Citations

BACKGROUND Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma occurring mainly in the anogenital region. Traditional management with wide local excision has shown high recurrence rates, thus Mohs micrographic surgery (MMS) has emerged as a promising treatment option. OBJECTIVE To compare long-term outcomes after treatment with MMS or excision for primary EMPD. METHODS AND MATERIALS Retrospective cohort review was conducted for 207 patients with EMPD treated at Mayo Clinic in Rochester, MN, between 1961 and 2012. RESULTS Of the 25 patients treated with MMS, 19 primary tumors were included for outcome analysis, with an estimated 5-year recurrence-free survival rate of 91% (95% confidence interval [CI], 75–100) using Kaplan–Meier curve analysis. Of 158 patients treated with local excision, 124 were included for the analysis, with an estimated 5-year recurrence-free survival rate of 66% (95% CI, 56–78). The hazard ratio (HR) for association of treatment was 0.4 (95% CI, 0.10–1.65; p = .20). Estimated 5-year overall survival rates were 79% for MMS (95% CI, 61–100) and 68% for excision (95% CI, 59–78) (HR, 1.39 [95% CI, 0.69–2.82]; p = .36). CONCLUSION Although treatment of primary EMPD with MMS versus excision did not show statistical difference, MMS demonstrated favorable long-term outcomes and was associated with a higher recurrence-free survival rate.

Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of Pdgfrα function in murine models are embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function. In this study, we generated a zebrafish pdgfra mutant line by gene trapping, in which the Pdgfra protein is truncated and fused with mRFP (Pdgfra-mRFP). Our results demonstrate that pdgfra mutants have defects in cardiac morphology as a result of abnormal fusion of myocardial precursors. Expression analysis of the developing heart at later stages suggested that Pdgfra-mRFP is expressed in the endocardium. Further examination of the endocardium in pdgfra mutants revealed defective endocardial migration to the midline, where cardiac fusion eventually occurs. Together, our data suggests that pdgfra is required for proper medial migration of both endocardial and myocardial precursors, an essential step required for cardiac assembly and development.

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Abstract Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods: The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results: Twenty-one guideline statements were established. Conclusions: Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Objectives.— To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. Methods.— The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Results.— Twenty-one guideline statements were established. Conclusions.— Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Abstract Pancreatic cancer is characterized by an inflammatory environment. Here we delineate the crosstalk between different macrophage populations with pancreatic cells carrying oncogenic Kras mutations. First, we show that pancreatic acinar cells that undergo oncogenic transformation by mutant Kras upregulate chemoattractants that attract inflammatory macrophages. These inflammatory macrophages contribute to acinar cell dedifferentiation to a progenitor-like cell type (acinar-to-ductal metaplasia; ADM). Resulting cells can give rise to PanIN lesions. We then provide insight at which stage of PanIN formation a switch between inflammatory and alternatively-activated macrophages occurs; and define one mechanism by which this can be mediated. Eventually, we provide insight of how alternatively-activated macrophages facilitate the further progression of PanIN lesions to a more aggressive phenotype. Citation Format: Geou-Yarh Liou, Heike Doeppler, Ligia Bastea, Peter Storz.{Authors}. Crosstalk of different macrophage populations with pancreatic acinar or PanIN cells and contribution to development of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A59.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor with slow infiltrative growth and local recurrence if inadequately excised. OBJECTIVE To compare long-term outcomes after Mohs micrographic surgery (MMS) and wide local excision (WLE). MATERIALS AND METHODS Records of patients with DFSP surgically treated with WLE or MMS from January 1955 through March 2012 were retrospectively reviewed. RESULTS Mean follow-up for patients treated with MMS (n = 67) and WLE (n = 91) was 4.8 and 5.7 years, respectively. Twenty-eight patients (30.8%) with WLE had recurrence (mean, 4.4 years), whereas only 2 (3.0%) with MMS had recurrence (1.0 and 2.6 years). Recurrence-free survival rates at 1, 5, 10, and 15 years were significantly higher with MMS (p < .001). Mean preoperative lesion sizes were similar (5–6 cm) between the 2 groups, whereas mean (standard deviation) postoperative defect sizes were 10.7 (4.3) cm and 8.8 (5.5) cm for WLE and MMS, respectively (p = .004). Primary closure was used for 73% of MMS cases, whereas WLE more commonly used flaps, grafts, or other closures (52%). Two Mohs layers typically were required for margin control. CONCLUSION Surgical excision with meticulous histologic evaluation of all surgical margins is needed for DFSP treatment to achieve long-term high cure rates and low morbidity.

BACKGROUND Hidradenitis suppurativa (HS) is a progressive, recurrent inflammatory disorder. OBJECTIVE To assess long-term satisfaction and postoperative perceptions among patients who underwent surgical management of HS. MATERIALS AND METHODS A questionnaire was mailed to 499 HS surgical patients to assess surgical outcome, satisfaction, and quality of life. RESULTS Of the 499 questionnaires mailed, 113 were returned (22.6% response rate) and 2 were excluded for redundancy. Of the 111 respondents, 65 (58.6%) were female, 91 (82.0%) had Hurley Stage III disease, 88 (79.3%) were treated with excision and 23 (20.7%) with unroofing, 45 (40.5%) had perianal or perineal disease, and 41 (36.9%) had axillary disease. Most patients were satisfied or very satisfied with their surgical results (84.7%; 94 of 111), were glad they underwent surgery (96.3%; 105 of 109), and would recommend surgery to a friend or relative (82.6%; 90 of 109). Most patients were satisfied or very satisfied with the appearance of their healed wound (62.4%; 68 of 109). Retrospective mean quality of life increased significantly from 5 preoperatively to 8.4 postoperatively (p < .001). CONCLUSION Hidradenitis suppurativa surgical management was well regarded by patients and should be considered by future patients to limit the morbidity of HS.