Efficacy of mesenchymal stem cells in treating tracheoesophageal fistula via the TLR4/NF-κb pathway in beagle macrophages.

Background: Tracheoesophageal fistula (TEF) remains a rare but significant clinical challenge, mainly due to the absence of established, effective treatment approaches. The current focus of therapeutic strategy is mainly on fistula closure. However, this approach often misses important factors, such as accelerating fistula contraction and fostering healing processes, which significantly increases the risk of disease recurrence. Methods: In order to investigate if Mesenchymal Stem Cells (MSCs) can enhance fistula repair, developed a TEF model in beagles. Dynamic changes in fistula diameter were monitored by endoscopy. Concurrently, we created a model of LPS-induced macrophage to replicate the inflammatory milieu typical in TEF. In addition, the effect of MSC supernatant on inflammation mitigation was evaluated. Furthermore, we looked at the role of TLR4/NF-κB pathway plays in the healing process. Results: Our research revealed that the local administration of MSCs significantly accelerated the fistula's healing process. This was demonstrated by a decline in TEF apoptosis and decrease in the production of pro-inflammatory cytokines. Furthermore, in vivo experiments demonstrated that the MSC supernatant was effective in suppressing pro-inflammatory cytokine expression and alleviating apoptosis in LPS-induced macrophages. These therapeutic effects were mainly caused by the suppression of TLR4/NF-κB pathway. Conclusion: According to this study, MSCs can significantly improve TEF recovery. They achieve this via modulating apoptosis and inflammatory responses, mainly by selectively inhibiting the TLR4/NF-κB pathway.

CT-guided Percutaneous Microwave Ablation Combined with Local Radiotherapy or Chemotherapy of Malignant Pulmonary Tumors.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the clinical efficacy of CT-guided microwave ablation (MWA) combined with 125I seed implantation or bronchial arterial infusion (BAI) chemotherapy in the treatment of malignant pulmonary tumors. METHODS: A total of 56 patients who underwent MWA, MWA combined with 125I particle implantation, or MWA combined with BAI chemotherapy for advanced lung cancer or metastatic lung cancer from January 2015 to June 2021 in Guangdong Provincial People's Hospital were enrolled. Among them, 21 patients were treated with MWA (MWA), 18 with MWA combined with 125I seed implantation (MWA+125I), and 17 with MWA combined with BAI chemotherapy (MWA+BAI). The short-term outcomes, complications, Eastern Cooperative Oncology Group (ECOG) performance score (Zubrod-ECOG-WHO, ZPS), survival, and factors related to survival were compared between the three groups. RESULTS: The response rate of the MWA group (9.52%) was significantly lower than that of the MWA+125I group (50.00%) and MWA+BAI chemotherapy group (47.06%), and the differences were statistically significant (p < 0.05). The incidence of complications in the MWA, MWA+125I, and MWA+BAI chemotherapy groups was 47.62%, 55.56%, and 52.94%, respectively, with no significant difference (p > 0.05). Three months after the treatment, the ZPS of the MWA+125I and MWA+BAI chemotherapy groups was significantly lower than before treatment and significantly lower than that of the MWA group in the same period; the differences were statistically significant (p < 0.05). The median survival time of the MWA+125I group was 18 (9.983, 26.017) months and that of the MWA+BAI chemotherapy group was 21 (0.465, 41.535) months, both of which were higher than that of the MWA group [11 (6.686, 15.314) months]; the differences were statistically significant (p < 0.05). Cox regression analysis was performed on the factors related to survival and revealed treatment mode as a protective factor [HR = 0.433, 95% CI = (0.191, 0.984), p = 0.046]. Other factors, such as gender, age, and tumor size, did not independently affect survival. CONCLUSION: CT-guided MWA combined with 125I seed implantation and MWA combined with BAI chemotherapy are safe and effective for the treatment of advanced lung cancer and metastatic lung cancer, and can control tumor progression and prolong survival time.

Optical navigation robot-assisted puncture system for accurate lung nodule biopsy: an animal study.

