Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-alpha Therapy

PURPOSE: Anti-tumor necrosis factor-alpha (TNF-alpha) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea. MATERIALS AND METHODS: We retrospectively studied patients who received anti-TNF-alpha therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-alpha therapy. Data concerning patient demographics, types of anti-TNF-alpha agents, concomitant immunosuppressive drugs use, and infection details were collected. RESULTS: A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results. CONCLUSION: Serious infections with anti-TNF-alpha therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-alpha therapy, especially in countries with a high prevalence of TB.

Two Cases of Uncommon Complication during Percutaneous Endoscopic Gastrostomy Tube Replacement and Treatment / 대한소화기학회지

We presented two interesting cases of gastrocolocutaneous fistula that occurred after percutaneous endoscopic gastrostomy (PEG) tube placement, and its management. This fistula is a rare complication that occurs after PEG insertion, which is an epithelial connection between mucosa of the stomach, colon, and skin. The management of the fistula is controversial, ranging from conservative to surgical intervention. Endoscopists should be aware of the possibility of gastrocolocutaneous fistula after PEG insertion, and should evaluate the risk factors that may contribute to the development of gastrocolocutaneous fistula before the procedure. We reviewed complications of gastrostomy tube insertion, symptoms of gastrocolocutaneous fistula, and its risk factors.

Is propofol safe when administered to cirrhotic patients during sedative endoscopy?

BACKGROUND/AIMS: In patients with liver cirrhosis, drugs acting on the central nervous system can lead to hepatic encephalopathy and the effects may be prolonged. Recently, misuse of propofol has been reported and the associated risk of death have become an issue. Propofol is commonly used during sedative endoscopy; therefore, its safety in high-risk groups must be further investigated. We performed a pilot study of the safety and efficacy of propofol during endoscopy in Korean patients with cirrhosis. METHODS: Upper gastrointestinal endoscopy was performed under sedation with propofol along with careful monitoring in 20 patients with liver cirrhosis and 20 control subjects. The presence or development of hepatic encephalopathy was assessed using the number connection test and neurologic examination. RESULTS: Neither respiratory depression nor clinically significant hypotension were observed. Immediate postanesthetic recovery at 5 and 10 minutes after the procedure was delayed in the cirrhotic patients compared with the control group; however, at 30 minutes, the postanesthetic recovery was similar in both groups. Baseline psychomotor performance was more impaired in cirrhotic patients, but propofol was not associated with deteriorated psychomotor function even in cirrhotic patients with a minimal hepatic encephalopathy. CONCLUSIONS: Sedation with propofol was well tolerated in cirrhotic patients. No newly developed hepatic encephalopathy was observed.

Small Bowel Pseudomelanosis Associated with Oral Iron Therapy

An accumulation of pigment deposits on mucosa, called melanosis or pseudomelanosis, of the small bowel is observed infrequently during endoscopic examination. We describe 6 cases of small bowel pseudomelanosis; the possible etiology of which was chronic iron intake. We observed numerous brown spots in duodenum, jejunum, and terminal ileum during upper and lower endoscopy. Interestingly, all patients have been taking oral iron for several years. Histology showed pigment depositions within macrophages of the lamina propria and a positive Prussian blue stain indicating hemosiderin deposition. Herein, we demonstrate that long term iron therapy may result in pseudomelanosis of small bowel, such as duodenum, jejunum, and ileum.

Two Cases of Cecal Schwannoma Which Were Removed by Endoscopic Mucosal Resection

Schwannoma in colorectum is a rare subepithelial polyp of mesenchymal origin, which is derived from the neural sheath, and most of reported cases were removed surgically. We, herein, describe two cases of schwannoma of the cecum, which were removed by endoscopic mucosal resection. A 34-year-old man and a 62-year-old man presented with abdominal discomfort and bowel habit change. The patients were diagnosed with a subepithelial tumor in the cecum on colonoscopy and underwent endoscopic mucosal resection under a tentative impression as neuroendocrine tumor, such as carcinoid tumor. Histopathology and immunohistochemistry confirmed the colonic lesion to be a benign schwannoma.

