Empiric vs. Targeted Embolization in Postpancreatectomy Hemorrhage

Transcatheter Arterial Embolization for Delayed Postpancreatectomy Hemorrhage: A Retrospective Study of 312 Patients

Clinical Question 

Is empiric embolization as effective and safe as targeted embolization for treating delayed postpancreatectomy hemorrhage?

Take Away Point 

Empiric embolization is safe and equally effective as targeted embolization in managing delayed postpancreatectomy hemorrhage, showing no significant difference in clinical success and 30-day mortality rates between the groups.

Reference 

Tan, Wenle, Yuan, Kai, Ji, Kan, Xiang, Tao, Xin, Hainan, Li, Xiaohui, Zhang, Wenhe, Song, Zhenfei, Wang, Maoqiang, & Duan, Feng. (2024). Transcatheter Arterial Embolization for Delayed Postpancreatectomy Hemorrhage: A Retrospective Study of 312 Patients. Journal of Vascular and Interventional Radiology, 35, 241–250. Click here for abstract

Study Design 

Retrospective observational cohort study

Funding Source 

Supported by the National Natural Science Foundation of China (No. 82172037)

Setting 

Single-center study at the Chinese PLA General Hospital, Beijing, People’s Republic of China.

Figure 

Figure 2A 66-year-old woman with adenocarcinoma of the duodenal papilla underwent pancreaticoduodenectomy. The patient developed severe abdominal bleeding 46 days after surgery with the hemoglobin concentration decreasing ≥3 g/dL. (a) Contrast-enhanced computed tomography showed a pseudoaneurysm of the hepatic artery. (b) Angiography showed a pseudoaneurysm of the hepatic artery. (c, d) The common hepatic artery was embolized with microcoils and gelatin sponge. Hemostasis was successful after targeted embolization.

Summary 

Conducted at the Chinese PLA General Hospital, this study retrospectively analyzed 312 patients with delayed postpancreatectomy hemorrhage treated from January 2012 to August 2022, comparing the outcomes of empiric embolization (EE) versus targeted embolization (TE).

Of the 312 patients, 185 patients were found to have positive digital subtraction angiography findings and 175 of them underwent targeted embolization based on the findings. Specifically, the common hepatic artery (30.3%), branches of the superior mesenteric artery (21.7%), splenic artery (20.0%) and left gastric artery (19.4%) were found to be the most frequently embolized arteries in the targeted embolization group.

No extravasation or any vascular abnormalities were detected in 137 (43.9%) patients by digital subtraction angiography. Of these patients, 68 patients were subjected to empiric embolization of the assumed ruptured arteries (EE group), and 69 patients received conservative treatment (NE group). In the cases with negative-result digital subtraction angiography, the principles for empirical embolization were as follows:

(a) computed tomography angiography before angiography highly suspected arterial bleeding;

(b) hemodynamic instability due to acute blood loss;

(c) patients with high suspicion of arterial bleeding according to the character and speed of bleeding;

(d) according to the intraoperative conditions of pancreatectomy, empirical embolization should be performed for bleeding arteries highly suspected by pancreatic surgeons without affecting the main functions of the organs.

In the empiric embolization group, the left gastric artery (42.6%), common hepatic artery (19.1%), splenic artery (14.7%), and stump of gastroduodenal artery (11.8%) were found to be the most frequently embolized arteries. In the absence of clear indications of hemorrhage, it was generally not recommended to perform empirical embolization on branches of the superior mesenteric artery for the purpose of preventing intestinal necrosis.

The clinical failure rates of targeted embolization, empiric embolization, and no embolization groups were 29.7%, 30.9%, and 49.3%, respectively. 243 cases in targeted embolization and empiric embolization groups were included in the follow-up prognostic analysis of this study. The 30-day mortality rates were 14.9% (26/ 175) and 10.3% (7/68) in the targeted embolization and empiric embolization groups, respectively. Embolization-related adverse events occurred in 19 patients. Six patients experienced liver abscesses (targeted embolization group, n = 5; empiric embolization group, n = 1), 1 of whom died of septic shock. Five patients in the targeted embolization group experienced splenic abscesses, and 1 patient in the empiric embolization group showed an abscess in the tail of the pancreas. A patient in the targeted embolization group who presented with ischemic necrosis of the bowel after embolization of the superior mesenteric artery branch underwent laparotomy.

