5 Safety

5 Safety

This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.

5.1 In a systematic review of innovative ablative therapies for locally advanced pancreatic cancer (LAPC) including 141 patients (from 4 studies) treated by irreversible electroporation (IRE), overall mortality rate was 3% (3/92) in 3 studies using IRE. Two of these deaths were in patients treated by an open approach and 1 was in a patient treated by a percutaneous approach. The IRE-related mortality rate was 2% (2/87) in patients treated by an open approach. Death within 90 days (median 26 days, range 8 to 42 days) after an IRE procedure was reported in 11% (6/50) of patients in a case series of 50 patients with LAPC (T4 lesions) treated by IRE for primary treatment (n=29) or margin extension (n=24). Five of these deaths were in the primary treatment group (n=29) and 1 was in the margin-extension group (n=24).

5.2 In the systematic review of 141 patients, 48% (44/92) of patients reported complications. Of these, 51% (41/81) were in patients treated by an open approach and 27% (3/11) were in patients treated by a percutaneous approach. Overall, 13% (5/38) of complications were related to an IRE procedure (open 15% [4/27]; percutaneous 9% [1/11]). Morbidity related to IRE mainly consisted of duodenal leakage (in patients with transduodenal needle placement or stent removal), pancreatic leakage, bile leakage and progression of portal vein thrombosis.

5.3 Pancreatic complications (including pancreatic leakage, pancreatitis and pancreatic failure) were reported in 4% (2/50) of patients in the IRE plus resection group (n=50) and none in the IRE alone group (n=150) at 90-day follow-up in a registry of 200 patients with stage 3 LAPC treated by IRE. Pancreatic fistula (treated with a stoma bag and antibiotics) in 1 patient and peripancreatic abscess (treated with percutaneous drainage and antibiotics) in 1 patient were reported in a case series of 21 patients with unresectable pancreatic cancer treated by IRE.

5.4 Liver complications (including ascites, biliary stricture, liver dysfunction and failure) were reported in 14% (7/50) of patients in the IRE plus resection group (n=50) and 9% (13/150) of patients in the IRE alone group (n=150) at 90-day follow-up in the registry of 200 patients. Biliary peritonitis, cholangitis and liver abscess (needing revision surgery and antibiotics) were reported in 1 patient in the case series of 21 patients. Duodenal and bile duct necrosis (needing trans-hepatic drain insertion) and haemorrhage (needing transfusion) were reported in 1 patient in the case series of 50 patients. Bile duct obstruction and biliary stent obstruction after IRE treatment were reported as the most common reasons for readmission in another case series (conference abstract) of 50 patients with LAPC treated by IRE. Bile leakage was reported in 3 patients in a case series of 48 patients with borderline resectable pancreatic cancer or LAPC treated by IRE. Liver insufficiency was reported in 4 patients in a case series of 65 patients with LAPC treated by IRE.

5.5 Severe complications including bowel perforation (abscess formation and perforation of the duodenum and transverse colon close to the stent) and bleeding from a pancreatic branch of the superior mesenteric artery (due to pseudo-aneurysm) leading to death were reported after IRE treatment in a case report of 1 patient with pancreatic cancer who had a metallic stent in the common bile duct. Duodenal leakage (from transduodenal IRE needle placement) was reported in 1 patient in 1 study included in a systematic review of 74 patients with LAPC treated by IRE. Fistula and abscess in the abdominal wall (treated with drainage and antibiotics) was reported in 1 patient in the case series of 21 patients. Delayed gastric emptying (needing total parenteral nutrition and percutaneous endoscopic gastrostomy tube insertion) in 4 patients, upper gastrointestinal bleeding (needing transfusion and medical management) in 3 patients, duodenal cutaneous fistula in 1 patient and perforated gastric ulcer (needing drain placement) in 1 patient were reported in the case series of 50 patients. Ileus was reported in 5 patients in the case series of 65 patients treated with IRE. Small bowel leakage (grade 2) was reported in 1 patient in the case series of 48 patients. Other gastrointestinal complications (including anorexia, dehydration, gastritis, heartburn, nausea, vomiting) were reported in 16% (8/50) of patients in the IRE plus resection group (n=50) and 25% (38/150) of patients in the IRE alone group (n=150) at 90‑day follow-up in the registry of 200 patients.

5.6 Vascular complications (including deep vein thrombosis, pseudo-aneurysm, hepatic arterial thrombosis, non-occlusive superior mesenteric vein/portal vein thrombosis) were reported in 8% (4/50) of patients in the IRE plus resection group (n=50) and 5% (7/150) of patients in the IRE alone group (n=150) at 90‑day follow-up in the registry of 200 patients. Intraoperative haemorrhage (needing transfusion) and angiogram embolisation of the gastroduodenal artery leading to multi-organ failure was reported in 1 patient in the case series of 50 patients. Disseminated intravascular coagulopathy (leading to death 7 days after IRE because of intracranial haemorrhage) was reported in 1 patient in a case series of 8 patients with borderline resectable PC or LAPC treated by IRE. Hepatic artery graft failure was reported in 1 patient in the case series of 48 patients. Partial splenic infarction (needing no treatment) in 1 patient was reported during percutaneous IRE ablation in a case series of 15 patients with LAPC or metastatic disease treated by IRE.

5.7 Cardiovascular complications (including atrial fibrillation) were reported in 4% (2/50) of patients in the IRE plus resection group (n=50) at 90–day follow-up in the registry of 200 patients. Arrhythmia developed in 2 patients during IRE procedures in the case series of 8 patients.

5.8 Pneumothorax (n=1) and pulmonary problems (n=3) were reported in the studies included in the systematic review of 74 patients.

5.9 Sepsis needing reoperation was reported in 1 patient in the case series (conference abstract) of 50 patients treated by IRE. The patient died postoperatively. Infection was reported in 6% (3/50) of patients in the IRE plus resection group (n=50) and 9% (13/150) of patients in the IRE alone group (n=150) at 90‑day follow-up in the registry of 200 patients. Deep surgical site infection (needing drain placement) was reported in 3 patients in the case series of 50 patients treated by IRE.

5.10 In the registry of 200 patients other complications included urinary tract problems (in 7 patients), renal failure (in 1 patient), wound problems (in 6 patients), neurological changes (in 4 patients), haematological events (in 2 patients) and other adverse events (in 23 patients). The case series of 48 patients also reported complications such as hepatojejunostomy stricture (in 1 patient), pain (in 1 patient) and postoperative bleeding (in 2 patients).

5.11 In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse events: vessel occlusion (permanent or transient and due to oedema post-IRE causing compression of an involved superior mesenteric vein). They considered that the following were theoretical adverse events: damage to major arteries or veins, gastrointestinal tract injury (for example, stomach, duodenum, small or large bowel).

  • National Institute for Health and Care Excellence (NICE)