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Background The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. Methods This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. Results 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %–93.9 %] vs. 87.8 % [95 %CI 82.1 %–92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %–96.3 %] vs. 95.5 % [95 %CI 91.4 %–98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P Conclusions The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.

Objective The current IPMN risk stratification is based on clinical and histological features rather than molecular markers. We aimed to improve the current diagnostic criteria of IPMN performing spatial transcriptomic (ST) on lesions of different grade to identify novel markers that define IPMN degeneration to PDAC. Design We performed ST on two independent cohorts of IPMN samples grouped by morphology and degree of dysplasia using two innovative technologies: Visium ST on a discovery cohort of 18 samples from 14 patients: 4 low-grade IPMN (3 low-grade dysplasia (LGD), 1 intermediate dysplasia/Borderline), 9 high-grade IPMN characterized by a high-grade of dysplasia (HGD), including 4 invasive IPMN with associated PDAC, and 1 PDAC-associated normal duct). GeoMx ST on a validation cohort of 57 IPMN samples: 23 low-grade IPMN (6 low-grade dysplasia (LGD), 17 intermediate dysplasia/Borderline), 34 High-grade IPMN (13 HGD Gastric IPMN and 21 HGD Intestinal IPMN) from 40 patients. Results Novel subtype-specific markers were identified in the discovery cohort: HOXB3 and ZNF117 in LGD ; SPDEF, and gastric neck cell markers in Borderline; NKX6-2 and gastric isthmus cell markers in HGD Gastric IPMN. The spatial trajectory inference implicated NKX6-2 in progression of Gastric IPMN. Transcriptomic dissection highlighted the role of TNFα signalling and Myc activation in IPMN progression. The findings were confirmed in the independent validation cohort by GeoMx analysis. Conclusions Our results identify novel markers associated with IPMN morphology and dysplasia to be explored for clinical utility, to better delineate progression in patients, improve risk stratification and clinical management.

Background and study aims Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). Patients and methods Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. Results Mean cysts size was 36.7 mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45 %), serous cystadenoma (18.8 %), and mucinous cystadenoma (12.8 %). Fifty-eight (11.5 %) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09–2.14; p = 0.05), number of TTNB passes (OR from 2.17, 1.32–4.34 to OR 3.16, 2.03–6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31–0.95; p = 0.02), and diagnosis of IPMN (OR 4.16, 2.27–7.69; p Conclusion TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

A dedicated ultrasound (US) score, the Gemelli Ultrasound Chronic Pancreatitis (USCP) score, could be useful in the follow-up of patients with chronic pancreatitis (CP). However, its role in the diagnosis of CP has not been investigated. We aimed to evaluate the role of the Gemelli USCP score in the diagnosis of CP and the agreement with standard imaging techniques. Ninety-three patients clinically suspected of having CP and referred to the pancreatic outpatient clinic of A. Gemelli Hospital for endoscopic ultrasound (EUS) were prospectively enrolled. All patients underwent pancreatic US to calculate the Gemelli USCP score. A receiver operating characteristic curve analysis was also performed to assess the performance of the US score in CP diagnosis. The Gemelli USCP score was inversely related to the Rosemont score for both total value (p0.0001) and each parameter evaluated (p0.0001). This score was significantly higher in patients with CP with an excellent area under the receiver operating characteristic curve (0.946) and the optimal cutoff of 5. Moreover, we found a significant correlation between the Gemelli USCP score and laboratory parameters related to pancreatic exocrine insufficiency (p0.0001). The development of a dedicated ultrasound score could be useful as a non-invasive tool in the diagnosis of CP.

Therapeutic EUS has witnessed exponential growth in the last decade, but it has been considered investigational until recently. An increasing body of good-quality evidence is now demonstrating clear advantages over established alternatives, adding therapeutic EUS to management algorithms of complex hepato-pancreato-biliary (HPB) and gastrointestinal (GI) conditions. In this review, the available evidence and clinical role of therapeutic EUS in established and evolving applications will be discussed. A Graphical Summary for each scenario will provide (1) technical steps, (2) anatomical sketch, (3) best-supporting evidence, and (4) role in changing current and future GI practice. Therapeutic EUS has accepted well-established applications such as drainage of symptomatic peripancreatic fluid collections, biliary drainage in failed endoscopic retrograde cholangiopancreatography, and treatment of acute cholecystitis in unfit-for-surgery patients. In addition, good-quality evidence on several emerging indications (e.g., treatment of gastric outlet obstruction, local ablation of pancreatic solid lesions, etc.) is promising. Specific emphasis will be given to how these technical innovations have changed management paradigms and algorithms and expanded the possibilities of gastroenterologists to provide therapeutic solutions to old and emerging clinical needs. Therapeutic EUS is cementing its role in everyday practice, radically changing the treatment of different HPB diseases and other conditions (e.g., GI obstruction). The development of dedicated accessories and increased training opportunities will expand the ability of gastroenterologists to deliver highly effective yet minimally invasive therapies, potentially translating into a better quality of life, especially for oncological and fragile patients. ispartof: ENDOSCOPIC ULTRASOUND vol:12 issue:1 pages:16-28 ispartof: location:China status: accepted

