Development of an antibody-ligand fusion protein scFvCD16A-sc4-1BBL in Komagataella phaffii with stimulatory activity for Natural Killer cells.

BACKGROUND: Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost. RESULTS: In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice. CONCLUSION: Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.

The Role of Contrast-Enhanced Ultrasound Plus Color Parametric Imaging in the Differential Diagnosis of Subpleural Pulmonary Lesions.

OBJECTIVES: To distinguish benign and malignant subpleural pulmonary lesions (SPLs) with contrast-enhanced ultrasound (CEUS) and color parametric imaging (CPI), and evaluate the role of CEUS plus CPI in the differential diagnosis of pathological types of SPLs. METHODS: One hundred and thirty-six patients underwent CEUS with a Logiq E9 XD Clear ultrasonic machine equipped with a 3.5- to 5.0-MHz C5-1 transducer in our center were enrolled in our study, including 27 cases of benign lesions and 109 cases of malignant lesions. The ultrasound contrast agent used in this study was SonoVue. CEUS images and CPI of all cases were reviewed and analyzed by the resident and staff radiologist groups separately. RESULTS: With CEUS alone, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while centripetal enhancement pattern occurred more frequently in malignant SPLs (P < .001). With CEUS plus CPI, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while those of malignant SPLs were centripetal (P < .001) and eccentric (P < .05). The diagnosis performance of CEUS plus CPI was significantly higher than that of CEUS alone in both the resident (area under the curve [AUC] = 0.857 vs 0.677, P < .001) and staff (AUC = 0.866 vs 0.681, P < .001) groups. Moreover, CPI offered remarkable inter-consistency improvements in the enhancement pattern determination between the two groups. CONCLUSION: The CEUS enhancement patterns would provide information of blood perfusion patterns in the differential diagnosis of benign and malignant SPLs. The diagnosis performance could be significantly improved by CEUS plus CPI compared with CEUS alone.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma.

OBJECTIVE: To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM). METHODS: Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0-6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model. RESULTS: Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM. CONCLUSION: RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

Initial adherence by psychiatric outpatients in a general hospital and relevant personal factors.

BACKGROUND: Initial adherence is a predictor of long-term adherence and thus is a crucial metric to explore and support. This study aimed to investigate initial adherence by psychiatric outpatients and relevant personal factors. METHODS: The study surveyed psychiatric outpatients using a 30-day timely return visit rate (TRVR) after the first visit to indicate initial adherence. All participants agreed to engage in the self-designed survey and assessments of the Eysenck Personality Questionnaire (EPQ) and Symptoms Checklist-90 (SCL-90). Clients who missed timely return visits received telephone follow-up to determine the main reasons. RESULTS: The overall TRVR was 59.4, and 40.6% of clients missed return visits. Logistic regression analysis revealed risk factors for initial adherence were work, tense family atmosphere, negative attitudes towards medication, higher EPQ psychoticism score, and lower SCL-90 phobic anxiety score. The main reasons given for non-timely return visits were improvement suggesting lack of need for a return visit, various barriers, no improvement, and side effects. CONCLUSION: Psychiatric outpatients had poor initial adherence related to multiple dimensional factors, including job, family, personality characteristics, mental status, and thoughts about mental illness and treatments.

Global 3'UTR shortening and down-regulation of repeated element related piRNA play crucial roles in boys with cryptorchidism.

BACKGROUND: Cryptorchidism is the most common congenital defect in children's genitourinary system. Decades of research have identified both environmental and genetic factors contribute to the etiology. METHODS: Small-RNA/mRNA-seq were performed on testicular tissues from cryptorchidism patients. Downstream analysis included mRNA expression, piRNA expression and miRNA expression. RESULTS: We find a global downregulation of repeated element related piRNA expression as well as a global 3'UTR shortening of mRNAs in patients with cryptorchidism. We also find that genes with shortened 3'UTR which are highly enriched in vascular endothelial growth and protein ubiquitination, tend to be up-regulated in cryptorchidism. These results indicate that boys with cryptorchidism may not have normal piRNA functions to protect developmental tissues from transposon invasion. Dysregulated shortened 3'UTR genes may affect normal testicular tissue development. CONCLUSION: In summary, our findings also provided the first landscape of gene regulation in cryptorchidism, especially in terms of post-transcriptional regulations.

The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for limited hepatocellular carcinoma (HCC), the efficacy of this treatment for recurrent HCC has not been thoroughly investigated. Purpose To compare the long-term outcomes and analyze the prognostic factors for outcomes after RFA for initial HCC versus as a second-line treatment for recurrent HCC. Materials and Methods This retrospective study included 560 patients with solitary tumors 5 cm or smaller (263 initial HCCs, 297 -recurrent HCCs) who underwent percutaneous US-guided RFA from January 2005 to December 2016. Of 297 patients with -recurrent HCC, 134 had previously undergone hepatectomy, 128 had undergone transarterial chemoembolization (TACE), and 35 had undergone local ablation therapy. Overall survival (OS) between initial HCC and recurrent HCC was compared before and after propensity score matching. Prognostic factors for all patients were analyzed with the log-rank test and Cox proportional hazards model. Results A total of 560 patients (mean age, 60 years ± 12 [standard deviation]; 441 men) were evaluated. Before matching, the OS rates at 1, 3, 5, and 10 years were 92.6%, 73.9%, 59.3%, and 39.6%, respectively, in patients with recurrent HCC and 92.8%, 75.4%, 63.3%, and 44.7% in patients with initial HCC (P = .27). After matching, the OS rates at 1, 3, 5, and 10 years were 94.8%, 75.7%, 61.6%, and 47.3% in the initial HCC group and 91.9%, 71.2%, 58.7%, and 45.2% in the recurrent HCC group (P = .32). Among patients with recurrent HCC, no significant difference in mean OS was noted for local recurrence versus distant recurrence (81.6 months ± 5.1 vs 83.8 months ± 6.6, P = .82) or previous treatment modality (82.0 months ± 7.3 in the resection group, 82.7 months ± 5.3 in the TACE group, and 79.3 months ± 10.8 in the local ablation group; P = .83). Local tumor progression after previous local ablation (10 of 35 [28.6%]) was higher than that after previous hepatectomy (15 of 134 [11.2%], P = .04). Multivariable analysis demonstrated that tumor size (hazard ratio, 1.58; 95% CI: 1.06, 2.36; P = .02), portal hypertension (hazard ratio, 1.52; 95% CI: 1.03, 2.26; P = .04), Child-Pugh class (hazard ratio, 2.01; 95% CI: 1.02, 3.96; P = .045), and serum α-fetoprotein level (hazard ratio, 1.62; 95% CI: 1.10, 2.39; P = .01) were independent predictive factors for recurrent HCC outcomes. Conclusion Radiofrequency ablation provides similar long-term survival for solitary hepatocellular carcinoma of 5 cm or less, regardless of whether treatment is initial or salvage therapy. © RSNA, 2021 Online supplemental material is available for this article.

Severe interstitial pneumonia caused by cetuximab: a case report and review of the literature.

Cetuximab is an IgG1 chimeric mAb against epidermal growth factor receptor, which can be used for chemotherapy failure or tolerance in patients with epidermal growth factor receptor expressed RAS wild-type metastatic colorectal cancer. We report on a patient who developed rapid-onset interstitial pneumonia while being treated with cetuximab plus XELOX (oxaliplatin, capecitabine) for metastatic colorectal cancer. A 75-year-old man patient was administered cetuximab plus XELOX regularly. After his cetuximab schedule was adjusted from 1 to 2 weeks, he rapidly developed interstitial pneumonia which led to acute respiratory distress syndrome. Our literature review indicated that, for patients with risk factors, a 2-week regimen of cetuximab might lead to interstitial pneumonia. Clinicians should closely monitor patients for adverse drug reactions to improve drug safety.

Productive transcription of miR-124-3p by RelA and RNA polymerase II directs RIP1 ubiquitination-dependent apoptosis resistance during hypoxia.

The K63-linked ubiquitination of RIP1 coordinates survival/death homeostasis by driving transcription of genes downstream of RelA. Previously, we demonstrated that EGF-dependent RelA transactivation overcomes hypoxia-initiated apoptosis, yet the underlying mechanisms remain mysterious. We report here that UBXN1 deficiency empowers apoptosis resistance against hypoxia through triggering IκBα degradation, for which K63-linked ubiquitination of RIP1 is required. MiR-124-3p is a bona fide inhibitor upstream of UBXN1, thereby antagonizing the hypoxia-initiated apoptosis. UBXN1 repression by miR-124-3p restores the K63-linked ubiquitination of RIP1, IKKß phosphorylation, IκBα-RelA disassembly, RelA nuclear localization and transactivation of EGF gene as well as EGF secretion under hypoxia. Reconstitution of wild-type UBXN1, but not a truncated UBXN1ΔUBA mutant, or pharmacological inhibition of RelA transactivation in miR-124-3p-replete cells compromises the apoptosis-resistant phenotypes of miR-124-3p. Hypoxia transcriptionally downregulates miR-124-3p by disassociating RelA and RNAP II from its promoter. EGFR activation renders the K63-linked ubiquitination of RIP1 and hypoxic tolerance in conjunction with miR-124-3p. Our findings identify a pivotal role of miR-124-3p in ubiquitin conjugation of RIP1 against hypoxic damage and underscore that productive transcription of miR-124-3p by RelA and RNAP II might be a switching mechanism for this process.

Regulation of Fn14 stability by SCFFbxw7α during septic acute kidney injury.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCFFbxw7α from Fn14, dismantles Lys48-linked polyubiquitination of Fn14 and stabilizes it. Pharmacological deactivation of Fn14 with monoclonal antibody ITEM-2 provides effective protection against lethal sepsis and AKI in mice. Our study underscores an adaptive mechanism whereby TLR4 regulates SCFFbxw7α-dependent Fn14 stabilization during inflammatory tubular damage and further supports investigation of targeting Fn14 in clinical trials of patients with septic AKI.

The value of KRAS gene status in predicting local tumor progression of colorectal liver metastases following radiofrequency ablation.

PURPOSE: We investigated the relationships between KRAS gene status and local tumor progression (LTP) of colorectal liver metastases (CLMs) after treatment with percutaneous ultrasound-guided radiofrequency ablation (RFA). MATERIALS AND METHODS: Clinical and imaging data from 76 patients (154 lesions) with CLM who underwent percutaneous ultrasound-guided RFA and had KRAS gene test results between January 2012 and June 2016 were analyzed. The average lesion size was 2.3 ± 1.0 cm (range 0.9-5.7 cm); 38 cases (82 lesions) had wild-type KRAS, and 38 cases (72 lesions) had KRAS mutations. RESULTS: The technique effectiveness was 98.1% (151/154), and the LTP rate was 18.2% (28/154) after RFA, which was performed between January 2012 and November 2017. The mean and median follow-up were 32.7 ± 2.5 and 32.0 ± 2.6 months (range 1-70 months), respectively. Cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA for all patients were 7.4, 14.5, 17.8 and 19.2%, respectively. The LTP rate for patients with mutant KRAS (27.8% [20/72]) was significantly higher than that in patients with wild-type KRAS (9.8% [8/82]; p = .004). The cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA were 4.0, 11.1, 11.1 and 11.1%, respectively, for patients with wild-type KRAS and 11.2, 18.4, 25.2 and 36.2%, respectively, for patient with mutant KRAS (p = .011). Univariate (p = .011) and multivariate analyses (p = .005) showed that KRAS genotype in liver metastases was predictive of LTP. Multivariate analysis also showed that ablation margin size (p< .001) and modified clinical risk score (CRS; p = .033) were independent prognostic factors for LTP. CONCLUSIONS: KRAS gene status of liver metastatic lesions was associated with LTP rates after RFA of CLM. Ablation margin size and modified CRS were also independent prognostic factors for LTP.

Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer.

OBJECTIVE: To evaluate the long-term efficacy and prognostic factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) for breast cancer liver metastasis (BCLM). METHODS: Between 2000 and 2015, 69 patients who underwent ultrasound-guided percutaneous RFA for BCLM and had regular follow-up examinations were included. All patients had undergone resection of the primary breast cancer and had received chemotherapy, endocrine therapy or both after surgery. The sample included two males and 67 females with an average age of 50.3 ± 10.0 years (31-76 y). The mean maximum diameter of metastatic lesions in the liver was 2.9 ± 1.4 cm (1.0-6 cm). Thirty-five patients had a single metastasis, while 34 patients had multiple liver metastases (2-5 lesions). Survival results were generated using Kaplan-Meier estimates and a multivariate analysis was performed using the Cox regression model. RESULTS: In total, 92 RFA sessions were performed and 135 BCLM lesions were treated. Major complications occurred in one of the 92 sessions (1.1%). Technical efficacy was achieved in 92.6% of lesions (125/135 lesions). Local tumor progression occurred in 11.6% (8/69) of patients and new intrahepatic metastasis occurred in 55.1% (38/69) of patients. From the time of initial RFA, the median overall survival was 26 months, and the one-, two-, three- and five -year survival rates were 81.8, 50.1, 25.3 and 11.0%, respectively. Based on the multivariate analysis, the following three factors were identified as independent prognostic factors for overall survival: tumor size (p = .017), positive estrogen receptor status (p = .009) and extrahepatic metastatic disease (p = .001). The median progression-free survival was 24 months, and the one-, two-, three- and five -year survival rates after RFA were 77.4, 47.0, 23.7 and 8.5%, respectively. Additionally, the independent prognostic factors for progression-free survival included tumor size (p = .011), ER positivity (p = .001), margin size (p = .017) and extrahepatic metastatic disease (p < .001). CONCLUSION: The results of this study showed that RFA is a safe and locally effective method for the treatment of BCLM, especially in patients with lesions measuring less than 3 cm in diameter, a single liver metastasis, positive estrogen receptor status and no extrahepatic metastases. Also, patients with margin size >10 mm had no local tumor progression.

Primary Amebic Meningoencephalitis: A Case Report.

Primary amebic encephalitis (PAM) is a devastating central nervous system infection caused by Naegleria fowleri, a free-living amoeba, which can survive in soil and warm fresh water. Here, a 43-year-old healthy male was exposed to warm freshwater 5 days before the symptom onset. He rapidly developed severe cerebral edema before the diagnosis of PAM and was treated with intravenous conventional amphotericin B while died of terminal cerebral hernia finally. Comparing the patients with PAM who has similar clinical symptoms to those with other common types of meningoencephalitis, this infection is probably curable if treated early and aggressively. PAM should be considered in the differential diagnosis of purulent meningoencephalitis, especially in patients with recent freshwater-related activities during the hot season.

PAX5 interacts with RIP2 to promote NF-κB activation and drug-resistance in B-lymphoproliferative disorders.

Paired box protein 5 (PAX5) plays a lineage determination role in B-cell development. However, high expression of PAX5 has been also found in various malignant diseases, including B-lymphoproliferative disorders (B-LPDs), but its functions and mechanisms in these diseases are still unclear. Here, we show that PAX5 induces drug resistance through association and activation of receptor-interacting serine/threonine-protein kinase 2 (RIP2; also known as RIPK2), and subsequent activation of NF-κB signaling and anti-apoptosis gene expression in B-lymphoproliferative cells. Furthermore, PAX5 is able to interact with RIP1 and RIP3, modulating both RIP1-mediated TNFR and RIP2-mediated NOD1 and NOD2 pathways. Our findings describe a new function of PAX5 in regulating RIP1 and RIP2 activation, which is at least involved in chemotherapeutic drug resistance in B-LPDs.

Percutaneous ablation of the tumor feeding artery for hypervascular hepatocellular carcinoma before tumor ablation.

OBJECTIVE: To evaluate the efficiency and safety of percutaneous ablation of the tumor feeding artery (PAA) before radiofrequency ablation (RFA) for hypervascular hepatocellular carcinoma (HCC) under ultrasound guidance. PATIENTS AND METHODS: In total, 94 patients with hypervascular HCC and tumor feeding artery visible by contrast-enhanced ultrasound were prospectively randomized to receive either PAA combined with RFA (RFA + PAA) or RFA alone. This study was registered at the clinical trials registry website (No. NCT03143140). The mean tumor size was 3.2 ± 0.9 cm (2.0-5.0 cm). The mean follow-up was 23.7 ± 9.7 months (4-44 months). The technical success, local tumor progression and intrahepatic distant recurrence rates were compared. Survival analysis was performed using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The local tumor progression rate was lower for the PAA + RFA group than for the RFA group (8.5% vs 21.3%, p < .082). No significant differences in the technical success and intrahepatic distant recurrence rates were observed between the two groups (97.9% vs 91.5%, p = .203 and 40.4% vs 42.6%, p = .834). The 1- and 3-year local tumor progression-free survival rates were 91.5% and 69.9% vs 68.1% and 52.1% for the PAA + RFA vs RFA groups, respectively (p = .052). The 1- and 3-year overall survival rates were 95.7% and 69.1% vs 89.4% and 66.6% in the PAA + RFA vs RFA groups, respectively (p = .744). The major complication rate was 4.3% in both groups. CONCLUSIONS: PAA appears to be an effective and safe technique for the treatment of hypervascular HCC, with a lower local tumor progression rate than that of conventional RFA.

Long-term outcome of percutaneous radiofrequency ablation in recurrent hepatocellular carcinoma after liver transplantation.

PURPOSE: To investigate the long-term outcome and prognostic factors of radiofrequency ablation (RFA) in recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: From 2004 to 2014, 15 patients with 23 hepatic recurrent HCCs after LT underwent ultrasound-guided percutaneous RFA. There were 14 males and 1 female aged 54.3 ± 9.5 years old (37-78 years old). The average tumour size was 3.3 ± 1.2 cm (1.7-6.0 cm). Seven patients had a single HCC and eight had 2-4 HCCs. Regular follow-up after RFA was performed to assess local response rates and long-term survival rates. Survival results were generated using Kaplan-Meier estimates, and a multivariate analysis was performed using the Cox regression model. RESULTS: The technical success rate was 95.7% (22/23 tumours). The minor complication rate was 7.7% (2/26 sessions), and there were no major complications. The follow-up period was 27.4 ± 18.9 months (12-116 months). The local progression rate and intrahepatic new lesion rate were 13.0% (3/23 tumours) and 53.3% (8/15 patients), respectively. Extrahepatic metastasis was found in four patients (26.7%). The 1-, 3- and 5-year estimated overall survival rates were 71.8%, 35.9% and 26.9%, respectively. Additionally, the multivariate analysis revealed that serum α-fetoprotein (AFP) before RFA, tumour number and extrahepatic metastasis were significantly related to overall survival after RFA. CONCLUSION: Ultrasound-guided percutaneous RFA of recurrent HCC after LT had a high technical success rate and local control. However, RFA cannot decrease the frequency of new tumours or extrahepatic metastasis. The AFP level and tumour number before RFA should be considered to predict the outcome.

Disequilibrium in the CD8+CD28+/CD8+CD28- T Lymphocyte Balance Is Related to Prognosis in Rats with Trinitrobenzenesulfonic Acid-Induced Colitis.

