No evidence to evaluate the potential benefits and harms of cryotherapy in the treatment of hepatocellular carcinoma

Liver cell cancer (hepatocellular carcinoma) is the most common primary cancer of the liver. Liver cancer is regarded as the third most commoncause of death from cancer. Only a minority of the patients are candidates for liver surgery or liver transplantation. Cold therapy (cryotherapy), where rapid freezing causes cancerous cells' destruction and death, is one of several 'minimally invasive treatment techniques' that have been recently developed. Currently, no large well-planned clinical investigations have been conducted to establish the potential benefits and harms associated with treating liver cell cancer patients with cryotherapy. Nor have any such investigations been undertaken to establish the superiority or inferiority of cryotherapy compared with other treatments for liver cell cancer. At present, there is no evidence to support or refute the alleged and potential benefits of cryotherapy. Large well-designed randomised clinical trials are feasible and are necessary to define the role of cryotherapy in the treatment of hepatocellular carcinoma.

Authors' conclusions: 

At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma. Randomised clinical trials with low-risk of bias may help in defining the role of cryotherapy in the treatment of hepatocellular carcinoma.

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Background: 

Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial.

Objectives: 

The aim of this review is to evaluate the potential benefits and harms of cryotherapy for the treatment of hepatocellular carcinoma.

Search strategy: 

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching national and topic-specific databases, bibliographies, conference abstracts, journals, and grey literature. Furthermore, we reviewed the reference lists and contacted the principal authors of the identified studies.

Selection criteria: 

Randomised clinical trials (irrespective of language or publication status) comparing cryotherapy with or without co-intervention(s) to placebo, no treatment, or other control interventions were considered for the review. Due to the absence of randomised clinical trials, we searched for quasi-randomised studies as well as prospective cohort studies and retrospective cohort studies.

Data collection and analysis: 

Two authors independently identified and assessed studies for their fulfilment of the inclusion criteria. Dichotomous data were expressed as risk ratio (RR) with 95% confidence intervals (CI). We performed the review following the recommendations of The Cochrane Collaboration.

Main results: 

We were unable to identify any randomised clinical trials. We were also unable to identify quasi-randomised trials. Instead, we identified two prospective cohort studies and two retrospective cohort studies. However, only one of these studies could be included for the assessment of benefit as the study results were stratified according to both the type of hepatic malignancy (primary or secondary) and the intervention group. This retrospective study compared percutaneous cryotherapy with percutaneous radiofrequency. The remaining studies were excluded for the analyses of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses.