Yang Suh Ku

Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti‐inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of “coxibs” (selective cyclooxygenase‐2 [COX‐2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID‐induced gastroduodenal damage beyond COX‐2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID‐associated gastroduodenal damage will be described.

A comparison of patient acceptance and preferences between CT colonography and conventional colonoscopy in colorectal cancer screening.

BACKGROUND/AIMS Mutations of the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) are important in the pathogenesis of lung cancer, and recent reports have revealed racial and geographical differences in mutation expression. METHODS This study was conducted to investigate the prevalence of EGFR and KRAS mutations and their correlation with clinical variables in Korean patients with adenocarcinoma of the lung. Formalin-fixed adenocarcinoma specimens from 104 randomly selected patients diagnosed at Kosin University Gospel Hospital from October 1996 to January 2005 were used for the study. RESULTS We found a high prevalence of EGFR mutations and a low prevalence of KRAS mutations. EGFR mutations were present in 24% (25 of 104) of the samples: one mutation in exon 18, 13 in exon 19, one in exon 20, and 10 in exon 21. The presence of an EGFR mutation was not associated with gender, smoking history, histological grade, age, bronchioalveolar components, or cancer stage in patients with adenocarcinoma of the lung. CONCLUSIONS Mutations of KRAS were present in 9.6% (9 of 94) of the samples: eight in codon 12 and one in codon 13. EGFR mutations were never found in tumors with KRAS mutations, suggesting a mutually exclusive relationship.

Factors influencing the severity of acute viral hepatitis A

Background/Aims Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results The incidence of fulminant hepatitis was 1.4% (10/713) in patients with acute hepatitis A. Thirty-three (4.6%) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection.

The efficacy of self-expanding metal stents for malignant colorectal obstruction by noncolonic malignancy with peritoneal carcinomatosis.

BACKGROUND: Although self-expanding metal stents for colorectal obstruction is preferred over emergency surgery, the efficacy of self-expanding metal stents in patients with malignant colorectal obstruction by a noncolonic malignancy with peritoneal carcinomatosis has not been demonstrated. OBJECTIVE: The aim of this study was to evaluate the survival and long-term clinical outcome of self-expanding metal stents as the initial interventional approach in patients with malignant colorectal obstruction due to a noncolonic malignancy with peritoneal carcinomatosis. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at 2 tertiary care academic medical centers in South Korea. PATIENTS: The patients were included who underwent self-expanding metal stent insertion for palliation of a malignant colorectal obstruction by a noncolonic malignancy with peritoneal carcinomatosis between July 2004 and January 2010. Inclusion criteria were incurable status, noncolorectal cancer, obstructive symptoms and/or signs, and colonoscopic findings of obstruction. MAIN OUTCOME MEASURES: The survival and success rate of patients undergoing self-expanding metal stents insertion was assessed. RESULTS: Twenty patients were included during the study period. Technical success of self-expanding metal stents was achieved in 18/20 (90.0%) patients, and obstructive symptoms were resolved within 72 hours in 17/20 (85.0%) patients. Ten patients (10/20, 50%) did not need further intervention during the follow-up period after the first stent insertion. Eight patients ultimately underwent surgery during the follow-up period. One of the remaining 2 patients underwent additional endoscopic treatment without surgery. Another patient refused further intervention and thus received conservative management. Mean event-free survival was 119.0 days, and the mean overall survival of the included patients was 156.3 days. LIMITATION: The number of study patients was small. CONCLUSION: Self-expanding metal stent insertion appears to be a reasonable first-treatment option in patients with malignant colorectal obstruction by noncolonic malignancy with peritoneal carcinomatosis.

[The significance of anti-HBc and occult hepatitis B virus infection in the occurrence of hepatocellular carcinoma in patients with HBsAg and anti-HCV negative alcoholic cirrhosis].

BACKGROUND/AIMS Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). METHODS Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. RESULTS Patients with HCC were older (60+/-11 years vs. 53+/-10 years, mean+/-SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739+/-448 kg vs. 603+/-409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). CONCLUSIONS Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC.

Usefulness of liver stiffness measurement for predicting the presence of esophageal varices in patients with liver cirrhosis

BACKGROUND/AIMS Bleeding from esophageal varices (EV) is a major cause of death in patients with liver cirrhosis. Endoscopic screening is recommended for diagnosing EV, but various noninvasive parameters can also be used to predict EV. The liver stiffness measurement (LSM), a noninvasive technique for estimating liver fibrosis, was recently reported to be strongly correlated with the hepatic venous pressure gradient. This study evaluated the usefulness of LSM for predicting the presence and size of EV in patients with cirrhosis. METHODS The relationships of LSM with the presence and size of EV were analyzed in 112 patients with liver cirrhosis. Liver cirrhosis was diagnosed histologically or clinically. The presence and size of EV were assessed by endoscopy, and LSM was determined by the Fibroscan technique. RESULTS LSM was strongly correlated with the presence of EV (P<0.0001): the LSM value was 42.7+/-21.9 kPa (mean+/-standard deviation) in patients with EV (n=82) and 19.1+/-12.6 kPa in patients without EV (n=30). The area under the receiver operating characteristic curve was 0.818 (95% CI, 0.732-0.904) for predicting the presence of EV, and an LSM value of 19.7 kPa was predictive of the presence of EV with a sensitivity of 87%, a specificity of 70%, a PPV of 89%, and a NPV of 66%. However, there was a weak correlation between LSM and the size of EV. CONCLUSIONS LSM is useful for predicting the presence of EV in patients with cirrhosis but not their size.

