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

BACKGROUND: Hepatic artery infusion pump (HAIP) with floxuridine/dexamethasone and systemic chemotherapy is an established treatment regimen, which had been reported about converting 47% of patients with stage 4 colorectal liver metastasis from unresectable to resectable.1,2 To this effect, HAIP chemotherapy contributes to prolonged survival of many patients, which otherwise may not have other treatment options. Biliary sclerosis, however, is a known complication of the HAIP treatment, which occurs in approximately 5.5% of patients receiving this modality as an adjuvant therapy after hepatectomy and in 2% of patients receiving HAIP treatment for unresectable disease.3 While biliary sclerosis diffusely affects the perihilar and intrahepatic biliary tree, a dominant stricture maybe found in select cases, which gives an opportunity for a local surgical treatment after failure of endoscopic stenting/dilations. While the use of minimally invasive approach to biliary surgery is gradually increasing,4 there have been no descriptions of its application in this scenario. In this video, we demonstrate the use of minimally invasive robotic technique for biliary stricturoplasty and Roux-en-Y (RY) hepaticojejunostomy to treat persistent right hepatic duct stricture after HAIP chemotherapy. PATIENT: A 68-year-old woman with history of multifocal bilobar stage 4 colorectal liver metastasis presented to our office with obstructive jaundice and recurrent cholangitis that required nine endoscopic retrograde cholangiopancreatographies (ERCPs) and a placement of internal-external percutaneous transhepatic biliary drain (PTBD) by interventional radiology within the past 2 years. Her past surgical history was consistent with laparoscopic right hemicolectomy 3 years prior, followed by a left lateral sectorectomy with placement of an HAIP for adjuvant treatment. The patient had more than ten metastatic liver lesions within the right and left lobe, ranging from 2 to 3 cm in size at the time of HAIP placement. The patient had a histologically normal background liver parenchyma before the HAIP chemotherapy treatment. The patient did not have any history of alcohol use, diabetes mellitus, metabolic syndrome, nonalcoholic steatohepatitis, or other underlying intrinsic liver disorders, which are known to contribute to the development of hepatic fibrosis. Despite a radiologically disease-free status, the patient started to have episodes of acute cholangitis 1 year after the placement of HAIP that required multiple admissions to a local hospital. The HAIP was subsequently removed once the diagnosis of biliary sclerosis was made despite dose reductions and treatment with intrahepatic dexamethasone for almost 1 year. In addition to this finding, the known liver metastases have shown complete radiological resolution. Therefore further treatment with HAIP was deemed unnecessary, and pump removal was undertaken. Magnetic resonance imaging showed a dominant stricture at the junction of the right anterior and right posterior sectoral hepatic duct. The location of the dominant stricture was confirmed by an ERCP and cholangioscopy. Absence of neoplasia was confirmed with multiple cholangioscopic biopsies. Multiple endoscopic and percutaneous attempts with stent placement failed to dilate the area of stricture. Postprocedural cholangiographies showed a persistent significant narrowing, which led to multiple recurrent obstructive jaundice and severe cholangitis. While the use of surgical approach is rarely needed in the treatment of biliary sclerosis, a decision was made after extensive multidisciplinary discussions to perform a robotic stricturoplasty and RY hepaticojejunostomy with preservation of the native common bile duct. TECHNIQUE: The operation began with a laparoscopic adhesiolysis to allow for identification of HAIP tubing (which was later removed) and placement of robotic ports. A peripheral liver biopsy was obtained to evaluate the degree of hepatic parenchymal fibrosis. Porta hepatic area was carefully exposed without causing an inadvertent injury to the surrounding hollow organs. Biopsy of perihepatic soft tissues was taken as appropriate to rule out any extrahepatic disease. The common bile duct and common hepatic duct with ERCP stents within it were identified with the use of ultrasonography. Anterior wall of the common hepatic duct was then opened, exposing the two plastic stents. Cephalad extension of the choledochotomy was made toward the biliary bifurcation and the right hepatic duct. The distal common bile duct was preserved for future endoscopic access to the biliary tree. After lowering the right-sided hilar plate, dense fibrosis around the right hepatic duct was divided sharply with robotic scissors, achieving a mechanical release of the dominant stricture. An intraoperative cholangioscopy was performed to confirm adequate openings of the right hepatic duct secondary and tertiary radicles, as well as patency of the left hepatic duct. A 4-Fr Fogarty catheter was used to sweep the potential biliary debris from within the right and left hepatic lobe. Finally, a confirmatory choledochoscopy was performed to ensure patency and clearance of the right-sided intrahepatic biliary ducts and the left hepatic duct before fashioning the hepaticojejunostomy. A 40-cm antecolic roux limb was next prepared for the RY hepaticojejunostomy. A side-to-side double staple technique was utilized to create the jejunojejunostomy. The common enterotomy was closed in a running watertight fashion. Once the roux limb was transposed to the porta hepatic in a tension-free manner, a side-to-side hepaticojejunostomy was constructed in a running fashion by using absorbable barbed sutures. The index suture was placed at 9 o'clock location, and the posterior wall of the anastomosis was run toward 3 o'clock location. This stabilized the roux limb to the bile duct. The anterior wall of the anastomosis was next fashioned by using a running technique from both corners of the anastomosis toward the middle (12 o'clock), where both sutures were tied together. This completed a wide side-to-side hepaticojejunostomy anastomosis encompassing the upper common hepatic duct, biliary bifurcation, and the right hepatic duct. A closed suction drain was placed before closing.5 RESULTS: The operative time was approximately 4 hr with 60 ml of blood loss. The postoperative course was uneventful. The patient was discharged home on postoperative Day 5 after removal of the closed suction drain, confirming the absence of bile leak. The patient had developed periportal/periductal fibrosis, cholestasis, and moderate-severe parenchymal fibrosis (F3-F4) based on liver biopsy, often seen in patients treated with a long course of floxuridine HAIP chemotherapy. The patient is clinically doing well at 1 year outpatient follow-up without any evidence of recurrent cholangitis at the time of this manuscript preparation. CONCLUSIONS: Robotic biliary stricturoplasty with RY hepaticojejunostomy for treatment of biliary sclerosis after HAIP chemotherapy is safe and feasible. Appropriate experience in minimally invasive hepatobiliary surgery is necessary to achieve this goal.

Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy for borderline resectable and unresectable colorectal liver metastases: phase II feasibility study.

BACKGROUND: Hepatic arterial infusion pump chemotherapy combined with systemic chemotherapy (HAIP-SYS) for liver-only colorectal liver metastases (CRLMs) has shown promising results but has not been adopted worldwide. This study evaluated the feasibility of HAIP-SYS in the Netherlands. METHODS: This was a single-arm phase II study of patients with CRLMs who received HAIP-SYS consisting of floxuridine with concomitant systemic FOLFOX or FOLFIRI. Main inclusion and exclusion criteria were borderline resectable or unresectable liver-only metastases, suitable arterial anatomy and no previous local treatment. Patients underwent laparotomy for pump implantation and primary tumour resection if in situ. Primary end point was feasibility, defined as ≥70% of patients completing two cycles of HAIP-SYS. Sample size calculations led to 31 patients. Secondary outcomes included safety and tumour response. RESULTS: Thirty-one patients with median 13 CRLMs (i.q.r. 6-23) were included. Twenty-eight patients (90%) received two HAIP-SYS cycles. Three patients did not get two cycles due to extrahepatic disease at pump placement, definitive pathology of a recto-sigmoidal squamous cell carcinoma, and progressive disease. Five patients experienced grade 3 surgical or pump device-related complications (16%) and 11 patients experienced grade ≥3 chemotherapy toxicity (38%). At first radiological evaluation, disease control rate was 83% (24/29 patients) and hepatic disease control rate 93% (27/29 patients). At 6 months, 19 patients (66%) had experienced grade ≥3 chemotherapy toxicity and the disease control rate was 79%. CONCLUSION: HAIP-SYS for borderline resectable and unresectable CRLMs was feasible and safe in the Netherlands. This has led to a successive multicentre phase III randomized trial investigating oncological benefit (EUDRA-CT 2023-506194-35-00). Current trial registration number: clinicaltrials.gov (NCT04552093).

Implementation of Infusion Pumps and Filtered Administration Sets for Stem Cell Transplantation.

Stem cell infusion practices vary widely among institutions. A nurse-driven quality improvement project sought to determine whether peristaltic pumps and filtered tubing compromised the safety of stem cell infusion. A preclin.

Does circle priming improve smart infusion pump and electronic health record interoperability for chemotherapy in a pediatric hematology/oncology setting?

INTRODUCTION: The objective of this project was to assess the percentage of interoperability compliance within our pediatric hematology/oncology patient care areas for intravenous chemotherapy medications before and after the implementation of circle priming. METHODS: We conducted a retrospective quality improvement project at an inpatient pediatric hematology/oncology floor and outpatient pediatric infusion center before and after implementation of circle priming. RESULTS: There was a statistically significant increase in percent interoperability compliance for the inpatient pediatric hematology/oncology floor from 4.1% prior to implementation of circle priming to 35.6% after (odds ratio 13.1 (95% CI, 3.96-43.1), p < 0.001), as well as for the outpatient pediatric infusion center from 18.5% to 47.3%, respectively (odds ratio 3.9 (95% CI, 2.7-5.9), p < 0.001). CONCLUSION: Implementation of circle priming has significantly increased the percentage of interoperability compliance for intravenous chemotherapy medications in our pediatric hematology/oncology patient care areas.

Pressure-adjusted venting eliminates start-up delays and compensates for vertical position of syringe infusion pumps used for microinfusion.

Microinfusions are commonly used for the administration of catecholamines, but start-up delays pose a problem for reliable and timely drug delivery. Recent findings show that venting of the syringe infusion pump with draining of fluid to ambient pressure before directing the flow towards the central venous catheter does not counteract start-up delays. With the aim to reduce start-up delays, this study compared fluid delivery during start-up of syringe infusion pumps without venting, with ambient pressure venting, and with central venous pressure (CVP)-adjusted venting. Start-up fluid delivery from syringe pumps using a microinfusion of 1 mL/h was assessed by means of liquid flow measurement at 10, 60, 180 and 360 s after opening the stopcock and starting the pump. Assessments were performed using no venting, ambient pressure venting or CVP-adjusted venting, with the pump placed either at zero, - 43 cm or + 43 cm level and exposed to a simulated CVP of 10 mmHg. Measured fluid delivery was closest to the calculated fluid delivery for CVP-adjusted venting (87% to 100% at the different timepoints). The largest deviations were found for ambient pressure venting (- 1151% to + 82%). At 360 s after start-up 72% to 92% of expected fluid volumes were delivered without venting, 46% to 82% with ambient pressure venting and 96% to 99% with CVP-adjusted venting. CVP-adjusted venting demonstrated consistent results across vertical pump placements (p = 0.485), whereas the other methods had significant variances (p < 0.001 for both). In conclusion, CVP-adjusted venting effectively eliminates imprecise drug delivery and start-up delays when using microinfusions.

A novel, small-volume subcutaneous furosemide formulation delivered by an abdominal patch infusor device in patients with heart failure: results of two phase I studies.

AIMS: Subcutaneous (SC) furosemide has potential advantages over intravenous (IV) furosemide by enabling self-administration or administration by a lay caregiver, such as facilitating early discharge, preventing hospitalizations, and in palliative care. A high-concentration, pH-neutral furosemide formulation has been developed for SC administration via a small patch infusor pump. We aimed to compare the bioavailability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of a new SC furosemide formulation with conventional IV furosemide and describe the first use of a bespoke mini-pump to administer this formulation. METHODS AND RESULTS: A novel pH-neutral formulation of SC furosemide containing 80 mg furosemide in ∼2.7 mL (infused over 5 h) was investigated. The first study was a PK/PD study of SC furosemide compared with 80 mg IV furosemide administered as a bolus in ambulatory patients with heart failure (HF). The primary outcome was absolute bioavailability of SC compared with IV furosemide. The second study investigated the same SC furosemide preparation delivered by a patch infusor in patients hospitalized with HF. Primary outcome measures were treatment-emergent adverse events, infusion site pain, device performance, and PK measurements.The absolute bioavailability of SC furosemide in comparison to IV furosemide was 112%, resulting in equivalent diuresis and natriuresis. When SC furosemide was administered via the patch pump, there were no treatment-emergent adverse events and 95% of participants reported no/minor discomfort at the infusion site. CONCLUSION: The novel preparation of SC furosemide had similar bioavailability to IV furosemide. Administration via a patch pump was feasible and well tolerated.

Evaluation of oncology infusion pharmacy practices: A nationwide survey.

PURPOSE: Oncology care continues to evolve at a rapid pace including provision of infusion-based care. There is currently a lack of robust metrics around oncology infusion centers and pharmacy practice. The workgroup completed a nationwide survey to learn about oncology-based infusion pharmacy services offered. The objective was to highlight consistent, measureable oncology-based infusion pharmacy metrics that will provide a foundation to describe overall productivity including emphasis on high patient-safety standards. METHODS: A nationwide survey was developed via a workgroup within the Vizient Pharmacy Cancer Care Group beginning in April 2019 and conducted electronically via the Vizient Pharmacy Network from September to November 2020. The survey was designed to capture a number of key metrics related to oncology-based infusion pharmacy services. RESULTS: Forty-one sites responded to the survey. Responses highlighted hours of operation (median = 11.5), number of infusion chairs (median = 45). Staffing metrics included 7.1 pharmacist full-time equivalent (FTE) and 7.6 technician FTE per week. 80.5% of sites had cleanrooms and 95.1% reported both hazardous and nonhazardous compounding hoods. 68.3% of sites reported using intravenous (IV) technology, 50.0% measured turnaround time, and 31.4% prepared treatment medications in advance. CONCLUSION: There was variability among oncology infusion pharmacy practices in regard to survey responses among sites. The survey results highlight the need for standardization of established productivity metrics across oncology infusion pharmacies in order to improve efficiency and contain costs in the changing oncology landscape. The survey provides insight into oncology infusion pharmacy practices nationwide and provides information for pharmacy leaders to help guide their practices.

Imaging of the hepatic arterial infusion pump: Primer for radiologists.

Hepatic arterial infusion (HAI) pumps are used to deliver liver-directed therapy by allowing the administration of selective chemotherapy to the liver via a catheter implanted most commonly into the gastroduodenal artery connected to a subcutaneous pump. This selective administration helps maximize the chemotherapeutic effect within the hepatic tumors while minimizing systemic toxicity. While HAI therapy has primarily been used to treat liver-only metastatic colorectal cancer, the indications have expanded to other malignancies, including intrahepatic cholangiocarcinoma. Radiologists play an important role in pre-operative planning, assessment of treatment response, and evaluation for potential complications using various imaging studies, including computed tomography angiography, magnetic resonance imaging, and perfusion scintigraphy. This article describes the radiologist's role as part of a multi-disciplinary oncology team to help maximize the success of HAI therapy and also helps radiologists familiarize themselves with various aspects of HAI pumps.

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

BACKGROUND: A 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. METHODS: We 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. RESULTS: In 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). CONCLUSIONS: This 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.

Clinical Trials for Oral, Inhaled and Intravenous Drug Delivery System for Lung Cancer and Emerging Nanomedicine-Based Approaches.

Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.

Technical note: 3D-printed MRI-compatible syringe pump.

BACKGROUND: A power injector is typically employed to deliver a contrast agent to a subject (e.g., humans, animals, phantoms) during MRI, but it is costly and cannot inject more than one subject at a time. Conventional syringe pumps housing multiple syringes are typically non-MRI compatible and, thus, should be placed outside the MRI room. PURPOSE: To develop the prototype of a cost-effective, easy-to-use, reliable syringe pump that could be deployed inside a clinical MRI bore and operated on during a scan. METHODS: The MRI-compatible syringe pump (MSP) was designed using Solidworks 3D modeling software and fabricated using a Raise3D Pro2 Printer. The MSP was designed to infuse up to three syringes simultaneously. The injection speed was mainly controlled with different gear sets in the escapement unit and further adjusted by changing the effective hairspring length via a pinch pin. The MSP was evaluated with three gear sets (gear ratios: 0.20:1, 0.56:1, and 1.09:1) and 10 different effective hairspring lengths at each gear ratio. A video was recorded while operating MSP at each injection speed to calculate the volume injection rate of a 5-mL syringe (mL/s). The MSP was operated five times repeatedly at each injection speed, and the mean and standard deviation of the volume injection rate were calculated. RESULTS: The volume injection rates produced by three gear ratios (0.20:1, 0.56:1, and 1.09:1) were 0.209 ± 0.003 mL/s, 0.411 ± 0.002 mL/s, and 0.625 ± 0.006 mL/s, respectively, at the full hairspring length. The injection rates of gear set 1 (gear ratio: 0.20:1) decreased from 0.273 ± 0.001 mL/s to 0.245 ± 0.001 mL/s with a decrement of 0.003 mL/s for 10 different effective hairspring lengths (r = 0.997, p < 0.001). The injection rates of gear set 2 (gear ratio: 0.56:1) decreased from 0.519 ± 0.003 mL/s to 0.469 ± 0.003 mL/s with a decrement of 0.006 mL/s (r = 0.987, p < 0.001), and that of gear set 3 (gear ratio: 1.09:1) decreased from 0.779 ± 0.012 mL/s to 0.709 ± 0.005 mL/s with a decrement of 0.007 mL/s (r = 0.963, p < 0.001). The coefficient of variation in the injection rate measurement was 0.727 ± 0.346%. CONCLUSIONS: The MSP is a portable device that can reliably deliver a liquid agent to multiple subjects inside a clinical MRI bore during a scan.

