Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma-A Prospective Feasibility Study.

PURPOSE: To evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: This prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. RESULTS: Twenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9-7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0-33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8-31.0 months) versus 10.7 months (95% CI, 8.0-13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7-20.7 months) versus 37.3 months (95% CI, 16.5-58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. CONCLUSIONS: First-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

Integrating a Disease-Focused Tumor Board as a Delivery-of-Care Model to Expedite Treatment Initiation for Patients With Liver Malignancies.

BACKGROUND: Patients with hepatobiliary malignancies are especially vulnerable to treatment delays. This study sought to evaluate the impact of implementing a new delivery-of-care model centered around a hepatobiliary multidisciplinary tumor board (HB-MTB) and integrated with an optimized patient workflow process to expedite treatment initiation. METHODS: A hybrid type 2 study (effectiveness-implementation) was performed. Implementation measures were examined prospectively using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) approach during 5 years after the HB-MTB program deployment (2015-2020). The primary outcome was effectiveness, measured as time to treatment initiation (TTI) using a before and after design (1 year each). The patients were grouped into before (BP) and after (AP) categories based on date of HB-MTB program implementation. Multivariable Cox and linear regression analyses were performed to examine and compare time to treatment initiation between groups. RESULTS: The HB-MTB program enrolled 2457 patients (reach). The RE-AIM measures were favorable and improved over time (P < 0.01 for all). The median TTI was lower for the AP group than for the BP group (17 vs 24 days; P < 0.01). In the multivariable Cox and linear regressions, treatment in the AP group was associated with a faster TTI (hazard ratio, 1.75; 95 % confidence interval, 1.31-2.35; p < 0.01), and a mean of 13 days faster treatment initiation than the BP group (P < 0.01). CONCLUSIONS: Implementation of an HB-MTB program integrated with an optimized patient workflow was successful and led to faster treatment initiation. This delivery-of-care model can serve as a blueprint to expedite treatment of patients with cancer.

Yttrium-90 Radioembolization for Liver-Dominant Metastatic Prostate Cancer: A Case Series.

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort.

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study.

PURPOSE: To retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease. MATERIALS AND METHODS: This retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months. RESULTS: Median overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5-87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0-86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0-84.1 months). Grade 1-2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1-2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment. CONCLUSIONS: TARE with 90Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.

Partial Splenic Artery Embolization in 35 Cancer Patients: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the safety and efficacy of partial splenic embolization (PSE) in cancer patients with different etiologies of splenomegaly/hypersplenism. MATERIALS AND METHODS: The medical records of 35 cancer patients who underwent 39 PSE procedures were analyzed. The splenomegaly/hypersplenism was due to chemotherapy (n = 17), portal hypertension (n = 10), or hematologic malignancy (n = 8). After the first 11 PSEs, celiac plexus neurolysis, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) were included in the post-procedural management. RESULTS: PSE led to 59 ± 16% (mean ± standard deviation) splenic infarcts. The infarct volume per 1 mL 300-500 µm tris-acryl gelatin microspheres was not significantly different between the chemotherapy-induced group (264 ± 89 cm3) and the portal hypertension group (285 ± 139 cm3) but was significantly higher in the hematology group (582 ± 345 cm3). Platelet count increased from 65.7 ± 19.7 k/µl to a peak platelet count of 221 ± 83 k/µl at 2 weeks after PSE. Patients with a follow-up period of more than 1 year had the most recent platelet count of 174 ± 113 k/µl. Platelet count increase was significantly higher in the chemotherapy-induced group than the portal hypertension group. Adding celiac plexus neurolysis, corticosteroids, and NSAIDs to the post-procedural management resulted in a decreased rate of major complications from 73% to 46% and a decrease in the rate of moderate or severe pain from 92% to 20%. CONCLUSIONS: PSE improved platelet counts in cancer patients despite different etiologies of splenomegaly. The addition of celiac plexus neurolysis, corticosteroids, and NSAIDS to the post-PSE treatment protocol reduced complications. Data from this study could help to predict the amount of 300-500 µm tris-acryl gelatin microspheres required to achieve a planned infarct size.

High-output chyle leak after breast-conserving surgery and sentinel lymph node biopsy.

Postoperative chyle leak is an exceedingly rare complication following breast and axillary surgery. We present the first described case of chyle leak following breast-conserving surgery and sentinel lymph node biopsy. Management should begin with appropriated conservative measures aimed at reduction of lymph production and flow. Intervention is warranted when conservative strategies fail and include sclerotherapy, lymphangiography, embolization, and surgery. Breast surgeons should be mindful of this potential complication when operating in the axilla and be familiar with its stepwise management.

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.

Liver-Directed Embolization for the Long-Term Control of Hypercalcemia of Malignancy in Metastatic Breast Cancer.

Hypercalcemia of malignancy is a common complication of certain types of cancers. No standard therapies exist for the treatment of hypercalcemia secondary to paraneoplastic syndromes that result in the long-term control of serum calcium levels. We report a case of metastatic breast cancer with parathyroid hormone-related protein associated with hypercalcemia of malignancy that was treated with transarterial embolization of the hepatic metastatic lesions.

Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.

Transarterial Yttrium-90 Radioembolization Treatment of Patients with Liver-Dominant Metastatic Renal Cell Carcinoma.

PURPOSE: To evaluate safety and efficacy of transarterial hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: From July 2010 to December 2014, 18 patients with liver-dominant metastatic RCC were treated with yttrium-90 glass microsphere radioembolization. Retrospective review of medical records and imaging studies was performed to evaluate toxicities, treatment response, and overall survival. The median follow-up period from radioembolization treatment was 17.8 months (range, 3-54.4 months). RESULTS: Median overall survival from RCC diagnosis was 64 months (95% confidence interval [CI], 0-144.1 months), from diagnosis of liver metastasis was 29 months (95% CI, 7.2-50.8 months), and from radioembolization treatment was 22.8 months (95% CI, 13.2-32.3 months). After treatment, 10 patients reported grade 1 clinical toxicities, and 8 patients had grade 1 or 2 biochemical toxicities. The best radiographic responses of 17 patients who underwent contrast-enhanced cross-sectional imaging showed complete response in 16 patients and partial response in 1 patient evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The last available imaging of these 17 patients demonstrated complete response in 14 patients, partial response in 1 patient, and progression of disease in 2 patients. Images of a patient who underwent noncontrast CT showed stable disease as best response and stable disease on the last available imaging evaluated by RECIST. CONCLUSIONS: Radioembolization is safe and effective and led to improved hepatic disease control and overall survival in patients with liver-dominant metastatic RCC.

Percutaneous liver-directed therapies of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a hepatobiliary malignancy which can manifest anywhere along the biliary tree. Intrahepatic cholangiocarcinoma occurs in the liver within or beyond the second order bile ducts. The prognosis for patients with intrahepatic cholangiocarcinoma is poor, even when successfully resected there is a very high rate of local recurrence. The available systemic therapies are currently limited and have high rates of toxicity. Percutaneous and transarterial liver-directed therapies can be used to treat intrahepatic cholangiocarcinoma with results comparable to current standard of care systemic therapies in some circumstances. This manuscript will review these the techniques and efficacy of percutaneous and transarterial liver-directed therapies for intrahepatic cholangiocarcinoma.

Safety and utility of transjugular liver biopsy in hematopoietic stem cell transplant recipients.

PURPOSE: Hematopoietic stem cell transplant (HSCT) recipients are at high risk in the setting of percutaneous liver biopsy as a result of comorbid coagulopathy and ascites, and are commonly referred to undergo transjugular liver biopsy. The present study was performed to assess the safety and utility of transjugular liver biopsy in HSCT recipients and to analyze the correlation between corrected hepatic sinusoidal pressure gradient (CHSPG) and pathologic diagnoses. MATERIALS AND METHODS: Data from reports of transjugular liver biopsy procedures, pathology reports, and laboratory values of 141 consecutive HSCT recipients who underwent transjugular liver biopsy with pressure measurement between January 2005 and August 2011 in a single institution were retrospectively reviewed and analyzed. RESULTS: A total of 166 biopsy procedures were performed in 141 patients. Technical success rate was 98.8%. Biopsy was diagnostic in 95.7% of patients. There were three major complications (1.8%), including one death. CHSPG in patients with venoocclusive disease (VOD) was significantly higher (P<.001) than in those without VOD (16.2 mm Hg±9.2 vs 5.6 mm Hg±3.7). A CHSPG of 10 mm Hg or higher was 90.8% specific and 77.3% sensitive for VOD. CONCLUSIONS: The present data show that transjugular liver biopsy is a relatively safe procedure that provides important information for the clinical management of patients with HSCT. Measurement of CHSPG during the procedure can support the diagnosis of VOD.

Contemporary management of adult intussusception: who needs a resection?

BACKGROUND: Surgical resection is often recommended in adults with intestinal intussusception (AI) because of its potential association with malignancy. We provide a contemporary algorithm for managing AI by focusing on the probability of discovering a lead point. METHODS: This is a retrospective study of adult patients with computed tomography (CT)-confirmed intussusception who underwent operative management of AI between 1996 and 2011 at a single academic institution. RESULTS: Sixty-four patients were diagnosed with AI by CT scan and then managed operatively. The incidence of colonic (CI), small bowel (SBI), and retrograde intussusception (RI) was 14, 55, and 31 %, respectively. All patients with CI had a lead point, whereas none were found among patients with RI. Some 46 % of patients with SBI had a lead point. The probability of discovering a lead point in SBI was increased by past history of malignancy (RR, 3.7, p < 0.001), a mass seen on preoperative CT scan (RR, 2.9, p = 0.005), and age over 60 years (RR, 2.2, p = 0.07). CONCLUSIONS: A pathologic lead point is likely with CI but not with RI. Patients with SBI who are over the age of 60 years and have a history of malignancy or a mass noted on CT scan have a higher likelihood of harboring a pathologic lead point.

