The safety and efficacy of benzbromarone in gout in Aotearoa New Zealand.

BACKGROUND: Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid. AIM: To assess the safety and efficacy of benzbromarone in a real-life setting. METHODS: All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified. Prescribers were sent a questionnaire for each individual. Information on demographics, efficacy of previous urate-lowering drugs and reasons for discontinuation were collected. Specific information about the dose, effect on serum urate, adverse effects and liver function tests after commencing benzbromarone was recorded. RESULTS: Completed questionnaires were returned for 123 of 164 (75%) patients. Mean (SD) serum urate prior to benzbromarone was 0.57 (0.12) mmol/L, and estimated glomerular filtration rate was 50.3 (22.8) mL/min/1.73 m(2) . The median dose of benzbromarone was 100 mg/day (25-200 mg/day). Six months after commencing benzbromarone, mean (SD) serum urate was 0.35 (0.12) mmol/L. Benzbromarone-related adverse events included rash (n = 4), diarrhoea (n = 9), nausea (n = 6) and urate stones (n = 3). Liver function test abnormalities were uncommon and tended to be mild. There were 14 patient deaths; none was considered related to benzbromarone. Allopurinol had been prescribed prior to benzbromarone in 117 of 123 patients; median maximum allopurinol dose was 200 mg/day (range 25-600 mg/day), and 19% patients received allopurinol >300 mg/day. CONCLUSION: Benzbromarone provides useful urate-lowering efficacy and does not appear unsafe in patients with gout. Urate-lowering therapy prescribing requires further optimisation.

Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories.

Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.

Are axillary recurrence and overall survival affected by axillary extranodal tumor extension in breast cancer? Implications for radiation therapy.

PURPOSE: To determine the overall survival and local recurrence significance of axillary lymph node extranodal tumor extension (ETE) and whether axillary/chest-wall irradiation influenced any of these outcomes. MATERIALS AND METHODS: The records of 81 breast cancer patients treated with radical or modified radical mastectomy at a single surgical practice were eligible for study. Thirty-four patients had ETE: 17 with focal ETE (< 10 x high-power field) and 17 with extensive ETE (> 10 x high-power field). RESULTS: With a median follow-up duration of 92 months, only two patients had an axillary recurrence (2%): one had focal ETE and one had no ETE. Neither of these patients received axillary radiation therapy. Overall survival and recurrence-free survival were significantly decreased with ETE in patients whether axillary radiation therapy had been administered or not. Analysis showed that the age of the patient correlated significantly with extensive ETE (P = .04) and that the number of positive lymph nodes (< or = three v > three) correlated significantly with ETE (whether focal or extensive) (P = .0001). A multivariate analysis of extranodal tumor extension and number of positive lymph nodes showed that ETE was associated with decreased survival (P = .05), although to a lesser degree than number of positive lymph nodes (P = .003). CONCLUSION: These results show that ETE is associated with decreased survival and increased recurrence rates regardless of the extent of the radiation therapy field. Also, ETE does not necessarily indicate a significantly increased incidence of axillary recurrence. Therefore, axillary irradiation based on this pathologic finding may not be indicated.

Mucins in breast carcinoma.

Mucins produced by breast carcinoma have been shown to be neutral and sialomucins. Colonic mucins were found to be sulfated with an o-acylated sialomucin component that was reported by Culling to be specific to normal colonic epithelium and colonic adenocarcinoma. This type of molecule gives a positive staining after potassium hydroxide/periodate borohydride (KOH/PBT) treatment. We studied the types of mucin in five medullary carcinomas, 10 infiltrating duct carcinomas, and 10 infiltrating lobular carcinomas of the breast. Twenty-two of 25 cases were positive for neutral mucins; 14 of 25 were positive for sialomucin. Sulfated mucins were found in five of 10 cases of infiltrating lobular carcinoma, and in six of 10 cases there was a positive periodic acid-Schiff reaction following KOH/PBT. This study illustrates the presence of sulfated mucin and o-acylated sialomucin in infiltrating lobular carcinoma of the breast. Thus, mucin stains cannot be used in differentiating metastatic breast carcinoma from colonic carcinoma. The significance of this finding and its relation to tumor histogenesis, typing, and biologic behaviors require further analysis.

Detection of human papillomavirus DNA by in situ hybridization and polymerase chain reaction in human papillomavirus equivocal and dysplastic cervical biopsies.

