Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

PURPOSE: Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. MATERIALS AND METHODS: This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. RESULTS: No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). CONCLUSION: There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

A Possible Newly Defined and Treatable Secondary Cause of Early Morning Wake-Up Headaches in an Older Hypermobile Woman: Nutcracker Physiology with Spinal Epidural Venous Congestion.

Introduction: Left renal vein compression (nutcracker physiology) with secondary spinal epidural venous congestion is a newly recognized cause of daily persistent headache. Presently, only women with underlying symptomatic hypermobility issues appear to develop headache from this anatomic issue. The hypothesized etiology is an abnormal reset of the patient's cerebrospinal fluid (CSF) pressure to an elevated state. Headaches that occur during sleep can have a varied differential diagnosis, one of which is elevated CSF pressure. We present the case of an older woman who began to develop severe wake-up headaches at midnight. She was found to have left renal vein compression and spinal epidural venous congestion on imaging. After treatment with lumbar vein coil embolization, which alleviated the spinal cord venous congestion, her headaches alleviated. Case Report: A 61-year-old woman with a history of hypermobile Ehlers-Danlos syndrome began to be awakened with severe head pain at midnight at least several times per week. The headache was a holocranial, pressure sensation, which worsened in the supine position. The headaches were mostly eliminated with acetazolamide. Because of her hypermobility issues and pressure-like headache, she was investigated for underlying nutcracker physiology and spinal epidural venous congestion. This was confirmed using magnetic resonance (MR) angiography and conventional venography, and after lumbar vein coil embolization her wake-up headaches ceased. Conclusion: The case report suggests a possible new underlying and treatable cause for early morning, wake-up headaches: nutcracker physiology with secondary spinal epidural venous congestion. The case expands on the clinical headache presentation of nutcracker physiology.

Radiation Segmentectomy for the Treatment of Hepatocellular Carcinoma: A Practical Review of Evidence.

Radiation segmentectomy is a versatile, safe, and effective ablative therapy for early-stage hepatocellular carcinoma. Advances in radiation segmentectomy patient selection, procedural technique, and dosimetry have positioned this modality as a curative-intent and guideline-supported treatment for patients with solitary HCC. This review describes key radiation segmentectomy concepts and summarizes the existing literary knowledgebase.

Abscopal downstaging of intermediate stage hepatocellular via combination cryoablation and immunotherapy with complete pathologic response.

The abscopal effect is a rare phenomenon characterized by disease regression in distant sites after tumoral locoregional therapy. Locoregional therapy, such as cryoablation, can induce an antitumor immunological response, potentially improving outcomes in cancer patients receiving immunotherapy. This report describes a patient with multifocal hepatocellular carcinoma who progressed through multiple locoregional therapies, was initially unresponsive to immunotherapy, and later achieved rapid and sustained disease regression with a combination cryoablation and immunotherapy. A 5-year sustained complete tumor response successfully bridged to liver transplantation.

A secondary daily persistent headache from onset with underlying nutcracker physiology and spinal epidural venous congestion: case series with lumbar vein embolization as a therapeutic approach.

The authors have published on a unique subset of patients whose headaches worsened in the Trendelenburg position and who on time-resolved MR angiography demonstrated left renal vein compression (nutcracker physiology) with retrograde left second lumbar vein (L2LV) flow and regional spinal epidural venous plexus (EVP) congestion. We hypothesized that the spinal EVP congestion subsequently causes a secondary congestion of the cerebral venous system, which then leads to an elevation of CSF pressure above that individuals CSF pressure set point. This results in a daily headache from onset. Thus, eliminating the spinal EVP could conceivably improve or eliminate the manifested headache syndrome. We now present a case series of four patients with long-term follow-up utilizing lumbar vein coil embolization as a new therapeutic approach. In each patient, the MR angiography findings were verified by catheter-based venography. Treatment consisted of endovascular embolization of the second lumbar vein. Four patients have had coil embolization of which three are 1 year or longer from their procedure while one is 10 months posttreatment. All patients were women. Duration of daily headache prior to embolization ranged from 4 to 8 years. Post-embolization: Three patients are either headache free or 90-95% improved with substantial pain free time. There were no procedure-related complications. Our results suggest that embolization of L2LV in a specific patient population with nutcracker physiology may substantially improve head pain issues. This is a minimally invasive outpatient technique with no apparent side effects.

Evaluating the Performance of a Commercially Available Artificial Intelligence Algorithm for Automated Detection of Pulmonary Embolism on Contrast-Enhanced Computed Tomography and Computed Tomography Pulmonary Angiography in Patients With Coronavirus Disease 2019.

Objective: To investigate the performance of a commercially available artificial intelligence (AI) algorithm for the detection of pulmonary embolism (PE) on contrast-enhanced computed tomography (CT) scans in patients hospitalized for coronavirus disease 2019 (COVID-19). Patients and Methods: Retrospective analysis was performed of all contrast-enhanced chest CT scans of patients admitted for COVID-19 between March 1, 2020 and December 31, 2021. Based on the original radiology reports, all PE-positive examinations were included (n=527). Using a reversed-flow single-gate diagnostic accuracy case-control model, a randomly selected cohort of PE-negative examinations (n=977) was included. Pulmonary parenchymal disease severity was assessed for all the included studies using a semiquantitative system, the total severity score. All included CT scans were sent for interpretation by the commercially available AI algorithm, Aidoc. Discrepancies between AI and original radiology reports were resolved by 3 blinded radiologists, who rendered a final determination of indeterminate, positive, or negative. Results: A total of 78 studies were found to be discrepant, of which 13 (16.6%) were deemed indeterminate by readers and were excluded. The sensitivity and specificity of AI were 93.2% (95% CI, 90.6%-95.2%) and 99.6% (95% CI, 98.9%-99.9%), respectively. The accuracy of AI for all total severity score groups (mild, moderate, and severe) was high (98.4%, 96.7%, and 97.2%, respectively). Artificial intelligence was more accurate in PE detection on CT pulmonary angiography scans than on contrast-enhanced CT scans (P<.001), with an optimal Hounsfield unit of 362 (P=.048). Conclusion: The AI algorithm demonstrated high sensitivity, specificity, and accuracy for PE on contrast-enhanced CT scans in patients with COVID-19 regardless of parenchymal disease. Accuracy was significantly affected by the mean attenuation of the pulmonary vasculature. How this affects the legitimacy of the binary outcomes reported by AI is not yet known.

Ablative radioembolization of hepatocellular carcinoma with total arterial supply originating from the superior adrenal artery achieved complete pathologic necrosis.

Exclusively extrahepatic arterial perfusion to previously untreated, early-stage, hepatocellular carcinoma (HCC) is uncommon. We present a case of right superior adrenal artery completely supplying a subcapsular HCC in a 68-year-old male. The extrahepatic arterial territory targeted excluded structures potentially vulnerable to radiation, which allowed safe ablative Y-90 radioembolization that achieved complete pathological necrosis.

Promoting Surgical Resection through Future Liver Remnant Hypertrophy.

An inadequate future liver remnant (FLR) can preclude curative-intent surgical resection for patients with primary or secondary hepatic malignancies. For patients with normal baseline liver function and without risk factors, an FLR of 20% is needed to maintain postsurgical hepatic function. However, the FLR requirement is higher for patients who are exposed to systemic chemotherapy (FLR, >30%) or have cirrhosis (FLR, >40%). Interventional radiologic and surgical methods to achieve FLR hypertrophy are evolving, including portal vein ligation, portal vein embolization, radiation lobectomy, hepatic venous deprivation, and associating liver partition and portal vein ligation for staged hepatectomy. Each technique offers particular advantages and disadvantages. Knowledge of these procedures can help clinicians to choose the suitable technique for each patient. The authors review the techniques used to develop FLR hypertrophy, focusing on technical considerations, outcomes, and the advantages and disadvantages of each approach. Online supplemental material is available for this article. ©RSNA, 2022.

Daily persistent headache with nutcracker physiology and spinal epidural venous congestion: Treatment with lumbar vein embolization.