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

The Effects of Combined Treatment with an HMG-CoA Reductase Inhibitor and PPARgamma Agonist on the Activation of Rat Pancreatic Stellate Cells

BACKGROUND/AIMS: Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands can modulate cellular differentiation, proliferation, and apoptosis through various pathways. It has been shown that HMG-CoA reductase inhibitors and PPARgamma agonists separately inhibit pancreatic stellate cell (PaSC) activation. We studied the effects of a combination of both types of drugs on activated PaSCs via platelet-derived growth factor (PDGF), which has not previously been reported. The present study was performed to elucidate the underlying mechanisms of these effects by focusing on the impact of the signaling associated with cell-cycle progression. METHODS: Primary cultures of rat PaSCs were exposed to simvastatin and troglitazone. Proliferation was quantified using the BrdU method, and cell-cycle analysis was performed using a fluorescent activated cell sorter. The protein expression levels of smooth muscle actin (SMA), extracellular signal-regulated kinase (ERK), and a cell cycle machinery protein (p27Kip1) were investigated using Western blot analysis. RESULTS: Simvastatin reversed the effects of PDGF on cell proliferation in a dose-dependent manner. The combination of a low concentration of simvastatin (1 mM) and troglitazone (10 mM) synergistically reversed the effects of PDGF on cell proliferation but had no effect on cell viability. The expression of a-SMA was markedly attenuated by combining the two drugs, which blocked the cell cycle beyond the G0/G1 phase by reducing the levels of phosphorylated ERK and reversed the expression of p27Kip1 interrupted by PDGF. CONCLUSIONS: Simvastatin and troglitazone synergistically inhibited cell proliferation in activated PaSCs by blocking the cell cycle beyond the G0/G1 phase. This inhibition was due to the synergistic modulation of the ERK pathway and the cell cycle machinery protein p27Kip1.

A Case of Severe Cholangitis Caused by Raoultella planticola in a Patient with Pancreatic Cancer / 감염과화학요법

While Raoultella planticola is a rare cause of human infection, we experienced a case of severe cholangitis caused by R. planticola. A 75-year-old male patient with cancer of the pancreatic head was admitted and found to have cholangitis. Following performance of percutaneous transhepatic biliary drainage for decompression and initiation of empirical antibiotics with cefotaxime and metronidazole. R. planticola, which was susceptible to cefotaxime, was isolated from both bile and blood. Despite administration of prompt and appropriate antibiotic therapy, the patient died 10 days after admission. We herein describe the first case of cholangitis caused by infection with R. planticola.

Small Bowel Carcinoma in Young Patient Detected by Double-balloon Enteroscopy / 대한소화기학회지

A 17-year old female presented with a chief complaint of melena and epigastric pain. She had a family history of colon cancer, her mother having been diagnosed with hereditary nonpolyposis colorectal carcinoma (HNPCC). After close examination including double-balloon enteroscopy, the patient was diagnosed with small bowel carcinoma, in spite of her young age. Here we report this rare case of small bowel carcinoma in a young patient with a family history of HNPCC.

Rifampin-induced Pseudomembranous Colitis with Rectosigmoid Sparing

Pseudomembranous colitis (PMC) is known to be associated with antibiotic treatment, but is not commonly related to antitubercular (anti-TB) agent, rifampin. PMC is frequently localized to rectum and sigmoid colon, which can be diagnosed with sigmoidoscopy. We report a case of rifampin-induced PMC with rectosigmoid sparing in a pulmonary tuberculosis patient. An 81-year-old man using anti-TB agents was admitted with a 30-day history of severe diarrhea and general weakness. On colonoscopy, nonspecific findings such as mucosal edema and erosion were found in sigmoid colon, whereas multiple yellowish plaques were confined to cecal mucosa only. Biopsy specimen of the cecum was compatible with PMC. Metronidazole was started orally, and the anti-TB medications excluding rifampin were readministerred. His symptoms remarkably improved within a few days without recurrence. Awareness of rectosigmoid sparing PMC in patients who develop diarrhea during anti-TB treatment should encourage early total colonoscopy.

