CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Percutaneous Nephroureteral Stent Placement and Antegrade Forceps Biopsy of Ureteral Obstruction.

PURPOSE: To evaluate the feasibility of percutaneous transluminal ureteral biopsy (PTUB) combined with percutaneous nephroureteral stent placement for ureteral obstruction under fluoroscopy. MATERIALS AND METHODS: From September 2011 to July 2021, 37 patients (27 men and 10 women; median age, 65.0 years) who experienced ureteroscopic biopsy failure or refused or were unable to undergo ureteroscopic biopsy underwent PTUB for ureteral obstruction during nephroureteral stent placement under fluoroscopic guidance. Data on technical success, early adverse events, and radiation dose were collected. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy (OA) of PTUB were analyzed. RESULTS: The technical success of PTUB was 89.2%, with a mean irradiation dose of 76.9 mGy·cm2 ± 12.2. A total of 67.6% (25/37) of the cases were correctly diagnosed with malignancy, whereas 8 cases were confirmed to be true negatives. There were 4 false negatives and no false positives. PTUB had a sensitivity, specificity, PPV, NPV, and OA of 86.2% (25/29), 100% (8/8), 100% (25/25), 66.7% (8/12), and 89.2% (33/37), respectively. Eleven patients (29.7%) experienced Grade 1 adverse events (transient aggravated hematuria). CONCLUSIONS: PTUB appears to be a safe and effective alternative to ureteroscopic biopsy for ureteral obstruction.

TACE sequential MWA guided by cone-beam computed tomography in the treatment of small hepatocellular carcinoma under the hepatic dome.

PURPOSE: An assessment is being conducted to determine the safety and effectiveness of using Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) sequentially to treat small hepatocellular carcinomas (HCCs) located in the hepatic dome. MATERIALS AND METHODS: Fifty-three patients with small HCCs in the hepatic dome who underwent TACE combined with simultaneous CBCT-guided MWA were studied. Inclusion criteria were a single HCCs ≤ 5.0 cm or a maximum of three. The safety and interventional-related complications were monitored, and local tumor progression (LTP), overall survival (OS), and prognostic factors for LTP/OS were evaluated. RESULTS: The procedures were successfully accomplished in all patients. According to Common Terminology Criteria for Adverse Events (CTCAE), adverse reactions and complications are mainly Grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated). Liver and kidney function and alpha-fetoprotein (AFP) levels remained within a reasonable range after 4 weeks of treatment (both p < 0.001). The mean LTP was 44.406 months (95% CI: 39.429, 49.383) and the mean OS rate was 55.157 months (95% CI: 52.559, 57.754). The combination treatment achieved 1-, 3-, and 5-year LTP rates of 92.5%, 69.6%, and 34.5%, respectively; and 1-, 3-, and 5-year OS rates of 100.0%, 88.4%, and 70.2%, respectively. Results from both univariate and multivariate Cox regression analyses showed that the tumor diameter (< 3 cm) and the distance to the hepatic dome (≥ 5 mm, < 10 mm) had a significant impact on the patient's LTP and OS, and were related to better survival. CONCLUSION: CBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of HCCs located under the hepatic dome.

Clinical outcomes of intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma.

BACKGROUND: We aimed to evaluate the safety and efficacy of intraluminal iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma. METHODS: From January 2014 to January 2023, 48 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted in 26 patients under c-arm CT and fluoroscopic guidance (Group A), and 22 patients underwent percutaneous nephrostomy without seed strand (Group B). The clinical outcomes (technical success rate, tumor sizes, hydronephrosis Girignon grade, complications, objective response rate (ORR), disease control rate (DCR), and survival time) were evaluated and compared. RESULTS: A total of 53 seed strands were successfully inserted and replaced in Group A, with a technical success rate of 100%. No procedure-related death or severe complications occurred in both group. Migration of seed strand or drainage tube was the most common complication. The Girignon grade of hydronephrosis was significantly improved 1, 3 and 6 months after procedure in both groups. DCR in Group A were 96.2%, 80.0%, and 70.0% at 1-, 3-, and 6-month follow up, respectively. At 1 and 6 months later, ORR in Group A were significantly higher than those in Group B (p < 0.05). The median overall survival were 30.0 months in Group A and 16.1 months in Group B, respectively (p = 0.04). The median progression-free survival were 11.1 months in Group A and 6.9 months in Group B, respectively (p = 0.09). CONCLUSION: Intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy is safe and effective in patients with ureteral carcinoma, with higher ORR and median overall survival than patients underwent percutaneous nephrostomy without seed strand.

Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.

PVP with or without microwave ablation for the treatment of painful spinal metastases from NSCLC: a retrospective case-control study.

OBJECTIVE: To compare the clinical efficacy of percutaneous vertebroplasty (PVP) alone and microwave ablation (MWA) combined with PVP for the treatment of painful spinal metastases from non-small cell lung cancer (NSCLC). METHODS: From October 2014 to October 2021, the data of 58 NSCLC patients with refractory painful spinal metastases (visual analog scale score ≥ 5) were retrospectively collected and analyzed. Patients in Group A (n = 30) and Group B (n = 28) received PVP alone and MWA combined with PVP, respectively. The primary endpoint was pain relief. The secondary endpoints were quality of life (QoL), local tumor progression (LTP), and complications. RESULTS: The technical success rate was 100% in both groups. Patients in both groups showed similar pain relief at 1-12 weeks, but patients in Group B still showed sustained pain relief at 24 weeks compared to those in Group A (p = 0.03). The assessment of QoL showed similar changes. LTP (33.00% vs. 7.14%, p = 0.02) and cement leakage rates (40.00% vs. 7.14%, p = 0.03) were lower in Group B. The multivariate analysis demonstrated spinal metastases with a maximum diameter ≤ 3.0 cm (p = 0.027) and MWA combined with PVP (p = 0.028) were two independent protective factors for LTP. For cement leakage, spinal metastases with vertebral body compression (p = 0.019) was an independent risk factor, while MWA combined with PVP (p = 0.042) was an independent protective factor. CONCLUSION: MWA combined with PVP for painful spinal metastases from NSCLC performed more sustained pain relief (>6 months) and ultimately improved QoL with lower LTP and cement leakage rates, compared to PVP alone.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization.

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

Peritumoral abnormalities on dynamic-enhanced CT after brachytherapy for hepatic malignancies: local progression or benign changes?

OBJECTIVES: To determine if dynamic CT can differentiate local progression from radioactive seed-induced peritumoral reaction (RSIPR) after brachytherapy with iodine-125 radioactive seeds (BIRS) for advanced hepatic malignancies. METHODS: Enhanced CT images of seed-implanted lesions between 2006 and 2018 were retrospectively evaluated. Hounsfield units of peritumoral parenchyma were measured and assessed quantitatively. The classification, conversion, consequences, and serological indicators during follow-up were recorded and quantified. Statistical differences were analyzed using a Pearson χ2 test. RESULTS: RSIPR was observed in 201 of 290 (69.3%) lesions (161 patients; median age, 55 years; range, 26-79 years), while local progression occurred in 53 lesions. The low density of local progression was much lower than that of RSIPR (p < 0.001), and the former did not exhibit iso-/high density in the portal or equilibrium phase. Ring-like enhancement in progressive lesions was also quite different from RSIPR. Local progression rate was lower for lesions with RSIPR than for those without RSIPR (14.9% vs 25.8%; p = 0.03), and their doses were different (397.2 Gy vs 120.3 Gy, p < 0.001). CONCLUSIONS: Radioactive seed-induced peritumoral reaction has characteristic manifestations on CT images, which is associated with a higher dose of lesions and lower local progression rate. Notably, the enhancement pattern of local progression was distinct from RSIPR and was clearly distinguishable on dynamic-enhanced CT. KEY POINTS: • Radioactive seed-induced peritumoral reaction after brachytherapy with 125I seeds for liver malignancies has characteristic manifestations on CT images, which is associated with a higher dose of lesions (397.2 Gy vs 120.3 Gy, p < 0.001), as a focal radiation injury. • Lesions with RSIPR were less likely to develop local progression, while those without RSIPR had a higher rate of local progression (14.9% vs 25.8%; p = 0.03). • The enhancement pattern of local progression after brachytherapy was distinct from radioactive seed-induced peritumoral reaction and was clearly distinguishable on dynamic-enhanced CT.

