Imaging and Interventions for Lymphatic and Lymphatic-related Disorders.

The lymphatic system is critical in fluid balance homeostasis. Yet, until recently, lymphatic imaging has been outside of mainstream medicine due to a lack of robust imaging and interventional options. However, during the last 20 years, both clinical lymphatic imaging and interventions have shown dramatic advancement. The key to imaging advancement has been the interstitial delivery of contrast agents through lymphatic-rich tissues. These techniques include intranodal lymphangiography and dynamic contrast-enhanced MR lymphangiography. These methods provide the ability to image and recognize lymphatic anatomy and pathologic conditions. Percutaneous thoracic duct catheterization and embolization became the first widely accepted interventional technique for the management of chyle leaks. Advances in interstitial lymphatic embolization, as well as liver and mesenteric lymphatic interventions, have broadened the scope of possible lymphatic interventions. Also, recent techniques of lymphatic decompression allow for the treatment of a variety of lymphatic disorders. Finally, immunologic studies of central lymphatic fluid reveal the potential of lymphatic interventions on immunity. These advances herald an exciting new chapter for lymphatic imaging and interventions in the coming years.

Curative-Intent Therapies in Localized Hepatocellular Carcinoma.

PURPOSE OF REVIEW: The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvants preparing patients for curative treatment. RECENT FINDINGS: For HCC < 3 cm, percutaneous thermal ablation provides oncologic outcomes similar to surgical resection and is now a recommended first-line therapy in the EASL guidelines. Both ablation and embolization are recommended as bridging therapies for HCC patients awaiting liver transplantation. T3 HCC can be downstaged by embolization to T2, allowing liver transplantation with similar outcomes to patients transplanted within Milan criteria. New and evolving techniques such as SBRT, radiation segmentectomy and lobectomy, and combination therapies show promise but require further prospective data before they can be integrated into treatment algorithms. Combinations of embolic, ablative, and extirpative therapies can increase access to curative-intent treatment of HCC. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location, and underlying liver cirrhosis.

Three-dimensional printing of patient-specific computed tomography lung phantoms: a reader study.

In modern clinical decision-support algorithms, heterogeneity in image characteristics due to variations in imaging systems and protocols hinders the development of reproducible quantitative measures including for feature extraction pipelines. With the help of a reader study, we investigate the ability to provide consistent ground-truth targets by using patient-specific 3D-printed lung phantoms. PixelPrint was developed for 3D-printing lifelike computed tomography (CT) lung phantoms by directly translating clinical images into printer instructions that control density on a voxel-by-voxel basis. Data sets of three COVID-19 patients served as input for 3D-printing lung phantoms. Five radiologists rated patient and phantom images for imaging characteristics and diagnostic confidence in a blinded reader study. Effect sizes of evaluating phantom as opposed to patient images were assessed using linear mixed models. Finally, PixelPrint's production reproducibility was evaluated. Images of patients and phantoms had little variation in the estimated mean (0.03-0.29, using a 1-5 scale). When comparing phantom images to patient images, effect size analysis revealed that the difference was within one-third of the inter- and intrareader variabilities. High correspondence between the four phantoms created using the same patient images was demonstrated by PixelPrint's production repeatability tests, with greater similarity scores between high-dose acquisitions of the phantoms than between clinical-dose acquisitions of a single phantom. We demonstrated PixelPrint's ability to produce lifelike CT lung phantoms reliably. These phantoms have the potential to provide ground-truth targets for validating the generalizability of inference-based decision-support algorithms between different health centers and imaging protocols and for optimizing examination protocols with realistic patient-based phantoms. Classification: CT lung phantoms, reader study.

Abnormal Pulmonary Lymphatic Flow on Novel Lymphangiographic Imaging Supports a Common Etiology of Lymphatic Plastic Bronchitis and Nontraumatic Chylothorax.

Background: This study evaluates whether dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) and thoracic duct lymphangiography (TDL) findings in adults with lymphatic plastic bronchitis (PB) and/or nontraumatic chylothorax (NTC) support a shared pathophysiology. Materials and Results: Retrospective review of clinical and imaging findings in patients who underwent DCMRL and TDL at a single institution from March 2017 to March 2019. Categorical variables were compared with Fisher's exact test. Twenty-eight patients (median age 61 ± 21 years, 15 women) presenting with lymphatic PB (n = 13), NTC (n = 10), or both (n = 5) were included. Lymphatic imaging demonstrated pulmonary lymphatic perfusion (PLP) in all patients. A patent thoracic duct (TD) with retrograde flow was seen in 53.4% (7/13) of patients with PB, 60% (6/10) of patients with NTC, and 20% (1/5) of patients with both (p = 0.69). An occluded TD with retrograde flow was seen in 30.8% (4/13) of patients with PB, 30% (3/10) of patients with NTC, and 80% (4/5) of patients with both (p = 0.12). Similar patterns of PLP between DCMRL and TDL were seen in 96.2% (25/26) of patients. Conclusions: DCMRL and TDL demonstrated similar findings in patients with lymphatic PB and/or NTC, supporting a common etiology. This supports the hypothesis that the clinical presentation depends on the proximity of abnormal lymphatic vessels to the pleural cavity, resulting in chylothorax, or bronchial mucosa, resulting in PB.