Conscious Sedation During Gastrointestinal Endoscopy: Midazolam vs Propofol / 대한소화기내시경학회지

Endoscopy is increasingly performed with the patient under conscious sedation in many countries. The majority of patients can be adequately and safely sedated during routine upper endoscopy and colonoscopy with a combination of a benzodiazepine and opioid. Midazolam is a water-soluble benzodiazepine that is characterized by a rapid onset of action and a shorter duration compared with that of the other drugs of the same class. The major side effect of midazolam is respiratory depression, which can be reversed by flumazenil, a benzodiazepine-specific antagonist. Propofol is a lipid-soluble agent that has the advantages of a more rapid onset of action and a shorter recovery time compared to that of midazolam. However, it should be used with caution since it can lead to hypotension and respiratory depression. Propofol can be safely and effectively administered by nonanesthesiology physicians and nurses provided that they have received adequate training. Two models have been proposed for the administration of propofol by endoscopists: nurse-administered propofol sedation (NAPS) and combination propofol (propofol plus other agents) sedation. In order to modify the pharmacological disadvantages of propofol, fospropofol sodium, a water-soluble prodrug of propofol, has recently been developed. In addition, new delivery systems have been devised: patient-controlled sedation and computer-assisted personalized sedation, in which the computer continuously monitors the patient's condition and adjusts the dose of propofol accordingly. Endoscopists must have a thorough understanding of the medications used for endoscopic sedation and they must acquire the skills necessary for the treatment of cardiopulmonary complications. Therefore, it is necessary to develop a practice guideline pertaining to endoscopic sedation and also training programs for physicians and nurses in Korea.

Clinical courses after administration of oral corticosteroids in patients with severely cholestatic acute hepatitis A; three cases / 대한간학회지

Acute hepatitis A is currently outbreaking in Korea. Although prognosis of acute hepatitis A is generally favorable, a minority of patients are accompanied by fatal complications. Severe cholestasis is one of the important causes of prolonged hospitalization in patients with acute hepatitis A. In such cases, higher chances of additional complications and increased medical costs are inevitable. We report three cases of severely cholestatic hepatitis A, who showed favorable responses to oral corticosteroids. Thirty milligram of prednisolone was initiated and tapered according to the responses. Rapid improvement was observed in all cases without side effects. We suggest that corticosteroid administration can be useful in hepatitis A patients with severe cholestasis who do not show improvement by conservative managements. Clinical trial will be needed to evaluate effectiveness of corticosteroids in these patients.

Two cases of toxic hepatitis caused by arrowroot juice / 대한간학회지

Herbal remedies and health foods are widely used, and their side effects have been reported. We describe two cases of symptomatic toxic hepatitis that developed in middle-aged women after ingesting arrowroot juice. The clinical manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic hepatitis was made using the Roussel Uclaf Causality Assessment Method score on the basis of the patient's history and laboratory data. After supportive care, the patients showed rapid improvements of clinical symptoms, laboratory findings, and liver stiffness. Clinicians should be aware that the consumption of arrowroot juice can cause toxic hepatitis.

Clinical Characteristics of Chronic Pancreatitis according to the History of Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: Chronic pancreatitis (CP) is characterized clinically by a broad spectrum of variable features depending on many factors such as etiology, stage of the disease, and the presence of local complications. The aims of this study were to investigate the clinical aspect of CP and to analyze the characteristics according to the history of pancreatitis. METHODS: Eighty nine medical records from the patients who were diagnosed as CP at Korea University Ansan Hospital from January 1997 through December 2007 were reviewed retrospectively. After patients were divided into two groups according to the previous history of pancreatitis: the group I (n=34, no history of pancreatitis) and II (n=43, history of pancreatitis more than once), the clinical characteristics of two groups were compared. RESULTS: The mean age was 50+/-13.2 years and the male to female ratio was 5:1. Alcohol was the cause of CP in 71.9%, and 23.6% had no evident cause. Age (53.4+/-15.5 vs. 46.2+/-11.5, p=0.021), etiology (idiopathic 41.2% vs. 11.6%, p=0.004), and the presence of abdominal pain (73.5% vs. 100%, p=0.030) were significantly different between group I and II. However, in comparison of other factors that reflected the advanced stage of CP such as presence of pancreatic calcification, complications, and Cambridge grade on ERCP, there was no significant difference. CONCLUSIONS: Since CP which present, as the first manifestation shows much an advanced stage, the method for early diagnosis of CP is particularly needed.

