ABSTRACT
BACKGROUND: Rebound pain is a common, yet under-recognised acute increase in pain severity after a peripheral nerve block (PNB) has receded, typically manifesting within 24 h after the block was performed. This retrospective cohort study investigated the incidence and factors associated with rebound pain in patients who received a PNB for ambulatory surgery. METHODS: Ambulatory surgery patients who received a preoperative PNB between March 2017 and February 2019 were included. Rebound pain was defined as the transition from well-controlled pain (numerical rating scale [NRS] ≤3) while the block is working to severe pain (NRS ≥7) within 24 h of block performance. Patient, surgical, and anaesthetic factors were analysed for association with rebound pain by univariate, multivariable, and machine learning methods. RESULTS: Four hundred and eighty-two (49.6%) of 972 included patients experienced rebound pain as per the definition. Multivariable analysis showed that the factors independently associated with rebound pain were younger age (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.97-0.99), female gender (OR 1.52 [1.15-2.02]), surgery involving bone (OR 1.82 [1.38-2.40]), and absence of perioperative i.v. dexamethasone (OR 1.78 [1.12-2.83]). Despite a high incidence of rebound pain, there were high rates of patient satisfaction (83.2%) and return to daily activities (96.5%). CONCLUSIONS: Rebound pain occurred in half of the patients and showed independent associations with age, female gender, bone surgery, and absence of intraoperative use of i.v. dexamethasone. Until further research is available, clinicians should continue to use preventative strategies, especially for patients at higher risk of experiencing rebound pain.
Subject(s)
Ambulatory Surgical Procedures/adverse effects , Autonomic Nerve Block/methods , Pain Measurement/methods , Pain, Postoperative/prevention & control , Peripheral Nerves/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Ambulatory Surgical Procedures/trends , Autonomic Nerve Block/trends , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement/trends , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Peripheral Nerves/drug effects , Retrospective Studies , Young AdultABSTRACT
A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6 mg/kg IV q2weeks. Of 34 panitumumab-treated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders. A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities. This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Receptor, ErbB-2/genetics , Aged , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Female , Genomics/methods , Humans , Male , Panitumumab , Prospective StudiesABSTRACT
PURPOSE: To evaluate the prognostic impact of cell-of-origin (COO) subgroups, assigned using the recently described gene expression-based Lymph2Cx assay in comparison with International Prognostic Index (IPI) score and MYC/BCL2 coexpression status (dual expressers). PATIENTS AND METHODS: Reproducibility of COO assignment using the Lymph2Cx assay was tested employing repeated sampling within tumor biopsies and changes in reagent lots. The assay was then applied to pretreatment formalin-fixed paraffin-embedded tissue (FFPET) biopsies from 344 patients with de novo diffuse large B-cell lymphoma (DLBCL) uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays. RESULTS: The Lymph2Cx assay provided concordant COO calls in 96% of 49 repeatedly sampled tumor biopsies and in 100% of 83 FFPET biopsies tested across reagent lots. Critically, no frank misclassification (activated B-cell-like DLBCL to germinal center B-cell-like DLBCL or vice versa) was observed. Patients with activated B-cell-like DLBCL had significantly inferior outcomes compared with patients with germinal center B-cell-like DLBCL (log-rank P < .001 for time to progression, progression-free survival, disease-specific survival, and overall survival). In pairwise multivariable analyses, COO was associated with outcomes independent of IPI score and MYC/BCL2 immunohistochemistry. The prognostic significance of COO was particularly evident in patients with intermediate IPI scores and the non-MYC-positive/BCL2-positive subgroup (log-rank P < .001 for time to progression). CONCLUSION: Assignment of DLBCL COO by the Lymph2Cx assay using FFPET biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression.
