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   Table of Contents - Current issue
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 2020
Volume 16 | Issue 2
Page Nos. 199-400

Online since Thursday, May 28, 2020

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EDITORIAL  

Management of pulmonary multifocal ground-glass nodules: How many options do we have? Highly accessed article p. 199
Baodong Liu, Xin Ye
DOI:10.4103/jcrt.JCRT_377_20  PMID:32474501
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ORIGINAL ARTICLES Top

Experimental study on radiation damage of125I seeds implanted in canine gastric wall tissue p. 203
Zaishuang Ju, Zhe Wang, Lin Wang, Jianxin Li, Zhong Wu, Xiang Li, Fuguang Wang, Ruoyu Wang
DOI:10.4103/jcrt.JCRT_544_19  PMID:32474502
Objective: The objective of the study was to investigate the radiation damage to125 I seeds implanted in canine gastric wall tissue. Materials and Methods: Eight beagles were randomly assigned to either the treatment or control group, with four beagles per group. For each beagle in the treatment group, six125 I seeds were implanted in the gastric wall in two rows, spaced at 1.0 cm, with a seed activity of 0.5 mCi and a half-life of 60.2 d. For each beagle in the control group, six 125 I seeds were similarly implanted as a cold source. After implantation, the beagles were scanned by computed tomography (CT) (slice thickness: 2 mm), the region of interest was labeled along the seed boundaries, and postoperative doses were verified. One beagle per group was sacrificed at the 1, 2, 3, and 4 half-lives to be used as gross specimens for observing histological and ultrastructural changes using light microscopy and electron microscopy, respectively. Results: Beagles from the treatment group who had125 I radioactive seeds implanted in their stomach walls had the most radiation damage after two half-lives, damage repair began after three half-lives, and the damage was stabilized and further repaired after four half-lives. In the control group, only mild inflammatory reactions were observed around the seeds. Conclusion: Appropriate and well-planned implantation of125 I radioactive seeds in beagle stomach walls is safe and reliable.
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Matrine inhibits proliferation and migration of HepG2 cells by downregulating ERK1/2 signaling pathways p. 209
Haipeng Yu, Bolan Zhu, Wan Yang, Qian Zhang, Wei Wang, Weichun Zhai, Lixia Lu, Ying Zheng, Zheng Dang, Bin Li, Chuyi Li, Bin Liang, Jiucong Zhang, Xiaohui Yu
DOI:10.4103/jcrt.JCRT_331_19  PMID:32474503
Objective: To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Methods: HepG2 cell was selected and divided into blank control group, experimental group (matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. Results: With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). Conclusion: Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.
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Berberine enhances the radiosensitivity of osteosarcoma by targeting Rad51 and epithelial–mesenchymal transition p. 215
Dapeng Wang, Ke Fen Zhang, Gang Du, Jun Wang, Jinmin Zhao
DOI:10.4103/jcrt.JCRT_293_19  PMID:32474504
Objective: Osteosarcoma is a malignant bone tumor and is generally treated with radiotherapy combined with radiosensitizers. The aim of the present study was to investigate the radiosensitization effects of berberine on osteosarcoma cells and the role of Rad51 in radiosensitivity by berberine. Materials and Methods: Cells from the human osteosarcoma cell line MG-63 were exposed to γ-ray irradiation (0, 2, 4, 6, and 8 Gy) and berberine (20 μM). Radiosensitivity was evaluated by determining cell viability using an MTT assay. Flow cytometry was used to determine cell cycle and apoptosis. Real-time PCR and western blot were performed to analyze the mRNA and protein expressions of Rad51. The protein levels of E-cadherin and vimentin were also measured to evaluate the epithelial–mesenchymal transition (EMT) process. Tumor invasion was determined by the Boyden chamber assay. Results: Berberine exacerbated the decline in viability of MG-63 cells exposed to γ-rays irradiation at various concentrations (25, 50, 75, and 100 μmol/L) and induced cell cycle arrest in the G2/M phase as well as apoptosis. The mRNA and protein expressions of Rad51 were significantly decreased by berberine in MG-63 cells. Inhibition of Rad51 by B02 enhanced the radiosensitivity of MG-63 cells. Berberine inhibited their invasive capability as well as increased E-cadherin and decreased vimentin protein levels; this indicated that berberine suppressed the EMT process in MG-63 cells exposed to γ-rays irradiation. Conclusion: Berberine enhances the radiosensitivity of MG-63 osteosarcoma cells. Rad51 is a potential target of berberine in the radiosensitization of osteosarcoma.
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Induction chemotherapy for unresectable Stage III non-small-cell lung cancer may improve survival of induction chemotherapy responders as predicted by elevated levels of carcinoembryonic antigen and cytokeratin fragment 19 and classification as stage N3 cancer p. 222
Qiang Li, Meng Jiang, Xiao Han, Zhe Yang, Weibin Shu, Xiao Ding
DOI:10.4103/jcrt.JCRT_710_19  PMID:32474505
Aims: The aim of this study is to investigate patients with unresectable Stage III non-small-cell lung cancer (NSCLC) receiving radiotherapy with induction and concurrent pemetrexed or docetaxel plus cisplatin (PP/DP) chemotherapy and to identify the subgroup most likely to benefit from induction chemotherapy (IC). Subjects and Methods: Patients with unresectable measurable Stage III NSCLC received two cycles of PP/DP IC followed by concurrent chemoradiotherapy at a dose of 60–66 Gy. Statistical Analysis Used: Cox regression analysis was performed to evaluate the prognostic factors for survival; logistic regression analysis was used to evaluate the predictors for response to IC, and the receiver operating characteristic curves were used to evaluate the independent factors predicting response. Results: Eighty patients were included; the median survival time (MST) was 22.1 months. Partial response (PR) to IC was an independent prognostic factor for overall survival. For patients in the PR and stable disease groups, the MST was 36.7 and 19.5 months, respectively. The independent predictors of PR to IC included classification as stage N3 cancer, baseline carcinoembryonic antigen (CEA) levels >10 ng/ml, and cytokeratin fragment 19 (CYFRA21-1) levels >6 ng/ml. With each additional independent predictor, the likelihood of having have PR to IC increased. Conclusions: Radiotherapy with induction and concurrent PP/DP chemotherapy is feasible for patients with unresectable Stage III NSCLC. IC may improve the survival of IC responders, as predicted by elevated CEA and CYFRA21-1 levels and classification as stage N3 cancer. Additional randomized trials on IC may consider these predictors to tailor individualized treatments.
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Analysis of treatment methods and prognostic factors in 354 cases of hilar cholangiocarcinoma: A cohort study p. 230
Zhaowei Sun, Yujie Feng, Hao Liu, Fangzhen Shen, Jinming Xiao, Xiaoliang Kang, Yongrong Zhao, Huazhi Xiao, Wei Zhao, Xiao Hu, Jinliang Li, Haoyue Ma, Guanghua Cao, Na Su, Bingyuan Zhang
DOI:10.4103/jcrt.JCRT_637_19  PMID:32474506
Context: Better management strategies are needed to improve the survival of patients with hilar cholangiocarcinoma (HCCA). Aims: This study was designed to examine the effects of different treatment methods on survival and prognostic factors in HCCA. Settings and Design: We retrospectively analyzed the clinical data of 354 patients with HCCA treated at our institution from 2003 to 2013. Materials and Methods: Patients were divided into three groups according to the treatment: the radical resection group, the nonradical resection group, and the biliary drainage-only group. Statistical Analysis Used: The Kaplan–Meier method was used to compare survival rates between the groups, and the independent prognostic factors were assessed using the Cox proportional hazards model. Results: There were 110 patients in the radical resection group, 93 patients in the nonradical resection group, and 151 patients in the biliary drainage-only group, and they showed differing survival rates: 1-year survival rates of 70.7%, 49.5%, and 31.3%; 2-year survival rates of 62.9%, 24.7%, and 9.0%; 3-year survival rates of 34.7%, 4.0%, and 0%; and median survival of 21.7 months, 13.6 months, and 8.7 months, respectively. The radical resection group had the longest overall survival (P< 0.001). Treatment method, albumin (ALB), total bilirubin (TBIL), postoperative pathological T-stage, and distant metastasis were identified as independent prognostic indicators of survival. Conclusions: Radical resection significantly increases survival in patients with HCCA, and an increase in ALB and a decrease in TBIL improve the prognosis of patients with HCCA.
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Para-aortic lymph node tracing and dissection in advanced gastric cancer: Effectiveness of carbon nanoparticles injection through the no. 12b lymph node p. 238
Guangchuan Mu, Yuan Huang, Chengzhi Wei, Zhibai Chen, Xianghua Wu, Xingan Qin, Yanjun Zeng
DOI:10.4103/jcrt.JCRT_506_19  PMID:32474507
Background and Objectives: The relative effectiveness of tracers in guiding para-aortic lymph node dissection (PAND) in advanced gastric cancer is undefined. In this single-center, prospective study, we aimed to discuss the effectiveness of such tracers. Materials and Methods: Between January 2015 and January 2016, 90 consecutive patients with stage T4a gastric cancer were evenly assigned to receive 0.2 mL of carbon nanoparticles (a), methylene blue (b), or no tracer (c) injection through no. 12b lymph nodes before PAND. Results: There was no difference in the baseline characteristics between the three groups. Group A vs. B or C had a higher number of dissected lymph nodes (34.1 ± 9.8, 25.5 ± 5.5, and 22.6 ± 3.7; P < 0.001; B vs. C: P =0.321) and no. 16a2/b1 para-aortic lymph nodes (PANs; 11.8 ± 4.8, 7.0 ± 1.2, and 5.5 ± 1.2; P < 0.001; B vs. C: P =0.178) and similar rates of lymph node metastasis (20.9 ± 17.5%, 19.1 ± 15.1%, and 23.6 ± 19.7%; P = 0.511), positive dissected PAN (23.3% [7/30], 16.7% [5/30], and 16.7% [5/30]), surgery duration (252.9 + 35.4, 244.4 ± 29.0, and 250.3 + 29.9 min; P = 0.421), and blood loss (266.7 ± 115.5, 270.0 ± 82.6, and 260.0 ± 116.3 mL, P = 0.933). There was no common bile duct damage by tracer injection, and one case of duodenal stump fistula, one abdominal infection, and two anastomotic leakages in Groups A–C, respectively, were treated successfully. Conclusions: In advanced gastric cancer treatment, carbon nanoparticle injection into no. 12b nodes appears to better trace no. 16a2/b1 PAN.
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A comparison between drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis of six randomized controlled trials p. 243
Hongye Wang, Cheng Cao, Xiyi Wei, Kangjie Shen, Yimei Shu, Xiaojie Wan, Jinyu Sun, Xiaohan Ren, Yuxiang Dong, Yihai Liu, Bo Zhai
DOI:10.4103/jcrt.JCRT_504_19  PMID:32474508
Objective: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate hepatocellular carcinoma. Drug-eluting beads (DEB)-TACE is a promising approach expected to improve the efficiency and safety of conventional (c) TACE. However, controversy remains whether DEB-TACE performs better than cTACE. This meta-analysis aimed to compare cTACE and DEB-TACE in terms of overall survival (OS), adverse events, and response rate. Literature search was performed in PubMed, Cochrane, Embase, and Web of Science. Complete response (CR), partial response (PR), disease control (DC), stable disease (SD), OS, and major complications were compared between these two modalities. The pooled relative risk and 95% confidence interval were calculated for assessment. Six randomized controlled trials were included for further analysis after a comprehensive search. No significant difference was found in overall response at 3, 6, 9, and 12 months, CR, PR, DC (SD), OS and complications between cTACE and DEB-TACE. Conclusion: DEB-TACE had similar therapeutic effects to those of cTACE. Furthermore, major complications in both therapies were similar. The superiority of DEB-TACE over cTACE remains unclear, and further research with high-quality evidence is needed.