Background: As lung cancer is one of the most significant factors seriously endangering human health, a robot-assisted puncture system with high accuracy and safety is urgently needed. The purpose of this investigation was to compare the safety and effectiveness of such a robot-assisted system to the conventional computed tomography (CT)-guided manual method for percutaneous lung biopsies (PLBs) in pigs. Methods: An optical navigation robot-assisted puncture system was developed and compared to the traditional CT-guided PLB using simulated lesions in experimental animals. A total of 30 pulmonary nodules were successfully created in 5 pigs (Wuzhishan pig, 1 male and 4 females). Of these, 15 were punctured by the optical navigation robot-assisted puncture system (robotic group), and 15 were manually punctured under CT guidance (manual group). The biopsy success rate, operation time, first needle tip-target point deviation, and needle adjustment times were compared between groups. Postoperative CT scans were performed to identify complications. Results: The single puncture success rate was higher in the robotic group (13/15; 86.7%) than in the manual group (8/15; 53.3%). The first puncture was closer to the target lesion (1.8±1.7 mm), and the operation time was shorter (7.1±3.7 minutes) in the robotic group than in the manual group (4.4±2.8 mm and 12.9±7.6 minutes, respectively). The angle deviation was smaller in the robotic group (3.26°±2.48°) than in the manual group (7.71°±3.86°). The robotic group displayed significant advantages (P<0.05). The primary complication in both groups was slight bleeding, with an incidence of 26.7% in the robotic group and 40.0% in the manual group. There was 1 case of pneumothorax in the manual group, and there were no deaths due to complications in either group. Conclusions: An optical navigation robot-assisted system for PLBs guided by CT images was developed and demonstrated. The experimental results indicate that the proposed system is accurate, efficient, and safe in pigs.

CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription.

Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1-500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth.

Predictive value of a novel lncRNA LINC02518 in evaluating the prognosis of patients with hepatocellular carcinoma.

Aim: The potential of long noncoding RNA in hepatocellular carcinoma (HCC) has led to promising insights into therapeutic intervention. The clinical significance of LINC02518 in HCC is unclear. This study aimed to evaluate the predictive value of a novel long noncoding RNA, LINC02518, for the prognosis of patients with HCC. Methods: Between December 2005 and November 2011, 125 and 75 HCC patients in the training and validation groups, respectively, who underwent liver surgery were included in our study. The LINC02518 expression of HCC and corresponding nontumor liver tissues was detected using microarray and reverse transcription quantitative polymerase chain reaction (RT-qPCR). These HCC patients were assigned into high and low LINC02518 expression groups based on the threshold of the receiver operating characteristic curve. Kaplan-Meier analysis was performed to determine the prognosis of HCC patients. Results:LINC02518 expression was upregulated in paired tumor samples compared with corresponding nontumor samples in the two groups. The area under the receiver operating characteristic curve for the levels of LINC02518 in the diagnosis of HCC was 0.66, 95% CI: 0.59-0.73. HCC patients with high LINC02518 expression had significantly worse tumor recurrence-free, metastasis-free, disease-free and overall survival than those with low LINC02518 expression. Conclusion:LINC02518 is negatively correlated with the prognosis of HCC and provides a promising strategy for the treatment and prognosis of HCC.

Feasibility and Clinical Value of CT-Guided 125I Brachytherapy for Pain Palliation in Patients With Breast Cancer and Bone Metastases After External Beam Radiotherapy Failure.

Objectives: To evaluate the feasibility and clinical value of CT-guided iodine-125 (125I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure. Methods: From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both 125I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B). Results: In Group A, 45 125I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of 125I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in "worst pain," "least pain," "average pain," and "present pain" 3-day after treatment and could achieve a 12-week-remission for "worst pain," "least pain," "average pain," and "present pain." The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B. Conclusion: The CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

OBJECTIVE: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). METHODS: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. RESULTS: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. CONCLUSIONS: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. KEY POINTS: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

Percutaneous endobiliary radiofrequency ablation and stents in management of hepatocellular carcinoma with bile duct tumor thrombus: Initial single-institution experience.

AIM: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is a rare condition, but it can lead to hepatic failure and is associated with poor prognosis. Treatment for HCC with BDTT remains a challenge. This study aimed to retrospectively evaluate the safety and feasibility of percutaneous endobiliary radiofrequency ablation (EB-RFA) and biliary metal stent placement as an alternative treatment for patients with HCC with BDTT. METHODS: From October 2014 to December 2016, nine patients (all men, mean age 53.2 ± 12.0; range 40-70) who underwent percutaneous EB-RFA and biliary metal stent placement for HCC with BDTT were included. Stent patency, overall survival, technical and clinical success rate and complications were investigated. RESULTS: Median stent patency from the time of the first EB-RFA was 6.0 months (95% CI, 5.4-6.6 months) and survival from the time of diagnosis was 6.0 months (95% CI, 2.2-9.8 months). Two of 9 patients underwent bilateral EB-RFA and stent placement, one underwent unilateral EB-RFA and stent-in-stent procedure, and one EB-RFA as treatment for biliary metal stent occlusion. One patient who presented with stent occlusion underwent repeat ablations 182 days after the first ablation procedure and 53 days after the re-ablation procedure. Combination therapy was administered to five patients. The technical and clinical success rate were 100% and 89% per patient. After treatment, serum direct bilirubin levels were notably decreased in eight patients. No major complications were observed. Minor complications included one bile duct bleeding, three postoperative abdominal pain and two cholangitis. CONCLUSION: Percutaneous EB-RFA and biliary metal stent placement might be technically safe and feasible therapeutic options for patients with HCC with BDTT.

Hepatic fibrosis and short-term clinical efficacy after hepatic artery embolization for unresectable hepatocellular carcinoma using doxorubicin-eluting HepaSphere.

BACKGROUND: Hepatocellular carcinoma (HCC) is most common malignancies around world. Transcatheter arterial chemoembolization (TACE) is recognized as the first-line treatment for HCC by NCCN, and its efficacy is widely reported. However, repeated TACE induces hepatic fibrosis. How to reduce hepatic fibrosis and retard cirrhosis is an urgent problem in treatment of HCC. To verify the efficacy of doxorubicin-eluting HepaSphere for TACE in the treatment of unresectable HCC. METHODS: We retrospectively analyzed 91 patients with unresectable HCC underwent TACE from June 2015 to June 2018. Among which, 51 cases were treated with HepaSphere-and 40 cases were treated with iodized oil. The primary endpoint was got according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Type IV collagen (IV-C), layer mucin (LN), amino-terminal propeptide of type III procollagen (PIIINP), and hyaluronic acid (HA) were tested before and after TACE treatment. RESULTS: Serologic factors of the groups were re-examined 3 days after TACE, which showed higher ALT and AST in the conventional TACE group than in the HepaSphere-TACE group (P<0.05). The postoperative efficacies were evaluated according to the mRECIST criteria. No difference in the short-term efficacy between these two groups (P>0.05) were found. Moreover, serologic factors for fibrosis were further re-examined 6 months later, showing no differences for IV-C and PIIINP (P=0.906 and 0.574, respectively). However, LN and HA were slightly higher in C-TACE group than HepaSphere-TACE group (P=0.045 and 0.048, respectively). CONCLUSIONS: HepaSphere-TACE is prevents the occurrence of late hepatic fibrosis effectively.

Relationship between circulating tumor cells undergoing EMT and short-term efficacy following interventional treatment in patients with hepatocellular carcinoma.

OBJECTIVE: A growing number of studies have indicated that epithelial-mesenchymal transition (EMT) phenotypes and the number of circulating tumor cells (CTCs) are significant indicators of tumor characteristics and treatment efficacy, and thus have a broad range of potential applications in the diagnosis and treatment of malignant tumors. The value of data on CTC phenotypes and CTC counts in the diagnosis of hepatocellular carcinoma (HCC) and assessment of efficacy after comprehensive interventional therapy remains unclear. METHODS: Data of 107 patients who exhibited space-occupying lesions in the liver on enhanced CT/MRI scans at the Guangdong Provincial People's Hospital (a tertiary medical center) between August 2017 and October 2018, were retrospectively analyzed. All enrolled patients were treated with transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA). An imFISH CTC assay was used to isolate and count CTCs with different EMT phenotypes in the patients' peripheral blood, which facilitated an analysis of the value of CTC phenotype and CTC count data in the diagnosis or treatment of HCC. RESULTS: The CTC count and EMT phenotypes in HCC patients were not associated with patient characteristics such as age, sex, Hepatitis B Virus (HBV)-DNA status, alcohol consumption history, Aspartate Transaminase (AST) to Platelet Ratio Index (APRI) score, Eastern Cooperative Oncology Group (ECOG) score, Child-Pugh score, alpha-fetoprotein (AFP), number and size of tumors, vascular invasion, or metastasis (P â€‹> â€‹0.05). The CTC count and EMT phenotypes in HCC patients before treatment were not predictive of short-term efficacy (P â€‹> â€‹0.05). Comprehensive interventional therapy reduced the total CTC count and mesenchymal CTC count (P â€‹= â€‹0.034 and 0.022, respectively). CONCLUSION: TACE in combination with ablation reduced the total CTC count and mesenchymal CTC count. The CTC count and EMT phenotypes may be associated with long-term efficacy.

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.

Efficacy and safety of sorafenib versus apatinib in the treatment of intermediate and advanced hepatocellular carcinoma: a comparative retrospective study.

OBJECTIVE: To compare the efficacy and safety profiles of sorafenib and apatinib in patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC). METHODS: This was a single-center, retrospective study where we collected the clinical data of 72 patients, diagnosed with intermediate or advanced HCC from January 2014 to December 2016. Depending on the treatment received, 38 patients were categorized into group S (sorafenib group) and 34 into group A (apatinib group). The patients in group A received the initial recommended dose of 750 mg once daily (QD), which was reduced to 250 mg QD in the case of any class 3 or 4 adverse event (AE). Sorafenib was administered orally 400 mg twice daily (BID), and dose was modified to 400 mg or 200 mg QD in the case of grade 3 or 4 AEs. The median overall survival (OS), progression-free survival (PFS), and AEs reported in the two groups were analyzed and compared. RESULTS: Among the 38 patients treated with sorafenib, one patient had complete response (CR), 5 patients had partial response (PR), and 10 patients had stable disease (SD), and among the 34 patients treated with apatinib, 6 patients had PR and 7 patients had SD with no cases of CR. PFS in group S was significantly longer compared with that in group A (7.39 vs 4.79 months, respectively, P=0.031). Similar observations were made for median OS (10.4 months in group S vs 7.18 months in group A, P=0.011). However, there was no significant difference in the objective response rates (ORRs) among the study population (15.7 vs 17.6%, P=0.829). Common AEs in group S included hand and foot syndrome (HFS) and diarrhea, whereas common AEs in group A included hypertension, proteinuria, and increased transaminase. CONCLUSION: Our study showed promising clinical outcome with apatinib, but the sorafenib group exhibited better clinical efficacy with no significant difference in safety profile.

Microwave ablation versus radiofrequency ablation for the treatment of pulmonary tumors.

To retrospectively compare the efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) in the treatment of pulmonary tumors, a total of 75 patients with lung tumor who underwent thermal ablation therapy in Guangdong General Hospital into the study from March 2007 to December 2014 were enrolled. Of the patients, 43 received radiofrequency ablation and 32 received microwaves ablation. The response rates, overall survival (OS), and complications rates between the RFA group and MWA group were compared. There were no significant differences in the baseline characteristics between two groups. The overall response rates of in RFA and MWA groups were 79% (34/43) and 69% (22/32), respectively, and there was no statistically significant difference between two groups (P = 0.309). The 1-, 2-, 3-, 5-year overall survival (OS) rates in RFA group and MWA group were 77%, 55%, 42%, 34% and 75%, 44%, 40%, 27%, respectively. No significant differences were found in the OS rates between two groups (P = 0.653). The complication rates were 49% (21/43) in RFA group and 50% (16/32) in MWA group; there was no significant difference between two groups (P = 0.921). No patients died during the perioperative period. Our study shows that no significant differences exist in efficacy and safety between RFA and MWA for the treatment of pulmonary tumors, which indicates that MWA could be a substitute therapy for RFA in terms of effectiveness and safety for treating pulmonary tumors.

[Transarterial oily chemoembolization combined with interstitial laser thermotherapy for treatment of hepatocellular carcinoma].

OBJECTIVE: To evaluate the therapeutic effects and adverse effects of transarterial oily chemoembolization combined with interstitial laser thermotherapy (TOCE+ILT) in the treatment of hepatocellular carcinoma. METHODS: Totally 120 patients with hepatocellular carcinoma were randomized into two groups and received interventions with TOCE+ILT or TOCE combined with percutaneous ethanol injection (TOCE+PEI). The treatment was repeated when necessary until the tumor was completely ablated, after which the therapeutic effects were evaluated and the patients were the followed up for observing long-term clinical outcome. RESULTS: Of the 120 patients enrolled in this observation, 105 were followed up for two years (54 in TOCE+ILT group and 51 in TOCE+PEI group). The complete tumor necrosis rate of TOCE+ILT group was significantly higher than that of the TOCE+PEI group (84.8% vs 73.9%,Chi(2)=4.405, P=0.036), and TOCE+ILT was associated with a significantly higher negative conversion rate of AFP positivity (77.8% vs 56.1%, Chi(2)=4.592, P=0.032). The 1-year survival rate were similar between two groups, but the 2-year survival rate was significantly higher in patients with TOCE+ILT (79.6% vs 60.8%, Chi(2)=4.477, P=0.034). The hepatic function was comparable between the two groups before treatment, and 1 week after treatment, the ALT level in patients undergoing TOCE+ILT was significantly lower than that in patients with TOCE+PEI (95.90-/+56.06 U/L vs 116.31-/+45.27 U/L, t=2.04, P=0.043). Post-embolization syndrome was observed in the patients in two groups, but no severe adverse events were found. CONCLUSION: TOCE+ILT has good therapeutic effects and mild side effects in the treatment of hepatocellular carcinoma.