Background It is unknown whether there is an advantage to using the wet-suction or slow-pull technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with new-generation needles. We aimed to compare the performance of each technique in EUS-FNB. Methods This was a multicenter, randomized, single-blind, crossover trial including patients with solid lesions of ≥ 1 cm. Four needle passes with 22 G fork-tip or Franseen-type needles were performed, alternating the wet-suction and slow-pull techniques in a randomized order. The primary outcome was the histological yield (samples containing an intact piece of tissue of at least 550 μm). Secondary end points were sample quality (tissue integrity and blood contamination), diagnostic accuracy, and adequate tumor fraction. Results Overall, 210 patients with 146 pancreatic and 64 nonpancreatic lesions were analyzed. A tissue core was retrieved in 150 (71.4 %) and 129 (61.4 %) cases using the wet-suction and the slow-pull techniques, respectively (P = 0.03). The mean tissue integrity score was higher using wet suction (P = 0.02), as was the blood contamination of samples (P Conclusion Overall, the wet-suction technique in EUS-FNB resulted in a higher tissue core procurement rate compared with the slow-pull method. Diagnostic accuracy and the rate of samples with adequate tumor fraction were similar between the two techniques.

Purpose of review The objective of this study is to answer few key questions in order to establish the best possible available diagnostic strategy for incidentally discovered pancreatic cystic lesions (PCLs). Recent findings Advances in EUS-guided sampling techniques, cross-sectional and intracystic confocal imaging, molecular biomarkers analysis, determination of cyst fluid glucose, and artificial intelligence, appear to be associated with an improved diagnostic accuracy in distinguishing mucinous from non-mucinous PCLs. Summary The diagnostic process has the aim of recognizing cysts with malignant potential and identifying those with high-risk stigmata and/or worrisome features. Clinicians should avoid performance of unnecessary tests from one side and misdiagnosis from the other, which can easily result in inadvertent surgery of an otherwise benign lesion or malignant progression of a precancerous cyst. Clinical studies to validate recent reported results utilizing novel diagnostic tests are needed, in order to gradually incorporate and combine them into updated guidelines.

Background and Aims Electrocautery-tip lumen-apposing metal stents (EC-LAMSs) have extended the indications of therapeutic EUS. We aimed to retrospectively evaluate safety and technical and clinical success of a newly developed EC-LAMS, the Hot-Spaxus (Taewoong Medical Co, Gimpo, Korea), for various EUS-guided procedures. Methods We included and retrospectively analyzed consecutive patients at 8 tertiary care referral centers who had undergone EUS interventional procedures using the Hot-Spaxus between October 2018 and February 2021. Results Of 58 included patients (male-to-female, 36:22; mean age, 63.5 ± 14.9 years), 29 had undergone pancreatic fluid collection drainage (50%), 22 (37.9%) biliary drainage for malignant distal obstruction, 3 (5.1%) gallbladder drainage for acute cholecystitis, 3 gastroenteroanastomoses, and 1 (1.7%) pelvic collection drainage. Technical success was achieved in 54 of 58 patients (93.1%) and clinical success in all 58. Adverse events occurred in 6 patients (11.1%): 2 early (3.7%), 1 late (1.8%), and 3 long term (5.6%). The outcomes were similar to those observed in a control group of patients treated with the Hot-Axios (Boston Scientific, Marlborough, Mass, USA), the other available EC-LAMS. Conclusions Our study showed that the novel EC-LAMS has high technical and clinical success rates for various interventional EUS indications. Future multicenter prospective studies will better clarify the role of this new EC-LAMS for different indications.

Main Recommendations1 ESGE recommends the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) over percutaneous transhepatic biliary drainage (PTBD) after failed endoscopic retrograde cholangiopancreatography (ERCP) in malignant distal biliary obstruction when local expertise is available.Strong recommendation, moderate quality evidence.2 ESGE suggests EUS-BD with hepaticogastrostomy only for malignant inoperable hilar biliary obstruction with a dilated left hepatic duct when inadequately drained by ERCP and/or PTBD in high volume expert centers.Weak recommendation, moderate quality evidence.3 ESGE recommends that EUS-guided pancreatic duct (PD) drainage should only be considered in symptomatic patients with an obstructed PD when retrograde endoscopic intervention fails or is not possible.Strong recommendation, low quality evidence.4 ESGE recommends rendezvous EUS techniques over transmural PD drainage in patients with favorable anatomy owing to its lower rate of adverse events.Strong recommendation, low quality evidence.5 ESGE recommends that, in patients at high surgical risk, EUS-guided gallbladder drainage (GBD) should be favored over percutaneous gallbladder drainage where both techniques are available, owing to the lower rates of adverse events and need for re-interventions in EUS-GBD.Strong recommendation, high quality of evidence.6 ESGE recommends EUS-guided gastroenterostomy (EUS-GE), in an expert setting, for malignant gastric outlet obstruction, as an alternative to enteral stenting or surgery.Strong recommendation, low quality evidence.7 ESGE recommends that EUS-GE may be considered in the management of afferent loop syndrome, especially in the setting of malignancy or in poor surgical candidates.Strong recommendation, low quality evidence.8 ESGE suggests that endoscopic ultrasound-directed transgastric ERCP (EDGE) can be offered, in expert centers, to patients with a Roux-en-Y gastric bypass following multidisciplinary decision-making, with the aim of overcoming the invasiveness of laparoscopy-assisted ERCP and the limitations of enteroscopy-assisted ERCP.Weak recommendation, low quality evidence.

Surgery has been regarded as the only curative treatment for patients with small nonfunctional pancreatic neuroendocrine neoplasms (NF-PNENs) less than 2 cm. Due to the significant adverse event rates of surgery, the European Neuroendocrine Tumor Society issued guidelines favoring surveillance for those patients lacking criteria suggestive of an aggressive disease. Despite the above recommendations, a significant proportion of small NF-PNEN patients still undergo surgery. Recently, several studies have reported the safety and effectiveness of EUS-guided radiofrequency ablation (RFA) for the treatment of small NF-PNENs. The experience with EUS-RFA is, however, limited, but published results indicate a potential role as a minimally invasive alternative treatment for these patients, in particular in those in whom further progression is more probable, before they reach the absolute need for surgery. A step-up approach with EUS-RFA followed by surgery for the failure cases can become a valid option to be validated in clinical studies.

Intraductal papillary mucinous neoplasms (IPMN) are one of the main precursor lesions of Pancreatic Ductal Adenocarcinoma (PDAC). The number of patients diagnosed with IPMN is constantly increasing. While in most of the cases IPMN present as indolent and nonmalignant entities, some degenerate into PDAC. The main mechanisms behind the IPMN progression to malignancy is still not fully understood.This is mainly due to the technological limit of the analyzes and to cysts heterogeneity whose malignant transformation potential is estimated based on size and degree of dysplasia without take in consideration the transformation time and therefore the real malignancy potential.Moreover, there is a general lack of consensus diagnostic markers to discern the Low-grade nonmalignant from High-grade malignant IPMN. In this study, we used two different Spatial Transcriptomic technologies (Visium, and GeoMx) to investigate the transcriptome of Low-grade dysplasia nonmalignant IPMN, Borderline IPMN, and High-grade dysplasia malignant IPMN to dissect the main mechanism that drives carcingenesis and to find specific markers associated to risk of tumor progression.We performed Visium spatial transcriptomics on two TMAs containing three Low-grade dysplasia nonmalignant IPMN, one Borderline IPMN, two High-grade dysplasia malignant IPMN, and two PDAC.We identified three specific epithelial cell clusters that characterize Low-grade dysplasia IPMN, Borderline IPMN, and High-grade dysplasia malignant IPMN and three transcription factors whose expression is associated with each grade. High-grade malignant IPMN were characterized by high expression levels ofNKX6-2and other markers of gastric isthmus cell lineage such asMUC5AC, PSCA, FERIL6.TheSPDEFhigh IPMN cluster was found in Borderline IPMN and spotted in some regions of High-grade malignant IPMN. This cluster was characterized by high expression levels ofSPDEFand other goblet cell lineage markers such asTFF2, AQP5,andMUC6.Low-grade nonmalignant IPMN were characterized by high expression levels ofHOXB3, HOXB5, ZNF117.The association of these markers with the different grades was validated by GeoMx spatial transcriptomics on 43 additional IPMN samples divided according to their grade of dysplasia and malignancy.To better understand the transcriptomic changes along IPMN progression we performed spatial trajectory inference and we found thatSPDEFhigh IPMN cluster cells are likely to evolve intoNKX6-2high malignant IPMN, and we found that this switch is characterized by the expression ofNKX6-2and other gastric markers.Taken together, the results presented here not only shed more light in to IPMN and PDAC oncogenesis, but also provided a plethora of novel malignancy-associated markers to be tested in diagnostic routine, to better delineate IPMN progression in patients and improve clinical management.

