A 20-year observational cohort of a 5 million patient population-Tonsillectomy rates in the context of two national policy changes.

AIM: (a) To report national trends for tonsillectomy, tonsillitis, peritonsillar abscess and deep neck space infection in secondary care. (b) To report national trends in sore throat consultations in primary care. (c) To report national trends in antibiotic prescribing in both primary and secondary care between 2011 and 2015. DESIGN: Retrospective nationwide cohort study. Data requested from Information Statistics Department (ISD) Scotland for tonsillectomy, tonsillitis admissions, peritonsillar abscess admissions and deep neck space infection (DNSI) admissions in Scotland, between 1993/94 and 2015/16. Data for antibiotic prescriptions in general practice and hospital admissions between 2011 and 2015. SETTING: Scottish ENT departments and GP practices. PARTICIPANTS: Scottish patients who underwent tonsillectomy or were admitted to hospital with tonsillitis, peritonsillar abscess or deep neck space infection. Scottish patients that attended their GP with tonsillitis. RESULTS: Tonsillectomy rates between 1993/94 and 2015/16 decreased by 48% (P < 0.001). Over the same time period, there has been a corresponding 136% increase in tonsillitis admission (P < 0.001) and a 167% increase in peritonsillar abscess admissions, (P < 0.001). Between 1996/97 and 2015/16, there was a 500% increase in deep neck space abscesses (P < 0.001). CONCLUSION: There has been a significant decrease in tonsillectomy rates over the past two decades. Over the same time period, there has been a significant increase in admissions to secondary care with tonsillitis, peritonsillar abscess and deep neck space infection. These changes have happened in the context of two separate national policies being introduced-Scottish Intercollegiate Guideline Network (SIGN) guidelines for management of sore throat and the Scottish Reduction in Antibiotic Prescribing.

Transforming growth factor-ß directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas.

c-Myc transformed human Burkitt's lymphoma (BL) cells are highly sensitive to TGF-ß-induced apoptosis. Previously we demonstrated that TGF-ß-mediated cell death in BL cells is regulated via the mitochondrial intrinsic apoptosis pathway, which is dependent on the activation of BAX and/or BAK. TGF-ß directly induces transcription of the BH3-only protein BIK and represses expression of the pro-survival factor BCL-X(L) but has no effect on the direct BAX/BAK "activators" BIM or BID (tBID). Here we show that TGF-ß induces the BH3-only activator PUMA to aid induction of the intrinsic cell death pathway. TGF-ß also induced PUMA in normal germinal center CD77-positive centroblasts isolated from human tonsil tissue. PUMA was a direct TGF-ß target gene in B-cells, and we identify a putative Smad-binding region within the human PUMA promoter that recruits Smad3 and Smad4 in cells in response to TGF-ß signaling. Constitutive activity of the isolated Smad-binding region in luciferase reporter assays was dependent on Smad consensus sequences and was partially dependent on endogenous TGF-ß signaling and Smad4. Knockdown of PUMA in BL cells using lentiviral shRNA resulted in slower kinetics of the TGF-ß-mediated apoptotic response. Analysis of Eµ-Myc cell lines demonstrated that c-myc-driven murine lymphomas are also sensitive to TGF-ß-mediated apoptosis. Moreover, Puma(-/-) Eµ-Myc lines demonstrated significantly delayed kinetics of the apoptotic response when compared with wild type lymphomas. TGF-ß therefore induces a polygenic response in Myc-driven lymphomas involving transcription of PUMA, which is necessary for the rapid induction of cell death.

Investigation of serum calcium and vitamin D levels in superior semicircular canal dehiscence syndrome: A case control study.

Objective: It remains unknown whether calcium metabolism has any effect on the clinical presentation of superior semicircular canal dehiscence (SSCD). Our aim was to analyse the adjusted calcium and vitamin D levels in SSCD patients compared to a control group. Methods: This was a prospective case-control study performed in a tertiary referral center, university teaching hospital in the UK. It included all new patients with SSCD seen in a dedicated skull base clinic over a 5-year period (2015-2019) compared to a gender and age matched control group. The main outcome of the study was adjusted calcium and Vitamin D levels between the two groups. Results: A total of 31 SSCD patients were recruited with a matched number of control patients. The mean Vitamin D level on the SSCD group was 44.8 nmoL/l (SD: 20.8) compared to 47.5 nmoL/l (SD: 27.4) on the control group (p = 0.702). Mean Adjusted calcium level was 2.34 mmoL/l (SD: 0.7) for SSCD compared to 2.41 mmoL/l (SD: 0.11) for controls (p = 0.01), being within normal limits for both the SSCD and the control group. Conclusion: Our study did not identify a link between Vitamin D levels and presence of SSCD. Normal adjusted calcium values were found in both groups. Despite that a statistically significant lower calcium level was found in the SSCD group which could indicate that suboptimal levels of calcium may affect the micro-environment of the otic capsule at the SSC region.

Hemoglobin monitoring in head and neck cancer patients undergoing radiotherapy.

