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Microwaving livers – an effective and innovative therapy for liver cancer

Consultant surgeon Mr David Lloyd has spent more than a decade developing a microwave machine that treats liver cancer by burning away cancerous tissue

David M Lloyd
MBBS, FRCS, MD
Consultant liver surgeon
University Hospitals Leicester
UK

Liver cancer is now the third leading cause of cancer deaths world-wide. Millions of patients suffer from primary liver cancer (known as hepatocellular cancer, HCC) every year and other millions develop liver cancer by the spread of cancer to the liver from other sites such as breast or colon – known as secondary liver cancer or metastatic liver cancer. The majority of primary liver cancers (HCCs) are caused by liver cirrhosis induced by long-standing hepatitis B or C, as well as being caused by alcohol. These diseases are endemic in the Far East, China and Malaysia, which have the highest incidence of HCC. Because of the influx of hepatitis B and C to the USA, particularly in California due to the migrant population, there has been a three-fold rise in the number of patients getting primary liver cancer in the past decade. Removing tumours from cirrhotic livers is very dangerous because of the risks of bleeding and liver failure. Treating these tumours with a microwave probe for a few minutes is therefore very attractive and could prove to be the most effective and safest of all treatments. Although the new chemotherapy drug sorafenib (Nexavar from Bayer HealthCare) has been licensed for the treatment of HCC, this drug only prolongs survival for a few months and does not offer a cure. The National Institute for Health and Clinical Excellence (NICE), the governmental body which regulates healthcare in the UK, has recently withdrawn its support for the funding of this drug on the NHS.[1] However, NICE does support the treatment of liver tumours using microwave ablation.[2]
The other group of patients benefiting from microwave tumour ablation are those with secondary liver cancer. Out of the millions of patients worldwide dying each year with this condition, there are hundreds of thousands who benefit from chemotherapy and surgery. It is not all doom and gloom for all patients. In particular, those patients with spread of tumour from colorectal cancer do very well with liver surgery alone or used in combination with chemotherapy and microwave tissue ablation (MTA). If patients have secondary colorectal cancer confined to the liver, without spread to other organs, more than 50% of patients can be offered curative treatment with a combination of chemotherapy and surgery. With the   introduction of MTA, many more thousands  of patients can be treated with curative intent. The use of MTA adds flexibility and extends the options of treatments for the liver surgeon.

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Microwaves and the machine
Microwaves are part of the electromagnetic spectrum. It is well known that microwaves are very efficient at heating tissues, as their use is now commonplace in every household. The microwaves interact with polarised water molecules causing them to oscillate at around five million times per second. This rapid molecular movement causes immediate intense heating within the field of the microwaves. Working with Professor Nigel Cronin and Dr Peter Clegg in the department of physics at Bath University, UK, I developed the equipment so that the energy can be channelled down a wire or cable into a small thin probe resembling a knitting needle. The initial probes measured 8mm in diameter, but more recently they measure 5-6mm; the percutaneous probe is less than 2mm in diameter. Each of these probes can be placed inside a tumour which can be heated for several minutes to over 60˚C, at which point the tumour proteins and DNA are denatured and destroyed.
Several experiments were carried out to determine the optimal frequency for the destruction of liver cancer tissue. Together with research registrar Andy Strickland, we concluded that the most efficient frequency was 2.45GHz, which, of course, matches the frequency used in household machines. The end of the probe or ’emitting antenna’ was designed to produce a sphericalshaped area of tissue destruction. Because the majority of tumours in the liver are spherical in shape, most can be treated by MTA. By varying the power or wattage, the size of the burn or ablated area could be varied accordingly. Tumours measuring 3cm in diameter, for example, can be ablated using the 2.45GHz generator at 100Watts for 2-3 minutes. This rate of ablation is remarkable, as most other types of ablating devices take significantly longer. Moreover, even large tumours of 6cm or 7cm in diameter  can be ablated within four minutes using this equipment.[3]

Innovation
The new and innovative microwave generator built by Acculis Ltd, UK, focuses the microwave energy along a thin cable into a probe which can be placed in the centre of a tumour within the liver. After a few minutes, the tumour is heated and the cancer cells are immediately destroyed. It is so effective that the equipment is now being used by many of the world’s leading liver surgeons including those based in the UK, Europe and the USA. In fact, more than 50 liver centres throughout the world are treating cancer patients with microwaves. Microwave tumour ablation (MTA) is the term used to describe the technique whereby the cancerous tumours are ablated and destroyed by the intense heat of the microwave energy. Initially, it was used during open, conventional liver surgery as an aid to help the surgeon remove and destroy all the liver cancer. It can now be used alone to destroy the liver tumours either during open surgery or laparoscopic surgery. A new tiny probe has recently been developed which allows the tumours to be treated percutaneously in an outpatient setting. These recent developments are proving extremely effective for the treatment of liver cancers, but the equipment could also be used to destroy other solid tumours such as lung, kidney and breast. The current Acculis microwave equipment is portable and has a simple touch-screen front panel for ease of use (Acculis Sulis V generator). The new percutaneous microwave probe (pMTA) has a water-cooled shaft and is able to ablate
tumours of 5cm in diameter, despite being less than 2mm in diameter. The pMTA probe is very versatile and can be used under local anaesthetic with ultrasound or CT guidance. This is very convenient for the surgeon or radiologist and, of course, spares the patient a big operation.

The future MTA
With more than 50 centres world-wide currently using this microwave equipment, a recent publication in the European Journal of Surgical Oncology demonstrated significant survival in patients treated with MTA who were initially declared inoperable by conventional methods.[4]  Many other liver centres are now in the process of obtaining their own MTA equipment because of the success demonstrated by our unit in Leicester, UK. Furthermore, all the liver surgeons using the equipment have agreed to enter their data voluntarily on a MTA database held in Leicester. During 2009, there were 250 MTA treatments performed in 135 patients entered on to the database.
On behalf of the International Microwave Tumour Ablation Group (IMTAG), I have been invited to present the world-wide results at the International Hepato-Pancreatico-Biliary Association (IHPBA) Congress in Buenos Aires, Argentina, in April 2010. Currently, patients with primary liver cancer (HCC) and those with secondary colorectal cancer should be considered for microwave ablation – particularly if the patients are not suitable for conventional liver surgery. It remains to be seen whether other tumour types will respond as effectively to this treatment. There is no doubt, however, that microwaves are here to stay and microwave generators may well be as ubiquitous in hospitals as they are in every home. If the scope of treatments increases to include patients with lung, renal, bone, prostate and breast cancer, microwave ablation will certainly have a major impact on the survival of thousands of patients in the future.

References
1. Final appraisal determination Sorafenib for the treatment of advanced hepatocellular carcinoma.  www.nice.org.uk/nicemedia/pdf/STASorafenibAdvHCCFAD.pdf
2. NICE interventional procedure guidance 214 (2007). Available from www.nice.org.uk/IPG214
3. Strickland A. et al. Asian Journal of Surgery 2007;28(2):151-3
4. Bhardwaja N et al. EJSO 2009;36(3):264-8.

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