Immunogenicity and Optimal Timing of 13-Valent Pneumococcal Conjugate Vaccination during Adjuvant Chemotherapy in Gastric and Colorectal Cancer: A Randomized Controlled Trial / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Pneumococcal vaccination (13-valent pneumococcal conjugate vaccine [PCV13]) is recommended to cancer patients undergoing systemic chemotherapy. However, the optimal time interval between vaccine administration and initiation of chemotherapy has been little studied in adult patients with solid malignancies. @*Materials and Methods@#We conducted a prospective randomized controlled trial to evaluate whether administering PCV13 on the first day of chemotherapy is non-inferior to vaccinating 2 weeks prior to chemotherapy initiation. Patients were randomly assigned to two study arms, and serum samples were collected at baseline and 4 weeks after vaccination to analyze the serologic response against Streptococcus pneumoniae using a multiplexed opsonophagocytic killingassay. @*Results@#Of the 92 patients who underwent randomization, 43 patients in arm A (vaccination 2 weeks before chemotherapy) and 44 patients in arm B (vaccination on the first day of chemotherapy) were analyzed. Immunogenicity was assessed by geometric mean and fold-increase of post-vaccination titers, seroprotection rates (percentage of patients with post-vaccination titers > 1:64), and seroconversion rates (percentage of patients with > 4-fold increase in post-vaccination titers). Serologic responses to PCV13 did not differ significantly between the two study arms according to all three types of assessments. @*Conclusion@#The overall antibody response to PCV13 is adequate in patients with gastric and colorectal cancer during adjuvant chemotherapy, and no significant difference was found when patients were vaccinated two weeks before or on the day of chemotherapy initiation.

A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

Three-year colonoscopy surveillance after polypectomy in Korea: a Korean Association for the Study of Intestinal Diseases (KASID) multicenter prospective study

BACKGROUND/AIMS: Colonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy. METHODS: A total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics. RESULTS: Among 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence. CONCLUSIONS: A colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.

Risk score model for the development of hepatocellular carcinoma in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B

BACKGROUND/AIMS: This study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB). METHODS: We investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated. RESULTS: The cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001). CONCLUSIONS: The study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.

Randomized trial of subfascial infusion of ropivacaine for early recovery in laparoscopic colorectal cancer surgery / 대한마취과학회지

BACKGROUND: There is a need for investigating the analgesic method as part of early recovery after surgery tailored for laparoscopic colorectal cancer (LCRC) surgery. In this randomized trial, we aimed to investigate the analgesic efficacy of an inverse ‘v’ shaped bilateral, subfascial ropivacaine continuous infusion in LCRC surgery. METHODS: Forty two patients undergoing elective LCRC surgery were randomly allocated to one of two groups to receive either 0.5% ropivacaine continuous infusion at the subfascial plane (n = 20, R group) or fentanyl intravenous patient controlled analgesia (IV PCA) (n = 22, F group) for postoperative 72 hours. The primary endpoint was the visual analogue scores (VAS) when coughing at postoperative 24 hours. Secondary end points were the VAS at 1, 6, 48, and 72 hours, time to first flatus, time to first rescue meperidine requirement, rescue meperidine consumption, length of hospital stay, postoperative nausea and vomiting, sedation, hypotension, dizziness, headache, and wound complications. RESULTS: The VAS at rest and when coughing were similar between the groups throughout the study. The time to first gas passage and time to first rescue meperidine at ward were significantly shorter in the R group compared to the F group (P = 0.010). Rescue meperidine was administered less in the R group; however, without statistical significance. Other study parameters were not different between the groups. CONCLUSIONS: Ropivacaine continuous infusion with an inverse ‘v ’ shaped bilateral, subfascial catheter placement showed significantly enhanced bowel recovery and analgesic efficacy was not different from IV PCA in LCRC surgery.

Prediction of the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients after Sustained Virological Response by Aspartate Aminotransferase to Platelet Ratio Index

BACKGROUND/AIMS: Following sustained virological response (SVR) for chronic hepatitis C (CHC) infection, patients with advanced fibrosis require regular monitoring for hepatocellular carcinoma (HCC). The aspartate aminotransferase to platelet ratio index (APRI) is a simple noninvasive surrogate marker known to reflect fibrosis. METHODS: We retrospectively analyzed 598 patients who achieved SVR with interferon-based therapy for CHC. RESULTS: Over a median of 5.1 years of follow-up, there were eight patients diagnosed with HCC and a 5-year cumulative incidence rate of 1.3%. The median pretreatment APRI was 0.83, which decreased to 0.29 after achieving SVR (p<0.001). Both the pre- and posttreatment indices were associated with HCC development. The 5-year cumulative HCC incidence rates were 0% and 2.8% for patients with pretreatment APRI <1.0 and ≥1.0, respectively (p=0.001) and 0.8% and 12.8% for patients with posttreatment APRI <1.0 and ≥1.0, respectively (p<0.001). Pretreatment APRI at a cutoff of 1.0 had a 100% negative predictive value until 10 years after SVR. CONCLUSIONS: HCC development was observed among CHC patients who achieved SVR. The pre- and post-treatment APRI could stratify HCC risk, indicating that the APRI could be a useful marker to classify HCC risk in CHC patients who achieved SVR. However, given the small number of HCC patients, this finding warrants further validation.

T2-Weighted Liver MRI Using the MultiVane Technique at 3T: Comparison with Conventional T2-Weighted MRI

OBJECTIVE: To assess the value of applying MultiVane to liver T2-weighted imaging (T2WI) compared with conventional T2WIs with emphasis on detection of focal liver lesions. MATERIALS AND METHODS: Seventy-eight patients (43 men and 35 women) with 86 hepatic lesions and 20 pancreatico-biliary diseases underwent MRI including T2WIs acquired using breath-hold (BH), respiratory-triggered (RT), and MultiVane technique at 3T. Two reviewers evaluated each T2WI with respect to artefacts, organ sharpness, and conspicuity of intrahepatic vessels, hilar duct, and main lesion using five-point scales, and made pairwise comparisons between T2WI sequences for these categories. Diagnostic accuracy (Az) and sensitivity for hepatic lesion detection were evaluated using alternative free-response receiver operating characteristic analysis. RESULTS: MultiVane T2WI was significantly better than BH-T2WI or RT-T2WI for organ sharpness and conspicuity of intrahepatic vessels and main lesion in both separate reviews and pairwise comparisons (p < 0.001). With regard to motion artefacts, MultiVane T2WI or BH-T2WI was better than RT-T2WI (p < 0.001). Conspicuity of hilar duct was better with BH-T2WI than with MultiVane T2WI (p = 0.030) or RT-T2WI (p < 0.001). For detection of 86 hepatic lesions, sensitivity (mean, 97.7%) of MultiVane T2WI was significantly higher than that of BH-T2WI (mean, 89.5%) (p = 0.008) or RT-T2WI (mean, 84.9%) (p = 0.001). CONCLUSION: Applying the MultiVane technique to T2WI of the liver is a promising approach to improving image quality that results in increased detection of focal liver lesions compared with conventional T2WI.

Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels

Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-naive, HBV-related, compensated cirrhosis patients with elevated HBV DNA levels (> or =2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal ( or =40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels.

Relationship between Lower Urinary Tract Symptom and Hypertension: Coprevalence Rate and Symptom Severity / 대한비뇨기과학회지

PURPOSE: It is presumed that lower urinary tract symptom(LUTS) and hypertension are related to the age-dependent sympathetic activity. Thus, the attempt to elucidate a correlation between these two conditions can be important in their management. We investigated the relationship between LUTS and hypertension. MATERIALS AND METHODS: From 1995 to 1997, 1011 men(422 from routine physical checkup, 288 benign prostatic hyperplasia(BPH) patients, 301 hypertension patients) over 50 years were enrolled. The international prostate symptom score(IPSS) and blood pressure were recorded in all. 422 men from physical checkup were grouped into 4 categories according to the presence of LUTS(IPSS> or =8) or hypertension(systolic> or =140mmHg, diastolic> or =90mmHg). The prevalence of hypertension, and the degree of LUTS were evaluated. Statistical analysis was performed with t-test, chi-square test and Mantel-Haenszel test. RESULTS: The prevalence of hypertension was not significantly different between the LUTS(n=177) and non-LUTS groups(n=245)(38.4% vs 35.9%, p=0.600) in men from physical checkup. There was no difference according to age(p=0.513). The prevalence of hypertension was 39.6% in the BPH group(N=288) and was not different compared to the non-LUTS group(n=245)(p=0.385). No significant difference in the prevalence of LUTS was seen between hypertensives(n=156) and normotensives(n=266)(53.2% vs 48.2%, p=0.447) in the physical checkup group. However, their mean IPSS (8.9+/-6.5 vs 7.6+/-5.6) were significantly different(p=0.030). The mean IPSS between hypertensives(15.21+/-4.5) and normotensives(12.75+/-5.0) from the LUTS group(n=178) were significantly different(p=0.002). The mean IPSS of the patients with hypertension(n=301, 9.6+/-5.9) was significantly higher than normotensive men(n=266, 7.6+/-5.6) from physical checkup(p=0.001). CONCLUSIONS: Hypertension and LUTS including BPH do not correlate prevalence-wise, however, hypertension may affect the degree of IPSS.

Congenital Asymptomatic Cytomegalovirus Infection: A Comparison of Specific IgM Antibody Test and pp65 Antigenemia Assay

PURPOSE: It is increasingly important to diagnosis asymptomatic infections which make up a majority (90%) of congenital cytomegalovirus (CMV) infections and that they may have sequeles such as sensorineural hearing loss and mental retardation. Recently antigenemia assay has been developed by using monoclonal antibodies against early structural protein pp65 of CMV. This CMV antigenemia assay seems to be more quicker to diagnosis than conventional viral culture or other tests. In this study, we evaluated the CMV antigenemia assay in neonatal congenital asymptomatic CMV infections comparing it to the CMV specific IgM test that uses enzyme immunoassay. METHODS: From October 1995 to May 1996, 231 normal term newborns delivered with asymptomatic in St. Holy Hospital of Catholic University were included. The CMV antigenemia assay was performed with CMV-vueTM Kit by immunocytochemical staining and the CMV specific IgM test was performed with Enzygnost Anti-CMV/IgM by using an enzyme immunoassay. RESULTS: Three cases (male 2, female 1) were CMV pp65 antigenemia assay positive, but none of them were CMV specific IgM antibody test positive. The CMV pp65 antigenemia assay was more sensitive than CMV specific IgM antibody test for detection of congenital asymptomatic CMV infections by 1.3% and 0%, respectively. CONCLUSION: According to previous results, we suggest that the rate of congenital CMV infections using only CMV specific IgM tests have been underestimated. We recommend the CMV antigenemia assay as the preferred method for more rapid and accurate diagnosis of CMV infections. And congenital asymptomatic CMV infections should be diagnosed and followed up because of possible future sequeles.

Sample Size Estimation for Log-Rank Test for Phase III Clinical Trials / 한국역학회지

At first, we review a sample size estimation method for log-rank test in survival analysis. Although it is widely used these days, it has a weakness for practical use. We propose a modification method to avoid the weakness.