Johnson, C.D., Berry, D.P., Harris, S., Pickering, R.M., Davis, C., George, S., . . . Sutton, R. (2009). An open randomized comparison of clinical effectiveness of protocol-driven opioid analgesia, celiac plexus block or thoracoscopic splanchnicectomy for pain management in patients with pancreatic and other abdominal malignancies. Pancreatology: Official Journal of the International Association of Pancreatology 9(6), 755–763.

To assess the effectiveness, after two months, of celiac plexus block (CPB) versus thoracoscopic splanchnicectomy (TS) in patients receiving appropriate medical management (MM) for the pain of pancreatic and other abdominal malignancies

Patients were randomized to one of three treatment groups (MM, MM+CPB, or MM+TS) in blocks of three, stratified by treatment center, tumor type, and current opioid status (opioid naive, not taking strong opioids or started strong opioids within three days before recruitment, or taking strong opioids for more than three days prior to recruitment). Clinical assessments and data collection occurred at randomization, at weeks 2 and 4, and then monthly. Local researchers were not blinded to procedure. Patients completed a daily diary for two months and completed questionnaires at follow-up visits. Oral modified-release morphine was prescribed according to standard practice in each setting and increased 30%–50% as needed for pain control. Rescue medication for breakthrough pain was immediate-release oral morphine. Adjuvant analgesic agents—including amitriptyline, valproate, or gabapentin—were also used as needed for neuropathic pain. NSAIDs or dexamethasone was used for liver capsule pain. Opioid switching occurred as needed to avoid side effects or because of a patient's inability to take oral medications. Opioid rotation was not used. Patients maintained a daily diary of pain assessment.

• Of the 65 patients recruited, 47 completed the study. Authors analyzed data based on intention to treat. In the MM group were 24 patients; in the MM+CPB, 20 patients; in the MM+TS, 21 patients.
• Mean patient age in the MM group was 65.5 years; in the MM+CPB group, 60.5 years; in the MM+TS group, 60.2 years. The age range in all groups was 46–81 years.
• Of all patients, 50.8% were female and 49.2% were male.
• Patients had a confirmed unresectable malignancy of the pancreas or upper abdominal viscera and required opioid analgesia or they had pancreatic or gastric cancer before they had pain. Of the 65 patients recruited, 57 had pancreatic cancer, three had gallbladder cancer, one had bile duct cancer, one had duodenal cancer, and three had unknown malignancies.
• Patients were excluded from the study if they had had previous thoracic surgery or a history of tuberculosis or another intrathoracic inflammatory condition likely to cause extensive adhesions, if they were unfit for general anesthesia, or if they had a life expectancy of less than one month.

• Multisite
• Outpatient
• United Kingdom

Open randomized comparison

• Reduced version of the short form Brief Pain Inventory (BPI)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Core Module
• Adverse-event assessment by clinicians
• Opioid consumption
• Four-point Likert scale for pain assessment (assessments recorded in daily diary)

Pain relief was achieved in one third of patients at two weeks and in just under half of all patients at two months. Researchers observed no differences between groups in pain scores or total opioid consumption at any time point. Two months after randomization, 73% of subjects were taking opioids. Four serious adverse events occurred in three patients: One patient in the MM group was hospitalized for confusion eventually thought to be unrelated to the study medication, one patient was hospitalized for wound infection after TS, and one patient in the TS group had intraoperative bleeding that was resolved with sutures. Of all participants, 53% took opioids regularly during the study and 11.8% took adjuvant analgesics. Worst pain and average pain declined somewhat in all groups.

Authors reported no significant intergroup differences in pain scores or opioid consumption and no correlation between continued use of opioids and effective pain relief. The absence of any benefit from interventions led researchers to question the value of the interventions.

• The study had a small sample size, with fewer than 100 participants.
• Due to slow recruitment and poor pain responses, researchers elected to discontinue the study. Even in the MM group, one fourth of patients had stopped taking opioids at the two-month interval but reported no significant difference in pain control.
• This study did not assess the psychological and social effects of pain. This may have had an impact on pain reporting.
• Authors expressed concern about the possibility of the open design of the study influencing patients' perceptions of pain and patients' expectations regarding the treatment arm to which they were randomized.
• Authors did not report actual statistical results.
• The study was underpowered to detect differences.
• Authors did not report actual opioid doses or data regarding use of rescue medications.

The study presents insufficient evidence to support the efficacy of one treatment over the others.