Trans-arterial radioembolization in intermediate-advanced hepatocellular carcinoma: systematic review and meta-analyses.

Published onlineJournal ArticleThis is the final version of the article. Available from Impact Journals via the DOI in this record.Trans-arterial radioembolization (TARE) is a recognized, although not explicitly recommended, experimental therapy for unresectable hepatocellular carcinoma (HCC).A systematic literature review was performed to identify published studies on the use of TARE in intermediate and advanced stages HCC exploring the efficacy and safety of this innovative treatment.Twenty-one studies reporting data on overall survival (OS) and time to progression (TTP), were included in a meta-analysis. The pooled post-TARE OS was 63% (95% CI: 56-70%) and 27% (95% CI: 21-33%) at 1- and 3-years respectively in intermediate stage HCC, whereas OS was 37% (95% CI: 26-50%) and 13% (95% CI: 9-18%) at the same time intervals in patients with sufficient liver function (Child-Pugh A-B7) but with an advanced HCC because of the presence of portal vein thrombosis. When an intermediate and advanced case-mix was considered, OS was 58% (95% CI: 48-67%) and 17% (95% CI: 12-23%) at 1- and 3-years respectively. As for TTP, only four studies reported data: the observed progression probability was 56% (95% CI: 41-70%) and 73% (95% CI: 56-87%) at 1 and 2 years respectively. The safety analysis, focused on the risk of liver decompensation after TARE, revealed a great variability, from 0-1% to more than 36% events, influenced by the number of procedures, patient Child-Pugh stage and treatment duration.Evidence supporting the use of radioembolization in HCC is mainly based on retrospective and prospective cohort studies. Based on this evidence, until the results of the ongoing randomized trials become available, radioembolization appears to be a viable treatment option for intermediate-advanced stage HCC.The present study was funded by ASBM Srl through an unrestricted grant to CERGAS, Bocconi University, Via Roentgen 1, 20136 Milan, Italy

Are hematopoietic stem cells involved in hepatocarcinogenesis?

THE LIVER HAS THREE CELL LINEAGES ABLE TO PROLIFERATE AFTER A HEPATIC INJURY: the mature hepatocyte, the ductular "bipolar" progenitor cell termed "oval cell" and the putative periductular stem cell. Hepatocytes can only produce other hepatocytes whereas ductular progenitor cells are considerate bipolar since they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential and may be multipotent, being this aspect still under investigation. They originate in the bone marrow since their progeny express genetic markers of donor hematopoietic cells after bone marrow transplantation. Since the liver is the hematopoietic organ of the fetus, it is possible that hematopoietic stem cells may reside in the liver of the adult. This assumption is proved by the finding that oval cells express hematopoietic markers like CD34, CD45, CD 109, Thy-1, c-kit, and others, which are also expressed by bone marrow-derived hematopoietic stem cells (BMSCs). Few and discordant studies have evaluated the role of BMSC in hepatocarcinogenesis so far and further studies in vitro and in vivo are warranted in order to definitively clarify such an issue

Diagnostic performance of endoscopic ultrasound-guided tissue acquisition of splenic lesions: systematic review with pooled analysis

Background: Focal splenic lesions are usually incidentally discovered on radiological assessments. Although percutaneous tissue acquisition (TA) under trans-abdominal ultrasound guidance is a well-established technique for obtaining cyto-histological diagnosis of focal splenic lesions, endoscopic ultrasound (EUS)-guided TA has been described in several studies, reporting different safety and outcomes. The aim was to assess the pooled safety, adequacy, and accuracy of EUS-TA of splenic lesions. Methods: A comprehensive review of available evidence was conducted at the end of November 2021. All studies including more than five patients and reporting about the safety, adequacy, and accuracy of EUS-TA of the spleen were included. Results: Six studies (62 patients) were identified; all studies have been conducted using fine-needle aspiration (FNA) needles. Pooled specimen adequacy and accuracy of EUS-TA for spleen characterization were 92.8% [95% confidence interval (CI), 86.3%-99.3%] and 88.2% (95% CI, 79.3%-97.1%), respectively. The pooled incidence of adverse events (six studies, 62 patients) was 4.7% (95% CI, 0.4%-9.7%). Conclusion: EUS-FNA of the spleen is a safe technique with high diagnostic adequacy and accuracy. The EUS-guided approach could be considered a valid alternative to the percutaneous approach for spleen TA

Ultrasonographic evaluation of three approaches for botulinum toxin injection into tibialis posterior muscle in chronic stroke patients with equinovarus foot: An observational study