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.

3.0-T closed MR-guided microwave ablation for HCC located under the hepatic dome: a single-center experience.

PURPOSE: To analyze the clinical safety and efficacy of 3.0-T closed MR-guided microwave ablation (MWA) for the treatment of HCC located under the hepatic dome. METHODS: From May 2018 to October 2020, 49 patients with 74 HCCs located under the hepatic dome underwent MWA using 3.0-T closed MR guidance. The technical success rate, operative time, complete ablation (CA) rate, complications, local tumor progression (LTP), tumor-free survival (TFS) and overall survival (OS) were examined. Routine blood analysis, liver/kidney function and alpha fetoprotein (AFP) and protein induced by vitamin k absent or antagonist (PIVKA) levels were compared before and 2 months after MWA. RESULTS: All patients underwent MWA successfully, including 10 patients who underwent general anesthesia. The technical success rate was 100% without major complications. The CA rate was 95.9% (71/74) at the 2-month evaluation. The LTP rate was 2.7% during the median follow-up of 17.8 months (range: 4-43 months); the 6-, 12-, 18-month TFS rates were 97.8, 90.6, 68.1%, respectively, and the 6-, 12-, 18-month OS rates were 100, 97.6, 92.1%, respectively. There were no significant changes in routine blood tests and liver/kidney function (p > 0.05), while the AFP and PIVKA level decreased significantly at 2 months (p < 0.05). CONCLUSION: 3.0-T MR-guided MWA is safe and feasible for HCC lesions located under the hepatic dome.

Preliminary outcomes of raltitrexed eluting bead-transarterial chemoembolization using Callispheres® beads for gastrointestinal adenocarcinoma liver metastasis.

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) with Callispheres® beads (CB) is currently used in the treatment of hepatocellular carcinoma. However, clinical data regarding DEB-TACE using raltitrexed-eluting CB for gastrointestinal adenocarcinoma liver metastases (GALM) treatment is limited. We aimed to report the preliminary outcomes of DEB-TACE using CB in unresectable GALM patients. METHODS: This retrospective study enrolled unresectable GALM patients who were treated with DEB-TACE using raltitrexed-eluting CB from October 2018 to October 2021. Totally, 25 patients, 18 males and 7 females, mean age 66.8±9.5 years, were continuously enrolled. Postoperative treatment response, survival rates, and complication were calculated during the procedure and follow-up. RESULTS: Twenty-four patients were technically successful, with a technical success rate of 96.0%. The 3-month overall response rate and disease control rate were 21.7% and 73.9%, and 6-month overall response rate and disease control rate were 30.0% and 65.0%. The median survival time from diagnosis of GALM was 31.3 months. The median survival time and median PFS from first DEB-TACE was 21.3 months (95% confidence interval 9.1-33.5) and 10.7 months (3.7-17.7), respectively. Main adverse events included abdominal pain (36.0%), fever (12.0%), and nausea/vomiting (28.0%) after DEB-TACE. No treatment-related deaths and grade 3 or grade 4 adverse events were observed. CONCLUSIONS: DEB-TACE using raltitrexed eluting CB was demonstrated as a safe and efficient alternative choice for GALM.

Establishment and experimental validation of an immune miRNA signature for assessing prognosis and immune landscape of patients with colorectal cancer.

As essential regulators of gene expression, miRNAs are engaged in the initiation and progression of colorectal cancer (CRC), including antitumour immune response. In this study, we proposed an integrated algorithm, ImmuMiRNA, for identifying miRNA modulators of immune-associated pathways. Based on these immune-associated miRNAs, we applied the LASSO algorithm to develop a reliable and individualized signature for evaluating overall survival (OS) and inflammatory landscape of CRC patients. An external public data set and qRT-PCR data from 40 samples were further utilized to validate this signature. As a result, an immune-associated miRNA prognostic signature (IAMIPS) consisting of three miRNAs (miR-194-3P, miR-216a-5p and miR-3677-3p) was established and validated. Patients in the high-risk group possessed worse OS. After stratification for clinical factors, the signature remained a powerful independent predictor for OS. IAMIPS displayed much better accuracy than the traditional clinical stage in assessing the prognosis of CRC. Further analysis revealed that patients in the high-risk group were characterized by inflammatory response, abundance immune cell infiltration, and higher immune checkpoint profiles and tumour mutation burden (TMB). In conclusion, the IAMIPS is highly predictive of OS in patients with CRC, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer.

CELF2 is a candidate prognostic and immunotherapy biomarker in triple-negative breast cancer and lung squamous cell carcinoma: A pan-cancer analysis.

CUGBP Elav-like family member 2(CELF2) plays crucial roles in the development and activation of T cell. However, the impacts of CELF2 on tumour-infiltrating immune cells (TIICs) and clinical outcomes of tumours remain unclear. In this study, we found that elevated CELF2 expression was markedly correlated with prolonged survival in multiple tumours, particularly in breast and lung cancers. Notably, CELF2 only impacted the prognosis of triple-negative breast cancer (TNBC) with lymph node metastasis. Further investigation showed CELF2 expression was positively correlated with the infiltration abundance of dendritic cells (DCs), CD8+ T cells and neutrophils in breast invasive carcinoma (BRCA) and DCs in lung squamous cell carcinoma (LUSC). CELF2 also had strong correlations with markers of diverse TIICs such as T cells, tumour-associated macrophages and DCs in BRCA and LUSC. Importantly, CELF2 was significantly associated with plenty of immune checkpoint molecules (ICMs) and outperformed five prevalent biomarkers including PD-1, PD-L1, CTLA-4, CD8 and tumour mutation burden in predicting immunotherapeutic responses. Immunohistochemistry also revealed lower protein levels of CELF2 in TNBC and LUSC compared to normal tissues, and patients with high expression showed significantly prolonged prognosis. In conclusion, we demonstrated that increased CELF2 expression was closely related to better prognosis and superior TIIC infiltration and ICM expression, particularly in BRCA and LUSC. CELF2 also performed well in evaluating the immunotherapeutic efficacy, suggesting CELF2 might be a promising biomarker.

TTN/OBSCN 'Double-Hit' predicts favourable prognosis, 'immune-hot' subtype and potentially better immunotherapeutic efficacy in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide. Although treatment strategies for solid tumours have been revolutionized by immunotherapy, only a small subset of CRC patients benefit. Using two-independent cohorts, we found the common frequently mutated genes TTN and OBSCN had the significant correlation with higher tumour mutation burden (TMB) and favourable overall survival. TTN and OBSCN also displayed significant commutation phenomenon. Therefore, based on the status of TTN and OBSCN, we stratified patients into 'Double-WT' phenotype, 'Single-Hit' phenotype and 'Double-Hit' phenotype. Importantly, the 'Double-Hit' phenotype had favourable prognosis, low malignant events propensity, and highest TMB, immune cells infiltration abundance, POLE mutation rate, microsatellite instability ratio, as well as immune checkpoints expression compared with the other two phenotypes. These results indicated that the 'Double-Hit' phenotype suggested 'immune-hot' tumours and potentially better immunotherapeutic efficacy. Bioinformatic algorithm assessment of immunotherapy responses also confirmed this conclusion, and the 'Double-Hit' phenotype was found to be a better predictor of immunotherapy than PD-L1, PD-1, CTLA-4, TMB and microsatellite status. This study revealed CRC patients with TTN/OBSCN 'Double-Hit' was significantly associated favourable prognosis, 'immune-hot' subtype and potentially better immunotherapeutic efficacy.

A novel immune classification reveals distinct immune escape mechanism and genomic alterations: implications for immunotherapy in hepatocellular carcinoma.

BACKGROUND: The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC). METHODS: A total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated. RESULTS: We identified three phenotypes in HCC: TIME-1, the "immune-deficiency" phenotype, with immune cell depletion and proliferation; TIME-2, the "immune-suppressed" phenotype, with enrichment of immunosuppressive cells; TIME-3, the "immune-activated phenotype", with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. A pipeline was developed to classify single patient into one of these three subtypes and calculated the TI. CONCLUSIONS: We identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

Development and clinical validation of a novel six-gene signature for accurately predicting the recurrence risk of patients with stage II/III colorectal cancer.

BACKGROUND: A large number of patients with stage II/III colorectal cancer (CRC) have a high recurrence rate after radical resection. We aimed to develop a novel tool to stratify patients with different recurrence-risk for optimizing decision-making in post-operative surveillance and therapeutic regimens. METHODS: We retrospectively enrolled four independent cohorts from the Gene Expression Omnibus and 66 CRC tissues from our hospital. The initial signature discovery was conducted in GSE143985 (n = 91). This was followed by independent validation of this signature in GSE17536 (n = 111), GSE29621 (n = 40), and GSE92921 (n = 59). Further experimental validation using qRT-PCR assays (n = 66) was performed to ensure the robustness and clinical feasible of this signature. RESULTS: We developed a novel recurrence-related signature consisting of six genes. This signature was validated to be significantly associated with dismal recurrence-free survival in five cohorts GSE143985 (HR: 4.296 [2.612-7.065], P < 0.0001), GSE17536 (HR: 2.354 [1.662-3.334], P < 0.0001), GSE29621 (HR: 3.934 [1.622-9.539], P = 0.0024), GSE92921 (HR: 7.080 [2.011-24.924], P = 0.0023), and qPCR assays (HR: 3.654 [2.217-6.020], P < 0.0001). This signature was also proven to be an independent recurrent factor. More importantly, this signature displayed excellent discrimination and calibration in predicting the recurrence-risk at 1-5 years, with most AUCs were above 0.9, average C-index for the five cohorts was 0.8795, and near-perfect calibration. CONCLUSIONS: We discovered and experimental validated a novel gene signature with stable and powerful performance for identifying patients at high recurrence-risk in stage II/III CRC.

MR-guided microwave ablation of hepatocellular carcinoma (HCC): is general anesthesia more effective than local anesthesia?

BACKGROUND: Percutaneous magnetic resonance-guided (MR-guided) MWA procedures have traditionally been performed under local anesthesia (LA) and sedation. However, pain control is often difficult to manage, especially in some cases when the tumor is large or in a specific location, such as near the abdominal wall or close to the hepatic dome. This study retrospectively compared the results of general anesthesia (GA) and local anesthesia (LA) for MR-guided microwave ablation (MWA) in patients with hepatocellular carcinoma (HCC ≤ 5.0 cm) to investigate whether different anesthesia methods lead to different clinical outcomes. METHODS: The results of the analysis include procedure-related complications, imaging response, and the time to complete two sets of procedures. According to the type of anesthesia, the Kaplan-Meier method was used to compare the local tumor progression (LTP) of the two groups who underwent MR-guided MWA. RESULTS: All patients achieved technical success. The mean ablation duration of each patient in the GA group and LA group was remarkably different (P = 0.012). Both groups had no difference in complications or LTP (both P > 0.05). Notably, the tumor location (challenging locations) and the number of lesions (2-3 lesions) could be the main factors affecting LTP (p = 0.000, p = 0.015). Univariate Cox proportional hazard regression indicated that using different anesthesia methods (GA and LA) was not associated with longer LTP (P = 0.237), while tumor location (challenging locations) and the number of lesions (2-3 lesions) were both related to shorter LTP (P = 0.000, P = 0.020, respectively). Additionally, multivariate Cox regression further revealed that the tumor location (regular locations) and the number of lesions (single) could independently predict better LTP (P = 0.000, P = 0.005, respectively). CONCLUSIONS: No correlation was observed between GA and LA for LTP after MR-guided MWA. However, tumors in challenging locations and the number of lesions (2-3 lesions) appear to be the main factors affecting LTP.

