Optimal patient selection for yttrium-90 glass plus chemotherapy in the treatment of colorectal liver metastases: additional quality of life, efficacy, and safety analyses from the EPOCH study.

BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (N = 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEA ≥ 35 ng/mL from both treatment arms; subgroup B (N = 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (N = 143) demonstrated superior outcomes vs Chemo (N = 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided P = .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided P < .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided P = .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided P < .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).

Prognostic Value of Liver Biomarkers in Hepatocellular Carcinoma Patients Undergoing Yttrium 90 Transarterial Radioembolization (TARE): A Retrospective Pilot Study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide. The prognosis for HCC depends on the tumor stage, and curative therapies are more accessible in the early stages. However, effective treatments are available even in advanced stages. Transarterial radioembolization (TARE) is an alternative to transarterial chemoembolization (TACE) with reduced risk and extended disease progression time. Identifying prognostic indicators and treatment response biomarkers remains crucial. The purpose of this study was to assess the association between biomarkers related to fibrosis, liver function, and immune inflammation with tumor response to yttrium 90 transarterial radiotherapy (Y90 or TARE) in patients with HCC. METHODS: This study enrolled patients who underwent Y90 radiotherapy for bridging, downstaging, or palliative treatment after discussion in a multidisciplinary tumor board. Using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), tumor response was classified into two groups: "responders" (complete and partial response) and "non-responders" (stable and progressive disease). Logistic regression analysis was used to evaluate the association between predictors, biomarkers such as aspartate aminotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), albumin-bilirubin (ALBI) score, model for end-stage liver disease (MELD) score, MELD sodium, and the systemic immune-inflammatory indexes, at established cut-offs and tumor response. RESULTS: Of 35 patients, 22 (63%) were Whites and non-Hispanics, 32 (91%) were diagnosed with cirrhosis, and 14 (40%) of these had a viral etiology. According to mRECIST, 18 (51%) patients were classified as "responders." In multivariable logistic regression analysis, biomarkers associated with tumor response were ALBI score ≤-2.8 (odds ratio (OR) 6.1, 95%CI 2.7-14.4) and the neutrophil-to-lymphocyte ratio (NLR) ≤ 1.92 (OR 5.1, 95%CI 0.8-11.9). Biomarkers had moderate accuracy in predicting tumor response (C-statistic 0.75). CONCLUSION: The ALBI score is a reliable predictor of treatment response following TARE. The NLR index may offer further prognostic information, and both biomarkers can be used in combination; however, further research in larger sample sets is needed.

Percutaneous Biliary Interventions via the Modified Hutson Loop in Patients with Biliary-Enteric Anastomoses: A Retrospective Study.

PURPOSE: This study aimed to present the institutional experience and algorithm for performing biliary interventions in liver transplant patients using the modified Hutson loop access (MHLA) and the impact of percutaneous endoscopy via the MHLA on these procedures. METHODS: Over 13 years, 201 MHLA procedures were attempted on 52 patients (45 liver transplants; 24 living and 21 deceased donors) for diagnostic (e.g., cholangiography) and therapeutic (e.g., stent/drain insertion and cholangioplasty) purposes. The most common indications for MHLA were biliary strictures (60%) and bile leaks (23%). Percutaneous endoscopy was used to directly visualize the biliary-enteric anastomosis, diagnose pathology (e.g., ischemic cholangiopathy), and help in biliary hygiene (removing debris/casts/stones/stents) in 138/201 (69%) procedures. Technical success was defined as cannulating the biliary-enteric anastomosis and performing diagnostic/therapeutic procedure via the MHLA. RESULTS: The technical success rate was 95% (190/201). The failure rate among procedures performed with and without endoscopy was 2% (3/138) versus 13% (8/63) (P = 0.0024), and the need for new transhepatic access (to aid the procedure) was 12% (16/138) versus 30% (19/63) (P = 0.001). Despite endoscopy, failure in 2% of the cases resulted from inflamed/friable anastomosis (1/3) and high-grade stricture (2/3) obstructing retrograde cannulation of biliary-enteric anastomosis. Major adverse events (bowel perforation and injury) occurred in 1% of the procedures, with no procedure-related mortality. CONCLUSIONS: MHLA-based percutaneous biliary intervention is a safe and effective alternative to managing complications after liver transplant. Percutaneous endoscopy via the MHLA improves success rates and may reduce the need for new transhepatic access. Level of Evidence Level 4.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing Enteropathy.

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency ablation (RFA) were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease (CHD). Five procedures were performed in 4 patients (M/F = 3/1, median age: 49 years [range 31-71 years]). Transhepatic lymphangiography demonstrated abnormal peri-duodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RFA of the leakage sites followed by PTLE using 3:1 ethiodized oil to n-butyl cyanoacrylate glue resulted in improved symptoms and serum albumin (pre-procedure: 2.6 g/dL ± 0.2; post-procedure: 3.5 g/dL ± 0.4, p=0.004) over a median follow-up of 16 months (range 5-20). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RFA can be considered to treat patients with PLE.

Percutaneous Endoscopy and Image-guided Retrieval of Dropped Gallstones - A Case Series.

BACKGROUND: Recurrent abscesses can happen due to dropped gallstones (DGs) after laparoscopic cholecystectomy (LC). Recognition and appropriate percutaneous endoscopy and image-guided treatment options can decrease morbidity associated with this condition. MATERIALS AND METHODS: We report a minimally invasive endoscopy and image-guided technique for retrieval of dropped gallstones in a series of 6 patients (M/F=3/3; median age: 75.5 years [68 to 82]) presenting with recurrent or chronic intra-abdominal abscesses secondary to dropped gallstones. Technical success was defined as the visualization and retrieval of all stones. DGs were identified on pre-procedure imaging. Number of abscesses recurrence was 12 (1/6), 1 (3/6), and 0 (2/6) with a median interval of 2 months (1 to 21) between cholecystectomy and abscess development. RESULTS: Percutaneous endoscopy and fluoroscopy guidance were utilized in all cases. Technical success was achieved in 4 patients (66%). The median procedure time was 65.8 minutes (39 to 136). The median fluoroscopy time and dose were 12.6 min (3.3 to 67) and 234 mGy (31 to 1457), respectively. There were no intraprocedure and postprocedure complications. No abscess recurrence was reported among successful procedures during a median follow-up of 193 days (51 to 308). CONCLUSION: Percutaneous image and endoscopy-guided lithotripsy/lithectomy are safe and effective. This technique is a suitable alternative to open surgery for dropped gallstones. LEVEL OF EVIDENCE: Level 4, Case Series.

Multicenter Quantification of Radiation Exposure and Associated Risks for Prostatic Artery Embolization in 1476 Patients.

Background Prostatic artery embolization (PAE) is a safe, minimally invasive angiographic procedure that effectively treats benign prostatic hyperplasia; however, PAE-related patient radiation exposure and associated risks are not completely understood. Purpose To quantify radiation dose and assess radiation-related adverse events in patients who underwent PAE at multiple centers. Materials and Methods This retrospective study included patients undergoing PAE for any indication performed by experienced operators at 10 high-volume international centers from January 2014 to May 2021. Patient characteristics, procedural and radiation dose data, and radiation-related adverse events were collected. Procedural radiation effective doses were calculated by multiplying kerma-area product values by an established conversion factor for abdominopelvic fluoroscopy-guided procedures. Relationships between cumulative air kerma (CAK) or effective dose and patient body mass index (BMI), fluoroscopy time, or radiation field area were assessed with linear regression. Differences in radiation dose stemming from radiopaque prostheses or fluoroscopy unit type were assessed using two-sample t tests and Wilcoxon rank sum tests. Results A total of 1476 patients (mean age, 69.9 years ± 9.0 [SD]) were included, of whom 1345 (91.1%) and 131 (8.9%) underwent the procedure with fixed interventional or mobile fluoroscopy units, respectively. Median procedure effective dose was 17.8 mSv for fixed interventional units and 12.3 mSv for mobile units. CAK and effective dose both correlated positively with BMI (R2 = 0.15 and 0.17; P < .001) and fluoroscopy time (R2 = 0.16 and 0.08; P < .001). No radiation-related 90-day adverse events were reported. Patients with radiopaque implants versus those without implants had higher median CAK (1452 mGy [range, 900-2685 mGy] vs 1177 mGy [range, 700-1959 mGy], respectively; P = .01). Median effective dose was lower for mobile than for fixed interventional systems (12.3 mSv [range, 8.5-22.0 mSv] vs 20.4 mSv [range, 13.8-30.6 mSv], respectively; P < .001). Conclusion Patients who underwent PAE performed with fixed interventional or mobile fluoroscopy units were exposed to a median effective radiation dose of 17.8 mSv or 12.3 mSv, respectively. No radiation-related adverse events at 90 days were reported. © RSNA, 2024 See also the editorial by Mahesh in this issue.

Prostatic Artery Embolization in Patients with Refractory Lower Urinary Tract Symptoms after a Prior Minimally Invasive Surgical Treatment.

The purpose of this study was to report on prostatic artery embolization (PAE) outcomes in patients with refractory or recurrent lower urinary tract symptoms (LUTSs) due to benign prostatic hyperplasia (BPH) who had previously undergone a minimally invasive surgical technique (MIST). A single-center retrospective study identified 16 eligible patients. Baseline prostate volume at the time of PAE was 112.9 mL (SD ± 52.7). There were no adverse events throughout the follow-up period. There was significant improvement in International Prostate Symptom Score and quality of life from baseline of 23.5 (SD ± 5.1) and 4.9 (SD ± 0.9), respectively, to the last follow-up of 11.6 (SD ± 7.2) and 2 (SD ± 1.6), respectively. There was nonsignificant improvement in sexual function after PAE compared with baseline after MIST. PAE can be a safe and effective treatment in patients who have undergone prior MIST without negatively impacting erectile or ejaculatory function.

Adverse Events of Surgical Drain Placement: An Analysis of the NSQIP Database.

