Treatment strategies for hepatocellular carcinoma with extrahepatic metastasis.

Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) has increasingly been seen due to improved survival with effective management of intrahepatic lesions. The presence of EHM indicates an advanced stage of HCC, for which systemic therapy serves as the standard treatment modality. Since the approval of Sorafenib as the first systemic agent in 2007, it took almost a decade to show its efficacy in both first and further lines of setting until the landscape of systemic drugs was finally expanded. Moreover, with inspiring results from immunotherapy trials in HCC, it appears that the introduction of immunotherapy may lead to an evolution in the portfolio of HCC treatment. Although the locoregional approach in the management of EHM is not recommended for advanced-stage HCC, efforts have been made to demonstrate its efficacy in symptom relief and potential benefit for overall survival. This review provides a summary of recent updates of the systemic agents in the treatment of advanced HCC, with an emphasis on aggressive locoregional management of EHM by various treatment modalities.

Prevalence and prognostic value of elevated troponins in patients hospitalised for coronavirus disease 2019: a systematic review and meta-analysis.

BACKGROUND: The clinical significance of cardiac troponin measurement in patients hospitalised for coronavirus disease 2019 (covid-19) is uncertain. We investigated the prevalence of elevated troponins in these patients and its prognostic value for predicting mortality. METHODS: Studies were identified by searching electronic databases and preprint servers. We included studies of hospitalised covid-19 patients that reported the frequency of troponin elevations above the upper reference limit and/or the association between troponins and mortality. Meta-analyses were performed using random-effects models. RESULTS: Fifty-one studies were included. Elevated troponins were found in 20.8% (95% confidence interval [CI] 16.8-25.0 %) of patients who received troponin test on hospital admission. Elevated troponins on admission were associated with a higher risk of subsequent death (risk ratio 2.68, 95% CI 2.08-3.46) after adjusting for confounders in multivariable analysis. The pooled sensitivity of elevated admission troponins for predicting death was 0.60 (95% CI 0.54-0.65), and the specificity was 0.83 (0.77-0.88). The post-test probability of death was about 42% for patients with elevated admission troponins and was about 9% for those with non-elevated troponins on admission. There was significant heterogeneity in the analyses, and many included studies were at risk of bias due to the lack of systematic troponin measurement and inadequate follow-up. CONCLUSION: Elevated troponins were relatively common in patients hospitalised for covid-19. Troponin measurement on admission might help in risk stratification, especially in identifying patients at high risk of death when troponin levels are elevated. High-quality prospective studies are needed to validate these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020176747.

Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation.

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.

Supramolecular Photothermal Nanomedicine Mediated Distant Tumor Inhibition via PD-1 and TIM-3 Blockage.

Supramolecular nanoparticles for photothermal therapy (PTT) have shown promising therapeutic efficacy in the primary tumor and great potential for turning the whole-body immune microenvironment from "cold" to "hot," which allows for the simultaneous treatment of the primary tumor and the metastatic site. In this work, we develop a liposome-based PTT nanoparticle through the self-assembly of FDA-approved intravenous injectable lipids and a photothermal agent, indocyanine green (ICG). The obtained ICG-liposome shows long-term storage stability, high ICG encapsulation efficiency (>95%), and enhanced near-infrared (NIR) light-triggered photothermal reaction both in vitro and in vivo. The ICG-liposome efficiently eradicated the primary tumor upon laser irradiation in two colon cancer animal models (CT26 and MC38) and promoted the infiltration of CD8 T cells to distant tumors. However, PTT from ICG-liposome shows only a minimal effect on the inhibition of distant tumor growth in long-term monitoring, predicting other immunosuppressive mechanisms that exist in the distant tumor. By immune-profiling of the tumor microenvironment, we find that the distant tumor growth after PTT highly correlates to compensatory upregulation of immune checkpoint biomarkers, including program death-1 (PD-1), T-cell immunoglobulin, and mucin domain-containing protein 3 (TIM-3), in tumor-infiltrating CD8 T cells. Based on this mechanism, we combine dual PD-1 and TIM-3 blockade with PTT in an MC38 tumor model. This combo successfully clears the primary tumor, generates a systemic immune response, and inhibits the growth of the distant tumor. The ICG-liposome-combined PD-1/TIM-3 blockade strategy sheds light on the future clinical use of supramolecular PTT for cancer immunotherapy.

Application of Contrast-Enhanced Ultrasound in the Diagnosis of Solid Pseudopapillary Tumors of the Pancreas: Imaging Findings Compared With Contrast-Enhanced Computed Tomography.

OBJECTIVES: The purpose of this study was to assess the characterization and usefulness of contrast-enhanced ultrasound (CEUS) for diagnosing solid pseudopapillary tumors of the pancreas (SPTP) and compare the enhancement patterns with contrast-enhanced computed tomography (CECT). METHODS: Forty-three SPTP lesions proved by pathologic findings in 42 patients examined with CEUS and CECT were included in this study. The enhancement characteristics and typical CEUS features of the tumors were investigated. These characteristics were compared according to lesion sizes. The enhancement patterns of CEUS were compared with CECT. RESULTS: The most common enhancement levels of SPTP in the early phase and late phase for CEUS were isoenhancement (19 of 43 [44.2%]) and hypoenhancement (32 of 43 [74.4%]), respectively. The 4 most common enhancement patterns were hypo-hypo (16 of 43 [37.2%]), iso-iso (11 of 43 [25.6%]), hyper-hypo (8 of 43 [18.6%]), and iso-hypo (8 of 43 [18.6%]) enhancement. For the 43 SPTP lesions, typical CEUS features such as lesion membrane, intralesional vessel, and intralesional compartmentalization enhancements were detected in 30 (69.8%), 27 (62.8%), and 10 (23.2%) cases. Compared with CECT, isoenhancement during the early phase and hypoenhancement during the late phase were the most common imaging characteristics of CEUS. CONCLUSIONS: Lesion membrane, intralesional vessel, and intralesional compartmentalization enhancements are typical CEUS features of SPTP, especially for large lesions (lesion size ≥3.0 cm). Isoenhancement during the early phase and hypoenhancement during the late phase are the most common imaging characteristics of CEUS and CECT, making CEUS a viable alternative diagnostic method that is noninvasive.

Prophylaxis Against Atrial Fibrillation After General Thoracic Surgery: Trial Sequential Analysis and Network Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation/flutter (POAF) is associated with significant morbidity and mortality after general thoracic surgery, but the need for and the best agent for prophylaxis remains obscure. METHODS: A systematic literature search was performed to identify randomized controlled trials that compared regimens for POAF prophylaxis after general thoracic surgery. Random-effects meta-analyses with trial sequential analyses were performed to compare the effects of medical prophylaxis vs placebo/usual care. The risk of POAF among patients receiving various prophylactic regimens was subjected to Bayesian network meta-analysis. RESULTS: Twenty-two trials (2,891 patients and 11 regimens) were included. Overall, medical prophylaxis reduced the incidence of POAF (OR, 0.33; 95% CI, 0.22-0.49) but not short-term mortality (OR, 0.85; 95% CI, 0.41-1.73). There was no significant difference in patient withdrawal due to adverse events (OR, 1.67; 95% CI, 0.67-4.16). Trial sequential analysis showed that as of 2012, sufficient evidence had accrued in support of the effectiveness of medical prophylaxis in reducing POAF after general thoracic surgery. In network meta-analysis, ß-blockers, angiotensin-converting enzyme inhibitors, amiodarone, magnesium, and calcium channel blockers significantly reduced the risk of POAF compared with placebo/usual care. ß-Blockers had the highest probability of being the most effective agents (OR, 0.12; 95% credible interval [CrI], 0.05-0.27; probability of being best, 77.7%; number needed to treat, 5.2). CONCLUSIONS: The current literature supports the effectiveness and tolerability of medical prophylaxis and the superiority of ß-blockers in preventing POAF after general thoracic surgery. ß-Blockers are recommended, taking into consideration the status of the bronchopulmonary system.

Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis.

BACKGROUND: Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. METHODS AND PRINCIPAL FINDINGS: PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. CONCLUSIONS: Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available.

Pretreatment platelet count as a predictor for survival and distant metastasis in nasopharyngeal carcinoma patients.

The aim of the present study was to investigate the prognostic value of different pretreatment platelet (PLT) counts on the treatment outcome in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone. A total of 1,501 NPC patients, including 412 receiving CCRT and 1,089 receiving RT, were enrolled in the present study. The PLT count cut-off points for the CCRT and RT groups were 150 and 300×109/l, respectively, and the PLT counts were categorized it into three groups: Low (PLT≤150×109/l), moderate (150×109/l300×109/l). To identify independent predictors of overall survival (OS), the Cox proportional hazards model was used to determine local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates in the CCRT and RT patients. Furthermore, univariate and multivariate analysis indicated that compared with a moderate PLT count, a low PLT count was an independent unfavorable prognostic factor for OS rate in CCRT patients [hazard ratio (HR), 2.024; 95% confidence interval (CI), 1.165-3.516], and a high PLT count was an independent unfavorable prognostic factor for OS and DMFS rates in CCRT (OS: HR, 1.742; 95% CI, 1.090-2.786; DFMS: HR, 2.110; 95%CI, 1.084-4.108) and RT (OS: HR, 1.740; 95%CI, 1.283-2.362; DMFS: HR, 2.819; 95% CI, 1.766-4.497) patients. Compared with a low PLT count, a high PLT count was significantly and independently associated with a poor DMFS rate in the RT patients (P=0.025; HR, 2.454; 95% CI, 1.121-5.372). Therefore, the present study indicates that low and high PLT counts may be useful indicators of survival and distant metastasis in NPC patients who have undergone radiation treatment.