The study found no significant differences in clinical success or 30-day mortality rates between empiric embolization and targeted embolization, demonstrating that empiric embolization can be a viable option in cases with angiographically negative findings. Factors such as malignant disease, Grade C pancreatic fistula, intra-abdominal infection, and concurrent extraluminal and intraluminal hemorrhage were identified as risk indicators for clinical failure. Advanced age and intra-abdominal infection were risk factors for 30-day mortality.

Commentary 

The findings underscore the viability of empiric embolization as an effective treatment strategy for delayed postpancreatectomy hemorrhage, particularly in challenging cases where targeted embolization is not feasible due to negative angiographic findings. This study contributes valuable insights into the management of a complex and high-risk patient population with low clinical success rate of 70% and mortality of 13.6%, suggesting that treatment approach can be tailored based on specific clinical scenarios without compromising patient outcomes. Future prospective studies could further validate these findings and refine treatment protocols

Y90 for lung cancer mets to liver?

Y90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver

Clinical question

Is Yttrium-90 transarterial radioembolization safe and effective in patients with primary lung cancer metastasized to the liver?

Take away point

This retrospective analysis of 57 patients with lung cancer metastatic to the liver demonstrated effectiveness on local control and progression free survival. Overall, the treatment suggested an acceptable safety profile, with 11 severe or life-threatening adverse events within 30 days.

Reference

Yttrium-90 Transarterial Radioembolization of Primary Lung Cancer Metastases to the Liver. Alexander, E M.D. et al Journal of Vascular and Interventional Radiology, Volume 35, Issue 2, 214-225.

Click here for abstract

Study design

The study was a retrospective, observational, descriptive, single center study.

Funding Source

NIH/NCI Cancer Center Support Grant P30

Setting

Memorial Sloan Kettering Cancer Center, New York

Figure

Figure 1. A 55-year-old woman with EGFR-mutant NSCLC with progressing liver metastases in the left hepatic lobe. (a) Axial portal venous-phase CT image demonstrated a lesion in segment IV (arrow), resulting in biliary dilatation. (b) Coronal portal venous-phase CT image demonstrated the lesion (arrow). (c) Angiography of the celiac axis demonstrated the left hepatic artery (arrow) and the middle hepatic artery (arrowhead), where resin microspheres were delivered in a split administration. (d) Axial portal venous-phase CT image obtained 6 months after yttrium-90 radioembolization showed atrophy of the treated left hepatic lobe with persistence of biliary dilatation (arrow). (e) Coronal portal venous-phase CT image demonstrated marked size reduction of the tumor (arrow). CT = computed tomography; EGFR = epidermal growth factor receptor; NSCLC = non–small cell lung cancer.



Figure 4. Overall survival in months was estimated using the Kaplan–Meier (KM) method. NSCLC = non–small cell lung cancer; SCLC = small cell lung cancer.

Summary

Lung cancer is the second most diagnosed cancer in the United States with approximately 40% of patients presenting at diagnosis with metastatic disease. Patients with metastatic disease to the liver indicates a worse prognosis compared to metastasis at other sites, with an overall survival of 3 months for patients with non-small cell lung cancer or small cell lung cancer. Treatment options are limited to systemic therapies such as chemotherapy, targeted therapy, and immunotherapy. Several small case series have demonstrated the use of radioembolization with an acceptable safety profile that prompted further investigation.

The authors of this paper assessed the safety and effectiveness of yttrium-90 transarterial radioembolization in patients with primary lung cancer metastasized to the liver. They performed a retrospective study of 57 patients who were treated between August 2010 and May 2021. Treatments were delivered with either glass or resin microspheres. Primary outcomes of this study were safety, local progression-free survival, and overall survival after yttrium-90 treatment. Clinical laboratory values, biochemical toxicities and radiographic response were monitored approximately 1 month after treatment and at 3-month intervals thereafter.

Of the 79 treatments reviewed, 40 (51%) were associated with side effects within 1 month of yttrium-90 treatment. 29 of those patients experienced mild-moderate adverse events, which included self-limited post-embolic syndrome with symptoms of fatigue, abdominal pain, nausea, and weakness. There were 9 serious adverse events that required prolonged hospitalization or unplanned escalation of care. There was 1 life threatening event marked by acute renal failure and 1 death of a patient from pneumonia. Of note, there were statistically significant increases in aspartame transaminase and alkaline phosphatase at 1 month post treatment. At 3 months, these levels remained high with the addition of increases in total bilirubin, and alanine transaminase. 17 of the patients developed ascites with a median occurrence 19.2 months after treatment.

RECIST 1.1 was used to evaluate treatment response within 6 months of radioembolization, with median local progression free survival of 7.6 months for non-small cell lung cancer, 3.6 months for small cell lung cancer, and 30.6 months for lung carcinoids. Median overall survival was 8.3 months for non-small cell lung cancer, 4.1 months for small cell lung cancer, and 43.5 months for lung carcinoids. For non-small cell lung cancer, presence of bilobar disease, more tumors, and lobar treatment were negative predictors of overall survival. For lung carcinoids, tumor involvement of >50% was a negative predictor of overall survival.

Limitations of this study include the retrospective study design from a single institution and the small patient cohort. The difference in prognoses between the primary lung cancers and the differences in microsphere, volume, and formulation of the therapeutic treatment presented additional limitations.

Commentary

This study demonstrated that yttrium-90 transarterial radioembolization can treat primary lung cancers metastasized to the liver with an acceptable safety profile. The greatest effectiveness of the treatment was observed with lung carcinoid tumors, which had significantly longer baseline local progression-free survival and overall survival when compared to small cell and non-small cell lung cancer.

Historically, transarterial radioembolization was often used after failure of multiple lines of therapy. Liver decompensation and ascites due to overall disease progression and hepatotoxic medications are difficult to distinguish from adverse effects attributable to the yttrium-90 treatment. Since treating refractory tumors with larger tumor burden have known increased risks of late occurring adverse events, studies like this are important to assess yttrium-90 transarterial radioembolization’s safety profile and delineate its role in the treatment algorithm of lung cancer liver metastases.

In this author’s opinion, the next steps for this promising treatment option in patients with lung cancer metastases to the liver involve prospective studies targeting a single type of lung cancer with a uniform therapeutic delivery method. Prognostication models for late occurring adverse events should be investigated to better triage patients for yttrium-90 transarterial radioembolization and allow close-interval follow-ups. Lastly, combination therapies of yttrium-90 transarterial radioembolization and systemic therapies demand further investigation.

Post Author

Anthony M. Camargo, BA
MD candidate, Class of 2025
University of Massachusetts Chan Medical School
@anthonymcamargo

Percutaneous deep venous arterialization in an OBL setting

Percutaneous Deep Venous Arterialization in Patients with No-Option Critical Limb Ischemia Performed in an Office-Based Laboratory Setting

Clinical Question

Is percutaneous deep venous arterialization with commercially available devices safe and feasible in an office-based laboratory among patients with critical limb ischemia and no-option distal arterial occlusive disease?

Take Away Point

Percutaneous deep venous arterialization using commercially available devices in an office-based setting, despite having high rates of occlusion and reintervention, showed favorable rate of overall survival and amputation-free survival along with improved wound healing.

Reference

Shanmugasundaram S, Herman K, Rundback JH. Percutaneous deep venous arterialization in patients with no-option critical limb ischemia performed in an office-based laboratory setting. Journal of Vascular and Interventional Radiology. Published online October 2023. doi:10.1016/j.jvir.2023.10.003

Study Design

Retrospective, observation study consisting of 22 patients

Funding Source

No reported funding

Setting

Private, NJ Endovascular and Amputation Prevention Center, West Orange, New Jersey

Figure

Summary

Endovascular reconstructions have been one of the mainstays in addressing peripheral vascular disease. However, subsets of patients have severe degree of disease such that traditional approaches are not feasible due to lack of distal targets to re-establish flow, with high risks of amputation and mortality. The emergence of deep venous arterialization attempts to mitigate this challenge, and has evolved from a purely surgical technique to a percutaneous, office-based, procedure.

