Bun Kim

Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma

It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC).

Proximal disease extension and related predicting factors in ulcerative proctitis

Abstract Objective. Ulcerative colitis usually involves the rectum, may extend in a proximal and continuous fashion to involve varying portions of the bowel. However, the risk factors predictive of proximal extension have yet to be determined. The aim of this study was to evaluate both the natural course of disease and the risk factors influencing the proximal disease extension in ulcerative proctitis. Material and methods. We retrospectively analyzed 98 patients with ulcerative proctitis at the time of diagnosis who were regularly followed and underwent sigmoidoscopy or colonoscopy between January 2000 and December 2007. Results. The mean duration of follow-up was 109.2 ± 49.5 months. A total of 27 (27.6%) patients experienced proximal disease extension. Mayo scores were significantly higher in the extension group compared with patients whose ulcerative proctitis did not extend proximally (p < 0.001). Corticosteroid use at initial diagnosis was also more frequent in the extension group (p = 0.026). In addition, chronic, continuous disease activation within 6 months of the initial diagnosis was significantly higher in the extension group (p < 0.001), as was disease relapse and the number of hospitalizations over the entire follow-up period (p < 0.001 and p = 0.002). According to multivariate analysis, disease extension after the initial diagnosis was associated with chronic disease activation, disease relapse and hospitalization (p = 0.030, p = 0.042 and p = 0.044, respectively). Conclusion. Increased severity of disease upon diagnosis of ulcerative proctitis was associated with a higher probability of proximal disease extension during the follow-up period. Moreover, those with disease extension were more likely to experience relapse and to be hospitalized, indicating poor prognosis.

Dose- and time-dependent effects of recombinant human bone morphogenetic protein-2 on the osteogenic and adipogenic potentials of alveolar bone-derived stromal cells.

BACKGROUND AND OBJECTIVE Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP-2-induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose- and time-dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro. MATERIAL AND METHODS hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 (100 μg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8-wk healing period. To further understand the dose-dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d) effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma-2 and lipoprotein lipase, were assessed using quantitative RT-PCR. RESULTS rhBMP-2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose- and time-dependent manner with minimal deviation in vitro. The expression of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up-regulated by rhBMP-2. CONCLUSION The findings of the present study showed that rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose- and time-dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP-2.

Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance

We compared the viral suppressive efficacy of tenofovir disoproxil fumarate (TDF) mono‐rescue therapy (TDF group) and TDF plus entecavir (ETV) combination‐rescue therapy (TDF + ETV group) in chronic hepatitis B (CHB) patients with lamivudine resistance and entecavir resistance. One hundred and thirty‐three CHB patients with lamivudine and entecavir resistance were investigated. Ninety‐six patients were treated with TDF and 37 with TDF + ETV for at least 6 months. We compared the virologic response rate (HBV DNA level <20 IU/mL) between the two groups and identified the predictive factors of treatment outcome. There were no significant differences between the two groups in demographic characteristics. Up to 24 months [median: 18 (range 6‐24) months], 85.4% and 89.2% of the TDF group and TDF + ETV group, respectively, achieved a virologic response (P=.068). Only the HBV DNA level at baseline was significantly associated with a virologic response in the multivariate analysis. In a subanalysis of patients with HBV DNA levels ≥4 log (IU/mL) at baseline, a higher proportion of patients in the TDF + ETV group than the TDF group achieved a virologic response (92.9% vs 68.3%; P<.001), while 90% of patients with HBV DNA (IU/mL) levels <4 log in all both TDF and TDF + ETV groups achieved a virologic response. TDF mono‐rescue therapy is a reasonable option in patients with lamivudine resistance and entecavir resistance. However, the combination strategy should be considered in patients with high baseline HBV DNA levels.

Clinical meaning of BRAF mutation in Korean patients with advanced colorectal cancer

AIM To evaluate the clinicopathological features of colorectal cancer (CRC) with a v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and its molecular interaction with microsatellite instability (MSI) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in patients with advanced CRCs. METHODS From October 2009 to December 2011, 141 patients with stage III (n = 51) or IV (n = 90) CRCs who were tested for the BRAF mutation at Severance Hospital were included. Among 141 patients, five were excluded due to follow-up loss. Therefore, 136 patients were included in the study. The clinicopathological data, MSI status, and KRAS/BRAF mutation status were reviewed retrospectively. In addition, to evaluating the value of BRAF mutation status, progression-free survival and overall survival in all patients were collected and compared between the BRAF wild-type group and BRAF mutation group. RESULTS Of 136 patients, 80 (58.8%) were male and the mean age was 59 years. BRAF and KRAS mutations were detected in 9.6% and 35.3% of patients, respectively. Only 4.3% of patients had MSI-high tumors and there were no MSI-high in tumors with a BRAF mutation. BRAF mutations tended to be more frequent in stage IV than in stage III (11.76% vs 5.88%, P = 0.370). Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without (7.69% vs 38.21%, P = 0.033). Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis (P = 0.041) and multivariate analysis (HR = 2.195; 95%CI: 1.039-4.640; P = 0.039), while progression-free survival was not different according to BRAF mutation status. CONCLUSION CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.

