Necessity of routine ipsilateral hemithyroidectomy during laryngopharyngectomy for pyriform sinus cancer.

PURPOSE: The aim of this study was to revisit the role of hemithyroidectomy in the treatment of pyriform sinus cancer by determining the incidence of thyroid gland invasion by the tumor. MATERIALS AND METHODS: Medical records of 27 patients with pyriform sinus cancer who underwent laryngopharyngectomy with ipsilateral hemithyroidectomy from 1999 to 2010 at a National Cancer Institute-designated comprehensive cancer center were retrospectively reviewed. Computed tomographic scans of the neck, operative notes, and surgical specimens were examined to determine the presence of thyroid gland invasion by imaging, clinical appearance, and pathology. RESULTS: There were 19 male and 8 female patients (age range, 44-79 years; mean, 59.9 years). Most of the cases (85%) had advanced-stage disease. Extralaryngeal spread of tumor with thyroid cartilage invasion was noted in the computed tomographic scans of 5 patients; however, there was no radiologic evidence of thyroid gland invasion in any patient. No gross thyroid gland invasion by the tumor was appreciated in any patient during surgery. No histologic evidence of tumoral invasion of the thyroid gland was found in any of 27 surgical specimens. CONCLUSIONS: Results of this study suggest that thyroid gland invasion by pyriform sinus cancer is not common. Therefore, a routine ipsilateral hemithyroidectomy may not be necessary in the treatment of every patient with pyriform sinus cancer, unless there is evidence of thyroid gland invasion.

Re-examining the long-term effects of experiencing parental death in childhood on adult psychopathology.

This study examined whether the experience of the death of a parent in childhood increases risk for adult psychopathology. Participants consisted of 3481 men and women gathered through the Baltimore Epidemiologic Catchment Area study in 1981 and followed through 1994-1995. The Diagnostic Interview Survey was administered by trained interviewers and was used to assess DSM-III disorders including major depression, panic, and anxiety disorders. Maternal death was not a predictor of adult psychopathology. The death of the father during childhood more than doubled the risk for major depressive disorder in adulthood. This study did not find any significant interactions between gender of the deceased parent and gender of the participant nor did the current age of the participant or their age at the time of the death of a parent affect risk for adult psychopathology. The long-term effect on adult depression of the experience of the death of the father in childhood is attributed to likely financial stresses, which may have continued for years and possibly into early adulthood, complicating the family's adaptation to the initial loss.

Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs.

OBJECTIVES: Despite dramatic developments in drugs established for other malignancies, historically there have been few novel systemic agents available for the management of head and neck squamous cell carcinoma (HNSCC). However, the last decade has observed increased interest in targeted therapies for HNSCC. In 2006, cetuximab became the first major drug for HNSCC to gain Food and Drug Administration (FDA) approval in 3 decades. Recently, both pembrolizumab and nivolumab gained FDA approval for treatment of recurrent or metastatic HNSCC, and trials for other indications in HNSCC are actively underway. As older agents including cisplatin and 5-fluorouracil continue to play a significant role in the management of advanced HNSCC, an understanding of their legacy is paramount. This historical review is not meant to exhaustively catalog every finding relating to HNSCC systemic therapy, but rather is meant to highlight important advances. DATA SOURCES: Case series and clinical trials available in the literature. REVIEW METHODS: Historically significant series and trials evaluating HNSCC systemic therapy were evaluated. RESULTS: Standard regimens employed today are largely comprised of drugs discovered over 4 decades ago, although a number of recent phase III clinical trials have shown great promise, leading to the adoption of several new chemotherapeutic agents and treatment strategies. CONCLUSIONS: These findings reinforce the importance of supporting further HNSCC drug discovery as modern treatment strategies using systemic therapy have resulted in measurable improvements in oncologic outcomes. Laryngoscope, 127:2565-2569, 2017.

Outcomes of nonsurgical management of locally advanced carcinomas of the sinonasal cavity.

OBJECTIVE: To determine the outcome of definitive concurrent chemoradiation with platinum for locally advanced sinonasal carcinomas. STUDY DESIGN: Retrospective cohort. METHODS: Twenty-three nonsurgically and definitively treated patients diagnosed between July 1998 and February 2009 were analyzed. Patients with adenoid cystic carcinoma or adenocarcinoma were treated with photons and neutrons; the other histologies received photons alone. The vast majority received chemotherapy. Descriptive statistics were utilized, and Kaplan-Meier estimates were computed. RESULTS: Female (57%) and Caucasian (74%) preponderance were observed. Eighty-seven percent were unresectable; the maxillary and nasoethmoid sites were equally prevalent. Intensity-modulated radiation therapy (IMRT) and photons alone were utilized in 74% and 70%, respectively. Platinum agents were given in 95% of chemotherapy patients. Complete response was observed in 64% of patients. Median progression-free survival (PFS) and overall survival (OS) were 28.8 and 65.3 months, respectively. Three-year PFS and OS rates were 44% and 72%, respectively; 5-year PFS and OS rates were 30% and 60%, respectively. Intensity-modulated radiation therapy and a maxillary site of origin showed a trend toward superior PFS; higher-dose regimens were associated with somewhat shorter PFS. Relapse was observed in 59% of patients, predominantly local. There were few unanticipated adverse effects, and no grade IV/V events were reported. CONCLUSION: Advanced sinonasal carcinomas are chemoradiosensitive tumors, albeit with a high propensity for local relapse. There is a definite indication for IMRT and a potential curative role of platinum-based chemoradiation regimens. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:855-861, 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.

Histopathologic and cytopathologic diagnostic discrepancies in head and neck region: pitfalls, causes, and preventive strategies.

BACKGROUND: Clinicians commonly utilize fine needle aspiration biopsy (FNAB) for the primary investigation of head and neck masses. Correlation of these results with the surgical resection diagnosis is an essential part of quality control and assurance programs in all cytology laboratories. METHODS: Of 610 cases, 20 (3.3%) had corresponding surgical resections performed within 3 months of the FNAB, with a discrepant diagnosis identified through a search that involved all FNABs performed on the head and neck region, excluding the thyroid gland, at Wayne State University between 1999 and 2004. Sites of discrepant samples included the parotid or submandibular gland (n = 5), lymph nodes (n = 8), and paratracheal/paraesophageal neck masses (n = 7). RESULTS: The reasons of false-negative FNABs included sampling errors (n = 3), insufficient material for an adequate interpretation (n = 5), lack of triage necessary for ancillary studies (n = 4), and interpretation errors (n = 6). There were 2 false-positive FNABs, both reported as mucoepidermoid carcinoma and showed chronic sialadenitis in one and lymphoepithelial cyst in the other. CONCLUSIONS: FNAB is an effective tool for the diagnosis and triage of patients with head and neck masses that can be further improved with an onsite immediate adequacy evaluation and triage performed by a pathologist.

Biweekly gemcitabine and paclitaxel in patients with relapsed or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: We conducted a Phase II, clinical trial to evaluate the efficacy and safety of a biweekly gemcitabine and paclitaxel (GEMTAX) regimen as second-line treatment in patients with recurrent or metastatic unresectable, squamous cell carcinoma of the head and neck (SCCHN). The primary endpoint was response rate. PATIENTS AND METHODS: Patients with recurrent unresectable or metastatic platinum refractory SCCHN, who had performance status ≤2 and adequate organ function, were eligible. Gemcitabine (3000 mg/m(2) intravenous) and paclitaxel (150 mg/m(2) intravenous) was given on days 1 and 15of 4 weeks cycle, until patients had disease progression or unacceptable toxicity. RESULTS: Disease control (partial response [PR] + complete response [CR] + stable disease [SD]) was noted in 19 patients (54%) and overall response (CR + PR) was noted in 8 patients (23%). However, the most frequent response outcomes were progressive disease in 16 patients (46%) and SD in 11 patients (31%). The most frequent Grade 3-4 adverse events were lymphopenia in 38 patients (75%), anemia in 20 patients (39%), and infection in 16 patients (31%). Median progression-free survival was 3.6 months; median overall survival was 6.3 months. CONCLUSION: The biweekly GEMTAX regimen has statistically significant grade 3 and 4 adverse events and has meaningful clinical activity as a second-line treatment in patients with recurrent or metastatic SCCHN who have received prior chemotherapy. This regimen may particularly be a useful treatment option in patients who progressed in less than 6 months of concurrent chemoradiotherapy with high-dose cisplatin and/or have recurrent/metastatic platinum refractory SCCHN.

Pseudoaneuploid subpopulations detected in normal upper aerodigestive tract mucosa consistent with physiological apoptosis in normally differentiating squamous mucosa.

OBJECTIVES: While evaluating the validity of using normal human mucosal cells from the upper aerodigestive tract as diploid standards for DNA content studies of squamous cell cancer of head and neck by flow cytometry, pseudoaneuploidy was frequently detected. The purpose of this study was to further evaluate these DNA content abnormalities encountered in normal human mucosal cells and correlate them to physiological apoptosis. STUDY DESIGN: Thirty-two specimens of upper areodigestive tract mucosa from 18 surgical resections, 11 fresh autopsies, and 3 buccal scrapings were examined for DNA content by flow cytometry. RESULTS: Pseudoaneuploidy, which ranged from sub-G0/G1 peaks to hyperdiploid peaks with increased 90 degrees light scattering properties was found in 60% of these specimens. Fluorescent microscopic examination of the sorted DNA pseudoaneuploid cells demonstrated cells undergoing apoptosis. CONCLUSION: This unexpected pseudoaneuploidy in normal mucosal cells was a result of physiological apoptosis, a normal component of squamous differentiation. EBM RATING: B-2.

Voice and deglutition functions after the supracricoid and total laryngectomy procedures for advanced stage laryngeal carcinoma.

OBJECTIVES: This investigation compared speech and deglutition functions after alternative surgical treatments for advanced stage laryngeal carcinoma: the supracricoid laryngectomy (SCL) versus the total laryngectomy (TL). Study design and setting Cohort investigation at Wayne State University School of Medicine. METHODS: Quantitative studies of laryngeal biomechanics, acoustic and speech aerodynamic features, and deglutition skills of these individuals were coupled to listener and patient self-impressions of speech and voice characteristics for group comparative analyses. RESULTS: Results revealed that patients from each subgroup performed comparably relative to speech intelligibility and voice quality disturbances. Videostroboscopy of the neoglottal mechanisms in these two populations helped to explain these outcomes. Acoustic and speech aerodynamic testing demonstrated variably abnormal features in both surgical subgroups. Whereas the SCL patients eventually achieved full oral diets, they required many sessions of swallowing therapy to obtain this objective and eliminate tube feeding supplementation. The TL patients did not evidence protracted swallowing difficulties or the need for specific exercises in order to remove their feeding tubes postoperatively. References to organ preservation strategies in lieu of surgical management are included for completeness purposes. CONCLUSIONS: The SCL and TL surgical procedures for advanced stage laryngeal carcinoma resulted in equivalent speech and swallowing functional outcomes.

Correlation of histopathological variants, cellular DNA content, and clinical outcome in adenoid cystic carcinoma of the salivary glands.

OBJECTIVE: To study the correlation between flow cytometrically measured DNA ploidy with prognostically important histopathologic groups and clinical outcome in patients with adenoid cystic carcinoma of the salivary glands. STUDY DESIGN: 46 tumor specimens were analyzed flow cytometrically for DNA content and assessed for histological grade. Correlations were made between tumor DNA ploidy and histopathological grade, and disease-free and overall survival of these patients. RESULTS: Of the 46 patients, 31 had a cribiform/tubular histologic pattern, and 15 had a solid pattern. 84% of the tumors with cribriform/tubular pattern were DNA diploid, compared with 33% of tumors that were graded solid. This difference proved to be statistically significant (chi(2)11.75, P = 0.0006). Overall and disease-free survival periods were longer for patients with DNA diploid tumors in both groups, 63% vs. 36% and 62% vs 38%, respectively. CONCLUSIONS: Tumor DNA ploidy correlates with prognostically important tumor histopathology as well as overall and disease-free survival in patients with adenoid cystic carcinoma of the salivary gland. EBM RATING: B-3.

A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).

PURPOSE: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. METHODS AND MATERIALS: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. RESULTS: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. CONCLUSIONS: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

Pilot study of intraoperative chemotherapy with cisplatin and 5-fluorouracil in patients with advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Intraoperative manipulation of the tumor during cancer surgery has long been recognized as a source of metastasis and contamination of the surgical wound during tumor removal. We explored the use of intraoperative chemotherapy to minimize the risk of tumor cell implantation and metastasis during head and neck cancer surgery and conducted a dose escalating intraoperative chemotherapy clinical trial designed to assess the feasibility of this approach and associated toxicities in patients with advanced squamous cell carcinoma of the head and neck. METHODS: Fourteen patients were treated with 5-fluorouracil at a dose of 1000 mg/m(2) administered intravenously over an 8-hour period during the surgery with simultaneous cisplatin. The cisplatin dose was escalated and toxicity observed. Cisplatin at 75 mg/m(2) was chosen as the maximum tolerated dose level. RESULTS: One patient experienced a grade 3 nephrotoxicity, 1 patient a grade 1 neuropathy, and 5 patients grade 2 nausea (36%). There were no grade 4 toxicities. CONCLUSION: Intraoperative chemotherapy is feasible, and the combination of cisplatin at 75 mg/m(2) and 5-fluorouracil at 1000 mg/m(2) can be administered during surgery without significant toxicity.

Prognostic significance of G1 cell-cycle inhibitors in early laryngeal cancer.

BACKGROUND: Radiation therapy yields a 2-year local control rate of 80% to 90% in early laryngeal squamous cell carcinoma. However, a subset of early laryngeal cancers has a significantly higher rate of local recurrence and lower rate of overall survival. OBJECTIVE: The objective of this study was determine the prognostic significance of p53, p27, and p21 expression in patients with early laryngeal cancer. METHODS: Expression of p53, p27, and p21 proteins in pretreatment biopsies from sixty-eight patients was analyzed by using immunohistochemistry. Low (10% cells) levels of expression were measured. All patients were newly diagnosed and treated with external beam radiation. Other contributing factors were also studied, such as age, sex, race, tumor site, and stage. RESULTS: Forty (58.8%) and 28 (41.2%) lesions were staged as T1 and T2, respectively, whereas 16 (23.5%) and 52 (76.5%) were located in the supraglottis and glottis, respectively. Overexpression of p27, p53, and p21 was found in 36.7%, 60.6%, and 60% of cases, respectively. Overexpression of p27 was found to be a significant predictor of recurrence by multivariate analysis (RR 3.3, P = .017). Overexpression of p21 and/or p53 was not predictive of recurrence. No factor predicted disease specific or nonspecific overall survival. CONCLUSION: Our results indicate the significance of p27 overexpression as an indicator of recurrence in patients with early laryngeal squamous cell carcinoma.

Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501).

BACKGROUND: In 2004, level I evidence was established for the postoperative adjuvant treatment of patients with selected high-risk locally advanced head and neck cancers, with the publication of the results of two trials conducted in Europe (European Organization Research and Treatment of Cancer; EORTC) and the United States (Radiation Therapy Oncology Group; RTOG). Adjuvant chemotherapy-enhanced radiation therapy (CERT) was shown to be more efficacious than postoperative radiotherapy for these tumors in terms of locoregional control and disease-free survival. However, additional studies were needed to identify precisely which patients were most suitable for such intense treatment. METHODS: Both studies compared the addition of concomitant relatively high doses of cisplatin (on days 1, 22, and 43) to radiotherapy vs radiotherapy alone given after surgery in patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx. A comparative analysis of the selection criteria, clinical and pathologic risk factors, and treatment outcomes was carried out using data pooled from these two trials. RESULTS: Extracapsular extension (ECE) and/or microscopically involved surgical margins were the only risk factors for which the impact of CERT was significant in both trials. There was also a trend in favor of CERT in the group of patients who had stage III-IV disease, perineural infiltration, vascular embolisms, and/or clinically enlarged level IV-V lymph nodes secondary to tumors arising in the oral cavity or oropharynx. Patients who had two or more histopathologically involved lymph nodes without ECE as their only risk factor did not seem to benefit from the addition of chemotherapy in this analysis. CONCLUSIONS: Subject to the usual caveats of retrospective subgroup analysis, our data suggest that in locally advanced head and neck cancer, microscopically involved resection margins and extracapsular spread of tumor from neck nodes are the most significant prognostic factors for poor outcome. The addition of concomitant cisplatin to postoperative radiotherapy improves outcome in patients with one or both of these risk factors who are medically fit to receive chemotherapy.

Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature.

We present the clinical and histopathologic findings of a 38-year-old woman recently diagnosed with sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid (SMECE). This case is of particular interest because of its extremely aggressive clinical course. After total thyroidectomy, there was extensive bilateral thyroid lobe involvement with extension into perithyroidal soft tissues and the modified radical neck dissection contained 35 of 35 positive lymph nodes. This patient underwent 2 further surgeries; the first was a second right neck and supraclavicular surgery for lymph node metastases in which 8 of 11 were positive, followed a few months later by posterior neck surgery in which multiple lymph nodes were positive. Tumor was also documented by histological review from a right axillary lymph node. Imaging evidence of tumor in the lungs and liver was also present. Establishing the correct diagnosis of SMECE involves an awareness of the cyto- and histomorphologic features of this rare malignancy. As evidence that the biologic behavior of this neoplasm may well be more aggressive than previously considered, we briefly present the clinical and biologic course of this patient's neoplasm and a review of the literature.

Prognostic significance of p53 and FHIT in advanced oropharyngeal carcinoma.

OBJECTIVE: To determine the prognostic significance of p53 and fragile histidine triad (FHIT) expression in advanced oropharyngeal squamous cell carcinoma. STUDY DESIGN: A retrospective collection of clinical data was correlated with the protein expression. METHOD: The expression of p53 and FHIT in specimens from patients with previously untreated advanced squamous cell carcinoma of the oropharynx was determined by immunohistochemistry. The expression of p53 and FHIT was statistically correlated with survival outcome. The primary endpoints were overall survival and disease-free survival. RESULTS: Thirty-four patients were analyzed in this study. Overexpression of p53 was observed in 41.2% (14/34) of tumors and was associated with a trend toward an improved overall survival using univariate (P =.1088, risk ratio [RR] = 0.503) and multivariate (P =.1533, RR = 0.470) analyses. Marked reduction or complete absence of FHIT expression was observed in 57.6% (19/33) of tumors. Patients with tumors showing no reduction in FHIT expression had a lower overall survival using univariate (P =.04, RR = 2.27) and multivariate (P =.013, RR = 4.41) analyses. CONCLUSION: Overexpression of p53 predicted a trend toward an improved prognosis, whereas no reduction in FHIT expression predicted a significantly poorer outcome in patients with advanced oropharyngeal cancer.

Predictors of nodal metastasis in salivary gland cancer.

OBJECTIVES: This study was conducted to determine clinical and histologic factors that would predict nodal metastasis in patients with major salivary gland cancer. METHODS: A retrospective study of 40 patients who underwent surgery, including neck dissection, for major salivary gland cancer between 1975 and 1997 was performed. Patient charts were reviewed, and clinical and pathologic data were extracted along with outcome. Predictive factors were identified and survival curves were obtained. RESULTS: Neck dissections were performed in 40 patients, which revealed histologic evidence of tumor in lymph nodes in 15 cases. Histologically proven metastasis was found in 16% of specimens from elective and 73% of specimens from therapeutic neck dissection. Five-year overall and locoregional disease-free survival rates for histologically positive and negative groups were 40% versus 63% (P < 0.05) and 67% versus 69% (P = 0.59), respectively. Univariate analysis of the factors revealed that clinical evidence of nodal metastasis (P < 0.001) and high-grade cancer (P < 0.033) predicted histologic nodal involvement. Multivariate analysis revealed that only a positive neck examination was a significant predictive factor (OR = 31, 95%CI = 2.99-312). CONCLUSIONS: Our results suggest that clinical neck examination is a reliable predictor of regional metastasis in patients with major salivary gland cancer. In view of the low frequency of occult metastases, routine elective treatment of the neck is not recommended.