Radiofrequency versus microwave ablation for hepatocellular carcinoma within the Milan criteria in challenging locations: a retrospective controlled study.

PURPOSE: The aim of this study was to compare the safety and efficacy of radiofrequency ablation (RFA) with microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria in challenging locations. METHODS: This study retrospectively investigated 201 consecutive patients with Milan criteria HCCs who underwent RFA (RFA group, n = 150) or MWA (MWA group, n = 51) between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), local tumor control, and treatment-related complications were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Median follow-up duration was 36.7 months (range: 6.2-64.0 months). Cumulative 1-, 3-, and 5-year OS rates were 97.9%, 92.3%, and 80.6% in the MWA group and 96.4%, 87.4%, and 78.2% in the RFA group, respectively, (P = 0.450). Cumulative RFS rates at 1, 3, and 5 years were 93.2%, 74.4%, and 63.7% in the MWA group and 80.3%, 57.3%, and 49.6% in the RFA group, respectively, (P = 0.097). Multivariate analyses showed that variable categories "patient age above 65 years" (P = 0.004) and "more than one tumor" (P = 0.004) were associated with overall mortality, and "patient age above 65 years" (P = 0.048) and "tumor size greater than 3 cm" (P = 0.009) were associated with inferior RFS. The incidences of major complications were not significantly different between the two groups (3.3% vs 3.9%, P = 0.843). CONCLUSIONS: RFA and MWA were associated with comparable safety and efficacy for HCC within the Milan criteria in challenging locations. Further study in a large, multi-center patient cohort is necessary to validate the results.

Small single perivascular hepatocellular carcinoma: comparisons of radiofrequency ablation and microwave ablation by using propensity score analysis.

OBJECTIVES: We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC). METHODS: A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels. RESULTS: After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116). CONCLUSIONS: In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA. KEY POINTS: • Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. • There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. • The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.

Gold Nanoflares with Computing Function as Smart Diagnostic Automata for Multi-miRNA Patterns in Living Cells.

Investigating the multimolecule patterns in living cells is of vital importance for clinical and biomedical studies. Herein, we reported for the first time the engineering of gold nanoflares as smart automata to implement computing-based diagnosis in living mammalian cells. Defining the logic combinations of miR122 and miR21 as the detection patterns, the corresponding OR and AND diagnostic automata were designed. The results showed that they could recognize the correct patterns rapidly and sensitively. The automata could enter cells via self-delivery and have good biocompatibility. They enabled accurate diagnosis on miRNA signatures in different cell lines and differentiation of fluctuations in the same cell line at single cell resolution. Moreover, the automata afforded an innovative diagnostic mode. It simplified the complicated process of detecting, data-collecting, computing, and evaluating. The direct diagnosing result ("1" or "0") was exported according to the embedded computation code. It highlighted the new possibility of using smart automata for intelligent diagnostics and cancer therapy at single cell resolution.

Bronchobiliary fistula after ablation of hepatocellular carcinoma adjacent to the diaphragm: Case report and literature review.

BACKGROUND: Bronchobiliary fistula is a rare, but life-threatening complication after ablation of hepatocellular carcinoma. Few cases of bronchobiliary fistula have been reported and the treatment is controversial. METHODS: From 2006 to 2019, a total of 11 patients were diagnosed with bronchobiliary fistula after ablation and received nonsurgical treatment. RESULTS: All 11 patients presented with cough and bilioptysis. There were only two patients in which MRI revealed an obvious fistulous tract connecting the pleural effusion and biliary lesions. Pleural effusion, liver abscess and hepatic biloma were found in other patients. Three patients died of uncontrolled bronchobiliary fistula. CONCLUSIONS: Bronchobiliary fistula is a rare post-ablation complication but should be taken into consideration in clinical decisions. Minimally invasive interventional treatment is a relatively effective means of dealing with bronchobiliary fistula, but as for the more severe cases, greater clinical experience is required.

Computed tomography-guided radiofrequency ablation combined with transarterial embolization assisted by a three-dimensional visualization ablation planning system for hepatocellular carcinoma in challenging locations: a preliminary study.

OBJECTIVE: To assess the clinical efficacy and safety of computed tomography-guided radiofrequency ablation(CT-RFA) combined with transarterial embolization(TAE) assisted by a three-dimensional visualization ablation planning system(3DVAPS) for hepatocellular carcinoma(HCC) in challenging locations. METHODS: Data from 62 treatment-naive patients with hepatocellular carcinoma(HCC), with 83 lesions in challenging locations, and who met the Milan criteria and underwent CT-RFA between June 2013 and June 2016 were reviewed. Patients were divided into one of two groups according to different treatment modalities: study group (TAE combined with RFA assisted by 3DVAPS [n = 32]); and control (RFA only [n = 30]). Oncological outcomes included ablation-related complications, local tumor progression (LTP), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression analyses were performed to assess risk factors associated with LTP and OS. RESULTS: HCC lesions (mean size, 1.9 ± 1.0 mm in diameter) abutting the gastrointestinal tract (n = 25), heart and diaphragm (n = 21), major vessels (n = 13), and gallbladder (n = 3) were treated. A significant difference was detected in LTP between the two groups (P = 0.034), with no significant difference in OS between the two groups (P = 0.193). There were no severe complications related to ablation. Univariate analysis revealed that sex (P = 0.046) and child-turcotte-pugh (CTP) grade (P<0.001) were risk factors for OS, whereas CTP grade and treatment method (P<0.001) were risk factors for LTP. Multivariate analysis revealed that CTP grade B (P = 0.005) was independently associated with poor OS, and RFA alone (P<0.001) was independently associated with poor LTP. CONCLUSION: CT-RFA combined with TAE assisted by a 3DVAPS provided ideal clinical efficiency for HCC in challenging locations and was a highly safe treatment modality.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and therapeutic efficacy of adjuvant cytokine-induced killer (CIK) cells to minimally invasive therapies in unresectable hepatocellular carcinoma (u-HCC). MATERIALS AND METHODS: Hundred patients diagnosed with having u-HCC in our department from January 1, 2001, to July 31, 2018, were recruited. Forty-three patients received microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) together with autologous CIK cell treatment (TACE + MWA + CIK group), whereas 57 patients received TACE and MWA only (TACE + MWA group). Postprocedural complications and cumulative therapeutic effects were assessed in all patients. The disease control rate, median survival time (MST), and cumulative survival rate were compared between the cohorts using the Kaplan-Meier method and unpaired Student's t-tests. RESULTS: The overall response (complete response [CR] + partial response [PR]) rate was 74.42% (32/43) and 77.19% (44/57) for TACE + MWA + CIK and TACE + MWA groups, respectively (P = 0.243). Those of the TACE + MWA + CIK group had better rates of disease control (CR + PR + stable disease) in contrast to the TACE + MWA group (87.72% vs. 79.07%, respectively) but this failed to achieve statistical significance (P = 0.748). Based on the Kaplan-Meier survival graphs, those of the TACE + MWA + CIK groups possessed markedly increased overall survival (41 months vs. 24 months, P = 0.002) and progression-free survival (17 months vs. 10 months, P = 0.023) rates in compared to the TACE + MWA group. Survival rates were raised also TACE + MWA + CIK group than in TACE + MWA group (P = 0.002), with a MST of 6.13 ± 0.83 months and 11.61 ± 1.59 months in the TACE + MWA + CIK and TACE + MWA groups, respectively. Patients in the TACE + MWA + CIK group were not reported to have any severe complications. CONCLUSION: CIK cell immunotherapy as an adjuvant to TACE and MWA enhanced long-term prognosis and improved quality of life in patients with u-HCC. This regimen may be recommended as a novel treatment regime in u-HCC patients.

Radiofrequency Ablation Following Downstaging of Hepatocellular Carcinoma by Using Transarterial Chemoembolization: Long-term Outcomes.

Background Transarterial chemoembolization (TACE) is an effective downstaging procedure for hepatocellular carcinoma (HCC). However, knowledge of the effectiveness of radiofrequency ablation (RFA) after downstaging of HCC is currently lacking. Purpose To evaluate the clinical outcomes of RFA after downstaging of HCC by using TACE. Materials and Methods This retrospective study investigated a cohort of patients who underwent RFA with curative intent after downstaging with TACE to meet Milan criteria (one lesion up to 5 cm or no more than three lesions ≤3 cm without vascular invasion or extrahepatic metastasis) from January 2012 to July 2017. A control group of patients initially meeting the Milan criteria also underwent RFA as first-line treatment in the same period. Overall survival (OS), disease-free survival (DFS), and major complication rates were compared by using the log-rank test. To reduce potential bias, a propensity score analysis was also performed. Results There were 72 patients (median age, 56.5 years; range, 30-78 years; 67 men) in the downstaging group and 357 patients meeting the Milan criteria (median age, 58.0 years; range, 25-87 years; 313 men) included in this study. After propensity score matching, the 1-, 3-, and 5-year OS rates were 99%, 80%, and 66%, respectively, for the patients in the downstaging group and 94%, 84%, and 69%, respectively, for the patients in the Milan criteria group. The 1-, 3-, and 5-year DFS rate were 73%, 34%, and 24% for the downstaging group and 74%, 43%, and 37% for the Milan criteria group. There were no differences in the OS, DFS, or major complication rates between the two groups (P = .74, P = .39, P = .73, respectively). Conclusion The long-term patient survival and major complication rates of radiofrequency ablation following transarterial chemoembolization downstaging for hepatocellular carcinoma were similar to that of patients initially meeting the Milan criteria. © RSNA, 2019 See also the editorial by vanSonnenberg and Mueller in this issue.

Safety and effectiveness of multi-antenna microwave ablation-oriented combined therapy for large hepatocellular carcinoma.

BACKGROUND: In patients with a large, unresectable hepatocellular carcinoma (HCC), the primary recommendation is for transarterial chemoembolization (TACE) but used alone TACE is not typically curative. Combinations of TACE followed in a delayed fashion by single-applicator thermal ablation have also been suboptimal. As an alternative, we investigated the combination of TACE followed within 1-3 days by multi-antenna microwave ablation (MWA) in patients with a large HCC, to determine the feasibility, safety, local control, and short-term survival rates of this approach. METHODS: We retrospectively studied 43 patients with a large HCC (mean diameter, 8.8 cm; SD, 2.8 cm) treated between July 2015 and July 2018, who underwent TACE followed within 3 days by multi-antenna simultaneous MWA. We measured the liver and renal function before and after treatment, recorded complications, used three-dimensional software and imaging to calculate tumor necrosis rates at 1 month after therapy, and calculated overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. RESULTS: Mean follow up was 12.2 (range, 3.5-35.6) months. All patients completed the treatment protocol. At 1 month after combined therapy, tumor necrosis was complete in 16 (37.2%), nearly complete in 19 (44.2%), and partial in 8 (18.6%) patients. The 1- and 2-year OS rates were 64.0% and 46.8%, respectively, with a median OS of 23.0 months; and the 1- and 2-year PFS rates were 19.9% and 4.4%, respectively, with a median PFS of 4.2 months. A transient change in liver function occurred 3 days after MWA but resolved within 1 month. Only two patients had major complications, which were treatable and resolved. CONCLUSION: Multi-antenna MWA-oriented combined therapy is feasible and well tolerated, and it results in satisfactory initial local control and short-term survival in some but not all patients with a large HCC.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

Recombinant Fusion Streptavidin as a Scaffold for DNA Nanotetrads for Nucleic Acid Delivery and Telomerase Activity Imaging in Living Cells.

Efficient platforms for intracellular delivery of nucleic acids are essential for biomedical imaging and gene regulation. We develop a recombinant fusion streptavidin as a novel protein scaffold for DNA nanotetrads for highly efficient nucleic acid delivery and telomerase activity imaging in living cells via cross-linking hybridization chain reaction (cHCR). The recombinant streptavidin protein is designed to fuse with multiple SV40 NLS (nuclear localization signal) and NES (nuclear export signal) domains and prepared through Escherichia coli expression. The recombinant NLS-SA protein allows facile assembly with four biotinylated DNA probes via high-affinity noncovalent interactions, forming a well-defined DNA tetrad nanostructure. The DNA nanotetrads are demonstrated to confer efficient cytosolic delivery of nucleic acid via a caveolar mediated endocytosis pathway, allowing efficient escape from lysosomal degradation. Moreover, the nanotetrads enable efficient cHCR assembly in response to telomerase in vitro and in cellulo, affording ultrasensitive detection and spatially resolved imaging for telomerase with a detection limit as low as 90 HeLa cells/mL. The fluorescence brightness obtained in live cell imaging is found to be dynamically correlated to telomerase activity and the inhibitor concentrations. Therefore, the proposed strategy may provide a highly efficient platform for nucleic acid delivery and imaging of biomarkers in living cells.

Sequential and Simultaneous 4-Antenna Microwave Ablation in an Ex Vivo Bovine Liver Model.

AIMS: To determine the sizes and shapes of ablation zones in 4-antenna microwave ablation in ex vivo bovine liver model under different conditions of power delivery patterns, antenna spacings, and ablation durations, for further using of multi-antenna MWA strategies in the treatment of large hepatocellular carcinoma. METHODS: We tested protocols of eight ablations each on ex vivo bovine livers, involving simultaneous or sequential activation of four microwave antennas, spaced either 3 cm, 4 cm, or 5 cm apart, for either 10 or 15 min, at 60-W power. We determined the diameters, shapes, and temperatures of the ablation zones. RESULTS: Compared to sequential power delivery, simultaneous power delivery resulted in significantly larger ablation zone diameters (P < .001). The temperatures in ablation zones were significantly higher for simultaneous than for sequential power delivery. The largest ablation diameter (7.45 ± 0.06 cm) resulted from simultaneous delivery for 15 min using 4-cm antenna spacing. CONCLUSIONS: Simultaneous 4-antenna microwave ablation results in larger ablation zones than sequential ablation, and 4-cm antenna spacing with a 15-minute ablation duration creates the largest ablation zone. This information may provide multi-antenna MWA strategies for large HCC in the further clinical practice.

