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Background: The significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM., Patient and Methods: The PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed., Results: The main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor., Conclusion: Our findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A mid-50s woman presented with acute right upper quadrant pain 1-day post second cycle of pembrolizumab. She has a significant history for two concurrent malignancies: a solitary oligometastatic hepatic melanoma (NRAS mutant) of unknown primary diagnosed 2 months prior, and a 10-year history of breast carcinoma with pulmonary metastases on palliative chemotherapy. Multiphase CT scan demonstrated active venous bleeding without active arterial bleeding. The patient received two units of packed red blood cells, followed by selective transcatheter arterial embolisation (TAE) of the right hepatic artery branches to segment 7 and 8. Spontaneous rupture of solitary liver metastases are exceedingly rare. TAE is a safe and effective treatment choice in patients with spontaneous rupture. Given progressive tumour burden, changes in management with a different immunotherapy agent can be considered., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Various chemotherapy administration methods have been used to prevent liver metastasis (LM) in patients with colorectal cancer (CRC). This network meta-analysis evaluated the efficacy of these different methods in preventing LM in CRC patients who underwent curative surgery., Method: A systematic search of randomized controlled trials reporting the efficacy of various adjuvant chemotherapy methods in patients with colorectal cancer who underwent curative surgery was conducted. The primary outcome was the LM rate., Results: This network meta-analysis included 19 studies reporting on 12,588 participants, comparing portal vein infusion chemotherapy (PVIC) versus hepatic arterial infusion chemotherapy (HAIC) versus systematic chemotherapy (SC) versus surgery alone. The HAIC group had the lowest LM rate when compared to the other three groups (odds ratio [OR] of PVIC vs. HAIC: 1.86; OR of SC vs. HAIC: 1.98; and HAIC vs. surgery alone: 0.43). The LM rate did not differ significantly between PVIC, SC, and surgery alone. The recurrence rates were lower for PVIC and HAIC than for surgery alone (the ORs for PVIC and HAIC were 0.73 [95% CI: 0.58-0.92] and 0.45 [95% CI: 0.26-0.77]). The mortality rates of patients undergoing PVIC and HAIC were lower than that of patients undergoing surgery alone (the ORs for PVIC and HAIC were 0.77 [95% CI: 0.64-0.93] and 0.49 [95% CI: 0.24-0.98]). Anastomotic leakage, cardiopulmonary leakage, diarrhea, nausea and vomiting, oral ulceration, wound infection, or ileus did not differ significantly between the four groups. PVIC showed the highest hepatic toxicity rate compared to those for SC, HAIC, and surgery alone., Conclusion: HAIC might be a satisfactory method for preventing LM in patients with CRC undergoing curative surgery., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Liver surgery leads to a high degree of heterogeneity in the prognosis of hepatocellular carcinoma (HCC) patients. However, most previous studies focused on the postoperative therapeutic effects of other treatments, with relatively few studies on the impacts on liver function. This study investigated the impact of transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) on liver function after HCC resection from various angles., Methods: 138 HCC patients were enrolled, including 27 patients who received TACE and 80 patients who received HAIC. Besides routine treatment such as liver protection and antiviral therapy, 31 patients received no other treatment. The different groups were compared with various biological parameters with four types of scoring methods., Results: In the short term after TACE, the mean (±SD) alanine transaminase and aspartate transaminase values increased by 79.22 ± 117.43 U/L and 66.33 ± 94.54 U/L, respectively (p < 0.01). The mean (±SD) total bilirubin (TBIL) values increased by 4.02 ± 6.08 μmol/L (p < 0.01). The mean (±SD) albumin (ALB) values decreased by 3.54 ± 2.93 g/L (p < 0.001). The mean (±SD) albumin bilirubin (ALBI) scores increased by 0.39 ± 0.22 (p < 0.001). In the short term after HAIC, the mean (±SD) TBIL values increased by 2.11 ± 5.57 μmol/L (p < 0.01). The mean (±SD) ALB values decreased by 2.52 ± 3.26 g/L (p < 0.001), and the mean (±SD) ALBI scores increased by 0.21 ± 0.42 (p < 0.001). In both treatment groups, the long-term liver function was not significantly different from that before treatment and also from that of the untreated group (p > 0.05)., Conclusion: TACE after HCC resection has a significant impact on short-term liver function, whereas HAIC has a relatively small impact, but neither has a major impact on long-term liver function., (© 2023 S. Karger AG, Basel.)

Objectives: To investigate the effect of saline-diluted gadoxetic acid, done for arterial-phase (AP) artifact reduction, on signal intensity (SI), and hence focal lesion conspicuity on MR imaging., Methods: We retrospectively examined 112 patients who each had at least two serial gadoxetic acid-enhanced liver MRIs performed at 1 ml/s, first with non-diluted (ND), then with 1:1 saline-diluted (D) contrast. Two blinded readers independently analyzed the artifacts and graded dynamic images using a 5-point scale. The absolute SI of liver parenchyma, focal liver lesions (if present), aorta, and portal vein at the level of the celiac trunk and the SI of the paraspinal muscle were measured in all phases. The signal-to-norm (SI Norm ) of the vascular structures, hepatic parenchyma and focal lesions, and the contrast-to-norm (C Norm ) of focal liver lesions were calculated., Results: AP artifacts were significantly reduced with dilution. Mean absolute contrast-enhanced liver SI was significantly higher on the D exams compared to the ND exams. Likewise, SI Norm of liver parenchyma was significantly higher in all contrast-enhanced phases except transitional phase on the D exams. SI Norm values in the AP for the aorta and in the PVP for portal vein were significantly higher on the diluted exams. The C Norm was not significantly different between ND and D exams for lesions in any imaging phase. The interclass correlation coefficient was excellent (0.89)., Conclusion: Gadoxetic acid dilution injected at 1ml/s produces images with significantly fewer AP artifacts but no significant loss in SI Norm or C Norm compared to standard non-diluted images., Key Points: • Diluted gadoxetic acid at slow injection (1 ml/s) yielded images with higher SI Norm of the liver parenchyma and preserved C Norm for focal liver lesions. • Gadoxetic acid-enhanced MRI injected at 1 ml/s is associated with arterial-phase (AP) artifacts in 31% of exams, which may degrade image quality and limits focal liver lesion detection. • Saline dilution of gadoxetic acid 1:1 combined with a slow injection rate of 1 ml/s significantly reduced AP artifacts from 31 to 9% and non-diagnostic AP artifacts from 16 to 1%., (© 2022. The Author(s).)

