Latent class analysis of structured histopathology in prognosticating surgical outcomes of chronic rhinosinusitis with nasal polyps in Singapore.

BACKGROUND: Structured histopathology profiling is recommended when reporting chronic rhinosinusitis with nasal polyp (CRSwNP) tissue. The objective of this study is to identify features in structured histopathology that predict outcome after functional endoscopic sinus surgery (FESS) in a cohort of CRSwNP patients from Singapore. METHODS: Latent class analysis was performed on structured histopathology reports of 126 CRSwNP patients who had undergone FESS. Outcome measures were polyp recurrence, need for systemic corticosteroids, revision surgery or biologics, and disease control at 2 years post-FESS. RESULTS: Three classes were identified. Class 1 was characterised by mild, predominantly lymphoplasmacytic inflammation. Class 2 comprised of 100 eosinophils/HPF, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals. Classes 2 and 3 were significantly associated with uncontrolled disease at 2 years post-FESS. Class 3 was additionally associated with the need for systemic corticosteroids. CONCLUSIONS: Eosinophil count, degree of inflammation, predominant inflammatory type, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals predicted need for systemic corticosteroids and uncontrolled disease at 2 years post-FESS. The presence of >100 eosinophils/HPF should be reported, as this subset of tissue eosinophilia was associated with less favourable outcomes after FESS.

Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa.

BACKGROUND: The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway, with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13-induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs). METHODS: The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudostratified epithelium in air-liquid interface (ALI) culture. RESULTS: There were significant increases in IL-13, IL-13Rα1, and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r = .5886, P = .002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN, where the IL-13-induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 µmol/L) or dexamethasone (10-4 -10-7  mol/L) treatment. CONCLUSIONS: IL-13Rα2 has a potential role in IL-13-induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.

Melaena: an unusual presentation of a pseudoaneurysm of the internal carotid artery.

Pseudoaneurysm of the internal carotid artery is a rare but potentially fatal condition, and its clinical manifestations are often varied. Knowledge of this condition is essential to making the diagnosis. We describe a case of a 38-year-old man who presented with melaena. He also reported blood-stained sputum in the morning for several days. The only significant physical finding was a left peritonsillar mass. Initially worked up for a gastrointestinal bleed, computed tomography of the neck showed a large pseudoaneurysm of the internal carotid artery. A bypass from the proximal external carotid artery to the distal middle cerebral artery had to be created prior to angiographic embolisation of the pseudoaneurysm due to an inadequate supply from the contralateral cerebral hemisphere. The patient made an uneventful recovery with no neurological deficits.

Sphenoid sinus: an anatomic and endoscopic study in Asian cadavers.

An anatomic and endoscopic study of 48 cadaveric heads (96 sphenoid sinuses) was undertaken to describe the anatomy of the sphenoid sinus in Asians. Sellar type of sphenoid sinus is the most common, present in 53 out of 96 sides (55%). Forty-five of the 48 heads had a dominant sphenoid cavity, of which 11 contained vital structures from both sides of the sphenoid sinus. The incidence of accessory septae, carotid artery, optic nerve, maxillary nerve, and vidian nerve bulges were 70.8%, 67.7%, 69.8%, 61.5%, and 64.6%, respectively. There is a significantly higher number of overriding ethmoid sinuses in Asian cadavers (46/96 sides) compared to western studies (P < 0.0005). Seven (15%) of these 46 sides were also Onodi positive. The rest of the overriding ethmoid cells were Onodi negative. Surgeons should be aware of the significantly higher number of overriding posterior ethmoid cells in Asian populations during functional endoscopic sinus surgery (FESS). The optic nerve is at risk during FESS surgery if the sphenoid sinus is sought behind the deepest point of these posterior ethmoid cells. These overriding posterior ethmoid cells may also confuse the unwary surgeon that he has entered the sphenoid sinus where in fact he is still operating in the posterior ethmoid cells.

Endolymphatic sac tumour: a rare cause of recurrent vertigo.

Endolymphatic sac tumour occurring in a 32-year-old man presenting with Meniere's like symptoms of recurrent vertigo, hearing loss and tinnitus is described. Magnetic resonance imaging and computed tomography showed a vascular bone tumour centred over the retrolabyrinthine aspect of the temporal bone where the endolymphatic sac was located. Surgical excision via a translabyrinthine approach was performed. Endolymphatic sac tumours are rare papillary adenocarcinomas that arise from the endolympatic sac. It can be mistaken both on radiology and histology for other tumours such as paragangliomas, renal or papillary thyroid carcinoma metastases. Surgical excision is the treatment of choice but sacrifice of the auditory and facial nerve may be needed in advanced cases to achieve tumour clearance.

