Long-term changes in adipose tissue gene expression following bariatric surgery.

OBJECTIVE: Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women. RESULTS: In the obese women, the average body weight decrease was 38 kg 2 years postsurgery followed by an 8 kg weight regain between 2 and 5 years. Most of the long-term changes in WAT gene expression occurred during the first 2 years. However, a subset of genes encoding proteins involved in inflammation displayed a continued decrease between baseline, 2 and 5 years, respectively; that is an expression pattern independent of body weight regain. Expression of 71 of these genes correlated with measurements of adipocyte morphology or serum adipokine levels. CONCLUSION: The continuous improvement in WAT inflammatory gene expression, despite body weight relapse, may contribute to the sustained effects on adipose morphology after bariatric surgery.

Epigenetic regulation of diabetogenic adipose morphology.

OBJECTIVE: Hypertrophic white adipose tissue (WAT) morphology is associated with insulin resistance and type 2 diabetes. The mechanisms governing hyperplastic versus hypertrophic WAT expansion are poorly understood. We assessed if epigenetic modifications in adipocytes are associated with hypertrophic adipose morphology. A subset of genes with differentially methylated CpG-sites (DMS) in the promoters was taken forward for functional evaluation. METHODS: The study included 126 women who underwent abdominal subcutaneous biopsy to determine adipose morphology. Global transcriptome profiling was performed on WAT from 113 of the women, and CpG methylome profiling on isolated adipocytes from 78 women. Small interfering RNAs (siRNA) knockdown in human mesenchymal stem cells (hMSCs) was used to assess influence of specific genes on lipid storage. RESULTS: A higher proportion of CpG-sites were methylated in hypertrophic compared to hyperplastic WAT. Methylation at 35,138 CpG-sites was found to correlate to adipose morphology. 2,102 of these CpG-sites were also differentially methylated in T2D; 98% showed directionally consistent change in methylation in WAT hypertrophy and T2D. We identified 2,508 DMS in 638 adipose morphology-associated genes where methylation correlated with gene expression. These genes were over-represented in gene sets relevant to WAT hypertrophy, such as insulin resistance, lipolysis, extracellular matrix organization, and innate immunity. siRNA knockdown of ADH1B, AZGP1, C14orf180, GYG2, HADH, PRKAR2B, PFKFB3, and AQP7 influenced lipid storage and metabolism. CONCLUSION: CpG methylation could be influential in determining adipose morphology and thereby constitute a novel antidiabetic target. We identified C14orf180 as a novel regulator of adipocyte lipid storage and possibly differentiation.

Management of otoscierosis--an Irish perspective.

The last 30 years have seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice amongst Irish otolaryngology consultants by a questionnaire and to compare it with the practice currently followed in Great Britain. Thirty-eight responses (67.9%) were available for analysis. The overall trend is towards centralisation with a reduction in the number of surgeons undertaking stapes surgery (39%). The majority of consultants (67%) who undertake stapes surgery would operate for a unilateral conductive loss and 67% would undertake bilateral stapes surgery. Stapedotomy is the only operation performed (100%) with none of the consultants performing partial or total stapedectomies.

Management of otosclerosis in the UK.

The last 30 years has seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice among British otolaryngology consultants using a questionnaire, and to compare it with the practice reported in a survey 8 years ago. A total of 353 valid responses (64.5%) were available for analysis. The overall trend is towards centralization, with a reduction in the number of surgeons undertaking stapes surgery (49.9%). The majority of consultants (81.3%) who undertake stapes surgery would operate for a unilateral conductive loss and 75.1% would undertake bilateral stapes surgery. Stapedotomy is the operation of choice (82%), with a few consultants performing partial or rarely total stapedectomies. Postoperative restrictions and follow-up times vary widely amongst surgeons, with the senior surgeons tending to be more conservative than the younger consultants.

Disintegration of porous polyethylene prostheses.

A Plastipore (porous polyethylene) Total Ossicular Replacement Prosthesis gave an excellent initial hearing result which was maintained for 14 years. Hearing then began to deteriorate and revision surgery showed disintegration of the prosthesis and a defect in the stapes footplate. Histological examination confirmed previous findings in porous polyethylene with multinucleated foreign body giant cells and breakdown of the material.

A new approach to surgery for Menière's disease: talking about surgery.

Many patients experience a remission of their Menière's disease between the time that surgery is agreed and their admission to hospital for the procedure. In a series of 23 consecutive patients where surgery appeared to be indicated for control of the vertigo of Menière's disease, 12 settled within 6-8 weeks of agreeing that something would be done, and thereby avoided any surgical procedure. It is suggested that these patients may have been experiencing the same effect as provided by the conservative surgical procedures. In the absence of any clear evidence for a specific surgical effect from any conservative operation for Menière's disease, the authors put forward the suggestion that abandoning all the conservative procedures in favour of the protocol of planned surgery should be considered; wait for 2 months and, if the incapacitating episodic dizziness continues, one should proceed to a differenting procedure.

Small vestibular schwannomas in the elderly: a management dilemma.

Small vestibular schwannomas were diagnosed in two elderly patients and, for different reasons, a policy of watch and wait was instituted. One was reliable in attending for follow-up and lived for over 20 years without surgical intervention. The other was unreliable in follow-up, there was an unexpected and undetected acceleration of the growth rate and urgent surgery became imperative at the age of 77 years. This provided to be unsuccessful. A watch and wait policy is acceptable in the elderly but only if the patient can be relied upon to co-operate in follow-up attendance and imaging.

Long-term results of vestibular nerve section.

Records are available on 27 patients who had vestibular nerve section between 1975 and 1987 giving a follow-up time of 10 to 22 years with a mean of 16 years. Episodic vertigo was fully controlled in 26 patients, one needing a labyrinthectomy 18 months later. In addition to the patient who had labyrinthectomy, one patient had immediate post-operative profound hearing loss so that long-term follow-up of hearing was possible in 25 patients. After six months there was an overall average improvement in hearing of 1 dB. Thereafter there were average deterioration of 7 dB at two years, 15 dB at 10 years, 23 dB at 15 years and 29 dB at 20 years. This deterioration was more marked in those who had better hearing at the time of surgery, with all 10 whose hearing was classified as good deteriorating to poor by 15 years. At 10 years hearing deteriorated by 25 dB in those with good hearing and by 7 dB in those with poor hearing. In 20 per cent of patients there was audiological evidence of eventual involvement of the other ear. Tinnitus became worse in five patients but was a major problem in only one patient. One patient suffered a facial paralysis with partial recovery and, in addition, in one the frontal branch was divided in the incision.

Disability after labyrinthectomy.

A labyrinthectomy is known to relieve vertigo successfully in the majority of patients who suffer from Menière's disease and have non-serviceable hearing in the affected ear. It is assumed that the procedure reduces disability, helps the patient to return to work and improves the quality of life. Eighteen patients who underwent a transmastoid drill-out labyrinthectomy between 1980 and 1990 were interviewed and an attempt was made to evaluate the success of the operation in accordance with the guidelines set out by the AAO-HNS 1985. In the present series it was noted that although vertigo was relieved in 89 per cent of patients after labyrinthectomy, only 50 per cent of them returned to work. In this study, the age and occupation of the patient at the time of surgery and the relief of vertigo did not accurately predict whether or not a patient returned to work.

Bilateral acoustic neuromas.

This article reviews 12 patients with bilateral acoustic neuromas. The sex incidence was equal and the mean age at diagnosis was 26.2 years. The family history was positive in nine of the patients. Five patients have had incomplete surgical removal of acoustic neuromas on both sides. Two of them are completely deaf and the other three have severe sensorineural hearing loss in one ear and no hearing in the other ear. In five patients the tumour on one side has been operated on and the other side is being observed with at least short-term preservation of good hearing. The remaining two patients died of intra-cranial complications, one of them post-operatively. Four patients developed facial palsy immediately following surgery and one developed facial weakness 6 months after surgery. Guidelines are discussed for the care of these patients including the timing of surgery and alternative treatment options (observation, radio-surgery and chemotherapy). This is essentially a group of young individuals who have had multiple operations for bilateral acoustic tumours and associated manifestations and for whom the disease and the sequelae of treatment can be tragic.

Non-surgical management of acoustic neuromas.

Watchful waiting is one of the options available in the management of acoustic neuromas and this article deals with 13 patients who were so managed. Non-operative management was advised because of age, poor general health, small size of tumour, only hearing ear, or in patients unwilling to undergo surgery for various reasons. This group was followed up at 6-12-monthly intervals and the follow-up period ranged from 1 to 18 years (mean 5.3 years). Ten patients had small tumours and only in 2 of these was increase in tumour size demonstrated on follow-up CT scan. In one this increase was later followed by regression. Two patients required partial removal of tumour because of increasing symptoms after 3 and 7 years of follow-up; one of them died on the twelfth post-operative day. There appears to be a small group of patients for whom delay is worth while rather than to subject all patients with acoustic neuroma to surgery from which full recovery cannot be guaranteed.

Acoustic neurinoma surgery in Belfast 1986-1989.