Crosslinking catalytic hairpin assembly for high-contrast imaging of multiple mRNAs in living cells.

A novel DNA nanotetrad mediated crosslinking catalytic hairpin assembly (CCHA) is reported to generate clumps of cross-linked mesh products for high-contrast and simultaneous imaging of multiple mRNAs in living cells.

Hydrochloric acid enhanced radiofrequency ablation for treatment of large hepatocellular carcinoma in the caudate lobe: Report of three cases.

BACKGROUND: To report on the use of percutaneous hydrochloric acid (HCl) enhanced radiofrequency ablation (HRFA) for the treatment of large (maximum diameter ≥ 5 cm) hepatocellular carcinoma (HCC) in the caudate lobe. CASE SUMMARY: Between August 2013 and June 2016, three patients with a large HCC (maximum diameter: 5.0, 5.7, and 8.1 cm) in the caudate lobe were treated by transarterial chemoembolization followed by computer tomography (CT) guided RFA using a monopolar perfusion RF electrode, which was enhanced by local infusion of 10% HCl at 0.2 mL/min (total volume, 3 to 12 mL). The output power of HRFA reached 100 W, and the average ablation time was 39 min (range, 15 to 60 min). Two patients each underwent one session of HRFA and one patient two sessions. After treatment, CT/magnetic resonance imaging showed that all the three lesions were completely ablated. There was no major complication. Two patients had asymptomatic bile duct dilatation. One patient died of tongue cancer 24 mo after ablation. The remaining two patients were alive and no area of enhancement is detected in the caudate lobe at 28 and 60 mo after ablation, respectively. CONCLUSION: Percutaneous CT-guided HRFA is safe and efficacious in treating large HCC in the caudate lobe.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Protein scaffolded DNA tetrads enable efficient delivery and ultrasensitive imaging of miRNA through crosslinking hybridization chain reaction.

Efficient intracellular delivery of nucleic acids to achieve sensitive detection and gene regulation is essential for chemistry and biology. Here we developed a novel protein scaffolded DNA tetrad, a four-arm DNA nanostructure constructed using streptavidin (SA) protein and four biotinylated hairpin DNA probes for efficient nucleic acid delivery and ultrasensitive miRNA imaging through crosslinking hybridization chain reaction (cHCR). DNA tetrads were easy to prepare and allowed precise control of the structure of the probes. DNA tetrads showed rapid intracellular delivery of DNA probes and high efficiency in lysosome escape by using confocal images for individual cells and flow cytometry for a large population of cells. cHCR allowed generating clumps of crosslinked hydrogel networks specifically to target miRNA, affording high sensitivity and spatial resolution for imaging. To our knowledge, this is the first time that HCR amplification has been realized in situ on nanostructures. Moreover, the FRET based design of cHCR conferred improved precision with the use of dual-emission ratiometric imaging to avoid false signals in biological systems. Intracellular imaging experiments further showed that DNA tetrad based cHCR could realize ultrasensitive and accurate miRNA imaging in living cells. Moreover, DNA tetrad based cHCR provided a potential tool for quantitative measurement of intracellular miRNA. The results suggested that this developed strategy provided a useful platform for nucleic acid delivery and low level biomarker imaging.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

BACKGROUND: It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. METHODS: One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. RESULTS: One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). CONCLUSIONS: This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Proton-Fueled, Reversible DNA Hybridization Chain Assembly for pH Sensing and Imaging.

Design of DNA self-assembly with reversible responsiveness to external stimuli is of great interest for diverse applications. We for the first time develop a pH-responsive, fully reversible hybridization chain reaction (HCR) assembly that allows sensitive sensing and imaging of pH in living cells. Our design relies on the triplex forming sequences that form DNA triplex with toehold regions under acidic conditions and then induce a cascade of strand displacement and DNA assembly. The HCR assembly has shown dynamic responses in physiological pH ranges with excellent reversibility and demonstrated the potential for in vitro detection and live-cell imaging of pH. Moreover, this method affords HCR assemblies with highly localized fluorescence responses, offering advantages of improving sensitivity and better selectivity. The proton-fueled, reversible HCR assembly may provide a useful approach for pH-related cell biology study and disease diagnostics.