Management of Pancreatico-duodenal Arterio-venous Malformation

doi:10.21203/rs.3.rs-794176/v1

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Management of Pancreatico-duodenal Arterio-venous Malformation

https://doi.org/10.21203/rs.3.rs-794176/v1

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published 03 Jan, 2022

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Purpose

To describe the interventional management and clinical outcome of pancreatico-duodenal arterio-venous malformations (PDAVMs).

Material and Methods

Seven patients presenting a PDAVM (6 women, 1 male; mean age: 61) were retrospectively reviewed. Technical, clinical success and complications of embolization and surgical management of symptomatic PDAVMs were assessed. Technical success was defined as a complete occlusion of the PDAVM and clinical success as no clinical symptom or recurrence during follow-up. Patients with asymptomatic PDAVMs were followed clinically, by Doppler ultrasound and CT-angiography.

Results

Mean follow-up time was 69 months (15-180). Five symptomatic patients presented with upper gastrointestinal bleeding (n=3), ascites (n=1), and abdominal pain (n=1). Two patients were asymptomatic. The PDAVMs were classified as follow: Yakes I (1), IIIa (2), IIIb (3) and IV (1). Five symptomatic patients were treated with 9 embolization sessions with arterial approach (onyxÒ, glue, coils) in 7 and venous approach in 2 (plugs, coils, covered stents, STS foam and onyxÒ). Technical success of embolization was 60% (3/5). Devascularization was incomplete for 2 Yakes IIIB patients. Clinical success of embolization was estimated at 80% (4/5) as one patient required additional surgery (Whipple) because of persistent bleeding. One splenic vein thrombosis was treated successfully by mechanical thrombectomy and heparin. No recurrence occurred during follow-up. No progression was documented in asymptomatic patients.

Conclusion

Embolization of symptomatic PDAVMs is effective and surgery should be performed in second intention. Complete devascularization is more difficult to obtain in Yakes III PDAVM.

Oncology

embolization

AVM

pancreas

percutaneous

Pancreatico-duodenal arterio-venous malformations (PDAVMs) are rare but a proper diagnosis is important to differentiate them from hypervascular tumors (1). PDAVMs are mostly congenital, and can be associated with Hereditary Hemorrhagic Telangiectasia, commonly known as Osler-Weber-Rendu Syndrome (2).

PDAVMs are often asymptomatic, but complications can arise, such as gastrointestinal bleeding, abdominal pain, portal hypertension and pancreatitis (3). CT is useful to make the diagnosis and identify feeding arteries and draining veins (4), however arteriography remains the gold standard.

There is no consensus on the management of asymptomatic PDAVMs (5). However, symptomatic PDAVMs can be treated by embolization and/or surgery (5, 6).

In previous case reports PDAVM embolization was technically successful in 84% of cases and led to clinical improvement in 100% of patients (7–10). Surgery is effective (6) but carries a high risk of intraoperative bleeding, and severe complications (11).

Yakes and Cho classification helps for determining proper treatment of patients affected by AVMs, by describing the angioarchitecture of the AVM (12). It will dictate the approach to eradicate the nidus of the AVM (intra-arterial, venous retrograde or direct puncture). Careful selection of the approach is important to reach the nidus while minimizing the risk of reflux of embolizing agents into normal arteries and veins.

The purpose of study is to present a series of PDAVMs and describe the safety and the efficacy of embolization according to the Yakes classification.

Study design

The Institutional Review Board approved this study and waived signed informed consent for this retroprospective study. Data were collected through review of medical and imaging reports.

All patients with a diagnosis of PDAVM between 2000 and 2019 were included. A search with the following index terms was performed in the radiological information system: arteriovenous malformation and pancreas or duodenum, embolization, CT, Doppler ultrasound, CT, CT angiography.

Transarterial embolization

For all patients having embolization, transarterial procedures were performed under local anesthesia and conscious sedation. After percutaneous introduction of a 5-Fr sheath in the right or left femoral artery, the celiac trunk and the superior mesenteric artery (SMA) were selectively catheterized using a 5F Chuang catheter and a hydrophilic guidewire 0.035 (Terumo®, Tokyo, Japan). Arteriography was performed to evaluate different feeders, localize the nidus, and visualize draining vein(s).

The nidus was accessed first by a trans-arterial approach using a microcatheter, either a Progreat Terumo® 2.4 Fr, Tokyo, Japan) or a Renegade (Boston Scientific®, USA), as close as possible to the nidus of the vascular malformation. The arterial feeders were embolized with a liquid agent, chosen based on the operator experience. Ethylene Vinyl Alcohol Copolymer (Onyx 18®, ev3 Irvine, CA, USA) (Fig. 1) or glue (Histoacryl; Braun Germany or Glubran; GEM, Italy) with lipiodol®(Guerbet, France) dilution between 1–2 and 1–3, or 300-500µm PVA particles (when onyx® was not available). Coils (Concerto®, Medtronic, Target® 360 Stryker, Fremont, CA, and Azur® CX 18, Terumo) were used to protect distal arteries not feeding the AVM, to complete proximal embolization following distal liquid embolization or to decrease arterial flow in combination with a transvenous approach.

Transvenous embolization

Transvenous procedures were performed in 2 patients under general anesthesia because of failure of previous trans-arterial embolization.

In one case, the AVM located in the head of the pancreas was draining in the gastroduodenal vein. A percutaneous portal access was performed under ultrasound with a micropuncture set. A coaxial technique was used with deployment of an Amplatzer® plug (Amplatzer®, St Jude medical, Plysmouth ,Minnesotta) in the proximal portion of the gastroduodenal vein. Using a microcatheter (Progreat® 2.7, Terumo, Tokyo, Japan) advanced distally to the plug, the connection between the gastroduodenal vein and the superior mesenteric vein was coiled to prevent reflux in the portal system. Then, the vein was embolized with foam made of two ml of Sodium Tetradecyl Sulfate (STS) 3% (60mg) mixed with 1.5 ml lipiodol and 4ml room air injected distally to the Amplatzer® plug using the pressure cooker technique to reflux into the nidus (13) (Fig. 2). In the second case, the AVM involving the tail of the pancreas was draining into the splenic vein, which was aneurysmal (Fig. 3). Since this patient has a chronic portal thrombosis, a transplenic access was performed. Two covered stent grafts were deployed (Viabahn, Gore, Newark, Deleware) of 6 mm X 7.5 cm in the splenic vein and of 8 mm X 2cm at the spleno-mesenteric vein junction) to exclude the venous aneurysm while maintaining its patency. The aneurysm sac was then embolized using Onyx® and coils after direct puncture of the aneurysm.

Image analysis

The PDAVMs were classified according to the Yakes classification (14) (Table 2) (Fig. 4).

Technical success was defined as a complete occlusion of the PDAVM on the CT imaging on the follow-up. Clinical success was defined as resolution of symptoms after the embolization during the follow-up.

Follow-up

Clinical and imaging follow up was performed for all patients at the interventional radiology clinic. All CTs had at least an arterial and portal phase. For patients with an active bleeding a delayed venous phase was also performed. On CT, the criteria for diagnosing the AVM were the presence of enlarged arterial feeders and draining vein and the early filling of the portal system on the arterial phase

A routine post-embolization contrast-enhanced CT scan with non-contrast, arterial and portal phases, and doppler ultrasound were performed 1 to 6 months after the embolization. Additional intervention was performed in case of PDAVM recurrence. Asymptomatic patients were followed for a mean period of 2 years and had a control CT scan and doppler ultrasound at last follow-up. The utility of Doppler ultrasound is to document the magnitude of AV fistulae (aliasing in the shunting area and arterialization of the portal flow).

Patients

Patient characteristics are summarized in Table 1. From 2000 to 2019, seven consecutive patients presenting a PDAVM (6 women, 1 man; mean age: 61.1, range 43–79) were analyzed. No patients were excluded during the study period. Two asymptomatic patients had no intervention and close imaging and clinical follow-up. Five symptomatic patients (2 massive upper gastrointestinal bleeding in emergency and 1 with repeated upper gastrointestinal bleeding for 3 patients, ascites for one, and persistent and resistant abdominal pain for one were treated with first intention embolization (1 male and 4 female). Patients presenting with massive upper gastrointestinal bleeding were initially imaged with CT (2 emergency procedure), and the others were imaged with CT and Doppler ultrasound. Mean follow-up time was 69 months (15–180)

Imaging findings

On CT and catheter angiography, the feeding arteries included the gastroduodenal artery (1), the anterior superior pancreatico-duodenal artery (1), the posterior superior pancreatico-duodenal arteries (4), the anterior inferior pancreatico-duodenal artery (1), the posterior inferior pancreatico-duodenal arteries (5), the great pancreatic arteries (pancreatica magna) (2), the dorsal pancreatic artery (1), the splenic artery (1), the hepatic artery (1), the left gastric artery (1).

Draining veins included the gastroduodenal vein (5), the splenic vein (2), and the right gastric vein (1).

Clinical outcome

Technical success of embolization was estimated at 60% (3/5). Devascularization was incomplete for 2 patients (25% for one patient, and 75% for one patient), both in Yakes IIIB PDAVMs. Clinical success of embolization was estimated at 80% (4/5) (Yakes 1, 2 Yakes 3a, Yakes 3b) as one patient (Yakes IIIB) required additional surgery (Whipple) because of persistent bleeding. This patient had a partial embolization (successive arterial and venous approaches) estimated at 25% devascularization.

One splenic vein thrombosis (Yakes IIIA), occurred after a stenting of aneurysmal splenic vein draining the AVM. It was successfully treated by mechanical thrombectomy followed by an overnight local infusion of heparin. The splenic vein thrombosis was treated to prevent an additional segmental portal hypertension to a chronic portal thrombosis with inherent risk of gastric or gastroesophageal bleeding.

No recurrence occurred during clinical and CT imaging follow-ups. One patient (Yakes IIIB) had 25% residual AVM without symptom recurrence during the follow-up.

The patient with splenic vein thrombosis and preexisting portal thrombosis was anticoagulated for 12 months with good patency of the covered stent-grafts, without recurrence of AVM. There was no other complication and no evidence of deterioration of liver, pancreatic and renal function on blood tests. Patient hospitalization ranged between 24 hours and 7 days.

Asymptomatic patients presented with a Yakes IIIb and IV, and had no evidence of AVM progression and did not require additional treatment.

In this study complete regression of symptoms of the AVM was reported at 80% while technical success of embolization was 60%. One of the 2 Yakes IIIB patients with incomplete embolization (25%) required additional surgery whereas the other with a 75% devascularization had a good evolution with conservative treatment.

Classification of AVMs is useful for planning optimal therapeutic approach, and predicting therapeutic outcomes (15). Cho et al (15) demonstrated better outcome in type II Cho AVMs involving extremities or the thoraco-abdominal region.

Yakes classification was preferred to Cho classification in this study because it was more representative of the angioarchitecture observed on imaging. The Yakes classification is more comprehensive especially the distinction between type IIIa and III b which applied for 42% (3/7) of our patients.

Ideally, the embolization endpoint is to obtain a complete nidus occlusion of the PDAVM. Transarterial approach was used in first intention to embolize the PDAVM. Transvenous approach was selected in second intention following failure of transarterial approaches or when multiple arterial feeders were present with a dominant draining vein.

Transvenous approach was useful, however embolization should be performed carefully to minimize the risk of splenic or portal thrombosis. We observed one case of the latter, which was successfully managed by mechanical thrombectomy and local heparin infusion.

