Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Background: Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. Methods: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. Results: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. Conclusion DA-2802 is considered an effective and safe treatment for patients with CHB.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒). Conclusion The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.

Moyamoya syndrome (MMS) associated with hyperthyroidism, such as Graves’ disease, is a rare condition that causes ischemic stroke with thyrotoxicity. A 43-year-old woman with symptoms of right hemiparesis was admitted. Brain magnetic resonance imaging revealed a small cerebral infarction in the left frontal lobe. Cerebral angiography revealed multi-vessel intracranial occlusive disease. Several days later, neurologic deterioration and aggravation of cerebral infarction developed due to a thyroid storm. A thyroid function test revealed the following: thyroid-stimulating hormone (TSH) ＜0.01 μunits/mL (reference range, 0.55–4.78 μunits/mL); triiodo-thyronine ＞8.0 ng/mL (reference range, 0.77–1.81 ng/mL); free thyroxine (T4) of 9.47 pmol/L (reference range, 11.4–22.6 pmol/L); and TSH receptor antibody of 37.10 U/L (reference range, 0–10 U/L). For thyroid storm management, we initiated treatment with methimazole, Gemstein’s solution, and hydrocortisone. Finally, the thyroid disease was controlled, and neurologic deficits improved. We describe a case of acute cerebral infarction combined with a thyroid storm in a patient with Moyamoya syndrome and Graves’ disease. Hyperthyroidism such as Graves’ disease should be considered in the differential diagnosis for patho-etiologic mechanisms associated with MMS. A cerebrovascular disease with a thyroid storm can lead to severe mortality and morbidity. Prompt diagnosis and strict treatment are important.

Objective: : Rapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. Methods: : From PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. Results: : Data from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32–0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32–0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34–0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37–0.80). Conclusion : This meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.

Objective: Cranioplasty (CP) and ventriculoperitoneal shunt (VPS) are required procedures following decompressive craniectomy (DC) for craniofacial protection and to prevent hydrocephalus. This study assessed the safety and efficacy of simultaneous operation with CP and VPS after DC, and determined the preoperative risk factors for postoperative complications. Methods: Between January 2009 and December 2019, 81 patients underwent CP and VPS in simultaneous or staged operations following DC. Cumulative medical records and radiologic data were analyzed using univariate analysis to identify factors predisposing patients to complications after CP and VPS. Results: CP and VPS were performed as simultaneous or staged operations in 18 (22.2%) and 63 (77.8%) patients, respectively. The overall postoperative complication rate was 16.0% (13/81). Patients who underwent simultaneous CP and VPS were significantly more likely to experience complications when compared with patients who underwent staged operations (33.3% vs. 9.6%, p<0.01). Univariate analysis revealed that simultaneous CP and VPS surgery was the only significant predictor of postoperative complications (p=0.031). Conclusion This study provided detailed data on surgical timing and complications for CP and VPS after DC. We showed that simultaneous procedures were a significant risk factor for postoperative complications.

Background: The aim of this study was to compare the effect of anemia on clinical outcomes according to age in patients with end-stage renal disease (ESRD). Methods: A total of 3,409 patients from the Clinical Research Center for ESRD were included and divided into three groups by age: age < 40 (n = 488), 40 ≤ age < 60 (n = 1,650), and age ≥ 60 (n = 1,271). We compared overall and cardiovascular mortality, and all-cause and cardiovascular hospitalization according to mean hemoglobin (Hb) concentration. Results: Among participants ≥ 60 years of age, the Hb < 10 g/dL group had greater all-cause mortality (adjusted hazard ratio [HR], 2.098; 95% confidence interval [CI], 1.567-2.808; P < 0.001) than the 10 ≤ Hb < 12 g/dL group, whereas among participants < 40 years of age, the Hb ≥ 12 g/dL group had greater mortality than the 10 ≤ Hb < 12 g/dL group. Moreover, in participants ≥ 60 years of age, the HR for all-cause hospitalization for the Hb < 10 g/dL group was significantly greater than that of the 10 ≤ Hb < 12 g/dL group (HR, 1.472; 95% CI, 1.057-2.051; P = 0.022), whereas it was significantly lower in the Hb ≥ 12 g/dL group (HR, 0.544; 95% CI, 0.362-0.820; P = 0.004) However, among participants < 40 years of age, the incidence of all-cause hospitalization did not differ according to the Hb concentration (HR, 1.273; 95% CI, 0.814-1.991; P = 0.290 for the Hb < 10 g/dL group; reference, 10 ≤ Hb < 12 g/dL; HR, 0.787; 95% CI, 0.439-1.410; P = 0.265 for Hb ≥ 12 g/dL group). Conclusion The impact of anemia on mortality was more significant in elderly ESRD patients. Strict monitoring and management of anemia should be required for elderly ESRD patients.

Objective: : Recent studies have reported that arachnoid plasty (ARP) using gelatin sponges with fibrin glue reduced the occurrence of chronic subdural hematoma (CSDH) following clipping surgery for unruptured intracranial aneurysm (UIA). This metaanalysis was conducted to collate further evidence for the efficacy of ARP in preventing postoperative CSDH. Methods: : Data of patients who underwent clipping surgery were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials by two independent reviewers. A random effects model was used to investigate the efficacy of ARP by using odd ratios (ORs) and 95% confidence intervals (CIs). A meta-regression analysis for male sex was additionally preformed. Results: : Data from six studies with 1715 patients were consecutively included. Meta-analysis revealed that ARP was significantly associated with lower rates of CSDH development after surgical clipping for UIA (ARP group vs. control group : 3.2% vs. 7.2%; OR, 0.40; 95% CI, 0.18–0.93; I2 =44.3%; p=0.110). Meta-regression analysis did not highlight any modifying effect of the male sex on postoperative CSDH development (p=0.951). Conclusion : This meta-analysis indicated that ARP reduced the incidence rates of CSDH following clipping surgery for UIA. If feasible, ARP would be implemented as an additional surgical technique to prevent postoperative CSDH development during surgical clipping of UIA.

Objective: : This study aimed to assess the relationship between increased intracranial pressure (ICP) and mastoid effusions (ME). Methods: : Between January 2015 and October 2018, patients who underwent intracranial surgery and had ICP monitoring catheters placed were enrolled. ICP was recorded hourly for at least 3 days. ME was determined by the emergence of opacification in mastoid air cells on follow-up brain imaging. C-reactive protein (CRP) levels, presence of endotracheal tube (ETT) and nasogastric tube (NGT), duration of intensive care unit (ICU) stay, duration of mechanical ventilator application, diagnosis, surgical modalities, and presence of sinusitis were recorded. Each factor’s effect on the occurrence of ME was analyzed by binary logistic regression analyses. To analyze the independent effects of ICP as a predictor of ME a multivariable logistic regression analysis was performed. Results: : Total of 61 (53%) out of 115 patients had ME. Among the patients who had unilateral brain lesions, 94% of subject (43/50) revealed the ipsilateral development of ME. ME developed at a mean of 11.1±6.2 days. The variables including mean ICP, peak ICP, age, trauma, CRP, ICU stays, application of mechanical ventilators and presence of ETT and NGT showed statistically significant difference between ME groups and non-ME groups in univariate analysis. Sex and the occurrence of sinusitis did not differ between two groups. Adding the ICP variables significantly improved the prediction of ME in multivariable logistic regression analysis. Conclusion : While multiple factors affect ME, this study demonstrates that ICP and ME are probably related. Further studies are needed to determine the mechanistic relationship between ICP and middle ear pressure.