Clinical Characteristics of Patients with Cryptogenic Hepatocellular Carcinoma in a Hepatitis B Virus-Endemic Area.

OBJECTIVES: Chronic hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma (HCC) in South Korea, but a high prevalence of metabolic diseases may result in increases in the incidence of cryptogenic HCC (cHCC). We studied characteristics of the cHCC in a single-center cohort. METHODS: A cohort of 1,784 HCC patients newly diagnosed and treated at the National Cancer Center, Korea, between 2004 and 2009 was reviewed and analyzed. RESULTS: The cause of HCC was categorized as cHCC, HBV, hepatitis C virus (HCV), or alcohol. Overall, 162 (9.1%) patients of the HCC cohort had cHCC, and their mean age was 61.9 years. The median survival of cHCC patients was 24.7 months, which was the second shortest among the four groups after HBV HCC. cHCC patients had the largest tumor size (mean 7.4 cm) and the second highest proportion of poor prognostic factors such as the proportion of poorly defined tumors and extrahepatic spread in imaging studies. cHCC patients had better survival than HBV HCC patients according to multivariate analysis. Among cHCC patients, 137 (84.6%) had anti-HBc IgG antibodies, but this sub-group had different clinical features to those of HBV HCC patients. The body mass index (BMI) and hyperglycemia and hypercholesterolemia levels in cHCC patients were similar to those in HCV and alcoholic HCC patients. CONCLUSIONS: Anti-HBc IgG antibodies were present in most cHCC patients, but cHCC patients had better survival than HBV HCC patients on multivariate analysis. However, cHCC patients had a larger mean tumor size and more aggressive tumor characteristics than HCV HCC or alcoholic HCC patients did. It is hoped that this study will contribute to a better understanding of cHCC in HBV-endemic areas.

Individual having a parent with early-onset gastric cancer may need screening at younger age.

AIM: To evaluate whether individuals with gastric cancer (GC) are diagnosed earlier if they have first-degree relatives with GC. METHODS: A total of 4282 patients diagnosed with GC at National Cancer Center Hospital from 2002 to 2012 were enrolled in this retrospective study. We classified the patients according to presence or absence of first-degree family history of GC and compared age at diagnosis and clinicopathologic characteristics. In addition, we further classified patients according to specific family member with GC (father, mother, sibling, or offspring) and compared age at GC diagnosis among these patient groups. Baseline characteristics were obtained from a prospectively collected database. Information about the family member's age at GC diagnosis was obtained by questionnaire. RESULTS: A total of 924 patients (21.6%) had a first-degree family history of GC. The mean age at GC diagnosis in patients having paternal history of GC was 54.4 ± 10.4 years and was significantly younger than in those without a first-degree family history (58.1 ± 12.0 years, P < 0.001). However, this finding was not observed in patients who had an affected mother (57.2 ± 10.0 years) or sibling (62.2 ± 9.8 years). Among patients with family member having early-onset GC (< 50 years old), mean age at diagnosis was 47.7 ± 10.3 years for those with an affected father, 48.6 ± 10.4 years for those with an affected mother, and 57.4 ± 11.5 years for those with an affected sibling. Thus, patients with a parent diagnosed before 50 years of age developed GC 10.4 or 9.5 years earlier than individuals without a family history of GC (both P < 0.001). CONCLUSION: Early-onset GC before age of 50 was associated with parental history of early-onset of GC. Individual having such family history need to start screening earlier.

Characteristics of gastric cancer according to Helicobacter pylori infection status.

BACKGROUND AND AIMS: The definition and incidence of gastric cancer (GC) without Helicobacter pylori (Hp) infection varies between studies. The aim of our study was to compare the characteristics of GC according to Hp infection status. METHODS: We evaluated the presence of Hp infection in 1833 GC patients with rapid urease tests, serology examinations, and histological evaluations. GC was classified as GC with current Hp infection (HpC-GC), GC with past Hp infection (HpP-GC), and GC not associated with Hp infection (HpN-GC). HpP-GC was defined as GC without current infection but with a positive serology test, glandular atrophy, and/or intestinal metaplasia. HpN-GC was defined as GC with negative Hp test results and no histological changes. RESULTS: The numbers of HpC-GC, HpP-GC, and HpN-GC were 1378 (75.2%), 412 (22.5%), and 43 (2.3%), respectively. Among GCs without current infection, 90.5% (412/455) were associated with HpP-GC. HpP-GCs were more common in older and male patients, had an increased incidence of synchronous cancer, and less frequently had a diffuse-type histology than HpC-GCs. HpN-GCs were more common in younger, female patients; had a higher proportion of diffuse-type cancers; and more frequently showed distant metastasis than HpP-GCs. In the 40s, the proportion of HpP-GCs with diffuse-type histology (41.9%) was lower than that of HpC-GCs (60.3%) (P = 0.016). The difference was also significant in the 50s (29.1% vs 40.1%, respectively, P = 0.004). CONCLUSIONS: Most GCs in Korea without current Hp infection showed evidence of past Hp infection. The proportion of GCs with diffuse-type histology decreased in patients with past infection.

Long-term outcomes of second treatment after initial transarterial chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: All outcome studies concerning the management of hepatocellular carcinoma (HCC) are based on the initial treatment. However, remaining, progressing or recurring tumours (RPRTs) after transarterial chemoembolization (TACE) are common; therefore, various second treatments are administered to HCC patients. Here, we investigated the long-term outcomes of second treatments for RPRT after initial TACE. METHODS: We enrolled 855 consecutive HCC patients who underwent TACE as the initial treatment at the National Cancer Center, Korea, from January 2004 to December 2010. RESULTS: The median follow-up was 43.4 months, and the median progression-free survival following initial TACE was 4.0 months, being 18.1 and 1.0 months for complete remission and progressive disease respectively. Second treatments were administered to 790 RPRT patients (92.4%); the most common was TACE (56.4%), followed by best supportive care (22.8%), systemic chemotherapy (9.4%), external radiotherapy (4.4%), radiation ablation (RFA; 2.9%), resection (2.0%) and liver transplantation (1.4%). Median overall survival (mOS) for initial TACE was 18.8 months [95% confidence interval (CI), 16.6-21.0 months]; after second treatments, it was 12.4 (95% CI, 10.6-14.2) months, differing significantly by mRECIST assessment, BCLC stage and RPRT type (28.0, 5.0 and 3.9 months for intrahepatic, vascular and extrahepatic RPRT, respectively; P < 0.001). Intrahepatic RPRT with a curative treatment as a second treatment showed the best OS. CONCLUSION: These novel insights into the patterns and long-term outcomes of second treatments for RPRT in HCC patients who underwent initial TACE are expected to aid in formulating treatment strategies for HCC patients.

Validation of a model to estimate survival in ambulatory patients with hepatocellular carcinoma: a single-centre cohort study.

BACKGROUND & AIMS: Survival of patients with hepatocellular carcinoma (HCC) is determined by hepatic function and tumour extent. Recently, a new Model to Estimate Survival in Ambulatory HCC patients (MESIAH) was proposed to predict overall survival in ambulatory HCC patients. This study aimed to evaluate the prognostic performance of the MESIAH score in an independent cohort of HCC patients. METHODS: A cohort of 1969 patients newly diagnosed with HCC at the National Cancer Center, Korea between January 2004 and December 2009 was used for validation of the MESIAH score. The model's performance was assessed using C-statistics, the likelihood ratio (LR) χ2 value and Akaike information criterion (AIC). RESULTS: Patients in the cohort had a median age of 56 years and 83.2% were men. Hepatitis B virus infection was present in 74.6 and 81.6% had a Child-Pugh class A. The median overall survival was 21.4 months. The MESIAH score had a higher degree of discrimination, with a C-statistic of 0.792 [95% confidence interval (CI), 0.782-0.803], when compared with the Barcelona Clinic Liver Cancer (BCLC) staging system [0.665 (95% CI, 0.653-0.678), P<0.001]. The LR χ2 value and the AIC of MESIAH were also better than those of BCLC, Cancer of the Liver Italian Program, Japan Integrated Scoring and Tokyo score. The observed survival in the cohort closely matched that predicted by the MESIAH score. CONCLUSIONS: The new prognostication model MESIAH accurately estimated the overall survival of Korean HCC patients and may be useful in future research as well as individual patient care.

Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in a hepatitis B virus-endemic area.