PURPOSE: The CD8+CD28+/CD8+CD28- T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8+CD28+/CD8+CD28- T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: The frequencies of blood CD8+CD28+ and CD8+CD28- T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry. The treated rats were administered with mesalazine and were euthanized after a 14-day treatment, as were the normal and model rats. The sensitivity and specificity of the CD8+CD28+/CD8+CD28- T lymphocyte balance in diagnosing early colitis were analyzed by receiver operating characteristics (ROC) curves. The frequencies of CD8+CD28+ and CD8+CD28- T lymphocytes in the colon tissue were tested via immunofluorescence. ELISA was used to measure the levels of the cytokines. Immunohistochemistry and Western blotting were used to detect the colonic expression of JAK3, STAT6, NFATc2, and GATA3. RESULTS: We found that the ratio of CD8+CD28+/CD8+CD28- T lymphocytes decreased, as did the level of interleukin-7, but not IL-12p40, IL-13, or IL-15, in the blood; however, the ratio increased along with JAK3, STAT6, NFATc2, and GATA3 in the colon of the rats with colitis. The changes were effectively reversed through the administration of mesalazine for 13 days. Surprisingly, the balance in the blood could sensitively distinguish rats with early colitis from normal rats. CONCLUSION: These data show that increase in CD8+CD28+ T cells in blood and decrease in CD8+CD28- T cells in colon are associated with experimental colitis.

Preliminary experience with direct percutaneous arterial embolisation combined with radiofrequency ablation for hypervascular HCC.

OBJECTIVE: The purpose of this study was to evaluate the outcomes of a novel technique consisting of ultrasound-guided percutaneous arterial embolisation (PAE) of the tumour-feeding artery before radiofrequency ablation (RFA) for hypervascular hepatocellular carcinoma (HCC). METHODS: Twenty-three HCC patients with hypervascular tumours who were non-TACE candidates were enrolled in the study. The mean size of the tumours was 4.6 ± 1.2 cm (3.2-6.0 cm). PAE was performed using 20-gauge catheter needles under greyscale and colour ultrasound guidance. Regular follow-up was performed to evaluate the outcomes and safety of this novel method. RESULTS: Post-PAE colour Doppler ultrasound revealed an immediate embolising effect in 29 feeding arteries, including 21 arteries that became invisible (72.4%) and 8 arteries that exhibited reduced flow velocity (27.6%). Based on the one-month enhanced CT/MRI, complete necrosis was achieved in 24 of 25 tumours (96.0%). The mean follow-up period was 42.7 ± 9.8 months. Local tumour recurrence was observed in 3 tumours (12.0%), and new intrahepatic tumours developed in 9 patients (39.1%). The probabilities of overall survival at 1, 3, 5 and 10 years were 77.3%, 40.0%, 25.0% and 18.8%, respectively. No major complications occurred in this group. CONCLUSIONS: The PAE method could help effectively to reduce or inhibit the blood supply of HCC. RFA followed by PAE treatment achieved 25.0% 5-year survival with no major complications. As a minimally invasive approach, PAE may provide a novel local therapy for hypervascular HCC patients who are non-TACE candidates.

Clinical application of hepatic wedge ablation for treating liver malignancies of the inferior margin: a new ablation technique.

PURPOSE: To determine the efficacy and safety of percutaneous hepatic wedge ablation in treating hepatic malignancies of the inferior margin. MATERIALS AND METHODS: Seventy-seven patients with hepatic malignancies at the inferior margin underwent percutaneous radiofrequency ablation (RFA). Thirty-two patients underwent hepatic wedge ablation and 45 patients underwent conventional tumour ablation. Comparative analysis of the two groups was performed including gender, age, tumour size, number of ablation cycles, ablation duration and injected hydrodissection volume. The rate of technical success, local tumour progression, intrahepatic distant recurrence, major complications and overall survival were assessed and compared. Survival analysis was analysed using the Kaplan-Meier method. Differences in the survival rates were compared with log-rank test. RESULTS: The mean number of ablation cycles and ablation duration were significantly higher in the hepatic wedge ablation group than conventional tumour ablation (1.6 ± 0.9 vs. 1.2 ± 0.4, p = .042, and 30.2 ± 18.5 vs. 22.5 ± 8.5 min, p = .031, respectively). The local tumour progression rate was significantly lower in hepatic wedge ablation group (0% vs. 17.78%, p = .038) at median follow-up of 21 months. The rate of technical success, intrahepatic distant recurrence, major complications and overall survival did not differ between the two groups. CONCLUSION: Hepatic wedge ablation appears to be a highly effective treatment for hepatic malignancies in the inferior margin and provides a better local control than conventional tumour ablation.