The authors of this paper performed a retrospective observational study to assess the safety and feasibility of percutaneous deep venous arterialization in an office-based laboratory for patients with no-option critical limb ischemia. The study consisted of 22 patients (10 males and 12 females) who underwent the procedure from January 2018 and November 2021. All 22 patients were classified as having no-option disease characterized as chronic total occlusion, previous failed endovascular/open surgical approaches, or absence of reconstituted arteries for surgical bypass in the lower leg or foot. Primary outcome was amputation-free survival at 6 months. Secondary outcomes comprised of primary and secondary graft patency of arteriovenous conduit, limb salvage, wound healing, change in Rutherford classification, reintervention rate and overall survival, all of which were tabulated at 30 days, 6 months, and 12 months. Technical success was defined as antegrade blood flow through the venous circuit. The technique is summarized in Figure 1.

The results demonstrated 95.5% technical success rate. While the primary graft patency significantly decreased over time and the reintervention rate subsequently increased, the amputation-free survival and overall survival plateaued at 70.3% and 83.6% respectively within the follow-up period. Furthermore, more than 75% of the patients in each time interval experienced improved wound healing and more than 50% experienced improvement in the Rutherford classification system throughout the 12 months.

These results show that percutaneous deep venous arterialization using commercially available devices helps delay amputation, improves survival, and enables wound healing. Of note, there are other larger trials which explored similar questions, namely PROMISE I, PROMISE II, and ALPS trial via Limflow system, and showed comparable results.

The occlusion rate of the arteriovenous conduit in a short period of time is a concern in this article as well as the aforementioned larger trials. The authors believe that the predominant cause is the progression of venous stenosis distal to the stent graft in the pedal venous outflow. As a result, self-expanding stents were used increasingly during posterior tibial percutaneous deep venous arterialization. The use of valvulotome in the Limflow system may also help address this. The other possible explanation for the high occlusion rate is that it is a consequence of venous arterialization akin to a hemodialysis fistula.

Despite the high occlusion rate of the arteriovenous conduit, the rate of wound healing was favorable across the 12-month span. The authors initially attributed the wound healing to retrograde flow through the presumed nonobstructed venous circuit into the retrograde capillary bed. The current hypothesis is that by promoting blood flow into the distal capillary beds of the leg/foot via intervention, oxygenation is improved and flow to hibernating collaterals is increased, leading to cascades of physiological responses including angiogenesis which promote wound healing.

The dissociation between high occlusion rates of the arteriovenous conduit and improved wound healing served as an important limitation of the study. It is unclear if the wound healing was attributed to the procedure alone or the improved wound care patients received through multidisciplinary approach. Additional limitation of the study was the retrospective nature of the study and inability to compare outcomes with a control group or those who underwent surgical deep venous arterialization. Additionally, multiple patients lost to follow-up over 12-month period made it difficult to assess the long-term effects or the durability of the procedure.

Commentary

The study investigated the feasibility of percutaneous deep venous arterialization in patients with critical limb ischemia. Despite the limitations of the study, the results were overall favorable to confidently allow appropriately trained specialists to offer it as an option to otherwise no-option patients with critical limb ischemia. More studies, such as the actively undergoing PROMISE III trial, can further aid in understanding of the intervention. If the Limflow system were to be approved for use in the United States, the dedicated valvulotome in the device can help combat the distal venous stenosis likely contributing to the high occlusion rate of the conduit.

One interesting aspect mentioned in the article is that it is unclear if the improved rate of wound healing was attributed to the procedure alone or the multidisciplinary approach of postprocedural wound care. My opinion is that this uncertainty actually highlights the effectiveness multidisciplinary approach can bring to the table. It fosters a holistic approach to patient care, enabling us to make tailored and coordinated clinical decisions to patients. In the long run, this integrates interventional radiology as an integral member of the treatment team and the proceduralists’ clinical opinions into consideration outside of the procedural room.

Post author

Naeem Patel, DO
Radiology Resident, PGY4
Department of Radiology, Interventional Radiology Division
Hartford Hospital, Hartford, CT
@Naeemp7Patel