoneal and hepatic mass. Both specimens were positive for human melanoma black-45 (HMB-45) on histological and immunohistochemical staining which was compatible with PEComas. Herein, we report a rare case of retroperitoneal PEComa with multiple metastases involving liver and bone at initial diagnosis that exhibited aggressive behavior and resulted in a devastating prognosis.

Predictive Factors of Subepithelial Tumor and Gastrointestinal Stromal Tumor in the Patients with Upper Gastrointestinal Subepithelial Lesions / 대한소화기학회지

BACKGROUND/AIMS: Differentiating subepithelial tumor (SET) from non-neoplastic gastrointestinal subepithelial lesion (SEL) and gastrointestinal stromal tumor (GIST) from leiomyoma are very important for proper management. This study was conducted to analyze factors that could predict the presence of SET and GIST in patients with upper gastrointestinal (UGI) SELs. METHODS: A total of 527 patients were diagnosed with UGI SELs endosonographically at Gyeongsang National University Hospital from January 2008 to June 2013. Among these patients, histologic diagnosis was made in 84 patients. Data were collected by retrospectively reviewing the medical records. Variables that could differentiate neoplastic from non-neoplastic SELs and GIST from leiomyoma were analyzed. RESULTS: Among 84 patients with SELs, 64 (76.2%) had SETs including GIST (42.9%) and leiomyoma (19.0%). The patients' mean age (p=0.047), peak age distribution (p=0.047), proportions of patient > or =50 years (p=0.015), and number of proper muscle-originated lesions (p=0.001) were higher in neoplastic than non-neoplastic group. There were no significant differences in gender (p=0.195), size (p=0.266) and echogenicity (p=0.051) of the lesions. Older age (57.7 vs. 47.0 years, p=0.049), age > or =50 years (p=0.016), location in gastric body (p or =50 years, size > or =30 mm, and proper muscle-origin of lesion were independent predictors of SET; however, there were no predictive factors that could differentiate GIST from leiomyoma. CONCLUSIONS: In patients with SEL, the possibility of having SET should be considered for patients > or =50 years with UGI SELs > or =30 mm that arise from the proper muscle. Thorough monitoring and aggressive management is warranted for those with gastric muscular SET since factors predictive of GIST are lacking.

Acute Respiratory Distress Syndrome after Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Case Report / 이화의대지

Transcatheter arterial chemoembolization (TACE) has become an effective alternative treatment strategy for patients with inoperable hepatocellular carcinoma (HCC). Although TACE is relatively safe, acute respiratory distress syndrome associated with pulmonary lipiodol embolism is a rare and potentially fatal complication. We report a rare case of acute respiratory distress syndrome after TACE for inoperable HCC. A 75-year-old man, with huge HCC in right lobe, was treated by TACE for the first time. Seven hours after uneventful TACE procedure, he felt dyspneic and his oxygen saturation recorded by pulse oximetry (SpO2) fell to 80% despite of applying non-rebreathing mask. He underwent mechanical ventilation with a protective ventilatory strategy. We experienced a case of acute respiratory distress syndrome after TACE for HCC.

The Clinical Features and Prognostic Factors of Nonvariceal Upper Gastrointestinal Bleeding in the Patients with Liver Cirrhosis

BACKGROUND/AIMS: Variceal rupture is the most common cause of upper gastrointestinal bleeding (UGIB) in cirrhotic patients and is well investigated. However, there are few documented studies on nonvariceal UGIB (NVUGIB) in these patients. This study was conducted to evaluate clinical features, in-hospital mortality rate and factors associated with mortality in cirrhotic patients with NVUGIB. MATERIALS AND METHODS: Among 399 cirrhotic patients who presented UGIB at Gyeongsang National University Hospital during 5 years since January 2007, patients with NVUGIB were selected by retrospective review of medical records. The patients' clinical and endoscopic findings, treatment outcomes, in-hospital mortality rates and its risk factors were investigated. RESULTS: NVUGIB was documented in 83 patients (20.8%). Mean age was 60.7+/-9.7 years, 85.5% was male. Child-Pugh class was A or B in 88%. Initial hemodynamic instability was reported in 25.3%, and 65.1% required blood transfusions. The major bleeding source was peptic ulcer 95.2% (79/83), and 44.6% (37/83) had endoscopic high risk bleeding stigmata and required endoscopic hemostasis. Rebleeding rate was 7.2% and in-hospital mortality rate was 8.4%. Hemodynamic instability (71.4% vs. 22.4%, P=0.013) and rebleeding (57.1% vs. 2.6%, P=0.000) were more frequent in the mortality group compared to the survival group. Hemodynamic instability was the risk factor for mortality at univariate and multivariate analyses. CONCLUSIONS: NVUGIB accounted for 20.8% of UGIB in liver cirrhosis and its development was not related to liver function. Peptic ulcer was the major cause and 45% required endoscopic hemostasis. It's in-hospital mortality rate was 8.4%, and hemodynamic instability was an independent risk factor of mortality in NVUGIB.