Background A validated classification of endoscopic ultrasound (EUS) morphological characteristics and consequent therapeutic intervention(s) in pancreatic and peripancreatic fluid collections (PFCs) is lacking. We performed an interobserver agreement study among expert endosonographers assessing EUS-related PFC features and the therapeutic approaches used. Methods 50 EUS videos of PFCs were independently reviewed by 12 experts and evaluated for PFC type, percentage solid component, presence of infection, recognition of and communication with the main pancreatic duct (MPD), stent choice for drainage, and direct endoscopic necrosectomy (DEN) performance and timing. The Gwet’s AC1 coefficient was used to assess interobserver agreement. Results A moderate agreement was found for lesion type (AC1, 0.59), presence of infection (AC1, 0.41), and need for DEN (AC1, 0.50), while fair or poor agreements were stated for percentage solid component (AC1, 0.15) and MPD recognition (AC1, 0.31). Substantial agreement was rated for ability to assess PFC–MPD communication (AC1, 0.69), decision between placing a plastic versus lumen-apposing metal stent (AC1, 0.62), and timing of DEN (AC1, 0.75). Conclusions Interobserver agreement between expert endosonographers regarding morphological features of PFCs appeared suboptimal, while decisions on therapeutic approaches seemed more homogeneous. Studies to achieve standardization of the diagnostic endosonographic criteria and therapeutic approaches to PFCs are warranted.

This is the fifth in a series of papers entitled 'Controversies in EUS.' In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.

BACKGROUND. Intraductal papillary mucinous neoplasm (IPMN) are the most prevalent pancreatic cystic neoplasms which may progress to pancreatic ductal adenocarcinoma (PDAC), the most lethal solid malignancy. Therefore, patients suffering from this condition represent the ideal population where to address the efforts of identifying prevention or interception strategies. Here, we used spatial transcriptomics on IPMNs of different grade to identify mechanisms that are associated to the progression of those lesions toward invasive carcinomas. METHODS. We analysed 43 IPMNs grouped according to their dysplasia grade by digital spatial whole transcriptome analysis (GeoMX Human Whole Transcriptome Atlas). The high-resolution of the technology gave us the opportunity to define the genes activated along progression of IPMN to cancer, ruling out the background given by the non-neoplastic cells. The gene signature identified was validated for expression in an external validation cohort of IPMN patients and in TCGA dataset and as therapeutic target in in vitro 3D models and in in vivo syngeneic orthotopic model of PDAC. RESULTS. By spatial transcriptome profiling of IPMNs with different dysplasia grades, we identified more than 3000 genes differentially expressed between LGD-, HGD- IPMNs and during transformation into invasive carcinoma. One of the top differentially regulated gene signature, mucins-specific O-Glycosylation, was both validated in a cohort of patients (n=9) by immunofluorescence (IF) analysis and in TCGA dataset. Preclinical models of pancreatic cancer, including in vitro 3D and in vivo experiments confirmed the role of GCNT3 and mucins in protecting tumor cells from T-cells recognition. CONCLUSIONS. We identified more than 3000 genes differentially expressed between LGD- and HGD- IPMNs and along the transformation from IPMN into invasive carcinoma. These results shed light on the role of mucin-specific O-glycosylation in the IPMN progression and in PDAC offering suitable markers for the early diagnosis. Moreover, we demonstrated in in vitro 3D models and in vivo experiment that GCNT3, the main regulator of mucins post-translational modification, is an actionable target in PDAC, paving the way for the development of novel strategies to target the protective mucin barrier to enhance PDAC chemotherapy efficacy.

