Hepatic arterial infusion chemotherapy combined with toripalimab and surufatinib for the treatment of advanced intrahepatic cholangiocarcinoma.

PURPOSE: The aim of the present study is to report the clinical results of patients with advanced intrahepatic cholangiocarcinoma (ICC) who received combination therapy of hepatic arterial infusion chemotherapy (HAIC), toripalimab and surufatinib. METHODS: The study cohort consisted of 28 patients with advanced ICC who were treated with HAIC (mFOLFOX6 regimen, Q3W) in combination with intravenous toripalimab (240 mg, Q3W) and oral surufatinib (150 mg, once daily). The cohort had 14 male and 14 female patients. The baseline characteristics of the study cohort were obtained. The tumor response and drug-associated toxicity were assessed and reported. RESULTS: During the follow-up period (median follow-up time: 11.3 months; range: 4-19 months), four patients died of tumor progression. The objective response rate and disease control rate were 58% and 79%, respectively. The mPFS was 9.5 months, and the overall survival rate was 83.3%. The most frequent adverse events were nausea and vomiting (100%) and abdominal pain (85.7%). Serious complications related to death were not observed. CONCLUSION: The combination treatment schedule for advanced ICC demonstrated positive efficacy and safety profiles. CLINICAL SIGNIFICANCE: This study provides promising clinical guidance for the treatment of advanced cholangiocarcinoma and is expected to modify the treatment strategy for this disease.

Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

Recent advances in hepatocellular carcinoma-targeted nanoparticles.

In the field of medicine, we often brave the unknown like interstellar explorers, especially when confronting the formidable opponent of hepatocellular carcinoma (HCC). The global burden of HCC remains significant, with suboptimal treatment outcomes necessitating the urgent development of novel drugs and treatments. While various treatments for liver cancer, such as immunotherapy and targeted therapy, have emerged in recent years, improving their transport and therapeutic efficiency, controlling their targeting and release, and mitigating their adverse effects remains challenging. However, just as we grope through the darkness, a glimmer of light emerges-nanotechnology. Recently, nanotechnology has attracted attention because it can increase the local drug concentration in tumors, reduce systemic toxicity, and has the potential to enhance the effectiveness of precision therapy for HCC. However, there are also some challenges hindering the clinical translation of drug-loaded nanoparticles (NPs). Just as interstellar explorers must overcome interstellar dust, we too must overcome various obstacles. In future researches, the design and development of nanodelivery systems for novel drugs treating HCC should be the first attention. Moreover, researchers should focus on the active targeting design of various NPs. The combination of the interventional therapies and drug-loaded NPs will greatly advance the process of precision HCC therapy.

Effect of probiotics and fecal microbiota transplantation in dirty rats with established primary liver cancer.

Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials & methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of ß-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.

Pyogenic liver abscess in non-liver cancer patients and liver cancer patients treated with TACE: Etiological characteristics, treatment, and outcome analysis.

Clinical, laboratory, and microbiological features, clinical outcomes, and pyogenic liver abscess (PLA) prognosis evaluation in non-liver cancer (Non-LC) and liver cancer patients treated with transarterial chemoembolization (TACE, LC-TACE). Clinical data of 48 consecutive PLA patients from January 2016 to December 2020 were retrospectively analyzed. Mortality between two PLA patient groups were compared, and mortality risk factors were evaluated. A total of 48 PLA patients (31 males and 17 females) from January 2016 to December 2020 met the study's inclusion criteria. There were 32 and 16 patients in the Non-LC and LC-TACE groups, respectively. Positive pus culture rate in the Non-LC group was 87.5% and positive pus culture rate in LC-TACE group was 81.3%. In the Non-LC group, 28 patients improved after treatment, 1 patient did not improve, and 3 patients died during hospitalization, with a 9.4% mortality rate. In the LC-TACE group, nine patients improved after treatment, three patients did not improve, and four patients died during hospitalization, with a 25% mortality rate. The Non-LC group cure time was 37.4 ± 23.1 days, while the LC-TACE group was 91.5 ± 49.7 days. PLA of the Non-LC group and the LC-TACE group were different in terms of pathogenic bacteria and cure time, and so on. A more comprehensive treatment should be considered for PLA after TACE.

Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression.

Purpose: The present retrospective study aimed to evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP). Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events (AEs). Risk factors for PFS were evaluated with logistic regression analysis. Results: A total of 41 patients were included. The objective response rates (ORR) and disease control rates (DCR) were 24.4% and 61.0% at 2 to 3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% confidence interval [CI]: 3.8 months, 8.2 months). Of the 41 patients, 23 received camrelizumab combined with TACE (hereafter, camrelizumab-TACE) on whom 52 combined TACE procedures were performed, with a median of 2 procedures (range: 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab-TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab-TACE group and 3 months in the camrelizumab monotherapy group (P < .001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least 1 type of AE after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 14, 34.1%) being the most common AE. Conclusion: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.

Safety and efficacy of Endovascular Management of high-grade blunt renal injury.

Objectives: To provide data on the safety and efficacy of renal arterial embolization (RAE) in patients with high-grade blunt renal injury. Materials and methods: Fifteen patients with high-grade blunt renal injury (AAST grades IV-V) admitted to our hospital from July 2014 to December 2019 were retrospectively reviewed in this study. Their clinical success rate and complications were investigated accordingly. Results: Fifteen patients with high-grade blunt renal injury, 13 men and 2 women with an average age of 41.6 years, including 11 hemodynamically unstable patients and 4 stable patients, were treated with RAE. Among these patients, 73.3% (11 of 15) had grade IV, and 26.7% (4 of 15) had grade V injuries, while 53.3% (8 of 15) patients had concomitant injuries. One patient received main RAE and 14 patients received selective RAE. The clinical success rate after the first embolization was 93.3% (14 of 15). RAE was repeated and was successfully performed in one patient with sustained hematuria. No significant difference in creatinine levels was found before and after embolization. During the follow-up period of 2-82 months, two patients required tube drainage due to urine leaks, one patient developed renal failure requiring renal replacement therapy, and one patient developed secondary hypertension. Conclusions: RAE can provide a high success rate of hemostasis for both hemodynamically stable and unstable patients with high-grade blunt renal injury, and only minor complications are observed with this procedure.

Endovascular repair of visceral artery aneurysms and pseudoaneurysms in 159 patients: twelve years' experience of clinical technique.

OBJECTIVES: The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment for patients with visceral and renal artery aneurysms (VRAAs). Twelve years of experience with interventional procedures and treatment options in our center were also worth discussing. METHODS: From January 2009 to December 2020, clinical data of 159 consecutive patients with VRAAs were retrospectively analyzed. Patients' demographic and clinical data were recorded, and the safety and efficacy of endovascular therapy were evaluated. In addition, interventional procedures were also described. RESULTS: A total of 159 patients underwent angiography, and 154 patients were successfully treated with endovascular therapy, with a technical success rate of 96.9%. Of the 154 patients with successful endovascular therapy, 3 patients died within 30 days of treatment, with a 30-day mortality rate of 1.9%, and the remaining patients were clinically successful, with a clinical success rate of 98.1%. Fifty-seven patients underwent emergency interventional treatment due to ruptured aneurysm. There were statistically significant differences in hemoglobin before and after emergency treatment (78.5 ± 22.0 g/dL vs. 93.8 ± 15.0 g/dL, P = 0.00). No other serious complications occurred except death in 3 patients. CONCLUSION: Endovascular treatment of VRRAs is safe and effective and can significantly improve the symptoms of patients, especially those with ruptured aneurysms.

Thoracic Endovascular Aortic Repair for Retrograde Type A Intramural Hematoma With Intimal Disruption in the Descending Aorta.

PURPOSE: To evaluate the safety and efficacy of thoracic endovascular aortic repair (TEVAR) for retrograde type A intramural hematoma (IMH) with intimal disruption in the descending aorta and report our endovascular therapeutic experience. MATERIALS AND METHODS: From January 2014 to October 2020, a total of 24 consecutive patients with retrograde type A IMH with intimal disruption (intimal tear or ulcer-like projection) in the descending aorta underwent TEVAR. The demographics, clinical characteristics, treatment details, imaging information, and follow-up results were reviewed. RESULTS: Among all patients with retrograde type A IMH, 13 (54.2%) patients presented with ulcer-like projection and 11 (45.8%) with intimal tear (aortic dissection) in the descending aorta. Successful TEVAR was achieved in all patients. There was no 30-day mortality. During a mean follow-up of 37.5 months, 1 patient (4.2%) developed permanent paralysis, 1 patient (4.2%) underwent reintervention due to the expansion of the aorta distal to the stent resulting from the enlargement of distal intimal tear at the 2 month follow up, and no other adverse events were observed. The latest computed tomographic angiography images showed that the maximum diameter of the ascending aorta and descending aorta significantly decreased after TEVAR (both p<0.001), and the IMH/false lumen in the ascending aorta and the descending thoracic aorta were completely absorbed. CONCLUSION: Thoracic endovascular aortic repair for selected patients with retrograde type A intramural hematoma that presented with intimal disruption in the descending aorta is feasible and efficient, but close surveillance is needed to manage aortic-related adverse events.

The Efficacy of Radiotherapy in the Treatment of Hepatocellular Carcinoma with Distant Organ Metastasis.

BACKGROUND: Recently, radiotherapy has been used in the treatment of hepatocellular carcinoma (HCC). However, there is no study analyzing the efficacy of radiotherapy in cases of advanced HCC. The objective of this investigation was to determine the efficacy of radiotherapy in patients with HCC invading distant organs. METHODS: The data of 2342 patients diagnosed between 2010 and 2015 with HCC invading distant organs were extracted from the SEER database. Propensity score matching (PSM) was used to reduce selection bias. RESULTS: Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group (mOS = 5 months, 95% CI: 4.5-5.5; mCSS = 5 months, 95% CI: 4.4-5.6) were longer than those in the nonradiotherapy group (mOS = 3 months, 95% CI: 2.8-3.2; mCSS = 3 months, 95% CI: 2.8-3.2; both P < 0.001). After PSM, mOS in the radiotherapy group (5 months, 95% CI: 4.5-5.5) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6-3.4; P < 0.001), and the mCSS in the radiotherapy group (5 months, 95% CI: 4.4-5.6) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6-3.4; P < 0.001). Before PSM, the multivariate analysis showed that all-cause and cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group. The adjusted Cox regression analysis for subgroups showed that, in the nonradiotherapy group, patients with bone metastases and multiorgan metastases had a worse survival than those in the radiotherapy group. CONCLUSION: HCC patients with metastases to distant organs obtain survival benefit from radiotherapy, particularly patients with bone metastases and multiorgan metastases.

Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome and Risk Signature Analysis.

OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with treatment-naïve hepatocellular carcinoma (TN-HCC) and recurrent HCC (R-HCC). In addition, risk signature analysis was performed to accurately assess patients' recurrence and survival. METHODS: This retrospective study assessed the consecutive medical records of TN-HCC and R-HCC patients from January 2014 to December 2018. In order to reduce the patient selection bias, propensity score matching (PSM) analysis was applied. Conditional inference tree was used to establish a risk signature. RESULTS: A total of 401 eligible patients were included in our study, including 346 patients in the TN-HCC group and 55 patients in the R-HCC group. Forty-seven pairs of patients were chosen after the PSM analysis. Before the PSM analysis, the objective tumor regression (ORR) and disease control rate (DCR) of R-HCC patients were better than that of TN-HCC patients; however, after the PSM analysis, there was no significant difference in the ORR and DCR between the two groups (P>0.05). Before the PSM analysis, the median overall survival (OS) and progression-free survival (PFS) in the R-HCC group were significantly greater than those of the TN-HCC group (OS: 24 months vs. 18 months, P =0.004; PFS: 9 months vs. 6 months, P =0.012). However, after the PSM analysis, the median OS and PFS in the R-HCC group were inferior to those in the TN-HCC group (OS: 24 months vs. 33 months, P= 0.0035; PFS: 10 months vs. 12 months, P = 0.01). The conditional inference tree divided patients into different subgroups according to tumor size, BCLC stage, and TACE sessions and shared different hazards ratio to recurrence or survival. CONCLUSION: Patients with R-HCC treated with TACE achieved satisfactory results, although survival after the PSM analysis was not as good as in the TN-HCC group. In addition, risk signature based on conditional inference tree analysis can more accurately predict the recurrence and survival in both groups of patients.

Quantitative dual-energy CT for evaluating hepatocellular carcinoma after transarterial chemoembolization.

We aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal-Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.

Single-Center Experience With Endovascular Treatment for Splenic Artery Aneurysms in Long-Term Follow-Up: A Retrospective Study.

OBJECTIVES: To reveal a single-center experience with endovascular treatment for splenic artery aneurysm (SAA) and analyze the safety and efficacy of the operation in the long-term follow-up. MATERIALS AND METHODS: A total of 49 patients with SAAs (21 men, 28 women; mean age, 52.4 ± 11.5 years) were enrolled in this study from July 2010 to December 2020. Baseline and characteristics of SAAs were collected. Parent artery coil embolization or combined with sac coil embolization of SAAs, graft-stent implantation, or bare-stent-assisted coil embolization were performed for the treatment of SAAs. Adverse events and follow-up data were recorded. RESULTS: The average diameter of SAAs was 3.3 ± 2.5 cm (range, 1.0-13.6 cm). An individual-tailed modality was conducted for three patients. A 100% technical success rate was achieved. No re-intervention procedure was performed in all patients. No major treatment-related adverse events were observed, and no expansion or rupture of SAAs occurred in the average follow-up period of 57.9 ± 27.3 months (19-125 months). CONCLUSION: Endovascular treatment of SAA, including the individual-tailed therapy for three cases, is safe, effective, and minimally invasive with high technical success rates and satisfactory outcomes during the long-term follow-up period.

TAT-Modified Gold Nanoparticles Enhance the Antitumor Activity of PAD4 Inhibitors.

PURPOSE: Histone citrullination by peptidylarginine deiminases 4 (PAD4) regulates the gene expression of tumor suppressor. In our previously study, YW3-56 (356) was developed as a potent PAD4 inhibitor for cancer therapy with novel function in the autophagy pathway. To enhance the antitumor activity, the PAD4 inhibitor 356 was modified by the well-established cationic penetrating peptide RKKRRQRRR (peptide TAT) and gold nanoparticles to obtain 356-TAT-AuNPs which could enhance the permeability of chemical drug in solid tumor. METHODS: 356-TAT-AuNPs were prepared, and their morphology were characterized. The antitumor activity of 356-TAT-AuNPs was evaluated in vitro and in vivo. RESULTS: 356-TAT-AuNPs exhibited higher anticancer activity against HCT-116, MCF-7 and A549 cells than 356 and 356-AuNPs. Compared with 356 and 356-AuNPs, 356-TAT-AuNPs entered the cytoplasm and nuclear, exhibited stronger anticancer activity by increasing apoptosis, inducing autophagy and inhibiting of histone H3 citrullination, and in HCT-116 xenograft mouse model, 356-TAT-AuNPs could improve the antitumor activity. CONCLUSION: The modified AuNPs with peptide TAT as drug delivery system are potent in delaying tumor growth and could be a powerful vehicle for profitable anticancer drug development. We believe that peptide TAT modification strategy may provide a simple and valuable method for improving antitumor activity of PAD4 inhibitors for clinical use.

Design and Synthesis of Biotinylated Bivalent Carboline Derivatives as Potent Antitumor Agents.

Compound 6, a novel ß-carboline comprising two 1-methyl-9H-ß-carboline-3-carboxylic acids and a biotin moiety conjugated together using tris(2-aminoethyl)amine, was synthesized and tested for its cytotoxicity toward MCF-7 and HepG2 cell lines and antitumor potency in an S180 tumor-bearing mouse model. Compound 6 was delivered via biotin receptor-mediated endocytosis and exerted its therapeutic effects by intercalation binding with DNA. In vivo antitumor evaluations of 6 revealed that it is efficacious and exhibits low systemic toxicity.

Correlation Between Chest CT Findings and Clinical Features of 211 COVID-19 Suspected Patients in Wuhan, China.

BACKGROUND: Chest computed tomography (CT) has been widely used to assess pulmonary involvement in COVID-19. We aimed to investigate the correlation between chest CT and clinical features in COVID-19 suspected patients with or without fever. METHODS: We retrospectively enrolled 211 COVID-19 suspected patients who underwent both chest CT and reverse transcription polymerase chain reaction in Wuhan, China. The performance of CT in patients with relevant onset of symptoms, with fever (n = 141) and without fever (n = 70), was assessed respectively. RESULTS: The sensitivity of CT for COVID-19 was 97.3%, with area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.66-0.76). There were 141 suspected patients with fever and 70 without fever. In the fever group, 4 variables were screened to establish the basic model: age, monocyte, red blood cell, and hypertension. The AUC of the basic model was 0.72 (95% CI, 0.63-0.81), while the AUC of the CT-aided model was 0.77 (95% CI, 0.68-0.85), a significant difference (P < .05). In the nonfever group, only dry cough was screened out to establish the basic model. The AUC was 0.76 (95% CI, 0.64-0.88), which was not significantly different than the CT-aided model (P = .08). CONCLUSIONS: Chest CT has a high sensitivity in patients with COVID-19, and it can improve diagnostic accuracy for COVID-19 suspected patients with fever during the initial screen, whereas its value for nonfever patients remains questionable.

The combination of balloon-assisted antegrade transvenous obliteration and transjugular intrahepatic portosystemic shunt for the management of cardiofundal varices hemorrhage.

OBJECTIVES: In this study, we propose a modified balloon-occluded retrograde transvenous obliteration (BRTO) strategy - balloon-assisted antegrade transvenous obliteration (BAATO), and explore the feasibility, efficacy and safety of BAATO combined with transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of cardiofundal varices (GOV2 or IGV1) hemorrhage. MATERIALS AND METHODS: In this retrospective cohort study, 15 patients with cardiofundal varices hemorrhage who received BAATO combined with TIPS procedures, from August 2017 to September 2019 in our center, were enrolled. They consisted of seven patients with GOV2 and eight patients with IGV1. The clinical efficacy and safety of BAATO + TIPS procedures were assessed by comparing the clinical symptoms, laboratory and imaging examinations before and after treatment. RESULTS: The technical success rate of BAATO + TIPS procedure was 100%. After the procedure, clinical symptoms were improved and complete regression of gastric varices (GVs) was observed in all patients, besides, the control efficiency of ascites and PVT which were 77.8 and 87.5%, respectively. No patient died or had a rebleeding during the follow up, but grade II hepatic encephalopathy (HE) occurred in two patients (13.3%) and shunt dysfunction was discovered in one patient (6.7%). CONCLUSION: For the treatment of GVs, the new technique BAATO is feasible, safe and effective, and it may be a more convenient and economical method than conventional BRTO. In addition, the combination of BAATO and TIPS may play a positive role in achieving hemostasis and improving the complications of portal hypertension such as ascites and PVT.

Transjugular intrahepatic portosystemic shunt for repeated bleeding of hemorrhoids caused by severe portal hypertension with ectopic varices: A case report.

BACKGROUND: Severe portal hypertension is life-threatening and can bring adverse complications such as ascites, gastroesophageal varices, and edema. It can, even cause variceal hemorrhage, which may lead to a high risk of death. There is a rare incidence in bleeding of hemorrhoids caused by severe ectopic varices. CASE PRESENTATION: We report the case of a female patient with a 20-year history of hepatitis B virus infection who presented with repeated bleeding of hemorrhoids caused by severe portal hypertension with ectopic varices that is connection between the superior mesenteric vein and rectal venous plexus. Laboratory results revealed a hemoglobin level of 74 g/L. Finally, the patient was successfully treated with transjugular intrahepatic portosystemic shunt (TIPSS) placement without variceal embolization after a multidisciplinary comprehensive opinion. In the two-month follow-up period, the patient had failed to develop hepatic encephalopathy or hematochezia, and computed tomography venography (CTV) indicated that the stent was unobstructed and ascites disappeared. CONCLUSIONS: TIPSS placement is effective for the case, and we hope this case can help improve clinicians' awareness of hemorrhoidal bleeding with severe portal hypertension. Portal hypertension should also be considered during the diagnosis and treatment, as opposed to hemorrhoidal bleeding alone. Moreover, abdominal CTV is recommended as an effective imaging examination method to determine the stent status after operation.

NRF2/ABCB1-mediated efflux and PARP1-mediated dampening of DNA damage contribute to doxorubicin resistance in chronic hypoxic HepG2 cells.

Transarterial chemoembolization (TACE)-induced hypoxia can trigger residual liver cancer cells to present a more aggressive phenotype associated with chemoresistance, but the underlying mechanisms are still unknown. In this study, the human liver cancer cell line HepG2 was pre-cultured in different oxygen environments to examine the possible mechanisms of hypoxia-induced doxorubicin resistance. Our study showed that HepG2 cells pre-cultured in a chronic intermittent hypoxic environment exhibited significant resistance to doxorubicin, evidenced by increased intracellular doxorubicin efflux, relatively higher cell proliferation, lower apoptosis, and decreased DNA damage. These changes were accompanied by high levels of NRF2 and ABCB1 under conditions of both chronic and acute hypoxia and PARP1 gene expression only under conditions of chronic hypoxia. SiRNA-mediated silencing of NRF2 gene expression downregulated the expression of ABCB1 and increased the intracellular doxorubicin accumulation and cell apoptosis both in acute and chronic hypoxic HepG2 cells. Moreover, silencing of PARP1 gene expression increased the doxorubicin-induced DNA damage and cell apoptosis in chronic hypoxic cells. On the basis of these findings, we concluded that NRF2/ABCB1-mediated efflux and PARP1-mediated DNA repair contribute to doxorubicin resistance in chronic hypoxic HepG2 cells.