|Year : 2022 | Volume
| Issue : 4 | Page : 205-210
Ablative therapies in primary and metastatic liver tumours: An early experience
Phani Chakravarty Mutnuru1, Shabana Begum1, Rammurti Susarla1, Bheerappa Nagari2, Surya Ramachandra Varma Gunturi2, Venu Madhav Thumma2, Sadashivudu Gundeti3
1 Department of Radiology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Surgical Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
|Date of Submission||04-Apr-2022|
|Date of Decision||26-May-2022|
|Date of Acceptance||27-May-2022|
|Date of Web Publication||04-Oct-2022|
Phani Chakravarty Mutnuru
Associate Professor, Department of Radiology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500 082, Telangana
Source of Support: None, Conflict of Interest: None
Background: Hepatic resection and hepatic transplantation are considered the only definitive treatment modalities capable of achieving cure for primary and metastatic liver tumours. As few patients qualify to receive these treatments, local ablative therapies are increasingly being used as treatment for primary and metastatic tumours of the liver.
Methods: During the period January 2018 to January 2022 we prospectively studied the utility of chemical and thermal ablation ablative therapy in 22 patients with primary and metastatic liver disease. All patients were followed at 1, 3 and 6 months.
Results: Percutaneous ethanol injection (PEI) was done in 2 patients. Radiofrequency ablation (RFA) was done in 13 patients [hepatocellular carcinoma (HCC) 8, metastases 5]. With RFA, out of eight HCC patients, complete ablation was seen in 4; 2 patients underwent partial hepatectomy; 2 patients died within a month of ablation due to associated co-morbidities. In 5 patients with metastases, 3 achieved complete ablation; partial hepatectomy and systemic chemotherapy was needed in 1 patient each. With microwave ablation (MA) (n=6; HCC 3, metastases 3), complete ablation was achieved in 3 HCC patients. In patients with metastases, complete ablation was seen in 2 and one patient in addition, underwent transarterial chemoembolization. One patient with metastasis underwent both RFA and MA; complete ablation was achieved; MA was repeated a few months after RFA as new lesion developed.
Conclusions: Our study results suggest that chemical and thermal ablation ablative therapies are effective both as palliative and curative in the management of primary and metastatic liver lesions.
Keywords: Liver tumour, microwave ablation, radiofrequency ablation
|How to cite this article:|
Mutnuru PC, Begum S, Susarla R, Nagari B, Varma Gunturi SR, Thumma VM, Gundeti S. Ablative therapies in primary and metastatic liver tumours: An early experience. J Clin Sci Res 2022;11:205-10
|How to cite this URL:|
Mutnuru PC, Begum S, Susarla R, Nagari B, Varma Gunturi SR, Thumma VM, Gundeti S. Ablative therapies in primary and metastatic liver tumours: An early experience. J Clin Sci Res [serial online] 2022 [cited 2022 Dec 5];11:205-10. Available from: https://www.jcsr.co.in/text.asp?2022/11/4/205/357845
| Introduction|| |
The liver is a common site for both primary malignancy and metastatic disease. Among the different primary liver cancers, hepatocellular carcinoma (HCC) is the most common solid tumour and the sixth-most common cancer worldwide, the third-leading cause of cancer-related deaths with an increasing incidence. The most common risk factors associated with HCC are hepatitis B virus and hepatitis C virus infections, other risk factors include smoking, alcohol use, haemochromatosis, aflatoxin exposure, etc. Emerging risk factors such as non-alcoholic fatty liver disease and obesity recently gained interest for associated with HCC.
The age-adjusted incidence rate of HCC in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2/100,000 of population per year. The age-standardised mortality rate for HCC in India for men is 6.8/100,000 and for women is 5.1/100,000 with a male-to-female ratio of 4:1.
Metastatic tumours of the liver are more common than primary tumours. The most common sites of primary tumour for liver metastasis are the lung, breast and colorectal regions. The high incidence of hepatic metastases has been attributed to two mechanisms. First, the dual blood supply of the liver from the portal and systemic circulation increases the likelihood of metastatic deposits in the liver. Second, the hepatic sinusoidal epithelium has fenestrations that enable easier penetration of metastatic cells into the liver parenchyma.
Conventionally, hepatic resection and to an extent hepatic transplantation are considered the only definitive treatment modalities or gold standard treatment, capable of achieving cure. Usually, patients with a single small HCC (up to 5 cm) or up to three lesions (<3 cm) are indicated for surgery. However, <20% of HCC patients qualify or are considered candidates for these treatments due to varying reasons. This has led to dividing patients into two categories. First, patients who are not fit for surgery due to the presence of tumours in unresectable locations, inadequate functional hepatic reserve with cirrhosis, presence of multiple comorbidities and the limited number of donor livers. Second, patients who are not willing for surgery. This led to increased role of minimally invasive techniques such as percutaneous ablation, transarterial embolisation, or combined therapies.
These minimally invasive therapies have been used mainly for palliation but have also increasingly been used with curative intent. According to newer studies, local ablative procedures can be considered better alternative to surgery. Tumour ablation not only allows local control but it also helps to downstage patients, which can then let some of these patients become qualified for potentially curative treatments.
The present study was designed to evaluate the profile and outcome in patients treated with local ablative therapies for primary and metastatic tumours of the liver; and evaluate the safety, efficacy, limitation and complications of local ablative therapies in the management of resectable and unresectable primary and metastatic tumours of the liver.
| Material and Methods|| |
A prospective study was conducted in the vascular and interventional radiology unit of the Department of Radiology, at our tertiary care teaching hospital at Hyderabad, Telangana State, India, over 4 years from January 2018 to January 2022 in a selected population of 22 patients. The study was approved by the Institutional Scientific Research Committee and Institutional Ethics Committee.
Patients with the Eastern Cooperative Oncology Group performance status 0 or 1; those with Child–Pugh score 7 (child A or B); patients with Barcelona-Clinic Liver Cancer staging classification O or A; and patients with histologically, radiologically or clinically diagnosed (for patients with difficulty in obtaining histological samples), primary or metastatic liver tumour were included in the study.
Presence of extrahepatic metastasis and patients with advanced liver disease; patients with a history of cardiac disease including congestive heart failure; active coronary artery disease or cardiac arrhythmias; patients with complete portal vein thrombosis or Child–Pugh stage C; Patients with haemoglobin <7 g/dL, absolute neutrophil count <1000/mm3, platelet count <50,000/mm3, inadequate clotting function: international normalised ratio >1.5; aspartate aminotransferase or alanine aminotransferase >5 times upper limit of normal (ULN); serum creatinine >1.5 times ULN and bilirubin >3 mg/dL were excluded from the study.
After taking history and conducting physical examination, all patients were counselled regarding their diagnosis and given realistic expectations of the potential outcome, complications and post-procedure course. Clinical, biochemical, and histopathological findings were recorded in all patients.
Pre-procedure imaging assessment was made with ultrasonography (USG), triphasic computed tomography (CT)/magnetic resonance imaging or positron-emission tomography-CT in all patients for adequacy in terms of demonstrating tumour number, location, margins with normal liver, proximity to or invasion of vessels and proximity to critical structures such as gallbladder, stomach and colon. Oral anticoagulants and antiplatelets were stopped 5–7 days before the procedure.
In our study, chemical ablation was performed under local anaesthesia and thermal ablation was performed under general anaesthesia. All cases were done under USG guidance. We did percutaneous ethanol ablation before the availability of thermal ablation devices in our institute. With the availability of thermal ablation devices, either radiofrequency ablation (RFA) or microwave ablation was done as per the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) guidelines. Lesions which are adjacent to vascular structures and adjacent to the gallbladder, stomach or colon were selected for microwave ablation due to the absence of heat-sink effect and the rapidity of the procedure. In the rest of the patients, we did RFA as it is cost-effective and has no significant variation as compared to microwave. There were no immediate complications and all patients tolerated well the ablation procedures.
Follow-up after ablative therapy included detailed clinical examination; serum alpha foeto protein (AFP) estimation (if > 20 ng/mL at enrolment); and imaging at 1, 3 and 6 months to assess response.
Continuous variables are summarised as mean standard deviation; categorical variables are summarised as percentages. Data were analysed using the Statistical Package for Social Sciences (SPSS) software version 22.0 (SPSS Inc., Armonk, NY, USA).
| Results|| |
In our study, 22 participants underwent local ablative procedures for primary and secondary liver tumours. Our study group was divided into two groups: primary liver tumours such as HCC and secondary liver tumours such as metastasis to the liver due to any other primary malignancy. In our study, we did liver tumour ablation on 22 patients between the age group of 40–75 years with a mean age of 60 years. Most of the lesions were seen in male patients (77%). Thirteen (59%) patients were diagnosed with cases of primary HCC and 9 (41%) patients were having liver metastases.