Ablative therapies for locoregional treatment of pancreatic neoplastic lesions developed over the last decade to be applied during surgery are now becoming also available to be utilized under endoscopic ultrasound (EUS) guidance. The advantage of this approach is clear because of the close proximity of the EUS transducer to the target lesion, coupled with developments of specifically designed ablation devices, making the procedure minimally invasive, and potentially sparing patients from the morbidity of this method when performed surgically. EUS-guided ablative techniques that have been applied to pancreatic neoplastic cysts, pancreatic functional and non-functional neuroendocrine neoplasms and pancreatic ductal adenocarcinoma include ethanol injection, radiofrequency ablation (RFA), a combination of bipolar RFA and cryoablation, laser therapy (LT) and photodynamic therapy (PDT). Up to now, most of these procedures have been applied to patients at high surgical risk or who refused surgery. However, more studies evaluating some of these treatments also in selected patients not at surgical risk are becoming available. These studies will pave the road to apply this therapeutic approach to a more extensive number of patients, alone or in association with other therapies, such as immunomodulating drugs. The present manuscript will critically review the available evidence in the field of EUS-guided local ablative treatment of solid and cystic pancreatic neoplasms.

Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens.Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed.Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482).Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.

The close proximity of the endoscopic ultrasound (EUS) probe to the pancreas, coupled with the ease with which a needle can be inserted into a pancreatic lesion, have contributed to the development of EUS-guided therapies for both adenocarcinoma and neuroendocrine pancreatic neoplasms. EUS-guided fine needle injection of different types of drugs, implantation of fiducial markers to facilitate stereotactic body radiation therapy or of radioactive seeds to perform brachytherapy, and the use of different thermal and nonthermal ablation devices and techniques have all been tested in preliminary human studies. This manuscript will present the available evidence accumulated thus far in the field of EUS-guided oncological treatment of pancreatic solid tumors, along with a look into possible future applications.

Background Head pancreatic cancers often present with clinical challenges requiring biliary drainage for chemotherapy or palliative scope. If usual endoscopic modalities fail or if percutaneous approach is not feasible, endoscopic ultrasound (EUS) guided biliary drainage can be considered. Here we describe and discuss an interesting clinical case in which EUS-guided gallbladder drainage (EUS-GBD) was chosen to treat acute severe cholangitis in a patient with advanced pancreatic cancer. Case summary An 84-year-old female with a previous EUS-biopsy proven diagnosis of head pancreatic cancer presented with clinical signs of acute cholangitis. In September 2018 she had positioned a biliary and duodenal stent to relieve jaundice and an initial duodenal substenosis. In the emergency ward, an abdominal computed tomography scan showed proximal biliary stent occlusion due to neoplastic progression, but endoscopic retrograde cholangiopancreatography was impossible because of worsening duodenal stenosis and the absence of a chance to reach the Vater's papilla area. EUS-guided choledocoduodenostomy was not technically feasible but because the cystic duct was free of neoplastic infiltration, an EUS-GBD using an Axios™ stent was successfully performed. The patient started to feed after 48 h and was discharged 1 wk later. No other hospitalizations due to cholangitis or symptoms of Axios™ stent occlusion/dysfunction were observed up until her death 6 mo later due to underlying disease. Conclusion This case demonstrated how different EUS therapeutic approaches could have a key role to treat critical and seemingly unsolvable situations and that they could play a more fundamental role in the next future.

Background The percutaneous approach allows for effective and safe treatment of liver lesions. But in case of subcapsular or left segments location, this approach seems to be less effective or unsafe. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a new technique used to treat pancreatic and neuroendocrine tumors in patients unfit for surgery. Methods Hereby, we describe the case of a 70-year-old patient with cirrhosis with a large subcapsular hepatocellular carcinoma (HCC) in II-III-IVb segments, in which surgery or percutaneous therapies were not feasible, treated with EUS-RFA. The HCC was treated using an EUS-RFA (EUSRA) system, which consists of a 19G water-cooled monopolar RFA needle and a dedicated generator system. Results After a multidisciplinary discussion, the lesion was ablated in two different sessions, which resulted in destruction of about 70 % of neoplastic tissue. A second step surgery was required but initially refused by the patient. Conclusions EUS-RFA could be an effective way to treat left hepatic lesions not manageable with conventional percutaneous methods. This case report does not highlight concerns about safety of this approach and this observation needs to be validated in a larger cohort of patients with cirrhosis.