The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer.

ABSTRACT Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).

Fecal calprotectin as a non-invasive biomarker for intestinal involvement of Behçet's disease.

The diagnostic and prognostic values of fecal calprotectin (FC) levels in patients with inflammatory bowel diseases have been proven. However, little is known about the usefulness of FC measurement in predicting intestinal involvement of Behçets disease (BD).

Efficacy of Adalimumab in Korean Patients with Crohn's Disease.

Background/Aims Adalimumab is effective for both remission induction and the maintenance of Crohn’s disease (CD) in Western countries. We evaluated the efficacy of adalim-umab in the conventional step-up treatment approach for CD in Korea. Methods We retrospectively reviewed 62 patients with CD who were treated with adalimumab. Their Crohn’s disease activity index (CDAI) was measured at weeks 4, 8, and 52. Clinical remission was defined as a CDAI score <150. Induction and maintenance outcomes were analyzed. Results Forty-one patients (66.1%) achieved a reduction of 70 CDAI points at week 8. Among them, 28 (45.2%) achieved clinical remission at week 8, 20 (32.3%) maintained remission at week 52. The absence of prior anti-tumor necrosis factor (TNF) therapy and Montreal classification L1 at baseline predicted clinical remission at week 8 in the multivariate logistic regression analysis. In the Cox proportional hazards model, the hazard ratio for the secondary loss of response during maintenance therapy after clinical remission induction was significantly higher in patients who showed initial mild CDAI severity or Montreal classification A3. Conclusions In our study, anti-TNF therapy-naive and Montreal classification L1 were associated with adalimumab efficacy as induction therapy in CD. Further studies are warranted to determine the prognostic factors for the long-term response after adalimumab therapy.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behçet's Disease in Actual Clinical Practice.

Background/Aims Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behçet’s disease (BD) in actual clinical practice. Methods We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. Results Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behçet’s Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (≥40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). Conclusions Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Conventional endoscopic features are not sufficient to differentiate small, early colorectal cancer.

AIM To evaluate the depth of invasion of small, early colorectal cancers (ECCs) using conventional endoscopic features. METHODS From January 2005 to September 2011, colonoscopy cohort showed that a total of 72 patients with small colorectal cancers with the size less than 20 mm underwent colonoscopy at the Yonsei University College of Medicine, Seoul, South Korea. Among them, 8 patients were excluded due to incomplete medical records. Finally, a total of 64 ECCs with submucosa (SM) invasion and size less than 20 mm were included. One hundred fifty-two adenomas with size less than 20 mm were included as controls. Nine endoscopic features, including seven morphological findings (i.e., loss of lobulation, excavation, demarcated and depressed areas, stalk swelling, fullness, fold convergence, and bleeding ulcers), pit patterns, and non-lifting signs, were evaluated retrospectively. All endoscopic features were evaluated by two experienced endoscopists who have each performed over 1000 colonoscopies annually for more than five years without knowledge of the histology. RESULTS Among the morphological findings, the size of deep submucosal cancers was bigger than that of superficial lesions (16.9 mm vs 12.3 mm, P < 0.001). Also, demarcated depressed areas, stalk swelling, and fullness were more common in deep SM cancers than in superficial tumors (demarcated depressed areas: 52.0% vs 15.7%, P < 0.001; stalk swelling: 100% vs 4.2%, P < 0.001; fullness: 25.0% vs 0%, P = 0.001). Among deep SM cancers, 96% of polyps showed invasive pit patterns, whereas 19.4% of superficial tumors showed invasive pit patterns (P < 0.001). A positive non-lifting sign was more common in deep SM cancers (85.0% vs 28.6%, P < 0.001). Diagnostic accuracy of invasive morphology, invasive pit patterns, and non-lifting signs for deep SM cancers were 71%, 82%, and 75%, respectively. CONCLUSION Conventional endoscopic findings were insufficient to discriminate small, deep SM cancers from superficial SM cancers by white light, standard colonoscopy.