In HCC patients, we performed percutaneous ethanol injection (PEI) in two patients before the availability of thermal ablative devices in our institute. Single session of RFA was done in seven patients, two sessions of RFA were done in one patient and microwave ablation was done in three patients [Table 1]. In liver metastases patients, we did single session of RFA in five patients, microwave ablation in three patients and RFA + microwave ablation in one patient (for new lesion adjacent to the portal vein after RFA) [Table 2].
|Table 1: Ablative therapy-wise distribution of cases in liver hepatocellular carcinoma|
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|Table 2: Ablative therapy-wise distribution of cases in liver metastases|
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PEI procedure was done in two primary HCC patients [Figure 1]. Due to poor tumour response, one patient had to undergo Transarterial chemoembolization (TACE) procedure in the second session. Other patients had systemic metastasis on follow-up studies and had to be referred to medical oncology for systemic chemotherapy.
|Figure 1: A 60-year-old male patient with HCC. CECT abdomen showing a small peripherally enhancing lesion in the right lobe of the liver (a), PET-CT showing FDG uptake by the lesion (b) USG showing ill-defined hypoechoic lesion in the liver (c), post-ethanol ablation shows hyperechoic foci in the lesion (d)|
HCC = Hepatocellular carcinoma; CECT = Contrast-enhanced computed tomography; PET-CT = Positron emission tomography-computed tomography; USG = Ultrasonography; FDG = 18Fluorodeoxy glucose
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RFA procedure was done in 13 patients (HCC 08 and metastasis 05) [Figure 2]. Out of eight HCC patients, complete ablation was seen in four patients. Two patients underwent partial hepatectomy due to partial response. Two patients died within a month of ablation due to associated comorbidities. In five metastatic patients, three patients achieved complete ablation. One patient underwent partial hepatectomy and one patient underwent systemic chemotherapy.
|Figure 2: A 75-year-old patient with biopsy proven HCC. CEMR shows enhancing lesion on arterial phase with washout in delayed phase (a), USG shows hypoechoic lesion in the liver (b), RFA shows hyperechoic foci (c), follow-up CEMR shows good response with reactive peripheral enhancement (d)|
HCC = Hepatocellular carcinoma; CEMR = Contrast enhanced magnetic resonance imaging; USG = Ultrasonography;
RFA = Radiofrequency ablation
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Microwave ablation was done in six patients (HCC 03 and metastasis 03). In three HCC patients, complete ablation was noted. In three metastatic patients, complete ablation was seen in two patients and one patient in addition underwent TACE [Figure 3]. One patient underwent both RFA and microwave ablation for liver metastasis and achieved complete ablation. Microwave ablation was done a few months after RFA as new lesion developed adjacent to the portal vein.
|Figure 3: A 62-year-old patient with carcinoma rectum with biopsy-proven liver metastasis. PET-CT shows FDG avid liver lesion (a), post-microwave ablation, PET-CT shows ablated lesion with peripheral uptake (b), hepatic arteriogram shows moderately vascular lesion (c), post-TACE, complete obliteration of tumour blush (d) |
PET-CT = Positron emission tomography-computed tomography; FDG = 18Fluorodeoxy glucose; TACE = Transarterial chemoembolisation
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| Discussion|| |
Primary liver malignancy is the sixth most common cancer worldwide with approximately 782,000 new cases and 745,000 deaths annually. Of all primary liver malignancies, HCC accounts for 85% of cases. In addition, metastases to the liver are very common, particularly from gastrointestinal primaries. As per the current treatment guidelines, surgical resection or liver transplantation is considered the gold standard for treating patients with very early-stage or early-stage HCC. Resection is also considered the standard of care for select patients with liver metastases. However, the majority of patients who are diagnosed with liver malignancies are not eligible for transplantation or resection due to the presence of medical comorbidities, prohibitive tumour location, inadequate liver function and multifocal or advanced disease. As a result, ablation is becoming increasingly utilised in the treatment of primary and metastatic liver tumours, both as destination therapy and as a bridge to transplantation.
Hepatic malignancy management has witnessed a lot of changes in the past decade. The newer ablative technologies have shifted the focus from simple palliation to potentially curative treatment. The 5-year survival following ablation of patients with liver tumours has improved dramatically, matching results to those obtained by liver transplantation or surgical resection in some of the studies. This has allowed increased utilisation of ablative techniques and expanded the criteria for ablation of hepatic malignancy. Furthermore, ablation is being increasingly combined with other treatments such as systemic chemotherapy, hepatectomy, transplantation or transarterial chemoembolisation (TACE) to increase the number of patients who may ultimately benefit from improved survival.
During the past two decades, considerable interest has developed in ablative therapies. Techniques that are being investigated include chemical, thermal, cryoablations and irreversible electroporation. Percutaneous chemical ablation with ethanol (95%) and acetic acid has worldwide acceptance for small hepatic tumours (<3 cm) due to relative ease of use and reduced cost. It causes chemical necrosis within the tumour. The resultant fibrotic reaction leads to microvasculature thrombosis and tumour ischaemia. The advantages are it can be done as outpatient procedure and avoids the problem of the 'heat-sink' effect adjacent to vessels [Figure 1]. The disadvantages are the need for multiple repetitions and uncertainty of ablative margin.
Thermal ablation techniques use heat to destroy tumour cells. RFA uses high-energy radio waves and microwave ablation uses electromagnetic waves to produce high temperatures in tumour. This heat produces coagulative necrosis and causes tumour ablation. Microwave ablation has advantages that it produces better ablation zones, can be used in larger masses and less affected by 'heat-sink effect'.
