The study, led by Claudio Sallemi of the Interventional Radiology Unit at Fondazione Poliambulanza Istituto Ospedaliero, describes four consecutive patients with ruptured hepatocellular carcinoma treated with an unusual embolic material: a low-viscosity ethylene vinyl alcohol copolymer marketed as Squid Peri12. These agents, known as non-adhesive liquid embolic agents, consist of the EVOH copolymer dissolved in dimethyl sulfoxide, a solvent that diffuses rapidly into the bloodstream once the mixture is injected. As the solvent leaves, the copolymer precipitates in a slow, controlled fashion, solidifying into a soft, cohesive cast that conforms precisely to the twisted architecture of tumor vessels. The behavior is often described by operators as a lava effect, a gradual filling rather than the near-instantaneous gluing seen with older cyanoacrylate adhesives. Squid Peri12 is notable as the only EVOH-based agent with a kinematic viscosity of just 12 centistokes, a watery consistency that allows it to travel deep into fragile, tortuous tumor feeders that thicker agents might never reach.

All four patients arrived with the classic signature of rupture: acute anemia, hemodynamic decompensation, and free blood in the abdomen visible on non-contrast computed tomography. None was a candidate for emergency surgery, whether because of the sheer extent of the tumors, serious comorbidities, or outright instability. Conservative management with fluids and transfusions had failed to stabilize them. The tumors themselves were formidable, with a median diameter of 8.2 centimeters and a range stretching to 12.7 centimeters, all intensely hypervascular and all meeting the strictest LI-RADS 5 imaging criteria for hepatocellular carcinoma. One patient carried two bleeding lesions, one in each lobe. Two showed ominous local extension, one with suspected invasion of the adrenal gland and inferior vena cava plus segmental portal vein thrombosis, the other with a bulky mass displacing the gastric wall. In two patients alpha-fetoprotein, the blood marker that often tracks liver cancer activity, was elevated to as much as 3500 nanograms per milliliter.

The technical execution reveals how much finesse modern embolization demands. Procedures were performed under local anesthesia with mild sedation, using a slender 5 French sheath inserted through the radial or femoral artery. After mapping the hepatic arterial tree with a 4 French catheter, the operators advanced a DMSO-compatible microcatheter barely wider than a human hair into the subsegmental or even intralesional vessels feeding the tumor. Squid Peri12 was then injected at a deliberately slow rate of roughly 0.2 milliliters per minute under continuous fluoroscopy, allowing the team to watch the polymer cast grow in real time and stop the instant it threatened to escape into healthy territory. When reflux toward a larger artery appeared, the operators paused briefly to let the material partially polymerize, then resumed injection to push the cast deeper, a maneuver they call cast and push, adapted from the neurointerventional suites where EVOH agents have long been used for brain vascular malformations.

The results were striking on every measure the team recorded. Technical success was achieved in all four cases, with immediate hemostasis confirmed on post-procedural angiography and total embolic volumes of only 1 to 2.5 milliliters per patient. Fluoroscopy times averaged just 12 minutes despite the vascular complexity of the lesions. Crucially, no procedure-related adverse events occurred at all: no non-target embolization, no catheter entrapment, no post-embolization syndrome, no rebleeding, and no portal vein thrombosis. Liver function remained stable in three patients, while the fourth showed a transient rise in the liver enzyme AST from 63 to 358 units per liter, formally graded as a CTCAE version 5.0 grade 3 event but without any clinical deterioration or symptoms. Every patient was discharged home within three to five days, an outcome that would have been unthinkable a generation ago for patients bleeding to death from a burst liver tumor.

What followed over the next six months is what elevates this report from a hemostasis story to an oncology story. Follow-up CT scans at one, three, and six months, analyzed with modified RECIST criteria and semi-automatic volumetric software, showed sustained devascularization and consistent tumor shrinkage in every patient, with an average volume reduction approaching 60 percent and no additional transarterial or systemic therapy of any kind. Two patients, including the one whose tumor had appeared to invade the adrenal gland and vena cava, became eligible for curative-intent surgery after the embolization alone. In the operating room the suspected adrenal invasion was confirmed, an adrenalectomy was performed, and the resection was completed with preservation of the kidney. A third patient, initially inoperable because of gastric wall displacement and an alpha-fetoprotein level of 3500 nanograms per milliliter, experienced such marked regression that her marker fell to 27 nanograms per milliliter, rendering her a surgical candidate, though she ultimately declined the operation. The fourth patient achieved a complete radiologic response and remained disease-free without any further treatment.

The mechanistic explanation for this unexpected anti-tumor effect likely lies in the depth and permanence of the embolic cast. Particulate agents, the workhorses of conventional embolization, occlude vessels at a certain caliber but leave distal vascular networks patent, allowing tumors to reconstitute their blood supply over time. Cyanoacrylate glues polymerize on contact with blood, achieving rapid occlusion but demanding considerable operator skill and carrying a real risk of gluing the catheter in place or showering adjacent vessels with unintended emboli. The gradual precipitation of EVOH, by contrast, permits progressive, controlled filling of the entire intratumoral vascular bed, from feeding artery down to the smallest sinusoidal channels. A tumor stripped of its vasculature at that level cannot easily recover, and the ischemic injury may extend well beyond what a temporary particulate occlusion inflicts. The authors suggest this could explain both the sustained devascularization and the volume reductions observed without any adjunctive chemotherapy or immunotherapy.

The implications reach beyond the emergency setting. Hepatocellular carcinoma is typically diagnosed in patients with chronic liver disease, where every milliliter of functioning hepatic reserve matters and where treatment options for large or locally advanced tumors are painfully limited. If a single embolic session can downstage locally advanced disease to resectability, as it apparently did in two of these four patients, the low-viscosity EVOH approach could earn a place in planned, non-emergent treatment algorithms, potentially in combination with or as an alternative to conventional chemoembolization and radioembolization. The authors are careful to frame this as a hypothesis rather than a conclusion, noting that prior multicenter work has already established the safety of EVOH agents in acute non-neurovascular abdominal bleeding, but that their role in ruptured hepatocellular carcinoma had never been explored until now.

Honest caveats temper the enthusiasm. This was a retrospective case series of four patients, the weakest tier of clinical evidence, formally classified as Level 4. The absence of a comparison group means the tumor shrinkage cannot be definitively attributed to the embolic agent rather than to the general effect of devascularization, and rare complications may simply not have surfaced in so small a cohort. The team itself, which also included Maria Parmigiani, Marco Garatti, and Massimo Graffeo, calls explicitly for larger prospective studies to confirm the findings and define the role of EVOH agents beyond emergent indications. Still, the combination of flawless technical outcomes, preserved portal vein patency, stable liver function, and two unexpected conversions to curative surgery is difficult to dismiss as coincidence.

For a complication that has long carried a grim prognosis, the message of this small study is quietly revolutionary: the material used to plug a bleeding liver tumor in the middle of the night may also be a weapon against the tumor itself. If prospective trials bear out what these four patients experienced, the emergency catheter lab could become an unexpected starting point on the road to cure for some of the sickest liver cancer patients in the hospital.

Subject of Research: Emergency transarterial embolization of ruptured hepatocellular carcinoma using a low-viscosity EVOH copolymer and its potential tumor-shrinking effects

Article Title: Transarterial embolization with a low-viscosity ethylene vinyl alcohol (EVOH) copolymer for ruptured hepatocellular carcinoma: an oncologic role beyond hemostasis

Article References: Sallemi, C., Parmigiani, M., Garatti, M., & Graffeo, M. (2025). Transarterial embolization with a low-viscosity ethylene vinyl alcohol (EVOH) copolymer for ruptured hepatocellular carcinoma: an oncologic role beyond hemostasis. CVIR Oncology, 1(1), Article 24. https://doi.org/10.1007/s44343-025-00023-1

Image Credits: AI Generated

DOI: 10.1007/s44343-025-00023-1

Keywords: hepatocellular carcinoma, ruptured HCC, transarterial embolization, EVOH copolymer, Squid Peri12, liquid embolic agent, interventional radiology, tumor downstaging, liver cancer, hemostasis, alpha-fetoprotein, DMSO-compatible microcatheter