A cross-sectional study of the association of dental health factors with progression and all-cause mortality in men diagnosed with HPV-associated oropharyngeal cancer.

BACKGROUND: Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC. METHODS: A cross sectional study of men diagnosed with HPV-OPC between 2014-2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality. RESULTS: Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4-4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43-19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72-16.26). CONCLUSIONS: Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes.

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. METHODS: An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. RESULTS: The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. CONCLUSIONS: HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.

Frequent somatic mutations of the transcription factor ATBF1 in human prostate cancer.

Cancer often results from the accumulation of multiple genetic alterations. Although most malignancies are sporadic, only a small number of genes have been shown to undergo frequent mutations in sporadic cancers. The long arm of chromosome 16 is frequently deleted in human cancers, but the target gene for this deletion has not been identified. Here we report that ATBF1, which encodes a transcription factor that negatively regulates AFP and MYB but transactivates CDKN1A, is a good candidate for the 16q22 tumor-suppressor gene. We narrowed the region of deletion at 16q22 to 861 kb containing ATBF1. ATBF1 mRNA was abundant in normal prostates but more scarce in approximately half of prostate cancers tested. In 24 of 66 (36%) cancers examined, we identified 22 unique somatic mutations, many of which impair ATBF1 function. Furthermore, ATBF1 inhibited cell proliferation. Hence, loss of ATBF1 is one mechanism that defines the absence of growth control in prostate cancer.

Phase 1 Dose Escalation of Stereotactic Body Radiation Therapy and Concurrent Cisplatin for Reirradiation of Unresectable, Recurrent Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN. METHODS AND MATERIALS: Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival. RESULTS: Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years. CONCLUSIONS: Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.

MKK4 suppresses metastatic colonization by multiple highly metastatic prostate cancer cell lines through a transient impairment in cell cycle progression.

Metastatic dissemination in prostate cancer is often early, but not all cancer cells form clinical metastases. Map kinase kinase 4 (MKK4) suppresses metastasis in a preclinical prostate cancer model. We hypothesize that MKK4 will specifically inhibit metastatic colonization through impaired proliferation. Three highly metastatic rat prostate cancer cell lines (AT6.1, Mat-Lu and AT3.1) were employed. Stably over-expressing HA-MKK4 or vector control lines were injected into immunocompromised mice. These experiments validated that HA-MKK4 specifically affects metastatic colonization and increases survival. Median survival (days) with HA-MKK4 vs. vector was 42 vs. 28 (p < 0.0001) for AT6.1, 25 vs. 19 (p < 0.0001) for Mat-Lu and 27 vs. 20 (p < 0.0001) for AT3.1. HA-MKK4 suppresses colonization within 14 days post dissemination, after which exponential proliferation resumes. Although overt metastases retain HA-MKK4, it is inactive within these lesions. Nonetheless, metastasis-derived cell lines were shown to retain functional HA-MKK4 and like their parental HA-MKK4 line are suppressed for experimental metastasis formation in vivo. Disseminated AT6.1-HA-MKK4 cells were analyzed and were found to have an alteration in cell cycle. Specifically, there was an accumulation of cells in G1-phase (p = 0.024) and decrease in S-phase (p = 0.037) compared with vector. In multiple prostate cancer lines, HA-MKK4 suppresses an early step in metastatic colonization. These data support a model in which MKK4 activation at the metastatic site causes a cell-cycle arrest, which is eventually overcome despite presence of functional HA-MKK4. Further studies will specifically interrogate the regulation of MKK4 activation within the metastatic microenvironment and the down-stream molecular events critical for metastasis suppression.

A Case of Medullary Microcarcinoma in the Setting of Cowden's Syndrome.

Cowden's syndrome (CS) is a rare inherited condition characterized by hamartomas in various organs including the thyroid and mucocutaneous tissues as one of the most distinctive features. We present a rare case of Cowden's syndrome with medullary microcarcinoma of the thyroid, in a 56 year old male with a history of hamartomatous colon polyps, papillomas of the tongue, skin tags, learning disability in the spectrum of autism and macrocephaly. This was evident on immunohistochemical examination of a nodule in the right thyroid lobe. Calcitonin and carcinoembryonic antigen (CEA) positivity along with C-cell hyperplasia were consistent with a medullary microcarcinoma. Total thyroidectomy was performed. Post-operatively margins were uninvolved by carcinoma. Perineural and lymphatic invasion was not identified. Considering the rarity of this condition and the unique presentation of our patient we believe that reporting this case would add more information to the existing fund of knowledge.

Sclerosing Polycystic Adenoma: Conclusive Clinical and Molecular Evidence of Its Neoplastic Nature.

Sclerosing polycystic adenosis, initially considered a non-neoplastic salivary gland lesion and classified as such in the 2017 WHO Classification of Head and Neck Tumors, has been the subject of controversy regarding its possible neoplastic nature. The reporting of recurrent PI3K pathway alteration represents evidence to support these lesions as being neoplastic and more appropriately referred to as sclerosing polycystic adenoma (SPA). Herein, we provide additional evidence that supports the classification of SPA as a true neoplasm. Eight cases of SPA were identified in our database and consultation files. All cases were subjected to PTEN immunohistochemistry (IHC) and next-generation sequencing (NGS). In addition, one patient underwent genetic counseling and germline testing. The cases included 5 men and 3 women with a mean age of 41 years (range 11-78) and all tumors arose in the parotid gland. One patient had multiple recurrences over a period of 2 years. Morphologically the tumors were circumscribed and characterized by an admixture of acini, ducts and cysts embedded in a fibrotic/sclerotic stroma. The cells lining the ducts and cysts showed variable granular, vacuolated, foamy and apocrine cytoplasmic features, as well as acinar cells contained intracytoplasmic brightly eosinophilic granules. The apocrine intraductal proliferations showed mild to moderate atypia in 6 cases. One case showed overt malignant morphology that ranged from intraductal carcinoma to invasive salivary duct carcinoma. Seven cases tested for PTEN IHC showed loss of nuclear expression in the acinar and ductal cells with retained PTEN expression in the myoepithelial cell and stroma. NGS detected PIK3CA or PIK3R1 genetic alterations in 7 cases, including a novel TFG-PIK3CA fusion. Coexisting PTEN mutations were seen in 4 cases, including in a patient with clinical stigmata of Cowden syndrome and confirmed by germline genetic testing. Our findings herein documented including recurrence of tumor, malignant transformation, high prevalence of PI3K pathway oncogenic alterations and the possible heretofore undescribed association with Cowden syndrome add support to classifying SPA as true neoplasms justifying their designation as adenoma, rather than adenosis.

Genome-Wide Association Study and Genomic Prediction for Bacterial Wilt Resistance in Common Bean (Phaseolus vulgaris) Core Collection.

Common bean (Phaseolus vulgaris) is one of the major legume crops cultivated worldwide. Bacterial wilt (BW) of common bean (Curtobacterium flaccumfaciens pv. flaccumfaciens), being a seed-borne disease, has been a challenge in common bean producing regions. A genome-wide association study (GWAS) was conducted to identify SNP markers associated with BW resistance in the USDA common bean core collection. A total of 168 accessions were evaluated for resistance against three different isolates of BW. Our study identified a total of 14 single nucleotide polymorphism (SNP) markers associated with the resistance to BW isolates 528, 557, and 597 using mixed linear models (MLMs) in BLINK, FarmCPU, GAPIT, and TASSEL 5. These SNPs were located on chromosomes Phaseolus vulgaris [Pv]02, Pv04, Pv08, and Pv09 for isolate 528; Pv07, Pv10, and Pv11 for isolate 557; and Pv04, Pv08, and Pv10 for isolate 597. The genomic prediction accuracy was assessed by utilizing seven GP models with 1) all the 4,568 SNPs and 2) the 14 SNP markers. The overall prediction accuracy (PA) ranged from 0.30 to 0.56 for resistance against the three BW isolates. A total of 14 candidate genes were discovered for BW resistance located on chromosomes Pv02, Pv04, Pv07, Pv08, and Pv09. This study revealed vital information for developing genetic resistance against the BW pathogen in common bean. Accordingly, the identified SNP markers and candidate genes can be utilized in common bean molecular breeding programs to develop novel resistant cultivars.

Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and RAS Mutations.

