Telemedicine trends at a comprehensive cancer center during the first wave of the COVID-19 pandemic.

INTRODUCTION: This article reports on the effects of an early outbreak during the COVID-19 pandemic on visit volume and telehealth use by various specialists at a comprehensive cancer center. MATERIALS AND METHODS: The number of on-site and telehealth visits (THV) for medical and surgical specialties were obtained from scheduling software. RESULTS: Total visits were most drastically limited in April 2020 to a low point of 3139; THV made up 28% of all visits. For head and neck surgery, THV made up 54% and 30% of visits in April and May, respectively. Other specialties, such as psychiatry and palliative care, had higher levels of THV. For most specialties, the rebound in June through September did not make up for visits lost during the outbreak, and fiscal year  (FY) 2020 had a 9% loss from FY 2019 with 5786 fewer total annual visits across all specialties. CONCLUSIONS: While telemedicine was a helpful part of this cancer center's response to the initial COVID-19 surge, it was not able to replace the in-person services offered at the same center. The main strategy of physicians at this cancer center was to defer care, with telemedicine being an auxiliary response.

Targeting the unfolded protein response in head and neck and oral cavity cancers.

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.

AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.

Risk stratification based on thyroid cytology: can we rely on national data?

PURPOSE: Determine correlation of malignancy rates between fine needle aspiration (FNA) biopsy and surgical specimen in an urban academic environment. METHODS: Retrospective review at an academic medical center of fine needle aspiration biopsies and surgical specimens in a head and neck otolaryngology practice between 2000 and 2012. RESULTS: Of the 74 biopsies diagnosed as follicular lesion, 34 (45.9%) were malignant. Of the 45 biopsies diagnosed as follicular neoplasm, 22 (48.9%) were malignant. These results are significantly higher than the average risk of malignancy cited by the American Thyroid Association of 5%-10% and 20%-30% for follicular lesions and neoplasms respectively. CONCLUSIONS: The rate of malignancy based on a FNA diagnosis of indeterminate cytology (follicular lesion or follicular neoplasm) can vary greatly among different institutions. Thyroid surgeons should be aware of their local pathology practices to better guide therapy and counsel patients.

Using telemedicine to facilitate social distancing in otolaryngology: A systematic review.

OBJECTIVES: As the coronavirus 2019 pandemic puts strains on current models of otolaryngology practice, telemedicine is an attractive way for otolaryngologists to reduce in-person appointments while still addressing the health of their patients. This systematic review of the literature aims to identify the evidence basis for using telemedicine in otolaryngology practice to limit person-to-person interactions while achieving comparable quality to in-person services. METHODS: The authors gathered articles from three databases (Embase, PubMed and Web of Science), performed a comprehensive literature review of articles published on telemedicine since 2002, and selected articles for inclusion based on their relevance to otolaryngology and the potential of the intervention to improve patient social distancing. RESULTS: A total of 7153 articles were identified from the initial query. After review, 35 met the inclusion criteria. Of the included articles, 32 (91%), found their specific telemedicine intervention to be effective when compared to in-person services. Twenty articles (57%) were related to remote otoscopy. Other telemedical interventions included videoconferencing for peri-operative visits, diagnosis of peritonsillar abscess, telephone-based voice evaluations and evaluation of nasal fractures. CONCLUSIONS: Video-otoscopy is the most well-supported telemedical intervention which limits physical contact between otolaryngologists and their patients. Other interventions have also demonstrated efficacy but have yet to be as widely validated as video-otoscopy. Telehealth facilitators play a key role in providing high-quality telehealth services. More invasive procedures, such as laryngoscopy, require further evidence to demonstrate definite benefits in a telemedicine setting.

Long term trends at a comprehensive cancer center during the COVID-19 pandemic.

BACKGROUND: As the ongoing public health crisis from Coronavirus Disease 2019 (COVID-19) pandemic puts strains on current models of cancer care, many health care centers had to adapt to minimize the risk of exposure and infection. The effects of the COVID-19 pandemic in a comprehensive cancer center were determined. AIMS: To measure the impact of the COVID-19 pandemic on care delivery at a comprehensive cancer center. METHODS: The number of on-site and telehealth visits (TH) were obtained from scheduling software. Multiple factors including total visits, telehealth visits, screenings for cancer diagnosis, and cancer treatments were tracked from 2 years before the pandemic onset through 2022. The length of stay (LOS) and Case Mix Index (CMI) were calculated using hospital database. RESULTS: In the third quarter of FY 2020, telehealth visits (TH) represented a fifth of total patient encounters. Cancer treatments, such as chemotherapy, radiation therapy, and surgery, decreased during the pandemic with number of surgeries being most affected (23% decrease in 2020 compared to the previous fiscal year). The average length of stay (LOS) was also longer with less discharges per given time during the pandemic. The increased LOS was related to increased severity of patient illnesses since CMI was higher. Screening mammograms decreased to a nadir of 58% in 2021 as compared to those screened in pre-pandemic fiscal years. CONCLUSION: The COVID-19 pandemic impacted many aspects of care, such as treatment and screenings. Many of these factors had to be postponed due to the fear of acquiring COVID-19 and access to care. The findings presented implicate that the delays and changes in cancer care during the pandemic resulted in less screening and treatment of more advanced disease.

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

PURPOSE: The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model. MATERIALS AND METHODS: A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined. RESULTS: Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone. CONCLUSION: Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer.

Craniocervical necrotizing fasciitis with and without thoracic extension: management strategies and outcome.

OBJECTIVE: First objective was to review cases of craniocervical necrotizing fasciitis (CCNF) at Wayne State University/Detroit Medical Center (Detroit, MI) for the last 18 years. Second was to analyze patients with and without thoracic extension for contributing factors. METHODS: Retrospective review of 660 patients with necrotizing fasciitis treated at WSU/DMC from January 1989 to January 2007 was conducted. Data regarding source/extent of infection, presenting signs/symptoms, computed tomography, microbiology, antibiotics, comorbidities, number/type of operations, hyperbaric oxygen (HBO) therapy, hospital duration, complications, and overall outcome were compared/analyzed between patients with and without thoracic extension. RESULTS: Twenty patients with CCNF for the past 18 years met the inclusion criteria. Ten patients had thoracic extension, and 10 patients did not have. Individuals in the thoracic extension group were likely to be older, had increased comorbidity, required more surgical debridement, experienced increased postoperative complications, and had lower overall survival. Three patients with thoracic extension underwent HBO therapy and 66% survived. CONCLUSION: This is the largest single institutional review of CCNF comparing patients with and without thoracic extension. Patients with thoracic extension have a poorer outcome as follows: 60% (6/10) survival vs 100% (10/10) for those without thoracic extension (P < .05). The CCNF patients without thoracic extension treated at our institution all survived after prompt medical and surgical intervention. Overall survival of CCNF patients without thoracic extension may be attributed to rigorous wound care, broad spectrum intravenous antibiotics, aggressive surgical debridement, and vigilant care in surgical intensive care unit. The HBO therapy should be included if the patient can tolerate it.

Breast cancer expressing the activated HER2/neu is sensitive to gefitinib in vitro and in vivo and acquires resistance through a novel point mutation in the HER2/neu.

