HPV overtakes smoking as the leading cause of oropharyngeal cancer in Ireland: experience of a head and neck surgery tertiary referral centre.

BACKGROUND: Worldwide, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV), a sexually transmitted virus, is increasing. This increase has yet to be demonstrated in an Irish cohort. AIMS: To evaluate the number of OPSCC presentations locally, to stratify cases by HPV status and to estimate if any changes in the patient population had occurred over a 10-year period. METHODS: A STROBE-compliant, retrospective evaluation of patients with OPSCC at St James's Hospital between 2012 and 2022 was performed. Patients with non-SCC histology, undocumented HPV status and residual or recurrent tumours were excluded. RESULTS: We included 294 patients with a mean age of 60.4 years (95% CI 59.2-61.5 years) and 175 (59.5%) patients had HPV+ OPSCC. The number of new OPSCC diagnoses increased from 115 patients (39.1%) between 2012 and 2016 to 179 patients (60.9%) between 2017 and 2021. This was associated with an increased proportion of HPV-linked OPSCC (50.4% 2012-2016 vs. 65.4% 2017-2021, p = 0.011). Over time, more patients had a functionally limiting comorbidity (p = 0.011). The mean age of HPV+ OPSCC cases increased by 3.6 years (p = 0.019). Patients with HPV+ OPSCC had greater 2-year OS (83.9% vs. 54.9%; p < 0.001) and 2-year DFS (73.5% vs. 45.6%; p < 0.001). The 2-year OS and DFS did not change over time for HPV+ or HPV- patients. CONCLUSIONS: In our institution, the number of patients with OPSCC is increasing due to an escalation in cases associated with HPV. Population-level interventions such as vaccination programs may alter the current increase in the incidence of these tumours.

Fatal cerebritis and ventriculitis secondary to tracheoesophageal prosthesis.

Tracheoesophageal puncture and voice prosthesis placement is the preferred method of voice restoration following total laryngectomy. Although this is a safe and effective means of optimizing voice, severe complications can occur. We present the case of a patient who developed cerebritis and ventriculitis secondary to a tracheoesophageal prosthesis eroding his cervical vertebrae 20 years following pharyngo-laryngo-esophagectomy. Despite optimal antimicrobial therapy, he deteriorated and succumbed to his disease. Although tracheoesophageal prostheses are a safe and effective means of voice restoration, life-threatening complications can occur. This case report highlights a rare but severe case of cervical osteomyelitis, epidural abscess, and cerebritis and ventriculitis secondary to tracheoesophageal prosthesis. Clinicians must be aware of this severe complication in postlaryngectomy patients with tracheoesophageal prostheses.

The role of surgery for anaplastic thyroid carcinoma in the era of targeted therapeutics: A scoping review.

Background: Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant-targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods: A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results: The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) (<9 months in the 12 studies using a combination of surgery and chemoradiotherapy). In the three studies utilizing targeted therapy in addition to surgery, OS was notably improved while surgical resection following neoadjuvant therapy was less extensive. Conclusions: There is no clear agreement in the literature regarding the limits of surgical resection in locoregionally advanced ATC. A definition of surgically resectable disease will be required to guide surgical decision making in ATC, particularly with the potential to reduce tumor burden using neoadjuvant targeted treatment in suitable patients. Level of evidence: III.

Training in Endoscopic Ear Surgery: A Scoping Review.

OBJECTIVE: Despite the increasing popularity of Endoscopic Ear Surgery (EES), there is a lack of evidence to guide trainees as they introduce EES into practice. This review aims to evaluate training in EES including the optimal introductory procedures, methods of training, the learning curve, and the determination of competency in EES. In addition, this review seeks to identify any areas falling within these themes requiring further clarification. DATA SOURCES: A database search of Pubmed, Embase and the Cochrane Library was conducted in June 2022. Original articles, systematic reviews, and meta-analyses reporting on training in EES, introduction into practice, learning curves, and competency assessment were included. REVIEW METHODS: A scoping review was carried out in accordance with the Joanna Briggs Institute guidelines and reported according to PRISMA guidelines for scoping reviews. A qualitative assessment of results grouped thematically was performed. RESULTS: Twenty-eight studies met the inclusion criteria, with 24 rating as "fair" or "good" on quality assessment. Surgical simulation was the most frequently described method of training as utilized in 11 studies. The most suggested introductory procedure was tympanoplasty which was advocated for in five studies. Heterogeneity existed in the outcomes and methodologies used to measure EES learning curves, with an overreliance on surgical times. No robust definition of competency in EES procedures exists at present. CONCLUSIONS: Surgical simulation appears to be a beneficial training methodology for EES. However, there is a marked lack of objective data to describe the optimal introductory procedures or assessment of competency in EES. Laryngoscope, 133:3269-3278, 2023.

Trans-canal tragal cartilage myringoplasty; a comparative analysis of endoscopic and microscopic approaches.

BACKGROUND: The advent of Endoscopic Ear Surgery (EES) has allowed otologists an improved view of the surgical field compared with conventional Microscopic Ear Surgery (MES). EES presents different challenges for surgeons and a learning curve is necessary. AIMS: The purpose of this study was to compare the efficacy of EES and MES for trans-canal tragal cartilage myringoplasty, an entry level EES. METHODS: We retrospectively analysed patients who underwent push through trans-canal tragal cartilage myringoplasty in our institution over 5 years (2016-2020). Exclusion criteria were: patients with prior ear surgery, non-tragal cartilage tympanic membrane graft, additional procedure at time of surgery and patients with insufficient follow up. EES and MES groups were compared using outcomes such as graft success rate, changes in pure tone audiometry (PTA), operative time and complications. RESULTS: Seventy-four patients met inclusion criteria (MES = 38, EES = 36). Mean age of included patients was 29.3 years with no significant demographic differences between groups. Graft success rate at 12 months was higher among the EES group versus MES (94.4% v 86.8%, p = 0.43). Mean operative time was reduced in the EES group (47.3 min v 53.8 min, p = 0.04). Hearing outcomes did not differ significantly between groups. No major operative complications occurred in either group. CONCLUSIONS: Outcomes were marginally better in the cohort who underwent EES. This supports that EES offers an otologic choice to complement established practice for trans-canal myringoplasty and may be used to facilitate introduction to EES for trainees and otologists wishing to learn this technique.

Endoscopic Versus Microscopic Type-1 Tympanoplasty: A Meta-Analysis of Randomized Trials.

OBJECTIVES: Totally endoscopic ear surgery is becoming increasingly utilized in otologic practice. Although the well-established microscope-assisted tympanoplasty remains the most common technique to repair a tympanic membrane defect, the merits of endoscopic approaches have been well-documented. This systematic review and meta-analysis compares the outcomes of endoscopic to microscopic tympanoplasty incorporating only randomized trials. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive search of PubMed/MEDLINE, Scopus, Cochrane Library, and EMBASE was conducted. All randomized studies comparing endoscopic to microscopic tympanoplasty were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Quality assessment was carried out utilizing the Risk of Bias 2. RESULTS: The initial search identified 1711 studies, of which 9 met the inclusion criteria comprising of 540 patients (microscopic tympanoplasty 51.5%; endoscopic tympanoplasty 49.5%). The mean age was 32.5 years with a similar number of males (50.1%) and females (49.9%). Both endoscopic and microscopic groups had comparable outcomes with regards to graft success rate (RD 0.00; 95% confidence interval [CI], -0.04 to. 0.05; p = 0.87) and hearing improvement (MD 0.57 dB; 95% CI, -1.23 to 2.36; p = 0.54). A significantly shorter operative time was noted in the endoscopic group (MD, -24.73 min; 95% CI, -38.56 to -10.89; p = 0.0005). CONCLUSION: Our results, assimilating level 1 evidence, demonstrates that endoscopic and microscopic-assisted type-1 tympanoplasty have similar outcomes in both graft success and hearing improvement, with endoscopic approaches yielding a shorter operative time. LEVEL OF EVIDENCE: 1 Laryngoscope, 133:1550-1557, 2023.

Clinical decision making in paediatric otitis media: A pilot quality improvement study.

OBJECTIVES: This study aimed to improve local management of paediatric otitis media using the 2022 American-Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) Clinical Practice Guideline for Tympanostomy Tubes in Children. METHODS: A SQUIRE 2.0 compliant quality improvement study was carried out within the outpatient department of our otolaryngology tertiary referral centre. Local outpatient management of paediatric otitis media was compared to the AAO-HNS guidelines, specifically focussing on the decision to offer tympanostomy tubes. Following initial audit of practice, an educational session was performed within the otolaryngology department and local practice was subsequently re-evaluated. RESULTS: Overall, 88 children were included (46 pre-intervention and 42 post-intervention) with a mean age of 7.6 years (range 1-12 years). Sixty-four (72.7%) children presented with suspected otitis media with effusion. The remainder presented with recurrent or persistent acute otitis media (24/88, 27.3%). Twenty-six children were offered tympanostomy tubes (29.5%). Initial evaluation of practice identified that the decision to offer tympanostomy tubes was guideline appropriate in 76.1% of children (35/46). This significantly improved following an educational session (40/42, 95.2%, p = 0.02). The reasons for non-guideline compliance included: otitis media with effusion <3 months, no evidence of middle ear fluid and patients meeting criteria for tympanostomy tube insertion not being offered. CONCLUSIONS: A focussed educational intervention may improve local adherence to guidelines in the management of paediatric otitis media. Continued re-evaluation of local practice is essential in order to ensure children are managed in accordance with the guidelines.

Hypocalcaemia following thyroidectomy among patients who have previously undergone bariatric surgery: systematic review and meta-analysis.

BACKGROUND: Hypocalcaemia is a common complication after thyroidectomy. Bariatric surgery is associated with significant changes in calcium metabolism. Some studies have identified bariatric surgery as a risk factor for hypocalcaemia after thyroidectomy. This systematic review and meta-analysis assessed whether a history of bariatric surgery was associated with an increased risk of hypocalcaemia after thyroidectomy. METHODS: This prospectively registered systematic review (PROSPERO; CRD42021295423) was performed in accordance with PRISMA guidelines. Meta-analysis was undertaken using the Mantel-Haenszel method, with outcomes reported as ORs with 95 per cent confidence intervals. RESULTS: Twenty studies were included in the qualitative synthesis. Five studies incorporating 19 547 patients met the inclusion criteria for meta-analysis, of whom 196 (1.0 per cent) had a history of bariatric surgery. Patients with a history of bariatric surgery were more likely to develop hypocalcaemia after thyroidectomy (30.6 versus 13.0 per cent; OR 3.90, 95 per cent c.i. 1.50 to 10.12; P = 0.005). Among those with a history of bariatric surgery, patients who underwent a bypass procedure were more likely to develop hypocalcaemia after thyroidectomy than those who had a restrictive procedure (38 versus 23 per cent; OR 2.12, 1.14 to 3.97; P = 0.020). CONCLUSION: Patients with a history of bariatric surgery have a significantly greater risk of hypocalcaemia after thyroidectomy, with a heightened risk among those who have had a bypass procedure. Surgeons performing thyroid surgery should be aware of the increased risk of hypocalcaemia after thyroidectomy among these patients.

Low calcium levels are a common complication after surgical removal of the thyroid gland. Patients who have had weight loss surgery (bariatric surgery) have altered calcium metabolism and are prone to low calcium levels. This study assessed whether previous weight loss surgery increased the risk of low calcium levels after thyroid surgery. A search was made of previously published studies assessing the relationship between previous weight loss surgery and low calcium levels after thyroid surgery. Studies have shown that previous weight loss surgery makes patients more than three times more likely to have low calcium levels after thyroid surgery. Management of low calcium in these patients is more challenging than in patients who have not had weight loss surgery. Surgeons performing thyroid surgery need to be aware of whether a patient has previously had weight loss surgery as they have an increased risk of low calcium after thyroid surgery.

The academic impact of 20 years of Irish otolaryngology society conferences.

BACKGROUND: & Purpose: The Irish Otolaryngology Society (IOS) conference takes place annually. This conference allows surgeons and surgical trainees from Ireland and abroad an opportunity to showcase research ideas from their respective centres. This allows them to disseminate results, accept critique, and obtain different perspectives. We sought to examine research presented at the IOS meetings over 20 years. We aimed to analyse the publication rates, impact factor of journals, and citation rates of presented abstracts. METHODS: All oral presentations from IOS conferences were analysed between 2000 and 2019. Presentation titles and authors were searched using Pubmed, Google Scholar and Research Gate. We identified scientific publications which resulted from the research presented and the characteristics of each publication. RESULTS: Of 703 presentations made at the conferences spanning 20 years, 30.15% (n = 212) went on to publish their research averaging 19 citations per publication. Median time to publication was 2 years (-1-11). Each year there have been an increasing number of oral presentations with a declining publication rate. CONCLUSION: The Irish otolaryngology society meeting is a high-quality meeting with comparable publication rates to similar international conferences. Despite this, many presentations do not have any lasting impact as they are not published. The increasing pressure for trainees to rapidly present research projects without emphasis on completion of projects may explain the declining publication rate. Our study highlights the importance of completing high-quality research projects through publication. Meaningful conclusions from these projects can add to the body of knowledge and contribute to evidence-based practice.

Transoral robotic surgery in Ireland: the beginning.

BACKGROUND: Transoral robotic surgery (TORS) has shown promising results in the treatment of myriad head and neck pathologies but is now most commonly used in the investigation and management of oropharyngeal squamous cell carcinoma. AIMS: The aim of this study was to report our cases of the newly introduced TORS, particularly its role in identifying primary of unknown origin and the potential implications for patients. A literature review and our early experience should begin to debunk some of the criticisms of TORS including setup times and cost. METHODS: Prospective data was collected from all patients undergoing transoral robotic surgery including demographics, indication, histology results in primary of unknown origin and complications. RESULTS: We have performed 36 TORS procedures in total ranging from intermediate to major complex. Our complication rate is low, and this has improved with the passage of time. Haemorrhage rates remain at 5.6% (n = 2), and the average length of stay is 1 day. Successful identification of a primary tumour in cancer of unknown primary was 80% (n = 8). CONCLUSIONS: We anticipate the integration of TORS into routine practice in the investigation and management of a number of ENT pathologies following robust clinical trials.

The psychological impact of COVID-19 on ear, nose and throat (ENT) specialists.

INTRODUCTION: Ear, nose and throat (ENT) specialists are a high-risk group for COVID-19. Although the implications of SARS-CoV-2 infection on physical health are well-documented, the psychological impact is frequently overlooked. AIMS: The aim of this study was to gauge the psychological impact of COVID-19 on ENT specialists in Ireland. METHODS: A national, cross-sectional, web-based survey was distributed to ENT specialists during the peak of the COVID-19 pandemic (21st May 2020-21st June 2020). The questionnaire collected sociodemographic and COVID-19 related data. The GAD-7 was utilized to measure symptoms of clinically significant anxiety disorder. RESULTS: Thirty-eight ENT specialists (M/F:24/12, median age, 38.7 years (23-60 years)) completed the survey. About 34% (n = 13) of participants screened positive for an anxiety disorder, of which 2 (5%) had moderate symptoms. The majority of participants (n = 32, 84%) felt ENT specialists had increased exposure to SARS-CoV-2 compared with other medical specialties. Additionally, 32% (n = 12) felt incapable of protecting themselves from infection. An encouraging proportion of ENT specialists (n = 22, 58%) were aware of psychological support available from national and institutional organizations. CONCLUSIONS: The long-term psychological sequelae of COVID-19 will be felt as the physical burden eases. As we adjust to new normalities, ENT surgeons must be conscientious of the mental health issues that arise from the working environment. Sources of anxiety emanated from a lack of control over infection risk, increased vulnerability to COVID-19 relative to other specialties and the implications this has for ENT specialists and their families. Future interventions must focus on increasing awareness of the available psychological support services for our healthcare workers.

Twin pathologies: synchronous leiomyosarcoma and squamous cell carcinoma of the larynx.

The synchronous discovery of leiomyosarcoma (LMS) and squamous cell carcinoma (SCC) of the larynx is extremely rare. We describe our experience of managing a patient with this unusual presentation. A 35-year-old man was initially diagnosed with advanced stage (T4bN1M0) laryngeal LMS. Neoadjuvant sarcoma-directed chemotherapy and radiation therapy allowed a successful pharyngolaryngo-oesophagectomy to be performed in an otherwise inoperable cancer. Histological examination of the resection specimen revealed poorly differentiated SCC, indicating the underlying diagnosis was a sarcomatoid carcinoma of the larynx. Considering our limited experience of managing synchronous LMS and SCC of the larynx, it is important to carefully evaluate the natural history, route of spread and pathological characteristics of both tumours, when determining treatment.

