The Deterioration of Sarcopenia Post-Transarterial Radioembolization with Holmium-166 Serves as a Predictor for Disease Progression at 3 Months in Patients with Advanced Hepatocellular Carcinoma: A Pilot Study.

PURPOSE: The aim of this pilot study is to explore the relationship between changes in sarcopenia before and after one to three months of Transarterial Radioembolization (TARE) treatment with Holmium-166 (166Ho) and its effect on the rate of local response. Our primary objective is to assess whether the worsening of sarcopenia can function as an early indicator of a subgroup of patients at increased risk of disease progression in cases of hepatocellular carcinoma (HCC). METHODS: A single-center retrospective analysis was performed on 25 patients with HCC who underwent 166Ho-TARE. Sarcopenia status was defined according to the measurement of the psoas muscle index (PMI) at baseline, one month, and three months after TARE. Radiological response according to mRECIST criteria was assessed and patients were grouped into responders and non-responders. The loco-regional response rate was evaluated for all patients before and after treatment, and was compared with sarcopenia status to identify any potential correlation. RESULTS: A total of 20 patients were analyzed. According to the sarcopenia status at 1 month and 3 months, two groups were defined as follows: patients in which the deltaPMI was stable or increased (No-Sarcopenia group; n = 12) vs. patients in which the deltaPMI decreased (Sarcopenia group; n = 8). Three months after TARE, a significant difference in sarcopenia status was noted (p = 0.041) between the responders and non-responders, with the non-responder group showing a decrease in the sarcopenia values with a median deltaPMI of -0.57, compared to a median deltaPMI of 0.12 in the responder group. Therefore, deltaPMI measured three months post-TARE can be considered as a predictive biomarker for the local response rate (p = 0.028). Lastly, a minor deltaPMI variation (>-0.293) was found to be indicative of positive treatment outcomes (p = 0.0001). CONCLUSION: The decline in sarcopenia three months post-TARE with Holmium-166 is a reliable predictor of worse loco-regional response rate, as evaluated radiologically, in patients with HCC. Sarcopenia measurement has the potential to be a valuable assessment tool in the management of HCC patients undergoing TARE. However, further prospective and randomized studies involving larger cohorts are necessary to confirm and validate these findings.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol.

BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.

Possible use of Digital Variance Angiography in Liver Transarterial Chemoembolization: A Retrospective Observational Study.

PURPOSE: Digital variance angiography (DVA), a recently developed image processing technology, provided higher contrast-to-noise ratio (CNR) and better image quality (IQ) during lower limb interventions than digital subtraction angiography (DSA). Our aim was to investigate whether this quality improvement can be observed also during liver transarterial chemoembolization (TACE). MATERIALS AND METHODS: We retrospectively compared the CNR and IQ parameters of DSA and DVA images from 25 patients (65% male, mean ± SD age: 67.5 ± 11.2 years) underwent TACE intervention at our institute. CNR was calculated on 50 images. IQ of every image set was evaluated by 5 experts using 4-grade Likert scales. Both single image evaluation and paired image comparison were performed in a blinded and randomized manner. The diagnostic value was evaluated based on the possibility to identify lesions and feeding arteries. RESULTS: DVA provided significantly higher CNR (mean CNRDVA/CNRDSA was 1.33). DVA images received significantly higher individual Likert score (mean ± SEM 3.34 ± 0,08 vs. 2.89 ± 0.11, Wilcoxon signed-rank p < 0.001) and proved to be superior also in paired comparisons (median comparison score 1.60 [IQR:2.40], one sample Wilcoxon p < 0.001 compared to equal quality level). DSA could not detect lesion and feeding artery in 28 and 36% of cases, and allowed clear detection only in 22% and 16%, respectively. In contrast, DVA failed only in 8 and 18% and clearly revealed lesions and feeding arteries in 32 and 26%, respectively. CONCLUSION: In our study, DVA provided higher quality images and better diagnostic insight than DSA; therefore, DVA could represent a useful tool in liver TACE interventions. LEVEL OF EVIDENCE: III Non-consecutive study.

Fluorescence-guided lung nodule identification during minimally invasive lung resections.