The HER2/neu oncogene is an important diagnostic and prognostic factor and therapeutic target in breast and other cancers. We developed and characterized a breast cancer cell line (Bam1a) that overexpresses the activated HER2/neu and ErbB-3 and has a gene expression profile consistent with the ErbB-2 genetic signature. We evaluated the effects of the epidermal growth factor receptor (EGFR)/HER2 inhibitor, gefitinib, on this breast tumor line in vitro and in vivo. We characterized the effects of gefitinib on EGFR, HER2, and ErbB-3 phosphorylation by Western blot and determined the effects on downstream signaling through growth, survival, and stress pathways and the effect on proliferation, cell cycle, and apoptosis. Gefitinib treatment diminished phosphorylation of the ErbB-3 > EGFR > HER2/neu and signal transducers and activators of transcriptions in a dose-dependent fashion. Downstream mitogenic signaling through mitogen-activated protein (MAP)/extracellular signal regulated kinase kinase, p44/42 MAP kinase (MAPK) and stress signaling through c-Jun-NH(2)-kinase (JNK) 1 and c-Jun was impaired (1 micromol/L, 4-24 h), leading to cytostasis and cell cycle arrest within 24 h by decreased cyclin D1, cyclin B1, and p(Ser795)Rb and increased p27. Proliferation and colony formation were inhibited at 0.5 and 1 micromol/L, respectively, and correlated with altered gene expression profiles. Diminished survival signaling through Akt, induction of bim, loss of connexin43, and decreased production of vascular endothelial growth factor-D preceded caspase-3 and poly(ADP)ribose polymerase (PARP) cleavage and apoptosis (>50% 2 micromol/L, 48 h). Oral administration of gefitinib was able to prevent the outgrowth of Bam1a tumor cells from palpable lesions, shrink established tumors, eliminate HER2 and HER3 phosphorylation, and decrease MAPK and Akt signaling in vivo. A variant of the Bam1a cell line, IR-5, with acquired ability to grow in 5 micromol/L gefitinib was developed and characterized. IR-5 bears a novel point mutation in the HER2/neu that corresponds to a L726I in the ATP-binding pocket and correlates with a log decrease in sensitivity to gefitinib, increased heterodimerization with EGFR and HER3, and impaired down-regulation. Gene expression profiling of IR-5 showed increased expression of EMP-1, NOTCH-1, FLT-1, PDGFB, and several other genes that may contribute to the resistant phenotype and sustain signaling through MAPK and Akt. This model will be useful in understanding the differences between intrinsic drug sensitivity and acquired resistance in the context of therapeutic strategies that target oncogene addicted diseases.

Disulfiram (Antabuse) Activates ROS-Dependent ER Stress and Apoptosis in Oral Cavity Squamous Cell Carcinoma.

A paucity of advances in the development of novel therapeutic agents for squamous cell carcinomas of the head and neck, oral cavity (OSCC) and oropharynx, has stagnated disease free survival rates over the past two decades. Although immunotherapies targeted against checkpoint inhibitors such as PD-1 or CTLA-4 are just now entering the clinic for late stage disease with regularity the median improvement in overall survival is only about three months. There is an urgent unmet clinical need to identify new therapies that can be used alone or in combination with current approaches to increase survival by more than a few months. Activation of the apoptotic arm of the unfolded response (UPR) with small molecules and natural products has recently been demonstrated to be a productive approach in pre-clinical models of OSCC and several other cancers. The aim of current study was to perform a high throughput screen (HTS) with a diverse chemical library to identify compounds that could induce CHOP, a component of the apoptotic arm of the UPR. Disulfiram (DSF, also known as Antabuse) the well-known aversion therapy used to treat chronic alcoholism emerged as a hit that could generate reactive oxygen species, activate the UPR and apoptosis and reduce proliferation in OSCC cell cultures and xenografts. A panel of murine embryonic fibroblasts null for key UPR intermediates (e.g., Chop and Atf4) was resistant to DSF suggesting that an intact UPR is a key element of the mechanism regulating the antiproliferative effects of DSF.

Gefitinib prevents cancer progression in mice expressing the activated rat HER2/neu.

We tested the efficacy of gefitinib in the prevention of HER2/neu-mediated breast cancer development in BALB-NeuT transgenic mice. Oral administration of gefitinib to female transgenic mice from 5 to 14 weeks of age reduced tumor multiplicity from 9.6 +/- 0.82 to 0.58 +/- 1.1 (83%). We observed a decrease in the number and size of lobules and lobular nodules in treated mice with a reduction in the overall disease burden per gland. Normal duct development in the mammary glands was not affected by gefitinib. The development of acinic cell carcinoma in the parotid glands of these animals was also reduced coincident with decreased stromal involvement during progression. Gefitinib eliminated phosphorylation of HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasias and carcinomas. At the same time MAPK activity and cytokine production in splenocytes and lymph nodes was increased in gefitinib-treated animals coincident with an increase in lymph node size. Delaying gefitinib treatment until mammary glands exhibited atypical lobular hyperplasias reduced efficacy. These studies demonstrate the critical role of HER2 signal transduction in the onset and progression of HER2/neu-dependent breast cancer and suggest a role for specific inhibitors to prevent the outgrowth of early hyperplastic disease.

Dissecting the Akt/mammalian target of rapamycin signaling network: emerging results from the head and neck cancer tissue array initiative.

PURPOSE: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. EXPERIMENTAL DESIGN: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. RESULTS: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. CONCLUSIONS: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.

Autoantibody approach for serum-based detection of head and neck cancer.

Currently, no effective tool exists for screening or early diagnosis of head and neck squamous cell carcinoma (HNSCC). Here, we describe an approach for cancer detection based on analysis of patterns of serum immunoreactivity against a panel of biomarkers selected using microarray-based serologic profiling and specialized bioinformatics. We biopanned phage display libraries derived from three different HNSCC tissues to generate 5,133 selectively cloned tumor antigens. Based on their differential immunoreactivity on protein microarrays against serum immunoglobulins from 39 cancer and 41 control patients, we reduced the number of clones to 1,021. The performance of a neural network model (Multilayer Perceptron) for cancer classification on a data set of 80 HNSCC and 78 control samples was assessed using 10-fold cross-validation repeated 100 times. A panel of 130 clones was found to be adequate for building a classifier with sufficient sensitivity and specificity. Using these 130 markers on a completely new and independent set of 80 samples, an accuracy of 84.9% with sensitivity of 79.8% and specificity of 90.1% was achieved. Similar performance was achieved by reshuffling of the data set and by using other classification models. The performance of this classification approach represents a significant improvement over current diagnostic accuracy (sensitivity of 37% to 46% and specificity of 24%) in the primary care setting. The results shown here are promising and show the potential use of this approach toward eventual development of diagnostic assay with sufficient sensitivity and specificity suitable for detection of early-stage HNSCC in high-risk populations.

Transoral carbon dioxide laser supraglottic laryngectomy and irradiation in stage I, II, and III squamous cell carcinoma of the supraglottic larynx: report of Southwest Oncology Group Phase 2 Trial S9709.

OBJECTIVE: To evaluate feasibility, functional outcome, and disease control of endoscopic surgery and irradiation in patients with squamous cell carcinoma of the supraglottic larynx. DESIGN: Prospective, single-arm, phase 2 multi-institutional trial. SETTING: Southwest Oncology Group trial S9709. PATIENTS: Thirty-four patients diagnosed as having stage I, stage II, or selected stage III (T1-2N1M0) supraglottic laryngeal carcinoma enrolled from September 15, 1997, to December 1, 2001. INTERVENTIONS: Transoral supraglottic laryngectomy by carbon dioxide laser followed by planned postoperative radiotherapy. MAIN OUTCOME MEASURES: Three-year progression-free survival, proportion of patients requiring tracheostomy as a result of surgery, and time to adequate oral intake. RESULTS: All 34 patients underwent surgery without major protocol deviation. Thirty-two patients (94%) completed planned postoperative radiotherapy without major deviation. At the time of analysis, only 1 patient (3%) had documented local disease recurrence at the primary disease site and required salvage total laryngectomy, and 2 patients (6%) had documented regional recurrence and required salvage neck dissection. Estimated 3-year progression-free survival and overall survival were 79% and 88%, respectively. No subjects required tracheostomy as a direct consequence of endoscopic resection. Patients who required tracheostomy before endoscopic resection due to either obstructive tumor bulk or unfavorable anatomy that precluded safe intubation (4 patients [12%]) were all decannulated in the early postoperative period (

Head and Neck Cancer.

Despite a considerable expansion in our therapeutic repertoire for management of other malignancies, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Upon normalizing National Institutes of Health-awarded R01 and R01-equivalent grants by incidence, thyroid cancer ($214) and HNC ($1329) received the fewest funding dollars. Upon adjusting funding totals by mortality, HNC was 7th out of 9 cancers evaluated ($6138). These findings highlight HNC as an underfunded disease versus other cancers. As data detailing grant applications (including unsuccessful grants) are not publicly available, it is not clear if these disparities stem from fewer applications or fewer opportunities. Our hope is that this commentary will spur further investigation into strategies to increase HNC inquiry and funding for trainees as well as early-stage and established investigators.

Recent trends in oropharyngeal cancer funding and public interest.

OBJECTIVES/HYPOTHESIS: The incidence of oropharyngeal cancer (OPC) has increased in the United States. This has been driven by an increase in human papillomavirus (HPV)-positive OPC. Our objective is to determine trends in National Institutes (NIH)-supported research funding and public interest in OPC. METHODS: The NIH Research Portfolio Online Reporting Tools database was evaluated for projects related to OPC between 2004 and 2015. Projects were evaluated for total funding, relation to HPV, principal investigator departmental affiliation and degree, and NIH agency or center responsible for grant. The Google Trends database was evaluated for relative Internet search popularity of oropharyngeal cancer and related search terms between 2004 and 2015. RESULTS: In terms of NIH funding, 100 OPC-related projects representing 242 grant years and $108.5 million were funded between 2004 and 2015. Total NIH funding for OPC projects increased from $167,406 in 2004 to $16.2 million in 2015. Funding for HPV-related OPC increased from less than $2 million yearly between 2004 and 2010 up to $12.7 million in 2015. Principal investigators related to radiation oncology ($41.8 million) and with doctor of medicine degrees ($52.8 million) received the largest share of total funding. Relative Internet search popularity for oropharyngeal cancer has increased from 2004 to 2015 compared to control cancer search terms. CONCLUSION: Increased public interest and NIH funding has paralleled the rising incidence of OPC. NIH funding has been driven by projects related to the role of HPV in OPC. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:1345-1350, 2017.

Tumor Differentiation as a Prognostic Factor for Major Salivary Gland Malignancies.

Objective The effect of tumor differentiation on prognosis of major salivary gland malignancies is controversial. The aim of this study was to determine the effect of tumor differentiation on prognosis by stage in patients with major salivary gland malignancies and to analyze which patient factors are associated with tumor differentiation. Study Design and Setting Cross-sectional analysis of Surveillance, Epidemiology, and End Results (SEER) database. Subjects and Methods In total, 9810 patients who had a major salivary gland malignancy from 2004 to 2012 were identified using the SEER database. Patients with no staging information or no information on histologic differentiation were excluded. A total of 5366 patients were included in the study. For analysis, patients were categorized by American Joint Committee on Cancer (AJCC) stage and subdivided by tumor differentiation. Multivariate analysis was used to analyze the impact of tumor differentiation on survival, tumor location (parotid, submandibular, sublingual), and sex within each AJCC stage of disease. Results Data analysis demonstrated a significant difference in histologic differentiation by stage, with P < .0001. Within stages II, III, and IV, tumor differentiation was significantly associated with a decrease in survival. There was no significant difference in tumor differentiation between the parotid and submandibular gland. Conclusion For patients with stage II, III, and IV disease, tumor differentiation was an independent predictor of survival. This information can be useful when discussing prognosis and can potentially influence management of disease.

Organ preservation for advanced resectable cancer of the base of tongue and hypopharynx: a Southwest Oncology Group Trial.

PURPOSE: The Southwest Oncology Group designed a phase II trial for patients with base of tongue or hypopharyngeal cancer to evaluate the complete histologic response rate at the primary site after induction chemotherapy followed by chemoradiotherapy for responders. Secondary end points were the rate of organ preservation and the need for salvage surgery. PATIENTS AND METHODS: Fifty-nine eligible patients were enrolled; 37 had base of tongue cancer, and 22 had hypopharynx cancer. Forty-two percent had stage III disease, and 58% had stage IV disease. Induction chemotherapy was two cycles of cisplatin 100 mg/m(2) and fluorouracil 1,000 mg/m(2)/d for 5 days. Patients who had a greater than 50% response at the primary site were treated with radiation 72Gy and concurrent cisplatin 100 mg/m(2) for three cycles. Patients with less than partial response at the primary had immediate salvage surgery. RESULTS: Forty-five patients (76%) had a greater than 50% response at the primary after induction chemotherapy; 43 went on to receive definitive chemoradiotherapy. Thirty-two patients (54%) achieved a histologic complete response at the primary site, and an additional nine patients had a complete clinical response, but biopsy was not done. Seventy-five percent of patients did not require surgery at the primary tumor site. The 3-year overall survival was 64%. The 3-year progression-free survival with organ preservation was 52%. CONCLUSION: Patients with base of tongue or hypopharyngeal cancer treated with this regimen of induction chemotherapy followed by definitive chemoradiotherapy have a good rate of organ preservation without compromise of survival.

Visual risks of facial fracture repair in the setting of traumatic optic neuropathy.

OBJECTIVE: To identify whether facial fracture repair in patients with traumatic optic neuropathy results in visual deterioration. DESIGN: A retrospective analysis was performed of all patients admitted from 1992 through 1997 with the diagnosis of facial fracture and traumatic optic neuropathy. Vision was recorded before and after fracture repair using logarithm of the minimum angle of resolution measurements. Visual outcome was compared with a nonsurgically treated group of patients with a similar diagnosis. SETTING: University trauma hospital. PATIENTS: A total of 700 medical charts were reviewed, and 54 patients met study criteria. All patients received megadose corticosteroid treatment and were divided into 3 groups: (1) facial fracture repair alone, (2) optic nerve decompression (OND) + facial fracture repair, or (3) nonsurgical treatment. RESULTS: For the 16 patients in the fracture repair alone group, 12 (75%) had improved vision and 4 (25%) had no change postoperatively. For the 10 patients in the OND + fracture repair group, 3 (30%) had improved vision, 5 (50%) had no change, and 2 (20%) had worsened vision postoperatively. For the 28 patients in the nonsurgical group, 18 (64%) had improved vision, 9 (32%) had no change, and 1 (4%) had worsened vision by discharge. Facial fracture repair alone and the nonsurgical groups both demonstrated significant visual improvement by discharge. The amount of improvement was not significantly different between all 3 groups (facial fracture repair, 0.38 +/- 0.40; OND + facial fracture repair; 0.32 +/- 1.38; and nonsurgical, 0.69 +/- 1.07). CONCLUSIONS: Facial fracture repair in the setting of traumatic optic neuropathy had no adverse effect on vision. Patients requiring OND + fracture repair had a significantly worse visual prognosis.

Proteome-wide analysis of head and neck squamous cell carcinomas using laser-capture microdissection and tandem mass spectrometry.

Remarkable progress has been made to identify genes expressed in squamous cell carcinomas of the head and neck (HNSCC). However, limited information is available on their corresponding protein products, whose expression, post-translational modifications, and activity are ultimately responsible for the malignant behavior of this tumor type. We have combined laser-capture microdissection (LCM) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins expressed in histologically normal squamous epithelium and matching SCC. The protein fraction from approximately 10,000-15,000 normal and tumor cells was solubilized, digested with trypsin, and the resulting peptides were analyzed by LC-MS/MS. Database searching of the resulting sequence information identified 30-55 proteins per sample. Keratins were the most abundant proteins in both normal and tumor tissues. Among the proteins differentially expressed, keratin 13 was much lower in tumors, whereas heat-shock (Hsp) family members were highly expressed in neoplastic cells. Wnt-6 and Wnt-14 were identified in both normal and tumor tissues, respectively, and placental growth factor (PIGF) was detected only in tumors. Immunohistochemical analysis of HNSCC tissues revealed lack of keratin 13 in tumor tissues, and strong staining in normal epithelia, and high expression of Hsp90 in tumors. Our study, by combining LCM and proteomic technologies, underscores the advantages of this approach to investigate complex changes at the protein level in HNSCC, thus complementing existing and emerging genomic technologies. These efforts may likely result in the identification of new biomarkers for HNSCC that can be used to diagnose disease, predict susceptibility, and monitor progression in individual patients.