Infections of the external ear.

Otitis externa is one of the most common conditions seen in the otolaryngology practice. It encompasses a wide range of conditions, from those that cause mild inflammation and discomfort to those that are life-threatening. The management of these conditions requires a clear understanding of the anatomy and physiology of the ear canal, the microbiology of pathogens and familiarity with the clinical presentation.

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma.

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin < 12 g dl(-1) (score 4) and disease-free interval (DFI) (DFI < or = 6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0-3; intermediate, 4-8; poor, > or = 9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P = 0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials.

Acute isolated sphenoid sinusitis.

INTRODUCTION: Acute isolated sphenoid sinusitis is seen in fewer than 3% of all cases of sinusitis. It is frequently misdiagnosed because of its vague symptoms and the paucity of clinical findings. We report 2 cases of isolated acute isolated sphenoid sinusitis with unusual presentations. CLINICAL PICTURE: Both patients presented with acute headache, eye pain and fever, and were provisionally diagnosed as meningitis. In 1 case, the symptoms were on the contralateral side of the sphenoid infection. Intracranial complications were also present. TREATMENT: Treatment included intravenous antibiotics and endoscopic sphenoidotomy. OUTCOME: Both patients recovered with no residual neurological disability. CONCLUSION: Acute sphenoiditis usually presents with subtle symptoms and elusive physical findings and hence a high index of suspicion is necessary. Complications may arise due to the close proximity of important structures to the sphenoid sinus. Uncomplicated cases can resolve with optimal antibiotic therapy if diagnosed and treated early. Persistence or progression of disease with development of intracranial complications are indications for immediate surgical drainage.

Peritonsillar infections: local experience.

INTRODUCTION: The disease pattern and management of peritonsillar infections in Singapore General Hospital are studied. Other objectives are to determine if a seasonal variation exists and to examine the role of routine bacterial cultures and interval tonsillectomy. METHODS: This is a retrospective review of the management and outcome of patients with peritonsillar infections who were admitted acutely to Singapore General Hospital over a three-year period. RESULTS: Of 185 patients studied, 151 (81.6 percent) had peritonsillar abscess or quinsy and 34 (18.4 percent) had peritonsillar cellulitis. There were 139 males and 46 females, with a racial predisposition among Malays (p value is less than 0.0005). There may be a seasonal variation with a bi-annual trend, though no correlation with upper respiration tract infections was noted. Treatment consisted mainly of incision and drainage (66 percent) or needle aspiration (34 percent). No significant difference in the length of stay was noted in patients receiving penicillin alone, penicillin with metronidazole, or broad-spectrum antibiotics (p value is equal to 0.062). Fourteen (7.6 percent) patients had recurrences, all of which occurred after the first month. Two patients (1 percent) had bilateral quinsy. CONCLUSION: Peritonsillar infections remain a common admitting diagnosis to the Otolaryngology department. A single episode of infection should no longer be an indication for tonsillectomy as the incidence of recurrence is low.

The development of sphenoid sinus in Asian children.

OBJECTIVES: (1) To study the developmental changes of sphenoid sinus in Asian children and (2) to test the hypothesis that the sphenoid sinus may be developing slower in Asian, by comparing the growth patterns between Asian and Caucasian children. MATERIALS AND METHODS: Review of MR imaging of the skull of 220 Asian children less than 15 years of age in a tertiary hospital. The results were compared to a representative Caucasian study by Szolar et al. [Surg. Radiol. Anat., 16 (1994) 193]. RESULTS: Grade 1 sphenoid was present in all children less than 6 months old. Conversion from marrow to fat of the sphenoid sinus (Grade 2) began at 7 months and was present in patients up to 6 years old. Signs of pneumatization (Grade 3) of the sphenoid sinus were first noted in patients at 10 months old. Almost 100% pneumatization was seen in all the children after 6 years old except for one child with Grade 1 sphenoid at 11 years old. Compared to Caucasian children, there was a significantly higher proportion of Grade 3 cases in Asian children from 0 to 4 years of age (P = 0.05). No difference in the distribution of cases was noted from 4 to 8 years (P = 0.466) and 8-15 years (P = 1.00). CONCLUSION: The developmental changes of the sphenoid sinus in Asian children were determined and found to be similar when compared to Caucasian children. The findings did not support the hypothesis that the Asian sphenoid sinus is developing slower compared to that of the Caucasians.

Design of a prognostic index score for metastatic nasopharyngeal carcinoma.