Novel Subdiaphragmatic Ligation of Left Thoracic Duct for Refractory Postoperative Left Chylothorax.

A postoperative chylothorax is an uncommon but problematic surgical complication in 0.5% to 4.0% of surgical cases that nevertheless still plagues every busy thoracic surgeon. Fortunately, most chylothoraces are low volume and are readily controlled by conservative measures. A high-volume chylothorax (>1 L/24 h) fortunately occurs in less than one-third of patients, usually responding to the published treatment algorithms and generally requiring invasive techniques. We report a case of a postlobectomy high-volume, left-sided chylothorax refractory to all the usual recommended interventions that ultimately was successfully treated by novel computed tomography lymphangiography-guided transabdominal surgical ligation of the aberrant left-sided lymphatics with complete, prompt chylothorax control.

Safety of CT-Guided Microwave Ablation of Subcardiac Liver Tumors.

PURPOSE: The purpose of this study was to investigate the safety of CT-guided microwave ablation (MWA) of subcardiac hepatic tumors. MATERIALS AND METHODS: This retrospective study included 19 patients (11 males and 8 females, age: 64.0 years (IQR: 58.3, 71.0) who underwent CT-guided MWA of 22 subcardiac tumors from January 2016 through December 2020. The subcardiac tumors consisted of 6 hepatocellular carcinomas and 16 metastases. Hydrodissection or other thermal protection technique was not used during the ablation. Subcardiac ablation was defined as the ablation zone extended ≤ 0.5 cm from myocardium or coronary artery. The safety of MWA of subcardiac tumors was evaluated based on procedural and post-procedural complications and intra-procedural ECG changes. Local tumor progression (LTP) was also analyzed and correlated with tumor and ablation zone sizes. RESULTS: The primary efficacy rate was 100%. The median follow-up was 20.5 months (IQR: 6.0, 29.8). There was no 30-day mortality. One grade 3 complication occurred (severe shoulder and chest pain), and there were 19 events of grade 1 or 2 complications. No instances of cardiac complications or significant procedural ECG changes were observed. There were 22 events of grade 1 and 2 laboratory toxicity and 1 event of grade 3 elevated bilirubin. The LTP was 13.6% at 1 year and 22.7% at 2 years. There was no significant correlation between LTP and tumor or ablation zone sizes. CONCLUSION: CT-guided MWA of subcardiac hepatic tumors is safe, and MWA should be considered as an option for managing subcardiac tumors. LTP rates for MWA of subcardiac tumors may be inferior to ablation of tumors in common location. LEVEL OF EVIDENCE III: Cohort Study.

Unresectable Intrahepatic Cholangiocarcinoma Treated with Radiation Segmentectomy/Lobectomy Using Yttrium 90-labeled Glass Microspheres.

Background: There is no curative treatment option for patients with unresectable intrahepatic, cholangiocarcinoma (IHC). The aim of this study was to evaluate the efficacy of; radiation segmentectomy/lobectomy using Y90-labeled glass microspheres in patients with; unresectable IHC. Methods: This IRB-approved, single-center study included, 16 patients (age: 67 ± 7.7 years) with IHC who received radiation segmentectomy or lobectomy, treatment using Y90-labeled glass microspheres between May 2009 and October 2019. Radiation, segmentectomy/lobectomy was defined as at least 190 Gy dose delivered into treated liver; volume. Results: The median OS from IHC diagnosis was 22.7 months (95% CI: 13.9-66.1) and from, radioembolization it was 7 months (95% CI: 4.33-54.17). Patients who did not receive, chemotherapy before the radioembolization had significantly longer median OS (26.8 vs. 5.9, months, P = 0.03). Four patients had >20 months survival after radioembolization, including 2, patients with survival of 42 and 54 months. There was no 30-day mortality and no severe, complications. Conclusion: Radiation segmentectomy/lobectomy is safe with minimal side effects. The median, OS of the study group is modest; however, 4 patients (25%) showed excellent survival. These results suggest a need for a larger study to define the IHC patient group who could, most benefit from this procedure.

Transarterial Yttrium-90 Glass Microsphere Radioembolization of Chemotherapy-Refractory Breast Cancer Liver Metastases: Results of a Single Institution Retrospective Study.

PURPOSE: Our purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease. METHODS AND MATERIALS: This retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors. RESULTS: Median overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%. CONCLUSIONS: The treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

A to Z of extraskeletal Ewing sarcoma family of tumors in adults: imaging features of primary disease, metastatic patterns, and treatment responses.

OBJECTIVE: Though classically thought of as an osseous-based sarcoma of children and adolescents, it is important to recognize that approximately 20% of all cases of Ewing sarcoma family of tumors (ESFT) occur in patients older than 18 years, often with extraskeletal disease. Understanding the specific imaging features, manners of presentation, and patterns of behavior of ESFT is therefore important in all settings. CONCLUSION: This article presents the imaging findings of ESFT in the adult, with specific attention to extraskeletal manifestations.