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Transarterial chemoembolization combined with microwave ablation and apatinib in patients with Barcelona clinic liver cancer Stage C hepatocellular carcinoma: A propensity score matching analysis p. 250
Chen Shuanggang, Lujun Shen, Zhiyu Qiu, Han Qi, Fei Cao, Lin Xie, Weijun Fan
DOI:10.4103/jcrt.JCRT_345_19  PMID:32474509
Context and Aims: Apatinib combined with transarterial chemoembolization (TACE) has shown promising results in cases of Barcelona clinic liver cancer Stage C (BCLC C) hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of TACE in combination with microwave ablation (MWA) and apatinib. Materials and Methods: A retrospective, single.center study was undertaken using a one.to.one propensity score matching (PSM) analysis design and involved BCLC C HCC patients who underwent treatment with TACE.MWA.apatinib or TACE alone between January 2013 and June 2018. The patients were recommended to administer 500mg apatinib per day, combined with MWA and TACE. The adverse effects of apatinib, MWA. and TACE.related complications, progression.free survival (PFS), and overall survival (OS) were assessed. Results: Of the 149 patients with BCLC C HCC who underwent TACE.MWA.apatinib or TACE alone, 131 were included in our study. Among them, 21 (16.0%) received TACE.MWA.apatinib and 110 (84.0%) underwent TACE alone. After PSM, twenty pairs were enrolled into different treatment groups. Patients in the TACE.MWA.apatinib group had a significantly longer median PFS than patients in the TACE.alone group on both before (median, 8.9 vs. 1.7 months, P = 0.0002) and after PSM (median, 5.4 vs. 2.1 months, P = 0.001). They also had a significantly longer median OS than patients in the TACE.alone group on before (median, 24.4 vs. 5.8 months, P = 0.000007) and after PSM (median, 24.4 vs. 5.4 months, P = 0.00005). Conclusions: The combination of apatinib, TACE, and MWA in BCLC C HCC patients is safe and effective. Toxicity is manageable by adjusting the apatinib dosage.
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Analysis of imaging-guided thermal ablation puncture routes for tumors of the hepatic caudate lobe p. 258
Yuan Yan, Zheng-Yu Lin, Jin Chen
DOI:10.4103/jcrt.JCRT_341_19  PMID:32474510
Aims: The goal of this study was to analyze the puncture routes of imaging-guided thermal ablation for tumors of the hepatic caudate lobe. Materials and Methods: The imaging-guided thermal ablation puncture routes of 12 cases of hepatic caudate lobe tumors were collected in our hospital from January 2013 to February 2019. The puncture routes were retrospectively analyzed, and the experience of thermal ablation therapy for hepatic caudate lobe tumors was summarized. Results: Among the 12 cases of hepatic caudate lobe tumors, puncture routes were divided into the anterior (through the left lobe of the liver) approach (six cases), the right hepatic approach (five cases), and the transthoracic approach (one case). Different ablation electrodes were selected according to the puncture route and method of guiding. No serious postoperative complications were noted. Conclusion: The hepatic caudate lobe is surrounded by the inferior vena cava, hepatic vein, and hepatic hilum, leading to great difficulties and risks in performing minimally invasive treatment of hepatic caudate lobe malignancies. Therefore, selecting an appropriate puncture route is an important factor in the success of the treatment.
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Luteolin-loading of Her-2-poly (lactic-co-glycolic acid) nanoparticles and proliferative inhibition of gastric cancer cells via targeted regulation of forkhead box protein O1 p. 263
Jian Ding, Qiu Li, ShanShan He, Jie Xie, XiaoFei Liang, Ting Wu, Dan Li
DOI:10.4103/jcrt.JCRT_438_18  PMID:32474511
Background: Developing the natural medicine that allow for the specific targeting cytotoxicity is a very important research area in the development of anti-tumor drugs. Aims and Objectives: This study was conducted to determine the targeted inhibitory effects of luteolin-loaded Her-2-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on gastric cancer cells and to delineate the mechanism underlying the inhibition of tumors by luteolin. Materials and Methods: Luteolin-loaded Her-2-PLGA NPs (Her-2-NPs) were prepared, physically and chemically characterized, and their effects on gastric cancer cells were investigated. The rate of NP uptake by cells and the cell morphology were observed using confocal microscopy; the rates of cell proliferation and apoptosis were identified using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay and flow cytometry, respectively; and the mRNA and protein expression levels of forkhead box protein O1 (FOXO1) were determined using quantitative polymerase chain reaction and Western blotting, respectively. Results: Compared with nontargeted microspheres, Her-2-NPs led to significantly enhanced uptake of luteolin by SGC-7901 cells. Luteolin-loaded Her-2-NPs also significantly inhibited the proliferation of gastric cancer cells, weakened their migratory ability, and increased both the mRNA and protein expression levels of FOXO1. Conclusion: Luteolin-loading of Her-2-NPs could potentially be used as a novel anti-cancer drugs for targeted cancer therapy.
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Clinical significance of hypoxia-inducible factor 1α, and its correlation with p53 and vascular endothelial growth factor expression in resectable esophageal squamous cell carcinoma p. 269
Na Shao, Yue Han, Liang Song, Wei Song
DOI:10.4103/jcrt.JCRT_781_19  PMID:32474512
Background: Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are important factors that facilitate tumor progression. The aims of our study were to investigate the expression of HIF-1α, p53, and VEGF in esophageal squamous cell carcinoma (ESCC) treated by curative surgery and to analyze their association with clinicopathological parameters and clinical outcome. Materials and Methods: The surgical specimens from 120 patients who had undergone potentially curative resection for ESCC were immunohistochemically assessed using monoclonal antibodies against HIF-1α, p53, and VEGF. Results: Positive rates of HIF-1α, p53, and VEGF expression were 61.7%, 56.7%, and 78.3%, respectively. No significant relationship was found between HIF-1α, p53, VEGF expression, and the analyzed clinicopathological parameters. There was no significant correlation between the expression of HIF-1α, p53, and VEGF. Univariate analysis revealed that overexpression of HIF-1α was associated with poor disease-free and overall survival (P = 0.023 and 0.01, respectively). Multivariate analysis demonstrated that upregulation of HIF-1α is an independent predictor for poor overall survival (P = 0.044). Conclusions: HIF-1α was a useful independent prognostic factor for surgically treated ESCC. Further studies with larger sample size are required to determine the relationship between the expression of HIF-1α, p53, VEGF, and clinicopathological parameters.
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In vivo microscopy of arterial distribution embolic particles in rabbit mesenteric artery p. 276
Wei Li, Jun Yang, Chengtao Gu, Yu Yin, Zhi Li, Caifang Ni
DOI:10.4103/jcrt.JCRT_435_19  PMID:32474513
Purpose: To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy.To study the arterial distribution of embosphere microsphere (EM) and polyvinyl alcohol (PVA) particles in rabbit mesenteric artery using in vivo microscopy. Methods: Sixteen New Zealand rabbits were divided into four groups, namely large PVA (560–710 μm), small PVA (150–350 μm), large EM (500–700 μm), and small EM (100–300 μm). The mesenteric arteries of the experimental animals were embolized under fluoroscopic guidance and visualized using in vivo microscopy. The embolized vessel diameter and arterial distribution of embolic agents were compared. Results: The diameters of occluded vessels in large PVA, small PVA, large EM, and small EM groups were 430.60 ± 67.30, 200.95 ± 70.54, 387.79 ± 92.51, and 143.81 ± 39.65 μm, respectively. PVA occluded significantly larger vessels than EM when the particle size was similar (P < 0.001). The proportion of EM at the bifurcation of the artery was significantly higher than that of PVA particles (large PVA < large EM, χ2 = 4.325, P < 0.038; small PVA < small EM, χ2 = 6.68, P < 0.01). Conclusion: Both PVA and EM could occlude vessels smaller than the particle size, and EM resulted in deeper penetration. The location of embolic particles in the artery is mainly related to the shape of particles.
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Irreversible electroporation and adjuvant chemoradiotherapy for locally advanced pancreatic carcinoma p. 280
Kai Xu, Yongliang Chen, Junjun Su, Ming Su, Li Yan
DOI:10.4103/jcrt.JCRT_773_18  PMID:32474514
Context: The safety and efficacy of irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) are well established. However, whether adjuvant chemoradiotherapy after IRE increases, the survival rate remains unknown. Therefore, this study evaluated the effect of chemoradiotherapy combined with IRE in patients with LAPC. Subjects and Methods: We retrospectively analyzed 42 patients with LAPC between July 2015 and December 2016 at PLA General Hospital treated with IRE or IRE combined with radiation and/or chemotherapy. These patients were divided into the IRE group and the combined-therapy group. All patients underwent computed tomography (CT), magnetic resonance imaging, and positron-emission tomography-CT and no signs of metastases were found. The prognosis of these patients was observed. Results: The times after operation and after diagnosis in the combined-therapy group (304.20 ± 118.54) and (334.40 ± 114.07) days, respectively, were better those than in the IRE group (214.36 ± 95.68) and (244.68 ± 110.61) days, respectively. Moreover, patients in the combined-therapy group had a significantly better survival rate than the IRE group (80 vs. 45.45%, P < 0.05). Conclusions: IRE combined with radiotherapy or chemotherapy was superior to IRE alone for the treatment of LAPC, as it prolonged the survival time and improved the survival rate, making it worthy of wide dissemination and clinical application.
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A newly designed biliary brachytherapy drainage catheter for patients with malignant biliary obstruction: A pilot study p. 286
Dechao Jiao, Xueliang Zhou, Zongming Li, Yonghua Bi, Quanhui Zhang, Jing Li, Lei Li, Jianzhuang Ren, Xinwei Han
DOI:10.4103/jcrt.JCRT_804_19  PMID:32474515
Aim: Self.expandable metallic stent (SEMS) placement has been considered as the preferred treatment to relieve jaundice in nonsurgical patients. However, 50% of stents become stenosed within 3.6 months due to tumor ingrowth and epithelial hyperplasia. This study aims to evaluate the feasibility and efficacy of a newly designed brachytherapy biliary drainage catheter (BBDC) loaded with 125I seeds for palliation of malignant biliary obstruction (MBO). Methods: In this prospective study, patients with unresectable MBO underwent BBDC placement after SEMS placement at our center from September 2017 to April 2019. Results: A total of 21 patients with MBO were enrolled. The technical and clinical success rates were 100%. Total bilirubin, direct bilirubin, alanine aminotransferase, alkaline phosphatase, cancer antigen 19.9, and carcinoembryonic antigen levels significantly decreased during the 1.month follow.up (P < 0.05). Four patients (19%) had minor complications. During the median follow.up of 299 days, 13 patients (61.9%) developed stent occlusion. The 6.month stent patency and survival rates were 73.5% and 79.2%, respectively. The median stent patency and survival were 279 and 454 days, respectively. Conclusion: The use of BBDC loaded with 125I seeds is a feasible and effective method to prolong biliary stent patency in patients with MBO.
