Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. STUDY DESIGN: A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). RESULTS: Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). CONCLUSIONS: These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

Are Outcomes of Temporomandibular Joint Arthroscopy Influenced by Central Sensitization?

PURPOSE: A proportion of subjects with internal derangements of the temporomandibular joint (TMJ) may have a central sensitization disorder that may affect pain perception after surgery. This study aims to estimate the association between fibromyalgianess (FMness) score, a summed score of the Widespread Pain Index (WPI) and Symptom Severity Sore (SSS), and outcomes following TMJ arthroscopy. METHODS: A retrospective cohort study including individuals who received arthroscopy for TMJ internal derangement at Michigan Medicine between 2011 and 2020 was performed. A predictor variable, FMness score, was assigned via the sum of WPI and SSS. Univariate and bivariate analyses were performed. Linear-mixed effects models were used to analyze 6 different outcomes, each in their own model: pain, jaw functional limitation scale (JFLS), JFLS-mobility domain, pain-related disability, comfortable maximum interincisal opening, and active maximum interincisal opening. Covariance structure was selected based on null model fit separately for each outcome. RESULTS: Thirty-one subjects were included in the study sample. Twenty-eight subjects were female. Average age was 45.9 years. Bivariate analysis demonstrated that subject's FMness score was not correlated with pain (b = 0.03 [-0.10, 0.17] P = .59) or JFLS score (b = 1.00 [-.80, 2.81] P = .27). However, subject's FMness score was significant for predicting JFLS-mobility domain score (b = .61, [0.05, 1.18] P = .04). CONCLUSION: A greater extent of central sensitization was associated with lower comfortable mouth opening after surgery, greater limitations in opening wide enough to eat various foods (higher JFLS-mobility scores), and higher pain-related disability. Future studies with larger sample sizes and reconstructive TMJ operations such as total TMJ arthroplasty may help clarify the impact of SSS and WPI scores on outcomes of TMJ surgery.

An International Survey on Temporomandibular Joint Surgeon's Implementation and Management of Discectomy in Treating Temporomandibular Joint Internal Derangement.

PURPOSE: To survey temporomandibular joint (TMJ) surgeons to determine current practice trends and perceptions regarding the role of discectomy for the treatment of TMJ internal derangements. METHODS: An anonymous 5-part web-based survey was sent to TMJ surgeons. The survey was created and distributed, and the data were collected with the University of Michigan Qualtrics platform. Responses were compared based on operative volume, tendency to replace the disc, and likelihood of requiring temporomandibular joint replacement (TJR) after discectomy. Spearman correlations were used to test statistically significant differences. Domain-level analyses were also performed by summarizing items into 3 domain scores. Analyses were performed in SAS V9.4 (SAS Institute Inc., Cary, NC, USA). RESULTS: Fifty-nine surgeons (33.9%) completed the survey. Discectomy was not considered to be a useful procedure by 85% of respondents, and 74% would not consider discectomy as a first surgical option. Most would consider discectomy (64%) before alloplastic total joint replacement. Discectomy was preferred over discopexy for the management of anterior disc displacement with reduction by high volume surgeons (89%), but most (72%) did not feel that discectomy was beneficial over arthroscopy in the treatment of anterior disc displacement without reduction and concomitant degenerative bony changes. In managing symptomatic disc perforation, 66% agreed that discectomy is the procedure of choice and 49% felt that interpositional tissue is indicated in most cases after discectomy. Respondents who reported fewer re-operations requiring alloplastic TJR after discectomy had, on average, more positive perceptions of discectomy on the benefits domain (P = .03), better than alternatives domain (P = .03), and fewer concerns on the perceived adverse effects domain (P = .03). CONCLUSIONS: TMJ surgeons do not employ TMJ discectomy in most cases of TMJ internal derangement. However, discectomy is considered useful in cases of disc perforation or for persistent symptomatic disc displacement without reduction, in an attempt to avoid alloplastic TJR. Common adverse effects included joint noises and osteoarthrosis, and the use of interpositional disc replacement tissue did not alter the incidence of adverse effects or complications reported.