Utilizing a suture-constrained covered stent for shunt reduction to treat transjugular intrahepatic portosystemic shunt-related refractory hepatic encephalopathy: a retrospective study.

PURPOSE: Refractory hepatic encephalopathy (RHE) can occur as a consequence of excessive shunting following the creation of a transjugular intrahepatic portosystemic shunt (TIPS). We describe a technique that utilizes a suture-constrained covered stent for shunt reduction to treat TIPS-related RHE. MATERIALS AND METHODS: Between January 2017 and September 2023, 25 patients with TIPS-related RHE who underwent shunt reduction utilizing a suture-constrained covered stent were reviewed. The procedure involved reducing the diameter of a polytetrafluoroethylene-covered stent from 8 to 5 mm with a non-absorbable suture and inserting it into the existing TIPS stent to reduce shunt flow. RESULTS: Twelve of the 25 patients were evaluated. Shunt reduction was technically successful in all patients and no immediate complications related to the procedures were observed. Varying degrees of improvement in HE symptoms were observed after shunt reduction, with a mean increase in portosystemic gradient of 5 mmHg compared to pre-procedure, and complete disappearance of symptoms was observed in seven (58.3%) individuals. After a median follow-up of 8.3 months, HE recurred in 4 patients (33.3%) and TIPS indication recurred in 2 patients (16.7%) in the form of ascites and variceal bleeding, respectively. One patient (8.3%) developed shunt dysfunction detected by Doppler ultrasound and was accompanied by the presence of hepatic hydrothorax and ascites. At the end of the study, 5 patients (41.7%) were alive, 5 (41.7%) succumbed to liver failure, and 2 (16.7%) succumbed to pneumonia. CONCLUSIONS: Constraining the stent diameter with a suture is feasible, and using this suture-constrained covered stent for shunt reduction can effectively improve TIPS-related RHE. Further investigations are warranted to precisely delineate the impact of the increased portosystemic gradient and to optimize patient survival.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Iodine-125 seed implantation in the treatment of malignant tumors.

Malignant tumors are major causes of morbidity and mortality in China. Despite advances in surgical, radiological, chemotherapeutic, molecular targeting, and immunotherapeutic treatments, patients with malignant tumors still have poor prognoses. Low-dose-rate brachytherapy, specifically 125I seed implantation, is beneficial because of its high local delivery dose and minimal damage to surrounding tissues. Consequently, it has gained increasing acceptance as a treatment modality for various malignant tumors. In this study, we explored the fundamental principles, clinical applications, and new technologies associated with 125I radioactive seed implantation.

Clinical efficacy of CT-guided 125I brachytherapy in patients with local residual or recurrent hepatocellular carcinoma after thermal ablation.

OBJECTIVES: Treatment methods of local residual or recurrent hepatocellular carcinoma (HCC) after thermal ablation are limited. Therefore, our study aimed to explore the efficacy and prognostic factors of 125I brachytherapy for local residual or recurrent lesion after thermal ablation. METHODS: A total of 114 patients with 212 local residual or recurrent HCC tumors after thermal ablation underwent 125I brachytherapy. Local progression-free survival (LPFS) and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. RESULTS: After a 6-month follow-up, the percentage of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) was 57%, 13.2%, and 5.2%, respectively. The 1-, 2-, and 3-year LPFS rates were 58.7%, 50.0%, and 41.2%, respectively. Portal vein tumor thrombus (PVTT) (p = 0.03), the number of intrahepatic tumors (p = 0.01), and AFP level (p = 0.02) were independent risk factors for local tumor progression (LTP). The median LPFS in patients without PVTT (22 months) was much longer compared to those with PVTT (10 months). The median LPFS in patients with less than three intrahepatic lesions improved from 17 to 24 months. The median LPFS was only 5 months in the high AFP group, but was prolonged with a decrease in AFP level (24 months). No severe complications were recorded. All complications were controllable and treatable. CONCLUSIONS: CT-guided 125I brachytherapy was a safe and effective treatment for patients with local residual or recurrent HCC after thermal ablation to improve local control rate.

Transcriptome sequencing-based personalized analysis of hepatocellular carcinoma patients with portal vein tumor thrombus.

BACKGROUND: The mechanism of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) has been widely studied, and numerous diagnostic and prognostic biomarkers for HCC with PVTT have been identified. We aimed to evaluate the extent to which these biomarkers may aid the personalized precision therapy of HCC with PVTT. METHODS: Matched tissue specimens [primary HCC tumor (PT), adjacent normal (N) liver, and PVTT tissues] were acquired from 3 Chinese HCC patients who underwent surgery at Sun Yat-sen University Cancer Centre between 2019 and 2020. Ribonucleic acid (RNA) sequencing was performed on the 9 tissue samples. GFOLD (generalized fold change) algorithm was used to analyze the differently expressed genes (DEGs) between the PVTT, PT, and normal tissues from each patient. Genes with a P<0.01 and a |GFOLD value| >1 were identified as having significantly different expression. RESULTS: In total, 3,543, 32,472, and 12,901 tumorigenesis-associated genes, and 2,919, 17,679, and 14,825 metastasis-associated genes, were detected in Patient 1 (P1), Patient 2 (P2), and Patient 3 (P3), respectively. We analyzed the expression levels of genes associated with hypoxia, macrophage recruitment and cancer stem cells (CSCs). The results showed that hypoxia and CSCs may have contributed to tumorigenesis but not to metastasis in P1. We also found the hypoxia microenvironment played an important role in tumorigenesis and metastasis in P2, and CSCs may have contributed to metastasis. Additionally, we found that CSCs played critical roles in metastasis but not in tumorigenesis in P3. The results also showed that the long non-coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) was greatly overexpressed in the PTs and PVTT in all 3 patients, and Heart and Neural Crest Derivatives Expressed 2-antisense RNA 1 (HAND2-AS1) was downregulated in PVTT compared with PTs in all 3 patients. Thus, MALAT1 and HAND2-AS1 may be robust biomarkers for metastasis in HCC patients with PVTT. CONCLUSIONS: Tumor-associated macrophages (TAMs)-targeted immunotherapy is a promising therapy for HCC patients with PVTT. LncRNAs MALAT1, and HAND2-AS1 may be promising targets for HCC therapy.

Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis.

Hepatocellular carcinoma (HCC) is a common histological class of primary liver cancer with dismal prognosis. Long noncoding RNAs (lncRNAs) are increasingly documented as participators in cancers. Present study aimed to explore the role of long intergenic nonprotein-coding RNA 467 (LINC00467) in HCC. LINC00467 was upregulated in HCC samples in TCGA database, and was confirmed to be elevated in HCC cell lines. Functionally, LINC00467 depletion impeded proliferation and invasion, induced apoptosis, and promoted cellular sensitivity to Axitinib in HCC. Mechanistically, LINC00467 performed as a sponge of microRNA (miR)-509-3p and upregulated the expression of platelet-derived growth factor receptor alpha (PDGFRA) in HCC cells. In conclusion, our study illustrated that LINC00467 promoted proliferation and invasion, impedes apoptosis, and contributed to Axitinib resistance of hepatocellular carcinoma through miR-509-3p/PDGFRA, indicating LINC00467 as a promising biological target for HCC treatment.

LncRNA OR3A4 participates in the angiogenesis of hepatocellular carcinoma through modulating AGGF1/akt/mTOR pathway.