OBJECTIVES: Anemia is a well-recognized factor for local recurrence and decreased survival in cancer patients undergoing radiotherapy. Additionally, lower hemoglobin (Hb) levels have a negative impact on radiotherapy efficacy and response rates. The objective of this audit was to investigate how frequently Hb levels were observed in head and neck cancer patients receiving radiotherapy within a multidisciplinary team setting. METHODS: We performed a retrospective first-cycle audit in a university hospital in Glasgow that is a tertiary referral center for head and neck cancer. Included were 78 patients with head and neck cancer who were undergoing radiotherapy. Online laboratory services and clinical case sheets were checked for each patient to monitor the frequency of observation of Hb levels before, during, and after radiotherapy. RESULTS: Of these 78 patients, only 49 had their Hb level checked before radiotherapy treatment, only 9 during radiotherapy, and only 27 after completion of radiotherapy treatment (p < 0.0001). Of the 49 patients with preradiotherapy Hb levels available, 24% were found to be anemic; none of these patients had their Hb monitored during radiotherapy, and only 4 had Hb levels recorded after completion of treatment. CONCLUSIONS: This audit has highlighted that despite evidence emphasizing that anemia in cancer is an independent prognostic factor for recurrence, there is no formal protocol for Hb monitoring in head and neck cancer patients undergoing radiotherapy. The audit has also demonstrated that Hb monitoring is infrequently performed and that subsequent observation of the Hb level is suboptimal.

Gamma tubulin: a promising indicator of recurrence in squamous cell carcinoma of the larynx.

OBJECTIVE: Centrosome amplification as detected by gamma tubulin (GT) immunostaining is associated with genetic instability and tumor aggressiveness. We assessed GT for its ability to predict recurrence of squamous cell carcinoma of the larynx (SCCL). STUDY DESIGN: Case series with chart review. MATERIALS AND METHODS: Five micron sections of 35 archival SCCL samples were subjected to antigen retrieval and immunostaining with antibody to GT. The keratin antibody CK5 served as a positive control for antigen retrieval, and tonsillar tissue was used as a negative control. RESULTS: Of the 35 tumors analyzed, 22 were associated with recurrence(R) and 13 were not (NR). Fourteen of the 22 R tumors, but 0 of 13 of the NR tumours had a GT staining score of 2+ or 3+ (P < 0.0002). GT was also related to recurrence in node-negative tumors (P < 0.006) but was unrelated to T stage (P = 0.726). CONCLUSIONS: GT staining appears to be a better predictor of tumor recurrence than T stage and also predicts recurrence in N0 tumors.

Life threatening hemorrhage from osteoradionecrosis of the ribs and clavicle.

Osteoradionecrosis (ORN) is a familiar complication of radiotherapy. ORN of the clavicle and ribs is well documented after radiation therapy for breast and pulmonary malignancy. ORN of the clavicle after radiation therapy to the neck is very rare. We report the first case in which both clavicles and first ribs underwent ORN 14 years after neck irradiation and surgery for laryngeal malignancy. The presentation was atypical; erosion of the right internal mammary artery causing life-threatening hemorrhage. Otolaryngologists should be aware that ORN can occur at an unusual site and can have an atypical presentation.

Emergency department care of a patient after a total laryngectomy.

Patients who have undergone a total laryngectomy have altered anatomy and physiology. This results in unique and specific issues that must be recognized in order to ensure that this group of patients experience appropriate care. This article looks at the current literature and attempts to highlight specific areas of concern, so that emergency care providers can deliver an equally high standard of care to this patient group as they do to others. A Medline and Google scholar search was conducted using phrases associated with the complications of total laryngectomy. The results were analyzed to identify the most relevant articles that meet our objective. Articles were then organized into the different subheadings used within the article and reviewed. The most up-to-date articles or those that were in the opinion of the authors the most appropriate to convey our objective were included in our review.

Unintended benefits of immunosupression on autoimmune disease due to chemoradiation therapy for head and neck cancer.

The immune system is an important factor in the host's defenses against cancer. Immunosupression by radiation and/or chemotherapy is often associated with systemic and hematologic complications, opportunistic infections, and the development of malignancies, but immunosupression can also have beneficial effects, which are sometimes incidental. We report 2 patients with autoimmune diseases where immunosupression had beneficial effects. The first case is about a patient with carcinoma of the tonsil, with severe rheumatoid arthritis, who was treated with chemoradiation, which resulted in remission of his arthritis. The second case is about a patient with severe atopic eczema who was on long-term treatment with psoralen and ultraviolet A radiation and azathioprine; the patient developed metastatic carcinoma of the lip, which was treated with surgery and radiation that resulted in complete remission of his eczema.

Telomerase inhibition and the future management of head-and-neck cancer.

Telomeres are tandem repeats of DNA associated with specific proteins. These structures cap eukaryotic chromosomes and maintain the integrity of the chromosome ends. In the germline, telomeres are maintained by the enzyme telomerase, but in normal somatic cells the enzyme's activity is low or undetectable. Human tumours, including squamous-cell carcinoma of the head and neck (SCCHN), need telomerase to maintain telomere function; inhibition of the enzyme can lead to apoptosis. Furthermore, because most tumour cells have very short telomeres, they are more likely to succumb to telomerase inhibition than normal cells. Telomerase is therefore a potential selective anticancer target. The telomere is also involved in the repair of DNA double strand breaks, and telomere dysfunction provokes radiosensitivity. In this review we consider whether manipulation of telomere function may selectively sensitise SCCHN to radiotherapy and discuss the possible pitfalls. We also assess how some conventional treatments may affect the subsequent use of telomerase inhibitors.