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1.  Population Screening for Colorectal Cancer Means Getting FIT: The Past, Present, and Future of Colorectal Cancer Screening Using the Fecal Immunochemical Test for Hemoglobin (FIT) 
Gut and Liver  2014;8(2):117-130.
Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening.
PMCID: PMC3964261  PMID: 24672652
Population screening; Colorectal cancer; Fecal immunochemical test for hemoglobin; Colorectal cancer screening
2.  Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer 
Gut and Liver  2014;8(2):131-139.
Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world's population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.
PMCID: PMC3964262  PMID: 24672653
Stomach neoplasms; Inflammation; Helicobacter pylori; Immune cells
3.  Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats 
Gut and Liver  2013;8(2):140-147.
DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats.
A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting.
The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B.
DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.
PMCID: PMC3964263  PMID: 24672654
DA-9701; Gastrointestinal diseases; Visceral hypersensitivity; Colorectal distension; Phosphorylated extracellular signal-regulated kinase
4.  Fatigue Severity and Factors Associated with High Fatigue Levels in Korean Patients with Inflammatory Bowel Disease 
Gut and Liver  2013;8(2):148-153.
Many patients with inflammatory bowel disease (IBD) often complain of fatigue. To date, only a few studies in Western countries have focused on fatigue related to IBD, and fatigue has never been specifically studied in Asian IBD patients. The aim of the present study was to investigate the fatigue level and fatigue-related factors among Korean IBD patients.
Patients in remission or with mild to moderate IBD were included. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue and the Brief Fatigue Inventory. Corresponding healthy controls (HCs) also completed both fatigue questionnaires.
Sixty patients with Crohn disease and 68 patients with ulcerative colitis (UC) were eligible for analysis. The comparison group consisted of 92 HCs. Compared with the HCs, both IBD groups were associated with greater levels of fatigue (p<0.001). Factors influencing the fatigue score in UC patients included anemia and a high erythrocyte sedimentation rate (ESR).
Greater levels of fatigue were detected in Korean IBD patients compared with HCs. Anemia and ESR were determinants of fatigue in UC patients. Physicians need to be aware of fatigue as one of the important symptoms of IBD to better understand the impact of fatigue on health-related quality of life.
PMCID: PMC3964264  PMID: 24672655
Fatigue; Inflammatory bowel diseases; Crohn disease; Colitis, ulcerative
5.  Endoscopic Experience Improves Interobserver Agreement in the Grading of Esophagitis by Los Angeles Classification: Conventional Endoscopy and Optimal Band Image System 
Gut and Liver  2013;8(2):154-159.
Interobserver variation by experience was documented for the diagnosis of esophagitis using the Los Angeles classification. The aim of this study was to evaluate whether interobserver agreement can be improved by higher levels of endoscopic experience in the diagnosis of erosive esophagitis.
Endoscopic images of 51 patients with gastroesophageal reflux disease (GERD) symptoms were obtained with conventional endoscopy and optimal band imaging (OBI). Endoscopists were divided into an expert group (16 gastroenterologic endoscopic specialists guaranteed by the Korean Society of Gastrointestinal Endoscopy) and a trainee group (individuals with fellowships, first year of specialty training in gastroenterology). All endoscopists had no or minimal experience with OBI. GERD was diagnosed using the Los Angeles classification with or without OBI.
The mean weighted paired κ statistics for interobserver agreement in grading erosive esophagitis by conventional endoscopy in the expert group was better than that in the trainee group (0.51 vs 0.42, p<0.05). The mean weighted paired k statistics in the expert group and in the trainee group based on conventional endoscopy with OBI did not differ (0.42, 0.42).
Interobserver agreement in the expert group using conventional endoscopy was better than that in the trainee group. Endoscopic experience can improve the interobserver agreement in the grading of esophagitis using the Los Angeles classification.
PMCID: PMC3964265  PMID: 24672656
Gastroesophageal reflux; Agreement; Experience
6.  The Risk Factors and Quality of Life in Patients with Overlapping Functional Dyspepsia or Peptic Ulcer Disease with Gastroesophageal Reflux Disease 
Gut and Liver  2013;8(2):160-164.
Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and peptic ulcer disease (PUD) impact the daily lives of affected individuals. The aim of this study was to compare the risk factors and impacts on life quality of overlapping FD or PUD in patients with GERD.
Data from patients diagnosed with GERD were collected between January and November 2009. FD was defined using the Rome III diagnostic criteria. The overlapping GERD-FD or GERD-PUD groups were classified as concomitant GERD and FD or peptic ulcers. The characteristics of these individuals were analyzed.
There were 63, 48, and 60 patients in the GERD only, overlapping GERD-FD, and overlapping GERD-PUD groups, respectively. Significantly younger age, female gender, lower body weight and body mass index, and higher rates of tea consumption were noted in the GERD-FD group. Patients in the GERD-FD group exhibited the lowest quality of life scores, both with respect to physical and mental health, on the Short Form 36 domains.
Patients with concomitant GERD and FD were more likely to be younger and female. Overlapping GERD and FD had the worst impact on the quality of life of the affected individuals.
PMCID: PMC3964266  PMID: 24672657
Functional dyspepsia; Gastroesophageal reflux disease; Organic dyspepsia; Peptic ulcer disease; Quality of life
7.  Symptom Characteristics and Psychosomatic Profiles in Different Spectrum of Gastroesophageal Reflux Disease 
Gut and Liver  2013;8(2):165-169.
Gastroesophageal reflux disease (GERD) is diagnosed based on symptoms of heartburn and regurgitation but is a heterogeneous condition which can be subclassified according to endoscopy and esophageal reflux monitoring. The aim of this study was to identify differences in demographic characteristics and reflux symptom patterns among patients with various spectrum of GERD.
Patients having weekly heartburn or acid regurgitation were classified into four pathophysiological subgroups according to endoscopy and pH monitoring: reflux esophagitis (RE), endoscopy-negative reflux disease with pathological reflux (PR+), hypersensitive esophagus (HE), and normal acid exposure with negative symptom association (pH-).
A total of 195 patients were enrolled. The numbers of patients in the subgroups were: RE, 39.0%; PR+, 20.0%; HE, 10.3%; and pH-, 30.8%. Grossly, reflux symptom patterns and relieving/exacerbating factors did not differ between subgroups. Prevalence of extraesophageal syndrome was higher in patients with PR+ than in other groups. Overlapping functional dyspepsia was common in all groups. The SCL-90-R depression score was higher in PR+ patients than in RE patients (p<0.05).
Demographic characteristics and reflux symptom patterns cannot differentiate pH- group from GERD subtypes. Esophageal pH monitoring could be considered for the initial evaluation of GERD in the tertiary referral setting.
PMCID: PMC3964267  PMID: 24672658
Gastroesophageal reflux; Demographic characteristics; Symptom characteristic; Psychosomatic factor; Esophageal reflux monitoring
8.  Relationship between the Severity of Diversion Colitis and the Composition of Colonic Bacteria: A Prospective Study 
Gut and Liver  2013;8(2):170-176.
Diversion colitis is the inflammation of the excluded segment of the colon in patients undergoing ostomy. It has been suggested that a change in colonic flora may lead to colitis; however, direct evidence for this disease progression is lacking. The aim of this study was to evaluate the relationship between the severity of diversion colitis and the composition of colonic bacteria.
We used culture methods and polymerase chain reaction to analyze the colonic microflora of patients who underwent rectal cancer resection with or without diversion ileostomy. In the diversion group, we also evaluated the severity of colonoscopic and pathologic colitis before reversal.
This study enrolled 48 patients: 26 in the diversion group and 22 in the control group. Significant differences were observed between the two groups in the levels of Staphylococcus (p=0.038), Enterococcus (p<0.001), Klebsiella (p<0.001), Pseudomonas (p=0.015), Lactobacillus (p=0.038), presence of anaerobes (p=0.019), and Bifidobacterium (p<0.001). A significant correlation between the severity of colitis and bacterial composition was only observed for Bifidobacterium (p=0.005, correlation coefficient=-0.531).
The colonic microflora differed significantly between the diversion and control groups. Bifidobacterium was negatively correlated with the severity of diversion colitis.
PMCID: PMC3964268  PMID: 24672659
Diversion colitis; Colonic bacteria; Rectal neoplasms; Polymerase chain reaction
9.  Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma 
Gut and Liver  2013;8(2):177-185.
α-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC.
We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis.
The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors.
The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.
PMCID: PMC3964269  PMID: 24672660
Hepatocellular carcinoma; Glypican-3; Osteopontin
10.  The Expression of Programmed Death-1 in Circulating CD4+ and CD8+ T Cells during Hepatitis B Virus Infection Progression and Its Correlation with Clinical Baseline Characteristics 
Gut and Liver  2013;8(2):186-195.
Programmed death-1 (PD-1) expression was investigated in CD4+ and CD8+ T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages.
PD-1 expression in circulating CD4+ and CD8+ T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0.
PD-1 expression in CD4+ and CD8+ T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4+ and CD8+ T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent.
PD-1 expression in peripheral CD4+ and CD8+ T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury.
PMCID: PMC3964270  PMID: 24672661
Programmed death-1; Hepatitis B virus; Hepatitis B, chronic; Liver cirrhosis; Carcinoma, hepatocellular
11.  Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma 
Gut and Liver  2013;8(2):196-204.
To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing.
An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay.
The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation.
CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.
PMCID: PMC3964271  PMID: 24672662
Hilar cholangiocarcinoma; Neural invasion; CXCR4; RNA interference
12.  Elevated Hemoglobin A1c Levels Are Associated with Worse Survival in Advanced Pancreatic Cancer Patients with Diabetes 
Gut and Liver  2013;8(2):205-214.
Pre-existing diabetes mellitus (DM) has been identified as an adverse prognostic variable associated with increased mortality in various cancers. Although DM and hyperglycemia are considered risk factors for pancreatic cancer (PC), antidiabetic treatments for patients with advanced PC have been overlooked. This study aimed to evaluate the impact of hemoglobin A1c (HbA1c) levels on PC survival.
We retrospectively reviewed the medical records of first-diagnosed patients with advanced PC who were admitted to Konkuk University Medical Center from 2005 to 2011.
A total of 127 patients were enrolled, and there were 111 deaths (87.4%) within the 7-year observational period. The most common etiology was disease progression (n=108). DM before PC diagnosis was observed in 65 patients (51.1%), including 28 patients with new-onset DM. The overall median survival times in patients with and without DM were 198 and 263 days, respectively (p=0.091). Survival time according to HbA1c was significantly different between the <7.0% and ≥7.0% groups (362 and 144 days, respectively; p=0.038). In the HbA1c ≥7.0% group, the median overall survival time was 273 days for the metformin group and 145 days for the nonmetformin oral agent group; however, there was no significant difference between the two groups (p=0.058).
A high HbA1c level may be associated with worse survival in patients with advanced PC with DM. Antidiabetic treatment, metformin in particular, was associated with an improved outcome.
PMCID: PMC3964272  PMID: 24672663
Pancreatic neoplasms; Diabetes mellitus; Glycosylated hemoglobin A; Metformin
13.  Severe Bleeding and Perforation Are Rare Complications of Endoscopic Ultrasound-Guided Fine Needle Aspiration for Pancreatic Masses: An Analysis of 3,090 Patients from 212 Hospitals 
Gut and Liver  2013;8(2):215-218.
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful for the pathological diagnosis of pancreatic masses, but patients are susceptible to severe bleeding and perforation. Because the incidence and severity of these complications have not been fully evaluated.
We aimed to evaluate severe bleeding and perforation after EUS-FNA for pancreatic masses using large-scale data derived from a Japanese nationwide administrative database.
In total, 3,090 consecutive patients from 212 low- to high-volume hospitals were analyzed. Severe bleeding requiring transfusion or endoscopic treatment occurred in seven patients (0.23%), and no perforation was observed. No patient mortality was recorded within 30 days of EUS-FNA. The rate of severe bleeding in low-volume hospitals was significantly higher than that in medium- and high-volume hospitals (0.48% vs 0.10%, p=0.045).
Severe bleeding and perforation following EUS-FNA for pancreatic masses are rare, and the procedure is safe.
