Conditional survival estimate in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy with/without concurrent radiotherapy.

Conditional survival (CS) provides a prognosis of patients who have already survived several years after treatment. We investigated CS in Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) with or without concurrent radiotherapy (CRT). A total of 181 patients diagnosed with HCC who were treated with HAIC with or without CRT between 2011 and 2015 were retrospectively reviewed. Overall survival (OS) and CS were calculated and a subgroup analysis was performed. The 1- and 5-year survival rates of all patients were 57.0% and 24.3%. OS was significantly higher in patients with BCLC stage B than BCLC stage C patients. Patients who achieved disease control after treatment also showed longer OS than who did not respond to treatment. Provided that the patient had already survived for 0, 1, 2, and 3 years, the CS estimates of surviving an additional 2 years were 35.6%, 55.1%, 82.0%, and 77.4%, respectively. A subgroup analysis was performed to compare BCLC stage B and C patients and revealed that CS has a tendency to increase and the difference in CS between two groups decreased over time. CS reflects the change of prognosis over time and may provide a more accurate prognosis and hopeful message to patients who have already survived with treatment.

Association Between Level of Fibrosis, Rather Than Antiviral Regimen, and Outcomes of Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: We performed a propensity-score matched analysis to investigate whether entecavir, compared with lamivudine, can reduce risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B after adjusting for level of fibrosis. METHODS: We performed a retrospective study of 1079 patients with chronic hepatitis B who received first-line therapy with lamivudine (n = 435) or entecavir (n = 644) from 2006 through 2013. Only patients with available liver stiffness value measured by transient elastography were recruited. Liver cirrhosis was diagnosed by ultrasonography. To adjust for the imbalance of patients treated with lamivudine versus entecavir, we performed propensity-score matching (PSM), at a ratio of 1:1, using 7 factors (age, sex, hepatitis B e antigen, alanine aminotransferase, serum albumin, platelet count, and liver stiffness; PSM1) or 8 factors (variables of PSM1 plus ultrasonography measurements of cirrhosis; PSM2). Patients with virologic breakthrough or resistance mutations received rescue therapy. RESULTS: Over the 7-year period, 91 patients developed HCC and 104 had liver-related events in the entire cohort. In multivariate analyses, level of fibrosis, but not antiviral regimen, was independently associated with risk of HCC (P < .05). The PSM1 group included 342 pairs of patients and the PSM2 group included 338 pairs. Similar proportions of patients given lamivudine versus entecavir developed HCC in each model (10.5% given lamivudine vs 9.9% given entecavir in PSM1 and 11.9% vs 12.6% in PSM2; all P > .05). When PSM was applied to patients with liver stiffness value ≤13 kPa or >13 kPa, patients given lamivudine versus entecavir still had similar cumulative rates of HCC development (all P > .05). CONCLUSIONS: In a PSM analysis, we associated level of fibrosis, rather than antiviral regimen, with risk of HCC, when patients received appropriate rescue therapy in case of virologic breakthrough or resistance mutations.

Clinical Benefit of Hepatic Arterial Infusion Concurrent Chemoradiotherapy in Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

PURPOSE: The aim of this study was to evaluate whether hepatic arterial infusion concurrent chemoradiotherapy (CCRT) could improve overall survival (OS) in patients with locally advanced hepatocellular carcinoma (LAHCC). MATERIALS AND METHODS: Two databases were reviewed from Yonsei Cancer Center (YCC) and Korean Liver Cancer Study Group (KLCSG) nationwide multi-center hepatocellular carcinoma (HCC) cohort. The CCRT group included 106 patients, with stage III-IV, Child-Pugh classification A, Eastern Cooperative Oncology Group performance status 0 or 1, who underwent definitive CCRT as the initial treatment at YCC. We used propensity score matching to adjust for seven clinical factors, including age, tumor size, TNM stage by the Liver Cancer Study Group of Japan, T stage, Barcelona Clinic Liver Cancer (BCLC) staging system, etiology of HCC, and portal vein invasion, which all differed significantly in the two databases. From the KLCSG cohort enrolled at 32 institutions, 106 patients for the non-CCRT group were defined. RESULTS: After propensity score matching, all patient characteristics were balanced between the two groups. The CCRT group had better OS (median, 11.4) than the non-CCRT group (6.6 months, p=0.02). In multivariate analyses for all patients, CCRT (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.11 to 1.97; p=0.007), tumor size (HR, 1.08; 95% CI, 1.04 to 1.12; p < 0.001), and BCLC stage (HR, 0.54; 95% CI, 0.36 to 0.8; p=0.003) were independent prognostic factors for OS. CONCLUSION: CCRT showed better OS for LAHCC patients. In LAHCC patients with a good performance and normal liver function, CCRT could be a feasible treatment option. All of these findings need to be validated in prospective clinical trials.

Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis.

UNLABELLED: Early detection of liver cirrhosis in its subclinical stage is of paramount importance to identify high-risk individuals for developing hepatocellular carcinoma (HCC). This study investigated whether transient elastography (TE) can identify patients with subclinical cirrhosis (SCC) who are at increased risk of developing HCC among chronic hepatitis B (CHB) patients without clinical evidence of cirrhosis. A total of 2,876 CHB patients without clinical cirrhosis who received TE examinations between April 2006 and December 2012 were enrolled in this prospective study. SCC was defined as a nonclinical cirrhosis, but with a liver stiffness (LS) value ≥13 kilopascals (kPa). Mean age of the study population was 46.1 years, and male gender was predominant (n = 1,775; 61.7%). Mean LS value was 7.9 kPa, and SCC was identified in 285 (9.9%) patients. During the median follow-up period of 48.9 months (range, 6.6-96.2), HCC developed in 16 patients (13.3 per 1,000 person-years) in the SCC group and 36 (3.4 per 1,000 person-years) in the non-SCC group. Cumulative incidence rate of HCC in the SCC group was significantly higher than that in the non-SCC group (P < 0.001, log-rank test). On multivariate analysis, SCC was independently associated with a risk of developing HCC, regardless of antiviral therapy (without antiviral therapy: hazard ratio [HR]: 4.680; 95% confidence interval [CI]: 1.187-18.441; P = 0.027; with antiviral therapy: HR, 3.344; 95% CI: 1.526-7.328; P = 0.003). CONCLUSION: TE can identify CHB patients with SCC who are at increased risk of developing HCC, even when cirrhosis is not clinically apparent.

Transient elastography-based risk estimation of hepatitis B virus-related occurrence of hepatocellular carcinoma: development and validation of a predictive model.

BACKGROUND: The purpose of this study was to develop and validate a novel transient elastography-based predictive model for occurrence of hepatocellular carcinoma (HCC). METHODS: A total of 1,250 patients with chronic hepatitis B and baseline liver stiffness values were recruited between May 2005 and December 2007. The predictive model for HCC occurrence was constructed based on a Cox proportional hazards model. We estimated baseline disease-free probabilities at 3 years. Discrimination and calibration were used to validate the model. RESULTS: HCC occurred in 56 patients during a median follow-up of 30.7 months. Multivariate analysis revealed that age, male gender, and liver stiffness values were independent predictors of HCC (all P<0.05), whereas hepatitis B virus DNA ≥20,000 IU/L showed borderline statistical significance (P=0.0659). We developed a predictive model for HCC using these four variables, which showed good discrimination capability, with an area under the receiver operating characteristic curve (AUROC) of 0.806 (95% confidence interval 0.738-0.874). We used the bootstrap method to assess discrimination. The AUROC remained largely unchanged between iterations, with an average value of 0.802 (95% confidence interval 0.791-0.812). The predicted risk of occurrence of HCC calibrated well with the observed risk, with a correlation coefficient of 0.905 (P<0.001). CONCLUSION: This novel model accurately estimated the risk of HCC occurrence in patients with chronic hepatitis B.

Vitamin B(12) deficiency after gastrectomy for gastric cancer: an analysis of clinical patterns and risk factors.

