Prospective Head and Neck Cancer Research: A Four‐Decade Bibliometric Perspective

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139977/1/onco0584.pd

Tissue-preserving approach to extracting DNA from paraffin-embedded specimens using tissue microarray technology

Background. DNA extracted from tumor cells or normal cells contained in formalin-fixed, paraffin-embedded tissues is widely used in many laboratories. The 2 most common procedures to isolate cells for DNA extraction from paraffin-embedded tissues are scalpel microdissection and laser capture microdissection. A new tissue- and time-conserving method for rapid DNA isolation from small cores taken from paraffin-embedded tissue blocks is described in this report. Methods. DNA was extracted from small tissue cores collected from paraffin-embedded tissue blocks at the time of tissue microarray construction. The quality and quantity of the DNA extracted was compared to DNA collected by scalpel microdissection. DNA collected from tissue cores was used in polymerase chain reaction (PCR) and loss of heterozygosity (LOH) analysis. Results. The quality and quantity of DNA obtained using tissue cores was comparable to DNA obtained by traditional methods. The tissue core method of DNA extraction preserves the tissue blocks from which the cores are extracted for future use. Adequate quantities of DNA can be successfully extracted from small segments of tissue cores and used for PCR. DNA isolated by tissue microdissection and the tissue core method were comparable when used to assess allelic heterozygosity on chromosome arm 18q. Conclusion. The tissue core method of DNA isolation is reliable, tissue conserving, and time effective. Tissue cores for DNA extraction can be harvested at the same time as tissue microarray construction. The technique has the advantage of preserving the original tissue blocks for additional study as only tiny cores are removed. © 2007 Wiley Periodicals, Inc. Head Neck, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56021/1/20547_ftp.pd

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

Prevention of wound complications following salvage laryngectomy using free vascularized tissue

Background. Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach. Methods. We conducted a retrospective review of a prospective cohort and compared it with a historical group (surgical patients of Radiation Therapy Oncology Group (RTOG)-91-11 trial). Eligibility criteria for this study included patients undergoing salvage total laryngectomy following failed attempts at organ preservation with either high-dose radiotherapy or concurrent chemo/radiation therapy regimen. Patients were excluded if the surgical defect required a skin paddle for pharyngeal closure. The prospective cohort consisted of 14 consecutive patients (10 males, 4 females; mean age, 58 years) who underwent free tissue reinforcement of the pharyngeal suture line following total laryngectomy. The historical comparison group consisted of 27 patients in the concomitant chemoradiotherapy arm of the RTOG-91-11 trial who met the same eligibility criteria (26 males, 1 female; mean age, 57 years) but did not undergo free tissue transfer or other form of suture line reinforcement. Minimum follow-up in both groups was 12 months. Results. The overall pharyngocutaneous fistula rate was similar between groups—4/14 (29%) in the flap group, compared with 8/27 (30%) in the RTOG-91-11 group. There were no major wound complications in the flap group, compared with 4 (4/27, 14.8%) in the RTOG-91-11 group. There were no major fistulas in the flap group, compared with 3/27 (11.1%) in the RTOG-91-11 group. The rate of pharyngeal stricture requiring dilation was 6/14 (42%) in the flap group, compared with 7/27 (25.9%) in the RTOG-91-11 group. In our patients, the rate of tracheoesophageal speech was 14/14 (100%), and complete oral intake was achieved in 13/14 (93%) patients. Voice-Related Quality of Life Measure (V-RQOL) and Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) scores suggest that speech and swallowing functions are reasonable following free flap reinforcement. Conclusions. Free vascularized tissue reinforcement of primary pharyngeal closure in salvage laryngectomy following failed organ preservation is effective in preventing major wound complications but did not reduce the overall fistula rate. Fistulas that developed following this technique were relatively small, did not result in exposed major vessels, and were effectively treated with outpatient wound care rather than readmission to the hospital or return to operating room. Speech and swallowing results following this technique were comparable to those following total laryngectomy alone. © 2007 Wiley Periodicals, Inc. Head Neck 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56020/1/20492_ftp.pd

Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer

Background The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC). Methods Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray. Results The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease‐specific survival (DSS), overall survival (OS), and time to recurrence (TTR) ( p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR ( p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS ( p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome. Conclusions For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients. © 2012 Wiley Periodicals, Inc. Head Neck, 2013Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99017/1/23087_ftp.pd

Human papillomavirus–related oropharyngeal cancer: HPV and p16 status in the recurrent versus parent tumor

Background Although typically associated with a favorable prognosis, a minority of human papillomavirus (HPV)‐related (+) oropharyngeal cancers recur after chemoradiation. We postulated that a minor HPV‐negative tumor subfraction may be responsible for recurrences of HPV+ oropharyngeal cancer. Methods Paired untreated primary and recurrent tumor specimens were identified for 37 patients with oropharyngeal cancer who received definitive chemoradiotherapy at our institution. Concordance in HPV/p16 expression between primary and recurrent tumors was assessed. Results Among 31 patients with HPV+/p16+ primary tumors, 30 (97%) retained evidence of both HPV and p16 expression at recurrence (27 HPV+/p16+; 3 HPV+/p16‐partial). One (3%) initially HPV+/p16+ patient developed an HPV‐negative/p16‐negative lung squamous cell carcinoma (SCC), representing either a discordant oropharyngeal cancer metastasis or second primary tumor. Conclusion HPV‐related oropharyngeal cancers retain HPV+/p16+ expression at recurrence. Our results fail to provide evidence that a minor HPV‐negative tumor subfraction is responsible for biologically aggressive behavior of HPV+ oropharyngeal cancer that recurs after chemoradiation. © 2014 Wiley Periodicals, Inc. Head Neck 37 : 8–11, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109811/1/hed23548.pd

Optimizing the post-graduate institutional program evaluation process

Abstract Background Reviewing program educational efforts is an important component of postgraduate medical education program accreditation. The post-graduate review process has evolved over time to include centralized oversight based on accreditation standards. The institutional review process and the impact on participating faculty are topics not well described in the literature. Methods We conducted multiple Plan-Do-Study-Act (PDSA) cycles to identify and implement areas for change to improve productivity in our institutional program review committee. We also conducted one focus group and six in-person interviews with 18 committee members to explore their perspectives on the committee’s evolution. One author (MLL) reviewed the transcripts and performed the initial thematic coding with a PhD level research associate and identified and categorized themes. These themes were confirmed by all participating committee members upon review of a detailed summary. Emergent themes were triangulated with the University of Michigan Medical School’s Admissions Executive Committee (AEC). Results We present an overview of adopted new practices to the educational program evaluation process at the University of Michigan Health System that includes standardization of meetings, inclusion of resident members, development of area content experts, solicitation of committed committee members, transition from paper to electronic committee materials, and focus on continuous improvement. Faculty and resident committee members identified multiple improvement areas including the ability to provide high quality reviews of training programs, personal and professional development, and improved feedback from program trainees. Conclusions A standing committee that utilizes the expertise of a group of committed faculty members and which includes formal resident membership has significant advantages over ad hoc or other organizational structures for program evaluation committees.http://deepblue.lib.umich.edu/bitstream/2027.42/117363/1/12909_2016_Article_586.pd

Chemotherapy alone for organ preservation in advanced laryngeal cancer

Background. For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy. Methods. Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response. Results. A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively. Conclusion. Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site. © 2009 Wiley Periodicals, Inc. Head Neck, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77508/1/21285_ftp.pd

Weekly chemotherapy with radiation versus high‐dose cisplatin with radiation as organ preservation for patients with HPV‐positive and HPV‐negative locally advanced squamous cell carcinoma of the oropharynx

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Matted nodes: Poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status

Background Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis. Methods Seventy‐eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local‐regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity. Results The 3‐year disease‐specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively ( p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes. Conclusion Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de‐escalation of therapy. © 2012 Wiley Periodicals, Inc. Head Neck , 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94456/1/21997_ftp.pd