Hepatocellular carcinoma (HCC), as the commonest type in liver cancer, is in urgent need for better treatment target due to its high mortality and poor prognosis. The involvement of angiogenesis in HCC has been identified by multiple studies, but the underlying mechanism remains unclear. Long non-coding RNAs (LncRNAs) have been reported to regulate numerous cancers, including HCC. LncRNA-OR3A4 has been reported to exert oncogenic and angiogenetic functions in gastric cancer, but its role in HCC hasn't been elucidated. Present study aimed to uncover the biological role of OR3A4 in tumor progression and angiogenesis in HCC. The upregulation of OR3A4 in HCC tissues and cell lines and its prognostic significance were first identified. Loss-of-function assays, including CCK-8, transwell and tube formation assay, validated OR3A4 as a promoter for HCC progression and angiogenesis. The association of OR3A4 and AGGF1 with HCC and poor prognosis was identified by qRT-PCR and Kaplan-Meier analysis. Western blotting and spearman's correlation curve verified the effect of OR3A4 on AGGF1 level and their positive association. Rescue assays revealed that OR3A4 promoted cancer progression and angiogenesis in HCC via AGGF1/akt/mTOR. Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway.

Clinical study of transcatheter arterial chemoembolization combined with microwave ablation in the treatment of advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave ablation (MWA) in the treatment of advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Three thousand cases of advanced HCC patients were randomly divided into two groups: 1500 cases in the treatment group were treated with TACE combined with MWA and 1500 cases in the control group were treated with TACE. RESULTS: The effective rate of the treatment group and control group was 71.4% and 42.8%, respectively, and the difference between the two groups was statistically significant (P < 0.05). During the follow-up period at 6, 12, 18, and 24 months postoperatively, the survival rates of the treatment group were 88.1%, 73.8%, 52.3%, and 33.3%, and the survival rates of the control group were 76.2%, 57.1%, 30.9%, and 9.5%, respectively. There was no significant difference in postoperative complications between the two groups. CONCLUSION: It is safe and effective to use TACE combined with MWA in the treatment of advanced HCC, and the effect of combined treatment is better than that of TACE alone.

Experimentally observe the effect of spherical aberration on diffractive intraocular lens using adaptive optics.

We first investigated the similarity in optical quality of a batch of diffractive intraocular lenses (DIOLs), providing experimental evidence for one DIOL as representative of a batch. Using adaptive optics, we then evaluated one DIOL under different levels of Zernike spherical aberration (SA) by applying both a point spread function test and a psychophysical visual acuity test. We found that for small aperture size SA has the effect of shifting the through-focus curve of DIOL. Also, for a relatively large aperture size, it has different effects on the distant and near foci.

Subjective evaluation of intraocular lenses by visual acuity measurement using adaptive optics.

We present a new method for subjectively evaluating intraocular lenses (IOLs) without implantation surgery. To illustrate the method, three types of single-piece IOL (equispherical monofocal, rotational symmetric aspheric monofocal, and diffractive bifocal) were assembled into a model eye and evaluated using an ocular adaptive optics system by a single subject. To separate the spherical aberration of the crystalline lens, the subject's corneal topography and wavefront aberrations were measured and modeled. Three levels of Zernike spherical aberration were generated and superposed on the IOLs and the subject's eye. The corrected distance visual acuity was measured by psychophysical visual procedure.

Comparison of retinal image quality with spherical and customized aspheric intraocular lenses.

We hypothesize that an intraocular lens (IOL) with higher-order aspheric surfaces customized for an individual eye provides improved retinal image quality, despite the misalignments that accompany cataract surgery. To test this hypothesis, ray-tracing eye models were used to investigate 10 designs of mono-focal single lens IOLs with rotationally symmetric spherical, aspheric, and customized surfaces. Retinal image quality of pseudo-phakic eyes using these IOLs together with individual variations in ocular and IOL parameters, are evaluated using a Monte Carlo analysis. We conclude that customized lenses should give improved retinal image quality despite the random errors resulting from IOL insertion.

Intraocular lens implantation position sensitivity as a function of refractive error.

PURPOSE: To quantify the change in ocular aberrations due to intraocular lens (IOL) implantation position errors for pseudo-phakic eyes with different refractive errors. METHODS: The theoretical part of this work was based on ray-tracing in emmetropic and myopic eye models. The possible misalignments i.e. the decentration, tilt and axial translation, of the IOLs were statistically combined together and analysed using Monte-Carlo simulations. Spherical IOLs with a 3 and 5 mm pupil and an aspheric IOL with a 5 mm pupil were analysed as a function of refractive error. In the experimental part of the work, we built an IOL optical test bench including a model eye. The white light discrete point spread functions of misaligned IOLs were recorded by a CCD and we compared the change of the spread function as a result of misalignments for two spherical IOLs with different optical powers. RESULTS: The Monte-Carlo simulations showed that the average root-mean-square spot size at the retinal plane decreased with increasing myopic refractive error, i.e. lower power IOL. The experiments showed that a lower optical power spherical IOL had a less distributed point spread function than a higher optical power IOL, which supported the results of the simulation. CONCLUSION: Regarding IOLs designed for myopic patients, low power IOLs (for high myopes) were shown to be less sensitive to the misalignment than high power ones. Aspheric IOLs were more sensitive to position errors than spherical IOLs under the same conditions.

Subjective blur limits for higher order aberrations.

PURPOSE: We compared subjective blur limits for defocus and the higher-order aberrations of coma, trefoil, and spherical aberration. METHODS: Spherical aberration was presented in both Zernike and Seidel forms. Black letter targets (0.1, 0.35, and 0.6 logMAR) on white backgrounds were blurred using an adaptive optics system for six subjects under cycloplegia with 5 mm artificial pupils. Three blur criteria of just noticeable, just troublesome, and just objectionable were used. RESULTS: When expressed as wave aberration coefficients, the just noticeable blur limits for coma and trefoil were similar to those for defocus, whereas the just noticeable limits for Zernike spherical aberration and Seidel spherical aberration (the latter given as an "rms equivalent") were considerably smaller and larger, respectively, than defocus limits. CONCLUSIONS: Blur limits increased more quickly for the higher order aberrations than for defocus as the criterion changed from just noticeable to just troublesome and then to just objectionable.

Subjective blur limits for cylinder.

PURPOSE: The purpose was to compare subjective blur limits for cylinder and defocus. METHODS: Blur was induced with a deformable, adaptive-optics mirror when either the subjects' own astigmatisms were corrected or when both astigmatisms and higher-order aberrations were corrected. Subjects were cyclopleged and had 5-mm artificial pupils. Black letter targets (0.1, 0.35, and 0.6 logMAR) were presented on white backgrounds. RESULTS: For 10 subjects, blur limits were approximately 50% greater for cylinder than for defocus (in diopters). Although there were considerable effects of axis for individuals, overall, this was not strong, with the 0 degrees (or 180 degrees ) axis having approximately 20% greater limits than oblique axes. In a second experiment with text (equivalent in angle to N10 print at 40 cm distance), cylinder blur limits for six subjects were approximately 30% greater than those for defocus; this percentage was slightly smaller than for the three letters. Blur limits of the text were intermediate between those of 0.35- and 0.6-logMAR letters. Extensive blur limit measurements for one subject with single letters did not show expected interactions between target detail orientation and cylinder axis. CONCLUSIONS: Subjective blur limits for cylinder are 30 to 50% greater than those for defocus, with the overall influence of cylinder axis being 20%.

Effect of optical aberrations on the color appearance of small defocused lights.

We investigated influences of optics and surround area on color appearance of defocused, small narrow band photopic lights (1' arc diameter, lambda(max) 510-628 nm) centered within a black annulus and surrounded by a white field. Participants included seven normal trichromats with L- or M-cone biased ratios. We controlled chromatic aberration with elements of a Powell achromatizing lens and corrected higher-order aberrations with an adaptive optics system. Longitudinal chromatic aberrations, but not monochromatic aberrations, are involved in changing appearance of small lights with defocus. Surround field structure is important because color changes were not observed when lights were presented on a uniform white surround.

