A comparison between endoscopic and microscopic approaches for stapes surgery: experience of a tertiary referral center.

PURPOSE: Otosclerosis is a common ear disease causing ankylosis of the stapedio-vestibular joint and conductive hearing loss. Stapedoplasty is the most advisable surgical solution. The restoration of hearing depends on the condition of the patient and the surgery itself. The aim of our work was to compare the surgical and audiological results of stapedoplasty performed with endoscopic versus microscopic technique. METHODS: This is a retrospective study of 254 patients treated with stapedoplasty with a microscopic approach (91/254) or with an endoscopic approach (163/254) between 2014 and 2021 at our tertiary referral center. Statistical significance of differences between the two methods was determined using the Mann-Whitney test for quantitative variables and the Wilcoxon matched-pairs signed-rank test for repeated measures. Categorical variables were assessed with Fisher's exact test. RESULTS: Both techniques improved the hearing status of patients, with no statistically significant difference between them. There was also no statistically significant difference in reported complications between the two techniques. There is a statistical difference (p < 0.001) in operating time between the two techniques: the endoscopic technique had a mean operating time of 39 min versus 45 min for the microscopic technique. CONCLUSIONS: The two techniques are comparable in terms of results and the choice depends on the surgeon's preferences and experience.

To accelerate cancer prevention in Europe: Challenges for cancer registries.

The availability of population-based cancer registry (CR) data is paramount in the development of modern oncology. Major contributions consisted in accurately measuring cancer burden (incidence, survival and prevalence, beside mortality), identifying and quantifying risk factors (case control and cohort studies that, in the last two decades, included gene variant assessment) and evaluating outcomes of treatments and preventive interventions, including mass screening. Cancer registration coverage of European populations progressed slowly since 1940 and is now almost 50%. Areas lacking high-quality national population-based cancer registration still exist within large countries such as France, Italy, Romania and Spain, Germany and Poland having national plans and legislation to reach complete coverage. Depending on programme ownership, history and institutional organisation, European CRs showed huge variations in the scope (research domain), size, available resources and finally exploitation of collected data. This reflects their heterogeneous origins stemming from different professional backgrounds and healthcare systems. This review discusses not only the potential for contributing to acceleration of prevention but also the coverage expansion by and innovation of CR organizations. The latter can be attained not only by more standardisation in institutional organisation and operative methodologies but also by intensification of scientific production and risk communication. The CR's agenda should focus on cancers caused by identifiable risk factor(s) that are amenable to preventive actions, including early detection; short-term priorities usually are with tobacco, and medium-term priorities are with alcohol, occupational exposures, infection-related cancers and ultraviolet-related skin cancers, while obesity-related cancers are likely to increase gradually further in the long term.

Hearing threshold estimation by auditory steady state responses (ASSR) in children.

Hearing threshold identification in very young children is always problematic and challenging. Electrophysiological testing such as auditory brainstem responses (ABR) is still considered the most reliable technique for defining the hearing threshold. However, over recent years there has been increasing evidence to support the role of auditory steady-state response (ASSR). Retrospective study. Forty-two children, age range 3-189 months, were evaluated for a total of 83 ears. All patients were affected by sensorineural hearing loss (thresholds ≥ 40 dB HL according to a click-ABR assessment). All patients underwent ABRs, ASSR and pure tone audiometry (PTA), with the latter performed according to the child's mental and physical development. Subjects were divided into two groups: A and B. The latter performed all hearing investigations at the same time as they were older than subjects in group A, and it was then possible to achieve electrophysiological and PTA tests in close temporal sequence. There was no significant difference between the threshold levels identified at the frequencies tested (0.25, 0.5, 1, 2 and 4 kHz), by PTA, ABR and ASSR between the two groups (Mann Whitney U test, p < 0.05). Moreover, for group A, there was no significant difference between the ASSR and ABR thresholds when the children were very young and the PTA thresholds subsequently identified at a later stage. Our results show that ASSR can be considered an effective procedure and a reliable test, particularly when predicting hearing threshold in very young children at lower frequencies (including 0.5 kHz).

GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine.

The life expectancy for pancreatic cancer patients has seen no substantial changes in the last 40 years as very few and mostly just palliative treatments are available. As the five years survival rate remains around 5%, the identification of novel pharmacological targets and development of new therapeutic strategies are urgently needed. Here we demonstrate that inhibition of the G protein-coupled receptor GPR55, using genetic and pharmacological approaches, reduces pancreatic cancer cell growth in vitro and in vivo and we propose that this may represent a novel strategy to inhibit pancreatic ductal adenocarcinoma (PDAC) progression. Specifically, we show that genetic ablation of Gpr55 in the KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+ (KPC) mouse model of PDAC significantly prolonged survival. Importantly, KPC mice treated with a combination of the GPR55 antagonist Cannabidiol (CBD) and gemcitabine (GEM, one of the most used drugs to treat PDAC), survived nearly three times longer compared to mice treated with vehicle or GEM alone. Mechanistically, knockdown or pharmacologic inhibition of GPR55 reduced anchorage-dependent and independent growth, cell cycle progression, activation of mitogen-activated protein kinase (MAPK) signalling and protein levels of ribonucleotide reductases in PDAC cells. Consistent with this, genetic ablation of Gpr55 reduced proliferation of tumour cells, MAPK signalling and ribonucleotide reductase M1 levels in KPC mice. Combination of CBD and GEM inhibited tumour cell proliferation in KPC mice and it opposed mechanisms involved in development of resistance to GEM in vitro and in vivo. Finally, we demonstrate that the tumour suppressor p53 regulates GPR55 protein expression through modulation of the microRNA miR34b-3p. Our results demonstrate the important role played by GPR55 downstream of p53 in PDAC progression. Moreover our data indicate that combination of CBD and GEM, both currently approved for medical use, might be tested in clinical trials as a novel promising treatment to improve PDAC patients' outcome.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Trends in incidence of thick, thin and in situ melanoma in Europe.

BACKGROUND: We analysed trends in incidence for in situ and invasive melanoma in some European countries during the period 1995-2012, stratifying for lesion thickness. MATERIAL AND METHODS: Individual anonymised data from population-based European cancer registries (CRs) were collected and combined in a common database, including information on age, sex, year of diagnosis, histological type, tumour location, behaviour (invasive, in situ) and lesion thickness. Mortality data were retrieved from the publicly available World Health Organization database. RESULTS: Our database covered a population of over 117 million inhabitants and included about 415,000 skin lesions, recorded by 18 European CRs (7 of them with national coverage). During the 1995-2012 period, we observed a statistically significant increase in incidence for both invasive (average annual percent change (AAPC) 4.0% men; 3.0% women) and in situ (AAPC 7.7% men; 6.2% women) cases. DISCUSSION: The increase in invasive lesions seemed mainly driven by thin melanomas (AAPC 10% men; 8.3% women). The incidence of thick melanomas also increased, although more slowly in recent years. Correction for lesions of unknown thickness enhanced the differences between thin and thick cases and flattened the trends. Incidence trends varied considerably across registries, but only Netherlands presented a marked increase above the boundaries of a funnel plot that weighted estimates by their precision. Mortality from invasive melanoma has continued to increase in Norway, Iceland (but only for elder people), the Netherlands and Slovenia.

Completeness and timeliness: Cancer registries could/should improve their performance.

UNLABELLED: Cancer registries must provide complete and reliable incidence information with the shortest possible delay for use in studies such as comparability, clustering, cancer in the elderly and adequacy of cancer surveillance. Methods of varying complexity are available to registries for monitoring completeness and timeliness. We wished to know which methods are currently in use among cancer registries, and to compare the results of our findings to those of a survey carried out in 2006. METHODS: In the framework of the EUROCOURSE project, and to prepare cancer registries for participation in the ERA-net scheme, we launched a survey on the methods used to assess completeness, and also on the timeliness and methods of dissemination of results by registries. We sent the questionnaire to all general registries (GCRs) and specialised registries (SCRs) active in Europe and within the European Network of Cancer Registries (ENCR). RESULTS: With a response rate of 66% among GCRs and 59% among SCRs, we obtained data for analysis from 116 registries with a population coverage of ∼280 million. The most common methods used were comparison of trends (79%) and mortality/incidence ratios (more than 60%). More complex methods were used less commonly: capture-recapture by 30%, flow method by 18% and death certificate notification (DCN) methods with the Ajiki formula by 9%. The median latency for completion of ascertainment of incidence was 18 months. Additional time required for dissemination was of the order of 3-6 months, depending on the method: print or electronic. One fifth (21%) did not publish results for their own registry but only as a contribution to larger national or international data repositories and publications; this introduced a further delay in the availability of data. CONCLUSIONS: Cancer registries should improve the practice of measuring their completeness regularly and should move from traditional to more quantitative methods. This could also have implications in the timeliness of data publication.

Unplanned ultrasound-guided puncture of a tracheal balloon in a premature infant with congenital diaphragmatic hernia.

Temporary tracheal balloons have been shown to improve lung growth in fetuses with severe congenital diaphragmatic hernia. Fetoscopic Endoluminal Tracheal Occlusion (FETO) is performed at 26-28 weeks gestation, and then is removed in utero at 34 weeks gestation at highly specialized centers. In case of preterm labor at a hospital without a specialized team, a number of techniques have been used to remove the balloon, sometimes with death of the newborn. We have successfully performed an ultrasound-guided approach to puncture and remove the tracheal balloon in a premature infant in an emergency setting at birth. After that she was treated for congenital diaphragmatic hernia at our Newborn Intensive Care Unit.

Economic evaluation of cancer registration in Europe.

BACKGROUND: Little has been reported on costs of cancer registration, and standard indicators have not yet been identified. This study investigated costs and outcomes of a sample of 18 European registries covering a population of 58.8 million inhabitants. METHODS: Through a questionnaire, we asked registries for real cost data including personnel, information technology (IT), and infrastructure. Staff costs were grouped by professional position and by activity performed. As outcomes, besides the production of current data, we considered publications in peer-reviewed journals (last 5 years' impact factor [IF]) and characteristics of registry websites. RESULTS: In our sample, the average cost of cancer registration per inhabitant was €0.27 at purchasing power standard (PPS) (range €0.03-€0.97), while the mean cost per case registered was €50.71 PPS (range €6-€213). Personnel costs accounted for an average of 79 percent of total resources. Resources spent in routine activities (an average of 51 percent, range 28 percent-87 percent) were predominant with respect to those allocated to research, with a few exceptions. Website quality seemed to be independent of total registry budget. CONCLUSIONS: The variance in costs of cancer registration across Europe can be attributed mainly to the type of registry (whether national or regional), the size of the covered population, and the national economic profile, expressed as gross domestic product.

Hearing habilitation with auditory brainstem implantation in two children with cochlear nerve aplasia.

Patients with aplasia and hypoplasia of the cochlear nerve have no chance of having their hearing restored by stimulating the periphery of the auditory system using the traditional cochlear implant. A possible approach to auditory rehabilitation may be direct electrical stimulation of the cochlear nuclei with an auditory brainstem implant (ABI). Recently, two children, aged 4 and 3 years, respectively, with bilateral severe cochlear malformations and cochlear nerve aplasia received an ABI. The present paper reports the technique and the preliminary results of this experience. The classic retrosigmoid approach was used. The correct position of the electrodes was estimated with the aid of EABRs and neural response telemetry (NRT). No postoperative complications were observed. High-resolution CT scans with a bone algorithm reconstruction technique were taken postoperatively to evaluate electrode placement before discharge. The ABI was activated 30 days after implantation in both patients. To date 16 and 13 electrodes, respectively, have been activated in the two children. Three months after activation the first patient had achieved good environmental sound awareness, good speech detection and some speech discrimination. The second child, 1 month after activation, had achieved good environmental sound awareness and moderate speech detection. To the best of our knowledge this is the first report of patients with hypoplasia of the cochlea and aplasia of the cochlear nerve, aged below 5 years and treated with an ABI.

The retrosigmoid approach for auditory brainstem implantation.

OBJECTIVE: To describe our experience with the retrosigmoid-transmeatal (RS-TM) approach in auditory brainstem implantation (ABI) as well as the anatomosurgical guidelines for this route. STUDY DESIGN: Retrospective case review. SETTING: Ear, Nose, and Throat Department of the University of Verona. PATIENTS: Five patients with neurofibromatosis type 2 (NF2) were operated on for vestibular schwannoma removal with ABI implantation from April 1997 to June 1999. The patients were four men and one woman, whose ages ranged from 22 to 37 years. The tumor sizes ranged from 12 to 30 mm. The records of a total of 179 patients operated on for vestibular schwannoma (VS) removal via the RS-TM approach from January 1990 to June 1999 were also evaluated. Their ages ranged from 18 to 88 years (average 54 years). The tumor sizes ranged from 4 to 50 mm. Five patients had a solitary VS in the only hearing ear. INTERVENTION: The classic RS-TM approach was used in all patients. After tumor excision, for ABI implantation, the landmarks (seventh, eighth, and ninth cranial nerves, choroid plexus) for the foramen of Luschka were carefully identified. The choroid plexus was then partially removed, and the tela choroidea was divided and bent back. The floor of the lateral recess of the fourth ventricle and the convolution of the dorsal cochlear nucleus became visible. The electrode array was then inserted into the lateral recess and correctly positioned with the aid of electrically evoked auditory brainstem responses (EABRs). MAIN OUTCOME MEASURES: Intraoperative EABR and postoperative speech perception evaluation. RESULTS: Auditory sensations were induced in all patients with various numbers of electrodes. Different pitch sensations could be identified with different electrode stimulation. CONCLUSIONS: In the authors' experience, the RS-TM approach is the route of choice for patients who are candidates for ABI when there is a chance of hearing preservation during surgery. If auditory function is lost during surgery, anatomical preservation of the cochlear nerve may allow hearing restoration with a cochlear implant. Direct intraoperative recording of cochlear nerve action potentials (CNAPs) and round window electrical stimulation are mandatory for these purposes. In addition, decompression of the intrameatal portion of the vestibular schwannoma and planned partial tumor resection with hearing preservation are also possible with the RS-TM approach.

New approach for cochlear implantation: cochleostomy through the middle fossa.

The middle fossa approach was used in 11 patients with profound bilateral hearing loss for insertion of a cochlear implant. Fibroadhesive otitis media (n = 1), bilateral cavity radical mastoidectomy (n = 1), autoimmune inner ear disease (n = 2), previous cranial trauma (n = 1), genetic prelingual deafness (n = 5), and otosclerosis (n = 1) were the causes of deafness. A cochleostomy was performed on the most superficial part of the basal turn, and the electrode array was inserted up to the cochlear apex. Speech perception tests (1-9 months after cochlear implant activation) yielded better results in these patients compared with a homogeneous group of postlingually deaf patients operated on through the traditional transmastoid route. Insertion of the implant through the middle fossa cochleostomy furnishes the possibility of stimulating areas of the cochlea (ie, the middle and apical turns) where a greater survival rate of spiral ganglion cells is known to occur, with improvement of information regarding the formants relevant for speech perception.

Retrosigmoid approach for auditory brainstem implant.

The present paper reports our experience with the surgical retrosigmoid-transmastoid (RS-TM) technique for implanting auditory brainstem implants (ABIs). From April 1997 to August 1998, four patients with neurofibromatosis type 2 (NF2) were operated on for vestibular schwannoma removal with ABI implantation. The subjects (three men and one women) ranged in age from 22 to 31 years. Tumour size ranged from 12 to 30 mm. A classical RS-TM approach was performed. After tumour excision, identification of landmarks (VIIth, VIIIth and IXth cranial nerves, choroid plexus) to the foramen of Luschka was carefully carried out. The choroid plexus was partially removed and the tela choroidea divided and deflected. The floor of the lateral recess of the fourth ventricle and the convolution of the dorsal cochlear nucleus became visible. The electrode array was then inserted into the lateral recess and placed in the correct position with the help of electrically-evoked auditory brain stem responses. Auditory sensations were induced in all patients with various numbers of electrodes. Different pitch sensations could be identified with different electrode stimulation. Details of the results are presented. In our series, the RS-TM approach represents the elective route for ABI insertion.