Background:RAS gene family mutations are the most prevalent in thyroid nodules with indeterminate cytology and are present in a wide spectrum of histological diagnoses. We evaluated differentially expressed genes and signaling pathways across the histological/clinical spectrum of RAS-mutant nodules to determine key molecular determinants associated with a high risk of malignancy. Methods: Sixty-one thyroid nodules with RAS mutations were identified. Based on the histological diagnosis and biological behavior, the nodules were grouped into five categories indicating their degree of malignancy: non-neoplastic appearance, benign neoplasm, indeterminate malignant potential, low-risk cancer, or high-risk cancer. Gene expression profiles of these nodules were determined using the NanoString PanCancer Pathways and IO 360 Panels, and Angiopoietin-2 level was determined by immunohistochemical staining. Results: The analysis of differentially expressed genes using the five categories as supervising parameters unearthed a significant correlation between the degree of malignancy and genes involved in cell cycle and apoptosis (BAX, CCNE2, CDKN2A, CDKN2B, CHEK1, E2F1, GSK3B, NFKB1, and PRKAR2A), PI3K pathway (CCNE2, CSF3, GSKB3, NFKB1, PPP2R2C, and SGK2), and stromal factors (ANGPT2 and DLL4). The expression of Angiopoietin-2 by immunohistochemistry also showed the same trend of increasing expression from non-neoplastic appearance to high-risk cancer (p < 0.0001). Conclusions: The gene expression analysis of RAS-mutant thyroid nodules suggests increasing upregulation of key oncogenic pathways depending on their degree of malignancy and supports the concept of a stepwise progression. The utility of ANGPT2 expression as a potential diagnostic biomarker warrants further evaluation.

Operative findings in the frontal recess at time of revision surgery.

OBJECTIVE: Endoscopic sinus surgery is the gold standard for the treatment of medically refractory chronic rhinosinusitis. There is, however, a population of patients for whom persistent disease is a problem. Of all the sinuses, the frontal sinus is the most likely to have recurrent obstruction. We evaluated the findings causing frontal recess obstruction at the time of revision surgery. STUDY DESIGN AND SETTING: A retrospective review was performed in a tertiary care academic otolaryngology department. RESULTS: Findings obstructing the frontal recess at the time of revision sinus surgery were reviewed. Two hundred eighty-nine frontal sinuses were included. Seven findings were identified: mucosal disease (67%), retained ethmoid cells (53%), lateralized middle turbinates (30%), retained agger nasi cells (13%), scar (12%), retained frontal cells (8%), and neoosteogenesis (7%). Most frontal recesses had multiple etiologies for failure listed above, with an average of 1.6. CONCLUSIONS: Multiple findings can be identified that contribute to frontal recess obstruction requiring revision sinus surgery. A comprehensive approach to address all factors is necessary to prevent surgical failure among patients presenting for endoscopic frontal sinus surgery.

Mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase kinase 1 protein expression is subject to translational regulation in prostate cancer cell lines.

Mitogen-activated protein kinase kinase 4/c-Jun NH(2)-terminal kinase kinase 1 (MKK4/JNKK1; hereafter referred to as MKK4) is a dual-specificity kinase with a critical role in regulating the activity of c-Jun NH(2)-terminal kinase and p38 kinases. We identified a novel biological function for MKK4 in the regulation of growth of ovarian and prostate cancer metastases. Clinical correlative studies showed that MKK4 protein levels were reduced in high-grade prostate cancer and prostate and ovarian cancer metastases compared with normal tissue, which prompted investigation into the mechanism(s) responsible for down-regulation of MKK4 in a panel of cancer cell lines. Initial studies found that low levels of MKK4 protein did not correlate with either exon deletion or decreased levels of MKK4 mRNA, suggesting that MKK4 protein levels were regulated posttranscriptionally by either reduced translation or reduced protein stability. Endogenous MKK4 was highly stable and not subject to altered proteolysis. Instead, MKK4 biosynthesis seemed to be regulated by altered translation. In support of this assertion, we found that cytosolic MKK4 mRNA was shifted toward active polysomes in cells with higher levels of MKK4 protein, suggesting that MKK4 mRNA was translated more efficiently in these cells. This study supports a novel mechanism for the regulation of MKK4 protein levels. Further, these findings have potential therapeutic implications for modulating the expression of a signaling kinase involved in the regulation of metastatic growth.