CT Features of Lymphatic Plastic Bronchitis in Adults: Correlation with Multimodality Lymphatic Imaging.

Purpose: To distinguish CT patterns of lymphatic and nonlymphatic causes of plastic bronchitis (PB) through comparison with lymphatic imaging. Materials and Methods: In this retrospective study, chest CT images acquired prior to lymphatic workup were assessed in 44 patients with PB from January 2014 to August 2020. The location and extent of ground-glass opacity (GGO) was compared with symptoms and lymphatic imaging. Statistical analysis was performed using descriptive statistics, logistic regression, Pearson correlation coefficient, and unweighted κ coefficient for interobserver agreement. Sensitivity and specificity of GGO for lymphatic PB were calculated. Results: Lymphatic imaging was performed in 44 patients (median age, 52 years ± 21 [IQR]; 23 women): 35 with lymphatic PB and nine with nonlymphatic PB. GGO was more frequently observed in patients with lymphatic PB than in those with nonlymphatic PB (91% [32 of 35] vs 33% [three of nine]; P < .001). Univariate logistic regression confirmed this result by showing that GGO was a significant predictor of lymphatic PB (odds ratio, 21 (95% CI: 3.8, 159.7). The model areas under the receiver operating characteristic curve (AUCs) of GGO unadjusted and adjusted for demographics were 0.79 and 0.86, respectively. The location of GGO correlated with lymphatic imaging and bronchoscopic findings. Overall sensitivity and specificity of GGO for lymphatic PB were 91% (32 of 35; 95% CI: 76, 98) and 67% (six of nine; 95% CI: 30, 93), respectively. Conclusion: Patients with lymphatic PB predominantly had multifocal GGO with or without a "crazy paving" pattern; identification of GGO should prompt lymphatic workup in this frequently misdiagnosed condition.Keywords: Lymphography, Lymphatic, CT, Tracheobronchial Tree, Thorax© RSNA, 2022See also commentary by Kligerman and White in this issue.

Transjugular intrahepatic portosystemic shunt for the management of symptomatic malignant pseudocirrhosis.

Background: Pseudocirrhosis is defined by radiologic changes of the liver parenchyma secondary to metastatic disease and/or cancer treatments, and portends a high rate of morbidity and mortality from sequelae of portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension; however, TIPS is relatively contraindicated in the setting of hepatic metastases. The study aims to determine the technical efficacy and clinical outcomes of patients undergoing TIPS for symptomatic pseudocirrhosis. Methods: Retrospective analysis of patients with hepatic malignancy who underwent TIPS between 2008 and 2020 at a single tertiary care center. Patients with imaging findings of pseudocirrhosis and without history of primary liver malignancy or confounding causes of cirrhosis were included. West Haven scores assessing hepatic encephalopathy were obtained from chart review. Technical success was defined as successful TIPS creation with reduction in the portosystemic gradient (PSG). Clinical success was defined as resolution of variceal bleeding and/or ascites. Results: Nine patients (4 female/5 male), average (± SD) age 61.2±9.5 years with metastatic pseudocirrhosis were included for analysis. Primary malignancy was colorectal adenocarcinoma (n=5), neuroendocrine tumor (n=3), and malignant endothelial hemangioendothelioma (n=1). Average Model for End Stage Liver Disease (MELD-Na) score was 15.7±3.7. Technical success was 8/9 (89%) with average PSG reduced from 23.5±11.0 to 6.5±2.8 mmHg (P=0.001). Clinical success was 6/9 (67%). Two patients required TIPS revision after initial clinical success. Mild-moderate HE occurred in 6/9 patients post TIPS (67%), with a highest West Haven score of 2. Time from TIPS to death for acute variceal bleeding and ascites was 4.9±4.2 and 12±16.5 months, respectively. Cause of death was disease progression (n=5), variceal bleeding (n=1), or unavailable (n=2). Conclusions: TIPS in the setting of malignant pseudocirrhosis can be created safely with similar clinical outcomes to TIPS performed for benign disease. Rates of low-grade hepatic encephalopathy may be higher amongst patients undergoing TIPS for pseudocirrhosis.

Liver-directed therapy for hepatocellular carcinoma.

The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location and underlying liver cirrhosis. Surgical resection of anatomically limited tumors with adequate hepatic reserve provides long-term survival in more than half of patients and remains a standard first-line therapy. Eligibility for resection among newly diagnosed patients is low and recurrences in the remaining cirrhotic liver are common. Transplantation offers a higher chance of cure. Long wait times for the limited door pool require neoadjuvant loco-regional therapies to maintain transplant eligibility. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvant preparing patients for curative treatment. Percutaneous ablation in appropriately selected patients offers long-term survival similar to resection. New and evolving techniques such as stereotactic body radiotherapy (SBRT), radiation segmentectomy and lobectomy, and combination therapies employing both trans-arterial and ablative approaches show promise for curative-intent treatment but require further prospective data before they can be integrated into treatment algorithms. For palliativeintent therapy, conventional trans-arterial chemoembolization with lipiodol-based emulsions remains the only technique supported by clinical trials. Newer platforms such as drug-eluting embolics failed to improve survival over bland embolization in randomized trials and showed increased hepatobiliary toxicity. Transarterial radioembolization offers similar overall survival (OS) to transarterial chemoembolization (TACE) and non-inferiority to sorafenib in meta-analyses. The more favorable clinical toxicity profile makes it an appealing technique for patients willing to accept the longer time to response.

99mTc-Mebrofenin SPECT/CT in Hepatic Infarction.

A 68-year-old man with hereditary hypercoagulability was referred to nuclear medicine for elevated aminotransferases after a recent living-donor liver transplant. A hepatic infarction was suspected. A Tc-mebrofenin SPECT/CT was performed and showed decreased radiotracer uptake in a wedge-shaped distribution in the anterior liver suggestive of a hepatic infarction. Subsequently, an enhanced MRI corroborated the diagnosis. Oral anticoagulation therapy was then initiated, and aminotransferases soon normalized.

Early Interleukin-22 and Neutrophil Proteins Are Correlated to Future Lung Damage in Children With Cystic Fibrosis.

Cystic Fibrosis (CF) lung damage begins early in life. Lung function decline is associated with pulmonary infections, neutrophil infiltration and inflammation. In CF, neutrophils have an altered phenotype. In this pilot study, we aimed to determine if signals of dysfunctional neutrophil responses were evident early in life and whether these signals may be associated with lung damage in later childhood. We examined the pulmonary protein profiles of 14 clinical stable infants and pre-school children with CF employing the aptamer-based affinity platform, SOMAscan®. High resolution computed tomography (HRCT) was performed on all children after age 6 years and Brody score calculated. A Spearman's rank order correlation analysis and Benjamini-Hochberg adjustment was used to correlate protein concentrations in early life to Brody scores in later childhood. Early life concentrations of azurocidin and myeloperoxidase, were positively correlated with Brody score after age 6 (p = 0.0041 and p = 0.0182, respectively). Four other neutrophil associated proteins; Complement C3 (p = 0.0026), X-ray repair CCP 6 (p = 0.0059), C3a anaphylatoxin des Arginine (p = 0.0129) and cytokine receptor common subunit gamma (p = 0.0214) were all negatively correlated with Brody scores. Interestingly, patients with more severe lung damage after age 6 had significantly lower levels of IL-22 in early years of life (p = 0.0243). IL-22 has scarcely been reported to have implications in CF. Identification of early biomarkers that may predict more severe disease progression is particularly important for the future development of early therapeutic interventions in CF disease. We recommend further corroboration of these findings in prospective validation studies.

Interventional Oncology Approach to Hepatic Metastases.

Metastatic liver disease is one of the major causes of cancer-related morbidity and mortality. Locoregional therapies offered by interventional oncologists alleviate cancer-related morbidity and in some cases improve survival. Locoregional therapies are often palliative in nature but occasionally can be used with curative intent. This review will discuss important factors to consider prior to palliative and curative intent treatment of metastatic liver disease with locoregional therapy. These factors include those specific to the tumor, liver function, liver reserve, differences between treatment modalities, and patient-specific considerations.

Single-institution experience with selective internal radiation therapy (SIRT) for the treatment of unresectable colorectal liver metastases.

BACKGROUND: Liver metastases are the commonest cause of death for patients with colorectal cancer. Growing evidence supports the use of selective internal radiation therapy (SIRT) in combination with conventional chemotherapy regimens for liver-only or liver-dominant unresectable metastatic colorectal cancer. AIMS: To measure and evaluate outcomes of the first 20 consecutive patients with unresectable colorectal liver metastasis selected for SIRT in addition to their chemotherapy at a single Irish institution. METHODS: Retrospective case series was performed. Patient charts and medical records were reviewed. RESULTS: All 20 patients (100%) selected for angiographic workup were subsequently successfully treated with radioembolization. All patients were discharged 1 day post-SIRT. At initial imaging evaluation, 12 (60%) had a partial response in their liver, 2 (10%) had stable disease, and 6 (30%) had liver-specific progressive disease. Median follow up was 10 months (range 6-26). At last follow up, 14 (70%) patients were alive and 6 (30%) deceased. Most recent imaging demonstrated 2 (10%) with a complete response, 7 (35%) had a partial response, 2 (10%) had stable disease, and 9 (45%) had progressive disease within their liver. One patient was downstaged to hepatic resection, and one with a complete hepatic response had his primary sigmoid tumor resected 11 months post-SIRT. CONCLUSIONS: SIRT is a safe and effective therapy for certain patients with unresectable colorectal liver metastases. This case series supports our opinion that selected patients should be offered SIRT in concert with their medical oncologist, concomitant with their chemotherapy. Larger multi-center studies are required to more clearly define the patient groups that will derive most benefit from SIRT.