Thoracic Complications of Liver-Directed Therapy and Interventions.

ABSTRACT: Liver-directed percutaneous and endovascular therapies are effective methods to diagnose and treat various hepatic disorders and malignancies. Because of the close anatomic proximity of the liver to the right hemidiaphragm, pleura, and lung bases, complications can arise involving these structures. Although they are rare, awareness of intrathoracic complications associated with liver-directed therapies and their imaging features will ensure timely detection and management. We aim to review the clinical and imaging features of thoracic complications related to liver-directed therapy and interventions.

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.

Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres.

PURPOSE: To study the prognostic significance of neutrophil and lymphocyte dynamics in patients with hepatocellular carcinoma (HCC) treated with radioembolization. METHODS: A retrospective, single-center review of clinical records and treatment parameters (liver volume treated, administered activity, and radiation dose) in consecutive patients who received radioembolization for HCC was performed between August 20, 2015, and May 24, 2019. Neutrophil and lymphocyte variables associated with overall survival (OS) were determined by Barcelona Clinic Liver Cancer (BCLC) stage and were correlated with radioembolization treatment parameters. Statistical methods included Wilcoxon signed-rank test, univariate, and multivariate Cox regression analysis; receiver operating characteristic analysis; and the Kaplan-Meier method. RESULTS: One hundred sixty-three patients with a median 67.0 years of age were included for analysis. Eighty-one percent of patients received segmental radioembolization with a median treatment dose of 358 Gray (interquartile range 256-497). The post-treatment lymphocyte count decreased significantly in 94.5 % (p < 0.001) of patients but was not predictive of OS (p = 0.248). The pre-procedure neutrophil to lymphocyte ratio (NLRpre) was not predictive of OS (p = 0.891), and the 1-month post-procedure NLR was a borderline independent predictor of OS (p = 0.05). The NLR ratio (NLRR = NLRpost-procedure/NLRpre) (Hazard ratio [HR], 1.31; 95% Cl, 1.04-1.66) and change in NLR (ΔNLR= NLRpost-procedure - NLRpre) (HR, 1.09; 95% CI, 1.02-1.15) were associated with worse OS in BCLC C patients. NLRR (> 3.17) and ΔNLR (> 3.74) were independent predictors when adjusted for tumor presentation, treatment parameters, and liver function. Volume of liver treated and administered activity positively correlated with NLRR and ΔNLR (p < 0.001). CONCLUSION: A decrease in lymphocyte count is common after radioembolization, but of little clinical impact. Neither pre-treatment or post-treatment NLR was a predictor of survival in our study population. NLRR and ΔNLR were independent predictors of survival in BCLC stage C disease and had positive correlations with volume of liver tissue treated and administered activity.

Natural History of Incidental Enhancing Nodules on Cone-Beam Computed Tomography during Transarterial Therapy of Hepatocellular Carcinoma.

PURPOSE: To evaluate the natural history of incidental enhancing nodules (IENs) on contrast-enhanced cone-beam computed tomography (CT) during transarterial treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A single-center retrospective analysis of 100 patients with HCC who underwent contrast-enhanced cone-beam CT prior to transarterial treatment from August 2015 to June 2019 was performed. Inclusion criteria were patients with segmental distribution sublobar HCC, contrast-enhanced cone-beam CT of the target lesion and nontarget liver parenchyma, and follow-up cross-sectional imaging. Patients with IENs ≥3 mm that did not meet imaging criteria for HCC were analyzed. Exclusion criteria included biphenotypic tumors and IEN present inside the treated area of the liver. RESULTS: Fifty-six patients demonstrated 154 IENs on contrast-enhanced cone-beam CT, of which 13 IENs (8.5%) progressed to HCC. The mean primary tumor size was 29 mm (range: 10.2-189 mm). Ten patients had ≥4 IENs, and 46 patients had 1-3 IENs. The mean IEN size was 6.8 mm (range: 3.0-16.3 mm). The median follow-up interval after contrast-enhanced cone-beam CT was 282 days (interquartile range: 143-522). Increased alpha-fetoprotein before treatment (≥15.5 ng/mL, P = .035), having ≥4 IENs (P = .020), and hepatitis C virus (P = .015) were significantly correlated with IEN progression to HCC. No statistically significant differences were identified in baseline neutrophil-to-lymphocyte ratio, targeted HCC characteristics (size, macrovascular invasion, infiltrative pattern, enhancement pattern, and satellite lesions), and IEN size between those with IEN progression to HCC and those without. CONCLUSIONS: Most IENs of ≥3 mm on contrast-enhanced cone-beam CT in patients with segmental distribution sublobar HCC do not progress to HCC. Patients with segmental distribution sublobar HCC with ≥4 IENs, alpha-fetoprotein elevation (≥15.5 ng/mL), or hepatitis C virus have an increased risk of IEN progression to HCC.

