Citations

LINKED CONTENTThis article is linked to Grover et al and Elwing & Sayuk papers. To view these articles, visit https://doi.org/10.1111/apt.16591 and https://doi.org/10.1111/apt.16603

Objectives Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism. Methods Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package. Results A median of 34 somatic mutations were detected (range, 19–60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon. Conclusions Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.

Abstract Background The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. Methods In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4–5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. Results Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. Conclusions Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.