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.

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.

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.

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.

Catheter-based treatments for hepatic metastases from neuroendocrine tumors.

OBJECTIVE: The purpose of this article is to present our experience in treating patients with hepatic metastases from a neuroendocrine primary malignancy. CONCLUSION: The tumor and patient characteristics, vascular access, and features of treatment all play a role in the long-term management of patients with metatastic neuroendocrine tumors. Routine prophylactic measures are recommended to reduce the frequency and severity of crisis events related to hormone release in patients with neuroendocrine tumors.

Clinical and radiologic evaluation of patients before TIPS creation.

OBJECTIVE: The purpose of this article is to highlight the clinical and radiologic evaluation of patients referred for transjugular intrahepatic portosystemic shunt (TIPS) creation. CONCLUSION: TIPS creation is an effective procedure for portal diversion in the setting of recurrent variceal bleeding or diuretic refractory ascites secondary to portal hypertension. Close collaboration between hepatologists and interventional radiologists is important for appropriate patient selection. Pre-procedural clinical and radiologic evaluation is fundamental for successful management of these patients.

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.

Transjugular intrahepatic portosystemic shunt creation using intravascular ultrasound guidance.

PURPOSE: To describe the use of intravascular ultrasound (US) guidance for creation of transjugular intrahepatic portosystemic shunts (TIPSs) in humans. MATERIALS AND METHODS: The initial 25 cases of intravascular US-guided TIPS were retrospectively compared versus the last 75 conventional TIPS cases during the same time period at the same institution in terms of the number of needle passes required to establish portal vein (PV) access, fluoroscopy time, and needle pass-related complications. RESULTS: Intravascular US-guided TIPS creation was successful in all cases, and there was no statistically significant difference in number of needle passes, fluoroscopy time, or needle pass-related complications between TIPS techniques. Intravascular US-guided TIPS creation was successful in cases in which conventional TIPS creation had failed as a result of PV thrombosis or distorted anatomy. Intravascular US guidance for TIPS creation was additionally useful in a patient with Budd-Chiari syndrome and in a patient with intrahepatic tumors. CONCLUSIONS: Intravascular US is a safe and reproducible means of real-time image guidance for TIPS creation, equivalent in efficacy to conventional fluoroscopic guidance. Real-time sonographic guidance with intravascular US may prove advantageous for cases in which there is PV thrombus, distorted anatomy, Budd-Chiari syndrome, or hepatic tumors.

Safety and efficacy of preoperative right portal vein embolization in patients at risk for postoperative liver failure following major right hepatectomy.

BACKGROUND: Right portal vein embolization (RPVE) has been utilized with or without segment IV (RPVE + IV) prior to hepatectomy to induce hypertrophy and prevent liver insufficiency in patients with a predicted future liver remnant (FLR) of ≤30% or cirrhosis. METHODS: Records of patients who underwent RPVE during 2006-2010 were retrospectively reviewed. Patient demographics, operative outcomes and complications were analysed. Computed tomography-based volumetrics were performed to determine FLR volume and degree of hypertrophy. Patients were stratified by segment IV embolization. Short-term outcomes following RPVE and liver resection are reported. RESULTS: A total of 23 patients were identified. Ten patients underwent RPVE and 13 underwent RPVE + IV. The RPVE procedure resulted in a 38% increase in FLR volume. Liver volumes, hypertrophy rates and outcomes were similar in both groups. Rates of operative complications in the RPVE and RPVE + IV groups were similar at 50% and 54%, respectively, and most complications were minor. Complication rates as a result of embolization were 30% in the RPVE group and 31% in the RPVE + IV group. One patient underwent modified operative resection as a result of a complication of RPVE. CONCLUSIONS: Right portal vein embolization (±segment IV) is a safe and effective modality to increase FLR volume. Post-embolization complications and short-term outcomes after resection are acceptable and are similar in both RPVE and RPVE + IV.

Endovascular stent grafts in urgent blunt and penetrating thoracic aortic trauma.

A traumatic thoracic aortic injury is fatal in the majority of cases. Surviving the aortic injury in addition to the myriad of associated trauma requires comprehensive medical management from many medical services. Balancing these services and coordinating the medical care requires free and open communication between services. Although one might assume a thoracic aortic injury takes precedence over other injuries, an organized plan of care in which the morbidity of the injury as well as the consequences of treatment of each injury helps provide an appropriate "rank order" in the treatment process. A patient with a thoracic aortic injury can be observed for several days while additional injuries are treated, as long as appropriate blood pressure controls are observed. The treatment order for multiple injuries must be reevaluated on a regular basis to adjust for changes in the overall clinical condition. This rank order to treatment and scheduled treatment plan allows for appropriate imaging, evaluation, and coordination of services in preparation for the placement of a thoracic aortic stent graft. The goal of treatment is to reduce the risk of aortic rupture and subsequent fatal hemorrhage. Choosing an open surgical repair versus an endovascular stent graft depends upon physician expertise and clinical status of the patient. In the appropriate clinical setting, endovascular repair of the thoracic aortic injury has become the treatment of choice at the authors' institution in patients with significant operative risks and extensive comorbid injuries. Specific characteristics of the injured aorta also dictate the type of endovascular device required for repair. Case reviews of a patient with blunt trauma and a patient with penetrating trauma used to demonstrate clinical parameters, imaging options, and details of stent graft choice and placement, are presented followed by a review of the literature.

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.

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.

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."

Favorable early outcomes for patients with extended indications for thoracic endografting.

BACKGROUND: Endografts originally designed and approved for the treatment of thoracic aortic aneurysms have rapidly been adopted for nonapproved use in the treatment of disorders of the thoracic aorta, including aortic transection, dissection, pseudoaneurysms, and thoracoabdominal aneurysms. The purpose of this study was to evaluate the early outcomes of patients treated with thoracic endografts for nonapproved indications at our institution. METHODS: The medical records of patients undergoing thoracic endografting at our institution from August 2005 until March 2008 were reviewed. Patients undergoing endografting for uncomplicated thoracic aortic aneurysms were excluded. The outcomes of patients with extended indications for thoracic endografting were studied. RESULTS: During the study period, endografting was performed in 31 patients for nonapproved aortic conditions. Patients underwent endografting for a spectrum of indications, including aortic transection (n = 12), complications of type B aortic dissection including rupture (n = 9), thoracoabdominal aneurysm with visceral debranching (n = 6), aortic arch debranching (n = 2), and pseudoaneurysm associated with prior coarctation repair (n = 2). Early outcomes were favorable. All patients had successful endograft repair of their anatomic lesion. There were no endoleaks. There was no hospital mortality. Average hospitalization was 15 days for patients with aortic transection and 9 days for all other patients. CONCLUSIONS: Thoracic endografts are versatile devices that with appropriate expertise can be used effectively to treat a spectrum of disorders of the thoracic aorta, including acute emergencies. Early outcomes of patients with extended indications for thoracic endografting compare favorably to published series of patients treated with open procedures. Further study is required to assess the long-term efficacy of these devices.

Emergent aortic endovascular stent grafts for ruptured aortoiliac aneurysms.

A ruptured abdominal aortic aneurysm is an emergency anywhere in the world. Physician expertise and clinical status of the patient drive the treatment modalities in the majority of cases. Independent of treatment choice, the goal of therapy is to stabilize the patient as quickly as possible in a manner that establishes maximum survival and minimum morbidity and provides a long-lasting, durable result. Endovascular aortic repair has become an acceptable alternative to open surgical repair in a subset of patients presenting with ruptured aortoiliac aneurysms. Patient selection, physician preference, institutional experience, and availability of appropriate equipment make up a majority of factors influencing treatment choices. Once the decision has been made to treat the patient via endovascular techniques, then experience, planning, and the ability to improvise solutions "on the fly" become vital components to the success of the procedure. Two separate cases, requiring intraprocedural improvisation, are presented followed by a review of the literature.

Over-the-wire catheter exchanges: reduction of the risk of air emboli.

PURPOSE: This study evaluated the aerostatic properties of the catheter clamp during over-the-wire catheter exchanges and determined if protective devices reduce volumes of air emboli (AE). MATERIALS AND METHODS: A cuffed catheter was placed in an AE model in physiologic conditions and the volume of AE was recorded during 60 seconds (n = 10). Similarly, the volume of AE entering the model during 30 seconds was recorded with the catheter clamp open (n = 10) or closed over the wire (n = 10), and with the sliding clamp in the open position (n = 10). The volume of AE during 60 seconds was recorded with the sliding clamp closed over the wire (n = 10) and with the aerostatic valve with (n = 10) and without (n = 10) a wire in place. RESULTS: Without a wire, no AE occurred with the catheter clamp closed (60 seconds, n = 10). There was no statistically significant difference between the volumes of AE with the catheter clamp open or closed over the wire during 30 seconds (43 mL +/- 4 and 32 mL +/- 11, respectively). With the protective devices in place and the wire unchanged in position, no AE occurred during 60 seconds. A positive control (sliding clamp and catheter clamp open, n = 10) yielded AE volumes of 44 mL +/- 5 in 30 seconds. CONCLUSIONS: AE can occur with the catheter clamp closed over a wire. Protective devices reduce the volume of AE under simulated physiologic conditions and are recommended with over-the-wire catheter exchanges.