Image-guided microwave ablation of hepatocellular carcinoma (≤5.0 cm): is MR guidance more effective than CT guidance?

BACKGROUND: Given their widespread availability and relatively low cost, percutaneous thermal ablation is commonly performed under the guidance of computed tomography (CT) or ultrasound (US). However, such imaging modalities may be restricted due to insufficient image contrast and limited tumor visibility, which results in imperfect intraoperative treatment or an increased risk of damage to critical anatomical structures. Currently, magnetic resonance (MR) guidance has been proven to be a possible solution to overcome the above shortcomings, as it provides more reliable visualization of the target tumor and allows for multiplanar capabilities, making it the modality of choice. Unfortunately, MR-guided ablation is limited to specialized centers, and the cost is relatively high. Is ablation therapy under MR guidance better than that under CT guidance? This study retrospectively compared the efficacy of CT-guided and MR-guided microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC ≤ 5.0 cm). METHODS: In this retrospective study, 47 patients and 54 patients received MWA under the guidance of CT and MR, respectively. The inclusion criteria were a single HCC ≤ 5.0 cm or a maximum of three. The local tumor progression (LTP), overall survival (OS), prognostic factors for local progression, and safety of this technique were assessed. RESULTS: All procedures were technically successful. The complication rates of the two groups were remarkably different with respect to incidences of liver abscess and pleural effusion (P < 0.05). The mean LTP was 44.264 months in the CT-guided group versus 47.745 months in the MR-guided group of HCC (P = 0.629, log-rank test). The mean OS was 56.772 months in the patients who underwent the CT-guided procedure versus 58.123 months in those who underwent the MR-guided procedure (P = 0.630, log-rank test). Multivariate Cox regression analysis further illustrated that tumor diameter (< 3 cm) and the number of lesions (single) were important factors affecting LTP and OS. CONCLUSIONS: Both CT-guided and MR-guided MWA are comparable therapies for the treatment of HCC (< 5 cm), and there was no difference in survival between the two groups. However, MR-guided MWA could reduce the incidence of complications.

Making timely remedial measures after TACE based on the results of cone-beam CT liver perfusion.

OBJECTIVE: To evaluate the feasibility and safety of using cone-beam CT (CBCT) to measure changes in parenchymal blood volume (PBV) of patients with hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and to guide microwave ablation (MWA) for residual tumors. METHODS: A retrospective study was performed on 42 patients with HCC who completed TACE and received CBCT-guided perfusion imaging. The residual active lesions after TACE were supplemented with MWA to complete the treatment process according to the residual PBV. The outcomes were analyzed, including PBV changes, interventional-related complications, local tumor progression (LTP) and overall survival (OS). RESULTS: Technical success was achieved in all lesions. Correlation analysis revealed that greater volume of residual PBV after MWA is negatively correlated with LTP. (p = .000); and the decrease of PBV was positively correlated with LTP (p = .000). All adverse events and complications were CTCAE Grade 1/2. After combination treatment, the 1-, 3-, and 5-year LTP-free survival were 97.6%, 69.0% and 15.1%, respectively, with a median LTP of 49.0 months (95% CI:43.129,54.871). Multivariate Cox regression revealed that the residual PBV > 13 ml/1000 was an independent factor predicting a shorter OS and LTP (Both p< .05). For LTP, multivariate Cox regression showed that a tumor in a single lesion were independently predicted to have a longer LTP in patients with HCC (p = .033). CONCLUSION: CBCT is feasible and safe to use to measure changes in the PBV before and after TACE treatment, while it can also guide MWA for the treatment of residual tumors in one session.