OBJECTIVE: To identify risk factors for postgastrectomy vitamin B12 deficiency and the time course of its development. BACKGROUND: Postgastrectomy vitamin B12 deficiency worsens the quality of life of gastric cancer survivors, and vitamin B12-related neuropathy is irreversible if recognized late. However, the clinical pattern of vitamin B12 deficiency development after gastrectomy remains unclear. METHODS: We reviewed 645 patients with gastric cancer who underwent distal subtotal gastrectomy (DG; n = 469) or total gastrectomy (TG, n = 176) between 2003 and 2010. Univariate and multivariate analyses were performed to identify risk factors for vitamin B12 deficiency and time to deficiency. RESULTS: Cumulative vitamin B12 deficiency rates were 100% for TG and 15.7% for DG 4 years after surgery (P < 0.001). The median time to vitamin B12 deficiency was 15 months after TG, whereas the median time was not reached after DG. Preoperative vitamin B12 level was the only risk factor for vitamin B12 deficiency after TG, whereas both preoperative vitamin B12 level and age were risk factors after DG. There was positive linear correlation between preoperative vitamin B12 levels and the time to vitamin B12 deficiency after either TG (P < 0.001) or DG (P = 0.017). CONCLUSIONS: Vitamin B12 deficiency is an inevitable and rather early metabolic sequela after TG. Elderly patients with low preoperative vitamin B12 levels are more likely to experience vitamin B12 deficiency after DG. Thus, preoperative measurement and regular postoperative monitoring of vitamin B12 levels are necessary for early detection and treatment of postgastrectomy vitamin B12 deficiency.

Association between IL28B polymorphisms and spontaneous clearance of hepatitis B virus infection.

BACKGROUND/AIMS: Single-nucleotide polymorphisms (SNPs) near the interleukin 28B gene (IL28B; interferon [IFN]-λ-3) are associated with outcomes of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection treated with peginterferon (PEG-IFN) alpha-based antiviral therapy. In this study, we investigated the influence of IL28B polymorphisms on spontaneous clearance of HBV infection in a large Korean cohort. METHODS: Between January 2007 and June 2010, a total of 208 patients with chronic HBV infection and newly diagnosed HBV-related hepatocellular carcinoma were recruited as the CC group [HBsAg(+) for >6 months, anti-HBc(+), and anti-HBs(-)]. In addition, 351 organ donors were stratified into the UE group [n = 106; HBsAg(-), anti-HBc(-), and anti-HBs(-)] or the SC group [n = 245; HBsAg(-), anti-HBc(+), and anti-HBs(+)]. The SNaPshot ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA) was used for SNP detection. Direct full sequencing of the IL28B coding region was attempted. RESULTS: Regardless of group, rs12979860 CC was most frequently identified (85.0% in UE, 85.9% in SC, and 93.5% in CC, respectively), whereas rs12979860 TT was not identified in any group. Similarly, rs12980275 AA and rs8099917 TT were most frequently identified (≥85%) regardless of group, whereas rs12980275 GG was identified in only one subject in the SC group. In addition, rs8099917 GG was not identified. The prevalences of CC in rs12979860, AA in rs12980275, and TT in rs8099917 were significantly higher in the CC group when compared with the UE and SC group (all P<0.05). Among 19 novel SNPs in the IL28B coding region, the proportions of 6 SNPs were significantly different among the UE, SC, and CC groups (all P<0.05). CONCLUSIONS: The SNP upstream of IL28B that has the strongest genetic association with HCV recovery has an inverse influence on HBV recovery. Additional studies are needed to understand the mechanisms of this SNP in HBV infection.

Staging of adenocarcinoma of the esophagogastric junction: comparison of AJCC 6th and 7th gastric and 7th esophageal staging systems.

