Electrocoagulation for liver metastases.

BACKGROUND: 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 With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE). OBJECTIVES: To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019). SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion. MAIN RESULTS: We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559). AUTHORS' CONCLUSIONS: Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.

Percutaneous ethanol injection for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour. OBJECTIVES: To assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index - Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019). SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion. MAIN RESULTS: We identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm. Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases. The single included trial did not provide information on funding nor on conflict of interest. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.

Cryotherapy for liver metastases.

BACKGROUND: The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells. OBJECTIVES: To assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018. SELECTION CRITERIA: Randomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries. MAIN RESULTS: We found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87 men. The primary sites for the metastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.We identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P < 0.05). FUNDING: the trial did not provide information on funding. AUTHORS' CONCLUSIONS: The evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.

Cryotherapy for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. In cryoablation, liquid nitrogen or argon gas is delivered to the liver tumour, guided by ultrasound using a specially designed probe. Ice crystal formation during the rapid freezing process causes destruction of cellular structure and kills the tumour cells. OBJECTIVES: To study the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. SELECTION CRITERIA: We included all randomised clinical trials assessing the beneficial and harmful effects of cryotherapy and its comparators, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for our review, as well as information on the design and methodology of the trials. Bias risk assessment of and data extraction from the trials fulfilling the inclusion criteria were done by one author and checked by a second author. MAIN RESULTS: One randomised clinical trial fulfilled the inclusion criteria of the review. The trial was judged as a trial with high risk of bias due to the unclear report on the generation of the allocation sequence and allocation concealment, blinding, incomplete outcome data and the selective outcome reporting domain. The trial included 123 consecutive patients with solitary or multiple unilobar or bilobar liver metastases who were randomised into two groups, 63 received cryotherapy and 60 received conventional surgery. There were 36 females and 87 males. The primary sites for the metastases were colorectal (66.6%), stomach (7.3%), breast (6.5%), melanoma (4.9%), ovarian adenocarcinoma (4.1%), uterus (3.3%), kidney (3.3%), intestinal (1.6%), pancreatic (1.6%), and unknown (0.8%). The tumours were resectable and non-resectable.The patients were followed for up to 10 years (minimum five months). Mortality at the last follow-up was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group (RR 0.88; 95% CI 0.77 to 1.02); that is, no statistically significant difference was observed. In the cryotherapy group, 60%, 44%, and 19% of the participants survived 3, 5, and 10 years respectively, while in the conventional surgery group the percentages were 51%, 36%, and 8%. The hazard ratio calculated using the Parmar method was 0.71 (95% confidence interval (CI) 0.47 to 1.09). Recurrence in the liver was observed in 86% (54/63) of the patients in the cryotherapy group and 95% (57/60) of the patients in the conventional surgery group (relative risk (RR) 0.9; 95% CI 0.8 to 1.01); that is, no statistically significant difference was observed. Frequency of reported complications was similar between the cryotherapy group and the conventional surgery group except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the control group. However, it was not reported by the authors whether the differences were significant. No intervention-related mortality and no bile leakage were observed. AUTHORS' CONCLUSIONS: On the basis of one randomised clinical trial with high risk of bias, there is insufficient evidence to conclude if in patients with liver metastases from various primary sites cryotherapy brings any significant benefit in terms of survival or recurrence compared with conventional surgery. In addition, there is no evidence for the effectiveness of cryotherapy when compared with no intervention. At present, cryotherapy cannot be recommended outside randomised clinical trials.

Microwave coagulation for liver metastases.