Spastic equinovarus (SEV) foot deformity is commonly observed in patients with post-stroke spasticity. Tibialis posterior (TP) is a common target for botulinum toxin type-A (BoNT-A) injection, as a first-line treatment in non-fixed SEV deformity. For this deep muscle, ultrasonographic guidance is crucial to achieving maximum accuracy for the BoNT-A injection. In current clinical practice, there are three approaches to target the TP: an anterior, a posteromedial, and a posterior. To date, previous studies have failed to identify the best approach for needle insertion into TP. To explore the ultrasonographic characteristics of these approaches, we investigated affected and unaffected legs of 25 stroke patients with SEV treated with BoNT-A. We evaluated the qualitative (echo intensity) and quantitative (muscle depth, muscle thickness, overlying muscle, subcutaneous tissue, cross-sectional area) ultrasound characteristics of the three approaches for TP injection. In our sample, we observed significant differences among almost all the parameters of the three approaches, except for the safety window. Moreover, our analysis showed significant differences in cross-sectional area between treated and untreated. Advantages and disadvantages of each approach were investigated. Our findings can thus provide a suitable reference for clinical settings, especially for novice operators

Endoscopic Ultrasound Guided Biliary Drainage in Malignant Distal Biliary Obstruction

Malignant biliary obstruction (MBO) is a challenging medical problem that often negatively impacts the patient’s quality of life (QoL), postoperative complications, and survival rates. Endoscopic approaches to biliary drainage are generally performed by ERCP or, in selected cases, with a percutaneous transhepatic biliary drainage (PTBD). Recent advances in therapeutic endoscopic ultrasound (EUS) allow drainage where previous methods have failed. EUS has evolved from a purely diagnostic technique to one that allows a therapeutic approach in the event of ERCP failure in distal MBO. Moreover, the introduction of dedicated accessories and prostheses for EUS-guided transmural biliary drainage (EUS-BD) made these procedures more successful with regard to technical success, clinical outcomes and reduction of adverse events (AEs). Finally, lumen-apposing metal stents (LAMS) have improved the therapeutic role of the EUS. Subsequently, the electrocautery enhanced tip of the LAMS (EC-LAMS) allows a direct access of the delivery system to the target lumen, thereby simplifying and reducing the EUS-BD procedure time. EUS-BD using LAMS and EC-LAMS has proven effective and safe with a low rate of AEs. This review aims to evaluate biliary drainage techniques in malignant obstruction, focusing on the role of EUS biliary drainage by LAMS

Rare pancreatic/peripancreatic cystic lesions can be accurately characterized by EUS with through-the-needle biopsy — A unique pictorial essay with clinical and histopathological correlations

Due to their aspecific macroscopic appearance, uncommon pancreatic cystic lesions (PCLs) are often misdiagnosed as mucinous lesions and improperly resected. We aimed to evaluate the endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) capacity of the preoperative diagnosis of uncommon PCLs. Overall, 136 patients with PCLs who underwent EUS-TTNB between 2016 and 2022 were retrospectively identified. Common histotypes (e.g., IPMN, serous cystadenoma, and mucinous cystadenoma) were excluded and 26 (19.1%) patients (15 female, mean age 52.9 ± 10.4) were analyzed. The EUS findings, adverse events (AEs), and TTNB outcomes in uncommon PCLs were evaluated. The cysts histotype was accurately diagnosed by TTNB in 24/26 (92.3%) cases (seven cystic neuroendocrine tumors, four squamoid cysts, three acinar cells cystadenomas, two lymphoepithelial cysts, two mucinous non-neoplastic cysts, two bronchogenic cysts, two cystic lymphangiomas, one solid-pseudopapillary neoplasm, and one schwannoma). In the remaining two cases, lymphangioma was eventually diagnosed after resection. Surgery was performed in 15/26 (57.7%) patients. The mean follow-up of non-surgical patients was 32.5 months. One severe acute case of pancreatitis (3.8%) that required surgery occurred after EUS-TTNB. Uncommon pancreatic/peripancreatic lesions represent the 19.1% of PCLs in our series, with mainly benign histotypes. TTNB demonstrated a high diagnostic performance with a low rate of AEs in this setting, representing a reliable tool with which to avoid useless surgery

Diagnostic yield of endoscopic ultrasound-guided tissue acquisition in autoimmune pancreatitis: a systematic review and meta-analysis

Background and study aims There is limited evidence on the diagnostic performance of endoscopic ultrasound (EUS)-guided tissue acquisition in autoimmune pancreatitis (AIP). The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance of EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) in patients with AIP. Patients and methods Computerized bibliographic search was performed through January 2020. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy compared to clinical diagnostic criteria. Additional outcomes were definitive histopathology, pooled rates of adequate material for histological diagnosis, sample adequacy, mean number of needle passes. Diagnostic sensitivity and safety data were also analyzed. Results Fifteen studies with 631 patients were included, of which four were prospective series and one randomized trial. Overall diagnostic accuracy of EUS tissue acquisition was 54.7 % (95 % confidence interval, 40.9 %-68.4 %), with a clear superiority of FNB over FNA (63 %, 52.7 % to 73.4 % versus 45.7 %, 26.5 %-65 %; p < 0.001). FNB provided level 1 of histological diagnosis in 44.2 % of cases (30.8 %-57.5 %) as compared to 21.9 % (10 %-33.7 %) with FNA ( P < 0.001). The rate of definitive histopathology of EUS tissue sampling was 20.7 % (12.9 %-28.5 %) and it was significantly higher with FNB (24.3 %, 11.8 %-36.8 %) as compared to FNA (14.7 %, 5.4 %-23.9 %; P < 0.001). Less than 1 % of subjects experienced post-procedural acute pancreatitis. Conclusion The results of this meta-analysis demonstrate that the diagnostic performance of EUS-guided tissue acquisition is modest in patients with AIP, with an improved performance of FNB compared to FNA

The Derivation and External Validation of a Fibrosis Risk Model for Colorectal Tumours Undergoing Endoscopic Submucosal Dissection

Background: Endoscopic submucosal dissection (ESD) is an advanced technique that can become more challenging in the presence of submucosal fibrosis. Predicting the grade of fibrosis is important in order to identify technically difficult ESD. Aims and Methods: Our study aimed to derive and validate a prediction model to determine the preoperative degree of submucosal fibrosis in colorectal tumours undergoing ESD. A predictive model was developed to derive the probability of an increasing submucosal fibrosis in the derivation cohort and then externally validated. Results: 309 patients (age: 68 ± 10.9 years) underwent colorectal ESD between January 2016 and June 2020. F0, F1, and F2 fibroses were reported in 196 (63.4%), 70 (22.6%), and 43 (13.9%) cases, respectively. R0 resection was found in 266 (87%) lesions. At multivariable analysis in the derivation cohort, lesion morphology (OR = 0.37 and CI = 0.14–0.97 for LST-NG vs. 0-Is; OR = 0.29 and CI = 0.1–0.87 for the LST mixed type vs. 0-Is; and OR = 0.32 and CI = 0.1–1.03 for LST-G vs. 0-Is) and increasing size (OR = 1.02 and CI = 1.01–1.04 for a 1 mm increase) were significantly associated with an increasing degree of fibrosis. The model had fair discriminating ability in the derivation group (AUROC = 0.61 and CI = 0.52–0.69 for F1–F2 vs. F0 fibroses; AUROC = 0.61 and CI = 0.45–0.77 for F2 vs. F0–F1 fibroses) and in the validation group (AUROC = 0.71 and CI = 0.59–0.83 for F1–F2 vs. F0 fibroses; AUROC = 0.65 and CI = 0.52–0.77 for F2 vs. F0–F1 fibroses). Conclusions: Our findings introduce a new tool for the stratification of ESD technical difficulty based on lesion size and morphological characteristics which could become crucial during the procedure’s planning process

Endoscopic ultrasound fine-needle biopsy vs fine-needle aspiration for lymph nodes tissue acquisition: A systematic review and meta-Analysis

Background: Endoscopic ultrasound (EUS)-guided tissue acquisition represents the choice of methods for suspected lymph nodes (LNs) located next to the gastrointestinal tract. This study aimed to compare the pooled diagnostic performance of EUS-guided fine-needle biopsy (EUS-FNB) and fine-needle aspiration (EUS-FNA) for LNs sampling. Methods: We searched PubMed/MedLine and Embase databases through August 2021. Primary outcome was diagnostic accuracy; secondary outcomes were sensitivity, specificity, sample adequacy, optimal histological core procurement, number of passes, and adverse events. We performed a pairwise meta-Analysis using a random-effects model. The results are presented as odds ratio (OR) or mean difference along with 95% confidence interval (CI). Results: We identified nine studies (1,276 patients) in this meta-Analysis. Among these patients, 66.4% were male; the median age was 67 years. Diagnostic accuracy was not significantly different between the two approaches (OR, 1.31; 95% CI, 0.81-2.10; P = 0.270). The accuracy of EUS-FNB was significantly higher when being performed with newer end-cutting needles (OR, 1.87; 95% CI, 1.17-3.00; P = 0.009) and in abdominal LNs (OR, 2.48; 95% CI, 1.52-4.05; P &lt; 0.001) than that of EUS-FNA. No difference in terms of sample adequacy was observed between the two approaches (OR, 1.40; 95% CI, 0.46-4.26; P = 0.550); however, histological core procurement and diagnostic sensitivity with EUS-FNB were significantly higher than those with EUS-FNA (OR, 6.15; 95% CI, 1.51-25.07; P = 0.010 and OR, 1.87; 95% CI, 1.27-2.74, P = 0.001). The number of needle passes needed was significantly lower in the EUS-FNB group than in the EUS-FNA group (mean difference,-0.54; 95% CI,-0.97 to-0.12; P = 0.010). Conclusions: EUS-FNA and EUS-FNB perform similarly in LN sampling; however, FNB performed with end-cutting needles outperformed FNA in terms of diagnostic accuracy