Delays in lung cancer management pathways between rural and urban patients in North Queensland: a mixed methods study.

BACKGROUND: Despite advances in medical therapies, disparity in outcome between rural and urban patients remain in Australia and many Western countries. AIMS: To examine time delays in lung cancer referral pathways in North Queensland (NQ), Australia, and explore patients' perspective of factors causing these delays. METHODS: Prospective study of patients attending three cancer centres in Townsville, Cairns and Mackay in NQ from 2009 to 2012. Times along referral pathway were divided as follows: Onset of symptoms to treatment (T1), symptoms to general practitioner (GP) (T2), GP to specialist (T3) and Specialist to treatment (T4). Quantitative and qualitative methods were used for analysis. RESULTS: In total, 252 patients were participated. T1 was influenced by remoteness (125 days in Townsville vs 170 days for remote, P = 0.01), T2 by level of education (91 days for primary education vs 61 days for secondary vs 23 days for tertiary/Technical and Further Education (TAFE), P = 0.006), and age group (14 days for 31-50 years, 61 days for 51-70 years, 45 days for >71 years, P = 0.026), T3 by remoteness (15 days for Townville and 29.5 days for remote, P = 0.02) and T4 by stage of disease (21 days for Stage I, 11 days for Stage II, 34 days for Stage III 18 days for Stage IV, P = 0.041). Competing priorities of family and work and cost and inconvenience of travel were perceived as rural barriers. CONCLUSION: Remoteness, age and level of education were related to delays in various time lines in lung cancer referral pathways in NQ. Provision of specialist services closer to home may decrease delays by alleviating burden of cost and inconvenience of travel.

A Case of Burnt-Out Langerhans Cell Histiocytosis Presenting as Postpartum Hypopituitarism.

OBJECTIVE: To evaluate the case of a woman who presented with central hypogonadism and diabetes insipidus and further developed a persistent cough leading to an unexpected diagnosis of burnt-out Langerhans cell histiocytosis (LCH). METHODS: Clinical and laboratory endocrine evaluation, magnetic resonance imaging, high-resolution computed tomography, and open-lung biopsy results are discussed. RESULTS: A 28-year-old woman presented at 10 months postpartum with polydipsia, polyuria, and amenorrhea for 3 months. Her results showed a prolactin level of 25 µg/L (reference,<23.5 µg/L), estrogen level of 91 pmol/L (reference, 110-180 pmol/L), follicle-stimulating hormone level of 6 IU/L (reference, 2-20 IU/L), and luteinizing hormone level of 6 IU/L (reference, 2-70 IU/L). A water-deprivation test found a sodium concentration of 148 mmol/L (reference, 135-145 mmol/L), serum osmolality of 310 mmol/kg (reference, 275-295 mmol/kg), and urine osmolality of 107 mmol/kg (reference, 50-1450 mmol/kg) that improved to 142 mEq/L, 295 mmol/kg, and 535 mmol/kg, respectively, after desmopressin administration. Gadolinium-enhanced pituitary magnetic resonance imaging demonstrated a markedly thickened stalk with uniform enhancement. Chest high-resolution computed tomography confirmed bilateral upper-zone cystic lung disease suggestive of either pulmonary lymphangioleiomyomatosis or LCH. Eventual histology showed CD1a-positive burnt-out LCH. This differentiation was crucial as pulmonary lymphangioleiomyomatosis exacerbates with estrogen therapy and pregnancy, which the patient was able to successfully pursue without disease exacerbation. CONCLUSION: The patient's initial presentation was considered as lymphocytic hypophysitis, but subsequent cystic changes on high-resolution computed tomography led to a unifying definitive diagnosis of burnt-out LCH. This case highlights the importance of investigating for uncommon secondary causes of hypophysitis.

B-cell clonality determination using an immunoglobulin kappa light chain polymerase chain reaction method.

To augment the detection of clonality in B-cell malignancies, we designed a consensus primer kappa light chain gene (Igkappa) polymerase chain reaction (PCR) assay in combination with a consensus primer immunoglobulin heavy chain gene (IgH) PCR assay. Its efficacy was then evaluated in a series of 86 paraffin tissue samples comprising neoplastic and reactive lymphoproliferations. Analysis after PCR was accomplished by 10% native polyacrylamide gel electrophoresis after heteroduplex pretreatment of PCR products and by a post-PCR chip-based capillary electrophoresis analytic method. Overall, 49 of 68 (72%) of mature B-cell neoplasms yielded discrete Igkappa gel bands within the predicted size range with no clonotypic Igkappa products observed among reactive lymphoid or T-cell proliferations. The application of Igkappa PCR improved overall sensitivity from 81% with IgH PCR alone to 90% with combined Igkappa/IgH PCR, with this effect being most notable in germinal center-related lymphomas. Sequencing of positive Igkappa rearrangements revealed that most rearrangements involved members of the Vkappa1 (40%) and Vkappa2 (34%) gene families along with Jkappa1 (26%), Jkappa2 (23%), and Jkappa4 (51%) gene segments. Involvement of Vkappa pseudogenes was identified in 24% of cases with Vkappa-KDE rearrangements. Our results demonstrate the efficacy of Igkappa PCR in improving the detection rate of clonality in B-cell neoplasms and further introduce a novel post-PCR chip-based capillary electrophoresis analytic method for rapid PCR fragment size evaluation.

Nodular glomerulosclerosis in cystic fibrosis mimics diabetic nephropathy.

BACKGROUND/AIMS: Despite the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator, being widely expressed throughout the kidney, there is no clearly defined renal phenotype in patients with cystic fibrosis. As patients with cystic fibrosis survive longer progressive pancreatic destruction may lead to abnormal glucose tolerance and diabetes mellitus, which in the kidney may be associated with the characteristic changes of nodular glomerulosclerosis. METHODS: The adult cystic fibrosis service at the Alfred hospital consists of a cohort of 200 patients. We describe 3 cystic fibrosis patients with impaired renal function who had renal biopsies performed as part of their diagnostic work-up. All patients had fasting plasma glucose levels, oral glucose tolerance tests and measurements of HbA1c performed to assess for the presence of cystic fibrosis-related diabetes mellitus. RESULTS: The renal biopsies of all 3 patients showed histological changes characteristic of diabetic nephropathy. In all cases described characteristic Kimmelstiel-Wilson nodules were present. However, in all 3 patients the presence of impaired glucose tolerance and diabetes mellitus was excluded using standard biochemical diagnostic criteria. CONCLUSION: We describe 3 adult CF patients, who on renal biopsy had histological evidence of nodular glomerulosclerosis in the absence of abnormal glucose metabolism. We speculate that the pro-inflammatory cytokine profile, typical of cystic fibrosis, predisposes to the lesions described.