BACKGROUND: Primary liver cancer and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. Microwave coagulation involves placing an electrode into a lesion under ultrasound or computed tomography guidance. The microwave coagulator generates and transmits microwave energy to the electrode. Coagulative necrosis causes cellular death and destroys tissue in the treatment area, resulting in reduction of tumour size. OBJECTIVES: To study the beneficial and harmful effects of microwave coagulation compared with no intervention, other ablation methods, or systemic treatments in patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. SELECTION CRITERIA: We included all randomised clinical trials assessing beneficial and harmful effects of microwave coagulation and its comparators, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information on participant characteristics, interventions, and study outcomes and data on outcome measures for our review, as well as information on design and methodology of the studies. Bias risk assessment of trials, determination of whether they fulfilled the inclusion criteria, and data extraction from retrieved for final evaluation trials were done by one review author and were checked by a second review author. MAIN RESULTS: One randomised clinical trial fulfilled the inclusion criteria of the review. Forty participants with multiple liver metastases of colorectal cancer and no evidence of extrahepatic disease were randomly assigned. Thirty of these participants (14 females and 16 males) were included in the analysis: 14 participants received microwave coagulation and 16 underwent conventional surgery (hepatectomy or liver resection). The diagnosis of colorectal cancer (Stage IB to IIIC; tumour (T)2 node (N)0 to T3N2) and liver metastases was confirmed by histological assessment. Mean participant age was 61 years. The tumours were resectable. The risk of bias in the trial was judged to be high.Participants were followed for three years. Mortality at the last follow-up was 64% (9/14) in the microwave group and 75% (12/16) in the conventional surgery group (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.53 to 1.39), that is, no significant difference was observed. In the microwave coagulation group, 71%, 57%, and 14% survived 1, 2, and 3 years, and in the conventional surgery group, the percentages were 69%, 56%, and 23%. The hazard ratio calculated using the Parmar method was 0.91 (0.39 to 2.15).Mean survival time was 27 months in the microwave group and 25 months in the conventional surgery group, and the mean disease-free interval was 11.3 months in the microwave group and 13.3 months in the hepatectomy group. Differences for both outcomes were not statistically significant. Reported frequency of adverse events was similar between the microwave coagulation and conventional surgery groups, except for the required blood transfusion, which was more common in the conventional surgery group. No intervention-related mortality was observed. After treatment, the carcinoembryonic antigen level decreased significantly in both groups. AUTHORS' CONCLUSIONS: On the basis of one randomised clinical trial, which did not describe allocation concealment or blinding, and which excluded from analysis 25% of participants after random assignment, evidence is insufficient to show whether microwave coagulation brings any significant benefit in terms of survival or recurrence compared with conventional surgery for participants with liver metastases from colorectal cancer. The number of adverse events, except for the requirement for blood transfusion, which was more common in the liver resection group, was similar in both groups. At present, microwave therapy cannot be recommended outside randomised clinical trials.

Transarterial (chemo)embolisation versus no intervention or placebo intervention for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. Chemoembolisation is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Therefore, embolisation of the hepatic artery can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. OBJECTIVES: To study the beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. SELECTION CRITERIA: We included all randomised clinical trials assessing beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases, no matter the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures for our review as well as information on the design and methodology of the studies. Bias risk assessment of the trials, fulfilling the inclusion criteria, and data extraction from the retrieved final evaluation trials were done by one author and checked by a second author. MAIN RESULTS: One randomised clinical trial fulfilled the inclusion criteria of the review. Sixty-one patients with colorectal liver metastases were randomised into three intervention groups: 22 received hepatic artery embolisation, 19 received hepatic artery infusion chemotherapy, and 20 were randomised to control, described as "no active therapeutic intervention, although symptomatic treatment was provided whenever necessary". As hepatic artery infusion chemotherapy is not in the scope of this review, we have not included the data from this intervention group. In the remaining two groups that were of interest to the review, 43 of the participants were men and 18 women. Most tumours were synchronous metastases involving up to 75% of the liver and non-resectable. The risk of bias in the trial was judged to be high.Patients were followed-up for a minimum of seven months. Mortality at last follow-up was 86% (19/22) in the hepatic artery embolisation group versus 95% (19/20) in the control group (RR 0.91; 95% CI 0.75 to 1.1), that is, no statistically significant difference was observed. Median survival after trial entry was 7.0 months (range 2 to 44) in the hepatic artery embolisation group and 7.9 months (range 1 to 26) in the control group. Nine out of 22 (41%) in the hepatic artery embolisation group and five out of 20 (25%) in the control group developed evidence of extrahepatic disease (RR 1.64; 95% CI 0.60 to 4.07). Local recurrence was reported for 10 patients in the trial without details about the trial group. Most patients in the embolisation group experienced post-embolic syndrome (82%), and one patient had local haematoma. No other adverse events were reported. The authors did not report if there were any adverse events in the control group. AUTHORS' CONCLUSIONS: On the basis of one small randomised trial that did not describe sequence generation, allocation concealment or blinding, it can be concluded that in patients with liver metastases no significant survival benefit or benefit on extrahepatic recurrence was found in the embolisation group in comparison with the palliation group. The probability for selective outcome reporting bias in the trial is high. At present, transarterial (chemo)embolisation cannot be recommended outside randomised clinical trials.

