Clinician overconfidence in visual estimation of the posthepatectomy liver remnant volume: A proximal source of liver failure after major hepatic resection?

BACKGROUND: Post-hepatectomy liver failure is a source of morbidity and mortality after major hepatectomy and is related to the volume of the future liver remnant. The accuracy of a clinician's ability to visually estimate the future liver remnant without formal computed tomography liver volumetry is unknown. METHODS: Twenty physicians in diagnostic radiology, interventional radiology, and hepatopancreatobiliary surgery reviewed 20 computed tomography scans of patients without underlying liver pathology who were not scheduled for liver resection. We evaluated clinician accuracy to estimate the future liver remnant for 3 hypothetical major hepatic resections: left hepatectomy, right hepatectomy, and right trisectionectomy. The percent-difference between the mean and actual computed tomography liver volumetry (mean percent difference) was tested along with specialty differences using mixed-effects regression analysis. RESULTS: The actual future liver remnant (computed tomography liver volumetry) remaining after a hypothetical left hepatectomy ranged from 59% to 75% (physician estimated range: 50%-85%), 23% to 40% right hepatectomy (15%-50%), and 13% to 29% right trisectionectomy (8%-39%). For right hepatectomy, the mean future liver remnant was overestimated by 95% of clinicians with a mean percent difference of 22% (6%-45%; P < .001). For right trisectionectomy, 90% overestimated the future liver remnant by a mean percent difference of 25% (6%-50%; P < .001). Hepatopancreatobiliary surgeons overestimated the future liver remnant for proposed right hepatectomy and right trisectionectomy by a mean percent difference of 25% and 34%, respectively. Based on years of experience, providers with <10 years of experience had a greater mean percent difference than providers with 10+ years of experience for hypothetical major hepatic resections, but was only significantly higher for left hepatectomy (9% vs 6%, P = .002). CONCLUSION: A clinician's ability to visually estimate the future liver remnant volume is inaccurate when compared to computed tomography liver volumetry. Clinicians tend to overestimate the future liver remnant volume, especially in patients with a small future liver remnant where the risk of posthepatectomy liver failure is greatest.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

The State of Peptide Receptor Radionuclide Therapy and Its Sequencing among Current Therapeutic Options for Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs; however, this may change with emerging data to suggest that PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogs, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.

Conventional hepatic arterial anatomy? Novel findings and insights of a multi-disciplinary hepatic arterial infusion pump program.

INTRODUCTION: Variant hepatic arterial anatomy (vHAA) is thought to occur in 20-30% of patients. Hepatic arterial infusion (HAI) pump placement for liver cancers requires thorough hepatic artery dissection; we sought to compare vHAA identified during pump placement with established dogma. METHODS: Between 2016 and 2020, n = 30 patients received a HAI pump. Intra-operatively identified vHAA was characterized and compared with published data. RESULTS: vHAA was identified in 60% (n = 18) of patients, significantly higher than 19% (3671 of 19013) in the largest published series (P < 0.001). The most common variations were accessory left (n = 12; 40%) and replaced right (n = 6; 20%) hepatic arteries; six (20%) had ≥2 variants. Pre-operative imaging correctly identified 67% of variant hepatic arteries. DISCUSSION: Meticulous operative dissection of the hepatic arterial tree reveals vHAA not captured by imaging or cadaveric dissection. vHAA likely has a higher prevalence than previously reported and should be addressed to optimize therapeutic efficacy of HAI pump therapy.

Correction to: Yttrium-90 Radioembolization for BCLC Stage C Hepatocellular Carcinoma Comparing Child-Pugh A Versus B7 Patients: Are the Outcomes Equivalent?

The name of one of the co-authors was slightly misspelled. Kristian Enestvedt is listed currently as "Kristian K. Enestvedt" and should be listed instead as "C. Kristian Enestvedt."

Yttrium-90 Radioembolization for BCLC Stage C Hepatocellular Carcinoma Comparing Child-Pugh A Versus B7 Patients: Are the Outcomes Equivalent?

OBJECTIVE: To evaluate yttrium-90 (Y90) radioembolization outcomes across Child-Pugh scores in patients with advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From April 2005 to December 2018, 106 consecutive patients with BCLC Stage C HCC who underwent Y90 radioembolization were retrospectively analyzed. Exclusion criteria included additional malignancy (n = 7), death unrelated to liver disease (n = 2), metastases (n = 2), or lack of follow-up data (n = 4). Ninety-one patients were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method and compared between groups with the log-rank test. Cox regression modeling was used to evaluate the prognostic factors for survival. RESULTS: Mean age was 63 years and 85.7% were male. HCV infection was the most common etiology of liver disease (58.2%). Sixty-four (70.3%) patients were Child-Pugh A, 19 (20.9%) patients were B7, and eight (8.8%) patients were B8-9. Median OS after radioembolization was 20.2 [95% confidence interval (CI) 13.0-27.4], 6.0 (95% CI 4.4-7.6), and 5.5 (95% CI 2.5-8.5) months for Child-Pugh A, B7, and B8/9 groups, respectively (P < 0.001 for B7 vs. A; P = 0.537 for B7 vs. B8/9). The multivariable Cox regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score (P < 0.001), Child-Pugh class (P = 0.005), tumor morphology pattern (P = 0.012), and Y90 delivery location (P = 0.020) were significant independent predictors of overall survival. CONCLUSIONS: Outcomes from Y90 for BCLC C HCC for Child-Pugh B7 patients were equivalent to B8/9 patients and significantly worse compared to Child-Pugh A patients. Although further research is warranted, these results suggest continued cautious patient selection for radioembolization in advanced HCC.

Antiplatelet Therapy is Associated with Stent Patency After Iliocaval Venous Stenting.

PURPOSE: To examine the effectiveness of antithrombotic medications to prevent venous stent malfunction for iliocaval occlusive disease. MATERIALS AND METHODS: A retrospective analysis was performed on 62 patients who underwent technically successful endovascular iliocaval stent placement between May 2008 and April 2017. Clinical records were reviewed for demographic information, procedure details, post-stenting antithrombotic prophylaxis and stent patency on follow-up. Stent malfunction was defined as > 50% stenosis or occlusion at follow-up. Risk factors for stent malfunction were assessed with univariable and multiple Cox proportional hazard models. RESULTS: The median follow-up period was 11.6 months (range 0.1-76.4). Overall primary and secondary cumulative patency rates at 12 months were 70.0% and 92.4%, respectively. After stent placement, 97% of patients received anticoagulation with warfarin, enoxaparin or a factor Xa inhibitor. In addition, 61% received antiplatelet prophylaxis with aspirin, clopidogrel or a combination. In multiple Cox regression analysis, post-stenting antiplatelet use remained significantly associated with primary stent patency (HR = 0.28, P = 0.022). CONCLUSION: After iliocaval venous stenting, stent patency was best predicted by concomitant antiplatelet and anticoagulation therapy rather than anticoagulation alone. This novel finding warrants further research underlying mechanisms leading to venous stent thrombosis, and has implications for optimal medical management after venous stenting.

Skin ischemia and ulceration as a complication of inferior phrenic artery embolization for hepatocellular carcinoma.

Nontarget embolization from transarterial liver-directed therapy for hepatocellular carcinoma is a rare complication. We present a case of flank skin ulceration after embolization of the inferior phrenic artery supplying tumor. This complication of inferior phrenic artery embolization underscores caution when using small particles to embolize extrahepatic supply to hepatocellular carcinoma.

Long-Term Toxicity after Transarterial Radioembolization with Yttrium-90 Using Resin Microspheres for Neuroendocrine Tumor Liver Metastases.

PURPOSE: To evaluate long-term effects of yttrium-90 (90Y) transarterial radioembolization (TARE) for unresectable hepatic metastases of neuroendocrine tumors (NETs). MATERIALS AND METHODS: Retrospective analysis of 93 patients (47 women, 46 men; mean age 59 y) who underwent resin-based 90Y TARE was performed. Variables associated with overall survival were analyzed using univariate and multivariate models. Changes in serologic values and imaging characteristics were assessed with long-term follow-up. RESULTS: Unilobar TARE was performed in 48 patients, and staged bilobar TARE was performed in 45 patients. In multivariate analysis, ascites (P = .002) and extrahepatic metastases (P = .038) at baseline were associated with poor survival. Among 52 patients who had > 1 year of follow-up, significant increases in alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were observed; however, only 4 patients experienced grade 3 serologic toxicities. Imaging signs of cirrhosis-like morphology and portal hypertension were observed in 15 of 52 patients, more frequently in patients treated with bilobar TARE compared with unilobar TARE. Patients treated with bilobar TARE exhibited significantly increased hepatobiliary enzymes and decreased platelet count. Sustained increases in liver enzymes were observed in patients with > 4 years of follow-up. No radioembolization-related liver failure or grade 4 toxicity was observed. CONCLUSIONS: 90Y radioembolization using resin microspheres demonstrated a high safety profile for NET liver metastases, with low-grade, although sustained, long-term liver toxicity evident > 4 years after treatment. Bilobar treatment suggested a trend for treatment-related portal hypertension. Ongoing research will help define parameters for optimizing durable safety and efficacy of radioembolization in this setting.

Tailored treatment of patients with hepatocellular carcinoma with portal vein invasion: experience from a multidisciplinary hepatobiliary tumor program within a NCI comprehensive cancer center.

BACKGROUND: Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) has a poor prognosis with limited treatment options. Intra-arterial brachytherapy (IAB) and transarterial chemoembolization (TACE) yield local control but risk accelerating liver dysfunction. The outcomes, survival, and safety of selective liver-directed treatment are reported. METHODS: Thirty-seven consecutive patients with HCC and PVI treated between 2009 and 2015 were reviewed from a prospectively collected database. Univariate analysis, Kaplan-Meier plots using the log-rank method, and multivariate analyses were performed. Statistical significance was defined as P<0.05. Overall survival was reported in months (median; 95% CI). RESULTS: Most patients (59%) had PVI identified at initial HCC diagnosis. The liver-directed therapy group (n=22) demonstrated a survival advantage versus the systemic/supportive care group (n=14) [23.6 (5.8, 30.9) vs. 6.0 (3.5, 8.8) months]. Patients indicated for liver directed therapy had unilateral liver involvement (100% vs. 43%, P<0.0001), lower median alkaline phosphatase (105.5 vs. 208.0, P=0.002), and lower mean Child-Turcotte-Pugh (CTP) score (5.9 vs. 7.2, P=0.04) and tolerated treatment without serious complications. CONCLUSIONS: In HCC patients presenting with PVI, liver-directed therapy was safely performed in patients with limited venous involvement and preserved liver function. Liver-directed therapy extended survival for these patients indicated for palliative chemotherapy by traditional guidelines.

Symptom Distress in Patients With Hepatocellular Carcinoma Toward the End of Life.

PURPOSE/OBJECTIVES: To describe the presence, frequency, severity, and distress of symptoms in outpatients with advanced hepatocellular carcinoma toward the end of life, and the variability in psychological and physical symptom distress between and within patients over time. 
. DESIGN: A prospective, longitudinal, descriptive design. 
. SETTING: Outpatient clinics at two healthcare institutions. 
. SAMPLE: 18 patients (15 men and 3 women) with hepatocellular carcinoma and a mean age of 63.3 years (range = 54-81 years).
. METHODS: Data were collected monthly for six months. Patients completed the Memorial Symptom Assessment Scale, which reports a total score, and three subscales that provide global distress, psychological distress, and physical distress scores.
. MAIN RESEARCH VARIABLES: Global, psychological, and physical distress.
. FINDINGS: Patients reported lack of energy and pain as the most frequent and distressing symptoms. Problems with sexual interest or activity was the fourth most present symptom after drowsiness. Global Distress Index mean scores had notable variability between and within patients over time. During data collection, six patients died. None were referred to palliative care.
. CONCLUSIONS: Gaining knowledge about symptom distress and prevalent symptoms experienced by patients with advanced hepatocellular carcinoma is critical for designing symptom management strategies that are comprehensive and tailored to patients to optimize their quality of life as they approach death.
. IMPLICATIONS FOR NURSING: Nurses play a vital role in advocating for, initiating, and providing comprehensive holistic care based on individual patient needs by facilitating discussions about apparent and less apparent distressing symptoms, including those related to sexuality.

Tumor Dose Response in Yttrium-90 Resin Microsphere Embolization for Neuroendocrine Liver Metastases: A Tumor-Specific Analysis with Dose Estimation Using SPECT-CT.

PURPOSE: To evaluate dose-response relationship in yttrium-90 (90Y) resin microsphere radioembolization for neuroendocrine tumor (NET) liver metastases using a tumor-specific dose estimation based on technetium-99m-labeled macroaggregated albumin (99mTc MAA) single photon emission computed tomography (SPECT)-CT. MATERIALS AND METHODS: Fifty-five tumors (mean size 3.9 cm) in 15 patients (10 women; mean age 57 y) were evaluated. Tumor-specific absorbed dose was estimated using a partition model. Initial (median 2.3 months) follow-up data were available for all tumors; last (median 7.6 months) follow-up data were available for 45 tumors. Tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors (mRECIST) on follow-up CT. Tumors with complete or partial response were considered responders. Mean tumor absorbed dose was 231.4 Gy ± 184.3, and mean nontumor liver absorbed dose was 39.0 Gy ± 18.0. RESULTS: Thirty-six (65.5%) and 30 (66.7%) tumors showed response at initial and last follow-up, respectively. Mean absorbed doses in responders and nonresponders at initial and last follow-up were 285.8 Gy ± 191.1 and 128.1 Gy ± 117.1 (P = .0004) and 314.3 Gy ± 195.8 and 115.7 Gy ± 117.4 (P = .0001). Cutoff value of ≥ 191.3 Gy for tumor-specific absorbed dose predicted tumor response with 93% specificity, whereas < 72.8 Gy predicted nonresponse with 100% specificity at last follow-up. Estimated mean absorbed tumor dose per patient was significantly higher in responders versus nonresponders over the follow-up period (224.5 Gy ± 90.3 vs 70.0 Gy ± 28.0; P = .007). CONCLUSIONS: Tumor-specific absorbed dose, estimated with a partition model, was significantly associated with tumor response in NET liver metastases. An estimated dose ≥ 191.3 Gy predicted treatment response with high sensitivity and specificity.

Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

BACKGROUND: The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. PATIENTS AND METHODS: A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. RESULTS: During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence (P = 0.001 and < 0.0001, respectively). On ROC analysis, a threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor response (95% sensitivity, 93% specificity). CONCLUSIONS: Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

ACR Appropriateness Criteria Radiologic Management of Hepatic Malignancy.

Management of primary and secondary hepatic malignancy is a complex problem. Achieving optimal care for this challenging population often requires the involvement of multiple medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and loco-regional therapies, such as thermal ablation and transarterial embolization techniques. This article provides a review of treatment strategies for the three most common subtypes of hepatic malignancy treated with loco-regional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Emergent Endovascular Stent Grafts for Ruptured Aortic Aneurysms.

Ruptured aortic aneurysms uniformly require emergent attention. Historically, urgent surgical repair or medical management was the only treatment options. The development of covered stent grafts has introduced a third approach in the care of these critical patients. The clinical status of the patient and local physician expertise drive the treatment modalities in the majority of cases. The goal of therapy in these patients is to stabilize the patient as quickly as possible, establish maximum survival with minimum morbidity, and provide a long lasting result. The endovascular approach has become an acceptable treatment option in an increasing number of patients presenting with ruptured aneurysmal disease of both the descending thoracic and abdominal aorta. Major factors influencing treatment include patient clinical status, characteristics of the aorta, physician preference, institutional experience, and availability of appropriate equipment. Planning, experience, and the ability to improvise effective solutions are keys to the success of the procedure when endovascular techniques are utilized. Three separate cases, requiring intraprocedural improvisation, are presented followed by a review of the literature.

ACR appropriateness criteria radiologic management of infected fluid collections.

The best management of infected fluid collections depends on a careful assessment of clinical and anatomic factors as well as an up-to-date review of the published literature, to be able to select from a host of multidisciplinary treatment options. This article reviews conservative, radiologic, endoscopic, and surgical options and their best application to infected fluid collections as determined by the ACR Appropriateness Criteria Expert Panel on Interventional Radiology. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application, by the panel, of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Primary creation of an externally constrained TIPS: a technique to control reduction of the portosystemic gradient.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) creation increases the risk of hepatic encephalopathy due to overshunting. Techniques exist to secondarily reduce the shunt for refractory encephalopathy. The purpose of this article is to describe a technique for primary TIPS restriction using a balloon-expandable stent within the transvenous hepatic track followed by deployment of a self-expanding polytetrafluoroethylene-lined stent-graft within the balloon-expandable stent to create the TIPS. CONCLUSION: This technique enables control over the degree of portosystemic shunting in elective TIPS creation.