Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Transjugular approach in aspiration thrombectomy and angioplasty of a thrombosed straight arteriovenous graft compared to the direct hemodialysis access approach.

PURPOSE: To evaluate the efficacy and outcome of the transjugular approach in endovascular recanalization of a thrombosed straight arteriovenous graft (AVG) compared to those of the direct hemodialysis access approach (conventional approach). MATERIALS AND METHODS: We retrospectively assessed patients who underwent aspiration thrombectomy and percutaneous transluminal angioplasty for thrombosed straight AVG performed at a single institution between October 2006 and October 2021. A total of 138 thrombosed AVGs in 83 patients (39 male and 44 females) were divided into the transjugular approach group (Group A) and the conventional approach group (Group B). Technical and clinical success, postintervention primary patency, cumulative patency, and periprocedural complications were compared. RESULTS: There was no statistical difference in demographic data between groups A and B. The technical success rate of group A and B was 96.4% (80/83) and 98.2% 54/55, respectively (p > 0.05). The mean procedure time was 61.4 min (Group A) and 70.5 min (Group B) (p > 0.05). There was no statistically significant difference between the two groups in postintervention primary patency. The cumulative patency of Groups A and B was 911.9 days (range 122-6277) and 1062.3 days (range 72-2302 days), respectively (p > 0.05). One patient in Group B experienced a major graft rupture. Pseudoaneurysm formation at the sheath insertion site occurred in two patients in Group B. No cases of stenosis or thrombosis of the IJV or hematoma at the puncture site were observed in Group A. CONCLUSION: The transjugular approach is as safe and effective as the conventional approach for aspiration thrombectomy and percutaneous transluminal angioplasty of thrombosed straight AVGs.

Transjugular approach: comparison with conventional endovascular treatment of native arteriovenous fistulas.

OBJECTIVES: The aim of this study was to compare the outcomes of the transjugular approach with those of the conventional approach for endovascular treatment of arteriovenous fistulas (AVFs). METHODS: Between May 2015 and July 2019, 112 patients with endovascular treatment of dysfunctional or immature AVFs were included and divided into the transjugular (n = 46) and conventional (n = 66) groups. Electronic medical records and angiography of the patients were retrospectively reviewed to assess technical and clinical success rates, time to first fistulography, total procedure time, primary and secondary patency, and complications in both groups. RESULTS: There were no significant differences in technical success rate (87.0% vs 97.0%; P = .062), clinical success rate (80.4% vs 90.9%; P = .109), or total procedure time (60.2 vs 57.9 min; P = .670) between the groups. Cox proportional hazards models showed that the cumulative primary patency was significantly higher in the transjugular group than in the conventional group (P = .041; 6-month patency rates, 93.8% vs 91.5%). Also, a statistically significant difference was found between the cumulative secondary patency of the groups (P = .014; 6-month patency rates, 91.4% vs 86.5%). No major complications were observed. CONCLUSIONS: Transjugular endovascular treatment of AVFs was successful and effective. Longer patency periods were observed when treated via transjugular access. ADVANCES IN KNOWLEDGE: This article compared the outcomes of transjugular approaches with those of conventional approaches in the endovascular treatment of native AVFs and showed higher patency periods/rates in the transjugular group than in the conventional group.

Anatomical Structures to Be Concerned With During Peripherally Inserted Central Catheter Procedures.

BACKGROUND: The central line has been frequently used for drug and nutrition supply and regular blood sampling of patients with chronic diseases. However, this procedure is performed in a highly sensitive area and has several potential complications. Therefore, peripherally inserted central catheters (PICC), which have various advantages, are being extensively used. Although the number of PICC procedures is increasing, the anatomy for safe procedures has not yet been properly established. Therefore, we studied basic anatomical information for safe procedures. METHODS: We used 20 fixed cadavers (40 arms) donated to the Korea University College of Medicine. The mean age was 76.75 years (range, 48-94 years). After dissection of each arm, the distribution pattern of the basilic vein and close structures was recorded, and some important parameters based on bony landmarks were measured. In addition, the number of vein branches (axillary region) and basilic vein diameter were also checked. RESULTS: The mean length from the insertion site to the right atrium was 38.39 ± 2.63 cm (left) and 34.66 ± 3.60 cm (right), and the basilic vein diameter was 4.93 ± 1.18 mm (left) and 4.08 ± 1.49 mm (right). The data showed significant differences between the left and right arms (P < 0.05). The mean distance from the basilic vein to brachial artery was 8.29 ± 2.78 mm in men and 7.81 ± 2.78 mm in women, while the distance to the ulnar nerve was 5.41 ± 1.67 mm in men and 5.52 ± 2.06 mm in women. CONCLUSION: According to these results, the right arm has a shorter distance from the insertion site to the right atrium, and the left arm has a wider vein diameter, which is advantageous for the procedure. In addition, the ulnar nerve and brachial artery were located close to or behind the insertion site. Therefore, special attention is required during the procedure to avoid damaging these important structures.

Expression of Apurinic/Apyrimidinic Endonuclease 1 in Colorectal Cancer and its Relation to Tumor Progression and Prognosis.

BACKGROUND/AIM: Over-expression of apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated to be associated with cancer progression, chemo- and radioresistance in various cancers. This study examined the expression of APE1 and its relation to tumor progression and prognosis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: We investigated 193 patients with CRC who received curative surgery for whom formalin-fixed and paraffin-embedded blocks were available, and long-term tumor-specific survival rate analysis was possible. The expression of APE1 was investigated by reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry in CRC and lymph node tissues. The apoptosis, proliferation, and angiogenesis of CRC cells were determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and immunohistochemical staining for Ki-67 and CD34 antibodies. RESULTS: APE1 was over-expressed in CRC and metastatic lymph node tissues compared with normal colorectal mucosa and non-metastatic lymph node tissues. Over-expression of APE1 was significantly associated with advanced stage, lymphovascular invasion, perineural invasion, deeper tumor invasion, lymph node metastasis, distant metastasis, and poor survival. Multivariate analysis demonstrated that APE1, perineural invasion, and lymph node metastasis were the independent prognostic factors associated with overall survival. The mean Ki-67 labeling index value of APE1-positive tumors was significantly higher than that of APE1-negative tumors. However, there was no significant association between APE1 expression and the apoptotic index or microvessel density. CONCLUSION: Over-expression of APE1 is significantly associated with tumor progression and poor survival in patients with CRC. Therefore, APE1 may be a novel biomarker and present a potential prognostic factor for CRC.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Acute respiratory distress syndrome and severe pneumonitis after atezolizumab plus bevacizumab for hepatocellular carcinoma treatment: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a high mortality. However, the treatment options for advanced HCC are limited to tyrosine kinase inhibitors, such as sorafenib and lenvatinib. Since previous regimens have an insufficient efficacy, the combination therapy of atezolizumab and bevacizumab (Ate/Bev) has been investigated, which showed an improvement in progression-free and overall survival. However, the adverse events of this combination therapy in advanced HCC have not been established. Herein, we report a novel case of an unresectable HCC and acute respiratory distress syndrome (ARDS) after a combination therapy of Ate/Bev. CASE SUMMARY: An 82-year-old male visited our outpatient clinic for an incidentally detected liver mass. Liver magnetic resonance imaging and enhanced chest computed tomography (CT) were performed, which showed arterial hyperenhancement with washout in delayed phase suggesting HCC, and a well-defined metastatic solid nodule, respectively. F-18 fluorodeoxyglucose positron emission tomography (PET)-CT exhibited multiple hypermetabolic lesions in the iliac bone, lumbar vertebrae, and femur. Because of the high burden of the intrahepatic tumor, transarterial radioembolization was initially performed; after 37 d, a combination therapy of Ate/Bev was administered. The patient visited the emergency department three days after Ate/Bev treatment complaining of dyspnea. He was diagnosed with severe pneumonitis based on CT. Despite administering oxygen via a high-flow nasal cannula, the P/F ratio was only 74; therefore, the patient was diagnosed with ARDS based on the overall examination results. Low tidal volume with high positive end-expiratory pressure, sedative agents combined with a neuromuscular blocker, and a systemic steroid were promptly applied to manage the ARDS. However, the patient did not recover from the hypoxia and expired 31 h after being admitted. CONCLUSION: Clinicians should be aware of severe pneumonitis due to the immune-related adverse events of this combination therapy, and patients should be closely monitored after therapy.

Next-generation sequencing analysis of hepatitis C virus resistance-associated substitutions in direct-acting antiviral failure in South Korea.

BACKGROUND/AIMS: We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. METHODS: Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. RESULTS: RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. CONCLUSION: NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

CD47 mediates the progression of colorectal cancer by inducing tumor cell apoptosis and angiogenesis.

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.

Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer.

BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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-3ß 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. CONCLUSION: ELMO1 mediates tumor progression by increasing tumor cell motility and inhibiting apoptosis in human CRC.

Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study.