Pathologic Response of Hepatocellular Carcinoma Treated with Yttrium-90 Glass Microsphere Radiation Segmentectomy Prior to Liver Transplantation: A Validation Study.

PURPOSE: To evaluate the pathologic outcomes of hepatocellular carcinoma (HCC) treated with Yttrium-90 radiation segmentectomy using glass microspheres prior to liver transplantation and explore parameters associated with pathologic necrosis. MATERIALS AND METHODS: A single-institution retrospective analysis of HCC patients who received radiation segmentectomy prior to liver transplantation from November 2016 to May 2020 was performed. Patients were included if the treatment angiosome encompassed the entire tumor and could be correlated with available gross pathology. Archived histology slides were reviewed for percentage of pathologic necrosis. Thirty-three patients with 37 tumors were evaluated. The median tumor size was 2.3 cm (range, 1-6.7 cm). RESULTS: All tumors received a single treatment. The median time from radiation segmentectomy to transplantation was 206 days (range, 58-550 days). Objective response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was 92% (complete response, 76%; partial response, 16%). A total of 68% (n = 25) of tumors demonstrated ≥99% pathologic necrosis. Complete pathologic necrosis was present in 53% and 75% of tumors treated with >190 Gy (n = 18) and >500 Gy (n = 8) single-compartment Medical Internal Radiation Dose, respectively. Complete response per mRECIST, posttreatment angiosome T1 hypointensity, dose >190 Gy, microsphere specific activity >297 Bq, and a longer time between treatment and transplant were associated with ≥99% tumor necrosis (P < .05). No posttransplant tumor recurrences occurred within a median follow-up of 604 days (range, 138-1,223 days). CONCLUSIONS: Radiation segmentectomy can serve as an ablative modality for the treatment of HCC prior to liver transplant.

Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.

BACKGROUND: This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy. METHODS: Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met. RESULTS: In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention. CONCLUSION: In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.

Paravertebral block for radiologically inserted gastrostomy tube placement in amyotrophic lateral sclerosis.

INTRODUCTION: Radiologically inserted gastrostomy (RIG) placement in patients with amyotrophic lateral sclerosis (ALS) carries risks related to periprocedural sedation and analgesia. To minimize these risks, we used a paravertebral block (PVB) technique for RIG placement. METHODS: We retrospectively reviewed patients with ALS undergoing RIG placement under PVB between 2013 and 2017. RESULTS: Ninety-nine patients with ALS underwent RIG placement under PVB. Median (range) age was 66 (28 to 86) years, ALS Functional Rating Scale-Revised score was 27 (6 to 45), and forced vital capacity was 47% (8%-79%) at time of RIG placement. Eighty-five (85.9%) patients underwent RIG placement as outpatients, with a mean postanesthesia care unit stay of 2.3 hours. The readmission rate was 4% at both 1 and 30 days postprocedure. DISCUSSION: PVB for RIG placement has a low rate of adverse events and provides effective periprocedural analgesia in patients with ALS, the majority of whom can be treated as outpatients.

Increasing Yttrium-90 Dose Conformality Using Proximal Radioembolization Enabled by Distal Angiosomal Truncation for the Treatment of Hepatic Malignancy.