Nutcracker phenomenon (NCP) can cause various congestion syndromes secondary to the superior mesenteric artery (SMA) compressing the left renal vein (LRV) resulting in venous reflux. It has recently been suggested that reflux into the lumbar vein (LV) and epidural venous plexus (EVP) may cause headaches in some patients with NCP. This report illustrates an example of a patient with refractory headaches and imaging findings suggestive of NCP that underwent treatment with percutaneous LV embolization. The patient is a 60-year-old female with daily persistent headaches for 5 years that failed numerous headache preventative medications. Time-resolved magnetic resonance angiography demonstrated NCP with reflux and congestion of the LV and EVP. Catheter-based venography confirmed these findings and the patient was treated with percutaneous embolization of the LV. This case report demonstrates the use of LV embolization to prevent EVP reflux and treat daily headaches due to NCP. The patient's headache resolved the next day. She has been headache-free for 5 months post-treatment. These findings support prior data suggesting that NCP can cause retrograde LV flow, EVP congestion, and elevated cerebrospinal fluid pressures leading to daily persistent headaches. Percutaneous embolization of the LV may be a minimally invasive treatment option for refractory headaches in patients with NCP, retrograde LV flow, and EVP congestion.

Radiation Segmentectomy for the Treatment of Primary Hepatic Malignancies of the Caudate Lobe: A Case Series.

PURPOSE: Tumors involving the caudate lobe present a unique therapeutic challenge due to their complex anatomy and the safety and efficacy of locoregional therapy can be variable. The purpose of this study is to analyze the outcomes of radiation segmentectomy for primary caudate lobe tumors. MATERIALS AND METHODS: Eight patients [5 women and 3 men; median age = 69 y (range 50-79)] that underwent transarterial radioembolization (TARE) using yttrium-90 (Y90) glass microspheres for primary caudate lobe tumors (hepatocellular carcinoma = 6, intrahepatic cholangiocarcinoma = 2) from August 2017 to March 2021 were retrospectively analyzed. Descriptive statistics, treatment parameters, tumor response (using modified response evaluation criteria in solid tumors), adverse events [using common terminology criteria for adverse events (CTCAE)], and survival outcomes were evaluated. RESULTS: Eight primary caudate lobe tumors with a median size of 2.2 cm [interquartile range (IQR), 1.7-3.3] and Child-Pugh class A liver function underwent TARE of the caudate lobe. The median radiation dose was 596 Gy (IQR 356-1585), median total activity was 0.84 GBq (IQR 0.56-1.31), median specific activity was 473 Bq/sphere (IQR 226-671), and the median number of Y90 microspheres used was 1.4 million (IQR 1.2-3.4). All complications were CTCAE grade 1, and no clinically significant hilar plate complications were observed. In targeted tumors, complete response was seen in all patients.  At a median follow-up period of 16.6 months (IQR 6.6-21.6) 75% (6/8) of patients were alive with no in-field progression. CONCLUSION: Radiation segmentectomy of primary caudate lobe tumors appears effective and is well tolerated in this limited case series within the described treatment parameters. LEVEL OF EVIDENCE: Level 4, Case Series.

Role of Radioembolization in Metastatic Neuroendocrine Tumors.

The liver is the most common site of metastasis for neuroendocrine tumors originating from the gastrointestinal tract. Neuroendocrine liver metastases (NELMs) portend a worsening clinical course, making local management important. Local treatment options include surgery, thermal ablation, and trans-catheter intra-arterial therapies, such as radioembolization. Radioembolization is generally preferred over other embolotherapies in patients with colonized biliary systems. Current best practice involves personalized treatment planning, optimizing tumor radiation absorbed dose and minimizing radiation to the normal hepatic parenchyma. As part of a multidisciplinary approach, radioembolization is a versatile embolotherapy offering neoadjuvant, palliative, and ablative treatment options for patients with NELMs.

Focal Nodular Hyperplasia and Focal Nodular Hyperplasia-like Lesions.

Focal nodular hyperplasia (FNH) is a benign lesion occurring in a background of normal liver. FNH is seen most commonly in young women and can often be accurately diagnosed at imaging, including CT, MRI, or contrast-enhanced US. In the normal liver, FNH frequently must be differentiated from hepatocellular adenoma, which although benign, is managed differently because of the risks of hemorrhage and malignant transformation. When lesions that are histologically identical to FNH occur in a background of abnormal liver, they are termed FNH-like lesions. These lesions can be a source of diagnostic confusion and must be differentiated from malignancies. Radiologists' familiarity with the imaging appearance of FNH-like lesions and knowledge of the conditions that predispose a patient to their formation are critical to minimizing the risks of unnecessary intervention for these lesions, which are rarely symptomatic and carry no risk for malignant transformation. FNH is thought to form secondary to an underlying vascular disturbance, a theory supported by the predilection for formation of FNH-like lesions in patients with a variety of hepatic vascular abnormalities. These include abnormalities of hepatic outflow such as Budd-Chiari syndrome, abnormalities of hepatic inflow such as congenital absence of the portal vein, and hepatic microvascular disturbances, such as those that occur after exposure to certain chemotherapeutic agents. Familiarity with the imaging appearances of these varied conditions and knowledge of their association with formation of FNH-like lesions allow radiologists to identify with confidence these benign lesions that require no intervention. Online supplemental material is available for this article. ©RSNA, 2022.

Prospective evaluation of lymphatic embolization as part of the treatment in dogs with presumptive idiopathic chylothorax.

OBJECTIVE: To describe the embolization technique and short-term clinical outcome in dogs undergoing lymphatic embolization (LE) as part of treatment for presumptive idiopathic chylothorax (IC). Additionally, to document findings in computed tomography lymphangiography (CTLa) following embolization. STUDY DESIGN: Prospective case series. ANIMALS: Eight client-owned dogs. METHODS: Dogs underwent CTLa followed by thoracic duct ligation (TDL), pericardiectomy (PC) and LE. A mixture of 3:1 lipiodol: n-butyl cyanoacrylate embolic solution was injected through a catheterized mesenteric lymphatic vessel via limited abdominal approach using intraoperative fluoroscopy. CTLa was scheduled for 12 weeks postoperatively, and long-term follow-up was obtained via telephone contact. RESULTS: LE was technically successful in six of the eight dogs; and clinically successful in five of the six dogs. In the unsuccessful dog, a diagnosis of lymphangiosarcoma was determined, and the owners elected for euthanasia. Five dogs who underwent successful LE underwent CTLa at 12 weeks. Complete resolution of pleural effusion occurred in three dogs and scant pleural effusion in two dogs. A robust lymphatic embolus preventing antegrade continuation of radiocontrast was documented in all five dogs. Five of the six dogs that underwent LE, were alive and clinically normal at 358-960 days postoperatively. CONCLUSIONS: LE is a feasible part of treatment for dogs with IC. Additionally, a robust lymphatic embolus and lack of radiocontrast flow past the embolus was documented at 12 weeks following surgery. CLINICAL SIGNIFICANCE: LE has the potential to reduce surgical failure by reducing efferent lymphatic chyle flow, occluding missed lymphatic branches and preventing the development of collateral branches.

Hepatocellular carcinoma radiation segmentectomy treatment intensification prior to liver transplantation increases rates of complete pathologic necrosis: an explant analysis of 75 tumors.

PURPOSE: To verify the correlation between yttrium-90 glass microsphere radiation segmentectomy treatment intensification of hepatocellular carcinoma (HCC) and complete pathologic necrosis (CPN) at liver transplantation. METHODS: A retrospective, single center, analysis of patients with HCC who received radiation segmentectomy prior to liver transplantation from 2016 to 2021 was performed. The tumor treatment intensification cohort (n = 38) was prescribed radiation segmentectomy as per response recommendations identified in a previously published baseline cohort study (n = 37). Treatment intensification and baseline cohort treatment parameters were compared for rates of CPN. Both cohorts were then combined for an overall analysis of treatment parameter correlation with CPN. RESULTS: Sixty-three patients with a combined 75 tumors were analyzed. Specific activity, dose, and treatment activity were significantly higher in the treatment intensification cohort (all p < 0.01), while particles per cubic centimeter of treated liver were not. CPN was achieved in 76% (n = 29) of tumors in the treatment intensification cohort compared to 49% (n = 18) in the baseline cohort (p = 0.013). The combined cohort CPN rate was 63% (n = 47). ROC analysis showed that specific activity ≥ 327 Bq (AUC 0.75, p < 0.001), dose ≥ 446 Gy (AUC 0.69, p = 0.005), and treatment activity ≥ 2.55 Gbq (AUC 0.71, p = 0.002) were predictive of CPN. Multivariate logistic regression demonstrated that a specific activity ≥ 327 Bq was the sole independent predictor of CPN (p = 0.013). CONCLUSION: Radiation segmentectomy treatment intensification for patients with HCC prior to liver transplantation increases rates of CPN. While dose strongly correlated with pathologic response, specific activity was the most significant independent radiation segmentectomy treatment parameter associated with CPN.

Radiation Segmentectomy for the Treatment of Solitary Hepatocellular Carcinoma: Outcomes Compared with Those of Surgical Resection.

PURPOSE: To investigate the outcomes of radiation segmentectomy (RS) versus standard-of-care surgical resection (SR). MATERIALS AND METHODS: A multisite, retrospective analysis of treatment-naïve patients who underwent either RS or SR was performed. The inclusion criteria were solitary hepatocellular carcinoma ≤8 cm in size, Eastern Cooperative Oncology Cohort performance status of 0-1, and absence of macrovascular invasion or extrahepatic disease. Target tumor and overall progression, time to progression (TTP), and overall survival rates were assessed. Outcomes were censored for liver transplantation. RESULTS: A total of 123 patients were included (RS, 57; SR, 66). Tumor size, Child-Pugh class, albumin-bilirubin score, platelet count, and fibrosis stage were significantly different between cohorts (P ≤ .01). Major adverse events (AEs), defined as grade ≥3 per the Clavien-Dindo classification, occurred in 0 patients in the RS cohort vs 13 (20%) patients in the SR cohort (P < .001). Target tumor progression occurred in 3 (5%) patients who underwent RS and 5 (8%) patients who underwent SR. Overall progression occurred in 19 (33%) patients who underwent RS and 21 (32%) patients who underwent SR. The median overall TTP was 21.9 and 29.4 months after RS and SR, respectively (95% confidence interval [CI], 15.5-28.2 and 18.5-40.3, respectively; P = .03). Overall TTP subgroup analyses showed no difference between treatment cohorts with fibrosis stages 3-4 (P = .26) and a platelet count of <150 × 109/L (P = .29). The overall progression hazard ratio for RS versus SR was not significant per the multivariate Cox regression analysis (1.16; 95% CI, 0.51-2.63; P = .71). The median overall survival was not reached for either of the cohorts. Propensity scores were calculated but were too dissimilar for analysis. CONCLUSIONS: RS and SR were performed in different patient populations, which limits comparison. RS approached SR outcomes, with a lower incidence of major AEs, in patients who were not eligible for hepatectomy.

Superior mesenteric venous thrombosis: Endovascular management and outcomes.

BACKGROUND: Superior mesenteric venous thrombosis (SMVT) is a rare but fatal condition that is typically treated initially with anticoagulation therapy, and if this fails, with endovascular interventions. However, due to its rarity, there are not many studies that have explored the effectiveness of anticoagulation and endovascular therapies in treating SMVT. AIM: To evaluate patients diagnosed with SMVT who received endovascular therapy in addition to anticoagulation and report technical and clinical outcomes. METHODS: A retrospective analysis of the patients who underwent endovascular treatment for SMVT at Mayo Clinic from 2000-2019 was performed. Technical success was defined as angiographic improvement in SMV flow after intervention. Primary patency was defined as the interval from reestablishing mesenteric venous flow until the first repeat thrombotic event or need for additional intervention. Secondary patency was defined as successful restoration of flow after repeat intervention until rethrombosis or last follow-up. The adverse events were reported through Clavien-Dindo classification. RESULTS: Twenty-four patients were included for analysis. The median age at intervention was 60 years (35-74 years) and 16 (67%) were men. Nineteen patients presented with acute thrombosis (79.2%) and 5 with chronic thrombosis with acute manifestations (20.8%). The most commonly used endovascular modalities were thrombectomy in 12 patients (50.0%) and catheter-directed thrombolysis in 10 patients (41.7%). Technical success was achieved in 18 patients (75%). The 14-d and 30-d primary patency rates were 88.9% and 83.3%, respectively. Adverse events were reported in two patients (8.3%), one marked as grade IIIB, and 1 death marked as grade V. Five-year overall survival rate was 82% (58%-100%). CONCLUSION: Endovascular intervention with anticoagulation appears to be effective for managing SMVT. This treatment combination may be considered as first-line therapy for SMVT management in select patients.