Can electrocoagulation (high-frequency electrical current) applied locally destroy cancer spread to the liver?
Background
When cancer spreads to other sites in the body, one of the most common sites is the liver. Besides cancer of the liver (primary, or original liver cancer), liver metastases (new cancers that develop in parts of the body besides the original cancer) from colorectal cancer are the most common cancers affecting the liver. More than half of the people whose cancer spread to the liver die from complications. Metastases in the liver can be destroyed using several different methods; one of these is electrocoagulation by diathermy. This method requires that a special electrode be placed in or near the cancer site. The electrode is used to transmit high-frequency electrical currents, which generate high temperatures. This causes the proteins within the tissue to coagulate, or clot, thereby destroying it. The electrode is positioned by cutting into the abdomen with a laparotomy (open surgery) or a laparoscopy (keyhole surgery).
Methods
We looked for randomised clinical trials that assessed the effect of electrocoagulation by diathermy, administered alone or with another intervention, versus no intervention, or any other treatment, in people with cancer of any location that had spread to the liver. We looked at the effect of electrocoagulation on the risk of death, quality of life, adverse events (unwanted effects caused by the intervention), time to death, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, and tumour response.
Study characteristics
We last searched for evidence on 6 October 2020. We only identified one randomised clinical trial. The trial allocated participants at random to four intervention groups: electrocoagulation (use of diathermy) alone; electrocoagulation plus dimethyl sulphoxide; electrocoagulation plus allopurinol; versus a control group, which only received a solution of allopurinol by mouth. The treatment was started on the fifth day after surgical removal of the sigmoid colon (last section of the bowel), and participants were followed for five years. The trial included 306 participants, but data were only collected on 223 participants.
Key results
On the basis of one randomised clinical trial, at high risk of bias and few participants, we found insufficient evidence to detect whether electrocoagulation by diathermy alone, compared with a solution of allopurinol (control), made a difference in risk of death and post-operative death for people with liver metastases from colon cancer; electrocoagulation in combination with allopurinol or dimethyl sulphoxide may slightly decrease the risk of death compared with the control intervention, but the evidence is also insufficient and uncertain. It is very uncertain if there is a difference in post-operative death between the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control intervention. The data on other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response, and health-related quality of life were either lacking or insufficient for analysis.
Quality of evidence
We judged the evidence to be of low to very low certainty because the trial was not properly performed, putting it at high risk of bias regarding the reliability of the obtained data. The trial included a relatively small number of participants and it described overall few events. The reported results were insufficient as only few outcomes of interest to people with liver metastases and their doctors were reported.
Electrocoagulation by diathermy is no longer used in the way it is described in the trial as it has been replaced by other techniques. This could be a reason for the lack of further trials.
The evidence on the beneficial and harmful effects of electrocoagulation alone or in combination with allopurinol or dimethyl sulphoxide in people with liver metastases is insufficient, as it is based on one randomised clinical trial at low to very low certainty.
It is very uncertain if there is a difference in all-cause mortality and post-operative mortality between electrocoagulation alone versus control. It is also uncertain if electrocoagulation in combination with allopurinol or dimethyl sulphoxide may result in a slight reduction of all-cause mortality in comparison with a vehicle solution of allopurinol (control). It is very uncertain if there is a difference in post-operative mortality between the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus control. Data on other adverse events and complications, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life were most lacking or insufficiently reported for analysis.
Electrocoagulation by diathermy is no longer used in the described way, and this may explain the lack of further trials.
Primary liver tumours and liver metastases from colorectal carcinoma are two of the most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the people with metastatic liver disease will die from metastatic complications. Electrocoagulation by diathermy is a method used to destroy tumour tissue, using a high-frequency electric current generating high temperatures, applied locally with an electrode (needle, blade, or ball). The objective of this method is to destroy the tumour completely, if possible, in a single session. With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear.
To assess the beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus no intervention, other ablation methods, or systemic treatments in people with liver metastases.
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index – Science, CINAHL, ClinicalTrials.gov, ICTRP, and FDA to October 2020.
We considered all randomised trials that assessed beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus comparators, in people with liver metastases, regardless of the location of the primary tumour.
We used standard methodological procedures expected by Cochrane. We assessed risk of bias of the included trial using predefined risk of bias domains, and presented the review results incorporating the certainty of the evidence using GRADE.
We included one randomised clinical trial with 306 participants (175 males; 131 females) who had undergone resection of the sigmoid colon, and who had five or more visible and palpable hepatic metastases. The diagnosis was confirmed by histological assessment (biopsy) and by carcinoembryonic antigen (CEA) level. The trial was conducted in Iraq. The age of participants ranged between 38 and 79 years. The participants were randomised to four different study groups. The liver metastases were biopsied and treated (only once) in three of the groups: 75 received electrocoagulation by diathermy alone, 76 received electrocoagulation plus allopurinol, 78 received electrocoagulation plus dimethyl sulphoxide. In the fourth intervention group, 77 participants functioning as controls received a vehicle solution of allopurinol 5 mL 4 x a day by mouth; the metastases were left untouched. The status of the liver and lungs was followed by ultrasound investigations, without the use of a contrast agent. Participants were followed for five years.
The analyses are based on per-protocol data only analysing 223 participants. We judged the trial to be at high risk of bias. After excluding 'nonevaluable patients', the groups seemed comparable for baseline characteristics.
Mortality due to disease spread at five-year follow-up was 98% in the electrocoagulation group (57/58 evaluable people); 87% in the electrocoagulation plus allopurinol group (46/53 evaluable people); 86% in the electrocoagulation plus dimethyl sulphoxide group (49/57 evaluable people); and 100% in the control group (55/55 evaluable people). We observed no difference in mortality between the electrocoagulation alone group versus the control group (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.94 to 1.03; 113 participants; very low-certainty evidence). We observed lower mortality in the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control group (RR 0.87, 95% CI 0.80 to 0.95; 165 participants; low-certainty evidence). We are very uncertain regarding post-operative deaths between the electrocoagulation alone group versus the control group (RR 1.03, 95% CI 0.07 to 16.12; 152 participants; very low-certainty evidence) and between the electrocoagulation combined with allopurinol or dimethyl sulphoxide groups versus the control group (RR 1.00, 95% CI 0.09 to 10.86; 231 participants; very low-certainty evidence).
The trial authors did not report data on number of participants with other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life. Data on failure to clear liver metastases were not provided for the control group.
There was no information on funding or conflict of interest.
We identified no ongoing trials.