Chung-Hwa Park

Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma.

BACKGROUND & AIMS Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE). METHODS A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression. RESULTS The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p<0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p<0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p>0.05). CONCLUSIONS TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

Drug-eluting bead loaded with doxorubicin versus conventional Lipiodol-based transarterial chemoembolization in the treatment of hepatocellular carcinoma: a case―control study of Asian patients

Objective Lipiodol transcatheter arterial chemoembolization (TACE) is widely used to treat hepatocellular carcinoma (HCC). Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. The purpose of this study was to compare the efficacy and safety of intra-arterial injection of DEB loaded with doxorubicin versus conventional, Lipiodol-based TACE regimens in Asian patients with HCC. Methods The study was designed as a case–control, single-institution clinical trial. Twenty patients with HCC who received DEB loaded with 50 mg doxorubicin (‘cases’) were matched with 20 patients who had undergone conventional TACE (‘controls’). The primary efficacy endpoint was tumor response at 1 month according to modified Response Evaluation Criteria in Solid Tumors. The primary safety endpoint was liver toxicity. Results The rate of objective response by modified Response Evaluation Criteria in Solid Tumors was 85% (17 of 20 patients) in the DEB arm versus 30% (six of 20 patients) in the conventional TACE arm (P=0.001). Subgroup analyses conducted in patients with large (>5 cm) or multinodular tumor confirmed significantly higher objective response rates in patients receiving DEB as compared with those treated with conventional TACE (P=0.003 and P=0.005, respectively). At the dose of 50 mg doxorubicin, there was no statistically significant difference in liver toxicity between DEB and conventional TACE (P>0.05). Conclusion In Asian patients with HCC, transcatheter treatment with DEB loaded with doxorubicin offers a distinct advantage in objective tumor response rate as compared with conventional, Lipiodol-based TACE regimens.

The role of small intestinal bacterial overgrowth in postgastrectomy patients.

Background  Small intestinal bacterial overgrowth (SIBO) is expected in postgastrectomy patients; however, its role has not been clarified. This study was to estimate the prevalence of SIBO and investigate the clinical role of SIBO in postgastrectomy patients.

Predictive value of 18F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma

AIM To investigate the correlation of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) with clinical features and the prediction of treatment response. METHODS A total of 83 hepatocellular carcinoma (HCC) patients undergoing ¹⁸F-FDG PET before transarterial chemolipiodolization with systemic chemo-infusion between October, 2006 and May, 2009 were retrospectively enrolled. The patients included 68 men and 15 women (mean age, 60 ± 10.7 years). The effect of (18)F-FDG-monitored PET uptake on clinical features and on the evaluated treatment response was ascertained with modified Response Evaluation Criteria in Solid Tumors. The PET parameters of maximal standardized uptake value of the tumor (Tsuv(max)), the ratio of the tumor maximal standardized uptake value (SUV) to the liver maximal SUV (Tsuv(max)/Lsuv(max)) and the ratio of tumor maximal SUV to the liver mean SUV (Tsuv(max)/Lsuv(mean)) were tested as predictive factors. RESULTS Among the 3 SUV parameters, the Tsuv(max)/Lsuv(mean) ratio (cutoff value of 1.90) was significantly associated with tumor burden including tumor size, tumor number, α-fetoprotein levels and tumor stage (P < 0.001, P = 0.008, P = 0.011, P < 0.001, respectively). The objective response rates in patients with a high SUV ratio (≥ 1.90) were significantly better than those with a low SUV ratio (< 1.90) (P = 0.020). The overall survival rates of patients exhibiting a low Tsuv(max)/Lsuv(mean) ratio (< 1.90) and those with a high SUV ratio (≥ 1.90) was 38.2 and 10.3 mo, respectively (P < 0.01). However, the time to progression showed no significant difference between the groups (P = 0.15). CONCLUSION ¹⁸F-FDG PET can be an important predictor of HCC treatment. In particular, the Tsuv(max)/Lsuv(mean) ratio (cutoff value of 1.90) can provide useful information in treatment prognosis for HCC patients treated with locoregional therapy.

Early gastric cancer associated with gastritis cystica polyposa in the unoperated stomach treated by endoscopic submucosal dissection

Gastritis cystica polyposa (GCP) is an uncommon hyperplastic benign lesion, which is histologically characterized by hyperplastic foveolar epithelia and multicystically dilated glands inside the lesion. GCP is also called gastritis cystica profunda when the cystic lesion locates within the submucosa. GCP was at first described as polypoid tumors developed in the gastric mucosa adjacent to Billroth-II stoma. This relatively rare lesion usually develops in patients who previously underwent gastroenterostomy, especially for treatment of a benign lesion, eg, gastric ulcer. GCP is infrequently found in an unoperated stomach. Because GCP is usually found in the operated stomach, its etiology and pathogenesis have been considered to be chronic inflammation after surgical treatment. Mucosal prolapse or duodenogastric reflux of intestinal contents into the gastric remnant may be inferred to be a cause of GCP. Subsequent reports brought up some similar findings in various synonyms, and some of the cases reported were with accompanying carcinoma. However, the mechanism of GCP developing in the unoperated stomach is unclear. In some cases reported, it was suggested that GCP at a gastroenterostomy site may be a precancerous lesion because carcinoma is frequently found at old gastrojejunostomy stoma and the histologic features of GCP resemble the experimental stomal polyps preceding carcinoma after partial gastrectomy in rats. Herein, we report 2 cases of early gastric cancer (EGC) that accompanied GCP, which occurred in patients who had never undergone stomach surgery. The patients were treated with the endoscopic submucosal dissection (ESD) technique. The carcinoma cells were confined to the mucosal layer.

Chilaiditi syndrome caused by Fitz-Hugh-Curtis syndrome: multidetector CT findings

Chilaiditi syndrome is a condition in which the colon or small intestine is interposed temporarily or permanently between the liver and the diaphragm. Usually, it is an asymptomatic and incidental radiographic finding, but it may be a potential source of abdominal problems, ranging from intermittent mild abdominal pain to acute intestinal obstruction. We report multidetector computed tomographic findings of a case of Chilaiditi syndrome presenting as small bowel obstruction due to hepatodiaphragmatic interposition of the ileal loop, which was entrapped by adhesive bands caused by Fitz-Hugh-Curtis syndrome.

Outcome after discontinuing antiviral agents during pregnancy in women infected with hepatitis B virus

BACKGROUND Women who are taking antiviral agents and become pregnant have several options that include, continuing therapy, ceasing drugs, or switching to safer drugs. However, there are limited data on the outcome in pregnant women after withdrawal of antiviral agents. OBJECTIVES We aimed to investigate the outcome of stopping antiviral agents in pregnant women with chronic hepatitis B virus (HBV) infection. STUDY DESIGN In this single-center, retrospective cohort study, 12 pregnant patients who had received antiviral therapy for HBV and cease drugs after awareness of pregnancy between 2003 and 2010 were enrolled. We retrospectively studied virologic and biochemical flares during pregnancy and postpartum period. RESULTS Median age at pregnancy was 30.5 (range, 24-35) years, median duration of antiviral drug before pregnancy was 15.3 (range, 3.0-131.3) months, and median HBV DNA at withdrawal of therapy was 4.8 (range, 1.7-8.0) log(10) copies/mL. Eight out of twelve patients (66.7%) had a viral rebound after stopping antiviral drugs during pregnancy. Severe hepatitis flares, defined as a 5-fold increase in serum alanine aminotransferase (ALT), were observed in six patients (50%) during pregnancy. However, all of these patients spontaneously recovered without an event of hepatic decompensation. High pretreatment ALT was associated with severe hepatitis flares after cessation of therapy during pregnancy. Five patients with at least 1-year treatment before pregnancy maintained low hepatitis activity after delivery. CONCLUSIONS Pregnant women with high pretreatment ALT or those treated less than 1 year before pregnancy have high risk of severe hepatitis flares after cessation of antiviral agents.

RPL36 as a prognostic marker in hepatocellular carcinoma

Ribosomal proteins (RP) play key roles in the regulation of apoptosis, multidrug resistance and carcinogenesis. The aim of this study was to investigate the expression of ribosomal protein L36 (RPL36) in hepatocellular carcinoma (HCC) and to correlate it with clinicopathological parameters and clinical outcome. Liver specimens were obtained from 60 HCC patients who had undergone a partial hepatectomy. Expression of RPL36 in tumor tissue and surrounding non‐tumorous tissues was evaluated on a tissue microarray by immunohistochemistry. RPL36 was expressed in 45 of 60 (75%) HCC by immunohistochemistry, but was not detected in corresponding non‐tumors. RPL36 expression correlated significantly with serum levels of albumin (P= 0.044) and prothrombin time (P= 0.026), which reflect liver synthetic function. Moreover, expression of RPL36 was found to be higher in patients with early tumor stages (I/II) (P= 0.038) or without portal vein thrombosis (P= 0.005). In univariate analysis, patients with RPL36 expression revealed better overall survival (P= 0.037). By multivariate survival analysis, RPL36 expression was found to be an independent prognostic factor for overall survival (P= 0.026). Our data suggest that RPL36 may be involved in the early stage of hepatocarcinogenesis, and it can be used as an independent and potential prognostic marker for resected HCC.

Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND Sarcopenia and non-alcoholic fatty liver disease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skeletal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of other chronic liver disease. RESULTS Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, independent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence interval (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR=1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=1.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR=1.36; 95% CI: 1.20-1.54). CONCLUSIONS Low SMI is associated with the risk of FLI-defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ according to age group or menopausal status. Further studies are warranted to confirm this relationship.

Family history influences the early onset of hepatocellular carcinoma

AIM To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients. METHODS We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records. RESULTS Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P < 0.0001). Furthermore, among 1713 HCC patients with HBV infection, the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%), whereas those out of 1577 patients with negative family history was 197 (12.5%), suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P = 0.0028). CONCLUSION More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.