Isolated chemohyperthermal perfusion of the liver with melphalan in the treatment of unresectable liver metastases with uveal melanoma

Uveal melanoma belongs to rare malignant neoplasms, and the biological peculiarity of this tumor determines the high rate of distant metastasis, which reaches 60 %. Most frequently, uveal melanoma metastases are localized in the liver and have an isolated character. At the same time, despite the achievements of modern drug therapy, the treatment results of this category of patients remain unsatisfactory. Among the regional methods of treatment of metastatic uveal melanoma, surgical treatment is considered to be the most effective. Median survival rate in the group of radically operated patients (R0) is 27 months. At present, in the vast majority of cases, surgical treatment is impossible because of multiple bilobar metastasis and advanced cancer process. Median life expectancy of patients with liver metastases is only 9 months. A promising method of regional treatment of inoperable metastatic uveal melanoma is isolated liver chemoperfusion. Multidisciplinary team of Radiology Scientific Research Center and Kostroma Oncologic Dispensary for the first time in Russia presents a clinical case of a patient with isolated inoperable uveal melanoma liver metastases using an innovative method - isolated high-dose chemo hyperthermic liver perfusion with melphalan. The article describes in detail the method of the procedure, estimates immediate (partial response in 1 month after the procedure) and long-term results of the method (stabilization of the condition against the background of immunotherapy in 9 months after surgery). Based on the presented clinical observation, isolated liver chemoperfusion with melphalan for this category of patients is reasonable. However, despite the encouraging immediate results, clinical experience needs to be accumulated in order to be further evaluated in clinical trials.

Download Full-text

Short and long-term results of surgical treatment of non-colorectal liver metastases.

HPB ◽

10.1016/j.hpb.2019.10.767 ◽

2019 ◽

Vol 21 ◽

pp. S805

Author(s):

B. Pérez-Saborido ◽

M. Rodríguez-López ◽

E. Asensio-Díaz ◽

M. Bailón-Cuadrado ◽

F.J. Tejero ◽

...

Keyword(s):

Surgical Treatment ◽

Liver Metastases ◽

Colorectal Liver Metastases ◽

Long Term Results ◽

Short And Long Term

Download Full-text

Neoadjuvant treatment with weekly high-dose 5-fluorouracil as a 24h-infusion, folinic acid (AIO regimen) and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer: Long-term results of a phase II trial

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.15083 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 15083-15083 ◽

Cited By ~ 1

Author(s):

A. Wein ◽

H. Albrecht ◽

U. Reulbach ◽

G. Maennlein ◽

W. Hohenberger ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Folinic Acid ◽

Phase Ii ◽

Phase Ii Trial ◽

Neoadjuvant Treatment ◽

Long Term Results ◽

High Dose

Download Full-text

Fulminant Hepatic Failure after Chemosaturation with Percutaneous Hepatic Perfusion and Nivolumab in a Patient with Metastatic Uveal Melanoma

Case Reports in Oncological Medicine ◽

10.1155/2021/8870334 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Lindsey Teal ◽

Jeffrey Yorio

Keyword(s):

Liver Metastases ◽

Uveal Melanoma ◽

Fulminant Hepatic Failure ◽

Immune Checkpoint ◽

Hepatic Failure ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

High Dose ◽

Hepatic Perfusion ◽

Percutaneous Hepatic Perfusion

Immune checkpoint inhibitors, such as nivolumab, a programmed death receptor-1 (PD-1) inhibitor, have dramatically improved the treatment of advanced melanomas. Chemosaturation with percutaneous hepatic perfusion (PHP) delivers chemotherapy in high doses directly to the liver and is a potentially effective treatment modality in metastatic uveal melanoma with liver metastases. Its safety and effectiveness have not been studied in patients also receiving immunotherapy. A 46-year-old male with a history of uveal melanoma of the right eye was found to have liver metastases. He was treated with PHP using high-dose melphalan for 6 months with a partial response followed by progression. Two months after his last PHP treatment, the patient was started on nivolumab. After two doses of nivolumab, the patient developed severe hepatitis that progressed to fulminant hepatic failure and death despite treatment with high-dose corticosteroids and mycophenolate mofetil. Nivolumab and other immune checkpoint inhibitors have been effective in treating advanced melanoma and extending life. However, there are serious immune adverse events that can occur. While hepatitis after taking nivolumab has been documented, fulminant hepatic failure is rare. We believe that prior PHP treatment contributed to the severity of the hepatitis and, ultimately, fulminant hepatic failure. To our knowledge, this is the only case of fulminant hepatic failure secondary to a checkpoint inhibitor with preceding PHP. Specific precautions should be made in patients who have been exposed to PHP in the past, and further studies should be done to assess the safety of using checkpoint inhibitors after PHP.

Download Full-text

EP.TH.494Preclinical feasibility of in situ isolated normothermic liver chemoperfusion

British Journal of Surgery ◽

10.1093/bjs/znab309.056 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

Tamsyn Clark ◽

Georg Ebeling ◽

Daniel Voyce ◽

Luca Bau ◽

Constantin Coussios ◽

...

Keyword(s):

High Performance ◽

Liver Perfusion ◽

Vena Cava ◽

Systemic Circulation ◽

Hepatic Tissue ◽

High Dose ◽

Venous Bypass ◽

Tissue Levels ◽

Isolated Liver

Abstract Aims Up to 85% of patients with liver metastases have inoperable hepatic tumour burden. Isolated liver perfusion involves vascular isolation of the liver in situ and regional delivery of chemotherapy, avoiding dose-limiting extra-hepatic toxicity. In this series, we develop a surgical protocol to demonstrate the feasibility of isolated normothermic liver perfusion (INLP) and investigate short-term safety and feasibility of delivering high-dose chemotherapy. Methods Laparotomy and complete, vascular isolation of the liver was performed on 55-65Kg pigs (n = 6). The hepatic artery (HA), portal vein (PV) and inferior vena cava were cannulated and liver NMP established. Veno-venous bypass maintained systemic circulation. High-dose doxorubicin was administered to the isolated liver, circulated for 1 hour and vascular reconnection performed. Physiological parameters were measured and doxorubicin quantified in blood, bile and tissue by high-performance liquid chromatography. Results INLP with doxorubicin delivery achieved physiological flow rates (PV 0.7L/min (0.6-0.9L/min); HA 0.3L/min (0.2-0.4L/min)) and pH (median 7.3 (7.24-7.38)), with a median lactate of 0.42mmol/L. Median peak AST and ALT were 1045 U/L and 47 U/L respectively. Doxorubicin decay was fitted with a 2-compartmental model; distribution half-life was 1.9 minutes and plasma Cmax was higher than if given systemically resulting in mean hepatic tissue levels of 26+/-11.6 µg/g. There was no leak during INLP and doxorubicin was undetectable in kidney or heart. Conclusions Surgical isolation and NMP of the liver in situ, with concurrent veno-venous bypass is feasible and enables high-dose drug delivery resulting in therapeutic tissue levels with no off-target toxicity. Further safety studies are required.

Download Full-text

“Complex” hepatic echinococcosis

Annaly khirurgicheskoy gepatologii = Annals of HPB surgery ◽

10.16931/1995-5464.2021-4-32-40 ◽

2021 ◽

Vol 26 (4) ◽

pp. 32-40

Author(s):

A. B. Goncharov ◽

Y. A. Kovalenko ◽

Kh. A. Ayvazyan ◽

R. Z. Ikramov ◽

L. A. Marinova ◽

...

Keyword(s):

Surgical Treatment ◽

Lung Damage ◽

Long Term Results ◽

Tubular Structures ◽

National Medical ◽

Laparoscopic Intervention ◽

Hepatic Echinococcosis ◽

Isolated Liver ◽

Observation Period

Aim. To study the long-term results of surgical treatment in patients with “complex” hepatic echinococcosis.Materials and methods. The results of surgical treatment of 118 patients with hepatic echinococcosis from 2015 to 2020 at the A.V. Vishnevsky National Medical Research Center of Surgery were analyzed. The term “complex” hepatic echinococcosis has been proposed. A comparative analysis of the number and type of complications and surgical interferences 2 groups of patients was carried out: 66 patients with hepatic echinococcosis, 52 patients with complex hepatic echinococcosis.Results. During the observation period, no any recurrence was recorded. 55 (44%) of 118 patients had complex hepatic echinococcosis. Isolated liver damage was found in 74% of cases, combined liver and lung damage in 20% cases and with other organs – in 6%. In most cases, pericystectomy was performed (82%), 8% of patients underwent atypical hepatectomy, 4% – segmental resection, 3% – laparoscopic intervention, 3% – hemihepatectomy. Postoperative complications were recorded in 22 (18,6%) of cases. Accumulations of bile and biliary fistulas formed in 45% of cases, pneumotothorax or hydrothorax – in 23%, wound abscess – in 18%, hematomas in the hepatectomy zone – in 14% of the cases.Conclusion. Surgical treatment of complex hepatic echinococcosis requires an individual approach to the choice of the operation option. Preference should be given to parenchyma-preserving radical operations. When the liver lobe is totally replaced with a hydatid cyst and in case of cystobiliary fistulas hemihepatectomy should be performed, and it is acceptable to leave the fibrous capsule on large tubular structures.

Download Full-text