Sexual Behaviour and Human Papillomavirus-Positive Oral Cavity and Oropharyngeal Cancer: An Irish Perspective.

Background Characterization of the sexual behaviours and lifestyle factors associated with human papillomavirus (HPV)-positive oral cavity and oropharyngeal squamous cell carcinoma (OPSCC) is crucial to optimal counselling. Our study aims to investigate the relationship between sexual behaviours, lifestyle factors and HPV-positive OPSCC in an Irish population. Methods We performed a case-control study of 60 patients with newly diagnosed HPV-positive and HPV-negative oral cavity and OPSCC. Results Oral sexual activity was more common in the HPV-positive tumour subgroup; however, this association was insignificant on multivariate analysis. No association between age of onset of sexual activity, number of sexual partners or practicing anal sex and HPV-positivity was found. The HPV-positive tumour subgroup had significantly less tobacco use than their HPV-negative counterparts (OR 0.93, 95% CI 0.90-0.97). Conclusion The emergence of HPV-positive OPSCC means head and neck surgeons must adopt new roles as counsellors of sexually transmitted disease, in addition to their previous role of delivering a cancer diagnosis.

Activation of the NFAT-Calcium Signaling Pathway in Human Lamina Cribrosa Cells in Glaucoma.

Purpose: Optic nerve cupping in glaucoma is characterized by remodeling of the extracellular matrix (ECM) and fibrosis in the lamina cribrosa (LC). We have previously shown that glaucoma LC cells express raised levels of ECM genes and have elevated intracellular calcium ([Ca2+]i). Raised [Ca2+]i is known to promote proliferation, activation, and contractility in fibroblasts via the calcineurin-NFAT (nuclear factor of activated T-cells) signaling pathway. In this study, we examine NFAT expression in normal and glaucoma LC cells, and investigate the effect of cyclosporin A (CsA, a known inhibitor of NFAT activity) on [Ca2+]i and ECM gene expression in normal and glaucoma LC cells. Methods: [Ca2+]i was measured with dual-wavelength Ca2+ imaging and confocal microscopy using Fura-2-AM and Fluo-4 under physiological isotonic and hypotonic cell stretch treatment. Human donor LC cells were cultured under normal physiological conditions or using a glaucoma-related stimulus, oxidative stress (H2O2, 100 µM), for 6 hours with or without CsA. NFATc3 protein levels were examined using Western blot analysis. Profibrotic ECM gene transcription (including transforming growth factor-ß1 [TGFß1], collagen 1A1 [Col1A1], and periostin) was analyzed using quantitative real time RT-PCR. Results: Basal and hypotonic cell membrane stretch-induced [Ca2+]i were significantly (P < 0.05) elevated in glaucoma LC cells compared to normal controls. There was a significant delay in [Ca2+]i reuptake into internal stores in the glaucoma LC cells. NFATc3 protein levels were increased in glaucoma LC cells. CsA (10 µM) significantly inhibited the H2O2-induced expression of NFATc3 in normal and glaucoma LC cells. CsA also reduced the H2O2-induced NFATc3 dephosphorylation (and nuclear translocation), and also suppressed the H2O2-induced elevation in profibrotic ECM genes (TGFß1, Col1A1, and periostin), both in normal and in glaucoma LC cells. Conclusions: Intracellular Ca2+ and NFATc3 expression were significantly increased in glaucoma LC cells. CsA reduced the H2O2-induced enhancement in NFATc3 protein expression and nuclear translocation and the profibrotic gene expression both in normal and in glaucoma LC cells. Therefore, targeting the calcineurin-NFATc3 signaling pathway may represent a potential avenue for treating glaucoma-associated LC fibrosis.

Post mortem study of the depth and circumferential location of sympathetic nerves in human renal arteries--implications for renal denervation catheter design.

OBJECTIVES: The aims of this study were to examine human renal arteries and to accurately characterize their sympathetic innervation and location using CD-56 immunohistochemistry stains to highlight Neural Cell Adhesion Molecules (N-CAM). BACKGROUND: Porcine models have often formed the basis for design of denervation technology, with only a limited number of human studies available to detail the complex microarray of renal sympathetic nerves. METHODS: Post-mortem renal arteries (N = 14) were harvested and prepared into three sections (proximal, mid, and distal), and then stained using Hematoxylin and Eosin, followed by immunohistochemistry to characterize the expression of CD-56 renal neural tissue. Digital micro calipers were then used to measure the nerve distances and locations within the vessels. RESULTS: (i) Approximately 77% of nerves are located between 0.5 and 2.5 mm from the tunica intima layer, with 22.5% occurring in the 2.5-5.0 mm range, (ii) nerve bundles occur in 3-dimensional arborized arrays, (iii) the nerve bundles are evenly distributed throughout the proximal and distal vessel in this human study. Thickness of vessel wall correlated with proximity of the nerve bundles (r = 0.74, P < 0.01), and nerve bundle thickness (r = 0.62, P = 0.04). The larger the internal and external diameters and areas of the vessel were, the further the distance to the nearest nerve bundles were (r = 0.752, P =<0.01). CONCLUSIONS: In human renal arteries with larger diameters and thicker vessel parenchyma, the innervation is found further from the lumen, and the nerves increase in thickness. This has implications for catheter and system design, as well as depth and duration of energy required for effective ablations. Effective percutaneous transluminal denervation procedures in this population would need to be circumferential rather than interrupted, and to mediate tissue damage to depths beyond 2.5 mm from the tunica intima.

IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis.

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.

Discrepancies between clinical and autopsy diagnosis in liver transplant recipients - a case series.

The utility of the autopsy in patients who have undergone prior orthotopic liver transplantation (OLT) has not previously been defined. We sought to investigate the role of the autopsy in liver transplantation by comparing the clinically derived cause of death with the autopsy cause of death in a cohort of liver transplant recipients at our institution. This study was undertaken in the setting of declining autopsy rates worldwide. Between 2006 and 2011 twenty-nine patients died who had previously undergone OLT, of on whom 19 postmortem examinations were performed. We retrospectively reviewed all post mortem findings, and separately we examined the corresponding medical records to determine the clinical impression of the cause of death. Discrepancies between the post mortem and clinical findings were categorised according to a modification of Goldman's criteria. Our case series demonstrated a discrepancy between the clinical and post mortem examination (PME) findings in 54% of patients. Two patients had major diagnoses (Goldman Class 1) not detected clinically and in seven patients the PME revealed additional undetected minor diagnoses. This case series demonstrates that, even in the modern era of advanced diagnostic imaging techniques, the post mortem examination continues to be a valuable tool in confirming diagnostic accuracy and improving standards in the care of liver transplant recipients.

Idiopathic lymphocytic pleuritis: radiographic and high-resolution CT appearances and changes in response to therapy in two adults.

Inflammatory conditions of the pleura characterized by a predominantly lymphocytic infiltrate are described in several disorders. The commonest underlying aetiologies include tuberculous infection, autoimmune disorders (particularly Sjogren's syndrome), and post coronary artery bypass graft surgery. Idiopathic lymphocytic pleuritis (ILP) is a rare form of diffuse pleural inflammation characterized by extensive lymphocytic infiltration for which no cause is found. Radiological descriptions of ILP are limited. We describe the radiographic and high-resolution computed tomography (HRCT) imaging features and response to corticosteroid therapy of ILP in two adults. Both patients presented with bilateral diffuse pleural thickening of >10 mm thickness extending >10 cm craniocaudally with small focal areas of atelectasis. Both cases demonstrated marked improvement in the degree and extent of pleural thickening and rounded atelectasis following corticosteroid therapy. HRCT provided a useful noninvasive method of assessing disease response to therapy.

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Coassociation of estrogen receptor and p160 proteins predicts resistance to endocrine treatment; SRC-1 is an independent predictor of breast cancer recurrence.

PURPOSE: This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. EXPERIMENTAL DESIGN: The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. RESULTS: Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). CONCLUSIONS: SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.