A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma

An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patients condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.

Genetic polymorphism at codon 10 of the transforming growth factor-β1 gene in patients with alcoholic liver cirrhosis

Background/Aims Transforming growth factor beta1 (TGF-β1) is a key cytokine in the production of extracellular matrix. A genetic polymorphism at codon 10 of the TGF-β1 gene is associated with liver fibrosis. We investigated the effect of genetic polymorphisms at codon 10 on the development of alcoholic liver cirrhosis (ALC). Methods In total, 119 controls and 182 patients with ALC, were enrolled in the study. Clinical and laboratory data including total lifetime alcohol intake were collected at enrollment. The genotype at codon 10 was determined for each patient by single-strand conformation polymorphism. Results There were three types of genetic polymorphism at codon 10: homozygous proline (P/P), heterozygous proline/leucine (P/L), and homozygous leucine (L/L). Among the controls, the proportions of P/P, P/L, and L/L were 26.1%, 44.5%, and 29.4%, respectively in the ALC group, these proportions were 23.1%, 43.4%, and 33.5%, respectively. The genotype distribution did not differ between the controls and the ALC group. In the ALC group, age, total lifetime alcohol intake, and distribution of Child-Pugh class did not differ with the genotype. Of the male patients with ALC (n=164), the proportions of P/P, P/L, and L/L were 20.1%, 44.5%, and 35.4%, respectively the genotype distribution did not differ between the male controls and the male ALC patients. Conclusions The genotype at codon 10 in TGF-β1 does not appear to influence the development of ALC. Further study is needed to investigate other genetic factors that influence the development of ALC in patients with chronic alcohol intake.

Short-term Clinical Outcomes Based on Risk Factors of Recurrence after Removing Common Bile Duct Stones with Endoscopic Papillary Large Balloon Dilatation.

Background/Aims Recurrence is an important late complication of endotherapy of bile duct stones. Endoscopic papillary large balloon dilation (EPLBD) can be used as an alternative method of removing difficult bile duct stones. The aim of this study was to evaluate short term clinical outcomes after removing common bile duct (CBD) stones using EPLBD. Methods A retrospective review was performed based on the medical records of 141 patients who received EPLBD, with or without endoscopic sphincterotomy, between September 2008 and February 2010. Of these, 50 patients, were enrolled in the study. Clinical and endoscopic parameters were analyzed to identify risk factors for CBD stones recurrence. Results Male:Female ratio was 22:28 (mean age, 67.4±14.4 years). Recurrence rate was 24.0% (12/50). Mean follow-up period was 10.8±4.5 months. Nineteen (38.0%) had a history of surgery and 20 (40.0%) were comorbid with periampullary diverticula. Mean diameters of the stones and CBD were 13.8±4.3 mm and 20.1±7.2 mm, respectively. In univariate analysis, large CBD stones (≥12 mm) and angulated CBD (angle ≤145°) were identified as the significant predictors of recurrence. In multivariate analysis, angulated CBD (angle ≤145°) was the significant independent risk factor for recurrence. Conclusions Close follow-up seems necessary in patients with angulated CBD (angle ≤145°).

The short-term efficacy of entecavir in lamivudine-resistant chronic hepatitis B: Influence of sequential adefovir-refractoriness

BACKGROUND/AIMS Sequential antiviral therapy for chronic hepatitis B may lead to the selection of multidrug-resistant mutation. This study was carried out to assess the efficacy of entecavir in patients that have experienced adefovir monotherapy failure after the development of lamivudine resistance. METHODOLOGY Fifty-three patients with confirmed genotypic lamivudine-resistant chronic hepatitis B were treated with entecavir. Thirty patients were switched to entecavir directly (LAM-ETV group), whereas the remaining 23 were adefovir-refractory patients who were switched to entecavir (LAM-ADV-ETV group). These 23 patients included 9 patients with inadequate response (ADV-I subgroup) and 14 that exhibited adefovir resistance (ADV-R subgroup). RESULTS Significantly greater reductions in HBV DNA levels were observed after 24, 48 and 72 weeks of entecavir therapy in the LAM-ETV group than in the LAM-ADV-ETV group, respectively. However, between these two groups at 48 and 72 weeks, no significant differences were observed in cumulative proportions of virological response or breakthrough, respectively. Furthermore, efficacy of entecavir was not significantly different in the ADV-I and ADV-R subgroups. Four patients in the LAM-ETV group and six patients in the LAM-ADV-ETV group developed genotypic resistance to entecavir. CONCLUSIONS Entecavir therapy is less effective in adefovir-refractory patients with prior lamivudine resistance than in lamivudine-resistant patients.