A case of advanced hepatocellular carcinoma with portal vein tumor invasion controlled by percutaneous ethanol injection therapy / 대한간학회지

Portal vein invasion is a grave prognostic indicator in the setting of hepatocellular carcinoma (HCC). There is currently no effective method for preventing the invasion of HCC into the main portal vein. We report here a case of advanced HCC with portal vein tumor thrombosis that was effectively treated with percutaneous ethanol injection (PEI), having previously enabled subsequent successive transarterial chemoembolization (TACE). A 60-year-old male patient was diagnosed with a huge HCC, based on computed tomography and angiographic findings. Despite two sessions of TACE, the tumor invaded the right portal vein. PEI was performed on the malignant portal vein thrombosis, and three sessions thereof reduced the extent of tumor thrombi in the portal vein. Successive TACEs were performed to treat the HCC in the hepatic parenchyma. The patient was still living 19 months after the first PEI with no evidence of tumor recurrence, and his liver function remained well preserved.

Abdominal Obesity as a Risk Factor for the Development of Erosive Esophagitis in Subjects with a Normal Esophago-Gastric Junction

BACKGROUND/AIMS: Obesity is reported to be associated with erosive esophagitis (EE). However, the temporal association of obesity and abdominal obesity with EE is unclear. We conducted this study to investigate the temporal association of obesity, especially abdominal obesity with EE. METHODS: Among 1,182 subjects who underwent health screening examinations including upper endoscopy in both 2003 and 2006, a total 1,029 subjects with a normal esophagogastric junction on upper endoscopy in 2003 were enrolled. All subjects completed questionnaires and anthropometric measurements were obtained twice by trained personnels. The patients with newly developed EE were compared to the subjects without newly developed EE. RESULTS: Among 1,029 subjects, 42 (4.1%) were newly diagnosed with EE and 82 (8.0%) with hiatal hernia. The mean body mass index (BMI) in both examinations was significantly different between the two groups based on the development of erosive esophagitis (p90 cm vs <80 cm). CONCLUSIONS: Our study showed that abdominal circumference is an independent risk factor for EE, demonstrating a temporal relationship between abdominal obesity and EE.

Colorectal Neoplasm in Asymptomatic Average-risk Koreans: The KASID Prospective Multicenter Colonoscopy Survey

BACKGROUND/AIMS: The incidence of colorectal cancer is increasing in Korea, but the epidemiology of colorectal neoplasm is not clearly defined. We aimed to elucidate the prevalence of colorectal neoplasm in average-risk Koreans and explore the underlying risk factors. METHODS: A large-scale, multicenter, prospective study was conducted. Of the 19,460 subjects who underwent colonoscopy at 11 university hospitals, we analyzed 3,951 consecutive asymptomatic adults with no risk factors for colorectal cancer. RESULTS: The subjects were aged 52.1+/-11.6 years (mean+/-SD) and 60.1% of them were men. The prevalences of colorectal neoplasm and advanced neoplasm were 33.3% and 2.2%, respectively. The prevalence of a neoplasm increased with age (trend: p<0.001) and was higher in males (p<0.001). The prevalence of a proximal neoplasm was higher in subjects with a distal neoplasm than in those without a distal neoplasm (11.9% vs. 5.4%, p<0.001). However, 150 (52.1%) of the 288 subjects with a proximal neoplasm had no distal neoplasm. CONCLUSIONS: The overall prevalence of colorectal neoplasm in asymptomatic average-risk Koreans is comparable with that in Western countries. Being male and older are associated with a higher risk of colorectal neoplasm. Over half of proximal neoplasms are not associated with any distal sentinel lesions.

