Particle Embolization of Hepatic Neuroendocrine Metastases for Control of Pain and Hormonal Symptoms

doi:10.1016/S1051-0443(99)70055-2

Journal of Vascular and Interventional Radiology

Volume 10, Issue 4, April 1999, Pages 397-403

https://doi.org/10.1016/S1051-0443(99)70055-2 Get rights and content

Purpose

To evaluate treatment outcome with respect to the indication for treatment in patients with neuroendocrine tumors metastatic to the liver undergoing hepatic artery embolization with polyvinyl alcohol (PVA) particles.

Materials and Methods

Charts and radiographs were reviewed of 35 patients undergoing 63 separate sessions of embolotherapy between January 1993 and July 1997. Patient demographics, tumor type, indication for embolization, and complications were recorded. Symptomatic and morphologic responses to therapy were noted, as well as duration of response.

Results

Fourteen men and 21 women underwent embolization of 21 carcinoid and 14 islet cell tumors metastatic to the liver. These patients underwent 63 separate episodes of embolotherapy. Of 48 episodes that could be evaluated, response to treatment was noted following 46 episodes (96%). The duration of response was longest in patients treated for hormonal symptoms with (17.5 months) or without (16 months) pain, and was shortest (6.2 months) when the indication was pain alone. Complications occurred after 11 of the 63 embolizations (17%), including four (6%) deaths. Cumulative 5-year survival following embolotherapy was 54%.

Conclusion

Hepatic artery embolization with PVA particles is beneficial for patients with neuroendocrine tumors metastatic to the liver and may be used for control of pain as well as hormonal symptoms. This therapy should be used cautiously when more than 75% of the hepatic parenchyma is replaced by tumor.

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Citation Excerpt :
Neuroendocrine neoplasms, in response to a signal from the nervous system, release higher-than-normal amounts of hormones into the blood, such as chromogranin A (CgA), serotonin or 5-hydroxytryptamine (5-HT), synaptophysin, somatostatin, and neuron-specific enolase (NSE), which cause debilitating symptoms such as uncontrollable diarrhea, flushing, skin rashes, and heart failure. Although NE cancers are uncommon in incidence, they represent a significant clinical challenge because at the time of the diagnosis they are often associated with liver metastases [3,5–7]. As a consequence of widespread metastases or the degree of hepatic involvement by the NE cancers, surgical resection is often non-curative [8].
Due to the overexpression of somatostatin receptors in neuroendocrine (NE) cancers, drug nanocarriers conjugated with somatostatin analogs, such as octreotide (OCT), for targeted NE cancer therapy may offer increased therapeutic efficacies and decreased adverse effects. In this study, OCT-functionalized unimolecular micelles were prepared using individual hyperbranched polymer molecules consisting of a hyperbranched polymer core (Boltorn^® H40) and approximately 25 amphiphilic polylactide-poly(ethlyene glycol) (PLA-PEG) block copolymer arms (H40-PLA-PEG-OCH₃/OCT). The resulting micelles, exhibiting a uniform core-shell shape and an average hydrodynamic diameter size of 66 nm, were loaded with thailandepsin-A (TDP-A), a relatively new naturally produced histone deacetylase (HDAC) inhibitor. In vitro studies using flow cytometry and confocal laser scanning microscopy (CLSM) demonstrated that OCT conjugation enhanced the cellular uptake of the unimolecular micelles. Consequently, TDP-A-loaded and OCT-conjugated micelles exhibited the highest cytotoxicity and caused the highest reduction of NE tumor markers. Finally, the in vivo studies on NE cancer bearing nude mice demonstrated that TDP-A-loaded and OCT-conjugated micelles possessed superior anticancer activity in comparison with other TDP-A formulations or drug alone, while showing no detectable systemic toxicity. Thus, these TDP-A-loaded and OCT-conjugated micelles offer a promising approach for targeted NE cancer therapy.
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To determine the efficacy of radiofrequency (RF) ablation in neuroendocrine tumor (NET) liver metastases. A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight studies were included (N = 301). Twenty-six percent of RF ablation procedures were percutaneous (n = 156), with the remainder conducted at surgery. Forty-eight percent of patients had a concomitant liver resection. Fifty-four percent of patients presented with symptoms, with 92% reporting symptom improvement following RF ablation (alone or in combination with surgery). The median duration of symptom improvement was 14–27 months. However, recurrence was common (63%–87%). RF ablation can provide symptomatic relief in NET liver metastases alone or in combination with surgery.
Embolization of metastatic neuroendocrine tumor resulting in clinical manifestations of syndrome of inappropriate secretion of antidiuretic hormone
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Complications after hepatic artery embolization are usually minor and transient. This report describes a patient with a pancreatic neuroendocrine tumor with hepatic metastases who repeatedly developed clinical findings of syndrome of inappropriate secretion of antidiuretic hormone with hyponatremia (sodium < 130 mEq/L), low plasma osmolarity (< 275 mOsm/kg), and high urine osmolarity (> 500 mOsm/kg) after every session of hepatic artery embolization.

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^☆: From the Departments of Radiology (K.T.B., L.A.B., G.I.G., J.S.) and Surgery (Y.F., L.H.B.), Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

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Particle Embolization of Hepatic Neuroendocrine Metastases for Control of Pain and Hormonal Symptoms☆

Purpose

Materials and Methods

Results

Conclusion

Carcinoid tumors: development of our knowledge

World J Surg

An odyssey in the land of small tumors

J Clin Oncol

The malignant carcinoid syndrome

Surg Gynecol Obstet

Control of carcinoid syndrome with hepatic artery embolization

Radiology

The carcinoid syndrome: palliation by hepatic artery embolization

AJR

Durable hepatic tumor regression after arterial chemoembolization-infusion in patients with islet cell carcinoma of the pancreas metastatic to the liver

Cancer