BACKGROUND: 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. AIM: To investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes. METHODS: 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. RESULTS: 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 albumin < 4.0 g/dL, serum alkaline phosphatase > 100 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; P < 0.001). CONCLUSION: 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.

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.

BACKGROUND: 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. AIM: 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. METHODS: 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 (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS: 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 (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION: 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.

Clinical outcomes of palliative self-expandable metal stent placement in right- and left-sided malignant colon obstruction: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

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.

Endoscopic variceal obturation and retrograde transvenous obliteration for acute gastric cardiofundal variceal bleeding in liver cirrhosis.

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 < 0.05). In Cox regression analysis, EVO (vs. RTO) was the only significant predictor of higher GV rebleeding risk (hazard ratio 3.132, 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.

Fluoroscopy-guided trans-urethral exchange of double-J ureteral stents.

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.

Differences in clinical outcomes according to the time interval between the bridge to surgery stenting and surgery for left-sided malignant colorectal obstruction.

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.

A Phase I Study of Locoregional High-Dose Autologous Natural Killer Cell Therapy With Hepatic Arterial Infusion Chemotherapy in Patients With Locally Advanced Hepatocellular Carcinoma.

Background: To 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). Methods: Patients 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. Results: Of 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. Conclusion: The 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 Registration: cris.nih.go.kr, identifier KCT0003973.

PIVKA-II as a surrogate marker for prognosis in patients with localized hepatocellular carcinoma receiving stereotactic body radiotherapy.

PURPOSE: This study aimed to determine the correlation between protein induced by vitamin K absence or antagonist-II (PIVKA-II) and stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Sixty-one patients received SBRT between 2015 and 2020 with a median dose of 48 Gy (range, 39 to 60 Gy) with a median of 4 fractions. Changes in tumor markers before and after SBRT were analyzed. RESULTS: The median follow-up period was 31 months (range, 12 to 64 months). The estimated 2-year in-field failure-free survival, progression-free survival (PFS), and overall survival rates were 82.0%, 39.3%, and 96.7%, respectively. Patients with decreased PIVKA-II levels through SBRT had significantly few in-field failures (p = 0.005). Patients with PIVKA-II levels of ≤25 mAU/mL after SBRT had significantly long PFS (p = 0.004). CONCLUSION: PIVKA-II could be a useful surrogate marker for response or survival outcomes in patients with localized HCC receiving SBRT.

Amiodarone-Induced Multi-Systemic Toxicity Involving the Liver, Lungs, Thyroid, and Eyes: A Case Report.

Objectives: Amiodarone is widely used to treat arrhythmia. However, amiodarone is known for its severe toxicity to the liver, lungs, and thyroid. Amiodarone causes liver damage ranging from asymptomatic serum aminotransferase elevation to hepatic failure requiring liver transplantation. Although amiodarone toxicity has been reported, its simultaneous multi-organ toxicity is not well-known. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, lungs, thyroid, and eyes. Case Presentation: A 61-year-old woman visited the emergency room due to general weakness, nausea, visual disturbance, heat intolerance, and a non-productive cough. The patient had been using clopidogrel and amiodarone due to underlying atrial fibrillation. The total level of bilirubin was 0.71 mg/dL, aspartate aminotransferase was 358 U/L, alanine aminotransferase was 177 U/L, and prothrombin time was 27.1 s. Computed tomography showed diffuse increased liver intensity and scattered hyperattenuated nodular consolidations in both lungs. Transthoracic needle lung biopsy revealed fibrinoid interstitial inflammation with atypical change of type II pneumocytes and intra-alveolar foamy macrophages. In addition, the thyroid-stimulating hormone level was <0.008 µIU/mL, and free thyroxine was 4.67 ng/dL. The thyroid scan showed diffuse homogenous intake of technetium-99 m pertechnetate in both thyroid lobes. The ophthalmologic exam detected bilateral symmetrical corneal deposits in a vortex pattern. With these findings, we could diagnose amiodarone-induced hepatic, pulmonary, thyroid, and ophthalmologic toxicity. Liver function was restored after cessation of amiodarone, and thyroid function was normalized with methimazole administration. However, due to aggravated lung consolidations, systemic steroid treatment was administered, and improvement was seen 1 week after, at the follow-up exam. As her symptoms improved, she was discharged with a plan of steroid administration for 3 to 6 months. Conclusions: This case implies the possibility of multi-systemic amiodarone toxicity. Thus, the toxicity of amiodarone to multiple organs must be monitored. Prompt cessation of the drug should be considered upon diagnosis.