DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/ß-catenin signaling.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/ß-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/ß-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/ß-catenin pathway.

Carcinoma in situ of the larynx.

A series of 28 cases of carcinoma in situ of the larynx treated over the last 16 years is reviewed. The majority of the patients were treated with endolaryngeal stripping of the cords. In the few cases in which the treatment failed, early detection of disease was made and radiotherapy was successful in controlling the carcinoma. The use of radiotherapy is only advocated for selected cases because there is often difficulty in assessing a radiated larynx; radiotherapy may induce field changes, and if treatment fails, laryngectomy may have to be carried out as a salvage procedure.

Chronic laryngeal stenosis.

The results of treatment of 82 patients with chronic laryngeal stenosis during a 20-year period are presented. Road traffic accidents accounted for 30% of the cases and iatrogenic disease for 40%. Of the stenoses 10% were supraglottic, 20% glottic, 50% subglottic, and 15% combined. Virtually all patients with supraglottic stenosis had a good result as regards voice and airway, and we describe the use of a laryngeal widening operation for this group of patients. Over 80% of patients with glottic stenosis achieved good results. However, patients with a subglottic stenosis did badly, and only 60% were relieved of their tracheostomies. Patients with stenosis due to previous tracheostomy or to systemic disease such as Wegener's granuloma did badly.

Parapharyngeal abscesses.

Fifty-five patients with deep neck infections treated consecutively over a period of six and a half years between January 1983 and July 1989 were reviewed. Nine of these patients had abscesses localized to the pharapharyngeal space and form the basis of this study. The aetiology of the parapharyngeal abscess was odontogenic in two patients and remained unknown in the other seven. Five patients had associated systemic disease; four were diabetics and one patient had non-Hodgkin's Lymphoma. High dosage intravenous antibiotics directed towards the causative micro-organisms, airway control and early surgical intervention was the mainstay of treatment. All patients underwent open surgical drainage of the parapharyngeal abscess within 24 h of admission. Bacteriology results showed Klebsiella sp. to be the dominant micro-organism cultured in four patients. Morbidity was low; seven patients had no post-operative complications and were discharged from the hospital between 7-24 d (mean 12.9 d). There were two deaths. Early open surgical drainage remains the most appropriate method of treating parapharyngeal space infections; it avoids life threatening complications with rapid recovery.

Acute epiglottitis in adults (the Singapore experience).

Acute epiglottitis in adults is a potentially fatal but self-limiting disease of increasing incidence world-wide. Forty-two patients, seen consecutively over a four year period at the ENT Department, Singapore General Hospital were reviewed retrospectively. A strong male predominance with a peak age incidence in the sixth decade was noted. A severe sore throat and dysphagia with disproportionate signs of oropharyngeal inflammation was the main presenting picture. Only three patients had stridor on presentation. Vigilant monitoring of the airway with empirical high-dose intravenous ampicillin, cloxacillin and steroids resulted in a dramatic clinical improvement in most patients and none developed stridor after admission. The yield from throat swabs and blood cultures were low. Two patients developed complications, a Ludwigs angina and an epiglottic abscess. Recurrent epiglottitis was a problem in one patient. There was low morbidity and no mortality on the management regime outlined.

Deep neck abscesses--changing trends.

A retrospective review was conducted of 64 patients with deep neck abscesses. Based on clinical and operative findings, these abscesses were categorized as retropharyngeal abscess (29 patients), parapharyngeal abscess (10 patients), Ludwig's angina (19 patients), or necrotizing cervical fasciitis (six patients). Regional trauma from an ingested foreign body was the cause for 59 per cent of the patients with a retropharyngeal abscess. In 90 per cent of subjects with Ludwig's angina, an odontogenic cause was established; however, in the majority of cases of parapharyngeal abscess (80 per cent) and necrotizing fasciitis of the neck (85 per cent), aetiology was unknown. Fifty-five patients (86 per cent) required open neck drainage. In the remaining nine (14 per cent) endoscopic drainage of the abscess was possible. Eight patients (12 per cent) needed a tracheotomy for airway control. The overall mortality was eight per cent despite aggressive anti-microbial therapy and early surgical intervention. Thirty-four cultures grew aerobic organisms. Seventy-six per cent of these were gram-negative microorganisms. The bacteriological pattern of deep neck abscesses is changing and may be responsible for the considerable mortality rate with which the abscesses are still associated despite anti-microbial therapy.

Malignant mesenchymoma of the retropharyngeal space.

Malignant mesenchymoma is a very rare head and neck tumour. To date only 15 cases have been reported in world literature and all in children under 16 years of age. We present here a case of a 40-year-old man with malignant mesenchymoma of the retropharyngeal space. The clinical picture is that of progressive dysphagia, voice change, snoring and dyspnoea. CT scan showed a soft tissue space-occupying lesion of the retropharyngeal space which enhanced very well with intravenous contrast. The tumour was excised in toto and the patient given post-operative radiotherapy. Histopathology showed two unrelated differentiated tissue types (bone and fat) in addition to the fibrosarcomatous element thus satisfying Stout's criteria (Stout, 1948) for a diagnosis of malignant mesenchymoma.

Endoscopic anatomy of the sphenoid sinus and sella turcica.

