Targeting neuropilin-1 abolishes anti-PD-1-upregulated regulatory T cells and synergizes with 4-1BB agonist for liver cancer treatment.

BACKGROUND AIMS: Regulatory T cells (Tregs) are an obstacle to PD-1 blockade-mediated antitumor efficacy. However, the behaviors of Tregs response to anti-PD-1 in HCC and the characteristics of Tregs tissue adaptation from peripheral lymphoid tissues to the tumor are still unclear. APPROACH RESULTS: Here, we determine that PD-1 monotherapy potentially augments the accumulation of tumor CD4 + Tregs. Mechanistically, anti-PD-1 mediates Tregs proliferation in lymphoid tissues rather than in the tumor. Increased peripheral Tregs burden replenishes intratumoral Tregs, raising the ratio of intratumoral CD4 + Tregs to CD8 + T cells. Subsequently, single-cell transcriptomics revealed that neuropilin-1 (Nrp-1) supports Tregs migration behavior, and the genes of Crem and Tnfrsf9 regulate the behaviors of the terminal suppressive Tregs. Nrp-1 + 4-1BB - Tregs stepwise develop to the Nrp-1 - 4-1BB + Tregs from lymphoid tissues into the tumor. Moreover, Treg-restricted Nrp1 depletion abolishes anti-PD-1-upregulated intratumoral Tregs burden and synergizes with the 4-1BB agonist to enhance the antitumor response. Finally, a combination of the Nrp-1 inhibitor and the 4-1BB agonist in humanized HCC models showed a favorable and safe outcome and evoked the antitumor effect of the PD-1 blockade. CONCLUSION: Our findings elucidate the potential mechanism of anti-PD-1-mediated intratumoral Tregs accumulation in HCC and uncover the tissue adaptation characteristics of Tregs and identify the therapeutic potential of targeting Nrp-1 and 4-1BB for reprogramming the HCC microenvironment.

Ultrasound Molecular Imaging for Multiple Biomarkers by Serial Collapse of Targeting Microbubbles with Distinct Acoustic Pressures.

Ultrasound molecular imaging (UMI) has shown promise for assessing the expression levels of biomarkers for the early detection of various diseases. However, it remains difficult to simultaneously image multiple biomarkers in a single systemic administration, which is important for the accurate diagnosis of diseases and for understanding the dynamic intermolecular mechanisms that drive their malignant progression. The authors develop an ultrasound molecular imaging method by serial collapse of targeting microbubbles with distinct acoustic pressures for the simultaneous detection of two biomarkers. To test this, αv ß3 -targeting lipid microbubbles (L-MBα ) and VEGFR2-targeting lipid-PLGA microbubbles (LP-MBv ) are fabricated and simultaneously injected into tumor-bearing mice at 7 and 14 days, followed by the low-intensity acoustic collapse of L-MBα and high-intensity acoustic collapse of LP-MBv . The UMI signals of L-MBα and LP-MBv are obtained by subtracting the first post-burst signals from the first pre-burst signals, and subtracting the second post-burst signals from the first post-burst signals, respectively. Interestingly, the signal intensities from UMI agree with the immunohistochemical staining results for αv ß3 and VEGFR2. Importantly, they find a better fit for the invasive behavior of MDA-MB-231 breast tumors by analyzing the ratio of αv ß3 integrin to VEGFR2, but not the single αv ß3 or VEGFR2 levels.

Virtual navigation-guided radiofrequency ablation for recurrent hepatocellular carcinoma invisible on ultrasound after hepatic resection.

BACKGROUND: No reports are available on the technical efficiency and therapeutic response of virtual navigation (VN)-guided radiofrequency ablation (RFA) for patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection. The aim of this study was to investigate the overall technical performance and outcome of VN-guided RFA in recurrent HCC patients. In addition, a nomogram model was developed to predict the factors influencing the overall survival (OS). METHODS: This was a prospective study on 76 recurrent HCC patients who underwent VN-guided RFA between June 2015 and February 2018. The technical feasibility, success, and efficiency, OS, local tumor progression, and complications were evaluated. A multivariate Cox regression analysis was conducted to predict the significant factors, and a nomogram including independent predictive factors was subsequently plotted to predict OS. RESULTS: The technical feasibility, success, and efficiency rates of VN-guided RFA were 86.4%, 94.7%, and 97.4%, respectively. The cumulative OS rates at 1-, 2-, and 3-year were 88.1%, 79.7%, and 71.0%, respectively. The cumulative local tumor progression rates at 1-, 2-, and 3-year were 5.5%, 8.7%, and 14.0%, respectively. In addition, the minor and major complication rates were 5.3% and 3.9%, respectively. No intervention-related deaths occurred during the follow-up period. The C-index of the OS nomogram in this study was 0.737. CONCLUSIONS: VN-guided RFA is an effective therapeutic option in recurrent HCC patients and improves the long-term outcomes especially for the lesions that cannot be detected in the two-dimensional ultrasound. Besides, the nomogram may be a useful supporting tool in predicting OS to estimate the individual survival probability, optimize treatment options, and facilitate decision-making.

Endoscopic Ultrasonography-Guided Versus Percutaneous Drainage for the Recurrent Pancreatic Fluid Collections.

BACKGROUND Ultrasonography-guided percutaneous drainage for pancreatic fluid collections is associated with a high recurrence rate and endoscopic ultrasonography (EUS)-guided drainage is a valuable approach. Our aim was to compare the efficacy and safety of percutaneous and EUS-guided drainage for the recurrent pancreatic fluid collections. MATERIAL AND METHODS A retrospective analysis of percutaneous-guided and EUS-guided procedures for pancreatic fluid collections drainages at a single tertiary care center between February 2017 and May 2018 was performed. Treatment success, adverse events, recurrence, need for surgery, length of hospital stays, and number of follow-up computed tomography (CT) scan were assessed. RESULTS A total of 119 pancreatic fluid collections treated with initial percutaneous drainage were included in this study and 35 patients had recurrent pancreatic fluid collections. Recurrent patients were classified based on drainage method: EUS-guided drainage (18 patients) and the second percutaneous drainage (17 patients). EUS-guided drainage revealed a shorter length of hospital stays (P<0.001), less re-intervention (P=0.047), fewer number of follow-up CT scans (P=0.006) compared with the initial percutaneous drainage. Furthermore, we also compared the clinical outcomes between the EUS-guided drainage and the second percutaneous drainage for the recurrent PFC after initially failed percutaneous drainage. EUS-guided drainage showed higher clinical success (P=0.027), shorter length of hospital stays (P<0.001), less re-intervention (P=0.012), fewer number of follow-up CT scan (P<0.001) and less recurrence P=0.027) compared to the second percutaneous drainage procedure. CONCLUSIONS EUS-guided drainage is an effective and appropriate method to treat the recurrent pancreatic fluid collections after initially failed percutaneous drainage procedure, with the advantage of higher clinical success, shorter length of hospital stays, less re-intervention, fewer number of follow-up CT scan and less recurrence compared to the percutaneous drainage.

Value of Two-Dimensional Shear Wave Elastography for Assessing Acute Liver Congestion in a Bama Mini-Pig Model.

BACKGROUND: To date, liver congestion is one of the most significant clinical diseases. However, few studies have profoundly investigated the development, pathology, and prognosis of the important problems associated with acute hepatic congestion. AIMS: To explore the value of noninvasive two-dimensional shear wave elastography (2D-SWE) for assessing acute liver congestion in an animal model. METHODS: Six healthy Bama mini-pigs were used for this research and randomly divided into the experimental group and control group. We measured the basal liver stiffness (LS) by 2D-SWE and then clamped the inferior vena cava (IVC). LS was measured after 1, 5, 10, and 15 min. We reopened the IVC of experimental group pigs and detected the LS again. All pigs were killed and obtained for a pathological microscopic examination. RESULTS: LS was distinctly increased from 7.03 ± 0.48 to 17.18 ± 3.40 kPa (p < 0.01) within 15 min and reversed to almost normal values of 7.59 ± 0.77 kPa (p < 0.01) within 5 min. In addition, two-dimensional ultrasound images demonstrated the interesting phenomenon of spontaneous echo contrast. Most importantly, the pathologic results of experimental group pigs showed the central veins of the hepatic lobules and hepatic sinusoids were enlarged and filled with numerous erythrocytes; central lobular hepatocytic necrosis and edema were noted. CONCLUSIONS: In conclusion, 2D-SWE is a valuable, reliable, and quantitative approach to successfully assess acute liver congestion, and it is well consistent with histopathological characteristics. Besides, acute liver congestion is an important factor influencing LS that increases LS in a reversible way.

Diagnosis of pancreatic focal nesidioblastosis assisted by dual­nuclide tracer positron emission tomography/computed tomography: A case report.

Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults and its clinical features are similar to those of insulinoma with recurrent hypoglycemic attacks. The present study reports the case of a 48-year-old man who visited the Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a 5-year history of recurrent hypoglycemic symptoms such as dizziness and palpitations. Abdominal magnetic resonance imaging (MRI) showed a mass of ~1.2x1.0 cm in the head of the pancreas, which was suspected to be an insulinoma. For confirmation, the patient underwent both fluorine-18-fluorodeoxyglucose (18F-FDG) and gallium-68-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-teraacetic acid-d-Phel-Tyr3-Thr8-OC (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT), which showed a moderately increased uptake of 18F-FDG but no uptake of 68Ga-DOTATATE in the corresponding lesion. The patient subsequently underwent surgery to remove the lesion, which was pathologically confirmed as a pancreatic nesidioblastosis. This case showed that nesidioblastosis should be considered a differential diagnosis for insulinoma and that dual nuclear tracer PET/CT imaging is helpful for differentiating between the two. If conventional imaging techniques such as ultrasound, CT and MRI cannot identify the cause of hypoglycemia in future cases, dual-nuclide tracer PET/CT imaging should be considered.

Imaging of Merkel cell carcinoma of the eyelid: A case report.

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine carcinoma commonly found in older adults in areas of the skin that are susceptible to ultraviolet ray damage. The current study reports the case of a 79-year-old woman who presented to the Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a painless lump in the lower eyelid of the left eye accompanied by photophobic tears for 4 months. Head computed tomography (CT) and magnetic resonance imaging (MRI) showed a space-occupying lesion ~2.8×2.4 cm in size outside the left orbital muscle cone, which was poorly demarcated from the surrounding normal tissues. Markedly intense and tortuous walking vascular shadows were observed within the tumor tissues. Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT revealed increased 18F-FDG uptake in the corresponding lesions. Based on these imaging features, a malignant tumor was suspected. The patient subsequently underwent surgery. Postoperative pathology and immunohistochemistry revealed MCC. The clinical presentation of MCC is usually a painless soft-tissue nodule or mass that grows rapidly over a short period and is flesh-colored, bluish red or purple. A slightly hyperdense mass on CT, with equal T1-weighted and slightly longer T2-weighted MRI signals, and mild enhancement on contrast-enhanced scans, accompanied by significantly enhanced distorted vascular shadows and increased 18F-FDG uptake on PET/CT, are valuable in the diagnosis of eyelid MCC.

Cell-cycle dependent nuclear gene delivery enhances the effects of E-cadherin against tumor invasion and metastasis.

Gene delivery is the process by which foreign DNA is transferred to host cells, released from intracellular vesicles, and transported to the nuclei for transcription. This process is frequently inefficient and difficult to control spatiotemporally. We developed a gene delivery strategy that uses ultrasound to directly deliver plasmid DNA into nuclei via gas vesicles (GVs)-based intracellular cavitation. pDNA-binding GVs can be taken up by cells and cause intracellular cavitation when exposed to acoustic irradiation and delivering their pDNA payloads into nuclei. Importantly, GVs can remain stable in the cytoplasm in the absence of acoustic irradiation, allowing for temporally controlled nuclear gene delivery. We were able to achieve spatiotemporal control of E-cadherin nuclear gene delivery in this manner, demonstrating its efficacy in tumor invasion and metastasis inhibition. Interestingly, we discovered that nuclear gene delivery of E-cadherin during the G2/M phase of the cell cycle in C6 tumor cells inhibited tumor invasion and metastasis more effectively than during the G1 and S phases. The gene delivery of E-cadherin at the G2/M phase resulted in significantly lower expression of Fam50a, which reduced Fam50a/Runx2 interaction and led to reduced transactivation of MMP13, an important factor for epithelial-mesenchymal transition, as observed in a molecular mechanism assay. Thus, using remote acoustic control of intracellular cavitation of pDNA-GVs, we developed a high spatiotemporally controllable gene delivery strategy and achieved stronger tumor invasion and metastasis inhibition effects by delivering the E-cadherin gene at the G2/M phase.

Present and future of metal nanoparticles in tumor ablation therapy.