Intercostal cryonerve block versus elastomeric infusion pump for postoperative analgesia following surgical stabilization of traumatic rib fractures.

OBJECTIVE: Patients with blunt thoracic trauma requiring surgical stabilization of rib fractures (SSRF) frequently experience severe pain. Further, a rising prevalence of opioid-tolerant patients sustain traumatic injuries. The optimal pain management adjunct for concurrent use with SSRF remains uncertain. This study compared outcomes in patients undergoing SSRF with concomitant cryonerve block (CryoNB) or ropivacaine 0.2% elastomeric infusion pump (EIP). METHODS: A single-center retrospective comparative analysis was performed at a level II trauma center. A query of our institution's trauma registry of consecutive patients undergoing SSRF from October 2017 to November 2020 with either intercostal CryoNB or ropivacaine 0.2% EIP was conducted. Opioid consumption in oral morphine equivalents (OME), patient-reported pain scores by numerical rating scale, and pulmonary function measured by incentive spirometry effort (mL) were collected at baseline and on postoperative days 1-3. Results were analyzed using a linear-mixed-effects model. Length of stay (LOS), complications, and hospital charges were assessed as secondary outcomes. RESULTS: Twenty-six patients meeting inclusion criteria were evaluated. Patient demographics, injury, and surgical variables were similar between groups. The estimated effect for patients treated with CryoNB (n = 14) compared to EIP (n = 12) demonstrated a 25% (estimated -1.37 OME, 95% CI, -2.411 to -0.335, p = 0.01) reduction in hospital opioid requirements, fewer discharge opioids (41.3 mg (37.5-45) versus 175 mg (150- 200), p = 0.03), 22% (estimated -1.506, 95% CI, -2.722 to -0.290, p = 0.02) reduction in pain scores, and shorter postoperative LOS (4 days (4-5) versus 6 days (5-9.5), p = 0.04). Pulmonary function (estimated -48.8 mL, 95% CI, -312.74 to 215.05, p = 0.71), total hospital costs (CryoNB: $90,224 ± 34,633; EIP: $131,498 ± 73,072, p = 0.07), and complications were no different between cohorts. CONCLUSION: The addition of intercostal CryoNB as an adjunct to multimodal pain management in trauma patients undergoing surgical fixation of rib fractures may be of benefit. Based on our early data, this technique appears to be promising in reducing opioid requirements and providing an extended duration of pain control without increased costs or complications.

Combined Hepatic Arterial Infusion Pump and Systemic Chemotherapy in the Modern Era for Chemotherapy-Naive Patients with Unresectable Colorectal Liver Metastases.

PURPOSE: Chemotherapy-naive patients with unresectable colorectal liver metastases (CRLM) have been the best responders to hepatic arterial infusion (HAI) therapy. The current treatment paradigm has drifted away from HAI in the first-line setting. We aimed to analyze outcomes of combined first-line systemic therapy with HAI therapy (HAI+SYS) in the modern era. METHODS: We conducted a retrospective study of consecutive chemotherapy-naive patients with unresectable CRLM who received HAI+SYS between 2003 and 2019. Patients were selected from a prospectively maintained database. Outcomes included radiological response rate, conversion to resection (CTR) rate, and overall survival (OS). RESULTS: Fifty-eight chemotherapy-naive patients were identified out of 546 patients with unresectable CRLM managed with HAI. After induction treatment, 4 patients (7%) had a complete radiological response, including two durable responses. In total, 32 patients (55%) underwent CTR. CTR or complete response without resection was achieved after seven cycles of systemic therapy and four cycles of HAI therapy. Median OS for the whole cohort was 53.0 months (95% confidence interval 23.0-82.9). Three- and 5-year OS in patients who achieved CTR or complete response versus patients who did not was 88% and 72% versus 27% and 0% respectively. Of patients who underwent CTR, complete and major pathological response (no and <10% viable tumor cells, respectively) was observed in 7 (22%) and 12 patients (38%). CONCLUSIONS: Combined HAI+SYS in chemotherapy-naive patients resulted in durable and substantial response in a large proportion of patients. Nearly two-thirds of patients achieved a complete response or proceeded to conversion surgery, which was associated with prolonged survival.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases.

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day. With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

Chemotherapy induced phlebitis experienced by women with breast cancer following administration of epirubicin using a volumetric infusion pump: an observational study.

OBJECTIVE: To establish the incidence and severity of chemotherapy-induced phlebitis (CIP) following administration of epirubicin chemotherapy using a volumetric infusion pump (Hospira Plum 360), compared to a previous study of manual injection of epirubicin. Also the study aimed to gain insight into staff perceptions of ease of use and safety of infusion pump administration. METHODS: An observational study of women with breast cancer (n = 47) receiving epirubicin via volumetric infusion pump. Phlebitis was reported through a participant self-assessment questionnaire and graded by clinical assessment three weeks after each chemotherapy cycle. Staff perceptions were explored using questionnaires. RESULTS: Infusion pump administration delivered a significantly higher concentration of epirubicin (p < 0.001), a significantly higher rate of grade 3 and 4 participant reported CIP between cycles (p = 0.003) but demonstrated no significant difference in grade 3 and 4 CIP when assessed clinically three weeks after treatment (p = 0.157). CONCLUSION: Peripheral epirubicin administration will result in severe CIP being experienced by a proportion of patients irrespective of whether infusion pump or manual injection method is used. Those at high risk of severe CIP should be informed of the risk and offered a central line. For those with a lower risk of severe phlebitis use of the infusion pump appears to be a safe option.

Systemic exposure of floxuridine after hepatic arterial infusion pump chemotherapy with floxuridine in patients with resected colorectal liver metastases.

BACKGROUND: Floxuridine's high hepatic extraction ratio and short elimination half-life allows maximum liver exposure with minimal systemic side-effects. This study attempts to quantify the systemic exposure of floxuridine. METHODS: Patients undergoing continuous hepatic arterial infusion pump (HAIP) floxuridine after resection of colorectal liver metastases (CRLM) in two centres underwent six cycles of floxuridine at start dose 0.12 mg/kg/day. No concomitant systemic chemotherapy was administered. Peripheral venous blood samples were drawn during the first two cycles: pre-dose (only in the second cycle), 30 min, 1 h, 2 h, 7 h, and 15 days after floxuridine infusion. Foxuridine concentration in the residual pump reservoir was measured on day 15 of both cycles. A floxuridine assay with a lower boundary of detection of 0.250 ng/mL was developed. RESULTS: 265 blood samples were collected in the 25 patient included in this study. Floxuridine was mostly measurable at day 7 and day 15 (86 % and 88 % of patients respectively). The median dose corrected concentrations were 0.607 ng/mL [IQR: 0.472-0.747] for cycle 1 day 7, 0.579 ng/mL [IQR: 0.470-0.693] for cycle 1 day 15, 0.646 ng/mL [IQR: 0.463-0.8546] for cycle 2 day 7, and 0.534 ng/mL [IQR: 0.4257-0.7075] for cycle 2 day 15. One patient had remarkably high floxuridine concentrations reaching up to 44 ng/mL during the second cycle, without a clear explanation. The floxuridine concentration in the pump decreased by 14.7 % (range 0.5 %-37.8 %) over a period of 15 days (n = 18). CONCLUSION: Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient. Floxuridine concentration in the pump decreases over time.