BACKGROUND: Surgical site drainage is important to prevent hematoma, seroma, and abscess formation. However, the placement of drain placement also predispose patients to several postoperative complications. The aim of this study is to clarify the risk-benefit profile of surgical drain placement. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Procedure-Targeted Databases were used to identify patients who underwent hepatectomy, pancreatectomy, nephrectomy, cystectomy, and prostatectomy. Patients who underwent each procedure were divided into 2 groups based on intraoperative drain placement. Propensity score-matched cohorts of these 2 groups were compared in terms of postoperative adverse events, readmission, reoperation, and length of stay. RESULTS: Hepatectomy patients with drains experienced organ space infections (P < .001), sepsis (P < .001), and readmission (P = .021) more often than patients without drains. Patients who underwent pancreatectomy and had drains placed experienced wound dehiscence less frequently than those without drains (P = .04). For hepatectomy, pancreatectomy, nephrectomy, and prostatectomy populations, patients with drains had longer lengths of stay (P < .05). Matched populations across all procedures did not differ in terms of reoperation rate. DISCUSSION: Prophylactic surgical drain placement may be associated with increased infectious complications and prolonged length of stay. Further studies are needed to elucidate the complete adverse event profile of surgical drains. Nonetheless, outcomes may be improved with better patient selection or advancements in drain technology.

Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma.

PURPOSE: Investigate reproducibility of two segmentation methods for multicompartment dosimetry, including normal tissue absorbed dose (NTAD) and tumour absorbed dose (TAD), in hepatocellular carcinoma patients treated with yttrium-90 (90Y) glass microspheres. METHODS: TARGET was a retrospective investigation in 209 patients with < 10 tumours per lobe and at least one tumour ≥ 3 cm ± portal vein thrombosis. Dosimetry was compared using two distinct segmentation methods: anatomic (CT/MRI-based) and count threshold-based on pre-procedural 99mTc-MAA SPECT. In a round robin substudy in 20 patients with ≤ 5 unilobar tumours, the inter-observer reproducibility of eight reviewers was evaluated by computing reproducibility coefficient (RDC) of volume and absorbed dose for whole liver, whole liver normal tissue, perfused normal tissue, perfused liver, total perfused tumour, and target lesion. Intra-observer reproducibility was based on second assessments in 10 patients ≥ 2 weeks later. RESULTS: 99mTc-MAA segmentation calculated higher absorbed doses compared to anatomic segmentation (n = 209), 43.9% higher for TAD (95% limits of agreement [LoA]: - 49.0%, 306.2%) and 21.3% for NTAD (95% LoA: - 67.6%, 354.0%). For the round robin substudy (n = 20), inter-observer reproducibility was better for anatomic (RDC range: 1.17 to 3.53) than 99mTc-MAA SPECT segmentation (1.29 to 7.00) and similar between anatomic imaging modalities (CT: 1.09 to 3.56; MRI: 1.24 to 3.50). Inter-observer reproducibility was better for larger volumes. Perfused normal tissue volume RDC was 1.95 by anatomic and 3.19 by 99mTc-MAA SPECT, with corresponding absorbed dose RDC 1.46 and 1.75. Total perfused tumour volume RDC was higher, 2.92 for anatomic and 7.0 by 99mTc-MAA SPECT with corresponding absorbed dose RDC of 1.84 and 2.78. Intra-observer variability was lower for perfused NTAD (range: 14.3 to 19.7 Gy) than total perfused TAD (range: 42.8 to 121.4 Gy). CONCLUSION: Anatomic segmentation-based dosimetry, versus 99mTc-MAA segmentation, results in lower absorbed doses with superior reproducibility. Higher volume compartments, such as normal tissue versus tumour, exhibit improved reproducibility. TRIAL REGISTRATION: NCT03295006.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

Portal Vein Recanalization-Transjugular Intrahepatic Portosystemic Shunt (PVR-TIPS) Facilitates Liver Transplantation in Cirrhotic Patients with Occlusive Portal Vein Thrombosis.

Portal vein thrombosis (PVT) is a heterogeneous condition with multiple possible etiologies and to varying degrees has historically limited candidacy for liver transplant (LT) in the cirrhotic patient population due to resultant difficulties in constructing a robust portal vein anastomosis. While intraoperative approaches to managing PVT are well-described, methods which approximate normal portal physiology are not always feasible depending on the extent of PVT, and other nonphysiologic techniques are linked with substantial morbidity and poor long-term outcomes. Portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) creation is an efficacious method of restoring physiologic portal flow in cirrhotic patients prior to LT allowing for end-to-end PV anastomosis, and is the product of decades-long institutional expertise in TIPS/LT and the support of a multidisciplinary liver tumor board. To follow is a review of the pertinent pathophysiology of PVT in cirrhosis, the rationale leading to the development and subsequent evolution of the PVR-TIPS procedure, technical lessons learned, and a summary of outcomes to date.

Evolution of Personalized Dosimetry for Radioembolization of Hepatocellular Carcinoma.

Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that "personalizing" dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed.