First report of robotic retromuscular incisional hernia repair with Hugo Ras™ surgical system.

Treatment of incisional hernia is a rapidly evolving field of surgery, with actual trends being oriented toward retromuscular/preperitoneal mesh placement. The diffusion of robotic surgery is constantly growing in different surgical specialties and is gaining widespread acceptance for abdominal wall reconstruction. Recently, novel robotic platforms have entered into the market. In this study, we present the first transabdominal retromuscular incisional hernia repair performed with the new Hugo RAS™ system (Medtronic, Minneapolis, MN, USA). The surgical team had previous robotic experience and completed an official 2-day session running incisional hernia repair on human cadaver lab. Operating room setting and trocar layout were planned. The patient presented a 4 × 4 cm midline incisional hernia and was scheduled for transabdominal retromuscular incisional hernia repair at our Institution. A description of the operative room setup, robotic arm configuration and docking/tilt angles is provided. Docking time, operative time, and console time were 15, 95, and 75 min, respectively. All the surgical steps were completed without critical surgical errors or high-priority alarms. Neither intraoperative complications nor conversion to open surgery was recorded. Postoperative course was uneventful and the patient was discharged on postoperative day 2. The safety and the feasibility of these procedures will require further analysis and larger patients' sample sizes for procedural standardization and potential integration into minimally invasive abdominal wall reconstruction programs.

Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections.

BACKGROUND: The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. METHODS: A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). RESULTS: A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. CONCLUSIONS: ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.

Proposal of set-up standardization for general surgery procedures with the CMR Versius system, a new robotic platform: our initial experience.

BACKGROUND: The article describes our initial experience using CMR Versius platform for several procedures in general surgery. METHODS: Between September 2022 and April 2023, seventy patients underwent robotic surgery in a multi-robotic referral center (San Paolo University Hospital, Milan, Italy). Three surgeons with only laparoscopic experience performed 24 cholecystectomies, 13 inguinal hernia repairs, 9 ventral hernia repairs, 7 right hemicolectomies, 11 left hemicolectomies, 1 sigmoidectomy, 1 ileocecal resection, 1 ventral rectopexy, 1 Nissen fundoplication, 1 total splenectomy, and 1 exploration with multiple biopsies. RESULTS: All surgeries were full-robotic, with only one conversion to laparoscopy. The short length of stay and low rate of severe morbidity are promising findings. Although operative time was lengthened, clinical outcomes were not affected. CONCLUSIONS: Our experience demonstrates that the adoption of Versius system is safe and feasible in general surgery. The standardization of port placement and BSU set-up can certainly reduce the operative time.

Lynch Syndrome: From Multidisciplinary Management to Precision Prevention.

BACKGROUND AND AIMS: Lynch syndrome (LS) is currently one of the most prevalent hereditary cancer conditions, accounting for 3% of all colorectal cancers and for up to 15% of those with DNA mismatch repair (MMR) deficiency, and it was one of the first historically identified. The understanding of the molecular carcinogenesis of LS tumors has progressed significantly in recent years. We aim to review the most recent advances in LS research and explore genotype-based approaches in surveillance, personalized cancer prevention, and treatment strategies. METHODS: PubMed was searched to identify relevant studies, conducted up to December 2023, investigating molecular carcinogenesis in LS, surveillance strategies, cancer prevention, and treatment in LS tumors. RESULTS: Multigene panel sequencing is becoming the benchmark in the diagnosis of LS, allowing for the detection of a pathogenic constitutional variant in one of the MMR genes. Emerging data from randomized controlled trials suggest possible preventive roles of resistant starch and/or aspirin in LS. Vaccination with immunogenic frameshift peptides appears to be a promising approach for both the treatment and prevention of LS-associated cancers, as evidenced by pre-clinical and preliminary phase 1/2a studies. CONCLUSIONS: Although robust diagnostic algorithms, including prompt testing of tumor tissue for MMR defects and referral for genetic counselling, currently exist for suspected LS in CRC patients, the indications for LS screening in cancer-free individuals still need to be refined and standardized. Investigation into additional genetic and non-genetic factors that may explain residual rates of interval cancers, even in properly screened populations, would allow for more tailored preventive strategies.

Fashioning esophagogastric anastomosis in robotic Ivor-Lewis esophagectomy: a multicenter experience.

BACKGROUND: The aim of the present study is to compare outcomes of the robotic hand-sewn, linear- and circular-stapled techniques performed to create an intrathoracic esophagogastric anastomosis in patients who underwent Ivor-Lewis esophagectomy. METHODS: Patients who underwent a planned Ivor-Lewis esophagectomy were retrospectively analysed from prospectively maintained databases. Only patients who underwent a robotic thoracic approach with the creation of an intrathoracic esophagogastric anastomosis were included in the study. Patients were divided into three groups: hand-sewn-, circular stapled-, and linear-stapled anastomosis group. Demographic information and surgery-related data were extracted. The primary outcome was the rate of anastomotic leakages (AL) in the three groups. Moreover, the rate of grade A, B and C anastomotic leakage were evaluated. In addition, patients of each group were divided in subgroups according to the characteristics of anastomotic fashioning technique. RESULTS: Two hundred and thirty patients were enrolled in the study. No significant differences were found between the three groups about AL rate (p = 0.137). Considering the management of the AL for each of the three groups, no significant differences were found. Evaluating the correlation between AL rate and the characteristics of anastomotic fashioning technique, no significant differences were found. CONCLUSIONS: No standardized anastomotic fashioning technique has yet been generally accepted. This study could be considered a call to perform ad hoc high-quality studies involving high-volume centers for upper gastrointestinal surgery to evaluate what is the most advantageous anastomotic technique.

The use of Versius CMR for pelvic surgery: a multicentric analysis of surgical setup and early outcomes.

INTRODUCTION: Versius CMR is a novel robotic system characterized by an open surgical console and independent bedside units. The system has potentials of flexibility and versatility, and has been used in urological, gynecological, and general surgical procedure. The aim is to depict a comprehensive analysis of the Versius system for pelvic surgery. METHODS: This is a study involving two Institutions, ASST Santi Paolo and Carlo, Milan, and Apuane Hospital, Massa, Italy. All interventions performed in the pelvic area with the Versius were included. Data about indications, intra-, and post-operative course were prospectively collected and analyzed. RESULTS: A total of 171 interventions were performed with the Versius. Forty-two of them involved pelvic procedures. Twenty-two had an oncological indication (localized prostate cancer), the remaining had a non-oncological or functional purpose. The mostly performed pelvic procedure was radical prostatectomy (22) followed by annexectomy (9). No intra-operative complication nor conversion to other approaches occurred. A Clavien II complication and one Clavien IIIb were reported. Malfunctioning/alarms requiring a power cycle of the system occurred in 2 different cases. An adjustment in trocar placement according to patients' height was required in 2 patients undergoing prostatectomy, in which the trocar was moved caudally. In two cases, a pelvic prolapse was repaired concomitant with other gynecological procedures. CONCLUSIONS: Pelvic surgery with the Versius is feasible without major complications; either dissection and reconstructive steps could be accomplished, provided a proper OR setup and trocar placement are pursued. Versius can be easily adopted by surgeons of different disciplines and backgrounds; a further multi-specialty implementation is presumed and long-term oncological and functional outcomes are awaited.

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Robotic multiple sigmoid and rectal mucosa skinning in a multicentric deep infiltrating bowel endometriotic nodules: a case report.

Endometriosis is a benign gynecological disease characterized by the presence of endometrial tissue outside the uterus. The eradication of non-gynecological localizations represents the real surgical challenge. A 29-year-old woman underwent robotic surgery with the Da Vinci system (Intuitive Surgical Inc.) for a diagnosis of stage IV deep endometriosis. The patient presented with 5 cm left ovarian endometrioma, an infiltration of the left posterior parametrium, and bilateral ureteral endometriosis. Once inside the pelvic cavity, deep intestinal infiltrating endometriosis implants were confirmed as triple, multicentric, and multifocal lesions, affected distal sigmoid, rectosigmoid junction, and upper rectum. An expert multiple excision, sparing the intestinal mucosa, was performed. To our knowledge, this is the first description of a multiple robotic shaving of multicentric endometriotic intestinal lesions. After the surgery, a normal diet was quickly restored, accelerating the recovery of the physiological peristalsis and the overall recovery time.

Multimodular robotic systems (Hugo RAS and Versius CMR) for pelvic surgery: tasks and perspectives from the bed-side assistant.

The Hugo RAS and Versius are new robotic systems with a multimodular configuration, requiring a dedicated positioning of units, arms and trocars. While promising flexibility and multiquadrant opportunities-with an enhanced range of motion-the presence of multiple units around the patient should be effectively managed by the assistant and requires a new background of tasks. The article represents a practical guide while providing an overview on assistants' perspectives.

Safety of tracheostomy during extracorporeal membrane oxygenation support: A single-center experience.

