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.

Parapharyngeal metastasis in hepatocellular carcinoma-a rare entity.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It most commonly metastasizes haematogenously to the lungs and bones, less commonly via lymphatics to lymph nodes. However, metastasis to the parapharyngeal space has yet to be reported. This is the first clinical report of the treatment of parapharyngeal metastasis from HCC. The case of a 46-year-old man who was found to have a parapharyngeal soft tissue mass during routine follow-up 12 years post deceased-donor liver transplantation for hepatitis B-related HCC is reported here. This was investigated and diagnosed to be metastatic HCC. He underwent excision of the parapharyngeal metastasis, followed by adjuvant radiotherapy. Parapharyngeal metastasis is a rare occurrence in HCC. It is important to be cognizant of the possibility of disease spread to this location in order to ensure early detection and treatment. Surgical excision with adjuvant radiotherapy should be considered to achieve disease control.

Synchronous symptomatic parathyroid carcinoma and parathyroid adenoma with incidental follicular thyroid carcinoma.

We describe the case of an 89-year old Caucasian woman admitted with confusion and severe clinical manifestations of acute hypercalcaemia. There was no history suggestive of any malignancy and initial management included correction of the hypercalcaemia with intravenous fluid therapy. Sestamibi parathyroid scintigraphy and neck ultrasonography demonstrated a 4cm left-sided thyroid lesion and a nearly 2cm right-sided thyroid lesion. The patient underwent a total thyroidectomy and parathyroidectomy. Histology confirmed a concomitant parathyroid adenoma, parathyroid carcinoma and follicular thyroid carcinoma. To our knowledge, this is the first reported case in the literature.

Unusual metastatic presentations of a primary right parapharyngeal acinic cell adenocarcinoma.

Acinic cell adenocarcinoma (ACA) is a malignant epithelial neoplasm of the salivary glands. The patient reported herein presented with an unusual case of a metastatic ACA originating from the right parapharyngeal region, which eventually metastasized to the ipsilateral cavernous sinus and the contralateral mandibular ramus. The trigeminal nerve may have served as a channel for the spread of the cancer from the right parapharyngeal region to the cavernous sinus, and subsequently to the left mandibular ramus. The widening of the left inferior alveolar nerve canal was an early sign of metastasis in this case.

Pseudogout - a rare manifestation of hungry bone syndrome after focused parathyroidectomy.

Pseudogout, also known as calcium pyrophosphate deposition disease, is a rheumatological condition arising from accumulation of calcium pyrophosphate dihydrate crystals in connective tissues. We present a case of a 56-year-old Bangladeshi woman who underwent focused right inferior parathyroidectomy for primary hyperparathyroidism from a right inferior parathyroid adenoma. On the first post-operative day, she complained of left elbow painful swelling with redness and warmth. Arthrocentesis of left elbow was done due to suspicion of septic arthritis. Two weeks prior to this surgery, she had sudden bilateral knee swelling was diagnosed in her home country of bilateral knee osteoarthritis with effusion and arthrocentesis showed no crystals. Aspiration of left elbow showed calcium pyrophosphate crystals, associated with post parathyroidectomy hypocalcemia, hypomagnesemia confirming pseudogout. Her uric acid level was normal. Bilateral wrist x-rays showed triangular fibrocartilage complex chondrocalcinosis. The patient's condition improved with colchicine and naproxen, as well as calcium and magnesium replacement. Her left elbow swelling and pain resolved. Pseudogout flare is a rare but known sequelae after parathyroidectomy. Early recognition and expeditious treatment is essential.

The revolving door: antibiotic allergy labelling in a tertiary care centre.

