Joong Hyun Ahn

Small Hepatocellular Carcinoma: Radiofrequency Ablation versus Nonanatomic Resection—Propensity Score Analyses of Long-term Outcomes

PURPOSEnTo compare radiofrequency (RF) ablation with nonanatomic resection (NAR) as first-line treatment in patients with a single Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) and to evaluate the long-term outcomes of both therapies.nnnMATERIALS AND METHODSnThis retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Data were reviewed from 580 patients with HCCs measuring 3 cm or smaller (BCLC stage 0 or A) who underwent ultrasonographically (US) guided percutaneous RF ablation (n = 438) or NAR (n = 142) as a first-line treatment. Local tumor progression, intrahepatic distant recurrence, disease-free survival, and overall survival rates were analyzed by using propensity score matching to compare therapeutic efficacy. In addition, major complications and length of postoperative hospital stay were compared.nnnRESULTSnBefore propensity score matching (n = 580), the 5-year cumulative rates of local tumor progression for RF ablation and NAR (20.9% vs 12.7%, respectively; P = .093) and overall survival rates (85.5% vs 90.9%, respectively; P = .194) were comparable, while the 5-year cumulative intrahepatic distant recurrence rates (62.7% vs 36.6%, respectively; P < .001) and disease-free survival rates (31.7% vs 61.1%, respectively; P < .001) in the NAR group were significantly better than those in the RF ablation group. After matching (n = 198), there were no significant differences in therapeutic outcomes between the RF ablation and NAR groups, including 5-year cumulative intrahepatic distant recurrence (47.0% vs 40.2%, respectively; P = .240) and disease-free survival rates (48.9% vs 54.4%, respectively; P = .201). RF ablation was superior to NAR for major complication rates and length of postoperative hospital stay (P < .001).nnnCONCLUSIONnIn patients with one BCLC stage 0 or A (≤ 3 cm) HCC who received RF ablation or NAR as first-line treatment, there were no significant differences in long-term therapeutic outcomes; however, RF ablation was associated with fewer major complications and a shorter hospital stay after treatment.

Long-term Therapeutic Outcomes of Radiofrequency Ablation for Subcapsular versus Nonsubcapsular Hepatocellular Carcinoma: A Propensity Score Matched Study

Purpose To compare the long-term therapeutic outcomes of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in subcapsular versus nonsubcapsular locations by using propensity score matching. Materials and Methods RF ablation for subcapsular HCC is controversial because of a high risk of incomplete ablation or major complications. This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. Between April 2006 and December 2011, 508 consecutive patients (396 men, 112 women; age range, 30-80 years) with a single HCC (Barcelona Clinic Liver Cancer stage 0 or A) underwent ultrasonography-guided percutaneous RF ablation as a first-line treatment. The patients were divided into two groups according to tumor location: subcapsular (n = 227) and nonsubcapsular (n = 281). Subcapsular HCC was defined as an index tumor located within 0.1 cm of the liver capsule. The association of subcapsular location and therapeutic outcomes of RF ablation was evaluated, including (a) local tumor progression (LTP) by using a competing risk regression model and (b) overall survival (OS) by using a Cox proportional hazards model according to propensity score matched data. The major complication rates from both overall data and matched data were assessed. Results Matching yielded 163 matched pairs of patients. In the two matched groups, cumulative LTP rates were 18.8% and 20.9% at 3 and 5 years, respectively, in the subcapsular group and 13.2% and 16.0% in the nonsubcapsular group. Corresponding OS rates were 90.7% for 3 years and 83.2% for 5 years in the subcapsular group and 91.4% and 79.1%, respectively, in the nonsubcapsular group. Hazard ratios (HRs) for LTP (HR = 1.37, P = .244) and OS (HR = 0.86, P = .604) were not significantly different between the two matched groups. Additionally, differences in major complication rates were not significant between groups for the two sets of data (P > .05). Conclusion The differences in LTP, OS, and major complication rates of RF ablation for HCC were not significant between subcapsular and nonsubcapsular groups. (©) RSNA, 2016.

