527
Background: Most patients with malignant hilar biliary obstruction (MHBO) are ineligible for surgical resection due to distant metastasis, locally advanced disease, or poor performance status. ...These patients mostly undergo biliary drainage with endoscopic stents or percutaneous drains that cross the ampulla. This approach causes bacterial colonization of the bile ducts, recurrent cholangitis, and biliary reinterventions. Few patients become eligible for palliative systemic chemotherapy, because of inadequate drainage and drainage-related complications. The solution is primary percutaneous stenting (PPS) with one or more fenestrated self-expandable metal stent (SEMS) across the biliary obstruction, without crossing the ampulla. After PPS, the percutaneous transhepatic puncture tract is sealed with glue without leaving an external biliary drain. The aim of this study was to assess the safety, feasibility, and effectiveness of PPS in patients with unresectable MHBO. Methods: A single center prospective study was performed from October 2020 till September 2022 including 35 patients with MHBO who underwent PPS. We made a comparison with a historical cohort of 90 consecutive patients treated with primary endoscopic biliary drainage at our center from 2011 till 2020. Results: All 35 patients had technical successful percutaneous SEMS placement. Perihilar cholangiocarcinoma was present in 15 patients (43%), intrahepatic cholangiocarcinoma in 14 patients (40%), and gallbladder cancer in 6 patients (17%). Two patients required two attempts because the stricture could not be passed at the first attempt. Two patients developed cholecystitis and one patient had melaena due to intrahepatic bleeding of a portal venous branch requiring blood transfusion. One patient (3%) developed cholangitis after the first biliary drainage procedure because the tumor extended up to the ampulla, requiring additional stenting. No cholangitis was seen in the other 34 patients. We made a comparison with a historical cohort of 90 consecutive patients treated with primary endoscopic biliary drainage at our center from 2011 till 2020. Only 3 patients (9%) required a readmission and 3 patients (9%) a reintervention. Palliative systemic chemotherapy was administered in 26 patients (75%) versus 18 patients (20%) after primary endoscopic biliary drainage. The median overall survival was 10.6 months (95% CI 8.1 – not reached) versus 4.3 months (95% CI 3.1 – 6.4) after primary endoscopic biliary drainage. After PPS, no patients died because of cholangitis or drainage-related complications. Conclusions: Primary percutaneous stenting with fenestrated SEMS without crossing the ampulla is safe, feasible, and effective for palliative treatment of patients with MHBO. These promising results need to be confirmed in a randomized controlled trial. Clinical trial information: NL9624 .
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 .
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.
IMPORTANCE: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. OBJECTIVE: To compare the overall survival (OS) of patients with ...multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible. The HAIP group consisted of consecutive patients from a single center who underwent HAIP floxuridine chemotherapy for unresectable multifocal iCCA between January 1, 2001, and December 31, 2018. The resection group consisted of consecutive patients from 12 centers who underwent a curative-intent resection for multifocal iCCA between January 1, 1990, and December 31, 2017. Resectable metastatic disease to regional lymph nodes and previous systemic therapy were permitted. Patients with distant metastatic disease (ie, stage IV), those who underwent resection before starting HAIP floxuridine chemotherapy, and those who received a liver transplant were excluded. Data were analyzed on September 1, 2021. MAIN OUTCOMES AND MEASURES: Overall survival in the 2 treatment groups was compared using the Kaplan-Meier method and log-rank test. RESULTS: A total of 319 patients with multifocal iCCA were included: 141 in the HAIP group (median IQR age, 62 53-70 years; 79 56.0% women) and 178 in the resection group (median IQR age, 60 50-69 years; 91 51.1% men). The HAIP group was characterized by a higher percentage of bilobar disease (88.0% n = 124 vs 34.3% n = 61), larger tumors (median, 8.4 cm vs 7.0 cm), and a higher proportion of patients with 4 or more lesions (66.7% 94 vs 24.2% 43). Postoperative mortality after 30 days was 0.8% (95% CI, 0.0%-2.1%) in the HAIP group vs 6.2% (95% CI, 2.3%-9.7%) in the resection group (P = .01). The median OS for HAIP was 20.3 months vs 18.9 months for resection (P = .32). Five-year OS in patients with 2 or 3 lesions was 23.7% (95% CI, 12.3%-45.7%) in the HAIP group vs 25.7% (95% CI, 17.9%-37.0%) in the resection group. Five-year OS in patients with 4 or more lesions was 5.0% (95% CI, 1.7%-14.3%) in the HAIP group vs 6.8% (95% CI, 1.8%-25.3%) in the resection group. After adjustment for tumor diameter, number of tumors, and lymph node metastases, the hazard ratio of HAIP vs resection was 0.75 (95% CI, 0.55-1.03; P = .07). CONCLUSIONS AND RELEVANCE: This cohort study found that patients with multifocal iCCA had similar OS after HAIP floxuridine chemotherapy vs resection. Resection of multifocal intrahepatic cholangiocarcinoma needs to be considered carefully given the complication rate of major liver resection; HAIP floxuridine chemotherapy may be an effective alternative option.
Background
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.
Objective
This study aimed to compare perioperative outcomes of robotic versus open HAIP placement in patients with unresectable iCCA.
Methods
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).
Results
In total, 22 robotic and 28 open HAIP placements were performed. The median TTFR was 2 days 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).
Conclusion
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.
Background
Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed ...to analyse the outcomes of patients with pCCA in a nationwide cohort.
Methods
Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival.
Results
A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7‐5.7) months. Three‐hundred‐ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti‐cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2‐34.0), 12.2 (95% CI 11.0‐13.3), 14.5 (95%CI 8.2‐20.8) and 2.9 (95% CI 2.6‐3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non‐academic and 32% in academic centres (P < .001), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7‐11.7) months in academic centres compared to 4.9 (95% CI 4.3‐5.4) months in non‐academic centres (P < .001).
Conclusions
In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population‐based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients.
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
.
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