Cancer is an important factor affecting the quality of human life as well as causing death. Tumor ablation therapy is a minimally invasive local treatment modality with unique advantages in treating tumors that are difficult to remove surgically. However, due to its physical and chemical characteristics and the limitation of equipment technology, ablation therapy cannot completely kill all tumor tissues and cells at one time; moreover, it inevitably damages some normal tissues in the surrounding area during the ablation process. Therefore, this technology cannot be the first-line treatment for tumors at present. Metal nanoparticles themselves have good thermal and electrical conductivity and unique optical and magnetic properties. The combination of metal nanoparticles with tumor ablation technology, on the one hand, can enhance the killing and inhibiting effect of ablation technology on tumors by expanding the ablation range; on the other hand, the ablation technology changes the physicochemical microenvironment such as temperature, electric field, optics, oxygen content and pH in tumor tissues. It helps to stimulate the degree of local drug release of nanoparticles and increase the local content of anti-tumor drugs, thus forming a synergistic therapeutic effect with tumor ablation. Recent studies have found that some specific ablation methods will stimulate the body's immune response while physically killing tumor tissues, generating a large number of immune cells to cause secondary killing of tumor tissues and cells, and with the assistance of metal nanoparticles loaded with immune drugs, the effect of this anti-tumor immunotherapy can be further enhanced. Therefore, the combination of metal nanoparticles and ablative therapy has broad research potential. This review covers common metallic nanoparticles used for ablative therapy and discusses in detail their characteristics, mechanisms of action, potential challenges, and prospects in the field of ablation.

Effect of pulsed field ablation on solid tumor cells and microenvironment.

Pulsed field ablation can increase membrane permeability and is an emerging non-thermal ablation. While ablating tumor tissues, electrical pulses not only act on the membrane structure of cells to cause irreversible electroporation, but also convert tumors into an immune active state, increase the permeability of microvessels, inhibit the proliferation of pathological blood vessels, and soften the extracellular matrix thereby inhibiting infiltrative tumor growth. Electrical pulses can alter the tumor microenvironment, making the inhibitory effect on the tumor not limited to short-term killing, but mobilizing the collective immune system to inhibit tumor growth and invasion together.

Evaluation of the Efficacy and Performance of a New Nano-Drug Carrier in the Treatment of Recurrent Oral Ulcerper.

Recurrent oral ulcer is a common oral mucosal disease. Due to its periodic and recurrent characteristics, the onset of burning pain is unbearable, which brings great inconvenience to the patient's life and seriously affects the patient's quality of life. There are certain limitations to conventional drug therapy. With the rapid development of nanotechnology, the obvious advantages of nanotechnology such as targeting, controlled release, biocompatibility is obviously shown. The combination of nanotechnology and medical research has led to the emergence of polymer nanoparticles and ligands. Nano-drugs for gene therapy, and many other new nano-drug carriers, polymer micelle is a new type of nano drug carrier that has appeared in recent years. It has both a hydrophilic shell and a hydrophobic core, and has a variety of excellent properties, such as higher stability in vivo and in vitro, and poorly soluble drugs. In this paper, a new method for treating recurrent oral ulcers based on a new nano-drug carrier was studied. Because of the hydrophilicity and biocompatibility of oral cell surface proteins, the research progress of nanopharmaceutical carrier in the treatment of recurrent oral ulcers is reviewed. The experimental results show that the method has good reproducibility and high efficiency in the treatment of recurrent oral ulcers. It is used to explore the application and progress of nanotechnology in the diagnosis and treatment of recurrent oral ulcers, and to provide new ideas for the clinical diagnosis and treatment of recurrent oral ulcers. This new technical method has wide practical application value.

Early Detection and Reversal of Cell Apoptosis Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Focused ultrasound (FUS) combined with microbubbles (MBs) has recently emerged as a potential approach to open the blood-brain barrier (BBB) for delivering drugs into the brain. However, appropriate approaches are still lacking to monitor the sublethal damage during FUS-mediated BBB opening in vivo, especially the early stage cell apoptotic events. Here, we developed a kind of nanoprobe-loaded MBs (AV-ICG-NPs@MBs) which can monitor the apoptotic cells that occur during FUS-mediated BBB opening through encapsulating the annexin V-targeted nanoprobes AV-ICG-NPs into the cavity of lipid-PLGA hybrid MBs. When irradiated by FUS, AV-ICG-NPs@MBs in the cerebral blood vessels would produce cavitation, favoring the BBB opening. Meanwhile, AV-ICG-NPs@MBs would be destroyed and release their AV-ICG-NPs payload. These released AV-ICG-NPs can be further delivered into the brain via the destructed BBB and bind with the phosphatidylserine externalized on the membrane of apoptotic cells if this occurs, leading to the prolonged detention of fluorescent signals in the brain. Furthermore, we also provided an effective strategy to inhibit or reverse the possible damage to the brain from a FUS-mediated BBB opening technology, through developing AV-ICG-NPs/GAS@MBs that encapsulate the antioxidant gastrodin (GAS) into AV-ICG-NPs@MBs. Accompanied by FUS irradiation and bubble cavitation, GAS was released and delivered into the brain, where they scavenged the oxygen free radicals produced from cavitation, leading to significantly lower fluorescence signals in the brain due to the absence of externalized phosphatidylserine. In conclusion, our study provides an approach to monitor and inhibit cell apoptotic events during FUS-mediated BBB opening.

An acoustic field-based conformal transfection system for improving the gene delivery efficiency.

Ultrasound-activated microbubble destruction is a promising platform for gene delivery due to the low toxicity, non-invasiveness, and high specificity. However, the gene transfection efficiency is still low, especially for suspension cells. It is desirable to develop a universal gene delivery tool that overcomes the drawbacks existing in ultrasound-mediated methods. Here, we present a three-dimensional acoustic field-based conformal transfection (AFCT) system by designing a Sono-hole that can fit the three-dimensional acoustic field to maximally utilize the acoustic energy from bubble cavitation, thus greatly promoting the gene delivery efficiency. Surprisingly, compared with the traditional two-dimensional transfection system, the gene transfection efficiency of the AFCT system increased by more than 3 times, achieving nearly 30%. The parameters including acoustic pressure, duration, duty cycle, DNA concentrations, and bubble kinds were optimized to obtain higher gene transfection. In conclusion, our study provides an effective ultrasound-based gene delivery approach for gene transfection, especially for suspension-cultured cells.

Pre-operative Detection of Liver Fibrosis in Hepatocellular Carcinoma Patients Using 2D Shear Wave Elastography: Where to Measure?

The aim of this study was to pre-operatively investigate the diagnostic performance of 2D shear wave elastography (2D-SWE) for staging liver fibrosis and inflammation in patients with hepatocellular carcinoma (HCC) who then undergo surgery and to determine the optimal locations for measurement. In total, 106 patients were enrolled in this prospective study from March 2017 to May 2018. Two-dimensional SWE was used to measure liver stiffness (LS) in each patient 0-1, 1-2 and 2-5 cm from the tumor border (groups 1, 2 and 3, respectively). Spearman's correlation was used to evaluate the relationships between LS and hepatic fibrosis and between LS and inflammation. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of 2D-SWE. The technical success rate of SWE in tissue distant from the tumor (group 3) was significantly higher than that in peri-tumoral tissue (groups 1 and 2) (p < 0.001). Moreover, the area under the ROC for diagnosing cirrhosis (F4) and severe inflammation (A3) was higher for group 3 than for groups 1 and 2. Our results suggest that 2D-SWE is a helpful approach to assessment of hepatic fibrosis in HCC patients before hepatic resection. We found that to achieve a superior success rate and preferable diagnosis accuracy for patients with HCC, LS measurement should be performed 2-5 cm from the tumor margin.

Ultrasound and Contrast-enhanced Ultrasound Findings after Percutaneous Irreversible Electroporation of Hepatic Malignant Tumors.

The aim of this study was to describe ultrasound (US) and contrast-enhanced ultrasound (CEUS) findings immediately and 1 d after percutaneous irreversible electroporation (IRE) of hepatic malignant tumors. Immediately after IRE, the ablation zone was shown to be a gradually expanding hypo-echoic area around the electrodes. The microcirculation of the ablation zone was markedly reduced on CEUS (before vs. immediately after, p < 0.001), and the macrocirculation within the ablation zone was preserved. At 1 d after IRE, the ablation zones lost their hypo-echogenicity to become iso-echoic or hyper-echoic (before vs. 1 d after, p = 0.004; immediately after vs. 1 d after, p = 0.002). At this time, further elimination of microcirculation was confirmed on CEUS (before vs. 1 d after, p < 0.001; immediately after vs. 1 d after, p = 0.003). The size of the ablation zone, which measured by US, was strongly correlated with that measured by CEUS (length: r: = 0.929, width: r = 0.940, p < 0.001), was significantly enlarged immediately after IRE and shrunk 1 d after IRE.

Algorithm for the multidisciplinary management of hemorrhage in EUS-guided drainage for pancreatic fluid collections.