In the last few years, minimally invasive surgery has become the standard routine practice to manage lung nodules. Particularly in the case of robotic thoracic surgery, the identification of the lung nodules that do not surface on the visceral pleura could be challenging. Therefore, together with the evolution of surgical instruments to provide the best option in terms of invasiveness, lung nodule localization techniques should be improved to achieve the best outcomes in terms of safety and sensibility. In this review, we aim to overview all principal techniques used to detect the lung nodules that do not present the visceral pleura retraction. We investigate the accuracy of fluorescence guided thoracic surgery in nodule detection and the differences among the most common tracers used.

Cone-Beam CT-Guided Transarterial Tagging of Endophytic Renal Tumors with Indocyanine Green for Robot-Assisted Partial Nephrectomy.

PURPOSE: To evaluate the safety, efficacy, and clinical impact of preoperative cone-beam computed tomography (CT)-guided selective embolization of endophytic renal tumors with the fluorescent dye indocyanine green (ICG) and ethiodized oil in patients undergoing robot-assisted partial nephrectomy (RAPN) using near-infrared fluorescence imaging (NIR-FI). MATERIALS AND METHODS: Patients with renal endophytic tumors eligible for RAPN and transarterial embolization with ICG and ethiodized oil were prospectively enrolled. Technical success was defined as the completion of the embolization procedure. Radiographic success, defined as ethiodized oil accumulation in the nodule, was classified as poor, moderate, good, or optimal on the basis of postembolization cone-beam CT. Surgical visibility of the tumors during RAPN with the use of NIR-FI was classified as follows: (a) not visible, (b) visible with poorly defined margins, and (c) visible with well-defined margins. RESULTS: Forty-one patients underwent preoperative selective embolization. Technical success was 100%. Ethiodized oil accumulation on cone-beam CT was poor in 2 (4.9%), moderate in 6 (14.6%), good in 25 (61.0%), and optimal in 8 (19.5%) of 41 patients. During RAPN with NIR-FI, tumors were visible with well-defined margins in 26 (63.4%), visible with blurred margins in 14 (34.1%), and not visible in 1 (2.4%) of 41 cases. There were no adverse events following endovascular embolization. CONCLUSIONS: Preoperative transarterial superselective embolization of endophytic renal tumors with ICG and ethodized oil in patients undergoing RAPN is safe and effective, allowing accurate intraoperative visualization and resection of endophytic tumors.

In Vivo Comparison of Micro-Balloon Interventions (MBI) Advantage: A Retrospective Cohort Study of DEB-TACE Versus b-TACE and of SIRT Versus b-SIRT.

PURPOSE: The purpose of this study was to evaluate in vivo the role of the micro-balloon by comparing trans-arterial chemoembolization (DEB-TACE) and selective internal radiotherapy (SIRT) procedures performed with and without balloon micro-catheter (b-DEB-TACE and DEB-TACE/SIRT and b-SIRT) for the treatment of hepatocellular carcinoma (HCC). METHODS: The impact of a balloon micro-catheter on trans-arterial loco-regional treatment was analyzed using non-enhanced post-procedural cone-beam CT (Ne-CBCT) by comparing the attenuation values in the embolized area and the surrounding liver tissue before and after DEB-TACE versus b-DEB-TACE and by comparing 2D/3D dosimetry in single-photon emission computed tomography after SIRT versus b-SIRT, and by comparing the histological count of the beads following orthotopic liver transplantation in the DEB-TACE versus b-DEB-TACE subgroup. RESULTS: We treated 84 HCC patients using trans-arterial loco-regional therapy. Fifty-three patients (26 DEB-TACE and 27 b-DEB-TACE) were analyzed in the TACE group. Contrast, signal-to-noise ratio, and contrast-to-noise ratio were all significantly higher in b-DEB-TACE subgroup than DEB-TACE (182.33 HU [CI95% 160.3-273.5] vs. 124 HU [CI95% 80.6-163.6]; 8.3 [CI95% 5.7-10.1] vs. 4.5 [CI95% 3.7-6.0]; 6.9 [CI95% 4.3-7.8] vs. 3.1 [CI95% 2.2-5.0] p < 0.05). Thirty-one patients (24 SIRT and 7 b-SIRT) were analyzed in the SIRT group. 2D dosimetry profile evaluation showed an activity intensity peak significantly higher in the b-SIRT than in the SIRT subgroup (987.5 ± 393.8 vs. 567.7 ± 302.2, p = 0.005). Regarding 3D dose analysis, the mean dose administered to the treated lesions was significantly higher in the b-SIRT than in the SIRT group (151.6 Gy ± 53.2 vs. 100.1 Gy ± 43.4, p = 0.01). In histological explanted liver analysis, there was a trend for higher intra-tumoral localization of embolic microspheres for b-DEB-TACE in comparison with DEB-TACE. CONCLUSIONS: Due to the use of three different methods, the results of this study demonstrate in vivo, a better embolization profile of oncological intra-arterial interventions performed with balloon micro-catheter regardless of the embolic agent employed.

Sarcopenia Worsening One Month after Transarterial Radioembolization Predicts Progressive Disease in Patients with Advanced Hepatocellular Carcinoma.

(1) Background: To demonstrate correlation between skeletal muscle depletion measured before and after one month of TARE treatment and its induced local response rate. (2) Material and methods: For this retrospective, single center study, we evaluated 86 patients with HCC treated with TARE. Sarcopenia status was measured using the psoas muscle index (PMI). The PMI was calculated according to the formula: PMI [mm/m2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter of right psoas + major diameter of right psoas)/4]/height in m2. Population was divided in two groups according to the delta value of PMI measured at the time of TARE and one month after TARE, a group in which the delta PMI was stable or increased (No-Sarcopenia group; n = 42) vs. a group in which the delta-PMI decreased (Sarcopenia group; n = 44). Patient response was evaluated at 1, 3 and 6 months after TARE treatment with CT/MRI. (3) Results: When the radiological response of the tumor was evaluated according to the mRECIST criteria, the two groups were similar in terms of rates of complete response (p = 0.42), partial response (p = 0.26) and stable disease (p = 0.59). Progressive disease (PD) was more commonly observed in the Sarcopenia group (38.6% vs. 11.9%; p = 0.006). (4) Conclusions: Worsening of sarcopenia status measured one month after TARE is able to predict patients who will undergo disease progression.

Yttrium-90 Radioembolization in Unresectable Intrahepatic Cholangiocarcinoma: Results of a Multicenter Retrospective Study.

BACKGROUND: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). MATERIALS AND METHODS: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8 years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. RESULTS: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5 months (95% CI: 11.1-16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. CONCLUSION: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.

Transnephrostomic Indocyanine Green-Guided Robotic Ureteral Reimplantation for Benign Ureteroileal Strictures After Robotic Cystectomy and Intracorporeal Neobladder: Step-By-Step Surgical Technique, Perioperative and Functional Outcomes.

Objectives: To describe our surgical technique of robotic ureteroileal reimplantation (RUIR) for ureteroileal anastomosis strictures with the use of near-infrared fluorescence imaging (NIFI) after transnephrostomic antegrade injection of indocyanine green in patients previously treated with robot-assisted radical cystectomy and intracorporeal orthotopic neobladder. Materials and Methods: From March 2015 to December 2017, 10 consecutive patients underwent RUIR in our tertiary referral center. All patients previously underwent percutaneous nephrostomy and at least one antegrade stenting and stricture dilatation attempt. Clinical data were prospectively collected into our institutional dataset. Both perioperative and functional outcomes were assessed. Results: Median time from robotic cystectomy to ureteroileal anastomosis strictures diagnosis was 5 months (interquartile range [IQR] 2-6). Median stricture length was 1.5 cm (IQR 1-2). Median operative time was 140 minutes (IQR 81-155), and median length of stay was 5 days (IQR 3-9). Two patients experienced Clavien grade 2 complications (urinary tract infection requiring antibiotics and blood transfusion, respectively). One patient underwent ileum resection and anastomosis due to bowel perforation (Clavien IIIb). At a median follow-up of 19 months (IQR 14-39), one patient developed a stricture recurrence. No patient developed worsening of renal function (newly onset chronic kidney disease stage 3b-4). Conclusions: Robotic reimplantation for ureteroileal anastomosis strictures is a safe and highly effective procedure, with a high success rate and excellent perioperative and functional outcomes. NIFI provides an easy guide to identify and progressively dissect the ureter.

Metachronous Isolated Splenic Metastasis in a Young Patient With Renal Cell Carcinoma: Case Report and Literature Review.

Splenic metastasis is uncommon and is usually associated with widespread disease.1,2 Isolated splenic metastases from renal cancer are also rarer and are often an incidental finding. This eventuality may turn into a dangerous scenario due to a spontaneous splenic rupture leading to sudden death.2,3 At the best of our knowledge, only few cases of metastasis from renal cell carcinoma (RCC) have been documented in the literature.4-11 We hereby present a literature review of these cases and report a case of isolated splenic metastasis in a young man on active follow-up for a clear cell RCC clear cell Renal Cell Carcinoma (ccRCC).

"Ride the Green Light": Indocyanine Green-marked Off-clamp Robotic Partial Nephrectomy for Totally Endophytic Renal Masses.

BACKGROUND: Complexity of robot-assisted partial nephrectomy (RAPN) mostly depends on tumor size and location. Totally endophytic renal masses represent a surgical challenge in terms of both intraoperative identification and anatomical dissection. OBJECTIVE: To detail a novel technique for marking preoperatively endophytic renal tumors with transarterial superselective intrarenal mass delivery of indocyanine green (ICG)-lipiodol mixture, in order to enhance surgical margins control during purely off-clamp (OC) RAPN with the use of near-infrared fluorescence imaging. DESIGN, SETTING, AND PARTICIPANTS: Between June and July 2017, 10 consecutive patients with totally endophytic renal masses underwent preoperative ICG tumor marking immediately followed by RAPN. SURGICAL PROCEDURE: Preoperative superselective transarterial delivery of a lipiodol-ICG mixture (1:2 volume ratio) into tertiary-order arterial branches feeding the renal mass prior to transperitoneal OC-RAPN. MEASUREMENTS: Clinical data were prospectively collected in our institutional RAPN dataset. Perioperative, pathological, and functional outcomes of RAPN were assessed. RESULTS AND LIMITATIONS: Median tumor size was 3cm (interquartile range 2.3-3.8). The median PADUA score was 10 (9-11). Angiographic procedure was successful in all patients. Median operative time was 75min (65-85); median estimated blood loss was 250ml (200-350). No conversion to on-clamp PN or radical nephrectomy was needed. All patients had uneventful perioperative course; median hospital stay was 3 d (2-3). At discharge, median hemoglobin (Hgb) and percent estimated glomerular filtration rate (eGFR) drop were 3.3g/dl (2.1-3.3) and 11% (10-20%), respectively. Surgical margins were negative in all cases. One-year median ipsilateral renal volume and 1-yr eGFR percent decreases were 11.7% (6-20.9%) and 12.2% (5.3-13.7%), respectively. CONCLUSIONS: We described a novel technique to simplify challenging RAPN based on ICG superselective transarterial tumor marking. Key benefits include quick intraoperative identification of the mass with improved visualization and real-time control of resection margins. PATIENT SUMMARY: Robot-assisted partial nephrectomy (RAPN) for totally endophytic renal masses is a technically demanding surgical procedure, sometimes requiring radical nephrectomy. This novel technique significantly simplified surgical complexity in our Institution. Further studies with larger cohorts are warranted to confirm whether this technique provides relevant intraoperative and functional advantages.

Robotic Intracorporeal Padua Ileal Bladder: Surgical Technique, Perioperative, Oncologic and Functional Outcomes.

BACKGROUND: Robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction is a challenging procedure. The need for surgical skills and the long operative times have led to concern about its reproducibility. OBJECTIVE: To illustrate our technique for RARC and totally intracorporeal orthotopic Padua ileal bladder. DESIGN, SETTING, AND PARTICIPANTS: From August 2012 to February 2014, 45 patients underwent this technique at a single tertiary referral centre. SURGICAL PROCEDURE: RARC, extended pelvic lymph node dissection, and intracorporeal partly stapled neobladder. Surgical steps are demonstrated in the accompanying video. MEASUREMENTS: Demographics, clinical, and pathological data were collected. Perioperative, 2-yr oncologic and 2-yr functional outcomes were reported. RESULTS AND LIMITATIONS: Intraoperative transfusion or conversion to open surgery was not necessary in any case and intracorporeal neobladder was successfully performed in all 45 patients. Median operative time was 305min (interquartile range [IQR]: 282-345). Median estimated blood loss was 210ml (IQR: 50-250). Median hospital stay was 9 d (IQR: 7-12). The overall incidence of perioperative, 30-d and 180-d complications were 44.4%, 57.8%, and 77.8%, respectively, while severe complications occurred in17.8%, 17.8%, and 35.5%, respectively. Two-yr daytime and night-time continence rates were 73.3% and 55.5%, respectively. Two-yr disease free survival, cancer specific survival, and overall survival rates were 72.5%, 82.3%, and 82.4%, respectively. The small sample size and high caseload of the centre might affect the reproducibility of these results. CONCLUSIONS: Our experience supports the feasibility of totally intracorporeal neobladder following RARC. Operative times and perioperative complication rates are likely to be reduced with increasing experience. PATIENT SUMMARY: We report the outcomes of our first 45 consecutive patients who underwent robot-assisted radical cystectomy with intracorporeal neobladders. Perioperative, oncologic, and functional outcomes support this technique as a feasible and safe surgical option in tertiary referral centres.

Impact of 3D Rotational Angiography on Liver Embolization Procedures: Review of Technique and Applications.

In the last years, the interest into interventional applications of C-arm cone-beam CT (CBCT) progressively raised, widening its clinical application from the original field of interventional neuroradiology to the field of peripheral procedures. Liver embolization procedures, due to their complexity and potential treatment-related life-threatening complications, represent one of the main clinical applications of this novel angiographic technique. CBCT has been demonstrated to render procedures safer and technically easier, and to predict outcome as well as to avoid major complications in different treatment scenarios (trans-arterial embolization, trans-arterial chemoembolization, selective internal radiation therapy, percutaneous portal vein embolization). This review summarizes all technical, dosimetric and procedural aspects of CBCT techniques, underlying all its potential clinical advantages in the field of liver embolization procedures. Moreover, the paper provides all the instructions to obtain the best diagnostic performance out of this novel angiographic technique.

Dose evaluation for skin and organ in hepatocellular carcinoma during angiographic procedure.

PURPOSE: The purpose of this study is to evaluate the radiation dose in patients undergoing liver angiographic procedure and verify the usefulness of different dose measurements to prevent deterministic effects. Gafchromic film, MicroMOSFET data and DIAMENTOR device of the X-ray system were used to characterize the examined interventional radiology (IR) procedure. MATERIALS AND METHODS: A liver embolization procedure, the SIRT (Selective Internal Radiation Therapy), was investigated. The exposure parameters from the DIAMENTOR as well as patient and geometrical data were registered. Entrance skin dose map obtained using Gafchromic film (ESDGAF) in a standard phantom as well as in 12 patients were used to calculate the maximum skin dose (MSDGAF). MicroMOSFETs were used to assess ESD in relevant points/areas. Moreover, the maximum value of five MicroMOSFETs array, due to the extension of treated area and to the relative distance of 2-3 cm of two adjacent MicroMOSFETs, was useful to predict the MSD without interfering with the clinical practice. PCXMC vers.1.5 was used to calculate effective dose (E) and equivalent dose (H). RESULTS: The mean dose-area product (DAPDIAMENTOR) for SIRT procedures was 166 Gycm2, although a wide range was observed. The mean MSDGAF for SIRT procedures was 1090 mGy, although a wide range was experienced. A correlation was found between the MSDGAF measured on a patient and the DAPDIAMENTOR value for liver embolizations. MOSFET and Gafchromic data were in agreement within 5% in homogeneous area and within 20% in high dose gradient regions. The mean equivalent dose in critical organs was 89.8 mSv for kidneys, 22.9 mSv for pancreas, 20.2 mSv for small intestine and 21.0 mSv for spleen. Whereas the mean E was 3.7 mSv (range: 0.5-13.7). CONCLUSIONS: Gafchromic films result useful to study patient exposure and determine localization and amplitude of high dose skin areas to better predict the skin injuries. Then, DAPDIAMENTOR or MOSFET data could offer real-time methods, as on-line dose alert, to avoid any side effects during liver embolization with prolonged duration.