Xiang-Dong Wang, Nai-Jian Ge, Cheng-Jian He, Jun-Jun Zhu, Wei Xu, Ye-Fa Yang

Department of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China

Radical operation for hilar cholangiocarcinoma (HCCA) is the most effective treatment, but high rates of severe postoperative complication and death remain concerns due to the complexity of biliary and vascular anatomy of the hepatobiliary region.Delayed arterial hemorrhage (DAH) occurring＞24 h postoperatively usually causes life-threatening bleeding, and relaparotomy for DAH would be difficult and hazardous because of postoperative adhesions and critical general condition.As endovascular technique is less invasive and has improved over the recent decades, clinicians have begun to prefer endovascular treatment (EVT) to surgical treatment of DAH after hepatobiliary pancreatic surgery.However, to our knowledge, a relatively large series of patients dealing with the outcomes of EVT of DAH after surgery for HCCA has not been reported.Herein, we analyzed the technical and clinical outcomes of EVT in 17 patients to evaluate the efficacy and safety of EVT.

Between May 2014 and September 2021, 21 patients who underwent angiography to manage hemorrhage after radical operation for HCCA were identified in our database.DAH was identified in 17 patients on angiogram, and these patients were enrolled in this study.The clinical characteristics, endovascular procedures and outcomes of these patients are summarized in Table 1.Resection types included isolated bile duct resection in 9 patients and bile duct resection with partial hepatectomy in 8.All patients received biliary tract reconstruction and skeletonization of the hepatic arteries to complete lymphadenectomy within the hepatoduodenal ligament.The median interval between surgery and DAH was 10 days (range: 2-31 days).Clinical symptoms and signs in this cohort included bleeding from abdominal drain (n= 15), gastrointestinal tract (nasogastric tube, hematemesis, hematochezia or melena) (n= 6) and biliary drainage (T-tube) (n= 1).Four patients presented with hemorrhagic shock that responded to volume expansion when underwent the initial endovascular procedure.The origins of bleeding were the common hepatic artery (CHA,n= 2),the proper hepatic artery (PHA,n= 4), the (aberrant) right hepatic artery (RHA) and its branch (n= 5), the gastroduodenal artery(stump) (GDA,n= 4) and the GDA branch (n= 2).

Table 1Patient characteristics, endovascular procedures and outcomes.

Technical success was defined as the exclusion of the bleeding focus with no evidence of active bleeding on a completion angiogram.Clinical success was defined as the cessation of signs or symptoms of abdominal bleeding and no requirement for additional procedures (e.g., surgery, endoscopy, or EVT) within 30 days of the EVT.EVT failed to perform in one patient related to the pseudoaneurysm arising from the proximal CHA, preventing safe and effective treatment with embolization or covered stent implantation, and then converted to reoperation.Of the 16 patients who underwent EVT, transcatheter arterial embolization(TAE) were performed in 9 patients with a mix of coils, gelfoam,microspheres and N-butyl cyanoacrylate (NBCA); covered stents were placed in 7 patients.It was technically feasible to occlude the injured vessels in all the 16 patients on the completion angiography.Thus, EVT was technically successful in 94.1% patients (16/17)and a technical failure in 1 patient.Rebleeding occurred in 4 out of 16 patients within 30 days after the initial EVT, and the clinical success rates were 70.6% (12/17).During the first 30 days after the initial angiography, 7 patients died of multiorgan failure associated with hypovolemic shock in 3 patients, cardiac shock in 1 patient and sepsis in 3 patients, respectively.The alive 10 patients were discharged successfully, and the 30-day mortality was 41.2% (7/17).

A 55-year-old female (No.4, Fig.1 ) presented with bleeding from abdominal drain tube and hematemesis 8 days after bile duct resection with left liver and caudate lobectomy.Celiac axis angiography showed a pseudoaneurysm arising from the RHA.Covered stent placement would be difficult due to the anatomy situation of the RHA, so we tried to embolize the RHA from the distal to the proximal part of the pseudoaneurysm (sandwich technique).After superselection of the RHA using microcatheter and microguidewire, the patient suffered with severe abdominal pain and a significant drop in blood pressure.The subsequent angiography showed contrast extravasation from the ruptured pseudoaneurysm, and then emergency embolization of the ruptured pseudoaneurysm, RHA and PHA was performed.Unfortunately, this patient underwent acute hepatic failure due to sacrifice of hepatic artery (HA) blood flow and finally died of multiorgan failure associated with hypovolemic shock due to rebleeding 4 days later.No other serve complications related to the endovascular procedure were observed.

Fig.1.A: Celiac axis angiography showed a pseudoaneurysm (arrow) arising from the RHA.B: After the superselection of RHA using microcatheter and microguidewire, the patient suffered from severe abdominal pain and a significant drop in blood pressure.The subsequent angiography showed contrast extravasation (arrow) from the ruptured pseudoaneurysm.C: After embolization (arrow) of the ruptured pseudoaneurysm, RHA and PHA with microcoils, the completion angiogram showed complete cessation of the active bleeding.RHA: right hepatic artery; PHA: proper hepatic artery.

In our cases, the median time point of hemorrhage onset was 10 days after surgery for HCCA.At this point, it is reasonably difficult to precisely identify the responsible artery by reoperation due to the diversity of bleeding sites and postoperative adhesions.Furthermore, reoperation is associated with longer operative time,higher blood loss, longer intensive care unit time, as well as higher rates of morbidity and mortality [1].Angiography appears to be the most specific and sensitive diagnostic modality to detect arterial bleeding after abdominal surgery.In our study, arterial bleeding was identified in 81.0% (17/21) patients on angiogram, proving that immediate angiography is essential to detect whether visceral artery is injured in patients with DAH following HCCA surgery.Before referral to the interventional radiology unit, 4 out of 17 patients presented with hemorrhagic shock, proving the danger of DAH.With restoration of hemodynamic stability by volume loading and the subsequent EVT, all these 4 patients were technically and clinically successful in controlling the arterial bleeding.EVT is widely considered the potential first-line treatment in patients that are hemodynamically stable [2].In regard to the patients that are unstable, whether EVT is the preferred option keeps controversial [3].However, there is no doubt that the emergency surgery is challenging and associated with high failure rate.Our data clearly suggest that EVT is still a valuable choice in patients that are hemodynamically unstable due to massive hemorrhage.Inunstable patients, the restoration of hemodynamic stability should always be attempted because angiography will provide diagnostics and treatment within one intervention.

The present data showed that the technically successful rate was 94.1%.Despite these high rates of technical success, recurrent bleeding occurred in 4 of 16 patients (25%) after the initial EVT,which is not negligible.Ching et al.[4]reported that rebleeding was seen in 26.3% of patients and it was due to recurrent pseudoaneurysms, rebleeding from coiled vessels, blocked stents and endoleaks.In our study, 1 case underwent emergency embolization of the spasmodic RHA and PHA for intraprocedural ruptured pseudoaneurysm; rebleeding occurred 4 days later and it might be due to the previous coils insufficient to prevent rebleeding due to the RHA and PHA recanalized with a larger diameter.Unfortunately,the patient was not suitable for a second angiography to identify the rebleeding sites due to severe condition with massive bleeding and acute hepatic failure.Regarding clinical outcome, the 30-day mortality rate was 41.2%, underscoring the gravity of DAH after HCCA surgery.In 3 out of 7 cases, death was related to multiple organ failure associated with abdominal infection, despite successful management of the bleeding.Achieving hemostasis is therefore a critical step.However, the sequelae of an acute hemorrhage or a septic condition cannot be controlled in all cases [5].

The intraprocedural rupture of pseudoaneurysm occurred in 1 patient.It may be attributed to increased internal pressure in pseudoaneurysm during the injection of contrast agent or the manipulation of the microcatheter or microguidewire.Shimohira et al.[6]reported that the intraprocedural rupture of pseudoaneurysms occurred in 3 out of 47 visceral artery pseudoaneurysms treated with embolization and resulted in minor complications.In a recent study, one patient underwent the intraprocedural rupture of the GDA pseudoaneurysm, and then embolization of the PHA and CHA was performed; however, the patient died 1 week later from causes including insufficient blood volume and liver failure [7].Therefore, the rupture of pseudoaneurysm needs to be considered during procedures.Although embolization was promptly accomplished after rupture in our case, acute hepatic failure due to sacrifice of HA blood flow occurred and this complication was considered to be major.The liver has many potential collateral pathways that communicate with the adjacent arterial system.Additionally, the liver can tolerate considerable TAE without significant liver infarction because it has a dual blood supply from the HA and portal vein (PV).TAE of the HA for acute hemorrhage is generally considered to be safe.However, collateral arteries around the common bile duct were disrupted after bile duct resection [8].Nagino et al.[9]treated one patient who encountered postoperative hemorrhage after hepatectomy for HCCA and the patient suffered from hepatic failure following TAE used for rupture of the RHA.Miura et al.[8]reported that among four patients who underwent bile duct resection and hepatic lobectomy for biliary hilar malignancy, three patients died of hepatic failure after TAE.They suggested that TAE after major hepatectomy with extrahepatic bile duct resection may be nearly contraindicative.With the development of interventional techniques, it was reported that covered stent implantation is effective for both managing arterial hemorrhage and preserving vessel patency and end-organ perfusion [10].Our data showed that 5 out of 7 patients with covered stent implantation at the HA succeeded in hemostasis and none of them had hepatic ischemic complications.Therefore, stent implantation with preservation of HA flow, if technically possible, should be considered the first-choice; efforts should be made to prevent major hepatic complications.

In conclusion, EVT is effective and safe to manage DAH after surgery for HCCA, even in patients that are hemodynamically unstable.However, the intraprocedural rupture of pseudoaneurysm and postoperative acute hepatic failure due to sacrifice of HA blood flow may occur, and thus, care is needed during this procedure.

Acknowledgments

None.

CRediT authorship contribution statement

Xiang-Dong Wang :Data curation, Writing - original draft,Writing - review & editing.Nai-Jian Ge: Data curation, Funding acquisition.Cheng-Jian He :Data curation.Jun-Jun Zhu :Data curation.Wei Xu :Data curation.Ye-Fa Yang :Conceptualization, Supervision, Writing - original draft, Writing - review & editing.

Funding

This study was supported by a grant from the National Natural Science Foundation of China ( 31971249 ).

Ethical approval

This study was approved by Local Ethical Committee.Informed consent for publication was obtained from the patients.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.