Advantages of the retrosigmoid approach in auditory brain stem implantation.

From April 1997 to December 1999, six patients (five men and one woman), ranging in age from 22 to 37 years with neurofibromatosis type 2 (NF2) were operated on via the classic retrosigmoid-transmental (RS-TM) approach for removal of a vestibular schwannoma (VS) (tumor size from 12 to 40 mm) and for auditory brain stem implantation (ABI). After tumor removal, the floor of the lateral recess of the fourth ventricle and the convolution of the dorsal cochlear nucleos were reached, and the ABI was inserted. More recently, an ABI was implanted via the retrosigmoid approach in a 4-year-old boy with a cochlear malformation (common cavity) associated with cochlear nerve aplasia. Electrically evoked auditory brain stem responses (EABRs) and neural response telemetry (NRT) were performed to verify the correct positioning of the inserted electrodes. No major complications related to ABI were observed. ABI has been activated to date in five of the NF2 patients. Auditory sensations with various numbers of electrodes were evoked in all patients. We consider the RS-TM approach the route of choice for ABI insertion in patients with NF2 and good hearing, offering a chance of hearing preservation, and in patients with complete cochlear ossification, severe head trauma and cochlear fracture, or nerve disruption, or a combination of these. A new indication for ABI implantation via the RS approach is presented by patients with bilateral cochlear nerve aplasia.

Intraoperative monitoring for hearing preservation and restoration in acoustic neuroma surgery.

The present article reports on our experience with hearing preservation during 158 acoustic neuroma (AN) operations via the retrosigmoid-transmeatal (RS-TM) approach with the aid of intraoperative auditory monitoring. Several auditory monitoring methods are described. Of these, the bipolar cochlear nerve action potential (CNAP) was found to be the most helpful in preserving hearing. Of 106 patients with useful hearing preoperatively, more than 50% had useful hearing after surgery. Electrical auditory brainstem responses were useful in the placement of an auditory brain stem implant (ABI) in 4 patients with neurofibromatosis type 2 (NF2). All 4 reported speech perception benefit and use their ABIs regularly in their lives. It is our firm belief that intraoperative auditory monitoring has a pivotal role in the preservation and restoration of hearing in AN surgery.

Iatrogenic impairment of hearing during surgery for acoustic neuroma.

Isolated or combined labyrinthine, neural, and vascular damage account for failure to preserve hearing during removal of acoustic neuromas. However, the specific mechanisms of auditory impairment remain unclear unless surgical maneuvers can be related to peri- and postoperative hearing on the basis of intraoperative monitoring of auditory function.Among the different auditory monitoring techniques, recording of cochlear nerve action potentials (CNAPs) from the intracranial portion of the nerve has proven particularly useful for identifying the mechanisms of iatrogenic auditory injury.The present investigation analyzes intra- and postoperative auditory impairment in relation to surgical steps in a group of 38 subjects with acoustic neuroma (size ranging from 5 to 24 mm) undergoing removal via a retrosigmoid approach.Coagulation close to the cochlear nerve, drilling of the internal auditory canal, and removal of the intrameatal portion of the acoustic neuroma have prove to be the most critical surgical steps in hearing preservation.Changes were correlated with intra- and extrameatal tumor size, the relationship between the internal auditory canal and vestibule, and internal auditory canal enlargement, anatomic involvement of the cochlear nerve, preoperative auditory level, and ABR and ENG test findings.Changes in CNAP morphology and latency are detailed, and mechanisms of injury are analyzed and discussed as a function of these variables.