Late cholangitis after pancreatoduodenectomy: A common complication with or without anatomical biliary obstruction.

BACKGROUND: Postoperative cholangitis is a common complication after pancreatoduodenectomy that can occur with or without anatomical biliary obstruction. This study aimed to investigate the incidence, diagnosis, treatment, and risk factors of cholangitis after pancreatoduodenectomy. METHODS: We performed a retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy in 2 Dutch tertiary pancreatic centers (2010-2019). Primary outcome was postoperative cholangitis, defined as systemic inflammation with abnormal liver tests without another focus of infection, at least 1 month after resection. Diagnostic and therapeutic strategies were evaluated. Two types of postoperative cholangitis were distinguished; obstructive cholangitis (benign stenosis of the hepaticojejunostomy) and nonobstructive cholangitis. Potential risk factors were identified using logistic regression analysis. RESULTS: Postoperative cholangitis occurred in 93 of 900 patients (10.3%). Median time to first episode of cholangitis was 8 months (interquartile range 4-16) after pancreatoduodenectomy. Multiple episodes of cholangitis occurred in 44 patients (47.3%) and readmission was necessary in 83 patients (89.2%). No cholangitis-related mortality was observed. Obstructive cholangitis was seen in 37 patients (39.8%) and nonobstructive cholangitis in 56 patients (60.2%). Surgery was performed for cholangitis in 7 patients (7.5%) and consisted of revision of the hepaticojejunostomy or elongation of the biliary limb. Postoperative biliary leakage (odds ratio 2.56; 95% confidence interval 1.42-4.62; P = .0018) was independently associated with postoperative cholangitis. CONCLUSION: Postoperative cholangitis unrelated to cancer recurrence was seen in 10% of patients after pancreatoduodenectomy. Nonobstructive cholangitis was more common than obstructive cholangitis. Postoperative biliary leakage was an independent risk factor.

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.

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.

Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. PATIENTS AND METHODS: A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. RESULTS: After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0-39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. CONCLUSION: HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials.