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Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis. However, data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce.To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes.From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians' decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR.Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin4.0 g/dL, serum alkaline phosphatase100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (Hazard ratio, 6.77; 95% confidence interval, 4.81-9.52;Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.

Lenvatinib is an oral multikinase inhibitor approved for use as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, like other agents in this drug class, lenvatinib is associated with clinically important adverse events (AEs) that could adversely affect patient outcomes. Hypertension, diarrhea, decreased appetite/weight, hand-foot skin reaction, and proteinuria are among the most common AEs associated with lenvatinib therapy. This article provides strategies for the effective management of lenvatinib-associated AEs based on the expert opinion of authors and currently available literature. Due to the high risk of AEs in patients receiving lenvatinib, prophylactic measures and regular monitoring for AEs are recommended. Lenvatinib dose interruption, adjustment, or discontinuation of treatment may be required for patients who develop AEs. For grade 1 or 2 AEs, dose interruption is generally not required. For persistent or intolerable grade 2 or 3 AEs, lenvatinib treatment should be interrupted until symptoms improve/resolve to grade 0-1 or baseline levels. Thereafter, treatment should be resumed at the same or a lower dose. Disease progression may occur in patients who do not initially respond to treatment or receive a suboptimal lenvatinib dose following dose reduction, resulting in lack of efficacy. Therefore, to derive maximum treatment benefit and ensure long-term disease control, lenvatinib should be maintained at the highest possible dose when managing AEs. To conclude, lenvatinib-associated AEs can be managed with prophylactic measures, regular monitoring and symptomatic management, which can ensure continued treatment and maximum survival benefit in patients with advanced HCC receiving first-line lenvatinib therapy.

Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.

Engulfment and cell motility 1 (ELMO1) plays a crucial role in the process of migration, chemotaxis, and metastasis of tumor cells. ELMO1 has been implicated in the pathogenesis of various cancers. However, the distinct function of ELMO1 in colorectal cancer (CRC) is unclear. We determined whether ELMO1 affects the oncogenic behavior of CRC cells and investigated its prognostic value in CRC patients.We investigated the impact of ELMO1 on tumor cell behavior using small interference RNA (siRNA) in CRC cell lines, including SW480 and DLD1. The expression of ELMO1 was investigated by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) in cancer tissues and sera obtained from CRC patients.ELMO1 knockdown suppressed tumor cell proliferation in SW480 and DLD1 cells. ELMO1 knockdown-induced apoptosis through up-regulation of caspase-3, -7, and PARP activities and down-regulation of the anti-apoptotic Mcl-1 protein. ELMO1 knockdown-induced cell-cycle arrest by decreasing cyclin D1, cyclin-dependent kinase 2, 4 and 6, and the 25C cell division cycle (CDC25C). ELMO1 knockdown suppressed tumor cell invasion and migration. The expression of E-cadherin was increased, while that of Vimentin and Claudin 1 decreased following ELMO1 knockdown. The phosphorylation levels of PDK1, Akt, and GSK-3β and were down-regulated after ELMO1 knockdown. The expression of ELMO1 was found up-regulated in cancer tissues and sera taken from CRC patients. ELMO1 expression was significantly associated with tumor stage, lymph node metastasis, distant metastases, and poor survival.ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Background/Aims We retrospectively compared the effect of endoscopic variceal obturation (EVO) and retrograde transvenous obliteration (RTO) in acute cardiofundal variceal bleeding. Methods Patients with acute cardiofundal variceal bleeding treated with EVO or RTO at two hospitals were included. Results Ninety patients treated with EVO and 86 treated with RTO were analyzed. The mean model for end-stage liver disease score was significantly higher in EVO group than in RTO group (13.5 vs. 11.7, P = 0.016). The bleeding control rates were high (97.8% vs. 96.5%), and the treatment-related complication rates were low in both EVO and RTO groups (2.2% vs. 3.5%). During the median follow-up of 18.0 months, gastric variceal (GV) and esophageal variceal rebleeding occurred in 34 (19.3%) and 7 (4.0%) patients, respectively. The all-variceal rebleeding rates were comparable between EVO and RTO groups (32.4% vs. 20.8% at 2-year, P = 0.150), while the GV rebleeding rate was significantly higher in EVO group than in RTO group (32.4% vs. 12.8% at 2-year, P = 0.003). On propensity score-matched analysis (71 patients in EVO vs. 71 patients in RTO group), both all-variceal and GV rebleeding rates were significantly higher in EVO group than in RTO group (all P P = 0.005). The mortality rates were similar between two groups (P = 0.597). Conclusions Both EVO and RTO effectively controlled acute cardiofundal variceal bleeding. RTO was superior to EVO in preventing all-variceal and GV rebleeding after treatment, with similar survival outcomes.

Background Self-expandable metal stent (SEMS) placement is commonly used as a bridge to surgery (BTS) for left-sided malignant colorectal obstruction (MCO). However, the optimal time interval between BTS stenting and surgery for left-sided MCO is unclear, and the results of previous studies are conflicting. This study aimed to determine the differences in clinical outcomes according to the time interval between BTS stenting and surgery in left-sided MCO. Methods Data from 594 patients who underwent SEMS placement for MCO between January 2009 and December 2018 were reviewed. Among them, 148 patients who underwent SEMS placement as BTS treatment and curative surgery were enrolled. The enrolled patients were divided into three groups according to the interval between BTS stenting and surgery: group 1 (interval ≤2 weeks), group 2 (interval 2–3 weeks), and group 3 (interval >3 weeks). Results Group 2 and 3 patients underwent significantly higher rates of laparoscopic surgery than those in group 1 (83.7, 81.0 vs. 53.2 %, respectively; P=0.003, P=0.003, respectively). Also, rates of stoma formation directly after resection were significantly higher in group 1 compared to groups 2 and 3 (21.3 vs 2.3, 6.9%, respectively; P=0.008, P=0.043, respectively). Bridging interval had no effect on SEMS-related complications, resection-related complications, 90-day mortality, permanent stoma formation, 3-year disease-free survival, and 3-year overall survival. Conclusions A bridging interval of > 2 weeks between BTS stenting and surgery for left-sided MCO is preferable for lower stoma formation rates and higher rates of laparoscopic approach operation, with no difference in short-term and long-term outcomes including complication, mortality, and survival.

Background: Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment, which is the main reason for dose de-escalation or discontinuation of sorafenib in hepatocellular carcinoma (HCC) patients. Here, we aimed to investigate the role of urea cream in the prevention or amelioration of HFSR severity. Methods: HCC patients at 13 hospitals in Korea were recruited from May 2016 to May 2018. Patients were treated with placebo cream and urea cream for 12 weeks concomitantly with sorafenib treatment. Development of HFSR, score for Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire, and adverse event were assessed at 2, 4, 8, and 12 weeks. Findings: Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analyzed. The urea cream group showed lower cumulative incidence of any grade of HFSR (Log-rank, p=0.247) and severe HFSR of grade 2 or higher (Log-rank, p = 0.394) without statistical significance. In the incidence by time point, the development of severe HFSR of grade 2 or higher was significantly lower in the urea cream group than in the placebo control group at two weeks (13.8% vs. 23.9%, p=0.042). The urea cream group showed a significantly improved questionnaire score compared to the placebo control group (11.8 vs. 19.7, p=0.014) at 12 weeks. Interpretation: Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream could be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. Trial Registration: This study was registered at ClinicalTrial.gov (NCT03212625). Funding Statement: The Korea Liver Cancer Association and Hanmi Pharmacy (IIT-CAV-004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent. This study was approved by the institutional review board of each participating institute (2016GR0350).

Interventional medical radiation workers represent an under-studied population worldwide, although they receive relatively high occupational radiation doses. This study aimed to estimate the lifetime cancer risk from occupational radiation exposure among workers at interventional radiology departments. A field survey of interventional medical workers in nationwide branches of the Korean Society of Interventional Radiology was conducted in 2017. Organ-specific radiation doses were estimated using national dose registry data and conversion coefficients provided by the International Commission on Radiological Protection. Lifetime attributable risk (LAR) and lifetime fractional risk (LFR) were calculated based on realistic exposure scenarios using a radiation risk assessment tool. LARs from occupational radiation exposure until the age of retirement for all cancers combined were 338 (90.3–796.1), 121 (33.5–288.7), and 156 (41.1–390.6) per 100,000 individuals for male radiologists, male radiologic technologists, and female nurses, respectively. LFR for all cancers combined ranged from 0.22% (0.06–0.53) to 0.63% (0.17–1.47). Regarding the organ site, the highest LAR and LFR among all groups were observed for thyroid cancer. This study provides timely evidence of potential cancer burden from the current levels of occupational radiation exposure among workers at interventional radiology departments. The risks varied by occupational groups, and workers, particularly interventional radiologists, need to be carefully monitored for radiation.

Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries.To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR.This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

Background For patients with malignant ureteral obstruction or stricture who require long-term internal drainage, plastic double-J stents (DJ stents) represent the mainstay of therapeutic strategies. DJ stents should be replaced at least once every 6 months to avoid infection or obstruction. Although DJ stents are generally replaced under cystoscopy, successful fluoroscopy-guided retrograde replacement of DJ stents in the interventional suite has been described in the literature. Methods Between April 2004 and May 2020, we exchanged 143 DJ stents in 19 male and 22 female patients under fluoroscopic guidance using Nelaton catheters, snare catheters, and 8F DJ stents. All procedures were performed with patients under sedation and local anesthesia. There were 39 patients with malignant ureteral obstruction and two patients with benign ureteral strictures. This study was approved by the Institutional Review Board. Technical success, clinical success, complications, procedure time, and mean interval between two procedures were retrospectively reviewed, and the factors affecting the success rate of the procedure were analyzed. Results Obstruction was detected at the abdominal ureter in 4 patients, pelvic ureter in 29 patients, and intravesical ureter in 8 patients. Twenty-six patients underwent two or more sessions of the procedures, whereas 15 patients underwent single-session procedures. Total 34 outpatient-based procedures and 109 inpatient-based procedures were performed. Technical success and clinical success were achieved in 94.4% (135/143) and 93.3% (126/135) procedures, respectively. Mean procedure time was 21.5 min (range 9–192 min). Mean procedure interval was 101.8 days (range 5–306 days). Technical success was negatively affected by male sex and obstruction at the pelvic ureter and was positively affected by previous successful exchange. Left-sided ureteral stent placement and old age negatively influenced clinical success. Septic shock occurred in one patient and was treated with antibiotics. Conclusion Fluoroscopy-guided trans-urethral exchange of DJ stents is an effective and less painful procedure.

BackgroundTo explore the feasibility and safety of natural killer (NK) cell therapy in HCC, we performed a prospective, open-label, phase I trial to evaluate the synergistic effect of locoregional high-dose autologous NK cell therapy in combination with hepatic arterial infusion chemotherapy (HAIC).MethodsPatients with locally advanced HCC who were refractory to the standard treatment were eligible for this study. Patients received expanded and activated NK cells for 5 consecutive days in a dose-escalating manner (dose 2.5×108, 5×108, 10×108 NK cells/injection) through hepatic arterial infusion following 4 cycles of HAIC with 5-fluorouracil (750 mg/m2) and cisplatin (25 mg/m2). The primary endpoint was the safety of NK cell-based immunotherapy, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immunologic responses.ResultsOf the 11 patients enrolled, the confirmed ORR was 63.6% (complete response [CR]: 36.4%, confirmed partial response [PR]: 27.3%). Stable disease (SD) and progressive disease (PD) were observed in two patients (18.2%) each, resulting in a disease control rate (DCR) of 81.8%. The median PFS and OS were 10.3 and 41.6 months, respectively. There were no incidences of decompensation or severe adverse events during HAIC, and no adverse events related to NK cell infusion were noted.ConclusionThe combination of HAIC and locoregional high-dose NK cell therapy is a safe and effective treatment for locally advanced HCC patients who were refractory to the standard treatment. This result warrants further development of this novel treatment to establish its efficacy in HCC. Clinical Trial Registrationcris.nih.go.kr, identifier KCT0003973.

CD47 is an immunoregulatory protein that is found on the cell surface and plays significant roles in cellular functions such as proliferation, apoptosis, migration, and immune homeostasis. CD47 is overexpressed in various human cancers and is associated with tumor development, progression, and poor prognosis. In this study, we analyzed the expression of CD47 to determine whether it affected the oncogenic behavior of colorectal cancer (CRC) and investigated the prognostic value of CD47 expression in patients with CRC. We investigated 468 patients with CRC who underwent curative surgery and examined the expression of CD47 in tumor and lymph node tissues by performing RT-PCR and immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined via a TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. CD47 expression was increased in human CRC tumors and metastatic lymph nodes compared with normal colorectal mucosa and non-metastatic lymph node tissues. CD47 expression was significantly associated with perineural invasion, lymphovascular invasion, cell differentiation, cancer stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The mean apoptotic index and microvessel density value of CD47-positive tumors were significantly higher than those of CD47-negative tumors. However, no significant difference was observed between CD47 expression and Ki-67 labeling index or lymphatic vessel density. These results indicate that CD47 mediated the progression of CRC by inducing tumor cell apoptosis and angiogenesis.

OBJECTIVES: Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).METHODS: We used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).RESULTS: Among the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.CONCLUSIONS: As of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.

Background Thoracic endovascular aneurysm repair (TEVAR) has been used as a primary treatment for blunt traumatic aortic injury (TAI). However, the outcomes of midterm surveillance of Seal® stent-graft durability for TAI have not been extensively studied. Thus, we aimed to report the midterm outcomes of TEVAR using the Seal® stent graft for blunt TAI. Methods Patients with blunt TAI treated with TEVAR using the Seal® thoracic stent graft between 2007 and 2013 in Korea were included. Midterm outcomes included technical/clinical success, in-hospital death, aorta/procedure/device-related adverse events, secondary procedures, and 30-day and all-cause mortality. Results A total of 99 patients (54% men; mean age, 48 years) were included. Grade III or higher injuries were present in 95% of patients, including 15 free ruptures of the thoracic aorta, and 64% of injuries were located in zone III. The median procedure and hospitalization duration were 90 min and 11 days, respectively. The technical success rate was 98%. The number of in-hospital mortalities (n = 8) and stroke (n = 2) were observed at 30 days. Late stroke and paraplegia (>30 days) were not observed during the mean 49 ± 26 months of follow-up (median, 48 months; range, 0–117 months). There were no aorta-related mortalities or conversions to open repair. Secondary procedures were performed in 8 patients, all of which were carotid-subclavian bypasses for delayed left subclavian occlusion. The all-cause mortality rate was 5% at 30 days and 8% at 1 year. The survival rate was 95% at 30 days, 92% at 1 year, 92% at 3 years, and 89% at 5 years. One type Ia endoleak occurred at 18 months after the procedure. Conclusions TEVAR with the Seal® stent graft for TAI showed favorable midterm outcomes. The incidence of major adverse events after the procedure was low.

Background/Aims Patients with Hansen’s disease are the most vulnerable to hepatitis C. However, no data on the treatment efficacy of direct-acting antiviral agents (DAAs) are available in this group. Therefore, we elucidated the prevalence and clinical outcomes of hepatitis C in persons affected by leprosy in Sorokdo, Jeollanam-do, Korea. Methods We retrospectively included 50 leprosy patients with positive hepatitis C virus (HCV) RNA test results (group A) hospitalized at the Sorokdo National Hospital from May 2016 to March 2018 and 73 patients with chronic hepatitis C who were treated with DAAs at the Chonnam National University Hospital (group B) from May 2016 to December 2017. Results Overall, at the Sorokdo National Hospital, positive HCV antibody and HCV RNA rates were 18.4% and 11.0%, respectively. The mean participant age was 76.5±7 years, and 58% of participants were men. The genotypes were type 1b in 44% (22 out of 50) and type 2 in 56% (28 out of 50). Sustained virologic response was achieved at a rate of 95.5% (21/22) in genotype 1b and 92.9% (26/28) in genotype 2 patients. Ribavirin-induced hemolytic anemia occurred in 57.1% (16/28) of patients with genotype 2. Among these, 28.5% (8/28) received blood transfusions. Conclusions Treatment efficacy was not different between the leprosy-affected population and the general population. However, severe ribavirin-induced hemolytic anemia requiring transfusion was present in 28.5% of genotype 2 patients. Therefore, we suggest ribavirin-free DAAs for the treatment of genotype 2 hepatitis C in leprosy-affected persons in the future.

Self-expandable metal stent (SEMS) placement is commonly used for palliation of left-sided malignant colorectal obstruction (MCO). However, right-sided MCO is usually treated surgically. Recent studies that compared palliative SEMS insertion and emergency surgery in right-sided MCOs have reported conflicting results. This study aimed to compare the effectiveness of palliative SEMS placement in left-sided MCOs and right-sided MCOs and to investigate the predictive factors for clinical success and risk factors for complications. Data from 469 patients who underwent palliative SEMS placement for MCO at 6 hospitals in the Honam province of South Korea between 2009 and 2018 were reviewed. Among them, 69 patients with right-sided MCO and 400 patients with left-sided MCO who underwent SEMS placement for palliative purposes were enrolled. Clinical success, overall survival, complications, and predictive factors for clinical success and risk factors for complications were included as the main outcome measures. The clinical success rates were 97.1% (65/67) in right-sided MCO patients and 88.2% (353/400) in left-sided MCO patients. Complications including stent migration, tumor ingrowth, outgrowth, perforation, bacteremia/fever, and bleeding occurred in 10.1% (7/69) of right-sided MCO patients and 19.9% (79/400) of left-sided MCO patients. The mean overall survival of right-sided MCO was 28.02 months and 18.23 months for left-sided MCO. In multivariate logistic regression analysis, T3 stage tumors and the use of uncovered stents were significant factors for the clinical success of SEMS. The use of covered stents and performance status score of 0 to 2 were independent significant risk factors for complications. Palliative SEMS placement in right-sided MCO showed better clinical success rates than left-sided MCO. The use of uncovered stents is recommended for higher clinical success rates and lower complication rates.

BACKGROUND Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma (HCC) patients treated by immunotherapy. AIM To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients. METHODS From September 2019 to March 2020, we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second- or third-line systemic treatment. Fecal samples were collected before the start of immunotherapy. Fecal samples of patients with progression during treatment were collected at the time of progression, and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up. Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench. Microbiome data were analyzed according to therapeutic response. RESULTS All 8 patients were male, of which 6 had underlying chronic hepatitis B. A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy (P = 0.036). The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response. There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used. Several taxa specific to therapeutic response were designated as follows: Dialister pneumosintes, Escherichia coli, Lactobacillus reteri, Streptococcus mutans, Enterococcus faecium, Streptococcus gordonii, Veillonella atypica, Granulicatella sp., and Trchuris trichiura for the non-responders; Citrobacter freundii, Azospirillum sp. and Enterococcus durans for the responders. Of note, a skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response, whereas the presence of Akkermansia species predicts a good response. CONCLUSION The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.

Purpose: Compared with the conventional approach, the benefits of the transjugular approach in endovascular intervention for hemodialysis access avoids complications due to direct puncture and reduces direct radiation exposure to the hands of operator. The aim of this non-inferiority study was to evaluate the efficacy of the transjugular approach in endovascular intervention for hemodialysis access comparing with conventional approach. Methods: We retrospectively assessed endovascular intervention for hemodialysis access performed in our hospital from 2012 to 2016, divided into the conventional approach group and the transjugular approach group. The hemodialysis access survival rate, re-intervention survival rate, and lesion characteristics were comparatively evaluated. Results: We included 223 cases in 118 patients (146 cases with conventional approaches and 77 cases with transjugular approaches). There was a higher incidence of thrombosis with the conventional approach (p < 0.001), however, no significant difference in the hemodialysis access type or main lesion location. The transjugular approach showed either a better hemodialysis access survival rate (p = 0.017) and a trend toward improved re-intervention survival rate (p = 0.098) than the conventional approach. Following classification according to the presence of thrombus, there was no significant difference in either the hemodialysis access survival rate or the re-intervention survival rate between the approaches with or without thrombus. Conclusion: The transjugular approach could be performed in most cases and was similar to the conventional approach in terms of outcomes. The transjugular approach should be considered as an alternative to either replace or use in combination with the conventional approach in endovascular intervention for hemodialysis access.

Recent studies report a significant age-specific increase in hepatocellular carcinoma (HCC) development among persons over 75 years old. Therefore, there is an urgent need to determine the optimal treatment strategy in elderly patients with HCC. This systemic review examines the clinical characteristics, efficacy, and safety of first-line treatment modalities. The literature was searched regarding epidemiology and clinical outcomes in elderly patients (age ≥75 years) undergoing first-line treatment for HCC. Causative or comorbid conditions of HCC in elderly patients differed from those in younger patients. Radiofrequency ablation may be effective and safe in early stages. Surgical resection may also be feasible in the early stages for selected patients. Transarterial chemoembolization may be safe and effective for intermediate HCC, and sorafenib may be feasible in elderly patients with advanced HCC. Prospective randomized trials are needed to establish the treatment strategy for elderly patients with HCC.

The degree of height loss varies among individuals, and excessive height loss can be a vertebral fracture or bone loss manifestation. The objective of this study was to examine the relationships between height loss and bone mineral density (BMD) and to assess the prevalence of osteoporosis according to the height loss quartiles. Data from the Korea National Health and Nutrition Examination Survey were analyzed. A total of 2799 participants more than 60 years old were included and subdivided into quartiles according to height loss (Q1–Q4). Height loss was calculated with the difference between the self-reported maximum adult height and the actual measured height. BMD was measured by dual-energy X-ray absorptiometry at the total femur (TF), femoral neck, and lumbar spine. Multivariable linear and logistic regression analyses were conducted to study the height loss-BMD and the height loss-osteoporosis prevalence relationships, respectively. After adjustments for all covariates, height loss was negatively associated with BMD at all the 3 sites (TF and lumbar spine, p 0.001; femoral neck, p = 0.002) in men, but only at TF ( p = 0.008) in women. Men with Q4 height loss had an increased prevalence of osteoporosis compared with those with Q1 (odds ratio = 2.092 and 95% confidence interval = 1.076–4.068). In women, the prevalence of osteoporosis was not associated with height loss. In conclusion, Q4 height loss in elderly men was associated with the increased prevalence of osteoporosis in Korea.

To determine an accurate method for localizing rectal cancer using the distance from the anal verge on preoperative MRI. This prospective study included 50 patients scheduled for MRI evaluation of rectal cancer. After rectal filling with gel, MRI was performed with two markers attached at the anal verge. The distance between the tumor and the anal verge on a sagittal T2-weighted image (T2WI) was measured independently by two radiologists using six methods divided into three groups of similar measurement approaches, and compared to those obtained on rigid sigmoidoscopy. The anal verge location relative to the external anal sphincter was assessed on oblique coronal T2WI in reference to the markers. Correlation analysis was performed using the intraclass correlation coefficient (ICC) for verification, and a paired t test was used to evaluate the mean differences. The highest correlation (ICC 0.797–0.815) and the least mean difference (0.74–0.85 cm) with rigid sigmoidoscopy, and the least standard deviation (3.12–3.17 cm) were obtained in the direct methods group using a straight line from the anal verge to the tumor. The anal verge was localized within a range of − 1.4 to 1.5 cm (mean − 0.31 cm and − 0.22 cm) from the lower end of the external anal sphincter. The direct methods group provided the most accurate tumor distance among the groups. Among the direct methods, we recommend the direct mass method for its simplicity. Despite minor differences in location, the lower end of the external anal sphincter was a reliable anatomical landmark for the anal verge.

The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p

Background/Aims Regorafenib has been approved as a second-line systemic therapy for hepatocellular carcinoma (HCC) patients after the phase III RESORCE trial. This study analyzed real-world data to assess the clinical effectiveness and safety of regorafenib compared to the RESORCE trial. Methods This multicenter cohort study included HCC patients treated with regorafenib after sorafenib (n = 133). We evaluated the time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety in patients receiving regorafenib along with the predictors of prognosis. Results The median age was 60 years and 81.2% patients were men. Hepatitis B virus infection (68.4%) was the commonest etiology. Most patients were classified as Child-Pugh A (98.5%) and had extrahepatic metastasis (84%) and vascular invasion (45.1%). This study demonstrated similar characteristics apart from more frequent hepatitis B etiology and more vascular or extrahepatic involvement compared with the RESORCE trial. An objective response rate of 12.5% was obtained for response assessment (n = 112); the disease control rate was 34.8%. Thirty-eight patients died during follow-up. With regorafenib, the median OS, PFS, and TTP were 10.0, 2.7, and 2.6 months, respectively. In the exploratory analysis after sorafenib administration, the median OS was 25.8 months. The rate of response and survival were comparable to those in the RESORCE trial. Child-Pugh score > 5, alpha-fetoprotein > 400 ng/ml, and TTP for sorafenib ≥ median were independently associated with OS. Conclusions This real-word regorafenib study showed comparable effectiveness and safety to the RESORCE trial. Regorafenib improves the prognosis of patients with prolonged TTP during previous sorafenib therapy.

Background/aims The success rate of endoscopic variceal ligation (EVL) is about 85-94%. There is only a few studies attempting to determine the cause of EVL failure, and to date, on-site rescue treatments remains unestablished. This study aimed to elucidate the risk factors for EVL failure and the effectiveness of on-site rescue treatment. Methods Data of 454 patients who underwent emergency EVL at Chonnam National University Hospital were retrospectively analyzed. Enrolled patients were divided into two groups: the EVL success and EVL failure groups. EVL failures were defined as inability to ligate the varices due to poor endoscopic visual field, or failure of hemostasis after band ligation for the culprit lesion. Results Forty-seven patients experienced EVL failure. In the multivariate analysis, male patients, initial hypovolemic shock, active bleeding on endoscopy, and history of previous EVL were independent risk factors for EVL failure. During endoscopic procedure, we came across the common causes of EVL failure, including unsuctioned varix due to previous EVL-induced scars followed by insufficient ligation of the stigmata and inability to ligate the varix due to poor endoscopic visual field. Endoscopic variceal obturation using N-butyl-2-cyanoacrylate (48.9%) was the most commonly used on-site rescue treatment method, followed by insertion of Sangstaken Blakemore tube (14.9%), and EVL retrial (12.8%). The rescue treatments successfully achieved hemostasis in 91.7% of those in the EVL failure group. Conclusions The risk factors of EVL failure should be considered before performing EVL, and in case of such scenario, on-site rescue treatment is needed.

Background Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 − 11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov NCT01839773.

The effect of catheter diameter on left innominate vein stenosis in breast cancer patients after totally implantable venous access port placement.Purpose:To evaluate the effect of catheter diameter on left innominate vein stenosis in breast cancer patients after placement of totally implantable venous access ports.Materials and methods:Totally implantable venous access ports were placed via the left internal jugular vein in 241 women with right breast cancer from January 2010 to December 2014 (mean age, 51.5 years; range, 19–83 years). There were 67 totally implantable venous access ports with a 6.5F catheter and 142 totally implantable venous access ports with an 8F catheter. Medical records were retrospectively reviewed. The presence of significant left innominate vein stenosis and tip location of the catheter was evaluated on chest computed tomography images. Statistical analysis was performed.Results:Left innominate vein stenosis developed in 1 (1.5%) and 13 (9.2%) patients after implantation with 6.5 and 8F catheters, respectively. Difference in the cumulative incidence of left innominate vein stenosis was statistically significant between the two groups (log rank test p-value: 0.002). In Cox regression analysis, the hazard ratio for left innominate vein stenosis was 20.766 ( p = 0.005) for an 8F catheter.Conclusion:The incidence of left innominate vein stenosis was higher after implantation of totally implantable venous access ports with 8F catheter rather than with 6.5F catheter. Considering that using 8F catheter versus 6.5F catheter has no advantage in terms of performance of the device, the results of our study suggest that ports with catheters >7F should be avoided.

Background Hepatitis is the most important cause of hepatocellular carcinoma in Korea. This study evaluated the socioeconomic differences in self- and family awareness of hepatitis status among hepatitis B and C carriers and their cohabitants in rural Korea. Methods In total, 5,017 randomly selected rural residents participated in a seroepidemiologic and questionnaire survey. We found 326 hepatitis B surface antigen carriers or hepatitis C antibody carriers and 310 family members cohabiting with members of this group. Results Among the hepatitis B carriers and their family members, 48.1% were aware of their own status and 36.7% were aware of their cohabitant's hepatitis status, respectively. Only 28.1% of the hepatitis C carriers were aware of their own status, and only 23.3% of their cohabiting family members knew about their family member's hepatitis C status. A multivariate analysis including health-related factors, such as alcohol consumption, family history of liver disease, and recent acupuncture history, found that self-awareness was significantly lower in the older group and significantly higher in the more educated and higher-income groups. Family awareness was also increased in those working in salaried jobs. Conclusions Socioeconomic disparities in awareness of hepatitis status were found among hepatitis carriers and their families.

To evaluate preoperative CT features that predict the development of postoperative inguinal hernia after robot-assisted laparoscopic radical prostatectomy (RALRP). We enrolled 160 men who underwent CT, subsequent RALRP, and at least three years of follow-up. CT was retrospectively reviewed in consensus by two radiologists for the presence of asymmetric spermatic cord fat and scrotal fluid collection. The diagnostic power of each CT feature for the development of postoperative inguinal hernia was calculated. Multiple logistic regression was performed to evaluate the association between CT features, clinical variables, and postoperative inguinal hernia. Surgically confirmed postoperative inguinal hernia developed in 17 patients. Asymmetric spermatic cord fat was demonstrated in 13 patients, and scrotal fluid collection was seen in 59 patients. The diagnostic values of asymmetric spermatic cord fat and scrotal fluid collection for postoperative inguinal hernia were 58.8% and 88.2% sensitivity, 97.9% and 69.2% specificity, 76.9% and 25.4% positive predictive value, 95.2% and 98.0% negative predictive value, and 93.8% and 71.3% accuracy, respectively. On multiple logistic regression analysis, asymmetric spermatic cord fat, scrotal fluid collection, and low BMI were significant predictive factors for the development of postoperative inguinal hernia (odds ratios: 135.8, 31.6, and 0.7, respectively). The presence of asymmetric spermatic cord fat or scrotal fluid collection was significantly associated with the development of postoperative inguinal hernia.

Malformin A1 (MA1), a cyclic pentapeptide isolated from Aspergillus niger, has been found to possess a range of bioactive properties including antibacterial activity. However, it is unclear whether MA1 exerts an anticancer effect or not. In this study, we conducted in vitro experiments to investigate its anticancer properties in human colorectal cancer cells. The effect of MA1 on human colorectal cancer cells, SW480 and DKO1, was examined by the WST-1 cell viability assay, inverted microscopy, 5-bromo-2-deoxyuridine (BrdU) incorporation, flow cytometry, DNA fragmentation, wound healing, Transwell assays, and western blotting. MA1 treatment showed potent cytotoxic activities on human colorectal cancer cells. MA1 treatment induced apoptosis by activating the poly(ADP-ribose) polymerase (PARP), caspase‑3, -7, and -9. MA1 treatment led to the increase in p53 upregulated modulator of apoptosis (PUMA) and the decrease in X-linked inhibitor of apoptosis protein (XIAP) and Survivin. In addition, MA1 treatment induced cell cycle arrest in the sub-G1 phase. The pan-caspase inhibitor, Z‑VAD‑FMK, attenuated these MA1-induced apoptotic effects on human colorectal cancer cells. Moreover, MA1 treatment suppressed tumor cell migration and invasion. The phosphorylation level of p38 was upregulated by MA1 treatment, and the inhibitor of p38, SB203580, attenuated the MA1-induced p38 phosphorylation as well as caspase‑3 and PARP activation. These results indicate that MA1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through the stimulation of the p38 signaling pathway.

To investigate whether diffusion-weighted imaging (DWI) aids pre-operative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate additional lesions in breast cancer patients. DCE-MRI and DWI were performed on 131 lesions, with available histopathological results. The apparent diffusion coefficient (ADC) of each lesion was measured, and the cut-off value for differentiation between malignant and benign lesions was calculated. A protocol combining the ADC cut-off value with DCE-MRI was validated in a cohort of 107 lesions in 77 patients. When an ADC cut-off value of 1.11 × 10-3 mm2/s from the development cohort was applied to the additional lesions in the validation cohort, the specificity increased from 18.9% to 67.6% (P < 0.001), and the diagnostic accuracy increased from 61.7% to 82.2% (P = 0.05), without significant loss of sensitivity (98.6% vs. 90.0%, P = 0.07). The negative predictive values of lesions in the same quadrant had decreased, as had those of lesions ≥1 cm in diameter. The ADC cut-off value in the validation cohort was 1.05 × 10-3 mm2/s. Additional implementation of DWI for breast lesions in pre-operative MRI can help to obviate unnecessary biopsies by increasing specificity. However, to avoid missing cancers, clinicians should closely monitor lesions located in the same quadrant or lesions ≥1 cm. • DWI can be used to further differentiate lesions during pre-operative cancer staging. • ADC cut-off values were similar in the development and validation cohorts. • DWI improves both PPV and NPV in cases of multicentric lesions. • DWI improves both PPV and NPV in lesions

Accurate characterization of renal masses is essential for ensuring appropriate management. Low T2 signal intensity is a common feature of papillary renal cell carcinoma and fat-poor angiomyolipoma. Nonetheless, other types of renal cell carcinoma, oncocytoma, hemangioma, lymphoma, leiomyoma, and urothelial cell carcinoma also can show low signal intensities on T2-weighted imaging (T2WI). Histopathologic features that can lead to low T2 signal intensities in renal tumors include smooth muscle component, papillary architecture, a high nucleus-to-cytoplasm ratio, and hemorrhage. To establish an appropriate differential diagnosis for renal tumors on MRI, it is necessary to understand the relationship between the MR signal intensities and the histopathologic and morphologic features, in addition to contrast enhancement patterns and diffusion characteristics of the tumors.

Background The safety of gadolinium-based contrast agents is of fundamental importance. Purpose To determine the frequency and severity of immediate-type adverse reactions to approved doses of gadoteridol in patients referred for routine gadoteridol-enhanced MRI in actual clinical practice settings. Study type Prospective, observational. Population In all, 6163 subjects were enrolled (mean age: 56.7 ± 15.4 years; range: 6-93 years). Field strength/sequence 1.5T and 3.0T. Assessment Assessment was of immediate adverse reactions by the investigating radiologist using the MedDRA System Organ Class and preferred term. Statistical tests Summary statistics for continuous variables, descriptive statistics for demographic characteristics. Results Overall, 19 adverse events occurred in 13 (0.21%) patients, of which 15 in 10 (0.16%) patients were considered related to gadoteridol administration. These events were evenly distributed between male and female subjects and all occurred in adults. Twelve of the 15 related events in eight (0.13%) patients were considered mild in intensity (rapidly self-resolving), while the remaining three events in two patients (0.03%) were considered moderate in intensity. None were of severe intensity and no serious adverse events occurred. Data conclusion The rate of immediate-type adverse events following exposure to approved doses of gadoteridol is extremely low, and mostly limited to transient and self-resolving symptoms. Level of evidence 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:861-868.

Forkhead box A1 (FOXA1) functions as a tumor suppressor gene or an oncogene in various types of cancer; however, the distinct function of FOXA1 in colorectal cancer is unclear. The present study aimed to evaluate whether FOXA1 affects the oncogenic behavior of colorectal cancer cells, and to investigate its prognostic value in colorectal cancer. The impact of FOXA1 on tumor cell behavior was investigated using small interfering RNA and the pcDNA6‑myc vector in human colorectal cancer cell lines. To investigate the role of FOXA1 in the progression of human colorectal cancer, an immunohistochemical technique was used to localize FOXA1 protein in paraffin‑embedded tissue blocks obtained from 403 patients with colorectal cancer. Tumor cell apoptosis and proliferation were evaluated using a terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling assay and Ki‑67 immunohistochemical staining, respectively. FOXA1 knockdown inhibited tumor cell invasion in colorectal cancer cells, and induced apoptosis and cell cycle arrest. FOXA1 knockdown activated cleaved caspase‑poly (ADP‑ribose) polymerase, upregulated the expression of p53 upregulated modulator of apoptosis, and downregulated BH3 interacting domain death agonist and myeloid cell leukemia‑1, leading to the induction of apoptosis. FOXA1 knockdown increased the phosphorylation level of signal transducer and activator of tran-scription‑3. By contrast, these results were reversed following the overexpression of FOXA1. The overexpression of FOXA1 was associated with differentiation, lymphovascular invasion, advanced tumor stage, depth of invasion, lymph node metastasis and poor survival rate. The mean Ki‑67 labeling index value of FOXA1‑positive tumors was significantly higher than that of FOXA1‑negative tumors. However, no significant association was observed between the expression of FOXA1 and the mean apoptotic index value. These results indicate that FOXA1 is associated with tumor progression via the modulation of tumor cell survival in human colorectal cancer.

The national dose registry (NDR) contains essential information to help protect radiation workers from radiation-related health risks and to facilitate epidemiological studies. However, direct validation of the reported doses has not been considered. We investigated the validity of the NDR with a personal dosimeter monitoring conducted among Korean interventional radiologists. Among the 56 interventional radiologists, NDR quarterly doses were compared with actively monitored personal thermoluminescent dosimeter (TLD) doses as standard measures of validation. We conducted analyses with participants categorized according to compliance with TLD badge-wearing policies. A correlation between actively monitored doses and NDR doses was low (Spearman ρ = 0.06), and the mean actively monitored dose was significantly higher than the mean NDR dose (mean difference 0.98 mSv) in all participants. However, interventional radiologists who wore badges irregularly showed a large difference between actively monitored doses and NDR doses (mean difference 2.39 mSv), and participants who wore badges regularly showed no apparent difference between actively monitored doses and NDR doses (mean difference 0.26 mSv). This study indicated that NDR data underestimate the actual occupational radiation exposure, and the validity of these data varies according to compliance with badge-wearing policies. Considerable attention is required to interpret and utilize NDR data based on radiation workers’ compliance with badge-wearing policies.

Background: Feasibility of single-session mechanical thrombetomy, without thrombolytics, for the treatment of the subacute deep vein thrombosis (DVT) of the lower extremity remains poorly described. Purpose: To evaluate the feasibility and efficacy of single-session endovascular treatment of DVT of the lower extremity that is more than 10 days old. Materials and Methods: From January 2010 to December 2013, single-session endovascular treatment was performed in 21 limbs of 21 patients (8 men and 13 women) with DVT more than 10 days old at our hospital. The mean age of the thrombosis was 21.5 days (range 11-45 days). Two patients had malignancy-related obstructions. A 14F introducer sheath was inserted through the popliteal vein followed by aspiration thrombectomy with a large bore catheter. Balloon angioplasty and/or maceration of the thrombus were added when needed. Stent insertions were performed for patients with combined iliac vein stenosis. Technical success, clinical success, mean procedure time, and complications were evaluated. Results: The technical success rate was 90.5% (19 of 21 patients). Among the 19 successful cases, aspiration thrombectomy alone was performed in 16 (84.2%) patients, additional balloon angioplasty of the femoral vein was performed in 2 (10.5%) patients, and both balloon angioplasty of the femoral vein and rotational thrombectomy were performed in 1 (5.3%) patient. Iliac vein stenting was performed due to combined iliac vein narrowing in 13 (68.4%) of the 19 successful cases. The mean procedure time was 86 minutes (26-179 minutes). All of the patients with technical success (19 of 21 patients) showed marked improvement in symptoms at the time of discharge (clinical success). Unexplained gastrointestinal hemorrhage developed in 1 patient. Conclusion: Single-session endovascular treatment is feasible and effective even for patients with aged deep vein thrombosis of the lower extremity more than 10 days old.

Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic properties including tumor cell growth, survival, motility, angiogenesis and chemoresistance. In the present study, we evaluated whether RON affects chemosensitivity and oncogenic behavior of colorectal cancer cells and investigated its prognostic value in colorectal cancer. To evaluate the impact of RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer cells with small interfering RNAs specific to RON. This was followed by flow cytometric analyses and migration, Matrigel invasion and endothelial tube formation assays. The expression of RON was investigated by immunohistochemistry in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis by upregulating the activities of caspases and expression of proapoptotic genes. Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression of cyclins and cyclin‑dependent kinases and inducing that of p21. Furthermore, RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of colorectal cancer cells. The β-catenin signaling cascade was blocked by RON knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube formation and expression of VEGF-A and HIF-1α and increased angiostatin expression. Furthermore, it inhibited lymphatic endothelial cell tube formation and the expression of VEGF-C and COX-2. RON expression was observed to be associated with age, tumor size, lymphovascular and perineural invasion, tumor stage, lymph node and distant metastasis, and poor survival rate. The mean microvessel density value of RON-positive tumors was significantly higher than that of RON-negative ones. These results indicate that RON is associated with tumor progression by inhibiting chemosensitivity and enhancing angiogenesis in colorectal cancer.

Background/Aims: This study aimed to elucidate the epi demiological and clinical characteristics of chronic hepatitis C (CHC) patients in South Korea from 2007 to 2017 and to compare the treatment patterns between two periods before and after the first approval of direct-acting antivirals (DAA) in South Korea in 2015. Methods: This prospective, multicenter cohort enrolled 2,758 patients with hepatitis C virus (HCV) viremia at seven tertiary centers, and clinical data were prospectively collected with questionnaire surveys focused on lifetime risk factors related to HCV infection. Results: The HCV patients had a mean age of 57.3 years (50.8% male). Among them, 14.3% showed a positive history of transfusion before HCV screening and 5.6% reported intravenous drug use (IVDU), with significant differences in these risk factors between men and women. The proportions of patients with chronic hepatitis, liver cirrhosis and hepatocellular carci noma (HCC) were 69.5%, 18.9%, and 11.5%, respectively. The mean alanine aminotransaminase level was within the upper normal limit at 49.9%, and the major genotypes were 1b (48.2%) and 2 (46.4%). The overall treatment rate was 53.8%, showing a rapid transition from interferon-based therapy to DAA therapy. In the post-DAA-approval era, the untreated group was older, had a higher prevalence of HCC, and had less education than the treated group. Conclusions: More than 90% of CHC patients were over 40 years old, the major genotypes were 1b and 2, and IVDU was observed in less than 6% of CHC patients. Approximately half of the pa tients underwent antiviral therapy even in the DAA era, show ing an unmet need with regard to HCV elimination. (Gut Liver 2020;14:207-217)

This study aimed to investigate the efficacy and safety of sofosbuvir plus ribavirin for the treatment of hepatitis C virus (HCV) genotype 2 infection and to determine the optimal ribavirin dosage.From May 2016 to March 2017, 199 patients received sofosbuvir plus ribavirin treatment for HCV genotype 2 infection at four centers in Jeollanam-do Province, Korea. After excluding patients lost to follow-up and those with insufficient data, we retrospectively assessed the data for 194 patients. The treatment efficacy and safety of sofosbuvir plus ribavirin were evaluated.A sustained virological response was achieved in 189 patients (intention-to-treat [ITT] 97.4%; per protocol [PP]: 99.5%, both at 12 and 24 weeks) whose average ribavirin dosage was 937.1 mg/day. The most frequent adverse event was anemia (17.5%), and its incidence significantly increased (P0.001) with a higher ribavirin dosage per body weight. Discontinuation of ribavirin or dosage reduction occurred in 27 (14.2%). The ribavirin dosage reduction rate increased at a dosage of15 mg/kg (area under the receiver operating characteristic curve 0.652, 95% confidence interval [CI] 0.54-0.76, P = 0.01). Multivariate analysis showed that age ≥70 years, with liver cirrhosis, and female gender were associated with ribavirin dosage reduction.Remarkable outcomes were attained in patients with HCV genotype 2 infection treated with sofosbuvir plus ribavirin. Age ≥70 years, with liver cirrhosis, and female gender were associated with ribavirin dosage reduction. Thus, sustained virological response can be achieved with1000 mg of ribavirin, with an optimal dosage of 15 mg/kg.