PURPOSE: To evaluate safety and feasibility of improving radiation dose conformality via proximal radioembolization enabled by distal angiosomal truncation where selective administration was not practical. MATERIALS AND METHODS: Hepatic malignancies treated via angiosomal truncation between January 2017 and March 2019 were retrospectively evaluated. Thirty-three patients (8 women, 25 men; mean age, 62.2 y; range, 36-78 y) underwent 39 treatments. Of treatments, 74.3% (n = 29) were for hepatocellular carcinomas, 10.2% (n = 4) were for cholangiocarcinomas, and 15.4% (n = 6) were for metastatic tumors (1 colorectal adenocarcinoma, 1 pancreatic adenocarcinoma, 3 melanomas, and 1 endometroid carcinoma). Truncation was achieved using temporary embolic devices including a microvascular plug, detachable coil, gelatin slurry, and balloon microcatheter, after which proximal radioembolization was performed. Range of treatment activity was 0.47-5.75 GBq. Technetium-99m macroaggregated albumin and bremsstrahlung single photon emission computed tomography (CT)/CT threshold analysis was conducted to delineate and compare distribution of activity within the treatment angiosome before and after radioembolization. RESULTS: Dosimetric analysis of 14 patients demonstrated a significant reduction in nontarget liver radiation exposure at 5, 20, and 40% thresholds (P = .002, P = .001, and P = .008, respectively). There were no grade 3 or higher adverse events. There was no significant change in Albumin-Bilirubin grade and Eastern Cooperative Oncology Group Performance Status (P = .09 and P = .74) before and 3 months after the procedure. Truncated arteries were patent on subsequent angiography in 11 cases and on MR angiography or CT angiography in 38 of 39 cases. CONCLUSIONS: Proximal radioembolization enabled by distal angiosomal truncation is safe and decreases nontarget parenchymal radioembolization dose in cases not amenable to selective administration.

Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts.

BACKGROUND: Hepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers. METHODS: A total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT. RESULTS: Hepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts. CONCLUSION: We observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.

Single-institution experience of radioembolization with yttrium-90 microspheres for unresectable metastatic neuroendocrine liver tumors.

BACKGROUND AND AIM: The aim of this study was to assess the effectiveness of yttrium-90 (90 Y) microspheres for the treatment of unresectable metastatic liver neuroendocrine tumors (NET). METHODS: From February 2006 to September 2015, 36 patients (19 male and 17 female, age 63.6 ± 9.4 years) who underwent 90 Y therapy for unresectable liver metastases of NET were included and analyzed retrospectively. All patients received a variety of treatments before 90 Y therapy. The radiological response, symptoms improvement of carcinoid syndrome, tumor marker changes, complications, side effects/toxicity, survival, and factors related to survival were evaluated and analyzed. RESULTS: Of the 36 patients, the mean delivered dose of 90 Y was 1.8 ± 0.7 GBq with a total of 40 treatments. Overall disease control rate was 88.9% (32/36) at 3 months following therapy. In 16 patients with carcinoid syndrome, 15 (93.8%) patients had symptomatic improvement. Tumor marker response (5-hydroxyindoleacetic acid [n = 7] and chromogranin A [n = 13]) at 3 months after treatment were as follows: none (n = 0, 4), partial (n = 6, 7), and complete (n = 1, 2). Radiation-induced gastrointestinal ulcers (n = 2, 5.6%) were identified. Side effects included fatigue (n = 31, 86.1%), anorexia (n = 26, 72.2%), nausea (n = 15, 41.7%), vomiting (n = 14, 38.9%), abdominal pain (n = 10, 27.8%), and fever (n = 8, 22.2%). The mean follow-up was 27.0 ± 16.4 months, with a median survival of 41.0 months. Child-Pugh classification (P = 0.008) and lymph node metastases (P = 0.045) had statistically significant influence on overall survival. CONCLUSIONS: Yttrium-90 radioembolization can be effective in the treatment of unresectable liver metastases of NET who failed to respond to other treatments.

Abrupt occlusion of right gastroepiploic artery as an angiographic evidence of gastrointestinal hemorrhage.

Angiography plays an important role in both diagnosis and treatment of gastrointestinal (GI) bleeding; however, the sensitivity is low for diagnosis. We report a case of a 38-year-old woman who presented with recurrent upper GI bleeding following central pancreatectomy. Multiple selective arteriograms failed to reveal any active bleeding or other common signs of bleeding. There was an abrupt occlusion of the right gastroepiploic artery initially interpreted to be a surgical ligation. Upon direct superselective injection near the occlusion, an area of frank contrast extravasation was demonstrated immediately beyond the occlusion. The underlying vessel was embolized with n-butyl cyanoacrylate without recurrent bleeding up to 3-month follow-up.

Radiologic Characterization of Ischemic Cholangiopathy in Donation-After-Cardiac-Death Liver Transplants and Correlation With Clinical Outcomes.