Blur limits for defocus, astigmatism and trefoil.

We investigated the limits at which blur due to defocus, crossed-cylinder astigmatism, and trefoil became noticeable, troublesome or objectionable. Black letter targets (0.1, 0.35 and 0.6 logMAR) were presented on white backgrounds. Subjects were cyclopleged and had effectively 5mm pupils. Blur was induced with a deformable, adaptive-optics mirror operating under open-loop conditions. Mean defocus blur limits of six subjects with uncorrected intrinsic higher-order ocular aberrations ranged from 0.18+/-0.08 D (noticeable blur criterion, 0.1 logMAR) to 1.01+/-0.27 D (objectionable blur criterion, 0.6 logMAR). Crossed-cylinder astigmatic blur limits were approximately 90% of those for defocus, but with considerable meridional influences. In two of the subjects, the intrinsic aberrations of the eye were subsequently corrected before the defocus and astigmatic blur were added. This resulted in only minor reductions in their blur limits. When assessed with trefoil blur and corrected intrinsic ocular aberrations, the ratio of objectionable to noticeable blur limits in these two subjects was much higher for trefoil (3.5) than for defocus (2.5) and astigmatism (2.2).

Limits of spherical blur determined with an adaptive optics mirror.

We extended an earlier study (Vision Research, 45, 1967-1974, 2005) in which we investigated limits at which induced blur of letter targets becomes noticeable, troublesome and objectionable. Here we used a deformable adaptive optics mirror to vary spherical defocus for conditions of a white background with correction of astigmatism; a white background with reduction of all aberrations other than defocus; and a monochromatic background with reduction of all aberrations other than defocus. We used seven cyclopleged subjects, lines of three high-contrast letters as targets, 3-6 mm artificial pupils, and 0.1-0.6 logMAR letter sizes. Subjects used a method of adjustment to control the defocus component of the mirror to set the 'just noticeable', 'just troublesome' and 'just objectionable' defocus levels. For the white-no adaptive optics condition combined with 0.1 logMAR letter size, mean 'noticeable' blur limits were +/-0.30, +/-0.24 and +/-0.23 D at 3, 4 and 6 mm pupils, respectively. White-adaptive optics and monochromatic-adaptive optics conditions reduced blur limits by 8% and 20%, respectively. Increasing pupil size from 3-6 mm decreased blur limits by 29%, and increasing letter size increased blur limits by 79%. Ratios of troublesome to noticeable, and of objectionable to noticeable, blur limits were 1.9 and 2.7 times, respectively. The study shows that the deformable mirror can be used to vary defocus in vision experiments. Overall, the results of noticeable, troublesome and objectionable blur agreed well with those of the previous study. Attempting to reduce higher-order aberrations or chromatic aberrations, reduced blur limits to only a small extent.

Changes in through-focus spatial visual performance with adaptive optics correction of monochromatic aberrations.

We determined the influence of adaptive optics correction on through-focus illiterate-E visual acuity and through-focus contrast sensitivity under monochromatic conditions. In two subjects, adaptive optics improved high and low (12%) contrast in-focus visual acuity by 0.1 to 0.15logMAR, but resulted in more rapid and more symmetrical deterioration in visual acuity away from in-focus. In one subject, adaptive optics improved in-focus contrast sensitivity and resulted in more symmetrical and greater loss of contrast sensitivity about the peak sensitivity because of correction of higher-order aberrations. The results show that full correction of higher-order aberrations may worsen spatial visual performance in the presence of some defocus.

Applying SLODAR to measure aberrations in the eye.

As a proof of concept we apply a technique called SLODAR as implemented in astronomy to the human eye. The technique uses single exposures of angularly separated "stars" on a Hartmann-Shack sensor to determine a profile of aberration strength localised in altitude in astronomy, or path length into the eye in our application. We report on the success of this process with both model and real human eyes. There are similarities and significant differences between the astronomy and vision applications.