Association Between Presence of a Cardiac Intensivist and Mortality in an Adult Cardiac Care Unit

BACKGROUNDnDedicated intensive care unit (ICU) physician staffing is associated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data are available on the role of a cardiac intensivist in thexa0cardiac intensive care unit (CICU).nnnOBJECTIVESnThis study investigated the association of cardiac intensivist-directed care with clinical outcomes in adult patients admitted to the CICU.nnnMETHODSnThis study analyzed 2,431 patients admitted to the CICU at Samsung Medical Center in Seoul, South Korea, fromxa0January 2012 to December 2015. In January 2013 the CICU was changed from a low-intensity staffing model to axa0high-intensity staffing model managed by a dedicated cardiac intensivist. Eligible patients were divided into either a low-intensity management group (nxa0= 616) or a high-intensity management group (nxa0= 1,815). One-to-many (1:N) propensity score matching with variable matching ratios was also performed. The primary outcome was death in the CICU.nnnRESULTSnDeath in the CICU occurred in 55 patients (8.9%) in the low-intensity group versus 74 patients (4.1%) in the high-intensity group (pxa0< 0.001). Of 135 patients who underwent extracorporeal membrane oxygenation, the CICU mortality rate in the high-intensity group was also lower than that in the low-intensity group (54.5% vs. 22.5%; pxa0=xa00.001). On propensity score matching, high-intensity staffing was found associated with a lower CICU mortality rate in the matched cohort of patients (7.5% vs. 3.7%; adjusted odds ratio: 0.53; 95% confidence interval: 0.32 to 0.86; pxa0=xa00.010). In overall and propensity-matched patients, there were no substantive differences in either median length of CICU stay or readmission rates between the 2 groups.nnnCONCLUSIONSnThe presence of a dedicated cardiac intensivist was associated with a reduction in CICU mortality rates in patients with cardiovascular disease who required critical care.

Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil

BACKGROUNDnThe incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified.nnnMETHODSnThis single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy.nnnRESULTSnThe incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction.nnnCONCLUSIONSnFor patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.

Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma

Background/Aims: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. Methods: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. Results: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1–B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo’ (2–4) nodules of intermediate size (5–10 cm) when the AFP levels was <400 ng/ml, or ‘oligo’ (2–4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). Conclusion: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.

Impact of a cardiac intensivist on mortality in patients with cardiogenic shock

BACKGROUNDnThis study aimed to evaluate the association between high-intensity staffing by a dedicated cardiac intensivist and clinical outcomes in CS.nnnMETHODSnWe enrolled 2923 consecutive patients admitted to a cardiac care unit (CCU) from January 1, 2012 to December 31, 2015. In January 2013, the CCU changed from a low-intensity to high-intensity staffing unit managed by a dedicated cardiac intensivist. Patients were eligible if they required inotropes or vasopressors to maintain a systolic blood pressure>90mmHg, and had serum lactate≥2.0mmol/L. Eligible patients (n=513) were treated by low-intensity CCU (n=352) or high-intensity CCU (n=161). The primary outcome was CCU mortality.nnnRESULTSnCCU mortality occurred in 49 patients (30.6%) of the low-intensity group versus 62 patients (17.6%) of the high-intensity group (adjusted odds ratio [aOR] 0.44, 95% confidence interval [CI] 0.25-0.75, p<0.001). In-hospital mortality was not significantly different between the groups (33.1% vs 24.4%, aOR 0.75, 95% CI 0.43-1.29, p=0.29). Among 135 patients treated with extracorporeal membrane oxygenation, the high-intensity model was associated with lower CCU mortality (54.5% vs 22.5%, aOR 0.24, 95% CI 0.07-0.77, p=0.02) and in-hospital mortality (57.6% vs 29.4%, aOR 0.28, 95% CI 0.10-0.81, p=0.02).nnnCONCLUSIONnHigh-intensity staffed CCU managed by a dedicated cardiac intensivist was associated with a significant reduction of CS-related mortality.

