title: A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound.
abstract: BACKGROUND
  Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma.
  
  
  METHODS
  An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator forτ2, and Cochran's Q test for heterogeneity among studies. The I2was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.
  
  
  RESULTS
  The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study.τ2(variance among studies) was 0.195, and I2(percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86).
  
  
  CONCLUSIONS
  HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.
authors.affiliation: Medical Student, Sapienza University of Rome, School of Medicine, V.le Regina Elena, 324, 00180 Rome, Italy.
authors.forename: Susan
authors.initials: S
authors.lastname: Dababou
authors.affiliation: Medical Student, Sapienza University of Rome, School of Medicine, V.le Regina Elena, 324, 00180 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marrocchio
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305 USA.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305 USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Bitton
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305 USA.
authors.forename: Kim Butts
authors.initials: KB
authors.lastname: Pauly
authors.affiliation: Department of Radiological Sciences, MRgFUS & Cardiovascular Imaging Unit, Sapienza University of Rome, School of Medicine, V.le Regina Elena, 324, 00180 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Napoli
authors.affiliation: Gastroenterology Section, Harborview Medical Center, Bioengineering and Radiology, University of Washington, Box 359773, 325 Ninth Avenue, Seattle, WA 98104 USA.
authors.forename: Joo Ha
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Radiology, Lucas Center for Imaging, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305 USA.
authors.forename: Pejman
authors.initials: P
authors.lastname: Ghanouni
keywords: HIFU; High intensity focused ultrasound; Meta-analysis; Non-invasive treatment; Pain palliation; Pain relief; Pancreatic cancer