FYN is overexpressed in human prostate cancer.

OBJECTIVE: To test the hypothesis that FYN, a member of the SRC family of kinases (SFKs), is up-regulated in prostate cancer, as FYN is functionally distinct from other SFKs, and interacts with FAK and paxillin (PXN), regulators of cell morphology and motility. MATERIALS AND METHODS: Through data-mining in Oncomine (http://www.oncomine.org), cell-line profiling with immunoblotting, quantitative reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemical analysis, we described FYN expression in prostate cancer. The analysis included 32 cases of prostate cancer, nine of prostatic intraepithelial neoplasia (PIN) and 19 normal prostates. Samples were scored for the percentage of stained glands and intensity of staining (from 0 to 3). Each sample was assigned a composite score generated by multiplying percentage and intensity. RESULTS: Data-mining showed an eight times greater FYN expression in prostate cancer than in normal tissue; this was specific to FYN and not present for other SFKs. Expression of FYN in prostate cancer cell lines (LNCaP, 22Rv1, PC3, DuPro) was detected using quantitative RT-PCR and immunoblotting. Expression of FYN and its signalling partners FAK and PXN was detected in human tissue. Comparing normal with cancer samples, there was a 2.1-fold increase in median composite score for FYN (P < 0.001) 1.7-fold increase in FAK (P < 0.001), and a doubling in PXN (P < 0.05). There was a 1.7-fold increase in FYN (P < 0.05) and a 1.6-fold increase in FAK (P < 0.01) in cancer compared with PIN. CONCLUSIONS: These studies support the hypothesis that FYN and its related signalling partners are up-regulated in prostate cancer, and support further investigation into the role of the FYN as a therapeutic target.

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules.

BACKGROUND: The impact of oncogene panel results on the surgical management of indeterminate thyroid nodules (ITNs) is currently unknown. METHODS: Surgical management of 649 patients consecutively evaluated from October 2008 to April 2016 with a single nodule biopsied and indeterminate cytology (193 evaluated with and 456 without oncogene panels) was assessed and compared. Histological features of 629 consecutively resected ITNs (164 evaluated with and 465 without oncogene panels) were also characterized and compared. RESULTS: Oncogene panel evaluation was associated with higher rates of total thyroidectomy (45% vs 28%; P = .006), and central lymph node dissection (19% vs 12%; P = .03) without increasing the yield of malignancy or decreasing the rate of completion thyroidectomy. Most malignancies (64%), including 83% of those with driver mutation identified, were low-risk cancers for which a lobectomy could have been sufficient initial treatment. CONCLUSION: Current oncogene panel results seem insufficient to guide the surgical extent of solitary ITNs.

Association of Tumor Size With Histologic and Clinical Outcomes Among Patients With Cytologically Indeterminate Thyroid Nodules.

Importance: Tens of thousands of unnecessary operations are performed each year for diagnostic purposes among patients with cytologically indeterminate thyroid nodules. Whereas a diagnostic lobectomy is recommended for most patients with solitary indeterminate thyroid nodules, a total thyroidectomy is preferred for nodules larger than 4 cm. Objective: To determine whether histologic or clinical outcomes of indeterminate thyroid nodules 4 cm or larger are worse than those for nodules smaller than 4 cm, thus justifying a more aggressive initial surgical approach. Design, Setting, and Participants: In this retrospective cohort study, 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) with surgical follow-up were consecutively evaluated at an academic cancer center from October 1, 2008, through April 30, 2016. Exposure: Tumor size. Main Outcomes and Measures: Differences in cancer rates, rates of invasive features, cancer aggressiveness, and response to therapy between indeterminate thyroid nodules smaller than 4 cm and 4 cm or larger. Results: A total of 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) from 589 patients (mean [SD] age, 53.1 [13.8] years; 453 [76.9%] female) were studied. No differences were found in the baseline characteristics of patients or nodules between the 2 size groups. Tumor size was not associated with the cancer rate as a categorical (140 of 546 [25.6%] for nodules <4 cm and 33 of 106 [31.1%] for nodules ≥4 cm; effect size, 0.05; 95% CI, 0.002-0.12) or continuous (odds ratio [OR], 1.03; 95% CI, 0.92-1.15) variable. No association was found between nodule size and prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, or distant metastasis. Most malignant tumors were low risk in both size groups (70% in the nodules <4 cm and 72% in the nodules ≥4 cm), and tumor size was not associated with tumor aggressiveness as a categorical (effect size, 0.10; 95% CI, 0.03-0.31) or continuous variable (OR for intermediate-risk cancer, 0.91; 95% CI, 0.72-1.14; OR for high-risk cancer, 1.43; 95% CI, 0.96-2.15). At the last follow-up visit, 88 of 105 patients (83.8%) with malignant tumors in the smaller than 4 cm group and 21 of 25 (84.0%) in the 4 cm or greater group had no evidence of disease, and tumor size was not associated with response to therapy (effect size, 0.13; 95% CI, 0.07-0.33). Conclusions and Relevance: Most indeterminate thyroid nodules are benign or low-risk malignant tumors regardless of tumor size. In the absence of other indications for total thyroidectomy, this study suggests that a thyroid lobectomy is sufficient initial treatment for most solitary cytologically indeterminate thyroid nodules independent of the tumor size.

Cancer Risk Associated with Nuclear Atypia in Cytologically Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis.

BACKGROUND: Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios that are generally clustered for analysis and management recommendations. It has been suggested that aspirates exhibiting nuclear atypia have a higher risk of malignancy. This study aimed to assess whether cytologically indeterminate thyroid nodules with nuclear atypia have a significantly higher cancer risk than those without nuclear atypia. METHODS: On June 30, 2016, PubMed and EMBASE were searched for articles in English or Spanish using a search strategy developed by an endocrinologist and a librarian. Case reports were excluded, and no date limits were used. The references of all included studies were also screened for relevant missing studies. Studies were included if the prevalences of malignancy of cytologically indeterminate thyroid nodules with histological confirmation with and without nuclear atypia were reported. Studies were excluded if they had: (i) nodules suspicious for malignancy; (ii) nodules with non-indeterminate (B-III or B-IV) cytology on repeated biopsy, if performed; (iii) nodules not consecutively evaluated; or (iv) cohorts overlapping with another larger series. Two investigators independently assessed the eligibility and risk of bias of the studies. PRISMA and MOOSE guidelines were followed. Summary data were extracted from published reports by one investigator and independently reviewed by another. Data were pooled using a random-effects model. Heterogeneity was explored using subgroup analysis and mixed-effect model meta-regression. The odds ratio for malignancy of cytologically indeterminate thyroid nodules with nuclear atypia over cytologically indeterminate thyroid nodules without nuclear atypia was calculated. RESULTS: Of 2571 retrieved studies, 20 were eligible. The meta-analysis was conducted on summary data of 3532 cytologically indeterminate thyroid nodules: 1162 with and 2370 without nuclear atypia. The odds ratio for malignancy in cytologically indeterminate thyroid nodules with nuclear atypia was 3.63 [confidence interval 3.06-4.35]. There was no evidence of publication bias, and heterogeneity was insignificant (I2 < 0.01%, p = 0.40). CONCLUSIONS: Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.

Patient choice for high-volume center radiation impacts head and neck cancer outcome.

BACKGROUND: Studies suggest treatment outcomes may vary between high (HVC)- and low-volume centers (LVC). Radiation therapy (RT) for head and neck cancer (HNC) requires weeks of treatment, the inconvenience of which may influence a patient's choice for treatment location. We hypothesized that receipt of RT for HNC at a HVC would influence outcomes compared to patients evaluated at a HVC, but who chose to receive RT at a LVC. METHODS: From 1998 to 2011, 1930 HNC patients were evaluated at a HVC and then treated with RT at either a HVC or LVC. Time-to-event outcomes and treatment factors were compared. RESULTS: Median follow-up was 34 months. RT was delivered at a HVC for 1368 (71%) patients and at a LVC in 562 (29%). Patients were more likely to choose HVC-RT if they resided in the HVC's county or required definitive RT (all P < 0.001). HVC-RT was associated with a significant improvement in 3-year LRC (84% vs 68%), DFS (68% vs 48%), and OS (72% vs 57%) (all P < 0.001). On multivariate analysis (MVA), HVC-RT independently predicted for improved LRC, DFS, and OS (all P < 0.05). CONCLUSIONS: In patients evaluated at a HVC, the choice of RT location was primarily influenced by their residing distance from the HVC. HVC-RT was associated with improvements in LRC, DFS, and OS in HNC. As treatment planning and delivery are technically demanding in HNC, the choice to undergo treatment at a HVC may result in more optimal delivered dose, RT duration, and outcome.

Infrequent mutation of ATBF1 in human breast cancer.

Deletion at chromosome 16q is frequent in prostate and breast cancers, suggesting the existence of one or more tumor suppressor genes in 16q. Recently, the transcription factor ATBF1 at 16q22 was identified as a strong candidate tumor suppressor gene in prostate cancer, and loss of ATBF1 expression was associated with poorer prognosis in breast cancer. In the present study, we examined mutation, expression, and promoter methylation of ATBF1 in 32 breast cancer cell lines. Only 2 of the 32 cancer cell lines had mutations, although 18 nucleotide polymorphisms were detected. In addition, 24 of 32 (75%) cancer cell lines had reduced ATBF1 mRNA levels, yet promoter methylation was not involved in gene silencing. These findings suggest that ATBF1 plays a role in breast cancer through transcriptional downregulation rather than mutations.

Sigmoid sinus diverticulum: a new surgical approach to the correction of pulsatile tinnitus.

OBJECTIVE: Tinnitus represents a bothersome symptom not infrequently encountered in an otology practice. Tinnitus can be the harbinger of identifiable middle or inner ear abnormality; but more frequently, tinnitus stands alone as a subjective symptom with no easy treatment. When a patient complains of tinnitus that is pulsatile in nature, a thorough workup is indicated to rule out vascular abnormality. We report of a new diagnostic finding and method of surgical correction for select patients with pulsatile tinnitus. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care, academic referral center. PATIENTS: Among patients seen for complaints of unilateral or bilateral pulsatile tinnitus, five were identified with diverticula of the sigmoid sinus. All patients had normal in-office otoscopic, tympanometric, and audiometric evaluations. Patients with paragangliomas or benign intracranial hypertension were excluded. Auscultation of the pinna or mastoid revealed an audible bruit in most patients. All patients underwent computed tomographic angiography of the temporal bone. In all cases, this finding was on the side coincident with the tinnitus. INTERVENTION: Three of five patients underwent transmastoid reconstruction of the sigmoid sinus. MAIN OUTCOME MEASURE: Patients were evaluated clinically for presence or absence of pulsatile tinnitus after reconstructive surgery. RESULTS: All patients electing surgical reconstruction had immediate and lasting resolution of the tinnitus. CONCLUSION: Surgical reconstruction can provide lasting symptom relief for patients with pulsatile tinnitus and computed tomographic evidence of a sigmoid sinus diverticulum.

Correlation of the Voice Handicap Index (VHI) and the Voice-Related Quality of Life Measure (V-RQOL).

The purpose of this study was to investigate the correlation between the Voice Handicap Index (VHI) and the Voice-Related Quality of Life Measure (V-RQOL), and to test conversion of scores between the two instruments. Understanding the relationship between instruments will facilitate comparison of voice outcome studies using different measures. A retrospective medical chart review of 140 consecutive patients with a chief complaint related to their voice presenting for speech pathology voice evaluation following laryngology evaluation and diagnosis was adopted. Each patient who filled out the VHI and V-RQOL within a 2-week period with no intervening treatment was included in the study. Correlation analysis for total scores was performed for the patients meeting inclusion criteria (n=132). Correlations were also performed as a function of diagnosis. Calculated VHI score based on measured V-RQOL score was compared to measured VHI score. Pearson correlation between scores on the VHI and V-RQOL was -0.82. There was no significant difference between the mean measured and mean calculated VHI scores. For individual scores, however, regression analysis did reveal a significant difference between calculated and measured VHI. The VHI and V-RQOL are highly correlated; however, this study suggests that the two instruments are not interchangeable for individuals.