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To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature.Retrospective review.Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09).Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes.4 Laryngoscope, 131:E875-E881, 2021.

Objectives/Hypothesis: To evaluate reconstructive outcomes following oncologic temporal bone resection. Study Design: Retrospective review. Methods: Subjects consisted of 117 patients undergoing temporal bone resection and reconstruction between 2000 and 2010. Reconstructive outcomes, including results following facial nerve repair, were analyzed. Results: Reconstruction was performed with a regional flap in 27 patients and a microvascular free flap in 90 patients. Operative time was shorter for cases involving reconstruction with regional flaps compared to free flaps (6.9 vs. 11.2 hours, P < .0001), as were intensive care unit and hospital stays (0.4 vs. 3.4 days, P < .0001 and 4.1 vs. 8.6 days, P < .0001, respectively). Overall complication rates were similar for regional and free flap cases (22.2% vs. 23.3%, P = 1.00), although donor site complications were more common with free flaps (0% vs. 13.3%, P = .07). Facial nerve repairs were performed in 19 patients. Of 14 patients with more than 12 months of follow-up, 71.4% demonstrated signs of reinnervation and 42.9% achieved a House-Brackmann score of 3 or better. The mean time to reinnervation was 7.9 months. Recovery was not significantly affected by preoperative nerve function, postoperative radiation, or advanced age (P = 1.00 in each case). Conclusions: We recommend regional flaps for small defects based on minimal donor site morbidity, and shorter operative times, intensive care unit, and hospital stays. For extensive defects and in cases involving prior surgery or radiation, free flaps are preferred. Facial nerve repair should be attempted whenever feasible, even in the setting of preoperative weakness, planned postoperative radiation, and advanced age. Laryngoscope, 2012

Objectives/Hypothesis: Enlargement of the tracheoesophageal puncture (TEP) results in aspiration around the voiceprosthesis (VP) and may lead to pneumonia. The primary objective was to summarize control of leakage around the VP afterconservative management of enlarged TEP.Study Design: Retrospective cohort study.Methods: This 5-year cohort included 194 patients who underwent total laryngectomy (with or without pharyngec-tomy) and TEP at the University of Texas MD Anderson Cancer Center. Control of leakage around the VP was analyzed at lastfollow-up after enlarged TEP. Adverse events were compared in patients with and without enlarged TEP.Results: The incidence of enlarged TEP was 18.6% (36 of 194, 95% confidence interval [CI]: 13.0%-24.1%). Conserva-tive methods commonly attempted in lieu of complete TEP closure included placement of an enlarged-flange VP (34 of 36,94%), temporary VP removal (14 of 36, 39%), and TEP-site injection (8 of 36, 22%). At last follow-up, conservative methodscontrolled leakage around the VP in 81% (29 of 36) of patients. Only two patients required complete TEP closure due to per-sistent leakage after enlarged TEP. Unresolved leakage was more common in patients with recurrent cancer after laryngec-tomy (P ¼ .081) and irregular TEP contour (P ¼ .003). Relative to controls without TEP enlargement, patients with enlargedTEP had a three-fold higher risk of pneumonia (relative risk: 3.4, 95% CI: 1.9–6.2) and aspiration of the prosthesis (relativerisk: 3.3, 95% CI: 0.8–14.1).Conclusions: Although the rate of enlarged TEP is relatively low, the complication significantly elevates risk of pneumo-nia. Prosthetic leakage related to TEP enlargement can often be managed conservatively to avoid complete closure of the TEP.Key Words: Tracheoesophageal puncture, total laryngectomy, enlarged tracheoesophageal puncture, risk factors.Level of Evidence: 2b.Laryngoscope, 121:1455–1461, 2011

