Weak D type 102 allele (RHD*01W.102) carrying a missense variant (c.73A＞T, p.Ile25Phe) in exon 1 of the RHD has not been reported in Koreans to date. This is the first report of the weak D type 102 allele in the Korean population. The proposita, a 35-year-old woman, showed a serological weak D phenotype in routine RhD typing. Sequencing of all 10 RHD exons and zygosity testing targeting the hybrid Rhesus box revealed this proposita to harbor the weak D type 102 allele, as well as an RHD deletion (RHD*01W.102/RHD*01N.01). Family studies showed that the weak D type 102 allele was also present in her father and older brother (both assumed to be RHD*01W.102/RHD*01) but not in her mother and oldest brother (both assumed to be RHD*01/RHD*01N.01). In silico analysis of the replacement of isoleucine by phenylalanine at position 25 was done with PolyPhen-2, SIFT, and PROVEAN. While PolyPhen-2 predicted the variant as benign, SIFT and PROVEAN predicted it as damaging and deleterious, respectively, suggesting RHD c.73A>T (I25F) as the cause of serologic weak D phenotype. This patient should be treated as D-negative, when transfusion is needed.

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

BACKGROUND/AIMS: Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment. METHODS: We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/ A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/ validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses. RESULTS: Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p < 0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17). CONCLUSIONS: In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.
Bias (Epidemiology) ; Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; International Normalized Ratio ; Liver Neoplasms ; Recurrence ; Retrospective Studies

PURPOSE: The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). MATERIALS AND METHODS: Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. RESULTS: More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. CONCLUSION: Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).
Carcinoma, Hepatocellular* ; Diarrhea ; Humans ; Incidence ; Korea* ; Life Change Events ; Prospective Studies ; Skin

No abstract available.

OBJECTIVE: To evaluate their roles in the pathophysiology of preterm premature rupture of membranes (PPROM), we checked interleukin (IL)-6, lipid peroxide, oxygen-radical absorbance capacity (ORAC) and antioxidant vitamin in the venous plasma and amniotic fluid of women with PPROM. METHODS: Venous plasma and amniotic fluid was taken from 20 normal pregnant women and 20 PPROM pregnancy women. IL-6 levels was determined by enzyme-linked immunosorbent assay. Lipid peroxide levels were measured by thiobarbituric acid reaction. The ORAC levels and the antioxidant levels were measured by Cao's method and by high performance liquid chromatography. RESULTS: The IL-6 levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ORAC values/lipid peroxide levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.01, P<0.01). The ascorbic acid levels in the venous plasma and amniotic fluid of PPROM pregnancy women were significantly higher than normal pregancy (P<0.05, P<0.01). CONCLUSION: This result suggest that the increased inflammatory bioactivity, increased lipid peroxidation and decreased antioxidant activity may be involved in the pathophysiology of PPROM. Low levels of ascorbic acid appears to be an important determinant of PPROM.
Amniotic Fluid ; Ascorbic Acid ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-6 ; Interleukins ; Lipid Peroxidation ; Membranes ; Plasma ; Pregnancy ; Pregnant Women ; Rupture ; Thiobarbiturates ; Vitamins

BACKGROUND/AIMS: Indications for submucosal saline-epinephrine injection (SSEI) for prevention of postpolypectomy bleeding, in the colon, is variable among endoscopists. The aim of this study was to determine the proper indication for SSEI. METHODS: Clinical data of 1,745 polypectomies was evaluated. Postpolypectomy bleeding after snare polypectomy were evaluated in 1,039 polypectomies. Subgroup analysis was performed in 4 subgroups by size (< or = 8 mm or >8 mm) and gross morphology (pedunculated or sessile), also. RESULTS: Submucosal saline-epinephrine injection was used in 679 snare polypectomies. The size of polyps was 9.5+/-4.3 mm. Distribution of polyps showed left side shift in the colon. Sessile polyps (79.4%) and benign adenoma (75.3%) were predominant. Twenty seven episodes (2.6%) of bleeding occurred after snare polypectomy. Rectal polyp, malignant polyp and procedure without SSEI increased bleeding after snare polypectomy with odds ratio 4.71, 10.48 and 3.44, respectively. However, SSEI significantly reduced the bleeding only in patients who had >8 mm sized sessile polyps with odds ratio 16.41 regardless of location and histopathology. CONCLUSIONS: SSEI should be performed in colonoscopic snare polypectomy for >8 mm sized sessile polyps, and might be performed in others for prevention of bleeding at the discretion of the clinician.
Adenoma

PURPOSE: To evaluate the patterns and the treatment of instability after primary TKA. MATERIAL & METHOD: We studied 8 patients (9 cases) who had instability after TKA. We analyze the onset of symptom, patterns and main causes of instability, method of treatment, and results. The average follow-up period was 31 months. RESULT: Average onset of symptom after TKA was 10.1 month (8 day -4 years 4 month). The patterns of instability included anterior/posterior instability in 2, valgus/varus instability in 5 and global instability in 2. The treatments were thicker polyethylene exchange in 1, repair or reconstruction of collateral ligament with polyethylene exchange in 5, and revision with constrained or hinged implant in 3 when it was impossible to correct the imbalance of flexion-extension gap. All patients got stable knees and KSS functional and knee scores improved from average 55 and 56 points to 88.8 and 91 points respectively. CONCLUSION: Active repair or reconstruction of the ligament with polyethylene exchange wasone of the good options for treating instability after TKA. In cases of severe instability that could not be corrected by polyethylene exchange and repair or reconstruction of the ligament, revision with constrained or hinged implant was necessary.
Arthroplasty* ; Collateral Ligaments ; Follow-Up Studies ; Humans ; Knee* ; Ligaments ; Polyethylene

OBJECTIVE: The aims of this study were to compare the efficacy and morbidity of optimal debulking operation with those of suboptimal operation for patients with advanced gynecologic malignancies and to establish the precluding factors for performing the optimal cytoreductive surgery. METHODS: From January 1998 to December 2003, debulking operation for advanced gynecologic malignancy was performed in thirty-nine patients with ovarian cancer (32), tubal cancer (4), and primary peritoneal carcinoma (3) at the department of obstetrics and gynecology, Ghil Medical Center. Of them, 38 patients had FIGO Stage IIIC disease and only one patient had FIGO Stage IV disease. Most informations were obtained by hospital records and were analyzed retrospectively. RESULTS: The mean follow-up was 23 months (range, 1-62 months). The optimal debulking operation could be performed in 25 patients (64.1%). In multivariate analysis, the largest diameter of residual tumor was the most important prognostic factor. Two-year overall survival rate of optimally debulked patients was 86.5% and that of suboptimally debulked patients was 41.3% (p=0.015). Two-year disease free survival rates were 75.9% and 7.1%, respectively (p=0.0003). Complication rates associated with surgery were 40% in optimally debulked patients and 35.7% in suboptimally debulked patients (p=0.083). Major causes of suboptimal surgery were old age (>69 yrs), poor medical condition (cardiac problem, intraoperative unstable vital sign, bronchiectasis), no submission of permission, and involvement of the base of mesentery and small bowel. CONCLUSION: Optimal debulking operation is possible if there were no significant clinical problem and involvement of base of mesentery and small bowel. It appears acceptable surgical morbidity and better prognosis. Therefore, the surgeon should use every technique aimed at removing the tumor as much as possible.
Disease-Free Survival ; Follow-Up Studies ; Gynecology ; Hospital Records ; Humans ; Mesentery ; Multivariate Analysis ; Neoplasm, Residual ; Obstetrics ; Ovarian Neoplasms ; Prognosis ; Retrospective Studies ; Survival Rate ; Vital Signs

OBJECTIVE: Our purpose was to investigate lipid peroxide levels, total peroxyl radical-trapping antioxidative parameter (TRAP) values, and antioxidant vitamin levels in the maternal venous blood plasma of preterm premature rupture of membranes (PPROM) and to evaluate their roles of pathophysiology in PPROM. METHODS: Samples of maternal blood were obtained from women with normal pregnancy (n=23) and PPROM (n=20). Lipid peroxide levels of maternal venous blood plasma were measured by thiobarbituric acid reaction. The TRAP value of maternal venous blood plasma was measured by Wayner's method, although some reaction conditions were modified. Ascorbic acid and uric acid were measured by high performance liquid chromatography (HPLC) CoulArray detector of water-soluble antioxidants. Retinol, alpha-tocopherol, and gamma-tocopherol were measured by HPLC-CoulArray detector of fat-soluble vitamins RESULTS: Lipid peroxide levels in the maternal venous blood plasma of PPROM were significantly higher than that of normal pregnancy (3.87 +/- 0.24 vs. 3.04 +/- 0.24 nmol/mg protein, p<0.05). TRAP values in the maternal venous blood plasma of PPROM were significantly lower than that of normal pregnancy (0.33 +/- 0.02 vs. 0.40 +/- 0.02 mM, p<0.05). Ascorbic acid levels in the maternal venous blood plasma of PPROM were significantly lower than that of normal pregnancy (383.8 +/- 47.5 vs. 563.3 +/- 73.8 nmol/mg, p<0.05). There were no significant differences in maternal venous blood plasma uric acid, retinol, alpha-tocopherol, and gamma-tocopherol levels between two groups. CONCLUSION: This findings suggest that the imbalance of increased lipid peroxidation and decreased antioxidant activity in maternal blood may be involved in the pathophysiology of PPROM. Low levels of ascorbic acid in maternal blood appears to be an important determinant of PPROM.
alpha-Tocopherol ; Antioxidants ; Ascorbic Acid ; Chromatography, Liquid ; Female ; gamma-Tocopherol ; Humans ; Lipid Peroxidation* ; Membranes* ; Plasma* ; Pregnancy ; Rupture* ; Uric Acid ; Vitamin A ; Vitamins*