BACKGROUND: Patients frequently report antibiotic allergies; however, only 10% of labelled patients have a true allergy. AIM: We investigated the documentation of antibiotic 'allergy' labels (AAL) and the effect of labelling on clinical outcomes, in a West Australian adult tertiary hospital. METHODS: Retrospective cross-sectional analysis of patients captured in the 2013 and 2014 National Antimicrobial Prescribing Surveys was carried out. Data were collected on documented antibiotic adverse drug reactions, antibiotic cost, prescribing appropriateness, prevalence of multi-drug resistant organisms, length of stay, intensive care admission and readmissions. RESULTS: Of the 687 patients surveyed, 278 (40%) were aged 70 or above, 365 (53%) were male and 279 (41%) were prescribed antibiotics. AAL were recorded in 122 (18%) patients and the majority were penicillin labels (n = 87; 71%). Details of AAL were documented for 80 of 141 (57%) individual allergy labels, with 61 describing allergic symptoms. Patients with beta-lactam allergy labels received fewer penicillins (P = 0.0002) and more aminoglycosides (P = 0.043) and metronidazole (P = 0.021) than patients without beta-lactam labels. Five patients received an antibiotic that was contraindicated according to their allergy status. Patients with AAL had significantly more hospital readmissions within 4 weeks (P = 0.001) and 6 months (P = 0.025) of discharge, compared with unlabelled patients. The majority (81%) of readmitted labelled patients had major infections. CONCLUSIONS: AAL are common, but poorly documented in hospital records. Patients with AAL are significantly more likely to require alternative antibiotics and hospital readmissions. There may be a role for antibiotic allergy delabelling to mitigate the clinical and economic burdens for patients with invalid allergy labels.

MRI for transformation of preserved organs and their pathologies into digital formats for medical education and creation of a virtual pathology museum. A pilot study.

AIM: To evaluate the feasibility of magnetic resonance imaging (MRI) for the transformation of preserved organs and their disease entities into digital formats for medical education and creation of a virtual museum. MATERIALS AND METHODS: MRI of selected 114 pathology specimen jars representing different organs and their diseases was performed using a 3 T MRI machine with two or more MRI sequences including three-dimensional (3D) T1-weighted (T1W), 3D-T2W, 3D-FLAIR (fluid attenuated inversion recovery), fat-water separation (DIXON), and gradient-recalled echo (GRE) sequences. Qualitative assessment of MRI for depiction of disease and internal anatomy was performed. Volume rendering was performed on commercially available workstations. The digital images, 3D models, and photographs of specimens were archived into a workstation serving as a virtual pathology museum. RESULTS: MRI was successfully performed on all specimens. The 3D-T1W and 3D-T2W sequences demonstrated the best contrast between normal and pathological tissues. The digital material is a useful aid for understanding disease by giving insights into internal structural changes not apparent on visual inspection alone. Volume rendering produced vivid 3D models with better contrast between normal tissue and diseased tissue compared to real specimens or their photographs in some cases. The digital library provides good illustration material for radiological-pathological correlation by enhancing pathological anatomy and information on nature and signal characteristics of tissues. In some specimens, the MRI appearance may be different from corresponding organ and disease in vivo due to dead tissue and changes induced by prolonged contact with preservative fluid. CONCLUSIONS: MRI of pathology specimens is feasible and provides excellent images for education and creating a virtual pathology museum that can serve as permanent record of digital material for self-directed learning, improving teaching aids, and radiological-pathological correlation.

The positive impact of cytological specimens for EGFR mutation testing in non-small cell lung cancer: a single South East Asian laboratory's analysis of 670 cases.

OBJECTIVES: To compare the rejection rates of non-small cell lung cancer (NSCLC) samples obtained by differing sampling methods for testing by Sanger sequencing for epidermal growth factor receptor (EGFR) mutations. To assess the association between unsatisfactory outcomes and the quantity of DNA extracted from cytological versus histological samples. METHODS: Six hundred and seventy NSCLC samples referred to our centre from 2008 to 2010 were reviewed as a consequence of sample rejection, presence of EGFR mutations, cytological versus histological sampling methods, DNA quantity and the unsatisfactory genotyping rate. RESULTS: Eighty samples were rejected for testing in similar proportions of histological and cytological samples (11.9% versus 10.9%) usually (n = 75) because the amount of cellular material was judged insufficient in small biopsies or cytology samples. The remaining 590 samples on which EGFR testing was attempted yielded 51 (8.6%) unsatisfactory test outcomes caused by failure of the polymerase chain reaction (PCR) (n = 47 cases), uninterpretable Sanger chromatograms (n = 3 cases) and insufficient DNA extracted for PCR (n = 1 case). The difference in rates of unsatisfactory outcomes between cytological samples (seven of 147 samples or 4.7%) versus tissue samples (44 of 443 samples or 9.9%) was clinically relevant but not statistically significant (Mann-Whitney test; P < 0.081). There was no association between the concentration of DNA extracted and the likelihood of an unsatisfactory analysis; which was similar in all types of sections (large and small) while 0% of 37 cytology slides were unsatisfactory. CONCLUSIONS: Utilizing cytology samples for EGFR testing avoids unnecessary patient re-biopsing and yields a clinically superior satisfactory rate to the overall satisfactory rate of tissue biopsies of NSCLC. The quality rather than quantity of DNA extracted may be a more important determinant of a satisfactory result.