Purpose: To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods., Materials and Methods: The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm 3 liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20-30 μm were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion., Results: Overall, the degree of on-target deposition of the microspheres was 85% ± 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 × 10 5 microspheres achieving distal deposition vs 2 × 10 5 for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, α = 0.05)., Conclusions: The use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD administration method was associated with less favorable deposition characteristics of the microspheres., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

The patient underwent partial sigmoid colon resection for sigmoid colon cancer with hyper CEA blood(1,110.6 ng/mL) and concurrent liver metastases mostly in the right lobe of the liver, followed by systemic chemotherapy(SOX plus BEV). Seven courses of chemotherapy resulted in PR on imaging, and CEA was reduced to 5.0 ng/mL, which was within reference values. As he continued chemotherapy, frequent hematologic toxicities and adverse events forced frequent dose reductions and changes in the chemotherapy schedule. About 2 years after surgery(19 courses of SOX plus BEV), the liver metastases became slightly enlarged on imaging, and the CEA was also increasing. The patient did not wish to undergo systemic chemotherapy and requested hepatic arterial infusion chemotherapy(HAIC), which has relatively few side effects and adverse events. HAIC with pyrimidine fluoride alone is ongoing for 22 courses, and tumor markers have decreased again with PR on imaging. Performance status has been good without hematologic toxicity or adverse events for approximately 1 year during the course of HAIC. HAIC is a weakly recommended therapy in the colorectal cancer treatment guidelines, but it is considered one of the most effective therapies with relatively few side effects.

For advanced hepatocellular carcinoma, an 80's woman underwent right inguinal reservoir port implantation and hepatic arterial infusion chemotherapy. The patient developed sepsis caused by methicillin-resistant Staphylococcus aureus 40 days after starting treatment. After the reservoir port was removed, an infected pseudoaneurysm developed. Interventional radiology treatment could not be completed because of the shape of the aneurysm, and deep femoral artery suture closure was conducted surgically. Unfortunately, the pseudoaneurysm recurred two months after surgery, and treatment for hepatocellular carcinoma was discontinued. It is important to remember that the formation of pseudoaneurysms is a complication after reservoir port placement.

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. © RSNA, 2022.

Introduction: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients., Methods: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes., Results: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p &lt; 0.05), while the DCR in the HAIC group was higher (p &gt; 0.05). No notable difference was found between the two groups in median OS and PFS (p &gt; 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p &gt; 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS., Conclusion: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials., (© 2023 S. Karger AG, Basel.)

Objective: This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model., Methods: Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 μm polyvinyl alcohol (PVA), and (D) PGEL., Results: Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments., Conclusion: PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC., (© 2022. The Author(s).)

A 57-year-old man was diagnosed with an intrahepatic cholangiocarcinoma(ICC)located at segment 4, attached to the hilar bile ducts, with metastasis of the lymph nodes bordering the right hepatic artery. The ICC was unresectable, and chemotherapy with GCS was administered for 7 months. Although the primary tumor site did not change after the chemotherapy, the lymph nodes shrunk slightly and we decided to perform conversion surgery(CS). Radical resection by means of a left hepatectomy was safely performed, and the metastasis of lymph nodes were dissected from the right hepatic artery. Although the surgical indication for CS under chemotherapy for unresectable ICC is controversial, we herein report a successful case.

Background: Hepatic artery infusion (HAI) is a liver-directed therapy that delivers high-dose chemotherapy to the liver through the hepatic arterial system for colorectal liver metastases and intrahepatic cholangiocarcinoma. Utilization of HAI is rapidly expanding worldwide., Objective and Methods: This review describes the conduct of HAI pump implantation, with focus on common technical pitfalls and their associated solutions. Perioperative identification and management of common postoperative complications is also described., Results: HAI therapy is most commonly performed with the surgical implantation of a subcutaneous pump, and placement of its catheter into the hepatic arterial system for inline flow of pump chemotherapy directly to the liver. Intraoperative challenges and abnormal hepatic perfusion can arise due to aberrant anatomy, vascular disease, technical or patient factors. However, solutions to prevent or overcome technical pitfalls are present for the majority of cases. Postoperative HAI-specific complications arise in 22% to 28% of patients in the form of pump pocket (8%-18%), catheter (10%-26%), vascular (5%-10%), or biliary (2%-8%) complications. The majority of patients can be rescued from these complications with early identification and aggressive intervention to continue to deliver safe and effective HAI therapy., Conclusions: This HAI toolkit provides the HAI team a reference to manage commonly encountered HAI-specific perioperative obstacles and complications. Overcoming these challenges is critical to ensure safe and effective pump implantation and delivery of HAI therapy, and key to successful implementation of new programs and expansion of HAI to patients who may benefit from such a highly specialized treatment strategy., Competing Interests: The authors report no conflict of interests., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bleeding is a fatal complication after pancreatectomy. Although coil embolization is a widely accepted treatment option, ischemia of the remaining organs should be prevented. This study reports the successful treatment of intra-abdominal hemorrhage following distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using balloon-assisted coil embolization (BACE). A 59-year-old man was diagnosed with locally advanced pancreatic cancer. The tumor involves the common hepatic artery, splenic artery, and celiac artery. After four cycles of treatment with gemcitabine/nab-paclitaxel, the soft-density masses, surrounding the artery, shrunk. DP-CAR and R0 resections were performed. A minor postoperative pancreatic fistula occurred. Six months postoperatively, the computed tomography showed delayed asymptomatic bleeding from an anterior superior pancreaticoduodenal artery (ASPDA) pseudoaneurysm located near the gastroduodenal artery confluence. BACE was performed by placing a microballoon catheter in the region of confluence of the ASPDA and posterior superior pancreaticoduodenal artery (PSPDA) to prevent coil migration. After inserting the microballoon catheter, coil embolization was performed in the ASPDA. Hepatic blood flow was maintained from the PSPDA. BACE is a useful technique to preserve blood flow to the remnant organs when performing coil embolization for bleeding following a distal pancreatectomy, especially following a DP-CAR., (© 2022. The Author(s).)

To evaluate the clinical efficacy of targeted therapy and immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX and lipiodol embolization in the treatment of unresectable hepatocellular carcinoma. Patients included in the study were those who received targeted therapy and immunotherapy combined with HAIC of FOLFOX and lipiodol embolization in Zhongshan People's Hospital from December 2020 to June 2021 for unresectable hepatocellular carcinoma. Evaluation indicators included objective response rate (ORR), median progression-free survival (mPFS), median duration of response (mDOR), 1-year overall survival rate (OS), surgical conversion rate, and adverse events. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors (mRECIST and RECIST v1.1). A total of 35 patients were included in this study, 30 of whom completed treatment evaluation. According to mRECIST evaluation criteria, the objective response rate (ORR) was 83.3% (25/30); the complete response (CR) was 60% (18/30); the partial response (PR) was 23.3% (7/30), and stable disease (SD) was 16.7% (5/30). The mDOR was 10.3 months (95% Cl: 8.27-NE), and the mPFS was 13.2 months (95% CI: 10.3-NE); the surgical conversion rate was 30.0% (9/30). The 1-year OS was 96.7%. There were no serious surgical complications and grade 4 or 5 adverse events of targeted therapy, immunotherapy and HAIC. Some patients had grade 3 adverse reactions in gastrointestinal toxicity or hepatotoxicity, and the adverse reactions were improved after corresponding symptomatic treatment. We concluded that HAIC of FOLFOX and lipiodol embolization combined with targeted therapy and immunotherapy had a significant curative effect in the treatment of unresectable hepatocellular carcinoma, with no serious adverse reactions and a high rate of surgical conversion rate.

The first trials of hepatic artery infusion pump (HAIP) chemotherapy occurred in the 1990s. The high percentage of recurrent disease after curative resection of colon cancer and perioperative systemic chemotherapy has renewed.

There is no noninvasive method to estimate lung shunting fraction (LSF) in patients with liver tumors undergoing Yttrium-90 (Y90) therapy. We propose to predict LSF from noninvasive dynamic contrast enhanced (DCE) MRI using perfusion quantification. Two perfusion quantification methods were used to process DCE MRI in 25 liver tumor patients: Kety's tracer kinetic modeling with a delay-fitted global arterial input function (AIF) and quantitative transport mapping (QTM) based on the inversion of transport equation using spatial deconvolution without AIF. LSF was measured on SPECT following Tc-99m macroaggregated albumin (MAA) administration via hepatic arterial catheter. The patient cohort was partitioned into a low-risk group (LSF ≤&nbsp;10%) and a high-risk group (LSF >&nbsp;10%). Results: In this patient cohort, LSF was positively correlated with QTM velocity |u| (r = 0.61, F = 14.0363, p = 0.0021), and no significant correlation was observed with Kety's parameters, tumor volume, patient age and gender. Between the low LSF and high LSF groups, there was a significant difference for QTM |u| (0.0760 ± 0.0440 vs. 0.1822 ± 0.1225 mm/s, p = 0.0011), and Kety's Ktrans (0.0401 ± 0.0360 vs 0.1198 ± 0.3048, p = 0.0471) and Ve&nbsp;(0.0900 ± 0.0307 vs. 0.1495 ± 0.0485, p = 0.0114). The area under the curve (AUC) for distinguishing between low LSF and high LSF was 0.87 for |u|, 0.80 for Ve and 0.74 for Ktrans. Noninvasive prediction of LSF is feasible from DCE MRI with QTM velocity postprocessing.

Background: Arterial resection (AR) for pancreatic adenocarcinoma is increasingly considered at specialized centers. We aimed to examine the incidence, risk factors, and outcomes of hepatic artery (HA) occlusion after revascularization., Methods: We included patients undergoing HA resection with interposition graft (IG) or primary end-to-end anastomoses (EE). Complete arterial occlusion (CAO) was defined as "early" (EO) or "late" (LO) before/after 90 days respectively. Kaplan-Meier and change-point analysis for CAO was performed., Results: HA resection was performed in 108 patients, IG in 61% (66/108) and EE in 39% (42/108). An equal proportion (50%) underwent HA resection alone or in combination with celiac and/or superior mesenteric artery. CAO was identified in 18% of patients (19/108) with arterial IG least likely to occlude (p=0.019). Hepatic complications occurred in 42% (45/108) and correlated with CAO, symptomatic patients, venous resection, and postoperative portal venous patency. CAO-related operative mortality was 4.6% and significantly higher in EO vs LO (p = 0.046). Median CAO occlusion was 126 days. With change-point analysis, CAO was minimal beyond postoperative day 158., Conclusion: CAO can occur in up to 18% of patients and the first 5-month post-operative period is critical for surveillance. LO is associated with better outcomes compared to EO unless there is inadequate portal venous inflow., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite curative hepatectomy, most colorectal liver metastasis (CRLM) patients relapse locally within 2 years. Genomic predictors for hepatic recurrence are poorly understood. This study was designed to identify genomic signatures for recurrence in resected CRLM patients treated with adjuvant hepatic artery infusion (HAI) and/or systemic (SYS) chemotherapy., Methods: Patients undergoing curative hepatectomy and adjuvant HAI+SYS or SYS between January 2000 and October 2017 with next-generation sequencing data were catalogued. Gene and signaling-level alterations were checked for association with time to any (AR), liver (LR), and extrahepatic recurrence (ER) by using Kaplan-Meier analysis., Results: Of 172 receiving HAI+SYS, 100 patients recurred, with 69 LR and 83 ER. Five- and ten-year LR-free rates were 57% (95% confidence interval [CI] 48-65%) and 51% (95% CI 41-60%), respectively. Five- and 10-year ER-free, rates were 51% (95% CI 43-58%) and 45% (95% CI 36-54%), respectively. More ER was observed with tumors harboring altered KRAS (38% [95% CI 25-50%] vs. 63% [95% CI 53-71%], p-adj = 0.003) and RAS/RAF (36% [95% CI 25-48%] vs. 66% [95% CI 56-74%], p-adj < 0.001) than wild-type. Co-altered RAS/RAF-TP53 was associated with worse AR (26% [95% CI 14-40%] vs. 48% [95% CI 39-57%], p-unadj < 0.001), ER (30% [95% CI 17-45%] vs. 62% [95% CI 53-70%], p-unadj < 0.001), and LR rate (40% [95% CI 24-57%] vs. 70% [95% CI 60-77%], p-unadj = 0.002). On multivariable analysis, controlling for clinical risk score, ablation, margin status, and primary T-stage, co-altered RAS/RAF-TP53 was associated with increased risk for AR (HR = 2.14, 95% CI 1.38-3.31, p-unadj < 0.001), LR (HR = 1.79, 95% CI 1.06-3.02, p-unadj = 0.029), and ER (HR = 2.81, 95% CI 1.78-4.44, p-unadj < 0.001)., Conclusions: Altered KRAS, RAS/RAF, and RAS/RAF-TP53 associated with earlier local and distant recurrence in resected CRLM patients receiving adjuvant HAI+SYS. Co-altered RAS/RAF-TP53 was a novel predictor of LR warranting investigation of whether genomic cooperativity is associated with this relapsing phenotype. Systemic therapies tailored to high-risk tumor biology are needed to reduce distant relapse after hepatectomy., (© 2022. Society of Surgical Oncology.)

Background: Unresectable hepatocellular carcinoma (HCC) has a poor prognosis. We aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) for locally advanced HCC compared to transcatheter arterial chemoembolization (TACE)., Methods: A propensity score-matched cohort study was performed in patients with locally advanced HCC with ≥ 4 tumors or portal vein tumor thrombosis (PVTT) who underwent either HAIC using oxaliplatin plus raltitrexed or TACE at three institutions between June 2015 and December 2021. Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and adverse events (AEs) were compared between the groups., Results: After propensity score matching, 62 pairs of patients were evaluated. The HAIC group had longer OS (15.0 [95% CI: 12.1-17.9] vs. 9.0 [95% CI: 5.1-12.9] months; P = 0.034), better PFS (6.7 [95% CI: 5.1-8.3] vs. 4.0 [95% CI: 2.6-5.4] months; P = 0.020), and a higher ORR (RECIST 1.1: 54.8% vs. 11.3%; P < 0.001) than the TACE group in the intention-to-treat population. Compared with the TACE group, Grade 1-2 nausea and vomiting occurred significantly more frequently in the HAIC group., Conclusion: Compared to TACE, HAIC significantly increased the ORR of locally advanced HCC with multiple tumors or portal invasion and prolonged survival without causing a significant increase in severe AEs., (© 2022. The Society for Surgery of the Alimentary Tract.)

Objective: To examine genomic correlates of conversion to resection (CTR and overall survival (OS) in patients with initially unresectable colorectal liver metastasis (IU-CRLM) treated with combination systemic and hepatic artery infusion (HAI) chemotherapy., Background: In patients presenting with IU-CRLM, combination systemic and HAI chemotherapy enables CTR with associated long-term OS in a subset of patients. Genomic correlates of CTR and OS in IU-CRLM have not been previously explored., Methods: Specimens from IU-CRLM patients receiving systemic/HAI chemotherapy (2003-2017) were submitted for next-generation sequencing. Fisher Exact test assessed associations with CTR, and Kaplan-Meier/Cox methods assessed associations with OS from HAI initiation., Results: Of 128 IU-CRLM patients, 51 (40%) underwent CTR at median 6 months (range: 3-35) from HAI initiation. CTR and persistently unresectable cohorts differed significantly in preoperative systemic chemotherapy exposure, node-positive primary status, and size of largest liver metastasis. Median and 5-year OS was 66 months and 51%. CTR was associated with prolonged survival (time-dependent HR 0.23,95% CI: 0.12-0.46, P < 0.001). The most frequently altered genes were APC (81%), TP53 (77%), and KRAS (37%). Oncogenic mutations in SOX9 and BRAF were associated with CTR. BRAF mutations, any RAS pathway alterations, and co-altered RAS/RAF-TP53 mutations wereassociated with worse survival. Classification and regression tree analysis defined prognostically relevant clusters of genomic risk to reveal co-altered RAS/RAF-TP53 as the highest risk subgroup. Co-altered RAS/RAF-TP53 remained independently associated with worse survival (HR 2.52, 95% CI: 1.37-4.64, P = 0.003) after controlling for CTR, number of liver metastases, and preoperative extrahepatic disease., Conclusions: Distinct genomic profiles are associated with CTR and survival in patients with IU-CRLM treated with HAI/systemic chemotherapy. Presence of SOX9, BRAF , and co-altered RAS/RAF- TP53 mutations are promising biomarkers that, when validated in larger datasets, may impact treatment of IU-CRLM patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Acquired diaphragmatic hernia (ADH) is a rare complication after liver surgery in adult and pediatric patients. In the literature, a few low case series have been reported. Its incidence is estimated to be between 0.74% and 2.9%. Main descriptions of ADH concern liver resection for tumors, living donor hepatic donation in adult patients, and partial liver graft transplant in children [1,2]. We encountered a rare case of ADH in the postoperative time of a liver transplant with thrombosis of hepatic artery due to median arcuate ligament syndrome (MALS). The patient was a 65-year-old woman diagnosed with symptomatic hepatorenal polycystic disease who underwent a liver transplant with an isogroup graft from a cardiac-dead donor. During the first postoperative day, the rutinary color Doppler ultrasonography showed absent artery hepatic flow, and angiography suggested thrombosis of the hepatic artery (HA). With these findings, exploratory laparotomy was done. We performed thrombectomy and liberation of the celiac artery from the median arcuate ligament by dividing its fibers. At discharge, the liver function was normal, and Doppler showed good blood flow in the HA. At fourth postoperative month, she presented in the urgency unit with upper abdominal pain and vomiting. Radiologic and endoscopic evaluation revealed an incarcerated diaphragmatic hernia and signs of gastric ischemia. After emergency laparotomy and evaluation of the left hemithorax, we performed hernial sac reduction with recovery of gastric hypoperfusion. The diaphragmatic hernia was repaired. Diaphragmatic hernia is a rarely reported complication of liver transplant and should be considered a potential late complication [1]., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alternative treatment modalities are necessary because of the low response rates and unsuitability of molecular-targeted agents (MTA) and/or immune checkpoint inhibitors (iCIs) in HCC patients. Therefore, we analyzed whether drug-eluting beads (DEB)-transcatheter arterial chemoembolization (TACE) with low-dose-FP (Ultra-FP) therapy could improve the efficacy and safety of treatment in difficult-to-treat HCC patients, especially those with advanced stage HCC. From November 2017 to April 2021, 118 consecutive patients with non-resectable difficult-to-treat HCC were included in this study. All patients were treated with Ultra-FP therapy. After the weak DEB-TACE procedure, we administered low-dose FP for 2 weeks followed by resting for 4 weeks. The numbers of HCC patients CR/PR/SD/PD induced by Ultra-FP therapy were 36/52/17/13 (Modified RECIST) patients, respectively. The objective response rate of Ultra-FP therapy was 74.6% (88/118 patients). Tumor marker reduction was observed in 81.4% (96/118 patients). The objective response rate (ORR) in the HCC patients with portal vein tumor thrombosis (PVTT) was 75% (18/24 patients). Median overall survival (mOS) of all included HCC patients was 738 days. The mOS of HCC patients with PVTT (-)/PVTT (+) was 816 days/718 days. The proportion of patients based on ALBI grade system was not significantly different between pre- and after 3 course Ultra-FP therapy. Ultra-FP therapy might be an affordable treatment option for difficult-to-treat advanced HCC. ORR and overall survival after receiving Ultra-FP therapy were remarkable in comparison to various kinds of systemic therapy including MTA and iCIs., (© 2022. The Author(s).)

Liver and heart are anatomically and patho-physiologically related. In heart failure (HF) the increased right atrial pressure and volume overload cause histological changes in hepatocytes, leading to a condition known as "congestive hepatopathy" (CH), with consequent variations in liver functioning and ultrasound (US) findings. CH has specifical US findings especially regarding venous vessels aspect, easily detecting by gray-scale study, but many others can be distinguished by Doppler analysis. Usually, hepatic veins look enlarged and hypocollassing, together with signs of portal hypertension (hepatomegaly, ascites, splenomegaly, porto-systemic collaterals). Typically, in CH Doppler findings regard alterations in venous vessel flow and arterial resistance (venous system hyperpulsatility, reduced velocity flow, high resistance index in hepatic arterial Doppler spectrum). Sometimes CH and other primary hepatopathy can coexist, and therefore some of the expected variations may not manifest: it allows suspecting an unknown underlying liver disease. At last, US technologies of more recent applications, even if not routinely used, allow investigating additional aspects such as elastography that detects changes in liver elasticity or contrastographic US, able to show differences in hepatic venous opacification. However, most of these US signs are not pathognomonic, and therefore a multidisciplinary clinical reasoning must not be lacking. The aim of the present review is to easily provide US signs of liver alterations in HF, in particular right heart failure with volume overload, suggesting including liver US in instrumental diagnosis and therapeutic monitoring of HF., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Combined resection of the right hepatic artery (RHA) is sometimes required to achieve complete resection of hilar cholangiocarcinoma. The present study aimed to evaluate the feasibility of combined resection and subsequent reconstruction by continuous suture of the RHA during left hepatectomy for cholangiocarcinoma., Materials and Methods: We retrospectively compared the outcomes after left hepatectomy with biliary reconstruction for cholangiocarcinoma between patients with and without RHA resection and reconstruction., Results: Of the 25 patients who underwent left hepatectomy combined with biliary reconstruction, eight patients (32%) underwent combined resection and reconstruction of the RHA (AR group). The demographic characteristics were not different between the AR and non-AR groups. The amount of intraoperative bleeding was significantly greater in patients with AR (2350 mL vs. 900 mL, p = 0.017). The prevalence of early complications above grade III in Clavien-Dindo classification and late complications were not significantly different between the AR and non-AR groups. In the AR group, complications directly associated with AR, such as thrombosis or reanastomosis, were not observed. On Kaplan-Meier analysis, recurrence-free survival (p = 0.618) and overall survival (p = 0.803) were comparable between the two groups despite the advanced T stages in the AR group., Conclusions: Combined resection and subsequent reconstruction of the RHA during left-sided hepatectomy is a feasible treatment alternative for cholangiocarcinoma., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

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., (© 2022 Wiley Periodicals LLC.)

For patients with unresectable colorectal liver metastases (uCRLM), regional therapies leverage the unique, dual blood supply to the liver; the hepatic artery is the main blood supply for liver tumors, whereas the portal vein supplies most normal hepatic parenchyma. Infusion of cancer therapies via the hepatic artery allows selective delivery to the tumors with relative sparing of normal liver tissue and little extrahepatic exposure, thus limiting systemic side effects. There is a paucity of randomized controlled trial evidence to inform the optimal integration of regional therapies into the management of CRLM. Hepatic arterial infusion pump (HAIP) chemotherapy has a potential survival benefit when used in the adjuvant setting after resection of CRLM. HAIP chemotherapy can be safely given with contemporary systemic therapies and is associated with a high objective response and rate of conversion to resectability in patients with uCRLM. Drug-eluting beads coated with irinotecan transarterial chemoembolization is associated with high objective response rates within the liver and has a well-established safety profile in patients with uCRLM. Transarterial radioembolization achieves high rates of response within the liver but is not associated with improvements in overall survival or quality of life in the first- or second-line setting for uCRLM. The best treatment approach is the one that most aligns with a given patients' values, preferences, and philosophy of care. In the first-line setting, HAIP could be offered to motivated patients who hope to achieve conversion to resectability. After progression on chemotherapy, HAIP, transarterial chemoembolization, and transarterial radioembolization are valuable treatment options to consider for patients with liver-limited or liver-predominant CRLM who seek to optimize response rates and regional control., Competing Interests: Paul J. KaranicolasResearch Funding: Baxter (Inst)No other potential conflicts of interest were reported.

Background: The influence and risk associated with an aberrant right hepatic artery, a common anatomical variation, during pancreatoduodenectomy for pancreatic ductal adenocarcinoma has not been fully investigated. The present study analyzed the impact of an aberrant right hepatic artery on local recurrence after pancreatoduodenectomy for pancreatic ductal adenocarcinoma., Methods: A total of 169 patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy at 2 separate Japanese medical institutions were retrospectively analyzed., Results: Thirty of 169 patients (17.7%) presented with an aberrant right hepatic artery. The incidence of local recurrence was higher in the aberrant right hepatic artery group than in the normal right hepatic artery group (43.3 vs 21.5%, P = .017). The local recurrence-free survival was significantly poorer in the aberrant right hepatic artery group than in the normal right hepatic artery group (P = .011). A multivariate analysis found that the aberrant right hepatic artery was an independent risk factor for local recurrence (hazard ratio: 3.74, P = .017). In the aberrant right hepatic artery group, more frequent local recurrence was observed in patients with tumors situated ≤10 mm from the aberrant right hepatic artery root. However, local recurrence was not observed in 2 out of 3 patients with tumors ≤10 mm from the aberrant right hepatic artery root who underwent pancreatoduodenectomy with combined resection of the aberrant right hepatic artery., Conclusion: The presence of an aberrant right hepatic artery in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma may be associated with an increased risk of postoperative local recurrence. Combined resection of the aberrant right hepatic artery may reduce local recurrence, especially for tumors near the root of the aberrant right hepatic artery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The NCCN guidelines define pancreatic cancer that has contact with an aberrant right hepatic artery (A-RHA) as a borderline-resectable tumor. However, the impact of tumor contact with an A-RHA on surgical and survival outcomes has not been well discussed., Methods: A total of 541 patients who underwent pancreatoduodenectomy for resectable and borderline-resectable pancreatic cancer between 2002 and 2019 were retrospectively analyzed. The presence of an A-RHA and tumor contact with an A-RHA were evaluated based on the preoperative computed tomography findings. Patients with resectable tumors and tumors with A-RHA-contact (having contact with an A-RHA without involvement of the major arteries) were generally treated by upfront surgery, whereas those with borderline-resectable tumors generally underwent neoadjuvant therapy and subsequent resection., Results: Among the 541 patients, 116 (21.4%) had an A-RHA and 15 (2.8%) had tumor with A-RHA-contact. The A-RHA was resected in 12, and arterial reconstruction was performed in 8. The rates of morbidity and R1 resection in patients with an A-RHA (32.8 and 10.3%, respectively) were comparable to those without an A-RHA (27.3 and 11.3%, respectively). The overall survival in patients with A-RHA-contact was significantly worse than that in patients with borderline-resectable tumors (median survival time, 14.6 vs. 35.3 months, p = 0.048)., Conclusions: Although upfront resection was safely performed and led to a high R0 resection rate in patients with A-RHA-contact, the survival outcome was dismal. A tumor with A-RHA-contact should be regarded as technically resectable but oncologically borderline-resectable. Upfront surgery may not be appropriate for patients with A-RHA-contact., (© 2022. Society of Surgical Oncology.)

Background: Recently, hepatic arterial infusion chemotherapy (HAIC) plus lenvatinib has been frequently used to treat unresectable hepatocellular carcinoma (uHCC) in China. In the clinic, the hepatic arteries of some patients shrink significantly during this treatment, leading to improved short-term efficacy., Aim: To investigate the relationship between the shrinkage of hepatic arteries and the short-term effect of HAIC plus lenvatinib treatment., Methods: Sixty-seven participants with uHCC were enrolled in this retrospective study. The patients received HAIC every 3 wk, followed by oral lenvatinib after the first HAIC course. Hepatic artery diameters were measured on CT before treatment and after 1 and 2 mo of treatment. Meanwhile, the changes in tumor capillaries were also examined on pathological specimens before and after 1 mo of treatment. The antitumor response after 1, 3, and 6 mo of treatment was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The relationship between the changes in vessel diameters and the short-term effect of the combination treatment was evaluated by receiver-operating characteristic and logistic regression analyses., Results: The hepatic artery diameters were all significantly decreased after 1 and 2 mo of treatment ( P < 0.001), but there was no difference in the vessel diameters between 1 and 2 mo ( P > 0.05). The microvessel density in the tumor lesions decreased significantly after 1 mo of combination treatment ( P < 0.001). According to mRECIST, 46, 41, and 24 patients had complete or partial responses after 1, 3, and 6 mo of treatment, respectively, whereas 21, 21, and 32 patients had a stable or progressive disease at these times, respectively. Shrinkage of the tumor-feeding artery was significantly associated with the tumor response after 1, 3, and 6 mo of treatment ( P < 0.001, P = 0.004, and P = 0.023, respectively); however, changes in other hepatic arteries were not significantly associated with the tumor response. Furthermore, shrinkage of the tumor-feeding artery was an independent factor for treatment efficacy ( P = 0.001, P = 0.001, and P = 0.002 and 1, 3, and 6 mo, respectively)., Conclusion: The hepatic arteries shrank rapidly after treatment with HAIC plus lenvatinib, and shrinkage of the tumor-feeding artery diameter was closely related to improved short-term efficacy., Competing Interests: Conflict-of-interest statement: There was no conflict of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Surgical treatment is currently the only way to achieve the clinical cure for Klatskin tumor. However, whether combined vascular resection should be combined during surgeries is still controversial. The aim of this article was to analyze the effect of portal vein resection (PVR) and hepatic artery resection (HAR) on the long-term survival after surgery for Klatskin tumor., Methods: Articles about Klatskin tumor with PVR and HAR, which were published from 2000 to 2020, were searched using PubMed, Embase, and EBSCO. HR with a 95% CI of overall survival, recurrence-free survival, disease-free survival, 3- and 5-year survival rate, and median survival time were reported to evaluate prognosis., Results: A total of 17 articles were included. The total case number of these studies was 3150 (685 in the PVR group, 345 in the HAR group, and 2120 in the control group). Survival analyses showed that both vascular resection types were poor prognostic factors (PVR: HR = 1.50, 95% CI = 1.24-1.81, P < 0.001; HAR: HR = 1.68, 95% CI = 1.26-2.24, P < 0.001; the pooled effect size of the two groups: HR = 1.55, 95% CI = 1.32-1.82, P < 0.001). In general, the analyses of 3- and 5-year survival and median survival time showed that both vascular resection types tended to be poor prognostic factors, but most of recent researches showed that the PVR did not lead to a poor prognosis., Conclusion: PVR should be used when necessary to achieve R0 resection of Klatskin tumor and improve the long-term survival of patients. Whether HAR should be performed or not is still need to be evaluated., (© 2022. The Author(s).)

Background: Perihilar cholangiocarcinoma (pCCA) is often unresectable, because it includes crucial blood vessels in portal area. The prognosis of locally advanced unresectable cholangiocarcinomas is extremely poor. Recently, there have been several reports of the prognosis improving drastically with transplantation and combined chemoradiation therapy. However, liver transplantation for pCCA has 2 big problems. The first is that pCCA is located at a lethal position and its progress is sometimes rapid; therefore, the optimal timing of transplantation is sometimes lost. The second is vascular complications associated with neoadjuvant radiation, especially in living donor liver transplantation (LDLT). To overcome these problems, we performed conversion surgery using LDLT with simultaneous resection of the hepatic artery and portal vein, instead of neoadjuvant radiation. Herein, we report our experience of interposition reconstruction., Methods: A 31-year-old man with primary sclerosing cholangitis (PSC) was diagnosed with locally advanced unresectable pCCA. The patient underwent radical chemotherapy (gemcitabine/cisplatin/S-1) and avoided radiation because of PSC. After 6 months, positron emission tomography-computed tomography revealed no lymph node metastasis. There was no time to wait. We immediately performed LDLT with simultaneous resection of hepatic artery and portal vein, and microsurgical reconstruction using auto-vessel grafts., Results: The recipient recovered and was discharged 31 days posttransplant. His liver function improved, and he has had no recurrence after LDLT., Conclusion: LDLT with neoadjuvant radiation is associated with high risk of vascular complications. In some cases, conversion surgery after radical chemotherapy using good timing LDLT without radiation may increase chances of transplantation for locally advanced pCCA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investigate the radiation exposure of HAIC., Material and Methods: In this retrospective study, dose data from 841 procedures in 140 patients (mean age 65.3 ± 9.9 years, 74 female) who underwent HAIC between 06/2017 and 10/2021 at one of three different angiography systems were analyzed., Results: In the overall population, dose area product (DAP) (median (IQR)) was 1773 cGy·cm 2 (884-3688). DAP was significantly higher in the first intervention, where a complete diagnostic workup of the vasculature was performed, than in follow-up interventions: 5765 cGy·cm 2 (3160-8804) versus 1502 cGy·cm 2 (807-2712) (p < 0.0001). DAP also increased significantly with the number of infusion positions (median, (IQR)): one position 1301 cGy·cm 2 (633-2717), two positions 1985 cGy·cm 2 (1118-4074), three positions 6407 cGy·cm 2 (2616-11590) (p < 0.0001)., Conclusion: In uveal melanoma patients with liver metastases undergoing HAIC, radiation exposure is significantly higher both at the first intervention compared to follow-up interventions, but also with increasing number of infusion positions., (© 2022. The Author(s).)

Purpose: To model the effect of the injection location on the distribution of yttrium-90 ( 90 Y) microspheres in the liver during radioembolization using computational simulation and to determine the potential effects of radial movements of the catheter tip., Materials and Methods: Numerical studies were conducted using images from a representative patient with hepatocellular carcinoma. The right hepatic artery (RHA) was segmented from contrast-enhanced cone-beam computed tomography scans. The blood flow was investigated in the trunk of the RHA using numerical simulations for 6 injection position scenarios at 2 sites located at a distance of approximately 5 and 20 mm upstream of the first bifurcation (RHA diameters of approximately 4.6 mm). The 90 Y delivery to downstream vessels was calculated from the simulated hepatic artery hemodynamics., Results: Varying the injection location along the RHA and across the vessel cross-section resulted in different simulated microsphere distributions in the downstream vascular bed. When the catheter tip was 5 mm upstream of the bifurcation, 90 Y distribution in the downstream branches varied by as much as 53% with a 1.5-mm radial movement of the tip. However, the catheter radial movement had a weaker effect on the microsphere distribution when the injection plane was farther from the first bifurcation (20 mm), with a maximum delivery variation of 9% to a downstream branch., Conclusions: An injection location far from bifurcations is recommended to minimize the effect of radial movements of the catheter tip on the microsphere distribution., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

This work was to evaluate the therapeutic effect of lipid nanoparticle-loaded sorafenib combined with transcatheter artery chemoembolization (TACE) in patients with primary hepatocellular carcinoma (HC) complicated with microvascular invasion (MVI). In this work, 102 patients with primary HC combined with MVI after radical resection were divided into 4 groups according to different treatment methods. Experimental group 1 was treated with lipid nanoparticle-loaded sorafenib combined with TACE treatment group; experimental group 2 was treated with lipid nanoparticle-loaded sorafenib treatment group; experimental group 3 was TACE treatment group; control group was postoperative routine nursing group. Sorafenib lipid nanoparticles were prepared. The basic information, operation, MVI degree, tumor recurrence, and survival time of patients in each group were recorded and compared to evaluate the therapeutic effect of combined way. No great difference was found in MVI grade, average age, sex ratio, preoperative tumor markers, tumor size, number of patients with liver cirrhosis, operation time, and intraoperative bleeding among the four groups ( P > 0.05). In addition, the tumor free survival time (TFST), overall survival time (OST), and postoperative 1-year and 2-year survival rates of patients in test group 1 were greatly higher than those in single mode treatment group and control group ( P < 0.05). In summary, sorafenib nanoparticles combined with TACE can improve the survival status of patients after resection and delay the time of postoperative tumor recurrence., Competing Interests: The authors declare that they have no competing interest., (Copyright © 2022 Wendong Feng et al.)

Introduction: Metastatic progression occurs along the locoregional vasculature, and a common anatomic variant is an aberrant right hepatic artery (aRHA). This study evaluated the effect of an aRHA following pancreaticoduodenectomy, with a focus on hepatic metastases., Methods: This was a single-institution retrospective review of non-metastatic pancreatic cancer cases between 2012 and 2020. aRHA cases were compared with patients with conventional anatomy. The primary outcome was hepatic recurrence rates, while secondary analysis survival outcomes were measured by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was stratified by tumor resectability and utilization of systemic therapy., Results: Overall, 207 cases were reviewed, with 17.4% having aRHA anatomy. On multivariate analysis, aRHA increased hepatic recurrence for all-comers (odds ratio [OR] 4.76, 95% confidence interval [CI] 2.18-10.38; p < 0.001). aRHA was significant for resectable tumors (OR 2.58, 95% CI 1.89-6.66; p = 0.045) and borderline resectable tumors (OR 28.88, 95% CI 5.52-151.18; p < 0.0001) in regard to hepatic recurrence on univariate analysis. Increased hepatic recurrence correlated with decreased 3-year OS and DFS rates of 30.6% versus 50.3% (OR 0.44, 95% CI 0.20-0.94; p = 0.032) and 13.6% versus 36.9% (OR 0.27, 95% CI 0.08-0.97; p = 0.035). Systemic therapy limited the effects of aRHA., Conclusion: aRHA was associated with inferior survival outcomes due to the significantly increased risk of hepatic metastatic disease with aberrant anatomy. This study provides important prognostic information for a commonly encountered anatomic variant., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Hemobilia is an extremely rare cause of upper gastrointestinal bleeding. It often has intermittent manifestation, which may lead to significant diagnostic delay. In 65% of the cases, the causes are iatrogenic, in 7% the cause is malignancy, in 5% - gallstones, in 8% it is inflammation (cholecystitis, parasites, reflux cholangitis), vascular abnormality is the cause in 7% (most commonly pseudoaneurysm of the hepatic artery), and pancreatic pseudocyst causes hemobilia in 1%. In almost all cases, the bleeding originates from intrahepatic or extrahepatic bile ducts, and rarely from the pancreas., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established., Methods: Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics., Results: Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS)., Conclusion: Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing., (© 2021. The Society for Surgery of the Alimentary Tract.)

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131 I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131 I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131 I-metuximab group ( n = 160) and 3 mo in the TACE group ( n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131 I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131 I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To characterize the hepatic and abdominal angiographic anatomy of woodchucks and vascular changes associated with hepatocellular carcinoma (HCC)., Materials and Methods: Twenty-nine woodchucks (23 with viral-associated HCC, 6 without) underwent multiphasic computed tomography (CT). Fourteen woodchucks (8 with HCC) also underwent diagnostic angiography. Hepatic arterial diameters were measured on the CT scans. Woodchucks were divided into 3 groups: non-tumor-bearing, largest tumor supplied by the right hepatic artery (RHA), and largest tumor supplied by the left hepatic artery (LHA). Statistical analysis with a repeated measures model was performed to determine the effects of tumor location (right, left), vessel measured (RHA, LHA), and interaction between the 2 on vessel diameter. Lobar arteries supplying HCC were compared with those that did not., Results: CT anatomy and normal and variant vascular anatomy were defined. In woodchucks with HCC, LHA and RHA supplying tumors had mean diameters of 2.0 mm ± 0.3 and 1.6 mm ± 0.3 versus 1.5 mm ± 0.3 and 1.1 mm ± 0.2 for non-tumor-supplying arteries (P = .0002 and P < .0001), respectively. Lobar arteries supplying tumors were similarly ectatic. The right lateral lobe artery had the most profound increase in the mean diameter when supplying tumors, measuring 1.7 mm ± 0.1 versus 1.0 mm ± 0.1 in the non-tumor-supplying artery (P < .0001). There were no differences in the diameters of the aorta and celiac, common, and proper hepatic arteries between tumor- and non-tumor-bearing woodchucks. An angiographic atlas of the abdominal vessels was generated., Conclusions: HCC tumoral vasculature in woodchucks was ectatic compared with normal vasculature. This phenomenon recapitulates human HCC and may facilitate investigation of transcatheter and drug delivery therapies in an HCC animal model., (Published by Elsevier Inc.)

Background: The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM., Methods: PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design., Results: Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine., Conclusion: Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite increasing attention in the cardiac anesthesiology literature, continuous measurement of right ventricular pressure using a pulmonary artery catheter has not been described in orthotopic liver transplantation, despite similarities in the anesthetic approach to the two populations. We describe our preliminary experience with this technique in orthotopic liver transplantation, and by combining various derived measures with trans-esophageal echocardiography, make some early observations regarding the response of these measures of right ventricular function during the procedure., Methods: In this case series, ten patients (five men and five women) undergoing orthotopic liver transplantation in our institution had their surgeries performed while monitored with a pulmonary artery catheter with continuous right ventricular port transduction and trans-esophageal echocardiography. We recorded various right ventricular waveform (early-to-end diastolic pressure difference, right ventricular outflow tract gradient, right ventricular dP/dT and right ventricular end-diastolic pressure) and echocardiographic (right ventricular fractional area change, tricuspid annular plane systolic excursion, right ventricular lateral wall strain) and described their change relative to baseline at timepoints five minutes before and after portal vein reperfusion, immediately after hepatic artery reperfusion and on abdominal closure., Results: Except for tricuspid annular plane systolic excursion at five minutes prior to reperfusion (mean -0.8 cm; 95% CI-1.4, -0.3; p = 0.007), no echocardiographic metric was statistically significantly different at any timepoint relative to baseline. In contrast, changes in right ventricular outflow tract gradient and right ventricular dP/dt were highly significant at multiple timepoints, generally peaking immediately before or after reperfusion before reducing, but not returning to baseline in the neohepatic phase. Nine of 10 participants in this series demonstrated a degree of dynamic right ventricular outflow tract obstruction, which met criteria for hemodynamic significance (> 25 mmHg) in two participants. These changes were not materially affected by cardiac index., Conclusions: Dynamic right ventricular outflow tract obstruction of varying severity appears common in patients undergoing orthotopic liver transplantation. These results are hypothesis generating and will form the basis of future prospective research., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: The institution for which Lachlan F. Miles works has received financial support from Edwards LifeSciences, although he himself is not the recipient of any grants or funding. Cristhian Potes is an employee of Edwards LifeSciences. Laurence Weinberg is a member of the speaker bureau for Edwards LifeSciences and Masimo and has received financial support from both organizations. André Y. Denault reports grants from Edwards LifeSciences outside the submitted work. He is a member of the speaker bureau and a key opinion leader for CAE Healthcare and Masimo. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No other authors have any conflicts of interest to report.

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.

Objective: The objective of the study was to investigate the consequences of using CArm Cone-Beam computed Tomography (CBCT) on super-selective catheterization of Hepatic Artery (HA) branches during chemoembolization of hepatocellular carcinoma., Methods: Two groups of patients were created according to the dates of their treatment sessions. Group A and Group B included patients who had their treatment sessions in 2004 - 2005 and 2008 - 2010, respectively. The sessions performed in 2006 and 2007 were excluded to allow for the adoption and incorporation of CBCT imaging into clinical practice. All chemoembolized HA branches were categorized according to selection order (0-1, 2, or ≥3). Other procedure variables were documented., Results: A total of 58 and 183 sessions were included in Groups A and B, respectively, for 144 patients. C-arm CBCT was used in 2 (3%) sessions and 142 (78%) sessions in groups A and B, respectively. The average number of vessels treated was significantly higher in group B (1.8) compared to group A (1.3) (P < .0001). A shift to an increased selection order in group B (0-1, 44 [24%]; 2, 85 [46%]; ≥3, 54 [30%]) was more significant (P = .0004) than that in group A (0-1, 32 [55%]; 2, 18 [31%]; ≥3, 8 [14%]). The average duration of the procedure was significantly longer in group B (P = .0002)., Conclusion: Using C-arm CBCT during chemoembolization has a positive impact on increasing the number and order of HA selected and chemoembolized. This comes at the expense of an increase in the duration of the procedure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)