Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Endovascular Lymphatic Decompression via Thoracic Duct Stent Placement for Refractory Ascites in Patients with Cirrhosis: A Pilot Study.

PURPOSE: To evaluate the technical and clinical success of endovascular lymphatic decompression via thoracic duct (TD) stent placement in patients with cirrhosis with refractory ascites. MATERIALS AND METHODS: Nine patients (6 men and 3 women; median age, 66 [interquartile range {IQR}, 65-68] years; range, 62-78 years) who underwent TD stent placement for refractory ascites with contraindications for liver transplantation and transjugular intrahepatic portosystemic shunt creation were included in this retrospective study. TD stent placement was performed under local anesthesia using retrograde access from the venous system. Self-expanding stents from 5 to 8 mm in diameter were used and extended into the subclavian vein by approximately 1 cm. Technical (correct positioning of the stent) and clinical success (no more requirement of paracentesis) were evaluated. In addition, the safety of the procedure and TD pressure evolution were evaluated. RESULTS: The technical success rate was 100%, and 3 (33%) patients reported clinical success. Five (56%) patients reported 7 minor adverse events (Grade I), among which 2 TD perforations were induced by stent angioplasty, with no clinical manifestation or treatment required. The median TD pressure decreased from 19 mm Hg (IQR, 11-24 mm Hg) at the beginning of the procedure to 6 mm Hg (IQR, 5-11 mm Hg) after TD stent placement. The median survival time after the procedure was 7.1 months. CONCLUSIONS: Endovascular lymphatic decompression via TD stent placement is feasible and safe and was effective on ascites in some patients with cirrhosis with refractory ascites.

[Dasatinib-induced follicular lymphoid hyperplasia, an entity to know]. / Hyperplasie lymphoïde folliculaire induite par la prise de dasatinib, une entité à connaître.

Follicular lymphoid hyperplasia induced by dasatinib is an entity recently described. It is sometimes difficult to rule out the diagnostic of small B-cell lymphoma. Usually, the node is swollen, with follicular architecture conserved, composed by germinal centers with variable size and shape, with a hight number of mitoses and tingible bodies macrophages inside. Follicular lymphoid hyperplasia is isolated or associated with multiple reactive patterns. The immunohistochemical profil of germinal centers is CD20+, CD10+, BCL6+, BCL2-. Swollen node disappears in a short time after dasatinib discontinuation. Clinicians and pathologists need to be aware of this entity, so as not to avoid mistakenly suspect lymphoma when lymphadenopathy occurs in a patient with chronic myeloid leukemia treated with dasatinib.

Immunomodulation for hepatocellular carcinoma therapy: current challenges.

PURPOSE OF REVIEW: The emergence of novel immunotherapies, such as immune-checkpoint inhibitors has changed the landscape of systemic cancer treatment. In hepatocellular carcinoma (HCC) patients, despite initial enthusiasm, the proportion of responders to immune-checkpoint inhibitors remains low. We provide a brief update of this rapidly evolving field, with specific focus on the development in the field of predictive factors and the immunomodulation induced by locoregional therapies. RECENT FINDINGS: Even if the immune contexture of HCC before the treatment remains the most promising predictive marker for response to immunotherapies, recent findings show that the cause of HCC may have also a key role. Specific inflammatory mechanisms induced by NASH may result in limited efficacy of immunotherapy compared with viral HCC. Other recent findings showed that percutaneous ablations are responsible for intratumoral immune changes and systemic immune system activation that may help to prevent recurrence when combined with immunotherapies. In case of multifocal HCC, transarterial therapies (TACE and SIRT) may help to turn a cold tumor type to a hot tumor type and could be associated with immune-checkpoint inhibitors to improve outcomes. SUMMARY: The future HCC management will focus on patient stratification for specific immunotherapies depending on the signature and cause of HCC and the best combined approaches in which locoregional therapies may play a pivotal role.

Management of Symptomatic Vascularized Retained Products of Conception by Proximal Uterine Artery Embolization with Gelatin Sponge Torpedoes.

PURPOSE: To evaluate the effectiveness and safety of temporary proximal uterine artery embolization (UAE) for the treatment of highly vascularized retained products of conception (RPOCs). MATERIALS AND METHODS: This retrospective analysis included women who underwent treatment for vaginal bleeding after abortion, miscarriage, or delivery, with highly vascularized RPOCs detected by Doppler ultrasound (US) (ie, presence of an enhanced myometrial vascularity, a low resistance index of <0.5, and a peak systolic velocity of ≥0.7 m/s). A unilateral or bilateral embolization with torpedoes of gelatin foam was performed. From November 2017 to January 2021, 24 women with a median age of 30 years (interquartile range, 26.0-34.5 years) with symptomatic highly vascularized RPOCs were included. Clinical success was defined as bleeding arrest between the UAE and 1-month follow-up. Technical success was defined as the complete obstruction of at least 1 uterine artery supplying vascular abnormalities. The safety of the procedure according to the classification of the Society of Interventional Radiology and evolution of lesions on US were also reported. RESULTS: Technical success was achieved in all 24 (100%) patients, with bilateral arterial embolization in 19 (79%) patients and unilateral embolization in 5 (21%) patients. Clinical success was achieved in all 24 (100%) patients. Five patients still had uterine retention at the 1-month follow-up, including 2 patients with highly vascularized RPOCs. Two patients benefited from hysteroscopy, and 3 had noninvasive management. Four minor adverse events were reported (1 patient had infectious endometritis and 3 patients had a postembolization syndrome). CONCLUSIONS: Proximal UAE with torpedoes of gelatin foam is safe and effective for the management of symptomatic highly vascularized RPOCs.

Delayed Postoperative Hemorrhage Complicating Major Supramesocolic Surgery Management and Outcomes.

BACKGROUND: The place of surgery and interventional radiology in the management of delayed (> 24 h) hemorrhage (DHR) complicating supramesocolic surgery is still to define. The aim of the study was to evaluate outcomes of DHR using a combined multimodal strategy. METHODS: Between 2005 and 2019, 57 patients (median age 64 years) experienced 86 DHR episodes after pancreatic resection (n = 26), liver transplantation (n = 24) and other (n = 7). Hemodynamically stable patients underwent computed tomography evaluation followed by interventional radiology (IR) treatment (stenting and/or embolization) or surveillance. Hemodynamically unstable patients were offered upfront surgery. Failure to identify the leak was managed by either prophylactic stenting/embolization of the most likely bleeding source or surveillance. RESULTS: Mortality was 32% (n = 18). Bleeding recurrence occurred in 22 patients (39%) and was multiple in 7 (12%). Sentinel bleeding was recorded in 77 (81%) of episodes, and the bleeding source could not be identified in 26 (30%). Failure to control bleeding was recorded in 9 (28%) of 32 episodes managed by surgery and 4 (11%) of 41 episodes managed by IR (p = 0.14). Recurrence was similar after stenting and embolization (n = 4/18, 22% vs n = 8/26, 31%, p = 0.75) of the bleeding source. Recurrence was significantly lower after prophylactic IR management than surveillance of an unidentified bleeding source (n = 2/10, 20% vs. n = 11/16, 69%, p = 0.042). CONCLUSION: IR management should be favored for the treatment of DHR in hemodynamically stable patients. Prophylactic IR management of an unidentified leak decreases recurrence risks.

Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide and its incidence is rising. Percutaneous locoregional therapies, such as radiofrequency ablation and microwave ablation, are widely used as curative treatment options for patients with small HCC, but their effectiveness remains restricted because of the associated high rate of recurrence, occurring in about 70% of patients at five years. These thermal ablation techniques have the particularity to induce immunomodulation by destroying tumours, although this is not sufficient to raise an effective antitumour immune response. Ablative therapies combined with immunotherapies could act synergistically to enhance antitumour immunity. This review aims to understand the different immune changes triggered by radiofrequency ablation and microwave ablation as well as the interest in using immunotherapies in combination with thermal ablation techniques as a tool for complementary immunomodulation.

Radiological diagnosis of hepatocellular carcinoma does not preclude biopsy before treatment.

Background & Aims: The diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis relies on non-invasive criteria based on international guidelines. The advent of systemic therapies warrants reconsideration of the role of biopsy specimens in the diagnosis of HCC. Accordingly, we investigated the diagnostic performance of the LI-RADS 2018 and the AASLD 2011 criteria. Methods: Consecutive patients with cirrhosis who underwent a biopsy for suspected HCC between 2015 and 2020 were included. The available imaging studies (computed tomography and/or magnetic resonance imaging) were blindly reviewed by two independent radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for LI-RADS, AASLD, and biopsies. Results: In total, 167 patients underwent both available biopsy and imaging. Of the 137 relevant biopsies, 114 patients had HCC (83.2%), 12 (9%) had non-HCC malignant lesions, and 11 (8%) had benign nodules. The PPV and NPV of the biopsies were 100% and 62%, respectively; 30 biopsies were non-contributive. The PPV and NPV of the LI-RADS categories were 89% and 32.8% for LR-5 and 85.5% and 54.5% for LR-4 + 5 + TIV, respectively. The PPV and NPV of the 2011 AASLD criteria were 93.2% and 35.6%, respectively. The interobserver kappa (k = 0.380) for the LR-5 categories was reasonable. Of 100 LR-5 nodules, 11 were misclassified, in particular one case was a colorectal metastasis, and two cases were cholangiocarcinomas, of which nine were identified through biopsy, whereas six were correctly classified according to LI-RADS (LR-M or LR-TIV). Fifty percent of macrotrabecular HCC and 48.4% of poorly differentiated HCC (Edmonson 3 and 4) were not classified as LR-5. Conclusions: LI-RADS 2018 did not outperform the AASLD 2011 score as a non-invasive diagnosis of HCC. Tumor biopsy allowed restoration of an accurate diagnosis in 11% of LR-5 cases. A combined radiological and histological diagnosis should be considered mandatory for good treatment assessment. Impact and Implications: Although biopsy is not required for hepatocellular carcinoma diagnosis when the LI-RADS criteria are met according to current guidelines, our study underscores the limits of radiology and the need for biopsy when hepatocellular carcinoma is suspected. Histological findings could change therapeutics of liver tumors even if only for a small proportion of patients. Histological proof of the type of cancer is a standard in oncology.

PD1 and TIM3 Expression is Associated with Very Early Hepatocellular Carcinoma Recurrence After Percutaneous Thermal Ablation.

Purpose: Percutaneous thermal ablation (PTA) is a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). However, intrahepatic distant recurrence (IDR) occurs in the majority of patients after PTA. The aim of this study was to evaluate the immune signature associated with very early IDR. Patients and Methods: Thirty-one patients (26 men, 5 women; mean age:72.4 ± 8.6; age range:57-86 years) who underwent PTA for HCC were included in this study. After PTA for HCC, patients were followed and later divided into two groups: a "very early recurrence" group in case of IDR within 12 months after PTA, and a "prolonged recurrence-free" group in case of no recurrence before 12 months of follow-up. Freshly harvested intratumoral and nontumoral liver tissues and peripheral blood were obtained before PTA and explored by multiparametric flow cytometry. Results: The frequency of PD1+CD4+ T cells was higher in the early recurrence group than in the prolonged recurrence-free group in the peripheral blood (24.3%, IQR: 22.3-36.5 vs 14.0%, IQR: 11.5-16.4, p<0.0001), in the nontumoral liver (37.9%, IQR: 36.0-50.0 vs 22.5%, IQR: 18.0-29.9, p=0.0004), and in the tumor (37.6%, IQR: 32.3-39.3 vs 24.0%, IQR: 20.0-30.3, p=0.0137). Similarly, the frequency of TIM+CD8+ T cells was higher in the very early recurrence group in the peripheral blood (p=0.0021), non-tumoral liver (p=0.0012), and tumor (p=0.0239). Conclusion: The expression of immune checkpoint molecules, such as PD1 and TIM3 on T cells identified HCC patients at risk of very early IDR after PTA who would likely benefit from adjuvant immunotherapy. Thus, our study contributes to a better understanding of the potential association of PTA with adjuvant immunotherapies.

Preventive Proximal Splenic Artery Embolization for High-Grade AAST-OIS Adult Spleen Trauma without Vascular Anomaly on the Initial CT Scan: Technical Aspect, Safety, and Efficacy-An Ancillary Study.

The spleen is the most commonly injured organ in blunt abdominal trauma. Its management depends on hemodynamic stability. According to the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS ≥ 3), stable patients with high-grade splenic injuries may benefit from preventive proximal splenic artery embolization (PPSAE). This ancillary study, using the SPLASH multicenter randomized prospective cohort, evaluated the feasibility, safety, and efficacy of PPSAE in patients with high-grade blunt splenic trauma without vascular anomaly on the initial CT scan. All patients included were over 18 years old, had high-grade splenic trauma (≥AAST-OIS 3 + hemoperitoneum) without vascular anomaly on the initial CT scan, received PPSAE, and had a CT scan at one month. Technical aspects, efficacy, and one-month splenic salvage were studied. Fifty-seven patients were reviewed. Technical efficacy was 94% with only four proximal embolization failures due to distal coil migration. Six patients (10.5%) underwent combined embolization (distal + proximal) due to active bleeding or focal arterial anomaly discovered during embolization. The mean procedure time was 56.5 min (SD = 38.1 min). Embolization was performed with an Amplatzer™ vascular plug in 28 patients (49.1%), a Penumbra occlusion device in 18 patients (31.6%), and microcoils in 11 patients (19.3%). There were two hematomas (3.5%) at the puncture site without clinical consequences. There were no rescue splenectomies. Two patients were re-embolized, one on Day 6 for an active leak and one on Day 30 for a secondary aneurysm. Primary clinical efficacy was, therefore, 96%. There were no splenic abscesses or pancreatic necroses. The splenic salvage rate on Day 30 was 94%, while only three patients (5.2%) had less than 50% vascularized splenic parenchyma. PPSAE is a rapid, efficient, and safe procedure that can prevent splenectomy in high-grade spleen trauma (AAST-OIS) ≥ 3 with high splenic salvage rates.

A Retrospective Comparison of the Efficacy of Embolization with Imipenem/Cilastatin and Microspheres in the Management of Chronic Shoulder Pain.

PURPOSE: To compare the efficacy of embolization with imipenem/cilastatin and microspheres in chronic shoulder pain. METHODS: This retrospective study included 29 patients who underwent embolization for chronic shoulder pain between June 2017 and March 2022 with calibrated MSs from 100 to 250 µm or IMP/CS. The main objective was the clinical success evaluated by the Minimum Clinically Important Difference (MCID) at 3 months after the procedure, validated if the patient responded yes to 2 questions: (1) Is the pain less severe than before the procedure? (2) Are you satisfied with the procedure? The decrease in visual analogue pain scale scores and the safety of the procedure were evaluated. RESULTS: Embolization was achieved in all patients. In the MS group, 4/15 patients (26.7%) experienced clinical success at 3 months according to MCID versus 10/14 patients (71.4%) in the IMP/CS group (p = 0.02). The mean VAS decreases were respectively - 28.6% ± 34.6 in the MS group and - 36.8% ± 27.8 in the IMP/CS group at 1 month (p = 0.50), - 29.9% ± 29.0 and - 39.6% ± 23.0 at 3 months (p = 0.33) and - 30.6% ± 32.8 and - 46.6% ± 28.4 at 6 months after the procedure (p = 0.26). Eleven patients (73.3%) in the MS group and 3 patients (21.4%) in the IMP/CS group had complications (p = 0.01). Among them, 2/15 patients (13.3%) had transient skin ischaemia in the MS group. CONCLUSION: Embolization with IMP/CS may be more effective and safer than MSs in the management of chronic shoulder pain.

Left gastric vein embolization during TIPS placement for acute variceal bleeding has no effect on bleeding recurrence: Results of a multicenter study.

PURPOSE: The purpose of this study was to evaluate whether concomitant left gastric vein embolization (LGVE) during transjugular intrahepatic portosystemic shunt (TIPS) for acute variceal hemorrhage could reduce the risk of bleeding recurrence. MATERIAL AND METHOD: A national multicenter observational study was conducted in 14 centers between January 2019 and December 2020. All cirrhotic patients who underwent TIPS placement for acute variceal bleeding were included. During TIPS procedure, size of left gastric vein (LGV), performance of LGVE, material used for LGVE and portosystemic pressure gradient (PPG) before and after TIPS placement were collected. A propensity score for the occurrence of LGVE was calculated to assess effect of LGVE on rebleeding recurrence at six weeks and one year. RESULTS: A total of 356 patients were included (mean age 57.3 ± 10.8 [standard deviation] years; 283/356 [79%] men). Median follow-up was 11.2 months [interquartile range: 1.2, 13.3]. The main indication for TIPS was pre-emptive TIPS (162/356; 46%), rebleeding despite secondary prophylaxis (105/356; 29%), and salvage TIPS (89/356; 25%). Overall, 128/356 (36%) patients underwent LGVE during TIPS procedure. At six weeks and one year, rebleeding-free survival did not differ significantly between patients who underwent LGVE and those who did not (6/128 [5%] vs. 15/228 [7%] at six weeks, and 11/128 [5%] vs. 22/228 [7%] at one year, P = 0.622 and P = 0.889 respectively). A total of 55 pairs of patients were retained after propensity score matching. In patients without LGVE, the rebleeding rate was not different from those with LGVE (3/55 [5%] vs. 4/55 [7%], P > 0.99, and 5/55 [9%] vs. 6/55[11%], P > 0.99, at six weeks and one year respectively). Multivariable analysis identified PPG after TIPS placement as the only predictor of bleeding recurrence (hazard ratio = 1.09; 95% confidence interval: 1.02-1.18; P = 0.012). CONCLUSION: In this multicenter national real-life study, we did not observe any benefit of concomitant LGVE during TIPS placement for acute variceal bleeding on bleeding recurrence rate.

Evolution of Thoracic Duct Congestion after Portal Decompression by TIPS in Cirrhotic Patients.