Pancreatic fluid collections (PFCs), common sequelae of acute or chronic pancreatitis, are broadly classified as pancreatic pseudocysts or walled-off necrosis according to the revised Atlanta classification. Endoscopic ultrasound (EUS)-guided drainage is often considered a standard first-line therapy preferable to surgical or interventional radiology approaches for patients with symptomatic PFC. EUS-guided drainage is effective and successful; it has a technical success rate of 90%-100% and a clinical success rate of 85%-98%. Recent studies have shown a 5%-30% adverse events (AEs) rate for the procedure. The most common AEs include infection, hemorrhage, perforation and stent migration. Hemorrhage, a severe and sometimes deadly outcome, requires a well-organized and appropriate treatment strategy. However, few studies have reported the integrated management of hemorrhage during EUS-guided drainage of PFC. Establishing a practical therapeutic strategy is an essential and significant step in standardized management. The aim of this review is to describe the current situation of EUS-guided drainage of PFCs, including the etiology and treatment of procedure-related bleeding as well as current problems and future perspectives. We propose a novel and meaningful algorithm for systematically managing hemorrhage events. To our limited knowledge, a multidisciplinary algorithm for managing EUS-guided drainage for PFC-related bleeding has not been previously reported.

An analytical solution for temperature distributions in hepatic radiofrequency ablation incorporating the heat-sink effect of large vessels.

Fast prediction of the local thermal field induced by radiofrequency ablation (RFA) plays a critical role in hepatic RFA therapy. At present, it is still a challenging task to calculate and visualize the temperature distribution of RFA in real-time, especially when the heat-sink effect of adjacent large vessels is taken into account. To achieve this, the current investigation presented an analytical solution to calculate the temperature in RFA with an execution time of 0.05 s for three dimensional thermal field reconstruction. The presented temperature distribution is a combination of temperatures in homogeneous tissue and a quantification of the heat-sink effect of adjacent blood vessels. Temperatures in homogeneous tissue is calculated from a simplified Pennes bioheat equation, where several weighting parameters in the temperature expression are determined based on some reference point temperatures from the numerical simulation. The heat-sink effect is quantified based on a temperature factor, which measures the temperature difference between the vessel and the heated tissue, and a distance factor, which measures the distance to the vessel. The proposed method is validated to be able to gain similar temperature distributions to the numerical simulation but with its computational time being orders of magnitude smaller than that of numerical simulation, which improves the efficiency of interactive planning of RFA.

Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography.

Two-dimensional shear wave elastography (2D-SWE) is a rapid, simple and novel noninvasive method that has been proposed for assessing hepatic fibrosis in patients with chronic liver diseases (CLDs) based on measurements of liver stiffness. 2D-SWE can be performed easily at the bedside or in an outpatient clinic and yields immediate results with good reproducibility. Furthermore, 2D-SWE was an efficient method for evaluating liver fibrosis in small to moderately sized clinical trials. However, the quality criteria for the staging of liver fibrosis are not yet well defined. Liver fibrosis is the main pathological basis of liver stiffness and a key step in the progression from CLD to cirrhosis; thus, the management of CLD largely depends on the extent and progression of liver fibrosis. 2D-SWE appears to be an excellent tool for the early detection of cirrhosis and may have prognostic value in this context. Because 2D-SWE has high patient acceptance, it could be useful for monitoring fibrosis progression and regression in individual cases. However, multicenter data are needed to support its use. This study reviews the current status and future perspectives of 2D-SWE for assessments of liver fibrosis and discusses the technical advantages and limitations that impact its effective and rational clinical use.

Balloon dilator controls massive bleeding during endoscopic ultrasound-guided drainage for pancreatic pseudocyst: A case report and review of literature.

Pancreatic pseudocyst (PPC), a common sequela of acute or chronic pancreatitis, was defined by the revised Atlanta classification as "a collection." Endoscopic ultrasound (EUS)-guided drainage is often considered a standard first-line therapy for patients with symptomatic PPC. This effective approach exhibits 90%-100% technical success and 85%-98% clinical success. Bleeding is a deadly adverse event associated with EUS-guided drainage procedures, and the bleeding rate ranges from 3% to 14%. Hemostasis involves conservative treatment, endoscopy, interventional radiology-guided embolization and surgery. However, few studies have reported on EUS-guided drainage with massive, multiple hemorrhages related to severe pancreatogenic portal hypertension (PPH). Thus, the aim of this case report was to present a case using a balloon dilator to achieve successful hemostasis for PPH-related massive bleeding in EUS-guided drainage of PPC. To our knowledge, this method has not been previously reported.