OBJECTIVE: The purpose of this study was to define the cholangiographic patterns of ischemic cholangiopathy and clinically silent nonanastomotic biliary strictures in donation-after-cardiac-death (DCD) liver grafts in a large single-institution series. We also examined the correlation of the radiologic findings with laboratory data and clinical outcomes. MATERIALS AND METHODS: Data were collected for all DCD liver transplants at one institution from December 1998 to December 2011. Posttransplant cholangiograms were obtained during postoperative weeks 1 and 3 and when clinically indicated. Intrahepatic biliary strictures were classified by anatomic distribution and chronologic development. Radiologic findings were correlated with laboratory data and with 1-, 3-, and 5-year graft and patient survival rates. RESULTS: A total of 231 patients received DCD grafts. Cholangiograms were available for 184 of these patients. Postoperative cholangiographic findings were correlated with clinical data and divided into the following three groups: A, normal cholangiographic findings with normal laboratory values; B, radiologic abnormalities and cholangiopathy according to laboratory values; and C, radiologic abnormalities without laboratory abnormalities. Group B had four distinct abnormal cholangiographic patterns that were predictive of graft survival. Group C had mild nonprogressive multifocal stenoses and decreased graft and patient survival rates, although cholangiopathy was not detected in these patients according to laboratory data. CONCLUSION: Patterns and severity of nonanastomotic biliary abnormalities in DCD liver transplants can be defined radiologically and correlate with clinical outcomes. Postoperative cholangiography can depict the mild biliary abnormalities that occur in a subclinical manner yet cause a marked decrease in graft and patient survival rates in DCD liver transplants.

Long-term results of aortouniiliac stent grafts for the endovascular repair of abdominal aortic aneurysms.

BACKGROUND: Long-term follow-up of patients with aortouniiliac (AUI) grafts is lacking in the current literature. The purpose of this study was to review the outcomes of endovascular aneurysm repair (EVAR) using commercially available AUI devices with femorofemoral bypass in patients whose aortoiliac anatomy was unfavorable for bifurcated repair. METHODS: A retrospective review of 35 patients from September 2000 to February 2012, who underwent EVAR with commercially manufactured AUI devices, was performed. These comprised 35 of 372 (9.4%) patients who underwent EVAR during that period. Patient records were reviewed to determine morbidity, mortality, and survival after AUI repair. Patients were followed at 1-, 3-, 6-, and 12-month intervals with computed tomography (CT) scans during each visit. Median follow-up was 40 months (range: 2-135 months). RESULTS: Median age at surgery was 76 years (range: 60-93). The median preoperative aneurysm diameter was 57 mm (range: 45-71) and the median postoperative diameter was 53 mm (range: 29-80). Two type II endoleaks occurred on 1-month CT, whereas 10 endoleaks (type I [3], II [6], and III [1]) occurred during follow-up after 1 month. Migration of the stent graft occurred in 9% (n=3). Secondary procedures were required in 26% (n=9), whereas tertiary procedures were required in 3% (n=1). One patient required treatment for thrombosis of the iliac extension and 2 required treatment for thrombosis of the femorofemoral component. Mortality over the follow-up period was 34% (n=12) with no deaths occurring within 30 days. CONCLUSIONS: High-risk patients who present with aortoiliac anatomy unsuitable for bifurcated stent graft placement should be offered AUI graft placement as a potential alternative to open repair.

Segmental arterial mediolysis: a case of mistaken hemorrhagic pancreatitis and review of the literature.

CONTEXT: Segmental arterial mediolysis is an uncommon, non-atherosclerotic, non-inflammatory arteriopathy that involves areas of dissecting aneurysms and strictures that are caused by outer media lysis of the arterial wall from areas of medial necrosis of uncertain pathogenesis. It has a predilection for splanchnic arteries and often presents as abdominal pain or hemorrhage in late middle-aged and elderly patients. Diagnosis can be established by computed tomography angiography, magnetic resonance angiography, or angiogram by visualizing typical abnormalities, in addition to excluding other vasculitides. Histological confirmation is the gold standard but is not easily accessible and, as such, is not frequently performed. CASE REPORT: Here we present an updated review of the literature and a case of segmental arterial mediolysis that presented with spontaneous intra-abdominal bleeding near the pancreas that was originally misdiagnosed as hemorrhagic pancreatitis. CONCLUSION: Diagnosis is important because immunosuppressants for vasculitis can worsen the arteriopathy. Segmental arterial mediolysis can be self-limiting without treatment or may require urgent surgical or endovascular therapy for bleeding and carries a 50% mortality rate. Therefore, it should be included in the differential of causes of abdominal pain as well as in cases of unexplained abdominal hemorrhage.

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.