Point-prevalence study of inappropriate antibiotic use at a tertiary Australian hospital.

A point-prevalence study at a tertiary Australian hospital found 199 of 462 inpatients (43%) to be receiving antibiotic therapy. Forty-seven per cent of antibiotic use was discordant with guidelines or microbiological results and hence considered inappropriate. Risk factors for inappropriate antibiotic prescribing included bone/joint infections, the absence of infection, creatinine level >120 µmol/L, carbapenem or macrolide use and being under the care of the aged care/rehabilitation team. In the setting of finite antimicrobial stewardship resources, identification of local determinants for inappropriate antibiotic use may enable more targeted interventions.

Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases.

Acute respiratory distress syndrome, a severe form of acute lung injury (ALI), is a major cause of death during influenza pneumonia. We have provided evidence for the involvement of recruited neutrophils, their toxic enzymes such as myeloperoxidase and matrix metalloproteinases (MMPs), and neutrophil extracellular traps in aggravating alveolar-capillary damage. In this study, we investigated the effects of doxycycline (DOX), an inhibitor of MMPs, on influenza-induced ALI. BALB/c mice were infected with a sublethal dose of mouse-adapted virulent influenza A/Aichi/2/68 (H3N2) virus, and administered daily with 20mg/kg or 60 mg/kg DOX orally. The effects of DOX on ALI were determined by measuring inflammation, capillary leakage, and MMP activities. Furthermore, levels of T1-α (a membrane protein of alveolar type I epithelium) and thrombomodulin (an endothelial protein) in the bronchoalveolar lavage fluid were evaluated by Western blot analysis. Our results demonstrate significantly decreased inflammation and protein leakage in the lungs after DOX treatment. Levels of MMP-2 and MMP-9 activity, T1-α and thrombomodulin were also diminished in the DOX-treated group. These findings were corroborated by histopathologic analyses, which demonstrated significant reduction in lung damage. Although DOX treatment reduced ALI, there were no effects on virus titers and body weights. Taken together, these results demonstrate that DOX may be useful in ameliorating ALI during influenza pneumonia. Further studies are warranted to determine whether DOX can be used in combination with anti-viral agents to alleviate severe influenza pneumonia.

Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.

AIMS: To test the reproducibility of the current World Health Organization (WHO) classification of thymic epithelial tumours and to determine the level of interobserver variation within a group of pathologists, all with experience and expertise in thoracic pathology. METHODS AND RESULTS: Ninety-five thymic tumours were circulated to a group of 17 pathologists in the UK and The Netherlands over a 1-year period. Participants were asked to classify them according to WHO criteria. The diagnoses were subjected to statistical analysis and kappa values calculated. The overall level of agreement was moderate (kappa 0.45). When the categories were reduced in number by creating two groups, (A + AB + B1 + B2 and B3 + C), the level of agreement increased to 0.62. An alternative grouping (A + AB + B1 and B2 + B3 + C) increased it slightly further. The best agreement was in tumour types A and AB. Difficulties arose in distinguishing B1 tumours from B2 tumours and B2 tumours from B3 tumours. CONCLUSIONS: Although the WHO system describes a number of well-defined tumour types with clear diagnostic criteria, the overall level of agreement was moderate and improved if some groups were amalgamated.

A novel mutation in the XPA gene associated with unusually mild clinical features in a patient who developed a spindle cell melanoma.

BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun-exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER-defective form of XP of seven complementation groups, designated XP-A to XP-G. These complementation groups correspond to different proteins involved in the NER process. XP-A classically includes some of the most severely affected patients. OBJECTIVES: We describe a 61-year-old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene. METHODS: Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing. RESULTS: Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP-A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A-->G at the eighth nucleotide of intron 4 causing aberrant splicing and a nonfunctional truncated XP-A protein. However, a small amount of normally spliced mRNA was detected at <5% the level in normal cells. CONCLUSIONS: The small amount of normally spliced mRNA detected may be sufficient to explain the relatively mild clinical features in our patient.

Eczema-like plaques secondary to enoxaparin.

Low-molecular-weight heparins are used extensively in acute medicine. They are generally well tolerated but may cause a rare, eczema-like type IV hypersensitivity reaction. We report 3 cases of this eruption and speculate that it may be significantly under-reported due to misidentifying the causal drug, which may have serious consequences. We discuss treatment alternatives such as fondaparinux sodium, which may rarely cross-react.

The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic.

BACKGROUND: Previous studies have reached differing conclusions about the utility of anal cytology as a screening tool for anal intraepithelial neoplasia (AIN). There is a need also to establish whether HPV typing offers a useful adjunct to screening. METHODS: We analysed data from 99 consecutive homosexual/bisexual male patients (89 HIV-1 positive) who underwent high resolution anoscopy. Follow up visits for these patients were also included, giving a total of 160 anoscopic procedures. Comparison was made between results of anal cytology using the sampling method of Palefsky, and histological findings of biopsies taken from abnormal areas seen on high resolution anoscopic examination of the anal canal. Swabs taken concurrently with the cytology were analysed for the presence of human papillomavirus (HPV) DNA and compared with the cytological and histological findings. RESULTS: The sensitivity of the cytology was 83%, and the specificity 38% when compared with histology. At screening of 34 asymptomatic men, 83% had anal cytological dysplasia and 78% had AIN. There were no significant differences in the prevalence of hrHPV genotypes between different cytological or histological grades of abnormalities. CONCLUSION: Anal cytology by the Palefsky method is simple to undertake, has a sensitivity and specificity comparable with cervical cytology, and can therefore be used as the basis of a pilot screening project in centres with large cohorts of HIV positive homosexual men who have a high risk of developing anal carcinoma. HPV genotyping is not a useful adjunct to cytological screening.

The inframammary fold: contents, clinical significance and implications for immediate breast reconstruction.

The amount of breast tissue within the inframammary fold (IMF) is controversial. Preservation of the IMF during mastectomy facilitates breast reconstruction and led some surgeons to practice conservation of the IMF, contrary to traditional descriptions of total mastectomy. The aim of this study was to analyse the clinical significance of IMF tissue content. A total of 50 IMF specimens were studied from 42 patients who underwent mastectomy between January 2001 and December 2002. The amount of breast tissue within each IMF was evaluated. The median patient age was 46 (range 33-86) years. The median body mass index was 23.4 (18.1-38.3)kg/m(2). The median IMF volume resected was 2 (0.2-9.7)cm(3) which was 0.6 (0.1-2.0)% of the breast volume. Ten specimens (20%) contained breast tissue and one (2%) contained breast tissue and an inframammary lymph node. Three specimens (6%) containing fibrofatty tissue without breast parenchyma had intramammary lymph nodes within the IMF. One patient (2%) who had a mastectomy for invasive ductal carcinoma had IMF tissue containing a lymph node within the IMF with breast cancer metastasis. The presence of breast tissue or lymph nodes within the IMF was unrelated to patient age, body mass index, the amount of IMF tissue in relation to breast volume and absolute breast size. Our finding that breast tissue and intramammary lymph nodes are present in 28% of IMF specimens requires re-consideration of the safety of preserving the IMF at mastectomy. If IMF tissue is resected and the immediate breast reconstruction is performed, the superficial fascial system should be reconstructed after excision of the IMF tissue in order to recreate the inframammary crease.

Composition and protein quality of honeybee-collected pollen of Eucalyptus marginata and Eucalyptus calophylla.

The composition and protein quality of the two most important Western Australian export-quality pollens were investigated. Crude pollen protein content was 20.6% and 27.9% for Jarrah (Eucalyptus marginata) and Marri (Eucalyptus calophylla), respectively. Lysine was the limiting amino acid relative to the FAO protein scoring pattern (Food and Agriculture Organization of the United Nations), and the amino acid scores were 0.73 and 0.66 for Jarrah and Marri pollen, respectively. Apparent biological value (BV) was 61.7 for Jarrah pollen, 66.9 for Marri pollen and 71.4 for the casein controls. Adjusted protein efficiency ratio (PER) values were 2.5, 1.2 and 1.1 for casein and Jarrah and Marri pollens, respectively. Apparent net protein utilization (NPU) was significantly reduced for both pollens (32.8 for Jarrah and 39.5 for Marri) compared to casein (63.6). The low apparent NPU values result from the relatively low digestibility of pollens. Apparent digestibility was 52 and 59% for Jarrah and Marri pollen compared to 89% for casein. Although both Jarrah and Marri pollen are relatively high in protein and have favorable amino acid patterns, their relatively low digestibility will be a limiting factor in their usefulness as a food for humans and monogastric animals. The proximate analysis and mineral content of the pollens are also presented.