The survival outcome of patients with systemic cancer differs significantly between individuals even within the same tumour type. We set out to illustrate this by analysing the factors determining survival in patients with metastatic disease from nasopharyngeal carcinoma (NPC) and to design a scoring system based on these prognostic factors. Patients referred between January 1994 and December 1999 were retrospectively analysed. Factors analysed included patient (age group, gender, performance status (BS) at diagnosis of metastases), disease (number of metastatic sites, specific metastatic sites, disease-free interval (DFI), metastases at presentation, presence of locoregional recurrence), and laboratory factors (leucocyte count, haemoglobin level, albumin level). Univariate and multivariable analyses were performed using the Cox proportion hazards model. A numerical score was derived from the regression coefficients of each independent prognostic variable. The prognostic index score (PIS) of each patient was calculated by totalling up the scores of each independent variable. Independently significant, negative prognostic factors were liver metastasis, lung metastasis, anaemia, poor PS, distant metastasis at initial diagnosis, and a DFI of <6 months. Three prognostic groups based on the PIS were obtained: (i) good risk (PIS=0-6); (ii) intermediate risk (7-10); (iii) poor risk (>or=11). The median survivals for these groups were 19.5, 10, and 5.8, months, respectively, (log rank test: P<0.0001). The variable prognosis of patients with disseminated NPC can be assessed by using easily available clinical information (patient, disease and laboratory factors). The PIS system will need to be validated on prospectively collected data of another cohort of patients.

Bifrontal decompressive craniectomy for acute subdural empyema.

INTRODUCTION: Subdural empyema is an uncommon but serious complication of sinusitis. Despite the use of advanced imaging facilities, modern antibiotic therapy and aggressive neurosurgical protocols, this condition still carries significant morbidity and mortality. CASE REPORT: We report an unusual case of sinusitis-associated acute subdural empyema in a 13-year-old patient, presenting in a catastrophic manner with acutely raised intracranial pressure. Emergency bifrontal decompressive craniectomy was necessary both to reduce the intracranial pressure and to drain the subdural empyema. RESULTS: The full range of intracranial complications subsequently occurred, including brain abscesses, recurrent subdural empyema and ventriculitis. Despite this, the patient's outcome was good, with minimal intellectual deficits. CONCLUSION: In cases of severe intracranial infection, we therefore advocate an aggressive surgical approach coupled with appropriate antibiotics to ensure a good outcome.

Nasopharyngeal carcinoma in children.

Nasopharyngeal carcinoma (NPC) is rare in children. We report two cases from KK Women and Children's Hospital in Singapore, who presented with advanced locoregional disease. The various aspects of NPC in children are discussed. It is more common in males and black adolescents. The etiology is probably different from that in adult. Undifferentiated NPC or lymphoepithelioma is the commonest variety. Confusing symptoms like cervical lymphadenopathy and unilateral otitis media with effusion (OME) are among the commonest presentations. When children present with both conditions simultaneously, it is imperative to manage them like adult patients and perform nasendoscopy to rule out NPC. The disease stage at presentation is often more advanced compared with adults. These tumors are, however, associated with a higher cure rate as they are most radiosensitive. Radiotherapy with neo-adjuvant chemotherapy is currently the treatment of choice. Both cases achieved satisfactory control of the disease and are presently under close follow-up.

Concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma of the undifferentiated type.

The result with radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma (NPC) was disappointing. Encouraging results have been reported with the use of concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. Hence, we decided to explore the use of this treatment schedule in patients who presented with locally advanced disease (UICC/AJCC classification system). Between July 1995 and March 1996, 14 patients with locally advanced NPC were treated with the following schedule: radiation therapy was given conventionally to a total of 66 to 70 Gy to both the nasopharynx and neck with or without parapharyngeal/intracavitary boost; chemotherapy consisted of intravenous cisplatin at 20 mg/m2/day and intravenous 5-flurouracil 1000 mg/m2/day, infused over 8 hours on days 1 to 4 during the first and fifth week of radiation therapy. Depending on the patient's tolerability and clinical assessment of toxicity, a third cycle of chemotherapy was planned 4 to 5 weeks after the second cycle, upon the completion of the radiotherapy. Twelve patients completed all intended treatment. Two patients failed to do so due to treatment-related mortality. The median follow-up duration was 30 months. Limiting toxicities were myelosuppression and oropharyngeal mucositis. The overall response rate was a 100% at both the primary and nodal sites of disease. The median disease-free survival was 21 months. Forty per cent of the patients were alive at 3 years. This treatment schedule was associated with an unacceptable treatment-related death rate. As a result, this protocol was terminated.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.

Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma.

PURPOSE: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients. PATIENTS AND METHODS: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naive patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible. RESULTS: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3-4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive. CONCLUSIONS: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.