Animal study of a newly designed metal airway brachytherapy stent loaded with radioactive 125I seeds.

AIM: To evaluate dynamic tissue changes after airway stenting (AS) with a newly designed metal brachytherapy stent (BS) loaded with radioactive 125I seeds in normal rabbits. METHODS: Forty-five normal New Zealand white rabbits were divided into 3 groups (group A: stent without seeds; group B: stent with 0.4 mCi active seeds; group C: stent with 0.8 mCi active seeds) and underwent AS under C-arm guidance. Then, five rabbits were killed from each group at 2, 4, and 8 weeks for further examination. Laboratory tests (including routine blood tests, liver function, kidney function, and electrolytes), gross observations, and tissue changes of Masson/hematoxylin-eosin staining, plus immunohistochemistry of α-SMA, NOX4, and TGF-ß were performed at each time point. RESULTS: All animals underwent AS successfully without procedure-related death, but one animal died at 6 weeks due to severe pulmonary infection in group C. Apart from a transient increase in white blood cells (P < 0.05) and a gradual increase in ROS levels (P < 0.05), other blood test items showed no significant changes (P > 0.05). The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in group C was less severe than that in groups A and B (P < 0.05). Airway lateral fibrosis was observed in all groups by histopathologic analysis; however, fibrosis in group C was more severe than that in groups A and B (P < 0.05). CONCLUSION: The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8 weeks.

Preliminary application of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice.

AIM: To evaluate the efficacy and safety of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice. METHODS AND MATERIALS: 42 patients with obstructive jaundice because of extrahepatic cholangiocarcinoma were enrolled. 22 patients (group A) received a biliary stent with common drainage tube implantation, and 20 patients (group B) received a biliary stent with double-strand 125I seeds radiotherapy drainage tube placement. The length, location and pathological stage of biliary stricture were recorded in the two groups. Total bilirubin (TBIL), direct bilirubin (DBIL), IgA, IgG, IgM, alanine aminotransferase and white blood cell (WBC) count were measured before and after percutaneous transhepatic cholangial drainage (PTCD). Tumor diameter was measured before and three months after PTCD, and the difference were calculated. Stent patency time, survival time, and complications were recorded. RESULTS: There was no significant difference in the length, location and pathological stage of biliary stenosis between the two groups. There was no significant difference in TBIL, DBIL, IgA, IgG, IgM, alanine aminotransferase and WBC count between the two groups before or after PTCD (P > 0.05). Three months after PTCD, tumors growth in group A and tumors shrinkage in group B. The difference in tumor size between the two groups before and after PTCD was statistically significant (P < 0.05). The average stent patency times in groups A and B were 3.55 ± 0.76 months and 8.76 ± 1.85 months, respectively (P < 0.05). The average survival times in groups A and B were 133.5 ± 27.8 days and 252.5 ± 114.5 days, respectively (P < 0.05). There was no statistically significant difference in the incidence of complications between the two groups (P > 0.05). CONCLUSION: Double-strand 125I seeds radiotherapy biliary drainage tubes can safely and effectively control tumors, prolong the patency of biliary stents, and prolong patient survival.

125I seed implantation brachytherapy for glottic carcinoma: an experimental and clinical study.

125I seed implantation brachytherapy (ISIB) is the preferred treatment for prostate cancer. Is ISIB technically suitable for glottic carcinoma (GC)? This question has not been answered in the literature; thus, the present study was carried out to evaluate the feasibility and effect of ISIB on GC in animal and clinical studies. An animal model of Tu-212 cell laryngeal carcinoma xenografts (n = 20 animals) underwent ISIB treatments [experimental group (EG) using 0.8-mCi/seed, control group (CG) using 0-mCi/seed]; at 4 weeks, haematoxylin-eosin (HE) staining was performed, and the mRNA and protein expression of Bax, Bcl-2 and PCNA was analysed. Moreover, thirty healthy beagle dogs underwent ISIB under CT guidance (EG, 0.8 mCi/seed, CG, 0 mCi/seed), and injuries to the normal tissue were analysed by HE and Masson staining at 2, 4, and 8 weeks. Finally, twenty-one GC patients (T2-3N0M0) underwent percutaneous ISIB at a mean prescription dose of 116.8 Gy; the technical success, complications, local tumour response, voice quality, local progression and overall survival were analysed. The results showed that the xenograft tumours were significantly inhibited in the EG. The Bax protein levels were significantly increased in this group (P<0.05), while the Bcl-2 and PCNA protein levels were decreased (P<0.05). Moreover, the glottic injury scores increased with the dose accumulation (P<0.05), while the adjacent tissue did not show pathohistological injury, and the routine blood tests showed no change between the pre-treatment baseline levels and the levels 2, 4, or 8 weeks later (P>0.05). The clinical study found that the rate of technical success was 100% with no procedure-related complications; furthermore, complete response was achieved in all patients, and no local progression occurred. All patients survived and showed improvements in their voice quality (P<0.05) during the follow-up period (median 23.5 months). The results show that ISIB is a safe and effective treatment for GC; randomized controlled trials are needed to further evaluate its clinical efficacy.

Development and validation of a robust immune-related risk signature for hepatocellular carcinoma.

BACKGROUND: Increasing evidence has indicated immune-related genes (IRGs) play a key role in the development of hepatocellular carcinoma (HCC). Whereas, there have been no investigations proposing a reliable prognostic signature in terms of IRGs. This study aimed to develop a robust signature based on IRGs in HCC. A total of 597 HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were enrolled in this study. METHODS: The TCGA cohort was utilized for discovery, and the ICGC cohort was utilized for validation. Multiple algorithms were implemented to identify key prognostic IRGs and establish an immune-related risk signature. Bioinformatics analysis and R soft tools were utilized to annotate underlying biological functions. RESULTS: A total of 1416 differentially expressed mRNAs (DEMs) were screened, of which 90 were differentially expressed IRGs (DEIRGs). Using univariate Cox regression analysis, we identified 33 prognostically relevant DEIRGs. Using least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis, we extracted 8 optimal DEIRGs to construct a risk signature in the TCGA cohort, and the signature was verified in the ICGC cohort. We also built a nomogram to increase the accuracy of predicting HCC prognosis. By investigating the relationship of the risk score and 8 risk genes from our signature with clinical traits, we found that the aberrant expression of the immune-related risk genes is correlated with the development of HCC. Moreover, the high-risk group was higher than the low-risk group in terms of tumor mutation burden (TMB), immune cell infiltration, and the expression of immune checkpoints (programmed cell death protein 1 [PD-1], programmed cell death ligand 1 [PD-L1], and cytotoxic T-lymphocyte-related protein 4 [CTLA-4]), and functional enrichment analysis indicated the signature enriched an intensive immune phenotype. CONCLUSION: This study developed a robust immune-related risk signature and built a predictive nomogram that reliably predict overall survival in HCC, which may be helpful for clinical management and personalized immunotherapy decisions.

Investigation of a novel brachytherapy ureteral stent: trial studies on normal beagle dogs.

PURPOSE: To evaluate the safety and feasibility of a newly designed 125I brachytherapy ureteral stent (BUS) in normal dogs. METHODS: A BUS loaded with 10 125I seeds (Group A: 0.8 mCi, Group B: 0.4 mCi, Group C: 0 mCi) was designed and tested in 27 normal beagle dogs. Routine blood tests, gross observations, cumulative radiation doses, tissue reaction assessed by hematoxylin-eosin/Masson staining, mRNA analysis by RT-qPCR and protein expression of Caspase-3, Collagen I, PCNA, and α-SMA were performed at 2, 4 and 8 weeks. RESULTS: The BUS was implanted successfully in all dogs (27/27) without surgery-related death. The ureter diameter and radiation injury score increased along with radiation accumulation (p < 0.05). Histopathologic analysis showed necrotic tissue and lateral fibrosis to different extents in the ureteral walls that gradually increased in all groups (p < 0.05); however, epithelial cell proliferation in groups A and B was lighter than that in the control group (p < 0.05). CONCLUSION: Placement of the newly designed 125I BUS was safe and feasible in dogs, and clinical studies are required to test its use in humans.

Managing occluded stents in biliary obstruction using radiofrequency ablation combined with 125I-strand brachytherapy.

PURPOSE: We aimed to assess the effectiveness of percutaneous radiofrequency ablation (PRFA) combined with iodine-125 (125I) seed strand brachytherapy (125I-BT) for treatment of occluded biliary stents. METHODS: From November 2015 to September 2017, 13 consecutive patients with occluded biliary metal stents, implanted for malignant obstruction, underwent PRFA combined with 125I-BT to reopen the bile duct. Data included clinical and technical success, stent patency, complications, and overall survival. RESULTS: The clinical and technical success rates were both 100%. One month after treatment, the total serum bilirubin level had decreased significantly (P < 0.001). Early complications of cholangitis or hemobilia were experienced by one patient each. Three patients (23.1%) had late complications, including two cases of cholangitis and one case of cholecystitis. During the mean follow-up of 233±82.9 days (range, 88-365 days), the stent patency time was 239±26.5 days (95% CI, 187-291 days), and the 6-month stent patency rate was 68.4%. Five patents died; the mean survival time was 298±30.1 days (95% CI, 239-358 days). The 6-month survival rate was 83%. CONCLUSION: PRFA therapy combined with 125I-BT is feasible and safe for patients with occluded metal stents placed for malignant biliary obstruction. Nevertheless, randomized controlled trails are needed to confirm the effectiveness of this new approach.

Novel brachytherapy drainage tube loaded with double 125I strands for hilar cholangiocarcinoma: A case report.

BACKGROUND: Hilar cholangiocarcinoma (CC) is a common malignant tumor with high malignancy and poor prognosis. Most patients have lost the opportunity to undergo radical surgery when diagnosed. Although palliative drainage or biliary stent placement is a preferable choice, the tumor cannot be controlled. This study aimed to develop a novel brachytherapy drainage tube for low-dose-rate brachytherapy with an effective drainage, thereby prolonging the survival time of patients. CASE SUMMARY: A 54-year-old male patient had undergone choledochal stent implantation due to obstructive jaundice. He was admitted to the hospital because of the recurrence of jaundice. Preoperative imaging and pathological biopsy revealed hilar CC (Bismuth-Corlette type IIIa). First, the patient underwent percutaneous transhepatic cholangial drainage and the symptoms of jaundice gradually relieved. To further treat hilar CC and remove the biliary drainage tube as far as possible, the patient chose to use the novel brachytherapy drainage tube after a multi-disciplinary consultation. After 1 mo of brachytherapy, the re-examination revealed that the obstructive lesions disappeared, and the drainage tube was finally removed. During the following 10 mo of follow-up, the patient's hilar CC did not recur. CONCLUSION: The novel brachytherapy drainage tube may be a new choice for patients with unresectable hilar CC.