A 'chemical help' in middle-ear surgery? A systematic review on sodium 2-mercaptoethanesulfonate.

OBJECTIVE: Sodium 2-mercaptoethanesulfonate (Mesna) has been proposed as a chemical aid in any surgical procedure, including cholesteatoma surgery. This review investigated the benefits and safety of Mesna during surgical management of cholesteatoma and adhesive otitis media. METHOD: A systematic literature review was performed to identify clinical studies evaluating topical Mesna application during ear surgery (cholesteatoma or atelectasis). A qualitative analysis based on data extracted was conducted. RESULTS: From 27 articles, 5 retrospective studies were selected for a full analysis for a total of 607 patients (aged 5 to 72 years). Three studies evaluated cholesteatoma recidivism after Mesna application during cholesteatoma surgery, one study evaluated the surgical success rate of Mesna application for the treatment of atelectatic ears and adhesive otitis media, and one study evaluated potential ototoxicity of Mesna during cholesteatoma surgery. All the studies showed overall improvement in recurrence and residual cholesteatoma disease after Mesna application during surgery. Sensorineural hearing loss was not encountered after Mesna application. CONCLUSION: Mesna application in cholesteatoma surgery could represent a valid and safe support tool during surgical treatment carried out both with microscopy and endoscopy. More studies are required to confirm these promising results.

2019 John Insall Award: Fructosamine is a better glycaemic marker compared with glycated haemoglobin (HbA1C) in predicting adverse outcomes following total knee arthroplasty: a prospective multicentre study.

AIMS: The best marker for assessing glycaemic control prior to total knee arthroplasty (TKA) remains unknown. The purpose of this study was to assess the utility of fructosamine compared with glycated haemoglobin (HbA1c) in predicting early complications following TKA, and to determine the threshold above which the risk of complications increased markedly. PATIENTS AND METHODS: This prospective multi-institutional study evaluated primary TKA patients from four academic institutions. Patients (both diabetics and non-diabetics) were assessed using fructosamine and HbA1c levels within 30 days of surgery. Complications were assessed for 12 weeks from surgery and included prosthetic joint infection (PJI), wound complication, re-admission, re-operation, and death. The Youden's index was used to determine the cut-off for fructosamine and HbA1c associated with complications. Two additional cut-offs for HbA1c were examined: 7% and 7.5% and compared with fructosamine as a predictor for complications. RESULTS: Overall, 1119 patients (441 men, 678 women) were included in the study. Fructosamine level of 293 µmol/l was identified as the optimal cut-off associated with complications. Patients with high fructosamine (> 293 µmol/l) were 11.2 times more likely to develop PJI compared with patients with low fructosamine (p = 0.001). Re-admission and re-operation rates were 4.2 and 4.5 times higher in patients with fructosamine above the threshold (p = 0.005 and p = 0.019, respectively). One patient (1.7%) from the elevated fructosamine group died compared with one patient (0.1%) in the normal fructosamine group (p = 0.10). These complications remained statistically significant in multiple regression analysis. Unlike fructosamine, all three cut-offs for HbA1c failed to show a significant association with complications. CONCLUSION: Fructosamine is a valid and an excellent predictor of complications following TKA. It better reflects the glycaemic control, has greater predictive power for adverse events, and responds quicker to treatment compared with HbA1c. These findings support the screening of all patients undergoing TKA using fructosamine and in those with a level above 293 µmol/l, the risk of surgery should be carefully weighed against its benefit. Cite this article: Bone Joint J 2019;101-B(7 Supple C):3-9.

The protympanum, protiniculum and subtensor recess: an endoscopic morphological anatomy study.

OBJECTIVES: An anatomical study was performed to describe the endoscopic anatomy and variations of the protympanum, including classification of the protiniculum and subtensor recess. METHODS: A retrospective review was conducted of video recordings of cadaveric dissections and surgical procedures, which included visualisation of the protympanum, across 4 tertiary university referral centres over a 16-month period. A total of 97 ears were used in the analysis. RESULTS: A quadrangular conformation of the protympanum was seen in 60 per cent of ears and a triangular conformation in 40 per cent. The protiniculum was type A (ridge) in 58 per cent, type B (bridge) in 23 per cent and type C (absent) in 19 per cent. The subtensor recess was type A (absent) in 30 per cent, type B (shallow) in 48 per cent and type C (deep) in 22 per cent. CONCLUSION: The protympanum is an area that has been ignored for many years because of difficulties in visualising it with an operating microscope. However, modern endoscopic equipment has changed this, providing detailed anatomical knowledge fundamental to ensuring the safety of endoscopic surgical procedures in the region.

Can next generation sequencing play a role in detecting pathogens in synovial fluid?

AIMS: The diagnosis of periprosthetic joint infection can be difficult due to the high rate of culture-negative infections. The aim of this study was to assess the use of next-generation sequencing for detecting organisms in synovial fluid. MATERIALS AND METHODS: In this prospective, single-blinded study, 86 anonymized samples of synovial fluid were obtained from patients undergoing aspiration of the hip or knee as part of the investigation of a periprosthetic infection. A panel of synovial fluid tests, including levels of C-reactive protein, human neutrophil elastase, total neutrophil count, alpha-defensin, and culture were performed prior to next-generation sequencing. RESULTS: Of these 86 samples, 30 were alpha-defensin-positive and culture-positive (Group I), 24 were alpha-defensin-positive and culture-negative (Group II) and 32 were alpha-defensin-negative and culture-negative (Group III). Next-generation sequencing was concordant with 25 results for Group I. In four of these, it detected antibiotic resistant bacteria whereas culture did not. In another four samples with relatively low levels of inflammatory biomarkers, culture was positive but next-generation sequencing was negative. A total of ten samples had a positive next-generation sequencing result and a negative culture. In five of these, alpha-defensin was positive and the levels of inflammatory markers were high. In the other five, alpha-defensin was negative and the levels of inflammatory markers were low. While next-generation sequencing detected several organisms in each sample, in most samples with a higher probability of infection, there was a predominant organism present, while in those presumed not to be infected, many organisms were identified with no predominant organism. CONCLUSION: Pathogens causing periprosthetic infection in both culture-positive and culture-negative samples of synovial fluid could be identified by next-generation sequencing. Cite this article: Bone Joint J 2018;100-B:127-33.

Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.

BACKGROUND: Transcriptome profiling has helped characterise nodal spread. The interpretation of these data, however, is not without ambiguities. METHODS: We profiled the transcriptomes of papillary thyroid cancer nodal metastases, associated primary tumours and primary tumours from N0 patients. We also included patient-matched non-cancerous thyroid and lymph node samples as controls to address some limits of previous studies. RESULTS: The transcriptomes of patient-matched primary tumours and metastases were more similar than those of unrelated metastases/primary pairs, as previously reported in other organ systems. This similarity partly reflected patient background. Lymphoid tissues in the metastases confounded the comparison of patient-matched primary tumours and metastases. We circumvented this with an original data adjustment, revealing a differential expression of stroma-related gene signatures also regulated in other organs. The comparison of N0 vs N+ primary tumours uncovered a signal irreproducible across independent data sets. This signal was also detectable when comparing the non-cancerous thyroid tissues adjacent to N0 and N+ tumours, suggesting a cohort-specific bias also likely present in previous similarly sized studies. Classification of N0 vs N+ yielded an accuracy of 63%, but additional statistical controls absent in previous studies revealed that this is explainable by chance alone. We used large data sets from The Cancer Genome Atlas: N0 vs N+ classification was not better than random for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers. CONCLUSIONS: The clinical potential of gene expression to predict nodal metastases seems limited for most cancers.

Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence".

Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas.

BACKGROUND: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts. METHODS: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I. RESULTS: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation. CONCLUSION: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.

A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic.

Differentiation is central to development, while dedifferentiation is central to cancer progression. Hence, a quantitative assessment of differentiation would be most useful. We propose an unbiased method to derive organ-specific differentiation indices from gene expression data and demonstrate its usefulness in thyroid cancer diagnosis. We derived a list of thyroid-specific genes by selecting automatically those genes that are expressed at higher level in the thyroid than in any other organ in a normal tissue's genome-wide gene expression compendium. The thyroid index of a tissue was defined as the median expression of these thyroid-specific genes in that tissue. As expected, the thyroid index was inversely correlated with meta-PCNA, a proliferation metagene, across a wide range of thyroid tumors. By contrast, the two indices were positively correlated in a time course of thyroid-stimulating hormone (TSH) activation of primary thyrocytes. Thus, the thyroid index captures biological information not integrated by proliferation rates. The differential diagnostic of follicular thyroid adenomas and follicular thyroid carcinoma is a notorious challenge for pathologists. The thyroid index discriminated them as accurately as did machine-learning classifiers trained on the genome-wide cancer data. Hence, although it was established exclusively from normal tissue data, the thyroid index integrates the relevant diagnostic information contained in tumoral transcriptomes. Similar results were obtained for the classification of the follicular vs classical variants of papillary thyroid cancers, that is, tumors dedifferentiating along a different route. The automated procedures demonstrated in the thyroid are applicable to other organs.

[Salivary stones and stenosis. A comprehensive classification]. / Lithiases et sténoses salivaires. Une classification pratique des pathologies non tumorales.

INTRODUCTION: Sialendoscopy and sialo-MRI enable diagnosis of salivary gland obstructive pathologies, such as lithiasis, stenosis and dilatations. Therefore, a classification of these pathologies is needed, allowing large series comparisons, for better diagnosis and treatment of salivary pathologies. MATERIAL AND METHODS: With help from people from the European Sialendoscopy Training Center (ESTC), the results of sialographies, sialoMRI and sialendoscopies, a comprehensive classification of obstructive salivary pathologies is described, based on the absence or presence of lithiasis (L), stenosis (S) and dilatation (D) ("LSD" classification). DISCUSSION: It appears that a classification of salivary gland obstructive pathologies should be described. We hope it will be widely used and of course criticized to be improved and to compare the results of salivary gland diagnostic methods, such as sialography and sialendoscopy and also the results and indications for salivary gland therapeutic methods, such as lithotripsy, sialendoscopy and/or open surgery.

Salivary stones and stenosis. A comprehensive classification.

INTRODUCTION: Sialendoscopy and sialoMRI enables diagnosis of salivary gland obstructive pathologies, such as lithiasis, stenosis, and dilatations. Therefore, a classification of these pathologies is needed, allowing large series comparisons, for better diagnosis and treatment of salivary pathologies. MATERIAL AND METHODS: With help from people from the European Sialendoscopy Training Center (ESTC), the results of sialographies, sialoMRI and sialendoscopies, a comprehensive classification of obstructive salivary pathologies is described, based on the absence or presence of lithiasis (L), stenosis (S), and dilatation (D) ("LSD" classification). DISCUSSION: It appears that a classification of salivary gland obstructive pathologies should be described. We hope it will be widely used and of course criticized to be improved and to compare the results of salivary gland diagnostic methods, such as sialography and sialendoscopy, and also the results and indications for salivary gland therapeutic methods, such as lithotripsy, sialendoscopy, and/or open surgery.

Deafness in the developing world: the place of cochlear implantation.

INTRODUCTION: This paper attempts to review changes in the lives of hearing-impaired patients within the developing world, brought about by globalisation and development. The paper also explores limitations to improved care and addresses the collective moral responsibility of developed nations. METHODS: Analysis of literature. RESULTS: Within developing nations, large populations have emerged with a similar pattern of problems, access to information and aspirations as those living in developed nations. However, marked differences in income have persisted. These trends have resulted in a relative increase in the proportion of the hearing-impaired population in need of cochlear implantation, while at the same time restricting their access to such treatment. CONCLUSIONS: The emergence of global markets and media and a shared sense of destiny amongst the people of this planet should translate into a concerted, worldwide effort to assist the deaf in developing countries. Much more can be done within existing resources and frameworks to improve the quality of these peoples' lives.

Characteristics of sinus-related pain.

OBJECTIVES: The goal of this study was to determine possible distinctive features of facial pain when caused by chronic sinusitis and to validate the pain characteristics previously described in the literature. METHODS: Included were 82 patients with radiographic and endoscopic evidence of chronic sinusitis and significant facial pain who underwent functional endoscopic sinus surgery and were available for 1-year follow-up. A modified McGill pain questionnaire was filled out before surgery, and follow-up data were obtained at 1 year. RESULTS: At 1 year 38% of patients had persistent facial pain despite the lack of any evidence of persistent sinusitis. A consistent use of pain adjectives and other distinctive features was noted in patients reporting improvement of headache. There was no correlation between the severity of pain and the extent or location of mucosal disease. The site of pain did not correlate with the site of disease. CONCLUSIONS: Sinusitis-related pain has distinctive features that set it apart from primary headache disorders and other causes of facial pain. Nonsinus causes account for the headache in 1 of 3 patients undergoing sinus surgery.

Endoscopic management of cholesteatoma: long-term results.

OBJECTIVES: This report evaluates long-term results of transcanal endoscopic management and surveillance of cholesteatoma. METHODS: Sixty-nine ears with acquired cholesteatoma underwent endoscopic transcanal tympanotomy and atticotomy to access and completely remove the sac. Reconstruction with a composite tragal graft was performed in 38 ears, and the cavities were packed open in 31 ears. Office-based endoscopic surveillance and follow-up were performed. RESULTS: Forty-three ears were operated on with the patient under local anesthesia, and 58 were done on an outpatient basis. Three cases were converted into postauricular tympanomastoidectomy. There were no iatrogenic facial nerve injuries. Bone thresholds were stable, except in 1 patient with perilymphatic fistula. Mean follow-up was 41 months, and 19 ears underwent 5 years of follow-up. Six ears required revision surgery, and 9 required office-based minor procedures. CONCLUSIONS: An endoscopic technique allows transcanal, minimally invasive management and surveillance of cholesteatoma with long-term results that compare well to those of postauricular methods.

Endoscopic middle ear surgery.

One hundred sixty-five middle ear procedures were performed with an endoscope, a camera, and a video monitor instead of the microscope. The endoscope offers the following advantages: 1) it visualizes the whole tympanic membrane and the ear canal without having to manipulate the patient's head or the microscope, 2) it extends the operative field in transcanal procedures into structures usually hidden from the microscope (anterior tympanic perforation, posterior retraction pocket, facial recess, and hypotympanum), and 3) it visualizes structures from multiple angles as opposed to the microscope's single axis along the ear canal. Disadvantages of the endoscope include the one-handed surgical technique, a loss of depth perception, limited magnification, and the need for training. The endoscope holds the greatest promise in tympanoplasty and cholesteatoma surgery and should increase the utilization of transcanal over postauricular procedures.

Microdebrider-assisted uvulopalatoplasty.

This report describes 3 years' experience with the microdebrider as a safe and reasonable alternative to CO2 laser for uvulopalatoplasty. The cost and compact size of the equipment, as well as the ease of surgery, are the main advantages for microdebrider-assisted surgery.

Endoscopic management of acquired cholesteatoma.

OBJECTIVE: This study aimed to describe and evaluate endoscopic technique for treatment of acquired cholesteatoma. STUDY DESIGN: This study was a case series. SETTINGS: The study was performed in a private otolaryngology practice. PATIENTS: Thirty-eight adult patients with acquired cholesteatoma and no previous ear surgery composed the patient population. INTERVENTION: Thirty-six patients underwent transcanal endoscopic tympanotomy and extended atticotomy with removal of the cholesteatoma sac; the attic defect was reconstructed in 25 patients and was packed open in 11 patients. Two patients underwent traditional postauricular procedures. MAIN OUTCOME MEASURE: The main outcome measure was disease-free ears as evident on: 1) clinical examination at 1 year follow-up for 30 patients and at 2 years for 13 patients; and 2) surgical exploration in 6 patients at 2 years. RESULTS: There were no significant complications associated with the 36 endoscopic procedures: 29 of 30 patients were disease free at 1 year, 10 of 13 were disease free on clinical examination at 2 years, and 4 of 6 were disease free on surgical exploration at 2 years. CONCLUSIONS: Early results indicate that endoscopic removal of cholesteatoma offers a safe and effective transcanal alternative to postauricular procedures.

Transsinus reduction and one-point fixation of malar fractures.

OBJECTIVE: To describe and evaluate transsinus reduction and one-point miniplate fixation of the zygomaticomaxillary buttress for the treatment of tripod malar fractures. DESIGN: A consecutive case series. SETTING: Private otolaryngology practice. PATIENTS: A consecutive sample of 17 patients presenting with isolated tripod malar fractures over a 42-month period. INTERVENTION: A gingivobuccal sulcus incision is made. Access into the maxillary sinus was obtained through an invariably comminuted inferior fracture line. The zygoma was reduced by applying lateral and anterior traction force to the zygomatic recess of the maxillary sinus. Miniplate fixation of the zygomaticomaxillary buttress area was then performed bridging over an area of bone loss and comminution. MAIN OUTCOME MEASURES: Clinical assessment of facial symmetry by patients, physician, and roentgenographic studies. RESULTS: All patients presenting with no comminution of the orbital rim had complete restoration of their premorbid facial symmetry. One of the two patients presenting with comminuted orbital rim had poor results. CONCLUSIONS: This technique is simple, limited, and successful in treating most malar fractures. The lack of comminution of the orbital rim is crucial for the stability of the reduced zygoma. A simple and clinically relevant classification of malar fractures is proposed.

Finite element analysis of airflow in the nasal valve.

We digitized the outline of the nasal cavity from images obtained after applying contrast material to the nose. A computer-aided simulation of flow was undertaken in the sagittal plane in the anterior nasal cavity. Previous work on the nasal valve was reviewed. Our results showed that the nasal valve is an oblique structure bounded laterally by the caudal end of the upper lateral cartilage, medially by the septum, and ventrally by the inferior rim of the piriform aperture. We found that this rim, projecting from the floor of the nose, produces an uneven distribution of airflow through the valve with most of the flow occurring in the ventral segment. Removal of this rim should result in a more even distribution of flow across the valve.

Actinomycosis otomastoiditis.

We reviewed the reported experience with actinomycosis otomastoiditis in the international literature, along with a recent case from our experience. All recently reported cases presented with persistent drainage and partial response to multiple courses of antibiotics. Diagnosis was uniformly made postoperatively, and the outcome was excellent following a prolonged course of antibiotic treatment.