Trend in the eradication rates of Helicobacter pylori infection in the last 11 years / 대한내과학회지

BACKGROUND/AIMS: The standard triple therapy used as the first-line treatment for Helicobacter pylori that combines a proton pump inhibitor (PPI), amoxicillin, and clarithromycin had an initial eradication rate of 90%. However, many recent studies have not found this level of effectiveness. This study evaluated the trend in the eradication rates of H. pylori infection over the last 11 years. METHODS: This was a retrospective study of patients diagnosed with H. pylori infection between 1997 and 2007 and treated with triple therapy (PPI, amoxicillin, and clarithromycin). The patients answered questions about compliance and side effects within 2 weeks of completing their treatment. In addition, we assessed whether the H. pylori had been eradicated at least 4 weeks after the treatment using a 13C-urea breath test, rapid urease test, or histopathological examination. RESULTS: The eradication rate with first-line triple therapy decreased over the study period. There was no change in the eradication rate with second-line quadruple therapy (PPI, bismuth, metronidazole, and tetracycline). There were no differences in the eradication rate and recrudescence between 1- and 2-week regimens. CONCLUSIONS: The effectiveness of the recommended first-line triple therapy for H. pylori eradication has decreased significantly in the last decade. Therefore, the first-line therapy based on the combination of PPI, amoxicillin and clarithromycin may need to be changed in the near future.

Clinical Significance of Serum C-Reactive Protein in Patients with Colorectal Cancer

BACKGROUND/AIMS: C-reactive protein (CRP) is a general marker of inflammation and increased CRP level is reported in several cancers. It has been reported that CRP is an independent factor predicting survival in colorectal cancer patients, although this claim is still under debate. The aim of this study was to investigate the association between CRP and the characteristics of colorectal cancer patients. METHODS: One hundred eighty-four patients diagnosed with colorectal cancer between January 2007 and January 2009 were included. The patients with active infectious diseases, other tumors, cardiovascular disease, or inflammatory bowel disease were excluded. The CRP levels of colorectal cancer patients were compared with the control group comprised of 175 healthy adults with a normal colonoscopy. RESULTS: The median CRP in the colorectal cancer patients (3.36 mg/L) was higher than the control group (0.48 mg/L). There was a significant correlation between CRP and the stage of colorectal cancer (p<0.001). CRP was increased significantly in Dukes' stage D. CRP had a significant correlations with the CEA and CA 19-9 levels, the ESR, and the white blood cell count, and an inverse correlation with albumin. The CRP level in colon cancer patients was higher than rectal cancer patients (p=0.032). There were no significant difference in the CRP according to metastatic sites, such as the liver and peritoneum. CONCLUSIONS: Serum CRP levels were higher in patients with colorectal cancer and high CRP level is a predictor of advanced disease.

Clinical Significance of Serum C-Reactive Protein in Patients with Colorectal Cancer

BACKGROUND/AIMS: C-reactive protein (CRP) is a general marker of inflammation and increased CRP level is reported in several cancers. It has been reported that CRP is an independent factor predicting survival in colorectal cancer patients, although this claim is still under debate. The aim of this study was to investigate the association between CRP and the characteristics of colorectal cancer patients. METHODS: One hundred eighty-four patients diagnosed with colorectal cancer between January 2007 and January 2009 were included. The patients with active infectious diseases, other tumors, cardiovascular disease, or inflammatory bowel disease were excluded. The CRP levels of colorectal cancer patients were compared with the control group comprised of 175 healthy adults with a normal colonoscopy. RESULTS: The median CRP in the colorectal cancer patients (3.36 mg/L) was higher than the control group (0.48 mg/L). There was a significant correlation between CRP and the stage of colorectal cancer (p<0.001). CRP was increased significantly in Dukes' stage D. CRP had a significant correlations with the CEA and CA 19-9 levels, the ESR, and the white blood cell count, and an inverse correlation with albumin. The CRP level in colon cancer patients was higher than rectal cancer patients (p=0.032). There were no significant difference in the CRP according to metastatic sites, such as the liver and peritoneum. CONCLUSIONS: Serum CRP levels were higher in patients with colorectal cancer and high CRP level is a predictor of advanced disease.