Percutaneous ethanol injection for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. Percutaneous ethanol injection (PEI) causes dehydration and necrosis of tumour cells accompanied by small vessel thrombosis, leading to tumour ischaemia and destruction. OBJECTIVES: To study the beneficial and harmful effects of percutaneous ethanol injection compared with no intervention, other ablation methods, or systemic treatments in patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. SELECTION CRITERIA: We included all randomised clinical trials assessing the beneficial and harmful effects of percutaneous ethanol injection versus no intervention, other ablation methods, or systemic treatments in patients with liver metastases. DATA COLLECTION AND ANALYSIS: We extracted the relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures for our review, as well as information on the design and methodology of the studies. Quality assessment of the trials fulfilling the inclusion criteria and data extraction from the trials retrieved for final evaluation were done by one author and checked by a second author. MAIN RESULTS: One randomised clinical trial was included, comparing transcatheter arterial chemoembolisation (TACE) + percutaneous intratumour ethanol injection (PEI) versus TACE alone. Forty-eight patients with liver metastases were included; 25 received the intervention with PEI and 23 received TACE alone.Mortality data were not reported. The trial reported the survival data after one, two, and three years. In the TACE + PEI group, 92%, 80%, and 64% of the patients survived after 1, 2, and 3 years respectively; in the TACE group, 78.3%, 65.2%, and 47.8% of the patients survived after 1, 2, and 3 years respectively. The hazard ratio was 0.57 (95% CI 0.19 to 1.67). The local recurrence was 16% in the TACE + PEI group and 39.1% in the TACE group, resulting in a relative risk (RR) of 0.41 (95% CI 0.15 to 1.07). Forty-five tumours (66.2%) out of 68 tumours in total shrunk by at least 25% in the TACE + PEI group versus 31 tumours (48.4%) out of 64 tumours in total in the TACE group (RR 2.08; 95% CI 1.03 to 4.2). The authors reported some adverse events, but with very few details. AUTHORS' CONCLUSIONS: On the basis of one small randomised trial, it can be concluded that addition of PEI to TACE, as compared with TACE alone, in patients with liver metastases seems to bring no clear benefit in terms of survival and local recurrence. The size of the tumour necrosis was larger in the combined treatment group. No intervention-related mortality or major complications were reported. More trials are needed.

Electro-coagulation for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. Electro-coagulation is the coagulation (clotting) of tissue using a high-frequency electrical current applied locally with a metal instrument or needle with the aim of stopping bleeding. The object of this technique is to destroy the tumour completely, if possible, in a single surgical session. OBJECTIVES: To study the beneficial and harmful effects of electro-coagulation compared with no intervention, to other ablation methods, or systemic treatments in patients with liver metastases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. SELECTION CRITERIA: We included one randomised clinical trial that assessed beneficial and harmful effects of electro-coagulation and its comparators in patients with liver metastases, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures as well as information on the design and methodology of the trials. Risk of bias of the trials and data extraction was carried out by one author and checked by a second author. MAIN RESULTS: We included one randomised clinical trial that compared four groups: electro-coagulation alone, electro-coagulation + dimethyl sulphoxide, electro-coagulation + allopurinol, and control (Salim 1993). The risk of bias in the trial is high. In three groups, patients had their metastases destroyed with diathermy electro-coagulation (current set at No 5) and received: 1) solution of allopurinol by mouth 5 mL 4 x a day or 2) allopurinol by mouth 5 mL (50 mg) 4 x a day or 3) dimethyl sulphoxide by mouth 5 mL (500 mg) 4 x a day. In the control group patients received a solution of allopurinol by mouth 5 mL 4 x a day. The treatment was started in the fifth postoperative day and was continued for five years. Three hundred and six patients who had undergone resection of the sigmoid colon and who had five or more hepatic metastases were included; 75 received electro-coagulation alone (58 were evaluable), 76 received electro-coagulation plus allopurinol (53 were evaluable), 78 received electro-coagulation plus dimethyl sulphoxide (57 were evaluable), and 77 were in the control group (55 evaluable).The authors reported the number of deaths due to disease spread (100% in the control, 98% in electro-coagulation, 87% in electro-coagulation + allopurinol, and 86% in the electro-coagulation + dimethyl sulphoxide groups). There was a significant benefit in favour of the electro-coagulation + allopurinol (risk ratio (RR) 0.87 (95% confidence interval (CI) 0.78 to 0.96)) and electro-coagulation + dimethyl sulphoxide (RR 0.86 (95% CI 0.77 to 0.95)) groups compared to the control group, but no such benefit in the electro-coagulation alone group (RR 0.98 (95% CI 0.95 to 1.02)) compared to the control group. There were no local recurrences, no positive tests for occult blood, and observed pulmonary metastases were always with ultrasonographic evidence of hepatic secondaries and were not significantly different for the experimental groups compared to the control group (electro-coagulation: RR 1.11 (95% CI 0.4 to 3.09)), electro-coagulation + allopurinol (RR 0.86 (95% CI 0.28 to 2.66)), electro-coagulation + dimethyl sulphoxide (RR 0.8 (95% CI 0.26 to 2.48)). None of the adverse events were significantly associated with treatment. AUTHORS' CONCLUSIONS: On the basis of one randomised trial which did not describe its methodology in sufficient detail to assess risk of bias and quality, excluded 27% of patients after randomisation due to various reasons, and is probably not free from selective outcome reporting bias, there is insufficient evidence to conclude that in patients with colonic cancer liver metastases, electro-coagulation alone brings any significant benefit in terms of survival or recurrence compared with the control. In addition, there is insufficient evidence for the effectiveness of adding allopurinol or dimethyl sulphoxide to electro-coagulation. The probability for selective outcome reporting bias in the trial is high. More randomised trials are needed in order to sufficiently validate electro-coagulation with or without co-interventions.

Transarterial (chemo)embolisation versus no intervention or placebo intervention for liver metastases.

BACKGROUND: Primary liver tumours and liver metastases from colorectal carcinoma are the two 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 patients with metastatic liver disease will die from metastatic complications. Chemoembolisation is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Therefore, embolisation of the hepatic artery can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. OBJECTIVES: To study the beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to November 2011. SELECTION CRITERIA: We included all randomised clinical trials assessing beneficial and harmful effects of transarterial (chemo)embolisation compared with no intervention or placebo intervention in patients with liver metastases, no matter the location of the primary tumour. DATA COLLECTION AND ANALYSIS: We extracted relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures for our review as well as information on the design and methodology of the studies. Bias risk assessment of the trials, fulfilling the inclusion criteria, and data extraction from the retrieved final evaluation trials were done by one author and checked by a second author. MAIN RESULTS: One randomised clinical trial fulfilled the inclusion criteria of the review. Sixty-one patients with colorectal liver metastases were randomised into three intervention groups: 22 received hepatic artery embolisation, 19 received hepatic artery infusion chemotherapy, and 20 were randomised to control, described as "no active therapeutic intervention, although symptomatic treatment was provided whenever necessary". As hepatic artery infusion chemotherapy is not in the scope of this review, we have not included the data from this intervention group. In the remaining two groups that were of interest to the review, 43 of the participants were men and 18 women. Most tumours were synchronous metastases involving up to 75% of the liver and non-resectable. The risk of bias in the trial was judged to be high.Patients were followed-up for a minimum of seven months. Mortality at last follow-up was 86% (19/22) in the hepatic artery embolisation group versus 95% (19/20) in the control group (RR 0.91; 95% CI 0.75 to 1.1), that is, no statistically significant difference was observed. Median survival after trial entry was 7.0 months (range 2 to 44) in the hepatic artery embolisation group and 7.9 months (range 1 to 26) in the control group. Nine out of 22 (41%) in the hepatic artery embolisation group and five out of 20 (25%) in the control group developed evidence of extrahepatic disease (RR 1.64; 95% CI 0.60 to 4.07). Local recurrence was reported for 10 patients in the trial without details about the trial group. Most patients in the embolisation group experienced post-embolic syndrome (82%), and one patient had local haematoma. No other adverse events were reported. The authors did not report if there were any adverse events in the control group. AUTHORS' CONCLUSIONS: On the basis of one small randomised trial that did not describe sequence generation, allocation concealment or blinding, it can be concluded that in patients with liver metastases no significant survival benefit or benefit on extrahepatic recurrence was found in the embolisation group in comparison with the palliation group. The probability for selective outcome reporting bias in the trial is high. At present, transarterial (chemo)embolisation cannot be recommended outside randomised clinical trials.

Loneliness among women with rheumatoid arthritis: a cross-cultural study in the Netherlands and Egypt.