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US-guided percutanous microwave ablation for early-stage hepatocellular carcinoma in elderly patients is as effective as in younger patients: A 10-year experience p. 292
Yaxi Wang, Zhigang Cheng, Jie Yu, Xin Li, Guoliang Hao, Fangyi Liu, Zhiyu Han, Xiaoling Yu, Ping Liang
DOI:10.4103/jcrt.JCRT_1021_19  PMID:32474516
Objective: To compare the overall survival (OS), disease-free survival (DFS) and liver-cancer-specific survival (LCSS) of elderly (≥65 years) and younger patients (< 65 years) with early-stage hepatocellular carcinoma (HCC) using ultrasound-guided percutaneous microwave ablation (US-PMMA). Materials and Methods: From January 2002 to December 2017, 510 elderly and 1053 younger patients were diagnosed with early-stage HCC according to the Milan criteria. All of these patients were treatment-naïve to US-PMMA. Baseline characteristics were collected to identify any risk factors to determine the survival outcomes. OS, DFS, and LCSS probabilities were calculated with the Kaplan-Meier method and compared using the Log-rank test. Results: Complete ablation was achieved in all patients. Elderly patients were more likely to be, hepatitis C virus infection, comorbidities, cirrhosis, larger tumors, poor liver functional reservation, more ablation points, longer ablation time, longer hospital stays, and higher hospitalization costs (P < 0.05). Over the follow-up period (12–156 months), no significant differences were detected in OS, DFS, and LCSS between the two groups ( P = 0.092, 0.318, and 0.183). r-GT, ALB and ablation session were significant factors for OS, r-GT and ALB for LCSS, and cirrhosis, tumor number, AFP and ablation points for RFS in the multivariate analysis, respectively. No treatment-related deaths occurred in the two groups. Any complications were treated as appropriate. Conclusions: Although advanced age and comorbidities are intrinsic factors in elderly HCC patients, similar survival outcomes were obtained in elderly and younger HCC patients treated by US-PMWA, despite elderly patients having more comorbidities.
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Time to untreatable progression is an appropriate surrogate endpoint for overall survival in patients with hepatocellular carcinoma after transarterial chemoembolization p. 301
Hongyu Wang, Bin Li, Yu Wang, Jiang Zhang, Yanqin Wu, Wenzhe Fan, Jiaping Li
DOI:10.4103/jcrt.JCRT_898_19  PMID:32474517
Aims: The aim of the study was to determine whether the time to progression (TTP) or time to untreatable progression (TTUP) is an appropriate surrogate endpoint for overall survival (OS) in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Materials and Methods: Eighty-four patients with Barcelona clinic liver cancer (BCLC) stage B or C HCC underwent TACE. The correlations of TTP and TTUP with OS were evaluated after a log transformation of the indicated values. After identifying independent prognostic factors of TTP, TTUP, and OS, the partial correlations of TTP and TTUP with OS were analyzed in all patients and subgroups. Subsequently, the prognostic value of TTP and TTUP was compared by the multivariate survival analysis of OS. Results: Both the BCLC stage and tumor number were correlated with TTP and TTUP. In addition, the BCLC stage, initial treatment failure, and sorafenib administration were associated with OS. In all patients, the correlation coefficients of TTP and TTUP with OS were 0.559 and 0.789, respectively. Adjustment for independent prognostic factors yielded partial correlation coefficients which were 0.433 and 0.697, respectively. Furthermore, OS was found to be associated with TTUP (P = 0.003; hazard ratio: 0.253; 95% confidence interval: 0.10–0.63) but not with TTP. Conclusion: Untreatable progression is more representative of clinical progression in patients with HCC who underwent TACE. In the current study, TTUP is a more appropriate surrogate endpoint for OS than TTP. Future studies should explore whether untreatable progression is a valuable endpoint event in clinical trials or an indicator of the need for second-line therapy.
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Targeting EZH2 depletes LMP1-induced activated regulatory T cells enhancing antitumor immunity in nasopharyngeal carcinoma p. 309
Wei Sun, Lin Chen, Jun Tang, Chengcheng Zhang, Yihui Wen, Weiping Wen
DOI:10.4103/jcrt.JCRT_986_19  PMID:32474518
Objective: Regulatory T cells (Tregs) are critical factors that impair antitumor immunity. Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is one of the most pathogenic factors in nasopharyngeal carcinoma (NPC). However, the role of EBV-encoded LMP1 in regulating Treg generation in NPC remains unclear. Materials and Methods: The in vitro stability of activated Tregs (aTregs) influenced by LMP1 was analyzed by flow cytometry. The inhibitory effects of LMP1-HONE1 antigen-induced aTregs on tumor-associated antigen (TAA)-specific T cells were analyzed in vitro and in vivo. Finally, the expression of LMP1, Foxp3, and enhancer of zeste homolog 2 (EZH2) were analyzed in samples from 86 NPC patients by immunohistochemistry and immunofluorescence. Results: LMP1 upregulated the expression of EZH2, which increased the stability of aTregs in vitro. EZH2 inhibitor, DZnep, depleted LMP1-HONE1 antigen-induced aTregs in vitro and led to potent TAA-specific T cell antitumor immunity in vivo. In NPC tissues, LMP1 expression level was positively correlated with the number of EZH2+ Tregs, which was positively correlated with clinical stage and overall survival. Conclusions: EZH2 is essential for maintaining the stability and inhibitory functions of aTregs that are induced by EBV-encoded LMP1 in NPC.
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Comprehensive analysis of the association between tumor-infiltrating immune cells and the prognosis of lung adenocarcinoma p. 320
Yitong Pan, Yeqin Sha, Hongye Wang, Hao Zhuang, Xiaohan Ren, Xianji Zhu, Xiyi Wei
DOI:10.4103/jcrt.JCRT_954_19  PMID:32474519
Context: Increasing evidence has indicated an association between immune cell infiltration in lung adenocarcinoma (LUAD) and clinical outcomes. Aims: This study aimed to investigate the effect of 22 tumor-infiltrating immune cells (TIICs) on the prognosis of patients with LUAD. Settings and Design: This was a case–control study. Materials and Methods: The CIBERSORT algorithm calculated the proportion of cases from the Cancer Genome Atlas (TCGA) cohort. Cox regression analysis evaluated the effect of TIICs on the prognosis of LUAD. The immune risk score model was constructed based on a statistical correlation. Multivariate cox regression analysis investigated independent factors. P < 0.05 was considered to be statistically significant. Results: Certain immune cells had differential infiltration between normal tissues and LUAD. Univariate Cox regression analysis revealed that four immune cell types were statistically correlated with LUAD-related survival risk, and an immune risk scoring model was constructed. The results indicated that patients in the high-risk group were associated with poor outcomes. In addition, the multivariate cox analysis revealed that the immune risk scoring model was an independent factor for LUAD prognosis prediction. Ultimately, a nomogram was established to comprehensively predict the survival of LUAD patients. Conclusions: TIICs played an essential role in the prognosis of LUAD. Furthermore, the immune risk score was a poor predictive factor of LUAD, and the established model was reliable in predicting the prognosis of LUAD.
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Transarterial chemoembolization, ablation, tyrosine kinase inhibitors, and immunotherapy (TATI): A novel treatment for patients with advanced hepatocellular carcinoma p. 327
Min Meng, Wenhong Li, Xia Yang, Guanghui Huang, Zhigang Wei, Yang Ni, Xiaoying Han, Jiao Wang, Xin Ye
DOI:10.4103/jcrt.JCRT_101_20  PMID:32474520
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Currently, the main effective treatment options for HCC include resection, liver transplantation, various percutaneous modalities (such as transarterial chemoembolization [TACE] and thermal ablation), and tyrosine kinase inhibitors (TKIs). Herein, we have proposed a novel therapy which consists of TACE, ablation, tyrosine kinase inhibitors, and immunotherapy (TATI) for patients with advanced HCC). We reported the therapeutic effects of TATI in four patients with advanced HCC. All patients underwent TACE treatment at the beginning of disease diagnosis. During follow-up, all patients were treated with microwave ablation because of a residual tumor or recurrence. For tumor control, apatinib, a TKI, was administered after ablation. If the tumor was resistant to the TKI, we continued to apatinib therapy in combination with immunotherapy (camrelizumab). All the four patients had better survival benefits and no serious adverse effects.
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Correlation between the changes of serum COX 2, APE1, VEGF, TGF-β and TSGF levels and prognosis in patients with osteosarcoma before and after treatment p. 335
Qingxi Zhang, Guo Dong, Fuchuan Wang, Wenyuan Ding
DOI:10.4103/jcrt.JCRT_11_20  PMID:32474521
Context: Osteosarcoma (OS) is a progressive primary bone tumor that originates from immature stromal spindle cells. After chemotherapy, the serum-related indexes which are related to the prognosis. Aims: The aim of this study is to investigate the correlation between changes in serum cyclooxygenase-2 (COX-2), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and tumor-specific growth factor (TSGF) levels and prognosis of patients with osteosarcoma (OS) before and after treatment. Settings and Design: Data of 75 patients with OS (observation group) and 55 healthy controls (control group) were retrospectively analyzed. Materials and Methods: Chemotherapy was administered to the observation group. Serum lactate dehydrogenase, alkaline phosphatase, and TSGF levels were measured before and after treatment. The observation group patients were classified as normal or abnormal according to the changes in serum COX-2, bFGF, VEGF, TGF-β, and TSGF levels after chemotherapy. Patients were followed up for 7.5 years, and the survival rate was determined. Statistical Analysis Used: Single-factor influencing prognosis was included in the Cox model, and independent factors influencing prognosis were analyzed. Results: After chemotherapy, the mean serum COX-2, bFGF, VEGF, and TSGF levels decreased significantly in the observation group but were still higher than those in the control group. Furthermore, serum TGF-β levels increased in the observation group but were still lower than those in the control group. The 5-year survival rate of patients with normal serum COX-2, bFGF, VEGF, and TSGF levels was significantly higher in the normal subgroup than in the abnormal subgroup. Cox analysis showed that the Enneking stage and COX-2 level after chemotherapy were independent prognostic factors. Conclusions: The serum COX-2, bFGF, VEGF, and TSGF levels of patients with OS significantly changed after chemotherapy, and the short-term survival rate of patients with normal levels of these biomarkers after chemotherapy was high.
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Prediction of radiotherapy effect by diffusion-weighted imaging in esophageal carcinoma xenograft model p. 343
Andu Zhang, Xiaohua Su, Yanfei Wang, Gao-Feng Shi, Chun Han, Jun Zhang, Lan Wang, Ruohui Zhang
DOI:10.4103/jcrt.JCRT_627_19  PMID:32474522
Aim: This study was to evaluate the value of diffusion-weighted imaging (DWI) in predicting the efficacy of radiotherapy for esophageal cancer from xenograft model level. Subjects and Methods: Thirty-two tumor-bearing mice from the Eca-109 cell line nude mice models were established. The experimental group (n = 16) received a single dose of 15 Gy (6MV X-ray), whereas the control group (n = 16) did not receive any treatment. The tumor volume and apparent diffusion coefficient (ADC) were obtained. The cell density, tissue necrosis ratio, and CD31 expression were determined at matched time points. Results: The tumor volume was smaller in the experimental group than in the control group (P < 0.05) on the 7th day after radiotherapy (1.580 ± 0.965 cm3 vs. 2.671 ± 0.915 cm3). The ADC values were higher in the experimental group than in the control group on the 3rd day (P < 0.05) (998.15 ± 163.76 ×10− 6 mm2/s vs. 833.32 ± 142.15 ×10− 6 mm2/s). On the 3rd day after radiotherapy, the differences in cell density and necrosis ratio between the two groups were statistically significant; the tumor cell density was lower in the experimental group (25.56 ± 1.40%) than in the control group (33.48 ± 4.18%) (P < 0.05), and the proportion of tissue necrosis was higher in the experimental group (32.19 ± 1.21%) than in the control group (29.16 ± 2.16%) (P < 0.05). The negative and weak positive rate of CD31 expression in the experimental group was higher than the control group, whereas the generally positive and strong positive rate of CD31 expression was significantly lower than the control group in the early stage (P < 0.05). Conclusion: ADC values may change at the early stage before the morphological changes of tumors. Changes in cell density and necrosis ratio of transplanted tumors correspond to the changes in ADC values. DWI can be used for the early prediction of esophageal cancer radiotherapy efficacy.
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CSCO ablation expert workshop report: Recommendations for the management of tumor ablation during the coronavirus disease 2019 epidemic p. 350
Yehua Shen, Chien-shan Cheng, Peng Wang, Xu Zhu, Guangyan Lei, Yong Fang, Hailiang Li, Weijun Fan, Hongming Pan, Zhe Tang, Kuansheng Ma, Xiaoguang Li, Zhengyu Lin, Yiping Zhuang, Xin Ye, Bo Zhai, Yue Han, Jinhua Huang, Huixiong Xu, Rongqin Zheng, Rufu Chen, Jie Yu, Dong Xu, Zhongmin Wang, Zhiqiang Meng
DOI:10.4103/jcrt.JCRT_480_20  PMID:32474523
The coronavirus disease 2019 (COVID-19) has become a global pandemic since its outbreak in December 2019, which posed a threat to the safety and well-being of people on a global scale. Cancer patients are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and their critical morbidity and case fatality rates are high. The ablation expert committee of the Chinese Society of Clinical Oncology compiled corresponding expert recommendations. These recommendations summarize the preventive measures and management of tumor ablation treatment in medical institutions, including outpatient clinics, oncology wards, ablation operation room, and postablation follow-ups in accordance with the guidelines and protocols imposed by the National Health Commission of the People's Republic of China and the experience in management and prevention according to various hospitals. This consensus aims to reduce and prevent the spread of SARS-CoV-2 and its cross-infection between cancer patients in hospitals and provide regulatory advice and guidelines for medical personnel.
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Classification of hepatocellular carcinoma diameter by statistical technology and prognostic evaluation in patients after the combined use of transarterial chemoembolization and radiofrequency ablation p. 356
Yanyan Cao, Yanqiao Ren, Hong Ma, Chen Zhou, Jiacheng Liu, Qin Shi, Gansheng Feng, Chuansheng Zheng, Bin Xiong
DOI:10.4103/jcrt.JCRT_648_19  PMID:32474524
Objective: This study aimed to classify hepatocellular carcinomas (HCCs) according to their diameter using statistic technology and evaluate the prognosis of the classified groups after the combined use of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). Materials and Methods: Electronic medical records of 128 consecutive patients who underwent TACE-RFA as the initial treatment for HCC from January 2010 to April 2018 were retrospectively analyzed. TACE was initially performed with subsequent RFA performed after 3–7 days. The decision tree model was used to classify overall survival (OS), progression-free survival (PFS), local recurrence rate (LRR), and treatment complications in HCC. Results: The tumors were divided into three groups of sizes ≤2.9 cm, 2.9–4.8 cm, and >4.8 cm. The group of tumors >4.8 cm showed inferior OS, PFS, and LRR than the other two groups (P < 0.05) on long-term follow-up but not in thefirst 6 months (P > 0.05). The groups of tumors ≤2.9 cm and 2.9–4.8 cm showed no statistically significant difference in OS, PFS, and LRR (P > 0.05). Conclusions: The cutoff points of 2.9 and 4.8 cm were achieved using the objective decision tree model rather than the artificial division of 3 and 5 cm. The prognosis was not significantly different between the groups of tumors ≤2.9 cm and 2.9–4.8 cm, and the prognosis of the two groups was better than the group of tumors >4.8 cm in the long-term follow-up but not in thefirst 6 months.
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Use of contrast-enhanced ultrasound in evaluating the efficacy and application value of microwave ablation for adenomyosis p. 365
Chao Xu, Yanyan Tang, Yingying Zhao, Yongjie Li, Qingliang Feng
DOI:10.4103/jcrt.JCRT_769_18  PMID:32474525
Aim: This study aims to assess the use of contrast-enhanced ultrasonography (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the evaluation of percutaneous microwave ablation (PMWA) of localized adenomyosis. Materials and Methods: Sixty-six patients with single-onset adenomyosis who underwent PMWA at the Liaocheng Tumor Hospital of Shandong Province from January 2013 to February 2019 were enrolled. Venous CEUS and DCE-MRI examinations were performed before and 1-2 days after the surgery. The ablation rates calculated by CEUS and DCE-MRI were compared and analyzed for accuracy. Results: After microwave ablation (MWA), CEUS showed that the volume and ablation rate of the ablated zone were 52.03 28.39 cm3 and 90.90% 6.61%, respectively. By DCE-MRI, the ablation volume and ablation rate of adenomyosis were 52.20 28.65 cm3 and 90.88% 6.32%, respectively. Dysmenorrhea was significantly relieved within 3 months of the operation, and nonmenstrual hemoglobin levels were significantly improved at 3 and 6 months after the operation (P < 0.05). All 66 cases of adenomyosis were treated using PMWA. Postoperatively, 17 patients reported a change in vaginal fluid; however, no special treatment was required as this disappeared 2-11 days after surgery. Conclusions: CEUS can accurately evaluate the ablation rate of localized adenomyosis treated with MWA, which is consistent with DCE-MRI. It is convenient and easy to perform ablation of adenomyomas, with incomplete ablation and angiography, and is a method worthy of clinical promotion.
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Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases p. 372
Qicong Mai, Zhiqiang Mo, Jian He, Meng Chen, Qing Gou, Feng Shi, Xiaoming Chen
DOI:10.4103/jcrt.JCRT_597_19  PMID:32474526
Aims: The aim was to evaluate the feasibility and clinical value of computed tomography (CT)-guided125 I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases. Materials and Methods: A total of 23 patients with retroperitoneal lymph node metastases and those who had moderate-to-severe pain from January 2014 to December 2018 were enrolled in the study. The primary tumors included pancreatic (n = 12), gastric (n = 4), hepatocellular (n = 4), colorectal (n = 2), and esophageal carcinomas (n= 1). Patients were treated with CT-guided percutaneous125 I brachytherapy during the study. The Brief Pain Inventory-Short Form was used to record and compare pain intensity and interference by pain. Treatment-related complications were also evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Criteria. Statistical analysis was performed using SPSS software version 22.0 Results: The primary success rate of125 I seed implantation was 95.7% (22 of the 23 patients). As pain evolved, the patients achieved obvious pain palliation ratings for “worst pain” and “average pain” at 72 h and 4 weeks after brachytherapy, respectively, whereas “pain right now” at 12 weeks was significantly relieved after brachytherapy. No serious complications developed during the perioperative period. Conclusions: In the treatment of intractable carcinomatous pain in patients with retroperitoneal lymph node metastases, CT-guided125 I brachytherapy is a feasible and effective modality for pain palliation.
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REVIEW ARTICLE Top

Microwave ablation versus other interventions for hepatocellular carcinoma: A systematic review and meta-analysis p. 379
Rui Cui, Jie Yu, Ming Kuang, Feng Duan, Ping Liang
DOI:10.4103/jcrt.JCRT_403_19  PMID:32474527
We aim to evaluate the efficacy and safety of microwave ablation (MWA) versus other treatment modalities for hepatocellular carcinoma (HCC). This study was registered in Prospero (registration number CRD42017057046). A complete electronic search was conducted for studies on MWA versus other interventions for HCC using PubMed, EMBASE, Cochrane Library databases, and ISI Web of Science. Randomized and non-randomized clinical trials were included. Data on technical efficacy, local tumor progression (LTP), overall survival (OS), progression-free survival (PFS), and major complications were extracted from included studies and combined to be analyzed via random effects models. OS was set as the primary outcome measure. Fifteen clinical studies were identified. When comparing MWA with radiofrequency ablation (RFA), no significant difference was found in 3-year OS rates (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.66–1.34, P = 0.74), 5-year OS rates (OR 0.83, 95% CI 0.58–1.18, P = 0.29), 3-year PFS rates (OR 1.05, 95% CI 0.77–1.43, P = 0.74), 1-year LTP rate (OR 1.28, 95% CI 0.52–3.18,P = 0.59), technical efficacy rate (OR 1. 35, 95% CI 0. 85–2.15, P = 0.20), and major complication rate (OR 1.04, 95% CI 0.56–1.93, P = 0.90). When comparing MWA with hepatic resection, the 3-year OS rate was not significantly different (OR 0.89, 95% CI 0.59–1.35, P = 0.59). Compared with RFA and hepatic resection, MWA showed similar safety and efficacy for HCC, especially in OS rate and PFS. However, high-quality clinical trials are needed to validate the superiority of MWA.
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CASE REPORTS Top

Transcatheter arterial infusion of anti-programmed cell death 1 antibody pembrolizumab combined with temozolomide or nab-paclitaxel in patient with primary anorectal malignant melanoma: Four case reports p. 387
Shuanggang Chen, Xiaoshi Zhang, Lujun Shen, Han Qi, Weimei Ma, Fei Cao, Lin Xie, Ze Song, Ying Wu, Dandan Li, Xizhi Wen, Weijun Fan
DOI:10.4103/jcrt.JCRT_75_20  PMID:32474528
Primary anorectal malignant melanoma (ARMM) is an extremely rare but aggressive tumor. We assessed the efficacy and safety of transcatheter arterial infusion (TAI) with anti-PD-1 antibody pembrolizumab at a dosage of 100 mg with 0.9% NaCl at a volume of 100 mL administered over a 30-min period every 3 weeks, combined with temozolomide or albumin-bound paclitaxel (nab-paclitaxel) in four patients with ARMM. Temozolomide was administered orally once per day at a dosage of 200 mg/m2/d for five consecutive days about every 4 weeks. Nab-paclitaxel was administered at a dosage of 200mg/m2/d once about every 3 weeks. Among four patients with a median follow-up of 8.9 months, two cases showed Murine Double Minute 2 (MDM2) amplification. Case 1 with Stage II ARMM showed pathological complete response after four cycles of TAI with pembrolizumab combined with nab-paclitaxel. Case 4 was at Stage II and showed stable disease consistently throughout the treatment. Case 2 was at stage II and Case 3 was at stage III, and they showed partial response after four or three cycles, respectively, of TAI with pembrolizumab combined with temozolomide. No Grades 3–4 adverse reactions were observed. Therefore, a combination of TAI with pembrolizumab and temozolomide or with nab-paclitaxel appears to be a promising option for treating ARMM. However, multicenter clinical trials are required to confirm the efficacy and safety of this procedure.
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Robo1-specific chimeric antigen receptor natural killer cell therapy for pancreatic ductal adenocarcinoma with liver metastasis p. 393
Chaojie Li, Nannan Yang, Huashun Li, Zhongmin Wang
DOI:10.4103/jcrt.JCRT_190_20  PMID:32474529
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125I brachytherapy seeds implantation for an inoperable large retroperitoneal leiomyosarcoma p. 397
Xuemin Di, Yansong Liang, Huimin Yu, Jinxin Zhao, Zeyang Wang, Jing Zhao, Aixia Sui, Hongtao Zhang, Juan Wang
DOI:10.4103/jcrt.JCRT_66_18  PMID:32474530
Retroperitoneal leiomyosarcoma is relatively uncommon. Leiomyosarcoma has accounted for about 5%-10% of soft-tissue sarcoma, and 1/2–2/3 of the primary lesions were retroperitoneal, with a cumulative 5-year survival rate of only 35%.Leiomyosarcoma is one kind of soft-tissue sarcoma with the lowest survival rates due to the invasive growth, difficult treatment, and poor prognosis.The present study reported a case of a 78-year-old male diagnosed as left retroperitoneal leiomyosarcoma, who had received three operations. Computed tomography (CT) demonstrated a mass of approximately 12.9 cm × 6.9 cm × 6.6 cm in his retroperitoneal region. The Eastern cooperative oncology group and numerical rating scale scores of pain were 1 and 5, respectively. Multiple treatment strategies were administered, including the application of drainage and125I seed implantation. A total of 90125I seeds were implanted into the tumor through repetitious operations, with 30 seeds each time. Treatment planning system was involved to calculate the source distribution.125I seeds with the activity of 0.5 mCi were implanted under the guidance of CT, and dosimetric verification was performed after the operation. D90 (90% minimum prescription dose received by target volume) was 40 Gy. Follow-up was performed after 6 months, and complete response was achieved in the local lesions. However, there was no evidence-based treatment currently and the majority of our knowledge was based on results from case reports, thus further studies would be required.
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