BACKGROUND AND AIMS: To evaluate the clinical outcomes of patients with hepatocellular carcinoma (HCC) and compare the findings with that of a previous cohort. METHODS: Overall, 1972 HCC patients diagnosed and treated at the National Cancer Center, Korea between 2004 and 2009 were enrolled. The data of this cohort were compared with those of a previous cohort (2000-2003) from the same institution. RESULTS: In all (mean age, 56.4 years; 1642 men), 74.6% was hepatitis B virus (HBV) positive, 81.6% were Child-Pugh (CP) class A, and 64.4% was Barcelona Clinic Liver Cancer (BCLC) stage C. The modified Union for International Cancer Control (mUICC) stage I, II, III, IVa, and IVb was found in 8.9%, 29.6%, 24.8%, 23.1%, and 13.6% patients, respectively. The most common initial treatment was transarterial chemotherapy (58.3%), followed by resection (18.6%). The 5-year survival rate of BCLC stage 0, A, B, and C were 79.6%, 67.2%, 33.9%, and 17.1%, respectively. The performance status, BCLC stage, mUICC stage, CP class, model for end-stage liver disease score, tumor characteristics, portal vein tumor invasion, and serum alpha-fetoprotein level proved to be independent prognostic variables. Overall survival in the present cohort was better than that in the previous cohort (hazard ratio, 0.829; 95% confidence interval, 0.754-0.912), especially for advanced HCC patients with HBV-positive status. CONCLUSIONS: This cohort study provides valuable insights into the characteristics of HCC in Korean patients. Our findings may help develop clinical trials, treatment strategies, and prognosis systems for HCC patients in HBV-endemic areas.

Efficacy of argon plasma coagulation in the treatment of radiation-induced hemorrhagic gastroduodenal vascular ectasia.

OBJECTIVE: Radiation-induced hemorrhagic gastroduodenal vascular ectasia (GDVE) is rare but difficult to manage. Argon plasma coagulation (APC) has not yet been evaluated in the treatment of radiation-induced hemorrhagic GDVE. The efficacy of APC in patients with radiation-induced hemorrhagic GDVE has been investigated in this article. MATERIAL AND METHODS: Eighteen patients with upper gastrointestinal (GI) bleeding caused by radiation-induced GDVE, including 13 with hepatocellular carcinoma, 3 with pancreatic cancer, and 2 with cholangiocarcinoma, were treated with APC. The efficacy of APC was retrospectively evaluated, based on cessation of macroscopic GI bleeding, resolution or stabilization of anemia and transfusion dependence, endoscopic ablation of almost all vascular lesions, complications, and recurrence. RESULTS: Mean patient age was 59 years (range 42-80 years). The median time from radiation to GDVE diagnosis was 4.6 months (range 3.3-21.5 months). The median number of APC sessions per patient was 2.4 (range 1-4). All 18 patients showed an endoscopic response to APC treatment, with sustained increases in mean hemoglobin level, from 6.6 g/dL (range 2.9-9.5 g/dL) to 9.7 g/dL (range 7.1-12.7 g/dL) (p < 0.001), and decreased dependence on transfusion, from 9.1 (range 0-30) to 4.1 (range 0-15) units of packed red blood cells per patient (p = 0.038) after last endoscopic eradication by APC treatment. There were no major procedure-related adverse events or deaths. At a median follow up of 4.7 months (range 0.6-24.5 months), none of the patients experienced recurrence of GDVE. CONCLUSIONS: APC showed short-term effectiveness and safety in the treatment of radiation-induced hemorrhagic GDVE.

Granulocyte macrophage-colony stimulating factor (GM-CSF) augments acute lung injury via its neutrophil priming effects.

Granulocyte macrophage-colony stimulating factor (GM-CSF) has immuno-stimulatory effects. We hypothesized that GM-CSF plays an important role both in lipopolysaccharide (LPS)- and hemorrhage-induced acute lung injury (ALI). We also postulated that GM-CSF augments LPS-induced inflammation by priming neutrophils. ALI was induced in GM-CSF-/- or control C57BL mice either by LPS injection or by hemorrhage. Lung inflammation (by lung expression for tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin-1beta (IL-1beta), interleukin- 6 (IL-6), and keratinocyte-derived chemokine) and lung injury (by myeloperoxidase and Evans blue dye assay) were evaluated after ALI. Incremental doses of LPS (0, 1, 10, and 100 ng/mL) and GM-CSF (0, 1, 10, and 100 ng/mL) were added to bone marrow neutrophils. The expression of TNF-alpha, MIP-2, and IL-1beta was evaluated with enzyme linked immunosorbent assay. The mRNA expression of three cytokines, and the nuclear translocation of nuclear factor kappa B (NF kappa-B) were evaluated by reverse transcriptase-polymerase chain reaction and electrophoretic mobility shift assay, respectively. GM-CSF -/- mice showed decreased neutrophil infiltration, less leakage, and lower expression of cytokines in the lung after LPS or hemorrhage. GM-CSF augmented LPS-induced protein and mRNA expression of TNF-alpha, MIP-2 and IL-1beta, which was mediated by increased intra-nuclear translocation of NF-kappaB. GM-CSF plays an important role in high-dose LPS and hemorrhage-induced ALI, which appears to be mediated by its priming effect on neutrophils.