PMCID: PMC3964273  PMID: 24672664
Hemorrhage; Perforation; Endoscopic ultrasound-guided fine needle aspiration; Pancreas
14.  Focal Thickening at the Fundus of the Gallbladder: Computed Tomography Differentiation of Fundal Type Adenomyomatosis and Localized Chronic Cholecystitis 
Gut and Liver  2013;8(2):219-223.
The objective of our study was to identify useful computed tomography (CT) findings for differentiating fundal type adenomyomatosis from localized chronic cholecystitis involving the fundus of the gallbladder.
We retrospectively identified cases of 41 patients with pathologically proven adenomyomatosis (n=21) or chronic cholecystitis (n=20) who had fundal thickening of the gallbladder on preoperative abdominal CT. Analysis of the CT findings included evaluation of the thickness, contour, border, intralesional cystic area, adjacent gallbladder wall thickening, presence of inner layer enhancement, enhancement grade, enhancement pattern, and presence of stones. Statistical analyses were performed using the Mann-Whitney U test and Fisher exact test.
Oval contour, inner layer enhancement and intralesional cystic area were more frequently noted in adenomyomatosis than in chronic cholecystitis (p<0.05 for each finding). Flat contour and adjacent gallbladder wall thickening were more frequently observed in chronic cholecystitis than in adenomyomatosis. No differences between adenomyomatosis and chronic cholecystitis in terms of the thickness, enhancement grade, enhancement pattern and presence of stones were apparent.
CT may help to differentiate fundal type adenomyomatosis from localized chronic cholecystitis involving the fundus of the gallbladder.
PMCID: PMC3964274  PMID: 24672665
Adenomyomatosis; Chronic cholecystitis; Fundal type; Computed tomography
15.  A Patient with Eosinophilic Gastroenteritis Presenting with Acute Pancreatitis and Ascites 
Gut and Liver  2014;8(2):224-227.
Eosinophilic gastroenteritis (EGE) is a rare disease characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract, especially the stomach and duodenum. EGE has vague, nonspecific symptoms, including nausea, vomiting, abdominal pain, diarrhea, weight loss, ascites, and malabsorption. Here, we report a patient with EGE presenting with concurrent acute pancreatitis and ascites. A 68-year-old woman was admitted with abdominal pain, nausea, vomiting, and watery diarrhea. Laboratory findings revealed elevated serum titers of amylase, lipase, and peripheral blood eosinophil count. An abdominopelvic computed tomography scan showed a normal pancreas, moderate amount of ascites, and duodenal thickening. A esophagogastroduodenoscopy showed patchy erythematous mucosal lesions in the 2nd portion of the duodenum. Biopsies from the duodenum indicated eosinophilic infiltration in the lamina propria. The patient was successfully treated with prednisolone and montelukast. Despite its unusual occurrence, EGE may be considered in the differential diagnosis of unexplained acute pancreatitis, especially in a patient with duodenal edema on imaging or peripheral eosinophilia.
PMCID: PMC3964275  PMID: 24672666
Eosinophilic gastroenteritis; Pancreatitis; Eosinophilia; Ascites
17.  Clostridium difficile Infection: A Worldwide Disease 
Gut and Liver  2014;8(1):1-6.
Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices.
PMCID: PMC3916678  PMID: 24516694
Clostridium difficile; Epidemiology; Review; Asia
18.  Is a Preoperative Assessment of the Early Recurrence of Pancreatic Cancer Possible after Complete Surgical Resection? 
Gut and Liver  2013;8(1):102-108.
The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC.
A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators.
A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245).
PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.
PMCID: PMC3916679  PMID: 24516708
Pancreatic neoplasms; Early recurrence; Preoperative CA 19-9; Prognosis; Pancreatic adenocarcinoma
19.  Gemcitabine-Induced Hemolytic Uremic Syndrome in Pancreatic Cancer: A Case Report and Review of the Literature 
Gut and Liver  2014;8(1):109-112.
Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS may be caused by several different conditions, including infection, malignancy, and chemotherapeutic agents, such as mitomycin, cisplatin, and most recently, gemcitabine. The outcome of gemcitabine-induced HUS is poor, and the disease has a high mortality rate. This study reports a case of gemcitabine-induced HUS in a patient with pancreatic cancer in Korea.
