Pain in patients with pancreatic cancer: prevalence, mechanisms, management and future developments

Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients’ quality of life and survival

A multicenter assessment of interreader reliability of LI-RADS version 2018 for MRI and CT

Background: Various limitations have impacted research evaluating reader agreement for Liver Imaging-Reporting and Data System (LI-RADS). Purpose: To assess reader agreement of LI-RADS in an international multi-center, multireader setting using scrollable images. Materials and Methods: This retrospective study used de-identified clinical multiphase CT and MRI examinations and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 – August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS v2018 category was computed as a re-scored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1/2, LR-3, LR-4, LR-5/M/tumor in vein) was computed using intra-class correlation coefficients (ICC). Agreement was also computed for dichotomized malignancy (LR-4/LR5/LR-M/LR-tumor in vein), LR-5, and LR-M. Agreement was compared between researchversus-research reads and research-versus-clinical reads. Results: 484 patients (mean age, 62 years ±10 [SD]; 156 women; 93 CT, 391 MRI) were included. ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.62, 0.74), 0.63 (95% CI: 0.56, 0.71), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs. 0.62, P = .03) and for dichotomized malignancy (ICC, 0.63 vs. 0.53, P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion: There was moderate agreement for Liver Imaging-Reporting and Data System v2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study

Protocol modifications for CT perfusion (CTp) examinations of abdomen-pelvic tumors: Impact on radiation dose and data processing time

To evaluate the effect of CT perfusion (CTp) protocol modifications on quantitative perfusion parameters, radiation dose and data processing time. CTp datasets of 30 patients (21M:9F) with rectal (n = 24) or retroperitoneal (n = 6) tumours were studied. Standard CTp protocol included 50 sec cine-phase (0.5 sec/rotation) and delayed-phase after 70 ml contrast bolus at 5-7 ml/sec. CTp-data was sub-sampled to generate modified datasets (n = 105) with cine-phase(n = 15) alone, varying cine-phase duration (20-40 sec, n = 45) and varying temporal sampling-interval (1-3 sec, n = 45). The estimated CTp parameters (BF,BV,MTT&PS) and radiation dose of standard CTp served as reference for comparison. CTp with 50 sec cine-phase showed moderate to high correlation with standard CTp for BF&MTT (r = 0.96&0.85) and low correlation for BV (0.75, p = 0.04). Limiting cine-phase duration to 30 sec demonstrated comparable results for BF&MTT, while considerable variation in CTp values existed at 20 sec. There was moderate-to-high correlation of CTp parameters with sampling interval of 1&2 sec (r = 0.83-0.97, p > 0.05), while at 3 sec only BF showed high correlation (r = 0.96, p = 0.05). Increasing sampling interval (47-60%) and reducing cine-phase duration substantially reduced dose(30.8-65%) which paralleled reduced data processing time (3-10 min). Limiting CTp cine-phase to 30 sec results in comparable BF&MTT values and increasing cine-phase sampling interval to 2 sec provides good correlation for all CTp parameters with substantial dose reduction and improved computational efficiency