The objective of this study was to explain loneliness as experienced by women with rheumatoid arthritis (RA) in a cross-cultural context. We studied 36 Egyptian female RA patients and 140 female Dutch RA patients.. Self-report data were collected about loneliness, physical and psychological health status, social support and social network, needs for help, attitudes and feelings of guilt. Loneliness was significantly higher among Egyptian (44.2 +/- 32.3) than Dutch (12.9 +/- 18.9) female RA patients (F = 54.3, p < 0.001). In Egypt, 36% of the variance of loneliness could be explained by worse affect (anxiety and depression; beta = 0.51), fewer children (beta = 0.31), and higher negative social support for the patients (beta = 0.28) in multiple regression analysis. In the Netherlands, 35% of feeling lonely could be explained by worse affect scores (beta = 0.52), less positive social support for the patients (beta = 0.24), and a higher degree of disability (beta = 0.21). Age of the patients and disease duration only explained 4% and 3% of the loneliness of RA patients in Egypt and the Netherlands, respectively. Female Egyptian RA patients experienced more loneliness than Dutch patients. Affect is the most important and constant variable in explaining loneliness in both countries. The role of the family in perceived loneliness is greater in Egypt than the Netherlands. Low social support received by patients is important in explaining loneliness in the Netherlands but not in Egypt.

Systematic review of the (cost-)effectiveness of spinal cord stimulation for people with failed back surgery syndrome.

OBJECTIVES: We conducted a systematic review to assess the (cost)effectiveness of spinal cord stimulation (SCS) in relieving certain kinds of pain for people with chronic pain owing to failed back surgery syndrome (FBSS). METHODS: We considered randomized trials, controlled observational studies of adult patients with chronic pain owing to FBSS, and case series with at least 50 patients permanently implanted, at least 60% FBSS patients and at least 1-year follow-up. SCS was additional to usual care and compared with usual care. The primary outcome was reduction of pain. Medline, Embase, Lilacs, Cinahl, and Cochrane Library databases were searched from inception until September 2006. An update search was carried out in January 2008. RESULTS: For the effectiveness analysis, 1 fully published randomized controlled trial, one randomized controlled trial with 6 month results (both of moderate quality), 1 retrospective cohort study, and 13 case series (all of low quality) were included. The mean period of follow-up was between 6 months and 8.8 years. These studies show that SCS is effective in the treatment of FBSS in terms of pain reduction. The effect was consistent in all analyzed studies. Improvements were also reported for other outcomes, such as quality of life and functional status. All the studies reported some complications, most of which were technical problems. In terms of cost-effectiveness, 3 studies met the inclusion criteria and offered the same conclusion that SCS is both more effective and less costly in the long-term, but there is an initial high cost associated with device implantation and maintenance.

Need for high-quality studies in health technology assessments: the case of a systematic review of treatment for retinoblastoma.

OBJECTIVES: The aim of this study was to conduct a systematic review of the evidence for treatments for retinoblastoma in children. METHODS: Seventeen electronic databases were searched. Two reviewers independently selected studies. Studies of participants diagnosed with childhood retinoblastoma, any interventions, and all clinical outcomes were eligible. Randomized and nonrandomized controlled trials and cohort studies with clear comparisons between treatment groups were included. Methodological quality was assessed. RESULTS: Thirty-one observational comparative studies were included, of which twenty-seven were retrospective. The methodological quality was generally poor, with a high risk of selection bias in all studies. Although there were high levels of treatment success in many of the studies, due to the limitations of the evidence identified, it was not possible to make meaningful and robust conclusions about the relative effectiveness of different treatment approaches for retinoblastoma in children. CONCLUSIONS: Good quality randomized controlled trials are required. Where controlled trials are not feasible, only high quality prospective, nonrandomized studies should be given consideration, due to the generally higher risk of bias in retrospective studies.

Group education for patients with rheumatoid arthritis and their partners.

OBJECTIVE: To determine the effects of group education followed by booster sessions for people with rheumatoid arthritis (RA), and to determine whether participation of a significant other influenced the effects. METHODS: A total of 218 RA patients, each of them with a partner, took part in the study. Two-thirds of the patients received a 5-week group self-management education program, with booster sessions after 3, 6, and 9 months; half of them received the intervention with a partner, and half without. One-third of the patients received the same educational materials without group sessions. Data were collected 1 week before the group sessions began and 2, 6, and 12 months later. The assessments included health behavior, arthritis self-efficacy, health status, and social interactions. RESULTS: After 12 months, self-efficacy scores for coping with other symptoms were significantly higher for patients participating in the group education without a partner and significantly lower for patients participating in the group education with a partner. Fatigue increased in patients participating in the group education with a significant other and decreased in patients participating in the group education without a significant other. No other effects were found on health status, health behavior, or social interactions. CONCLUSION: Our findings suggest that participation of a significant other in psychoeducational programs does not have only positive effects. Instead of stimulating patients to adopt beneficial health behaviors and increase their self-efficacy expectations, participation of a significant other led in our program to decreases in self-efficacy and increased fatigue, whereas patients participating in group education without partners showed increases in self-efficacy and decreased fatigue. Booster sessions did not seem to influence results.