Focal Liver Lesions: Real-time 3-Dimensional Contrast-Enhanced Ultrasonography Compared With 2-Dimensional Contrast-Enhanced Ultrasonography and Magnetic Resonance Imaging.

OBJECTIVES: This study sought to evaluate the application of real-time 3-dimensional (3D) contrast-enhanced ultrasonography (US) to diagnose focal liver lesions and to compare these results with those from 2-dimensional (2D) contrast-enhanced US and contrast-enhanced magnetic resonance imaging (MRI). METHODS: Patients with focal liver lesions were examined by 2D contrast-enhanced US, 3D contrast-enhanced US, and contrast-enhanced MRI for lesion characterization, and biopsies and comprehensive clinical diagnoses served as reference standards. The sensitivity, specificity, area under the receiver operating characteristic curve, and intermodality agreement were assessed. The number of contrast agent injections and lesions observed per injection were calculated for 3D and 2D contrast-enhanced US. The number and display quality of the feeding arteries observed with 3D and 2D contrast-enhanced US were assessed. RESULTS: A total of 117 patients with 151 focal liver lesions were enrolled, including 67 cases of hepatocellular carcinoma, 51 cases of liver metastasis, and 33 cases of benign liver lesions. No significant differences were found among the modalities. The sensitivity values for 3D contrast-enhanced US, 2D contrast-enhanced US, and contrast-enhanced MRI were 96%, 95%, and 93%, respectively; the specificity values were 87%, 84%, and 89%; and the area under the receiver operating characteristic curve values were 0.92, 0.90, and 0.92. The intermodality agreement was excellent (κ > 0.77). Fewer contrast agent injections were needed, and more lesions and feeding arteries were more clearly displayed on 3D than 2D contrast-enhanced US (P < .001). CONCLUSIONS: Real-time 3D contrast-enhanced US is useful for diagnosing focal liver lesions and for observing feeding arteries with fewer contrast agent injections.

Long-term survival of hepatocellular carcinoma after percutaneous radiofrequency ablation guided by ultrasound.

BACKGROUND: The risk factors for recurrence and death after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remain poorly known. This study was aimed to study the 10-year overall survival (OS) of HCC treated by ultrasound (US)-guided RFA and the risk factors for recurrence and death. METHODS: Between June 2005 and June 2016, 1000 patients with HCC treated by US-guided RFA at 4 hospitals in China; among them, 525 patients met the criteria for radical ablation and 410 had high AFP levels before RFA treatment. Clinical and biochemical factors were tested for association with recurrence and survival. Patients were divided into the recurrence (n = 348) and no recurrence groups (n = 62). RESULTS: The 5- and 10-year survival rates were 66 and 35%, respectively. Tumor size (HR = 1.36, 95% CI 1.12-1.65), albumin levels (HR = 0.76, 95% CI 0.65-0.91), prothrombin time (HR = 2.18, 95% CI 1.54-3.10), and α-fetoprotein levels (HR = 1.13, 95% CI 1.00-1.26) were independently associated with mortality after RFA for HCC. Tumor size (HR = 1.27, 95% CI: 1.15-1.40), HBV-DNA (HR = 7.70, 95% CI 3.57-16.63), AFP levels before treatment (HR = 2.172, 95% CI 1.256-3.756, P = 0.006), and AFP response (HR = 4.722, 95% CI 1.053-21.184, P = 0.0427) were independently associated with the risk of recurrence of HCC after RFA. The median survival of the patients with and without recurrence after RFA was 54 (95% CI 45-58) and 62 (95% CI 48-80) months, respectively (log-rank, P = 0.04). CONCLUSIONS: Tumor size, albumin, prothrombin time, and α-fetoprotein levels were independently associated with mortality after US-guided RFA for HCC, while tumor size and HBV-DNA were independently associated with recurrence. Patients with recurrence had a poorer survival compared with those without.