BACKGROUND: Adenocarcinoma of esophagogastric junction (EGJ) is currently staged by the esophageal staging criteria according to the American Joint Committee on Cancer (AJCC) staging system, 7th edition. We compared the performance of 6th gastric (G6), 7th gastric (G7), and 7th esophageal (E7) staging systems. METHODS: A total of 202 curatively resected adenocarcinomas of EGJ were analyzed. Patient outcomes were assessed according to G6, G7, and E7 staging. Tumor invasion to the subserosal or serosa layer was regarded as invasion to the adventitia for E7 staging. Performance was measured based on monotonicity (decreasing survival with increasing stage), distinctiveness (survival difference between different stages), and homogeneity (homogenous survival in the same stage). RESULTS: Each staging system was monotonous except for T1-2N0 lesions of E7. This was related to the introduction of histologic grade in E7 staging. Distinctiveness in each staging system was variable. As for the homogeneity, patients whose disease was staged as Ib (E7) exhibited different survival when reassessed by G6 and G7; again, this was related to histologic grading. Patients with IIIb (G7) and IIIc (E7) disease had different survival when reassessed by G6 staging, reflecting the poorer survival of patients with more than 15 lymph node metastases. CONCLUSIONS: Staging of EGJ cancer based on the current AJCC, 7th edition, criteria of esophageal cancer staging has several limitations. We recommend considering modifications of the following in future updates of the staging system: accurate anatomical definition of tumor depth, removal of histologic grade from staging parameters, and classification of more than 15 lymph node metastases as a highly advanced stage.

Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis.

BACKGROUND: Transient elastography (TE), a non-invasive tool that measures liver stiffness, has been evaluated in meta-analyses for effectiveness in assessing liver fibrosis in European populations with chronic hepatitis C (CHC). However, these data cannot be extrapolated to populations in Asian countries, where chronic hepatitis B (CHB) is more prevalent. In this study, we performed a meta-analysis to assess the overall performance of TE for assessing liver fibrosis in patients with CHB. METHODS: Studies from the literature and international conference abstracts which enrolled only patients with CHB or performed a subgroup analysis of such patients were enrolled. Combined effects were calculated using area under the receiver operating characteristic curves (AUROC) and diagnostic accuracy values of each study. RESULT: A total of 18 studies comprising 2,772 patients were analyzed. The mean AUROCs for the diagnosis of significant fibrosis (F2), severe fibrosis (F3), and cirrhosis (F4) were 0.859 (95% confidence interval [CI], 0.857-0.860), 0.887 (95% CI, 0.886-0.887), and 0.929 (95% CI, 0.928-0.929), respectively. The estimated cutoff for F2 was 7.9 (range, 6.1-11.8) kPa, with a sensitivity of 74.3% and specificity of 78.3%. For F3, the cutoff value was determined to be 8.8 (range, 8.1-9.7) kPa, with a sensitivity of 74.0% and specificity of 63.8%. The cutoff value for F4 was 11.7 (range, 7.3-17.5) kPa, with a sensitivity of 84.6% and specificity of 81.5%. CONCLUSION: TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB.

Effect of sevoflurane on grafted kidney function in renal transplantation.

BACKGROUND: The objective of this retrospective study was to determine if there are any differences in grafted kidney function in recipients of kidney transplantation (KT) when donors and recipients were anesthetized with sevoflurane compared to desflurane. METHODS: Seventy-three pairs of donors-recipients were anesthetized with sevoflurane (Sevo group) and 71 pairs were anesthetized with desflurane (Des group). We retrospectively investigated the blood urea nitrogen (BUN) levels, creatinine (Cr) levels, and estimated glomerular filtration rates (eGFR) of the recipients in both groups for 1 year postoperatively. We tested non-inferiority for serum creatinine at discharge and 1 year after KT. Short-term (1 year) outcomes of KT were assessed by the incidence of delayed graft function (DGF), acute rejection episodes (ARE), and graft failure. RESULTS: There were no differences in BUN, Cr, eGFR, or outcomes of KT at 1 year postoperatively. Specifically, the 95% confidence interval for the difference in creatinine levels between the Sevo and Des groups was less than the margin of equivalence at the time of discharge and 1 year after surgery. The occurrences of DGF, ARE, and graft failure were comparable between the groups. CONCLUSIONS: Compared to desflurane, sevoflurane had no adverse effects on grafted renal function or on the short-term outcome of renal transplantation.