An endoscopic study of the sphenoid sinus was carried out, on 30 cadavers, to understand the important anatomical relationships of the sphenoid sinus, and the sella turcica. The aim was to study the endoscopic anatomy and the variants, and to determine if endoscopic instrumentation and techniques, could play a beneficial role in endoscopic management of sellar lesions. The results of this study are discussed, with particular reference to the important surgical anatomical features of the sphenoid sinus. A surgical technique for the endoscopic transsphenoid approach to the sella turcica was developed. Anatomical variants can be identified endoscopically, and endoscopic techniques have the advantages of improved visualization, magnification, angled vision, and a panoramic perspective of the intrasphenoid anatomy, compared to currently employed methods of pituitary/sellar surgery, using the operating microscope.

View from beneath: pathology in focus. Synovial sarcoma of hypopharynx.

Synovial sarcoma of the hypopharynx is a rare neoplasm. To date only 23 cases of synovial sarcoma of the hypopharynx have been reported in the literature. An additional case in an 18-year-old male is presented. This is the first case of synovial sarcoma in the hypopharynx to be reported in Singapore. The presentation was that of a mass in the hypopharynx; progressive dysphagia, intermittent hoarseness and gradual airway compromise. A CT scan was valuable in determining the site of origin and extent of the lesion. Histopathology was diagnostic. Treatment comprised of wide surgical excision of the tumour and post-operative radiotherapy.

Stapedectomy at the Singapore General Hospital--use of functional hearing analysis.

The results of stapedectomy surgery performed in Singapore General Hospital covering a period of over two years are reviewed. The diagnostic importance of selected clinical features and investigative procedures in otosclerosis is studied. The post-operative hearing status of twenty-six cases of primary stapedectomy is analysed using traditional audiometric and modern functional methods. Seventeen patients (65.4%) achieved closure of air-bone gap to less than 10 dB while the overall mean hearing gain was 28.6 dB. Using the Glasgow Plot parameter, 73.1% showed significant benefit from surgery, whilst the corresponding figure using the Belfast Rule of Thumb assessment technique was 57.7%. The validity of the foregoing evaluation techniques is compared. Different operative techniques, including variations in fenestra size and method of oval window seal showed statistically similar results. The scarcity of stapedectomy cases poses problems in the training of future specialists.

Parapharyngeal space tumours.

Parapharyngeal space tumours are rare, forming 0.5% of all head and neck tumours. They are of interest because of the varied histological types, diagnostic puzzle and challenge at surgical excision. Thirteen patients, seen over an eight year period (from 1981 to 1988) in the Department of Otolaryngology, Singapore General Hospital, are presented. Clinically most patients presented with a painless upper neck lump and on examination, a lateral pharyngeal wall bulge was noted. The main investigation after ruling out a nasopharyngeal primary tumour is a high resolution Computer Tomographic (CT) scan with intravenous contrast. Only if a vascular tumour is suspected on CT scanning, should angiography be performed. Pathologically, the commonest tumours are salivary gland tumours, neurolemmomas and paragangliomas. The surgical approaches at removing these tumours are discussed, emphasising maximal exposure and control of the vascular structures in the head and neck. Recognising these tumours enable the correct sequence of investigations to be performed rather than a 'lymph node' biopsy or 'tonsillectomy' which may be done resulting in an increased morbidity for the patient and an embarrassment for the attending physician.

Migrating foreign bodies in the upper digestive tract.

Migrating foreign bodies in the aerodigestive tract are not so uncommon. Two cases of penetrating and migrating extraluminal foreign bodies in the upper aerodigestive tract are presented. Both patients had ingested fish bones. Fish bones are the commonest of bones to be ingested. Sharp and pointed fish bones are more likely to penetrate extraluminally. A high index of suspicion is necessary to institute early treatment. A CAT scan is invaluable in locating the foreign body especially with regards to surgical landmarks at exploration. Early surgical intervention avoids life-threatening complications.

The surgical approach to recurrent pleomorphic adenoma of the parotid gland.

This is a retrospective study of 19 patients who were referred to the Department of Otolaryngology, Edinburgh Royal Infirmary with recurrent pleomorphic adenoma of the parotid gland. In the majority of patients, a superficial parotidectomy was performed as primary treatment. Recurrence of the tumour was either due to tumour implantation or inadequate surgical excision. Permanent facial paralysis occurred in three patients after revision parotidectomy. Change from pleomorphic adenoma at first operation to carcinoma in pleomorphic adenoma (malignant mixed tumour) at the second was noted in three patients who are still alive and free of recurrent tumour. Eighteen out of the 19 patients did not have further recurrences after revision parotidectomy. The surgical principles in the prevention of tumour recurrence and revision parotidectomy are discussed.

Radiotherapy of early glottic cancer Singapore, 1978-1981.

This study analyses the results of primary radiotherapy for 44 patients with early glottic cancer (Tis, T1 stage) given at the Therapeutic Radiology Department, Singapore General Hospital during the 4-year period from 1978 to 1981. Irradiation was delivered using cobalt teletherapy with free set-ups, and without "air-gap" compensation. Total doses of 55Gy to 64Gy were given in daily fractions of 1.8Gy, treating five times a week. The crude 5-year survival rate for Tis/T1a tumours was 88.9% and for T1b lesions, 81%. On correcting for deaths from intercurrent disease, the survival rates improved to 95.5% and 92.6% respectively. In 33 cases where the quality of voice after radiation was assessed, 15 patients (45.4%) retained good voice quality with an additional 11 patients (33.3%) having acceptable voice quality. In seven cases the voice after radiation was rated as poor. Nine patients had local recurrence, giving a rate of 20.4%. One other patient had cervical node metastasis and subsequently developed lung secondaries. Surgery, solely or with re-irradiation, was an effective treatment for local recurrence. Re-irradiation alone failed to control any case with recurrence.