Purpose: To evaluate the feasibility and the outcomes of transjugular percutaneous endovascular treatment of dysfunctional hemodialysis access in patients with chronic kidney disease. Methods: A total of 50 transjugular treatments in 38 patients with arteriovenous fistulas or arteriovenous grafts from September 2011 to May 2015 were included in this study. Medical records and angiographies were retrospectively reviewed. Success rate, patency rate, procedure time, and complications including internal jugular vein stenosis were evaluated. Results: A total of 50 sessions of transjugular treatments were performed in 38 patients. There were 31 native arteriovenous fistulas including 10 immature cases and 19 arteriovenous grafts. Among the 50 cases, technical success was achieved in 45 and clinical success was achieved in 44; 37 cases (74%) with multiple stenotic sites were treated by the transjugular approach without placement of cross-sheaths. The mean time from puncture of the internal jugular vein to first fistulography was 10 min, and the mean total procedure time was 64 min. The primary patency rate at 6 months was 77%, while the secondary patency rate at 6 months was 97%. Perforation occurred in two cases during conventional percutaneous transluminal angioplasty after failure of the transjugular approach. One dissection occurred during the transjugular approach. There was no newly developed internal jugular vein stenosis during a mean follow-up period of 19.3 months. Conclusion: For the treatment of dysfunctional or immature hemodialysis access, the transjugular approach is a feasible and effective option that avoids injury to the graft or draining vein, especially in immature fistulas.

Rationale: Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory. Patient concerns: A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain. Diagnoses: HCC and extra-hepatic metastases to the lung and RA. Interventions: Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib. During a follow-up evaluation computed tomography, he experienced a radio-contrast-induced anaphylaxis. After the event, treatment such as RT, TACE, and sorafenib were continued. Outcomes: His tumor burden decreased, finally leading to a complete response as per the modified Response Evaluation Criteria in Solid Tumors. The patient is still alive, 30 months after the episode. Subsequent blood tests showed increased natural killer (NK) cell activity, which was significantly higher than that seen in other age-matched HCC patients with an identical stage of the tumor, receiving sorafenib. This suggests that the increase in NK cells induced by anaphylaxis influenced the tumor burden. Lessons: We report here a rare case of long-term survival of an HCC patient with multiple metastases treated with multidisciplinary modalities, in which high NK cell activity was observed after a radio-contrast-induced anaphylactic reaction during follow-up investigations.

Background/aim The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) has been increasing. But there is no proper management based on age stratification in elderly patients. Therefore, we evaluated the clinical characteristics and outcomes of elderly HCC patients more than 75 years old in South Korea. Patients and methods Five hundred and fifty elderly patients with HCC were enrolled and divided into the oldest-old (age ≥85 years), middle-old (age between 80 and 85 years), and young-old groups (age between 75 and 80 years). Results Fifty-one, 153, and 346 patients were included in the oldest-old (mean age: 87 years), middle-old (mean age: 82 years), and young-old groups (mean age: 77 years), respectively. There was a significantly lower rate of alcohol-related and hepatitis B virus-related diseases in the oldest-old group than in the other groups, whereas there was no significant difference in other characteristics. With increasing age, conservative treatment was predominantly performed. Transarterial chemoembolization was the main modality of active treatment in all groups. In multivariate analysis, the performance score, model for end-stage liver disease score, modified Union for International Cancer Control staging, Barcelona Clinic Liver Cancer staging, presence of portal vein tumor thrombosis, ruptured HCC, and active treatment were risk factors of overall survival. Conclusion When the therapeutic approach is used in elderly patients with HCC, the patient's performance status, liver function, and stage of cancer should be considered, and its use should not be restricted to those of advanced age.

bBackgrounds/Aims:/bRebleeding of gastric varices (GVs) after endoscopic variceal obturation (EVO) can be fatal. This study was performed to evaluate the usefulness of computed tomography (CT) for the prediction of rebleeding after EVO GV bleeding.bMethods:/bPatients who were treated with EVO for GV bleeding and underwent CT before and after EVO were included. CT images of the portal phase showing pretreatment GVs and feeding vessels, and nonenhanced images showing posttreatment cyanoacrylate impaction were reviewed.bResults:/bFifty-three patients were included. Their mean age was 60.6±11.6 years, and 40 patients (75.5%) were men. Alcoholic liver disease was the most frequent underlying liver disease (45.3%). Complete impaction of cyanoacrylate in GVs and feeding vessels were achieved in 40 (75.5%) and 24 (45.3%) of patients, respectively. During the follow-up, GV rebleeding occurred in nine patients, and the cumulative incidences of GV rebleeding at 3, 6, and 12 months were 11.8%, 18.9%, and 18.9%, respectively. The GV rebleeding rate did not differ significantly according to the complete cyanoacrylate impaction in the GV, while it differed significantly according to complete cyanoacrylate impaction in the feeding vessels. The cumulative incidences of GV rebleeding at 3, 6, and 12 months were 22.3%, 35.2%, and 35.2%, respectively, in patients with incomplete impaction in feeding vessels, and there was no rebleeding during the follow-up period in patients with complete impaction in the feeding vessels (p=0.002).bConclusions:/bAbdominal CT is useful in the evaluation of the treatment response after EVO for GV bleeding. Incomplete cyanoacrylate impaction in feeding vessels is a risk factor for GV rebleeding.

Background Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. Methods A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. Results HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. Conclusion Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted., Graphical Abstract

Purpose To retrospectively compare long-term outcomes of conventional chemoembolization plus radiofrequency (RF) ablation vs those of surgical resection in patients with a single 3–5-cm hepatocellular carcinoma (HCC). Materials and Methods From January 2008 to December 2017, 139 of 623 patients who underwent surgical resection and 60 of 186 patients who underwent chemoembolization/RF ablation in a single center were compared with respect to local tumor progression (LTP), intrahepatic distant recurrence (IDR), disease-free survival (DFS), overall survival (OS), major complications, and hospital stay before and after propensity-score matching. Results Mean follow-up periods were similar in the chemoembolization/RF ablation and surgical resection groups (41.9 mo vs 48.4 mo). Three (5%) and 17 (28.3%) patients in the chemoembolization/RF ablation group and 12 (8.6%) and 57 (41.0%) patients in the surgical resection group showed LTP and IDR (P = .366 and P =.114, respectively). At 1, 3, and 5 years, respective DFS rates were 88.1%, 65.3%, and 49.0% for chemoembolization/RF ablation and 84.2%, 58.2%, and 46.5% for surgical resection (P = .294). Moreover, respective OS rates were 95.0%, 73.5%, and 54.0% for chemoembolization/RF ablation and 97.1%, 87.4%, and 75.0% for surgical resection (P = .055). After matching (n = 52), therapeutic outcomes remained similar (P = .370, P = .110, P = .230, and P = .760, respectively). Surgical resection was associated with higher complication rates (P = .015) and longer hospital stays (8.4 d ± 3.7 vs 16.9 d ± 7.0; P Conclusions Conventional chemoembolization combined with RF ablation may be feasible for single 3–5-cm HCCs, with comparable therapeutic outcomes vs surgical resection and shorter hospital stays.

To define and correlate multidetector CT (MDCT) findings of pancreatic fistula after pancreaticoduodenectomy with surgical grading based on the 2016 Revised International Study Group of Pancreatic Fistula (ISGPF) classification. Between May 2011 and December 2016, 235 patients with periampullary tumor underwent pancreaticoduodenectomy and postoperative MDCT. Patients were classified into three groups (clinically no pancreatic fistula (cNo-PF), grade B, and grade C) according to the ISGPF classification. MDCT images were retrospectively evaluated by two radiologists in consensus for the presence of pancreaticojejunostomy (PJ) dehiscence, PJ dehiscence diameter, PJ defect, acute necrotic collection (ANC), peripancreatic fluid collection, and imaging findings of complications. Categorical MDCT findings were compared among the three groups using Pearson’s chi-square test, and PJ dehiscence diameter was compared using the Kruskal–Wallis test. There was no significant difference in patient demographics among the groups (cNo-PF = 133, grade B = 68, and grade C = 34), but the MDCT findings were significantly different regarding the presence of PJ dehiscence (p

PURPOSE To evaluate the effects of the degree of ethiodized oil accumulation achieved by transarterial chemoembolization followed by radiofrequency (RF) ablation on the treatment efficacy for a single intermediate-sized hepatocellular carcinoma (HCC). MATERIALS AND METHODS A total of 153 consecutive patients who underwent chemoembolization and RF ablation for a single intermediate-sized HCC (2-5 cm) were included. On the basis of the degree of ethiodized oil accumulation in HCC on cone-beam CT images, patients who underwent chemoembolization and RF ablation were classified into 2 groups: compact accumulation (≥ 75%) and noncompact accumulation (< 75%). The rates of cumulative local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between groups. RESULTS Of the 153 patients, 89 were classified into the compact ethiodized oil accumulation group and 64 in the noncompact ethiodized oil accumulation group. There were no significant differences in patient demographic or HCC characteristics between groups except for the incidence of liver cirrhosis (P = .038) and the tumor margin morphology (P = .008). The cumulative LTP rate was significantly lower in the compact accumulation group than in the noncompact accumulation group (P = .013). There were no significant differences in the incidences of complications, DFS rates (P = .055), or OS rates (P = .184). CONCLUSIONS The degree of ethiodized oil accumulation does not play a role in decreasing the OS or DFS rate after chemoembolization and RF ablation for intermediate-sized HCC; however, it may contribute to reducing the rate of LTP.

This prospective observational study aimed at investigating the role of procalcitonin (PCT) in diagnosing bacterial infection and guiding antibiotic therapy for hepatocellular carcinoma (HCC) patients with fever after transarterial chemoembolization (TACE) and/or radiofrequency ablation (RFA). Ninety-seven cases (84 patients) were enrolled. Serum PCT, C-reactive protein (CRP), and white blood cell (WBC) counts were measured on the day of fever onset (day 0) and days 1, 3, 5, and 7 of fever. Empirical antibiotics were initiated only if PCT was ≥0.5 ng/mL or specific infection foci were suspected. An infectious cause was found in nine cases. PCT on day 0 of fever was significantly higher in patients with bacterial infection than in those without infection (P=0.035). The area under the receiver operating characteristic curve for PCT was 0.715 (95% confidence interval, 0.538–0.892) and was higher than that for CRP (0.598 (0.368–0.828)) or WBC counts (0.502 (0.307–0.697)). In patients undergoing TACE and/or RFA, a significantly lower number of antibiotics were prescribed during the study period than during the prestudy period (P<0.001). In conclusion, PCT might be a biomarker for diagnosing infection and guiding antibiotic treatment to reduce unnecessary antibiotic use in patients with fever after TACE and/or RFA.

Prospero homeobox 1 (PROX1) functions as a tumor suppressor gene or an oncogene in various cancer types. However, the distinct function of PROX1 in gastric cancer is unclear. We determined whether PROX1 affected the oncogenic behavior of gastric cancer cells and investigated its prognostic value in patients with gastric cancer. A small interfering RNA against PROX1 was used to silence PROX1 expression in gastric cancer cell lines AGS and SNU638. Expression of PROX1 in gastric cancer tissues was investigated by performing immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined by performing the TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. PROX1 knockdown induced apoptosis by activating cleaved caspase-3, caspase-7, caspase-9, and poly(ADP-ribose) polymerase, and by decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. PROX1 knockdown also suppressed tumor cell proliferation. In addition, PROX1 knockdown decreased lymphatic endothelial cell invasion and tube formation and the expression of vascular endothelial growth factor (VEGF)-C and -D and cyclooxygenase (COX)-2. However, PROX1 knockdown only decreased umbilical vein endothelial cell invasion, not tube formation. The mean Ki-67 labeling index and lymphatic vessel density value of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, no significant difference was observed between PROX1 expression and apoptotic index or microvessel density. PROX1 expression was significantly associated with age, cell differentiation, lymph node metastasis, cancer stage, and poor survival. These results indicate that PROX1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.

Purpose To evaluate effectiveness of breast fixation to reduce migration of the catheter tip of a totally implantable venous access port (TIVP) in women. Materials and Methods TIVPs were placed in 129 women via the right axillary vein from July 2012 to December 2014, with a final study population of 118 patients (mean age, 55.3 ± 13.8 years; range, 21-91 years). The patients were divided into two groups according to breast fixation during TIVP placement. A total of 56 patients received TIVP placement without breast fixation (Group 1); the remaining 62 received TIVP placement in the supine position after fixation of the ipsilateral breast on the abdominal wall in the sitting position (Group 2). Medical records were retrospectively reviewed for age, weight, height, body mass index, and underlying malignancy. We evaluated the difference in distance ratios between the port chamber and the catheter tip on supine chest and erect chest radiographs, respectively. Statistical analysis was performed using Student's t test. Results Differences in all parameters between Group 1 and Group 2 were not statistically significant. Mean distance ratio between the port chamber and the catheter tip was 1.95 ± 0.97 in Group 1 and 1.33 ± 0.59 in Group 2. Differences in distance ratios between the port chamber and the catheter tip were statistically significant between Group 1 and Group 2 (p = 0.001). Conclusions Breast fixation seems to be effective in reducing migration of the port chamber and catheter tip with position changes in female patients during TIVP placement.

The purpose of this study was to evaluate the diagnostic efficacy of acoustic structure quantification (ASQ) parameters [mode, average, and focal distribution (FD) ratio] in the staging of hepatic fibrosis in patients with chronic viral hepatitis and to compare it with transient elastography (TE) by using liver biopsy as reference standard. We studied 62 patients with chronic viral hepatitis. Each patient underwent ASQ evaluation and liver biopsy; 54 of these patients received TE. Thirty-six participants without any liver disease were enrolled as normal group, who also underwent ASQ evaluation and TE. All three parameters of ASQ were compared with the histologic fibrosis grade according to the METAVIR scoring (F0–F4). Statistical analysis was performed to investigate the correlations and the diagnostic values of ASQ parameters and compare them to TE. All three ASQ parameters and TE were significantly correlated with liver fibrosis stage. Of the ASQ parameters, the mode parameter showed the best correlation (P