Reproducibility of measurement of apparent diffusion coefficients of malignant hepatic tumors: effect of DWI techniques and calculation methods.

PURPOSE: To evaluate the effect of diffusion-weighted imaging (DWI) methods, apparent diffusion coefficient (ADC) calculation methods, and selection of b-values on the ADCs and the measurement reproducibility of malignant hepatic tumors. MATERIALS AND METHODS: Nineteen patients with pathologically confirmed malignant hepatic tumors underwent breath-hold DWI (b-values = 0, 50, 500 s/mm(2)) and respiratory-triggered DWI (0, 50, 300, 500, 1000 s/mm(2)) twice on a 1.5 T magnetic resonance imaging (MRI) scanner. ADCs were calculated using a two b-value and/or a multiple b-value method. The reproducibility of the ADC measurements was evaluated from the intraclass correlation coefficients (ICCs) and the 95% Bland-Altman limit-of-agreement (LOA). RESULTS: The ADCs were different according to the DWI methods (P = 0.040-0.282), ADC calculation methods (P = 0.003-0.825), and the choice of b-values (P < 0.001). The ADC tended to be more reproducible with use of breath-hold DWI (ICC: 0.898-0.933; LOA, 18.8%-24.0%) than respiratory-triggered DWI (ICC: 0.684-0.928; LOA, 15.0%-31.9%) (P = 0.008-0.122). For respiratory-triggered DWI, the multiple b-value method using five b-values had better reproducibility than the two b-value method for measurement of ADC (P = 0.009-0.221). CONCLUSION: The DWI method, ADC calculation method, and selection of b-values potentially influence the ADCs and the reproducibility of malignant hepatic tumors. ADCs calculated from breath-hold DWI are more reproducible than from respiratory-triggered DWI. A multiple b-value method may improve the reproducibility of respiratory-triggered DWI.

Low-dose abdominal CT for evaluating suspected appendicitis.

BACKGROUND: Computed tomography (CT) has become the predominant test for diagnosing acute appendicitis in adults. In children and young adults, exposure to CT radiation is of particular concern. We evaluated the rate of negative (unnecessary) appendectomy after low-dose versus standard-dose abdominal CT in young adults with suspected appendicitis. METHODS: In this single-institution, single-blind, noninferiority trial, we randomly assigned 891 patients with suspected appendicitis to either low-dose CT (444 patients) or standard-dose CT (447 patients). The median radiation dose in terms of dose-length product was 116 mGy·cm in the low-dose group and 521 mGy·cm in the standard-dose group. The primary end point was the percentage of negative appendectomies among all nonincidental appendectomies, with a noninferiority margin of 5.5 percentage points. Secondary end points included the appendiceal perforation rate and the proportion of patients with suspected appendicitis who required additional imaging. RESULTS: The negative appendectomy rate was 3.5% (6 of 172 patients) in the low-dose CT group and 3.2% (6 of 186 patients) in the standard-dose CT group (difference, 0.3 percentage points; 95% confidence interval, -3.8 to 4.6). The two groups did not differ significantly in terms of the appendiceal perforation rate (26.5% with low-dose CT and 23.3% with standard-dose CT, P=0.46) or the proportion of patients who needed additional imaging tests (3.2% and 1.6%, respectively; P=0.09). CONCLUSIONS: Low-dose CT was noninferior to standard-dose CT with respect to negative appendectomy rates in young adults with suspected appendicitis. (Funded by GE Healthcare Medical Diagnostics and others; ClinicalTrials.gov number, NCT00913380.).

A scoring system for prediction of lateral neck node metastasis from papillary thyroid cancer.

Lateral neck node metastasis is an important prognostic factor in thyroid carcinoma. We developed a scoring system for use in prediction of lateral neck node metastasis from papillary thyroid cancer. In this study, 161 consecutive patients were included in the training data set. This scoring system, named the Yonsei Estimated Value (YEV) for lymph node metastasis in papillary thyroid cancer, was developed on the basis of results from multivariate logistic regression analysis of preoperative clinical and radiologic data. Sixty eight consecutive patients were included for testing of the validity of the scoring system. The equation for prediction of lateral neck node metastasis was follows:YEV (Yonsei Estimated Value) = 1/(1+X)X = Exp (5.333-[0.902 × sex]+[0.036 × age]-[1.020 × tumor size]-[0.177 × lymph node size]-[0.032 × lymph node density])When the YEV was 0.3 or more, the probability of lateral neck node metastasis was 79.0%, with sensitivity of 76.3%, specificity of 69.8%, positive predictive value of 56.7%, and negative predictive value of 85.1% in the training set. When fine needle aspiration biopsy for suspicious lateral neck nodes is not possible, or the results are inadequate, our scoring system for prediction of lateral neck node metastasis can be helpful in optimization of the surgical extent for each patient.

The ratio of intra-tumoral regulatory T cells (Foxp3+)/helper T cells (CD4+) is a prognostic factor and associated with recurrence pattern in gastric cardia cancer.

BACKGROUND: TILs have been reported to be a prognostic factor in human cancers. We assessed the prognostic significance of tumor-infiltrating regulatory T cells in gastric cardia cancer. METHODS: We retrospectively reviewed the database of Severance Hospital for patients who underwent curative resection of gastric cardia cancer from Jan 2000 to Dec 2006 and identified 180 patients. Immunohistochemistry for TIL subsets was performed against CD3, CD4, CD8, Foxp3, and granzyme B in the resected tumor specimens. The absolute numbers and relative ratios of positively stained lymphocytes for each subset were evaluated. RESULTS: A high Foxp3/CD4 ratio was identified as an unfavorable prognostic factor for overall survival (OS) using univariate and multivariate analysis of all immunologic variables. Patients group with high Foxp3/CD4 ratio was associated with loco-regional recurrence (P = 0.033). In multivariate analysis for clinical and immunologic variables, the nodal status (hazards ratio--HR: 3.863, confidence interval--CI: 1.664-8.966, P = 0.002), depth of invasion (HR: 3.607, CI: 1.443-9.019, P = 0.006), and Foxp3/CD4 ratio (HR: 1.812, CI: 1.022-3.212, P = 0.042) were identified as independent prognostic factors for OS. CONCLUSIONS: A higher regulatory T cells/helper T cells ratio is associated with an unfavorable prognosis and loco-regional recurrence pattern in gastric cardia cancer.

Acute appendicitis in young adults: low- versus standard-radiation-dose contrast-enhanced abdominal CT for diagnosis.

PURPOSE: To compare low and standard radiation doses in intravenous contrast material-enhanced abdominal computed tomography (CT) for the diagnosis of acute appendicitis in young adults. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived informed consent. The study included 257 patients (age range, 15-40 years) who underwent CT for suspected appendicitis performed by using a low radiation dose (n = 125) or a standard radiation dose (n = 132). Receiver operating characteristic (ROC) analysis, Fisher exact tests, and Mann-Whitney U tests were used to compare the diagnosis of appendicitis and diagnostic confidence as recorded in prospective CT reports between the two groups. RESULTS: For 55 low-radiation-dose (median dose-length product, 122 mGy · cm) and 44 standard-dose (median dose-length product, 544 mGy · cm) examinations, one of two abdominal radiologists made primary reports that served as final reports. For the remaining examinations, on-call radiologists with differing levels of experience issued preliminary reports and the two abdominal radiologists then provided final reports. In the primary reports, the low- and standard-dose CT groups did not significantly differ in area under the ROC curve (0.96 vs 0.97, P = .76), sensitivity (90% [38 of 42] vs 89% [47 of 53], P > .99), or specificity (92% [76 of 83] vs 94% [74 of 79], P = .74) in the diagnosis of appendicitis. There was also no significant difference between the two groups in the confidence level when diagnosing (P = .71) or excluding (P = .20) appendicitis in the primary reports. Similar results were observed for the final reports. The two dose groups also did not significantly differ in terms of appendiceal visualization, diagnosis of appendiceal perforation, or sensitivity for alternative diagnoses. CONCLUSION: Low-dose CT may have comparable diagnostic performance to standard-dose CT for the diagnosis of appendicitis in young adults.

Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients.

BACKGROUND: Vitamin B12 deficiency is a common long-term sequelae after total gastrectomy. Intramuscular injection of vitamin B12 is the only known treatment. We investigated the efficacy and safety of oral vitamin B12 replacement for gastric cancer patients with vitamin B12 deficiency after total gastrectomy. METHODS: We performed a single-arm, open-label, fixed-drug dosage, prospective study (NCT00699478) involving gastric cancer patients who underwent total gastrectomy. Vitamin B12-deficient (<200 pg/ml) patients (n = 30) received daily oral vitamin B12 (dosage: 1500 µg mecobalamin) administration for 3 months. The primary outcome measurement was serum vitamin B12. The secondary outcome measurements were improvement of neurologic symptoms and hematologic findings (serum folate, homocysteine, ferritin, iron, total iron binding capacity, transferrin, and mean corpuscular volume). For comparison, another group of vitamin B12 deficient patients (n = 30) received intramuscular vitamin B12 injections (dosage: 1000 µg cyanocobalamin) weekly for 5 weeks and monthly thereafter for a total of 3 months in a separate study period. RESULTS: In both groups, mean serum vitamin B12 increased after 30 days of treatment and was maintained up to 90 days. No adverse effects related to oral or intramuscular vitamin B12 replacements were noted. Both groups showed decreased homocysteine levels. Before treatment, 29 patients in the oral vitamin B12 group had neurologic symptoms related to vitamin B12 deficiency. After oral vitamin B12 treatment, 28 patients experienced symptom relief, and 16 patients were symptom free. CONCLUSIONS: Oral vitamin B12 replacement is an effective and safe treatment for vitamin B12 deficiency in gastric cancer patients after total gastrectomy.

Prospective evaluation of longitudinal changes in human papillomavirus genotype and phylogenetic clade associated with cervical disease progression.

OBJECTIVE: Changes in the HPV genotype detected in patients over time could alter cervical disease progression. Identification of patterns in the alteration of HPV genotype should also be related to cytological and histological findings. Thus, we assessed the risk for low-grade squamous intraepithelial lesion (LSIL) or high-grade SIL (HSIL)/squamous cell carcinoma (SCC) associated with alterations in the HPV genotype detected, presence of multiple HPV genotypes, and individual genotyping or HPV clade grouping. METHODS: The 1052 participants were monitored by HPV chip and Pap smear. We calculated odds ratios and applied sequential association analysis (SAA) and decision tree analysis (DTA). RESULTS: We classified HPV alteration as persistence, regression (spontaneous vs. therapeutic), or metatyping (progressive vs. regressive). Spontaneous regression occurred in 71.9% of patients. Metatyping was strongly associated with progression (RR: 3.9, p=0.0242), with progressive metatyping showing a higher risk of progression (RR: 31.49, p=0.00448). Few patients with multiple infections were identified in the initial screen but 30.8% of patients had multiple infections in the final analysis. HPV-16, -35, -52, and -58 were commonly associated with HPV persistence. Univariate analysis determined that final diagnosis significantly associated with HPV type at the endpoint (p<0.0001), persistence (p=0.0001), and progressive metatyping (p=0.0022). SAA determined that HPV-66, -68, and -69 were significantly associated with HSIL, and HPV-16 and -18 persistence significantly association with SCC. DTA indicated an age less than 28 years had a peak in LSIL, and an age between 32 and 48 years had a peak in HSIL. A bimodal peak in SCC for HR-2 at the endpoint was observed in participants less than 32 and greater than 48 years of age. CONCLUSIONS: The alteration patterns of HPV infection detected included persistence, regression, and metatyping. HPV persistence and progressive metatyping are significant signatures of disease progression.

Childhood risk factors in Korean women with anorexia nervosa: two sets of case-control studies with retrospective comparisons.

OBJECTIVE: The aim of this study was to investigate the characteristics of the risk factors for anorexia nervosa (AN) in Korean women. METHOD: Two sets of case-control comparisons were conducted, in which 52 women with lifetime AN from Seoul, S. Korea, were compared with 108 Korean healthy controls and also with 42 women with lifetime AN from the UK in terms of their childhood risk factors. A questionnaire designed to conduct a retrospective assessment of the childhood risk factors was administered to all participants. RESULTS: The Korean AN women were more likely to report premorbid anxiety, perfectionism, and emotional undereating and were less likely to report having supportive figures in their childhood than the Korean healthy controls. There were no overall differences in the childhood risk factors between the Korean and British women with AN. DISCUSSION: Premorbid anxiety, perfectionism, less social support, and emotional undereating merit attention as risk factors in Korean AN. The current results are informative, but an epidemiologically robust prospective case-control study would be needed to validate these findings.

How can we enhance the performance of liver stiffness measurement using FibroScan in diagnosing liver cirrhosis in patients with chronic hepatitis B?

GOAL: This study aimed to enhance the diagnostic accuracy by defining different cutoff liver stiffness measurement (LSM) values according to alanine aminotransferase (ALT) level and combining LSM with noninvasive models in patients with chronic hepatitis B (CHB). BACKGROUND: Several studies have indicated that ALT influences LSM using FibroScan. STUDY: The study prospectively enrolled 200 patients (143 men, mean age 45.4 y) between June 2007 and November 2008 who had been diagnosed with CHB and underwent both liver biopsy and LSM on the same day. RESULTS: The area under the receiver operating characteristic curves (AUROC) of LSM for predicting cirrhosis in patients with ALT < or = upper limit of normal (ULN) was higher than that of all patients or those with ALT >ULN and < or = 2x ULN (AUROC=0.884 vs. 0.849 and 0.867). The cutoff LSM values for > or = F2, > or = F3, and F4 were 6.0, 7.5, and 10.1 kPa, respectively, in patients with ALT < or = ULN, whereas they were 8.9, 11.0, and 15.5 kPa, respectively, in those with ALT >ULN and < or = 2x ULN. The combination of LSM and the age-spleen-platelet ratio index performed the best at predicting cirrhosis, regardless of ALT level (AUROC=0.917 in patients with ALT < or = ULN, 0.909 in those with ALT < or = 2x ULN, and 0.894 in all patients). CONCLUSIONS: Different cutoff LSM values according to ALT level and combination with age-spleen-platelet ratio index can enhance the performance of LSM in CHB, regardless of ALT level.

Symptoms to use for diagnostic criteria of hwa-byung, an anger syndrome.

OBJECTIVE: The aim of this study was to identify the characteristic symptoms which can be used for the diagnosis of hwa-byung, a culture-related anger syndrome in Korea. METHODS: The symptoms of the Hwa-byung Scale were correlated with the Korean versions of the Hamilton Depression Rating Scale (K-HDRS) and the State and Trait Anger Inventory (K-STAXI) in 89 patients, who were diagnosed as having major depressive disorder, dysthymic disorder, anxiety disorders, somatoform disorders, or adjustment disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria and who had self-labeled hwa-byung. Also, the symptoms of the Hwa-byung Scale were correlated with each other. RESULTS: The symptoms of the Hwa-byung Scale which were significantly correlated with the state anger of the K-STAXI but not with the depressive mood (item 1 of K-HDRS) included feelings of unfairness, subjective anger, external anger, heat sensation, pushing-up in the chest, dry mouth, and sighing. The symptoms which were significantly correlated with state anger and depressed mood included respiratory stuffiness, "haan" and hate. The symptoms which were not significantly correlated with depressed mood and state anger included going-out, epigastric mass, palpitation, headache/pain, frightening easily, many thoughts, and much pleading. These symptoms also showed higher correlation with each other in the correlation matrix. CONCLUSION: Our findings suggest that hwa-byung is different from depressive syndrome in terms of its symptom profile, and suggest what symptoms should be included in the diagnostic criteria of hwa-byung, an anger disorder.