BACKGROUND: Some patients on extracorporeal membrane oxygenation (ECMO) require prolonged mechanical ventilation. An early tracheostomy strategy while on ECMO has appeared to be beneficial for these patients. This study aims to explore the safety of tracheostomy in ECMO patients. METHODS: This is a retrospective observational single-center study. RESULTS: Hundred and nine patients underwent tracheostomy (76 percutaneous and 33 surgical) during V-V ECMO support over an 8-year period. Patients with a percutaneous tracheostomy showed a significantly shorter ECMO duration [25.5 (17.3-40.1) vs 37.2 (26.5-53.2) days, p = 0.013] and a shorter ECMO-to-tracheostomy time [13.3 (8.5-19.7) vs 27.8 (16.3-36.9) days, p < 0.001] compared to those who underwent a surgical approach. There was no difference between the two strategies regarding both major and minor/no bleeding (p = 0.756). There was no difference in survival rate between patients who underwent percutaneous or surgical tracheostomy (p = 0.173). Patients who underwent an early tracheostomy (within 10 days from ECMO insertion) showed a significantly shorter hospital stay (p < 0.001) and a shorter duration of V-V ECMO support (p < 0.001). Our series includes 24 patients affected by COVID-19, who did not show significantly higher rates of major bleeding when compared to non-COVID-19 patients (p = 0.297). Within the COVID-19 subgroup, there was no difference in major bleeding rates between surgical and percutaneous approach (p = 1.0). CONCLUSIONS: Percutaneous and surgical tracheostomy during ECMO have a similar safety profile in terms of bleeding risk and mortality. Percutaneous tracheostomy may favor a shorter duration of ECMO support and hospital stay and can be considered a safe alternative to surgical tracheostomy, even in COVID-19 patients, if relevant clinical expertise is available.

International standardization and optimization group for intersphincteric resection (ISOG-ISR): modified Delphi consensus on anatomy, definition, indication, surgical technique, specimen description and functional outcome.

AIM: Intersphincteric resection (ISR) is an oncologically complex operation for very low-lying rectal cancers. Yet, definition, anatomical description, operative indications and operative approaches to ISR are not standardized. The aim of this study was to standardize the definition of ISR by reaching international consensus from the experts in the field. This standardization will allow meaningful comparison in the literature in the future. METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol. RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements. CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.

Robotic Total Mesorectal Excision for Low Rectal Cancer: A Narrative Review and Description of the Technique.

Robotic surgery may offer significant advantages for treating extraperitoneal rectal cancer. Although laparoscopy has been shown to be safe and effective, laparoscopic total mesorectal excision (TME) remains technically challenging and is still performed in selected centers. Robotic anterior resection (RAR) may overcome the drawback of conventional laparoscopy, providing high-quality surgery with favorable oncological outcomes. Moreover, recent data show how RAR offers clinical and oncological benefits when affording difficult TMEs, such as low and advanced rectal tumors, in terms of complication rate, specimen quality, recurrence rate, and survival. This series aims to review the most recent and relevant literature, reporting mid- and long-term oncological outcomes and focusing on minimally invasive RAR for low rectal cancer.

New Robotic Platforms in General Surgery: What's the Current Clinical Scenario?

Background and Objectives: Robotic surgery has been widely adopted in general surgery worldwide but access to this technology is still limited to a few hospitals. With the recent introduction of new robotic platforms, several studies reported the feasibility of different surgical procedures. The aim of this systematic review is to highlight the current clinical practice with the new robotic platforms in general surgery. Materials and Methods: A grey literature search was performed on the Internet to identify the available robotic systems. A PRISMA compliant systematic review was conducted for all English articles up to 10 February 2023 searching the following databases: MEDLINE, EMBASE, and Cochrane Library. Clinical outcomes, training process, operating surgeon background, cost-analysis, and specific registries were evaluated. Results: A total of 103 studies were included for qualitative synthesis after the full-text screening. Of the fifteen robotic platforms identified, only seven were adopted in a clinical environment. Out of 4053 patients, 2819 were operated on with a new robotic device. Hepatopancreatobiliary surgery specialty performed the majority of procedures, and the most performed procedure was cholecystectomy. Globally, 109 emergency surgeries were reported. Concerning the training process, only 45 papers reported the background of the operating surgeon, and only 28 papers described the training process on the surgical platform. Only one cost-analysis compared a new robot to the existing reference. Two manufacturers promoted a specific registry to collect clinical outcomes. Conclusions: This systematic review highlights the feasibility of most surgical procedures in general surgery using the new robotic platforms. Adoption of these new devices in general surgery is constantly growing with the extension of regulatory approvals. Standardization of the training process and the assessment of skills' transferability is still lacking. Further studies are required to better understand the real clinical and economical benefit.

Utility of near infrared fluorescent cholangiography in detecting biliary structures during challenging minimally invasive cholecystectomy.

BACKGROUND: Surgeons can minimize the risk of bile duct injury (BDI) during challenging mini-invasive cholecystectomy through technical standardization by means of a precise anatomical landmark identification (Critical View of Safety) and advanced technology for biliary visualization. Among these systems, the adoption of magnified stereoscopic 3-dimensional view provided by robotic platforms and near infrared fluorescent cholangiography (NIRF-C) is the most promising. METHODS: In this prospective cohort study, we evaluated all consecutive minimally invasive cholecystectomies (laparoscopic and robotic) performed with NIRF-C between May 2022 and January 2023 at General Surgery Unit, Department of Health Sciences, University of Milan, San Paolo Hospital (Milan, Italy). Inclusions criteria were as follows: (1) acute cholecystitis (emergency group), (2) history of chronic cholecystitis or complicated cholelithiasis (deferred urgent group), (3) difficult cases (patients affected by cirrhosis, with scleroatrophic gallbladder or BMI > 35 kg/m2). For each group, the detection rate and visualization order of the main biliary structures were reported (cystic duct, CD; common hepatic duct, CHD; common bile duct, CBD; and CD-CHD junction). RESULTS: A total of 101 consecutive patients were enrolled, including 83 laparoscopic and 18 robotic cholecystectomies. All patients were stratified into three subgroups: (a) emergency group (n = 33, 32.7%), (b) deferred urgent group (n = 46, 45.5%), (c) difficult group (n = 22, 21.8%). Visualization of at least one biliary structure was possible in 94.1% of cases (95/101). Interestingly, all four main structures were detected in 43.6% of cases (44/101). The CD was the structure identified most frequently, being recognized in 91/101 patients (90.1%), followed by CBD (83.2%), CHD (62.4%), and CD-CHD junction (52.5%). In the subset of patients that underwent emergency surgery for AC, the CD-CHD confluence was identified in only 45.5% of cases. However, early and precise identification of CBD (75.8%) and CD (87.9%) allowed safe isolation, clipping, and transection of the cystic duct. In the deferred urgent group, the CBD and the CD were easily identified as first structure in a high percentage of cases (65.2% and 41.3% respectively), whereas the CD-CHD junction was the third structure to be identified in 67.4% of cases, the highest value among the three subgroups. In the difficult group, NIRF-C did not prove to be a useful tool for biliary visualization. The rates of failure of visualization were elevated: CBD (27.3%), CD (18.2%), CHD (54.5%), and CD-CHD (68.2%). CONCLUSIONS: NIRF-C is a powerful real-time diagnostic tool to detect CBD and CD during minimally invasive cholecystectomy, especially when inflammation due to acute or chronic cholecystitis subverted the anatomy of the hepatoduodenal ligament.

Preliminary robotic abdominal wall reconstruction experience: single-centre outcomes of the first 150 cases.

PURPOSE: Robotic surgery offers new possibilities in repairing complex hernias with a minimally invasive approach. This study aimed to analyze our preliminary results. METHODS: Between November 2015 and February 2020, 150 patients underwent robotic reconstruction for abdominal wall defects (77 primary and 73 incisional). A retrospective analysis of a prospectively maintained database was conducted to evaluate the short-term outcomes. RESULTS: The mean operative time was 176.9 ± 72.1 min. No conversion to open or laparoscopic approach occurred. The mean hospital length of stay was 2.6 ± 1.6. According to Clavien-Dindo classification, two (grade III) complications following retromuscular mesh placement (1.3%) occurred. One patient (0.7%) required surgical revision due to small bowel occlusion following an intraparietal hernia. The 30-day readmission rate was 0.6%, and the mortality was nihil. CONCLUSIONS: Robotic surgery is valuable for safely completing challenging surgical procedures like complex abdominal wall reconstruction, with low conversion and complication rates. A stepwise approach to the different surgical techniques is essential to optimize the outcomes and maximize the benefits of the robotic approach.

A Comparison of Long-Term Outcomes in Patients Managed With Venovenous Extracorporeal Membrane Oxygenation in the First and Second Waves of the COVID-19 Pandemic in the United Kingdom.

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ 2 , 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.

Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.

Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.