Different embolic agents have been used in previous reports: particles and ethanol were described with good technical success (9), embolization with Onyx® showed complete regression of PDAVMs (7, 10), and Glue utilized as well (16). Liquid embolic agents are the most useful. Onyx® provides the best control for liquid agent and should be preferred to minimize the risk of non-target embolization (17). The speed of polymerization of glue is more difficult to predict and the slow injection rate of Onyx® give more chance to the operator to prevent non target embolization (18). Glue had a higher risk of bowel infarction and glue reflux into other vessels may result in non-target embolization. On the venous side, the combination of mechanical occlusion with coils or plugs with a liquid agent is recommended (12, 19). Insertion of a covered stent-graft combined with embolization of a venous aneurysm is an elegant approach to maintain the patency of splanchnic veins in case of an aneurysmal draining vein ( Yakes IIB, IIIA) (20). Ethanol embolization has the potential to cure the AVM, however it carries a higher-risk of non-target embolization and potential gastroduodenal ulcer or pancreatitis.

Reported complications included gastric ulcer, pancreatitis, portal vein thrombosis, bowel ischemia (21). The occurrence of duodenal ulceration following the arterial approach being the most frequent (7, 10). Selective TAE with NBCA in the pancreas caused localized ischemic necrosis without clinically significant pancreatitis in a swine model(22).

The transvenous approach for PDAVM was not reported yet. This approach carries a risk of portal, mesenteric or splenic vein thrombosis. It is important to control reflux of liquid embolic agent into the portal system by occluding potential re-entry in the portal system. This could be achieved by occluding draining veins connected to the portal system with plugs or coils. Intra-nidal sclerotherapy by direct puncture was not performed because the AVM were deeply located and difficult to image under ultrasound or non-contrast or delayed contrast enhanced CT. Moreover, this requires to puncture through digestive structures in most cases

In an emergent setting, microparticles were used because the operator was not used to liquid embolics. Using 300-500um particles, there was no significant complication as previously reported by Aina et al for gastroduodenal bleeding(23).

Radiotherapy has been reported (24), in asymptomatic patients, showing shrinkage of the AVM. TIPS was described in case of failure of PDAVM embolization, with good efficacy (25).

Total or partial pancreatectomy is the only complete cure treatment, however there is a risk of massive intraoperative bleeding, hypoglycemia, and pancreatic juice leakage (6)

The limitations of the study were the small number of patients and the retrospective design. Imaging follow-up were made by CT, thus, small residual AVMs with minimal AV shunting may have been overlooked. However, all patients did not have bleeding recurrence or evidence of portal hypertension during the follow-up. PDAVMs are rare, making a prospective study impossible in a reasonable time frame.

In conclusion, embolization of PDAVMs is a safe approach and can be effective. In case of persistent symptomatic PDAVM after embolization, surgery is a valid option. Yakes Grade IIIb PDAVM are more challenging and partial devascularization can be observed.

AVM: arterio-venous malformation.

PDAVM: pancreatico-duodenal arterio-venous malformation

Ethical Approval and consent to participate

The Institutional Review Board approved this study and waived signed informed consent for this retrospective study. Data were collected through review of medical and imaging reports.

Consent for publication

Images are entirely unidentifiable and there are no details on individuals reported within the manuscript making them at risk to be identified. The IRB waived specific informed consent form for this study.

Availability of data and material
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors report no conflict of interest.

Funding
No Funding Sources

Authors' contributions
CM was in charge of case review and manuscript writing. AP, PG, LB, ET, PP, MFG were involved in diagnostic and interventional procedures. GS was the senior author. He was involved in diagnostic and interventional procedures. He was in charge of data integrity and final review and approval of the manuscript. All authors read and approved the final manuscript

Acknowledgements
We would like to thank Mrs Shirley Abraham for her assistance in patient follow-up at the interventional radiology clinic.

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You are reading this latest preprint version

Management of Pancreatico-duodenal Arterio-venous Malformation

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Material And Methods

Study design

Transarterial embolization

Transvenous embolization

Image analysis

Follow-up

Results

Imaging findings

Clinical outcome

Discussion

Abbreviations

Declarations

References

Tables

Status:

Journal Publication

Version 1