Hepatic Arterial Infusion Pump Research Articles

ASO Author Reflections: Application of Robotic Technique for Treatment of Biliary Sclerosis from Hepatic Artery Infusion Pump Chemotherapy.

ASO Author Reflections: Application of Robotic Technique for Treatment of Biliary Sclerosis from Hepatic Artery Infusion Pump Chemotherapy.

Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.

Robotic Biliary Stricturoplasty and Roux-en-Y Hepaticojejunostomy After Hepatic Artery Infusion Pump Injury.

Recurrence patterns after complex multimodality therapy and hepatic arterial infusion for colorectal liver metastases: A reflection of biology and technique.

We characterized colorectal liver metastasis recurrence and survival patterns after surgical resection and intraoperative ablation ± hepatic arterial infusion pump (HAIP) placement. We estimated patterns of recurrence and survival in patients undergoing contemporary multimodal treatments. Between 2017 and 2021, patient, tumor characteristics, and recurrence data were collected. Primary outcomes included recurrence patterns and survival data based on operative intervention. There were 184 patients who underwent hepatectomy and intraoperative ablation. Sixty patients (32.6%) underwent HAIP placement. A total of 513 metastases were ablated, median total of 2 ablations per patient. Median time to recurrence was 31 [22-40] months. Recurrence patterns included tumor at ablative margin on first scheduled postoperative imaging (8, 4.3%), local tumor recurrence at ablative site (69, 37.5%), and non-ablated liver tumor recurrence (38, 20.6%). In patients who underwent HAIP placement, the rate of liver recurrence was reduced (45% vs 70.9%, p = 0.0001). Median overall survival was 64 [41-58] months and prolonged survival was associated with HAIP treatment (85 [66-109] vs 60 [51-70] months. Hepatic recurrence is common and combination of intraoperative ablation and HAIP treatments were associated with prolonged survival. These data may reflect patient selection however, future work will clarify preoperative tumor and patient characteristics that may better predict recurrence expectations.

Robotic Versus Open Hepatic Arterial Infusion Pump Placement for Unresectable Intrahepatic Cholangiocarcinoma.

Hepatic arterial infusion pump (HAIP) chemotherapy is an effective treatment for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). HAIP chemotherapy requires a catheter inserted in the gastroduodenal artery and a subcutaneous pump. The catheter can be placed using an open or robotic approach. This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA. We analyzed patients with unresectable iCCA included in the PUMP-II trial from January 2020 to September 2022 undergoing robotic or open HAIP placement at Amsterdam UMC, Erasmus MC, and UMC Utrecht. The primary outcome was time to functional recovery (TTFR). In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2days after robotic placement versus 5 days after open HAIP placement (p<0.001). One patient (4.5%) in the robotic group underwent a conversion to open because of a large bulky tumor leaning on the hilum immobilizing the liver. Postoperative complications were similar-36% (8/22) after robotic placement versus 39% (11/28) after open placement (p=1.000). The median length of hospital stay was shorter in the robotic group-3 versus 5 days (p<0.001). All 22 robotic patients initiated HAIP chemotherapy post-surgery, i.e. 93% (26/28) in the open group (p=0.497). The median time to start HAIP chemotherapy was 14 versus 18 days (p=0.153). Robotic HAIP placement in patients with unresectable iCCA is a safe and effective procedure and is associated with a significantly shorter TTFR and hospital stay than open HAIP placement.

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications

IntroductionThis study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. MethodsThe first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. ResultsPatients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0–2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. ConclusionMethylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.

433 Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Results: From January 2020 until September 2022, 50 patients with advanced iCCA were included. Combined HAIP and systemic chemotherapy was administered to 38 patients (76.0%). Eleven patients (22.0%) received HAIP chemotherapy alone, because they had received systemic treatment before enrollment. One patient (2.0%) didn’t start treatment, because he died 19 days after pump implantation due to COVID-19. The median follow-up was 26.4 months (95% CI: 21.7 – 39.0). The median OS was 22.1 months (95% CI: 19.7 – not reached). The 1-year OS rate was 80.0% (95% CI: 69.6% – 91.9%); the 3-year OS rate was 28.6% (95% CI: 16.0% – 51.2%). The median PFS was 10.0 months (95% CI: 8.7 – 12.2). An objective response on imaging (RECIST) was achieved in 27 patients (54.0%) and disease control at 6 months in 43 patients (86.0%). Four patients (8.0%) underwent a resection after HAIP chemotherapy of whom 2 patients had a complete pathologic response. Conclusions: Combined HAIP with systemic chemotherapy for patients with advanced iCCA was associated with a favorable 3-year OS of 28.6% compared with 2.8% after systemic chemotherapy alone in the ABC trials. Clinical trial information: NL8234 .

Phase II study evaluating the efficacy of PDS0301 in combination with hepatic artery infusion pump (HAIP) and systemic therapy for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma.

TPS586 Background: Treatment of advanced liver tumors continues to pose significant challenges. Despite advances in immunotherapies, including immune checkpoint blockade, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. The lack of robust clinical efficacy is likely myriad, including immunosuppression by the tumor microenvironment and poor susceptibility of these tumors to immune infiltration and surveillance. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with extensive anti-tumor properties, but therapeutic development of recombinant human IL-12 (rhIL-12) was halted due to significant systemic toxicities. PDS0301 (formerly M9241) is a novel human monoclonal antibody (NHS76) fused to two IL-12 heterodimers. The NHS76 antibody specifically targets histone/DNA complexes in regions of cellular necrosis resulting in accumulation within tumors. Importantly, recent Phase I trials have shown PDS0301 monotherapy to be well tolerated. We hypothesize that synchronization of PDS0301 administration with tumor cell death induced by locoregional and systemic chemotherapies will demonstrate increased efficacy over standard of care therapy. Methods: This is a single center, non-randomized Phase II study to determine the safety and efficacy of PDS0301 in combination with floxuridine (FUDR) administered by hepatic artery infusion pump (HAIP) and systemic chemotherapies in patients with either unresectable metastatic colorectal cancer (mCRC) or intrahepatic cholangiocarcinoma (ICC). Eligibility criteria include histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the liver (Cohort 1) or unresectable intrahepatic cholangiocarcinoma with no evidence of extrahepatic metastases (Cohort 2). Patients will receive HAIP-administered (FUDR) plus PDS0301 at a starting dose of 12mcg/kg in 28-day cycles. Beginning in cycle 2, systemic chemotherapy with FOLFOX (Leucovorin, 5-Fluorouracil [5-FU], and Oxaliplatin) or FOLFIRI (Leucovorin, 5-FU and Irinotecan) for mCRC or GemOx (Gemcitabine and Oxaliplatin) for ICC will be introduced. Patients will be evaluated for response at eight-week intervals. The primary endpoint is overall response rates to PDS0301 and HAIP/systemic combination therapy. Secondary objectives include hepatic progression-free survival (PFS), extra-hepatic PFS, overall survival, and safety. Scientific objectives include determination of microenvironment alterations through pre-and post-treatment biopsies as well as evaluation of peripheral immune subsets and cytokines. To date, we have enrolled 8 of 23 patients in Cohort 1. Clinical trial information: NCT05286814 .

A phase II trial of induction systemic mFOLFIRINOX followed by hepatic arterial infusion of floxuridine and dexamethasone given concurrently with systemic mFOLFIRI as a first-line therapy in patients with unresectable liver-dominant intrahepatic cholangiocarcinoma (HELIX-1).

511 Background: Most patients with intrahepatic cholangiocarcinoma (ICC) have unresectable or multifocal liver-dominant disease. Survival after first-line systemic therapy remains poor, with median progression-free (mPFS) and overall survival of 7.2 and 12.8 months, respectively. Hepatic arterial infusion (HAI) therapy with floxuridine maximizes liver-specific treatment with minimal systemic toxicity and potentially offers improved disease control when combined with systemic therapy. Methods: HELIX-1 (NCT04251715) is an investigator-initiated, first-line, single-center, single-arm phase II clinical trial for patients with liver-dominant unresectable or multifocal ICC. The trial was designed with a patient safety run-in evaluating toxicity from the combined therapy. Pre-trial screening included laparoscopy, biopsies, and PET/CT. Eligible patients were treated with systemic mFOLFIRINOX for 4 cycles in order to select those likely to benefit from HAI. Patients with disease control on restaging proceeded to HAI pump placement and treatment with HAI floxuridine for 14 days followed by systemic mFOLFIRI on a 28-day cycle. The co-primary objectives were to assess safety of the combined therapeutic strategy and the disease control rate (DCR) at 6 months (RECIST v1.1) at end of trial (EOT). Results: A total of n=5 patients with liver-only ICC enrolled in the trial and completed the entire study protocol. The median age was 60 years (range 42-69) with a dominant lesion size of 9.8cm (range 8.4-14.5). All patients had both right and left hemiliver involvement with a median of 9 intrahepatic tumors (range 1-15). No patients experienced grade 3 or 4 adverse events, or hepatic dysfunction leading to cessation of HAI therapy. The DCR at 6 months was 100%, with a mPFS of 18.2 months. All five patients achieved partial radiographic response (PR) while receiving HAI therapy, and remain alive with liver-only disease at a median of 18.4 months (range 12.7-20) after study enrollment. After continuing treatment with HAI and systemic mFOLFIRI beyond the EOT, two patients transitioned to HAI treatment only and then to biochemical and radiographic surveillance without therapy after demonstrating PR and CA19-9 normalization. Conclusions: Integration of HAI floxuridine with mFOLFIRI following mFOLFIRINOX induction for patients with liver-only advanced ICC is well-tolerated and demonstrates longer DCR in comparison to historical controls. The combined regimen minimized systemic toxicity and allowed a large proportion of patients to transition to liver-only HAI treatment with maintained disease control. Future directions include combining HAI with new first-line systemic regimens for patients with advanced ICC. Clinical trial information: NCT04251715 .

Robotic versus open placement of hepatic artery infusion pumps: a bi-institutional propensity score matching weights analysis

Robotic versus open placement of hepatic artery infusion pumps: a bi-institutional propensity score matching weights analysis

Adjuvant hepatic arterial infusion pump chemotherapy after repeat hepatectomy for patients with liver confined recurrence of colorectal cancer – a phase ii study

Adjuvant hepatic arterial infusion pump chemotherapy after repeat hepatectomy for patients with liver confined recurrence of colorectal cancer – a phase ii study

Postoperative hepatic arterial infusion pump chemotherapy after resection of multinodular colorectal liver metastases

Postoperative hepatic arterial infusion pump chemotherapy after resection of multinodular colorectal liver metastases

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Feasibility of hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for patients with colorectal liver metastases in the Netherlands: the PUMP-IT pilot study

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: a multicenter phase II trial

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: a multicenter phase II trial

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases: What Does the Colorectal Surgeon Need to Know?

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Expert Commentary on Hepatic Artery Infusion Pump Chemotherapy for Colorectal Liver Metastases.

Case-Based Clinical Guidance on Dosing and Management of the Hepatic Artery Infusion Chemotherapy Pump.

Hepatic artery infusion (HAI) delivers localized high-dose floxuridine directly to liver tumors through an implanted pump. While patients are undergoing active treatment, the pump is refilled with chemotherapy alternating with saline every 2 weeks using a specialized noncoring needle. Numerous clinical scenarios influence the dosing of floxuridine, which do not conform to the usual dose modification schema for systemic chemotherapy. This article aims to provide practical clinical management solutions to overcome the common challenges faced by oncologists in the real-world management of HAI pump therapy.

Embryology, anatomy and physiology of the liver: Review

The liver, located within the peritoneal cavity, is in the right upper quadrant of the abdomen. Additionally, it should be noted that the liver holds the distinction of being the largest gland within the human body, as well as the most extensive visceral tissue situated within the abdominal cavity. One of the factors contributing to the early migration of the developing intestines to an extracoelomic location during fetal development is their relatively bigger size in children, weighing between 1400 and 1800 g in adults. It contributes to the development of a distended abdomen in pediatric populations. The liver is situated in the right upper quadrant of the abdomen and spans across the midline to the left upper quadrant. The heart remains susceptible to regular injuries despite the protective presence of ribs and cartilage. The liver, functioning as an accessory organ in digestion, undertakes several metabolic processes, including drug metabolism, bile production, and bilirubin synthesis, alongside numerous other functions. For a considerable period, medical professionals and anatomists have encountered challenges in comprehending the complex functions of the liver. Significant advancements in the comprehension of liver anatomy have contributed significantly to the notable progress observed in various surgical and interventional radiologic procedures involving hepatic artery infusion pumps, liver ablation, transplantation, transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. The existence of hepatic structure is crucial for developing and implementing gradual therapies. This page aims to provide an academic overview of the embryology, anatomy, and function of the liver.

Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma

BackgroundA post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA.MethodsWe retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center.ResultsIn total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p < 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39).ConclusionsThis study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.

The Effect of Histopathological Growth Patterns of Colorectal Liver Metastases on the Survival Benefit of Adjuvant Hepatic Arterial Infusion Pump Chemotherapy

BackgroundHistopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM.MethodsPatients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan–Meier and Cox regression methods, respectively.ResultsWe included 1233 patients. In the dHGP group (n = 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (n = 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32–0.73, p < 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45–0.82, p < 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72–2.32, p = 0.40).ConclusionsThere is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM.

ASO Visual Abstract: Combined Hepatic Artery Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases.

ASO Visual Abstract: Combined Hepatic Artery Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases.