BackgroundThere is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.MethodsTwenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.ResultsFunctional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.ConclusionsThe novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.
SterEOS 3D reconstruction spine software creates reproducible measurements in all 3 planes of deformity in curves greater than 50°. Advancements in 3D scoliosis imaging are expected to improve our understanding and treatment of idiopathic scoliosis.
A high degree of coronal correction can be achieved in association with vertebral derotation without sacrificing sagittal plane alignment. High-strength rods aggressively bent to create kyphosis allow both restoration of kyphosis and axial plane derotation in thoracic idiopathic scoliosis.
Pseudomyxoma peritonei (PMP) is primarily the result of a ruptured mucinous appendix neoplasm (MAN). Often MAN is lumped with but biologically distinct from intestinal appendiceal adenocarcinoma. Nodal and systemic dissemination are rare with the peritoneal cavity being the primary site of recurrence. Routine performance of right hemicolectomy (RHC) for PMP/MAN has been extensively debated without consensus. Our objective was to ascertain whether RHC has a survival advantage over appendectomy. We hypothesize if RHC is mandatory, then increased tumor recurrence and mortality should be observed in appendectomy only. Retrospective chart review was carried out in patients with tumors that met the Ronnett classification for PMP/MAN. Demographics, tumor grade, extent, recurrence, and progression were recorded. We report the rate of nodal involvement/recurrence in patients treated with RHC versus appendectomy as well as the rate of systemic and peritoneal recurrence and survival. Multivariate logistic regression was done to identify factors that impact survival. Of 120 patients, 48 had appendectomy and 72 had RHC. Seven per cent of patients undergoing RHC had positive lymph nodes and no nodal failures (0%) in patients undergoing appendectomy. Appendectomy versus RHC recurrence rates (21 vs. 28%, P = 0.12) and death resulting from disease (8 vs. 22%, P = 0.27) were similar. Logistic regression revealed that the type of surgery had no impact on recurrence and mortality, only optimal resection score and performance status. There was no difference in tumor recurrence or survival based on treatment by appendectomy or RHC. Performance status and complete cytoreduction are the only factors associated with survival. Lymph node involvement is rare and selective RHC is safe in PMP/MAN.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.