Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Background/Aims: This nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS). Methods: The NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old). Results: We included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I–III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37). Conclusions Old patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.

Background/Aims: This nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS). Methods: The NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old). Results: We included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I–III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37). Conclusions Old patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.

Background: Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. Methods: Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. Results: Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. Conclusions A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.
Adenoviridae ; Aged ; Cell Differentiation ; DNA Damage ; DNA Replication ; DNA, Single-Stranded* ; DNA-Binding Proteins* ; Female ; Genome-Wide Association Study ; Humans ; In Vitro Techniques ; Introns ; Keratinocytes ; Polymorphism, Single Nucleotide ; Skin*

PURPOSE: Patients often complain of change of defecation pattern and it is necessary to quantify their symptoms. To quantify symptoms, use of questionnaire is ideal, so we adopted a simple and easily writable visual analogue scale for irritable bowel syndrome questionnaire (VAS-IBS). The aim of this study was to develop and validate the Korean version of VAS-IBS questionnaire (Korean VAS-IBS) that can adequately reflect the defecation pattern. METHODS: This study translated English VAS-IBS into Korean using the forward-and-back translation method. Korean VAS-IBS was performed on 30 patients, who visited the outpatient clinic and had no possibility of special defecation pattern. Detailed past medical history and Bristol stool chart was added to the questionnaire. The survey was conducted twice, and the median interval between the 2 surveys was 10 days (8–11 days). Cronbach α for internal consistency reliability and intraclass correlation coefficients for test-retest reliability were analyzed. RESULTS: Korean VAS-IBS achieved acceptable homogeneity with a Cronbach α coefficient of 0.66–0.79 showing adequate internal consistency reliability. In addition, intraclass correlation coefficients showed significant test-retest reliability with 0.46–0.80 except for the question assessing the “perception of psychological wellbeing.” CONCLUSION: The Korean VAS-IBS is a valid and reliable questionnaire for the measurement of the symptoms of defecation pattern changes.
Ambulatory Care Facilities ; Defecation* ; Humans ; Irritable Bowel Syndrome* ; Methods ; Reproducibility of Results ; Translations ; Visual Analog Scale

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.