Forty-seven acoustic neurinoma tumours have been operated on in 46 patients in the years 1987-1989. This is a considerable increase over the prevalence in the preceding ten years. Twenty-six were classified as large tumours, 18 as medium and one was small. Surgical excision was complete in 16 and incomplete in 31 cases. Two patients died in the early postoperative period. Facial nerve function was preserved in 36 (80%) of cases; of these 27 (60%) had good function and nine (20%) fair function. Useful hearing was prevented in only two patients. The overall complication rate has been low and often of a transitory nature.

Realities in ossiculoplasty.

The results of ossiculoplasty are frequently reported in terms of closure of the air-bone gap. This parameter is a reliable indicator of the degree of technical success, and is useful in comparing different materials and types of reconstructions. However, assessment of the operated ear alone does not evaluate the effect of surgery on binaural hearing ability, leading to the situation where sub-optimal advice may be given to patients pre-operatively. This article advocates a more patient orientated method of assessing the results of ossiculoplasty. Previous studies have indicated that the operated ear must reach an air conduction level of 30 dB for the speech frequencies, or be within 15 dB of the other ear, to ensure that the patient will gain significant benefit. A graphical method for the prediction of patient benefit is presented, and compared to the rule of thumb quoted above. The implications for surgeons and patients considering ossiculoplasty are obvious. Many statements routinely made to patients prior to surgery for conductive hearing loss are unduly optimistic and unrelated to the realities of reported results. There is a need to determine what types of such hearing losses can be helped surgically, and more importantly to what extent the patients hearing disability can be relieved.

Otological manifestations of a new familial polyostotic bone disorder.

Fifty members of a family with a unique autosomal dominant bone disease were investigated. Nineteen of the family members were either known to have, or were strongly suspected of having the disease. All but one of these had a hearing loss which was conductive in the younger age group and mixed in the older members. The common finding in those who had middle ear surgery was replacement of the long process of incus by a fibrous band. The histological features were similar to those found in Paget's disease. The age of onset, distribution of lesions and radiographic findings, however, were not typical of this disorder.

Realities in ossiculoplasty.

The results of ossiculoplasty are frequently reported in terms of closure of the air-bone gap. This parameter is a reliable indicator of the degree of technical success, and is useful in comparing different materials and types of reconstructions. However assessment of the operated ear alone does not evaluate the effect of surgery on binaural hearing ability, leading to the situation where sub-optimal advice may be given to patients pre-operatively. This article advocates a more patient orientated method of assessing the results of ossiculoplasty. Previous studies have indicated that the operated ear must reach an air conduction level of 30dB for the speech frequencies or be within 15dB of the other ear to ensure that the patient will gain significant benefit. A graphical method for the prediction of patient benefit is presented, and compared to the rule of thumb quoted above. The implications for surgeons and patients considering ossiculoplasty are obvious.

Role and results of cortical mastoidectomy and endolymphatic sac surgery in Menière's disease.

It is almost impossible to establish the natural history of Menière's disease and, by the same token, it is difficult to confirm the efficacy of endolymphatic sac surgery. The authors doubt the logic of sac operations. Only two controlled trials of sac surgery have been found and both cast doubt upon its value. There do not appear to be any controlled trials indicating that it works. In 14 cases of incapacitating Menière's disease, where vestibular nerve section was indicated, cortical mastoidectomy was offered and accepted in the expectation that two-thirds might be spared the more major procedure. In the event, the vertigo was controlled in eight out of 14 (57 per cent), the remaining six (43 per cent) requiring more major surgery. A surgical model illustrates that, of themselves, these results are essentially meaningless in assessing the efficacy of cortical mastoidectomy in Menière's disease. Until all cases in a community are considered and followed-up, we shall be in doubt about the value of sac surgery and most other treatments of Menière's disease.

Pneumatization of the posteromedial air-cell tract.

Sixty consecutive temporal bone specimens were examined histologically by light microscopy to determine the incidence of a pneumatized posteromedial air-cell tract extending into the posterior wall of the internal auditory meatus. Thirteen were found to have this air-cell tract. The main potential surgical hazards of opening this air-cell tract are CSF otorhinorrhoea and meningitis.

Transplanted ossicles after two decades.

The authors now report on the histological appearance of two very long-term ossicles, an autologous incus removed from the middle ear at revision surgery 21 years after repositioning and a homologous incus removed from the middle ear after 20 years. Having been placed in formalin immediately after removal from the ear, both specimens were later decalcified by ethylene diamine tetra-acetic acid, embedded in paraffin wax, serially sectioned and stained with haematoxylin and eosin.