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75u2009×u2009109/L were matched with 97 of 119 patients who had preoperative PLT >75u2009×u2009109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75u2009×u2009109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow‐up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR]u2009=u20093.09; 95% confidence interval [CI], 1.86‐5.14; Pu2009<u20090.001) and multivariate analyses (HRu2009=u20092.10; 95% CI, 1.23‐3.60; Pu2009=u2009 0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HRu2009=u20092.33; 95% CI, 1.36‐4.01; Pu2009=u2009 0.002) and multivariate analyses (HRu2009=u20091.90; 95% CI, 1.02‐3.54; Pu2009=u2009 0.04). Preoperative PLT had no interaction with the Milan criteria, alpha‐fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation‐based scores including neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and the inflammation‐based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation. Liver Transplantation 24 44–55 2018 AASLD.

Validation and Comparison of CS-IHC4 Scores with a Nomogram to Predict Recurrence in Hormone Receptor-Positive Breast Cancers

The aim of this study was to both develop and validate a nomogram based on the Ki-67 index to predict recurrence. We constructed a nomogram using the Cox proportional hazards model with 953 N0 and N1 postoperative hormone receptor (HR)-positive breast cancer patients and validated it in an external cohort of 895 patients. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four immunohistochemistry (IHC) markers (IHC4 score) was created and assessed by the likelihood ratio χ2 (LR-χ2) test using the bootstrapping method. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.75 (95% CI 0.72-0.77) in the training set. The validation set showed good discrimination with an AUC of 0.63 (95% CI 0.60-0.66). In the LR-χ2 test, the nomogram score was found to be more informative than the IHC4 with clinical score (CS) [LR-χ2 13.365 (1 d.f.); 95% CI 2.50-24.23 for CS-IHC4 + nomogram score vs. CS-IHC4] on distant recurrence-free survival. This study implies that the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score in HR-positive N0 and N1 breast cancer patients (NCT1273415).

Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors.

Objective: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. Background: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. Methods: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. Results: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. Conclusions: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Vasoactive Inotropic Score as a Predictor of Mortality in Adult Patients With Cardiogenic Shock: Medical Therapy Versus ECMO

INTRODUCTION AND OBJECTIVESnThis study investigated whether the vasoactive inotropic score (VIS) is independently predictive of mortality in cardiogenic shock (CS).nnnMETHODSnThis study was retrospective, observational study. Patients who were admitted to the cardiac intensive care unit from January 2012 to December 2015 were screened, and 493 CS patients were finally enrolled. To quantify pharmacologic support, the patients were divided into 5 groups based on a quintile of VIS: 1 to 10, 11 to 20, 21 to 38, 39 to 85, and > 85. The primary outcome was in-hospital mortality.nnnRESULTSnIn-hospital mortalities in the 5 VIS groups in increasing order were 8.2%, 14.1%, 21.1%, 32.0%, and 65.7%, respectively (P < .001). Multivariable analysis indicated that VIS ranges of 39 to 85 (aOR, 3.85; 95%CI, 1.60-9.22; P = .003) and over 85 (aOR, 10.83; 95%CI, 4.43-26.43; P < .001) remained significant prognostic predictors for in-hospital mortality. With multiple logistic regression to remove any confounding effects, we found that the localized regression lines regarding the odds of death intersected each others (medical therapy alone and combined extracorporeal membrane oxygenation group) path at VIS = 130. In contrast to linear correlation between VIS and mortality for patients treated with medical therapy alone, there was little association between a VIS of 130 or more and the probability of in-hospital mortality for patients who were treated with extracorporeal membrane oxygenation.nnnCONCLUSIONSnA high level of vasoactive inotropic support during the first 48hours was significantly associated with increased in-hospital mortality in adult CS patients.