Objectives: Nasopharyngeal carcinoma (NPC) is a rare cancer in the United States. An association between NPC and Epstein-Barr virus (EBV) is well-established for World Health Organization (WHO) types II and III (WHO-II/III) NPC but less well-established for WHO type I (WHO-I) NPC. Given the rise in oropharyngeal tumors positive for high-risk human papillomavirus (HPV) and the unique biology of WHO-I NPC, we examined the relationship between HPV and WHO-I NPC. Study Design: Retrospective case-comparison study. Methods: A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no prior cancer. Available paraffin-embedded tumor specimens (N = 30) were analyzed for oncogenic HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV-16 and HPV-18; EBV status by ISH; and p16 expression by immunohistochemistry. Demographic parameters, including race and smoking, were obtained from the medical records. Results: Among the 18 WHO-I NPC patients, 66% (N = 12) were smokers and 17% (N = 3) Asian; among the 165 WHO-II/III NPC patients, 44% (N = 73) were smokers and 24% (N = 39) Asian. Eight WHO-I NPC patients had available paraffin blocks; five of six were HPV-16-positive by PCR and four of eight were HPV-positive by ISH; only two of eight (25%) were EBV-positive. Twenty-two WHO-II/III NPC patients had available paraffin blocks; only 1 was HPV-positive by ISH, and 13 of 22 (60%) were EBV-positive. Conclusions: These results suggest that WHO-I NPC is associated with oncogenic HPV, although larger studies are needed to verify these findings. Laryngoscope, 2010

Objective/Hypothesis: To describe the clinical history and outcome of patients with adenoid cystic carcinoma (ACC) of the external auditory canal (EAC). Study Design: Retrospective case series. Methods: A search of our institution's tumor registry identified 22 patients with ACC of the EAC. Both clinical histories and pathology slides, when available, were reviewed. Results: The mean age at diagnosis was 42 years (median, 38.5 years), and the most common presenting complaints were otalgia and ear canal mass. Nine patients (41%) developed recurrences at a mean of 8 years (median, 8 years) after initial diagnosis, six died of ACC, and three were living with distant metastases at their last follow-up. The mean duration of symptoms at the time of diagnosis was 7.7 years (range, 2–30 years) for patients who developed a recurrence after treatment vs. 1.2 year (range, 0–2 years) for patients who remained disease-free (P = .137). Every patient who had recurrent disease reported a duration of symptoms of ≥2 years (P = .013), and every patient with a duration of symptoms >2 years recurred (P = .002). There was a trend for more local recurrences after limited resection (P = .061). Conclusions: ACC of the EAC often recurs many years after definitive treatment. Although our sample size was too small to make definitive conclusions, we recommend aggressive local therapy with lateral temporal bone resection and adjuvant postoperative radiotherapy. In addition to successful local therapy, early diagnosis may be the only other effective means of preventing distant metastases.

Background: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC. Hypothesis: Germline variants of double-strand break repair genes are markers of DTC risk. Objective: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls. Study Design: Case-control study. Methods: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype. Results: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P = .006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9–4.9; P = .078). Conclusions: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies.

To evaluate reconstructive outcomes following oncologic temporal bone resection.Retrospective review.Subjects consisted of 117 patients undergoing temporal bone resection and reconstruction between 2000 and 2010. Reconstructive outcomes, including results following facial nerve repair, were analyzed.Reconstruction was performed with a regional flap in 27 patients and a microvascular free flap in 90 patients. Operative time was shorter for cases involving reconstruction with regional flaps compared to free flaps (6.9 vs. 11.2 hours, P.0001), as were intensive care unit and hospital stays (0.4 vs. 3.4 days, P.0001 and 4.1 vs. 8.6 days, P.0001, respectively). Overall complication rates were similar for regional and free flap cases (22.2% vs. 23.3%, P = 1.00), although donor site complications were more common with free flaps (0% vs. 13.3%, P = .07). Facial nerve repairs were performed in 19 patients. Of 14 patients with more than 12 months of follow-up, 71.4% demonstrated signs of reinnervation and 42.9% achieved a House-Brackmann score of 3 or better. The mean time to reinnervation was 7.9 months. Recovery was not significantly affected by preoperative nerve function, postoperative radiation, or advanced age (P = 1.00 in each case).We recommend regional flaps for small defects based on minimal donor site morbidity, and shorter operative times, intensive care unit, and hospital stays. For extensive defects and in cases involving prior surgery or radiation, free flaps are preferred. Facial nerve repair should be attempted whenever feasible, even in the setting of preoperative weakness, planned postoperative radiation, and advanced age.

Objectives/Hypothesis: Single nucleotide polymorphisms (SNPs) in the 8q24 chromosomal region identified from genome-wide scans have been associated with the risk of several cancers, including breast (rs1562430), prostate (rs1447295), and colon (rs6983267). A genome-wide scan in 26 families with papillary thyroid cancer (PTC) also found susceptibility loci in 8q24, supporting a closer evaluation of this chromosomal region in relation to the risk of sporadic PTC. Study Design: Case-control study. Methods: We evaluated 157 tag SNPs in the 8q24 chromosomal region between 120.91 Mb and 128.78 Mb (including rs1562430, rs1447295, and rs6983267) in a case-control study of 344 PTC cases and 452 age and gender frequency-matched controls. We used logistic regression to estimate odds ratios and compute P values of linear trend for PTC with genotypes of interest. To account for multiple comparisons, we applied the false discovery rate (FDR) method. Results: We did not find a significant association between rs1562430, rs1447295, or rs6983267 and PTC risk. We found that one SNP (rs4733616) was associated with PTC risk at P = .003, and 12 other SNPs were associated with PTC risk at P < .05. However, no SNPs remained significant after FDR correction. Conclusions: Our findings do not support a strong association between SNPs in the 8q24 chromosomal region and risk of sporadic PTC, but several SNPs with small effects might exist.

Nasopharyngeal carcinoma (NPC) is a rare cancer in the U.S. that has a well-established association with Epstein-Barr virus(EBV) for WHO types II/III but less so for WHO type I. Given the rise in oropharyngeal tumors positive for high risk human papillomavirus (HPV) and the unique biology of WHO type INPC, we chose to examine the relationship between HPV and WHO type I NPC.Retrospective case comparison study.A search of a large multidisciplinary cancer center tumor registry identified 183 patients seen from January 1999 to December 2008 with incident NPC and no history of prior cancer. Available paraffin embedded tumor specimens (N=30) were analyzed for HPV status by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV 16 and 18, EBV status by ISH, and p16 expression by immunohistochemistry. Demographic parameters, including race, smoking, and alcohol exposure were obtained from the medical records.Patients with incident WHO-I NPC (N=18) tended to be smokers (66%) and only 17% were Asian, while for patients with incident WHO-II/III NPC (N=165), 44% were smokers and 24% were Asian. For WHO-I NPC patients with available paraffin blocks (N=8), 5 of 6 were HPV 16+ by PCR and 4 of 8 had HPV identified by ISH, while only 2 of 8 were EBV+. Of patients with WHO II/III NPC and available archival tissue (N=22), 60% were EBV+ and only one was HPV positive by ISH.These results suggest that WHO type I NPC may be associated with oncogenic HPV, though larger studies are needed to verify these findings.

Objectives/Hypothesis: To study the survival outcomes of patients with squamous cell carcinoma (SCC) of the temporal bone. A secondary purpose was to evaluate the University of Pittsburgh staging system as a predictor of survival. Study Design: Retrospective review. Methods: We performed a single-institution retrospective review of the medical charts of patients diagnosed with SCC of the temporal bone between 1945 and 2005. We identified the patients' demographic characteristics, presenting symptoms, physical examination findings, tumor histology, disease extent, treatment course, and clinical outcomes. We used the Pittsburgh staging system (2000) to determine the patients' tumor classification and disease state. We then compared the overall and disease-free survival rates between patients with early-stage versus late-stage disease. Results: We identified 124 patients with SCC of the temporal bone. Of these, 71 had incident (untreated) SCC, 26 had recurrent SCC, and 27 had persistent SCC after treatment elsewhere. The 5-year overall survival rate for patients with incident SCC was 38%, and the disease-free survival rate was 60%. The overall survival rate for patients with incident SCC was similar to that for patients with persistent disease and was significantly better than that for patients with recurrent SCC (P = .008). Patients with early-stage tumors (T1 or T2) had longer overall survival than those with late-stage tumors (T3 or T4; P = .004, log-rank). The 5-year overall survival rate was 48% for patients with early-stage disease and 28% for patients with late-stage disease. Furthermore, patients with T1 tumors had significantly longer overall survival than patients with T2 tumors (P = .039) and patients with T3 and T4 tumors (P = .0008). Overall survival (OS) and disease-free interval (DFI) were improved for T2 tumors when radiotherapy was combined with surgery (OS, P = .011; DFI, P = .02). T1 tumors did not benefit in a statistically significant way with combined therapy. T3 and T4 tumors had relatively poor outcomes in spite of combined therapy. Twenty-two patients (31%) experienced a recurrence within 1 year of treatment, whereas only one patient developed recurrence after 1 year. Lymph node metastasis, facial paralysis, or involvement of the carotid artery, jugular foramen, or infratemporal fossa were not significantly associated with overall or disease-free survival. Conclusions: Patients with recurrent SCC of the temporal bone had significantly shorter overall survival and disease-free interval than patients with incident SCC. In addition, patients with early-stage disease (T1 and T2) had significantly longer overall survival and disease-free survival than patients with late-stage tumors. Laryngoscope, 2010

Objective: To determine whether common (allele frequencies > 5%) single nucleotide polymorphisms located in exons 2, 7, 11, 13, 14, and 15 of the RET proto-oncogene are associated with risk of differentiated thyroid carcinoma (DTC). Study Design: Hospital-based case-control study. Methods: Patients with DTC or benign thyroid disease (BTD) were frequency matched with cancer-free controls on age and sex. Only non-Hispanic whites were included to avoid racial confounding. Polymerase chain reaction–restriction fragment-length polymorphism assays were used for genotyping. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype distributions were estimated using Bayesian analyses. Results: DTC cases and controls had similar rates of tobacco, alcohol, and radiation exposure. The genotype distributions were similar between DTC cases (n = 101) and controls (n = 174) except for RET 7 and RET 14 (P = .003 and P = .047, respectively) and between BTD cases (n = 62) and controls except for RET 14 (borderline; P = .064). Polymorphic allele frequencies were similar between the cases and controls except for RET 14 (borderline; P = .051 and P = .068 for DTC and BTD, respectively). The RET 7 heterozygous polymorphic genotype was associated with a significantly increased risk of DTC after multivariate adjustment (OR = 2.0, 95% CI = 1.2–3.4, P = .012). Compared with the most common haplotype (GGGTCC), no RET haplotype was associated with a significantly increased risk of DTC. Conclusions: Exon 7 (and possibly 14) polymorphism of RET may be associated with increased risk of DTC. However, the sample size is relatively small, and larger investigations are needed.

Antibodies directed against epidermal growth factor receptor (EGFr) impede proliferation and induce differentiation of EGFr-positive cancers. To explore the effectiveness of anti-EGFr monoclonal antibodies on acoustic neuromas (ANs), we first sought to evaluate EGFr expression by ANs. The records of all patients with the diagnosis of AN at our institution from January 1989 to July 1994 were reviewed. Immunohistochemical analysis for EGFr was performed on formalin-fixed, paraffin-embedded archival surgical specimens. Skin, liver, and placenta were used as positive tissue controls. Purified rabbit immunoglobulin G replacing the experimental antibody acted as a negative control, and normal eighth cranial nerve was evaluated for background staining. Slides were scored as 0, +, ++, or +++ and for percentage of positive cells by two pathologists, with Antoni A and Antoni B areas scored separately. Results demonstrate that most tumors are revealed to be EGFr positive with a mild degree of staining. Antoni A areas generally have greater staining than Antoni B regions, while normal eighth cranial nerves demonstrate minimal background staining. These results suggest that ANs express low levels of EGFr, with Antoni A areas having the highest levels. While further studies may more accurately quantitate EGFr levels in these tumors, the clinical efficacy of anti-EGFr-based therapies for ANs seems doubtful.

aChi-squared analysis comparing genotype distributions between case and control subjects. bAdjusted for age, sex, ethnicity, family history of cancer, tobacco use, alcohol use, and radiation exposure. OR = odds ratio; CI = confidence interval BRCA1 is a vital DNA repair gene, and the single nucleotide polymorphisms (SNPs) of this gene have been studied in diverse cancer types. In this study, we investigated the association between eight common BRCA1 SNPs (common allele frequencies >5%) and risk of differentiated thyroid carcinoma (DTC).