PURPOSE: To evaluate the thoracic duct (TD) diameter on CT scan in a population of cirrhotic patients before and after relief of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) insertion. To evaluate the association between the initial TD diameters and the cirrhosis severity, the morphological signs of portal hypertension and the clinical success of TIPS. METHODS: This retrospective monocentric study included 54 cirrhotic patients who underwent TIPS insertion between 2010 and 2020. Measurements of the TD were performed in CT scan at two distinct points: at the cisterna chyli (CC) and at the terminal TD near the lymphovenous junction. RESULTS: The mean diameter of the TD was 6.4 mm (± 2.9) at the CC and 6.9 mm (± 1.9) near the lymphovenous junction. After TIPS, the mean diameter decreased to 5.1 (± 2.1) at the CC (p < 0.001) and to 4.3 (± 1.5) at the terminal TD (p = 0.001). The initial TD diameter was associated with the presence of voluminous venous collaterals (p = 0.04 at CC and p = 0.04 junction). The initial terminal TD diameter was weakly associated with the largest axis of the spleen (r = 0.126, p = 0.03) and moderately associated with the azygos vein diameter (r = 0.511, p = 0.001). Initial TD diameter was not associated with Child-Pugh score (r = 0.276, p = 0.08 and r = 0.169, p = 0.7) or with clinical success of TIPS on ascites (p = 0.33 and 0.60) or on bleeding (p = 0.13 and 0.99). CONCLUSION: The diameter of the TD decreases after TIPS, but its initial diameter does not seem to be predictive of the clinical success of TIPS.

Feasibility of Neovessel Embolization in a Large Animal Model of Tendinopathy: Safety and Efficacy of Various Embolization Agents.

Targeting neovessels in chronic tendinopathies has emerged as a new therapeutic approach and several embolization agents have been reported. The aim of this study was to investigate the feasibility of embolization with different agents in a porcine model of patellar tendinopathy and evaluate their safety and efficacy. Eight 3-month-old male piglets underwent percutaneous injection of collagenase type I to induce patellar tendinopathies (n = 16 tendons). They were divided into four groups (2 piglets, 4 tendons/group): the control group, 50-100 µm microspheres group, 100-300 µm microspheres group, and the Imipenem/Cilastatin (IMP/CS) group. Angiography and embolization were performed for each patellar tendon on day 7 (D7). The neovessels were evaluated visually with an angiography on day 14. The pathological analysis assessed the efficacy (Bonar score, number of neovessels/mm2) and safety (off-target persistent cutaneous ischemic modifications and presence of off-target embolization agents). The technical success was 92%, with a failed embolization for one tendon due to an arterial dissection. Neoangiogenesis was significantly less important in the embolized groups compared to the control group angiographies (p = 0.04) but not with respect to histology (Bonar score p = 0.15, neovessels p = 0.07). Off-target cutaneous embolization was more frequently depicted in the histology of the 50-100 µm microspheres group (p = 0.02). Embolization of this animal model with induced patellar tendinopathy was technically feasible with different agents and allowed assessing the safety and efficacy of neovessel destruction. Particles smaller than 100 µm seemed to be associated with more complications.

Safety and Efficacy of Embolization with Microspheres in Chronic Refractory Inflammatory Shoulder Pain: A Pilot Monocentric Study on 15 Patients.

PURPOSE: Musculoskeletal (MSK) embolization is emerging in tendinopathy treatment. The objective of this study was to assess the efficacy and safety of MSK embolization with microspheres in the treatment of chronic shoulder pain. PATIENTS AND METHODS: This retrospective monocentric study included patients with chronic shoulder pain resistant to 6 months or more of conventional therapies who were treated with MSK embolization between 2017 and 2021. Embolization was performed using calibrated 100-250 µm microspheres. Clinical success was defined as pain reduction, i.e., a decrease in the visual analogue scale (VAS) pain score of ≥50% at 3 months after MSK embolization as compared to baseline. Adverse events were collected. RESULTS: Fifteen patients (11 women, 4 men) were included, with a median age of 50.3 years (IQR: 46.7-54.5). The median duration of symptoms was 26.6 months (20.6-39.8). The median VAS pain scores were 7.0 (7.0-8.0) at baseline, 6.0 (3.5-7.0) at 1 month, 5.0 (4.5-6.5) and 5.0 (3.0-7.4) at 3 months and 6 months (p = 0.002). Three patients (20%) reported clinical success at 3 months. Three patients experienced minor complications after embolization (paresthesia, n = 2; transient osteo-medullary edema, n = 1) and two patients had moderate complications (transient skin ischemia). CONCLUSION: MSK embolization with microspheres for treatment of refractory chronic shoulder pain showed moderate results in terms of clinical success and safety.