The Clinical Features and Prognostic Factors of Nonvariceal Upper Gastrointestinal Bleeding in the Patients with Liver Cirrhosis

BACKGROUND/AIMS: Variceal rupture is the most common cause of upper gastrointestinal bleeding (UGIB) in cirrhotic patients and is well investigated. However, there are few documented studies on nonvariceal UGIB (NVUGIB) in these patients. This study was conducted to evaluate clinical features, in-hospital mortality rate and factors associated with mortality in cirrhotic patients with NVUGIB. MATERIALS AND METHODS: Among 399 cirrhotic patients who presented UGIB at Gyeongsang National University Hospital during 5 years since January 2007, patients with NVUGIB were selected by retrospective review of medical records. The patients' clinical and endoscopic findings, treatment outcomes, in-hospital mortality rates and its risk factors were investigated. RESULTS: NVUGIB was documented in 83 patients (20.8%). Mean age was 60.7+/-9.7 years, 85.5% was male. Child-Pugh class was A or B in 88%. Initial hemodynamic instability was reported in 25.3%, and 65.1% required blood transfusions. The major bleeding source was peptic ulcer 95.2% (79/83), and 44.6% (37/83) had endoscopic high risk bleeding stigmata and required endoscopic hemostasis. Rebleeding rate was 7.2% and in-hospital mortality rate was 8.4%. Hemodynamic instability (71.4% vs. 22.4%, P=0.013) and rebleeding (57.1% vs. 2.6%, P=0.000) were more frequent in the mortality group compared to the survival group. Hemodynamic instability was the risk factor for mortality at univariate and multivariate analyses. CONCLUSIONS: NVUGIB accounted for 20.8% of UGIB in liver cirrhosis and its development was not related to liver function. Peptic ulcer was the major cause and 45% required endoscopic hemostasis. It's in-hospital mortality rate was 8.4%, and hemodynamic instability was an independent risk factor of mortality in NVUGIB.

Effectiveness of endoscopic clipping and computed tomography gastroscopy for the preoperative localization of gastric cancer / 대한외과학회지

PURPOSE: Before laparoscopic gastrectomy for gastric cancer can be planned, it is very important to know the precise location of the tumor. The aim of this study was to evaluate 3 methods of predicting the exact location of the tumor: preoperative gastrofibroscopy (GFS), preoperative computed tomography gastroscopy (CT), and intraoperative gastroscopy-guided laparoscopy (Lap). METHODS: In this study, 15 patients were prospectively identified, and endoscopic clips were preoperatively placed on the proximal 1 cm of the tumor, at the angle on the greater curvature and opposite the angle on the greater curvature. The distances between the pylorus and the proximal tumor clip (PT), the angle clip (PA), the greater curvature clip (PG), and the gastroesophageal junction were measured by preoperative GFS, preoperative CT, intraoperative Lap, and visual inspection (Vis). RESULTS: PT, PA, and PG values measured by preoperative GFS differed significantly from the Vis values (P < 0.01). However, preoperative CT measurements of PT, PA, and PG did not differ from the Vis values (P = 0.78, P = 0.48, and P = 0.53, respectively). Intraoperative Lap and Vis PT values differed by only 1.1 cm on an average (P = 0.10), but PA and PG values varied by 1.9 and 3.4 cm, respectively (P = 0.01 for both). CONCLUSION: Endoscopic clipping combined with preoperative CT gastroscopy is more useful than preoperative GFS for preoperatively predicting the location of early gastric cancers and will be helpful for planning laparoscopic gastrectomy.