Recently, combined therapies have been widely applied in the treatment of HCC, particularly in larger lesions (>3 cm). Ablation is being increasingly combined with other treatments such as TACE, systemic chemotherapy, hepatectomy, or transplant to increase the number of patients who may ultimately benefit from improved survival. Ablation + TACE increases the chance of peritumoral satellitosis clearance and reduces the possibility of tumour recurrence, thereby enhancing the possibility of complete tumour necrosis and conceivably improving the overall survival rate.
To summarise, in our study technical success was achieved in all patients (100%). Locoregional ablative therapies significantly contributed to patient management in both primary and metastatic liver tumours. These techniques particularly helped surgically unfit patients, patients who were waiting for a liver transplant and patients who were poorly responded to chemotherapy. These techniques have the advantages of being fast, easily available and the results are highly accurate. The disadvantages are the need for skilled operators and sometimes repeat or additional procedure requirements.
The sample size in the present study was small. Surgical resection is the treatment of choice for liver tumours whenever possible. However, in recent years, locoregional ablation therapies have become more and more central in the treatment of liver lesions, as the majority of patients are not eligible for surgery. Depending on tumour size and number, ablation can be chosen as the only treatment or can be combined with systemic therapies, surgery, or other regional treatments, to utilise a multimodality approach to the patient aimed at the best treatment result. Overall, the results of this prospective observational study suggest a survival advantage. Although our sample size might be insufficient for making decisive conclusions, we believe that local ablative therapies are effective in treating early-stage HCC and liver metastasis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ryan MJ, Willatt J, Majdalany BS, Kielar AZ, Chong S, Ruma JA, et al.
Ablation techniques for primary and metastatic liver tumors. World J Hepatol 2016;8:191-9.
Center MM, Jemal A. International trends in liver cancer incidence rates. Cancer Epidemiol Biomarkers Prev 2011;20:2362-8.
Pithawa AK. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, diagnosis, management. Med J Armed Forces India 2007;63:205.
Kumar A, Acharya SK, Singh SP, Arora A, Dhiman RK, Aggarwal R, et al.
2019 update of Indian National Association For Study Of The Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II recommendations. J Clin Exp Hepatol 2020;10:43-80.
Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: Worldwide incidence and trends. Gastroenterology 2004;127:S5-16.
Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol 2010;52:930-6.
Singla S, Hochwald SN, Kuvshinoff B. Evolving ablative therapies for hepatic malignancy. Biomed Res Int 2014;2014:230174.
Crocetti L, de Baére T, Pereira PL, Tarantino FP. CIRSE standards of practice on thermal ablation of liver tumours. Cardiovasc Intervent Radiol 2020;43:951-62.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011;365:1118-27.
Pons F, Varela M, Llovet JM. Staging systems in hepatocellular carcinoma. HPB (Oxford) 2005;7:35-41.
Gillams A, Goldberg N, Ahmed M, Bale R, Breen D, Callstrom M, et al.
Thermal ablation of colorectal liver metastases: A position paper by an international panel of ablation experts, The Interventional Oncology Sans Frontières meeting 2013. Eur Radiol 2015;25:3438-54.
Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An update. Hepatology 2011;53:1020-2.
Shibata T, Iimuro Y, Yamamoto Y, Maetani Y, Ametani F, Itoh K, et al.
Small hepatocellular carcinoma: Comparison of radiofrequency ablation and percutaneous microwave coagulation therapy. Radiology 2002;223:331-7.
Ueno S, Sakoda M, Kubo F, Hiwatashi K, Tateno T, Baba Y, et al.
Surgical resection versus radiofrequency ablation for small hepatocellular carcinomas within the Milan criteria. J Hepatobiliary Pancreat Surg 2009;16:359-66.
Georgiades CS, Hong K, Geschwind JF. Radiofrequency ablation and chemoembolization for hepatocellular carcinoma. Cancer J 2008;14:117-22.
Huo TI, Huang YH, Wu JC, Chiang JH, Lee PC, Chang FY, et al.
Sequential transarterial chemoembolization and percutaneous acetic acid injection therapy versus repeated percutaneous acetic acid injection for unresectable hepatocellular carcinoma: A prospective study. Ann Oncol 2003;14:1648-53.
European Association for the Study of the Liver Electronic address: [email protected]
; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182-236.
Lubner MG, Brace CL, Hinshaw JL, Lee FT Jr. Microwave tumor ablation: Mechanism of action, clinical results, and devices. J Vasc Interv Radiol 2010;21:S192-203.
Crocetti L, Bargellini I, Cioni R. Loco-regional treatment of HCC: Current status. Clin Radiol 2017;72:626-35.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]