[Portal Biliopathy Misdiagnosed as Hilar Cholangiocarcinoma].

Portal biliopathy refers to the changes in the bile duct caused by portal vein thrombosis or obstruction. It is assumed to be caused by cavernous transformation due to the development of the venous system surrounding the bile duct, but the exact pathology is still unknown. Biliary morphologic abnormalities of portal biliopathy are discovered incidentally on radiographic images, but it is sometimes difficult to differentiate them from cholangiocarcinoma. Given the poor prognosis of cholangiocarcinoma, a surgical approach can be considered when the diagnosis is uncertain. Herein, we report a case of portal biliopathy with bile ductal wall thickening, which was diagnosed after surgical resection was performed due to the presumed diagnosis of cholangiocarcinoma.

Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical significance and natural course.

BACKGROUND: Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC. METHODS: We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods. RESULTS: Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers. CONCLUSIONS: Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

Relationship between angiography timing and angiographic visualization of extravasation in patients with acute non-variceal gastrointestinal bleeding.

BACKGROUND: Angiographic embolization is now considered the first-line therapy for acute gastrointestinal (GI) bleeding refractory to endoscopic therapy. The success of angiographic embolization depends on the detection of the bleeding site. This study aimed to identify the clinical and procedural predictors for the angiographic visualization of extravasation, including angiography timing, as well as analyze the outcomes of angiographic embolization according to the angiographic visualization of extravasation. METHODS: The clinical and procedural data of 138 consecutive patients (mean age, 66.5 years; 65.9% men) who underwent angiography with or without embolization for acute non-variceal GI bleeding between February 2008 and July 2018 were retrospectively analyzed. RESULTS: Of the 138 patients, 58 (42%) had active extravasation on initial angiography and 113 (81.9%) underwent embolization. The angiographic visualization of extravasation was significantly higher in patients with diabetes (p = 0.036), a low platelet count (p = 0.048), high maximum heart rate (p = 0.002) and AIMS65 score (p = 0.026), upper GI bleeding (p = 0.025), and short time-to-angiography (p = 0.031). The angiographic embolization was successful in all angiograms, with angiographic visualization of extravasation (100%). The clinical success of patients without angiographic visualization of extravasation (83.9%) was significantly higher than that of patients with angiographic visualization of extravasation (65.5%) (p = 0.004). In multivariate analysis, the time-to-angiography (odds ratio 0.373 [95% CI 0.154-0.903], p = 0.029) was the only significant predictor associated with the angiographic visualization of extravasation. The cutoff value of time-to-angiography was 5.0 h, with a sensitivity and specificity of 79.3% and 47.5%, respectively (p = 0.012). CONCLUSIONS: Angiography timing is an important factor that is associated with the angiographic visualization of extravasation in patients with acute GI bleeding. Angiography should be performed early in the course of bleeding in critically ill patients.

VSX1 gene and keratoconus: genetic analysis in Korean patients.

PURPOSE: The visual system homeobox 1 (VSX1) gene variants have recently been shown to be associated with keratoconus. To replicate this finding, we performed a genetic analysis of the VSX1 gene in a Korean case-control sample. METHODS: Patients with keratoconus and healthy control subjects were recruited from Seoul National University Hospital. A diagnosis of keratoconus was made based on clinical examinations and the presence of characteristic topographic features. For all patients and controls, the whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing. RESULTS: Fifty-three patients with keratoconus and 100 healthy volunteers were included. We observed 2 novel missense substitutions (Leu17Val and Val199Leu) and 1 previously reported substitution (Gly160Val) in 6 of the 53 affected probands. Because these substitutions have been identified in unaffected individuals, they were not considered to be pathogenic. No intragenic polymorphism was associated with a significantly increased risk of keratoconus. CONCLUSIONS: We cannot confirm the previously reported association of the VSX1 gene variants with keratoconus. Our results suggest that the VSX1 gene and its mutations with amino acid changes do not play a major role in the pathogenesis of keratoconus.

Relative contribution of SCA2, SCA3 and SCA17 in Korean patients with parkinsonism and ataxia.

We examined the relative significance of SCA2, SCA3 and SCA17 in Koreans patients with parkinsonism and ataxia. We recruited patients with either parkinsonism (n = 524; PD = 386 and MSA = 138) or ataxia (n = 44) as their main clinical feature for two years. These patients were screened for SCA2, SCA3 and SCA17. Six cases carried SCA2; one, SCA3; and eight, SCA17. In SCA2 patients, one patient exhibited MSA-P phenotype, and the other five exhibited ataxia. The single patient with SCA3 showed ataxia. In SCA17 patients, one patient presented ataxia, the other seven patients showed parkinsonism (three PD and four MSA-P). Dopamine transporter (DAT) imaging was performed in a subset of ataxic or parkinsonian SCA2 or SCA17, all of whom showed decreased DAT binding. In Korean population, the mutation frequencies of SCA2 and SCA17 were similar. SCA2 was a more significant cause of ataxia, whereas SCA17 was a more significant cause of parkinsonism. Contribution of SCA3 to parkinsonism was insignificant.

Molecular genetic characteristics of X-linked retinoschisis in Koreans.

PURPOSE: X-linked retinoschisis (XLRS) is a recessively inherited disorder that causes macular degeneration and resultant visual defect in young males. Many genetic studies had focused on the patients in Western countries. We characterized the mutational spectrum of the RS1 gene in Korean patients with XLRS, and aimed to provide genetic information of XLRS in an Asian population. METHODS: This study enrolled 17 unrelated probands and their mothers for molecular genetic evaluation. All exons and the flanking intronic regions of RS1 were analyzed by direct sequencing. We performed gene dosage analysis by semiquantitative multiplex PCR to rule out the possibility of duplication in a patient without a sequence variation. We also tried RT-PCR analysis in a case with a putative splicing mutation. RESULTS: Genetic tests revealed 16 Korean patients (94.1%) had RS1 mutations. In one patient, neither sequence variation nor deletion or duplication in RS1 was detected. One case with de novo mutation was confirmed by familial analysis. Identified were 14 causative mutations, three of which were novel: one missense mutation (c.227T>G, p.V76G) and two splice-site mutations (c.78+1G>T and c.78+5G>A). No obvious genotype-phenotype relationship was observed. CONCLUSIONS: A missense mutation was the predominant type, and common or founder mutations were not observed in the Korean patients in this study who had XLRS. This study provides molecular genetic characteristics about an Asian population previously unexplored. The genetic characteristics of Korean XLRS will be helpful for understanding the worldwide spectrum of RS1 mutation.

Investigation of the association between normal-tension glaucoma and single nucleotide polymorphisms in natriuretic peptide gene.

PURPOSE: The expression of natriuretic peptides in the neural bundles of the anterior portion of the optic nerves and their functions in regulating vessel tone and blood flow may suggest a possible role in the pathogenesis of glaucoma. The purpose of this study was to investigate the association between normal-tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa) and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A, and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene were determined using the restriction fragment length polymorphism and the SNaPshot methods. The genotype and allele frequencies of these polymorphisms in patients with NTG and normal controls were compared using the Fisher's exact test and the chi-square test. RESULTS: In both groups, the genotype distributions were in accordance with the Hardy-Weinberg equilibrium. There was no significant difference in the frequency of the Nppa and Npr1 alleles or genotypes in the normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease.

Investigations on the association between normal tension glaucoma and single nucleotide polymorphisms of the endothelin-1 and endothelin receptor genes.

PURPOSE: In normal tension glaucoma (NTG), intraocular pressure is within normal the range; thus, some mechanism other than increased pressure contributes to the optic neuropathy. Endothelin may be an important contributor to the development of the optic neuropathy characteristic of glaucoma. We investigated whether polymorphisms of the endothelin-1, endothelin receptor type A, and endothelin receptor type B genes were associated with NTG. METHODS: Sixty-seven Korean NTG patients and 100 healthy Korean subjects were enrolled. DNA from peripheral blood leukocytes was extracted and genotype distributions of six polymorphisms in genes encoding endothelin-1 (EDN1:c.-131dupA, EDN1:c.594G > T), endothelin receptor type A (EDNRA:c.-231G > A, EDNRA:c.*70C > G, EDNRA:c.*1222C > T), and endothelin receptor type B (EDNRB:c.831A > G) were determined. Genotype and allele distributions were compared between patients and controls. In NTG subjects, untreated baseline intraocular pressure and age at the time of diagnosis, as well as the mean deviation and pattern standard deviation values of automated static perimetry were examined for an association with these genetic polymorphisms. RESULTS: The polymorphism of EDNRA:c.*1222C > T was significantly associated with NTG (p = 0.028, OR = 3.33, 95% CI 1.05-10.24). In addition, the AA genotype of the EDNRA:c.-231G > A polymorphism was associated with a lower baseline intraocular pressure than in the GG+GA genotype group (14.0 +/- 2.8 mm Hg versus 16.2 +/- 2.3 mm Hg, p = 0.047). No polymorphism was associated with visual field parameters. CONCLUSIONS: A polymorphism of the endothelin receptor type A gene is associated with NTG.

Molecular characterization of D- Korean persons: development of a diagnostic strategy.

BACKGROUND: D- frequencies show wide racial differences: in particular, in Korean persons it is approximately 1/100th of that in Caucasians (0.15% vs. 15%). The molecular mechanisms of D- may be unique to races, and thus specific molecular diagnostic approaches are necessary for individual races. Such marked racial differences have been attributed to the founder effect. It was hypothesized that D- frequencies may be affected by genomic variations of Rhesus boxes, which are instruments of unequal crossing-over. STUDY DESIGN AND METHODS: First, the molecular basis of D- in Korean donors was characterized. A total of 264 D- persons were analyzed by performing RHD exon polymerase chain reaction (PCR), Rhesus box hybrid PCR-PstI, RHD sequencing, and a novel RHD-CE-D hybrid PCR. Second, with sequencing analysis, Rhesus boxes in Korean and Caucasian persons were compared. RESULTS: Of 264 D- Korean individuals, 74 percent completely lacked RHD, 9 percent had RHD-CE-D hybrid, and 17 percent had point mutations. Three genetic causes, RHD deletion, RHD-CE(2-9)-D2, and 1227G>A, explained 99.4 percent of D- alleles in Korean persons. Three novel mutations were also found. The identity region of 10 Rhesus boxes in Korean persons was in complete concordance with that in Caucasian persons. CONCLUSION: In this study, a molecular diagnostic strategy was established and the genetic causes of almost all D- Korean persons was able to be diagnosed with a simple decision tree. The study provides a good example of the molecular diagnosis of D- persons, especially in low-frequency areas. Our hypothesis that D- frequencies are affected by genomic variations in Rhesus boxes was excluded. Rather, racial differences may be influenced by the founder effect.