PMCID: PMC3916680  PMID: 24516709
Hemolytic-uremic syndrome; Gemcitabine; Pancreatic neoplasms
21.  The Expression of Multiple Proteins as Prognostic Factors in Colorectal Cancer: Cathepsin D, p53, COX-2, Epidermal Growth Factor Receptor, C-erbB-2, and Ki-67 
Gut and Liver  2013;8(1):13-23.
A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients.
Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens.
Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002).
Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy.
PMCID: PMC3916682  PMID: 24516696
Cathepsin D; Prognostic factors; Colorectal neoplasms
22.  Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease 
Gut and Liver  2013;8(1):24-28.
Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients.
Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated.
Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed.
A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.
PMCID: PMC3916683  PMID: 24516697
Inflammatory bowel diseases; Crohn disease; Colitis, ulcerative; Polysaccharide vaccine; Switched memory B cells
23.  Ulcerative Colitis and Immunoglobulin G4 
Gut and Liver  2013;8(1):29-34.
Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.
Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.
UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).
UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.
PMCID: PMC3916684  PMID: 24516698
Colitis, ulcerative; Immunoglobulin G; Autoimmune pancreatitis
24.  The Relationship between Gastroesophageal Reflux Disease and Chronic Periodontitis 
Gut and Liver  2013;8(1):35-40.
The most common cause of chronic periodontitis is poor oral hygiene. Gastroesophageal reflux disease (GERD) enhances the proximal migration of gastric contents and may cause poor oral hygiene. We hypothesized that GERD may increase thse risk of chronic periodontitis and investigated this potential relationship.
A retrospective cross-sectional study was conducted in outpatients between January 1, 2010, and April 30, 2012. GERD was defined as being present based on at least two of the following criteria: etiologic agent(s), identifiable signs and symptoms, and consistent anatomic alterations. A total of 280 patients with chronic periodontitis and 280 controls were analyzed. Information regarding patient demographics and other potential confounding factors for chronic periodontitis were collected through individual medical records.
GERD was revealed to be independently associated with an increased incidence of chronic periodontitis (odds ratio [OR], 2.883; 95% confidence interval [CI], 1.775 to 4.682). The other three variables of dental caries (OR, 1.531; 95% CI, 1.042 to 2.249), tobacco use (OR, 2.335; 95% CI, 1.461 to 3.730), and history of medication (calcium channel blocker, cyclosporine, or phenytoin) (OR, 2.114; 95% CI, 1.160 to 3.854) were also determined to be independent risk factors.
The present study supported our hypothesis that GERD can be a risk factor for chronic periodontitis.
PMCID: PMC3916685  PMID: 24516699
Gastroesophageal reflux; Chronic periodontitis; Oral hygiene
25.  The Simple Predictors of Pseudomembranous Colitis in Patients with Hospital-Acquired Diarrhea: A Prospective Observational Study 
Gut and Liver  2013;8(1):41-48.
As the incidence rate of and mortality from pseudomembranous colitis (PMC) are increasing worldwide, it is important to study the simple predictive risk factors for PMC among patients with hospital-acquired diarrhea (HAD). This study focused on identifying the clinical risk factors that can easily predict PMC.
The presumed HAD patients were prospectively recruited at the Hallym University Kangdong Sacred Heart Hospital.
Age of 70 and older (adjusted odds ratio [OR], 1.76; 95% confidence interval [CI], 1.12 to 0.75), use of proton pump inhibitors (adjusted OR, 4.07; 95% CI, 2.512 to 6.57), use of cephalosporins (adjusted OR, 2.99; 95% CI, 1.82 to 4.94), and underlying cancer (adjusted OR, 1.72; 95% CI, 1.04 to 2.82) were independent risk factors for PMC in the multivariate logistic regression analysis. The prevalence of PMC was very low in the patients with HAD who exhibited no risk factors.
The risk factors for PMC in patients with HAD included cephalosporin use, proton pump inhibitor use, old age, and cancer. Considering the strongly negative predictive values of these risk factors, endoscopic evaluation can be delayed in patients with HAD without risk of developing PMC.
PMCID: PMC3916686  PMID: 24516700
Enterocolitis, pseudomembranous; Clostridium difficile; Risk factors; Predictors

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