One hundred twenty-one paraffin-embedded cervical biopsy specimens were tested for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction. By in situ hybridization using probes for HPV types 6/11, 16/18, 31/33/35, 42/43/44, 51/52, and 45/56, HPV DNA was found in none of 20 normal/squamous metaplasia biopsy specimens, in one of 76 HPV equivocal biopsy specimens, in seven of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of 13 moderate/severe dysplasia biopsy specimens. Polymerase chain reaction using HPV L1 consensus sequence primers followed by filter hybridization of the amplification products was positive for HPV DNA in two of 20 normal/squamous metaplasia biopsy specimens, in 23 of 76 HPV equivocal biopsy specimens, in eight of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of 13 moderate/severe dysplasia biopsy specimens. Among biopsies that tested positive by polymerase chain reaction but that were negative by in situ hybridization, the most commonly identified HPV was type 16. We conclude that although HPV equivocal biopsy specimens contain HPV DNA more frequently than histologically normal tissue, the majority of biopsy specimens in this category test negative for HPV DNA. The clinical significance of a positive test for HPV, in the absence of unequivocal histologic changes, remains to be determined.

Bone marrow involvement by lobular carcinoma of the breast cannot be identified reliably by routine histological examination alone.

The aims of this study were twofold: (1) to evaluate the ability of pathologists to recognize infiltration of bone marrow core biopsy specimens by breast carcinoma, particularly lobular carcinoma, using routine hematoxylin-eosin (HE) sections; and (2) if indicated, to determine the reasons for difficulties in diagnosis. Thirty-six bone cores obtained before bone marrow harvest were involved by breast carcinoma and were confirmed by pancytokeratin immunostains. Thirty of the 36 were ductal carcinomas and six were lobular carcinomas. Fourteen negative bone core biopsy specimens (from patients with breast cancer or lymphoma) were included as controls. These 50 bone cores were reviewed by three surgical pathologists. Lobular carcinoma was correctly identified in only 39% of positive specimens as compared with 88% for ductal carcinoma. After instruction, sensitivity for the detection of lobular carcinoma improved to 61% but at the expense of an unacceptably high rate of false-positive diagnoses (18%). None of the three pathologists was able to achieve both high sensitivity and high specificity in recognizing lobular carcinoma in the bone marrow. Lobular carcinoma was difficult to detect because of tumor cell size similar to hematopoietic cells, infiltration as single cells, presence of bland cytological features, and paucity of tissue reaction to the tumor. Although the number of cases of bone marrow involved by lobular carcinoma is small, these findings suggest that pancytokeratin stains should be performed routinely in the evaluation of bone core biopsy specimens from patients with lobular carcinoma, and probably from patients with ductal carcinoma whose HE-stained bone core biopsy specimens are considered negative for tumor.

Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast.

To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin-embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion.

Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening.

OBJECTIVE: To compare the cytologic diagnoses and specimen adequacy of a fluid-based, thin-layer preparation and conventional Papanicolaou tests. METHODS: A total of 7360 women from six separate sites-three screening centers and three hospitals-participated in split-sample/matched-pair, double-masked clinical trials. A conventional Papanicolaou test was performed, after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide (ThinPrep) was prepared using the ThinPrep 2000 automated slide processor (Cytyc Corp., Boxborough, MA). Conventional and ThinPrep slides were read independently. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. RESULTS: For the three screening centers, 65% more diagnoses of low-grade squamous intraepithelial lesions and higher were made on the ThinPrep slides (P < .001); for the three hospital centers, 6% more of these diagnoses were made with the ThinPrep method (P = .294). Comparison of specimen adequacy showed a significant increase in satisfactory specimens and a reduction in the number of "satisfactory but limited by" specimens using the ThinPrep method (P < .001). CONCLUSION: The fluid-based, ThinPrep method of sample preparation resulted in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method.

Comparison of tests for the lupus anticoagulant and antiphospholipid antibodies in systemic lupus erythematosus.

A variety of laboratory assays are used to screen for the presence of the lupus anticoagulant. Six commonly used coagulation tests, and the ELISA assay for antiphospholipid antibody using three different substrate phospholipids, have been evaluated in 110 patients with systemic lupus erythematosus or lupus-like disease. One or more coagulation assays was abnormal in 41% (45/110) of the patients. No individual test detected more than 78% of these abnormalities, indicating that a single phospholipid based coagulation test cannot be used to screen for a possible lupus anticoagulant. A combination of Actin FSL, DTTA and DRVVT detected all the abnormalities. The most sensitive two-test combination was Actin FSL and DRVVT. Approximately half (56%) of the patients with a positive clotting test had an abnormal antiphospholipid antibody assay. A similar proportion (58%) of the aPL positive patients had a prolonged coagulation test. The marked discordance between the coagulation assays and a positive antiphospholipid antibody test further complicates the laboratory definition of this abnormality, at least in patients with systemic lupus erythematosus.

Immunocytochemical staining of c-erb B-2 oncogene in fine-needle aspirates of breast carcinoma: a comparison with tissue sections and other breast cancer prognostic factors.

The role of fine-needle aspiration (FNA) in breast cancer management is expanding to include prognostic in addition to diagnostic studies. This study was undertaken to compare the immunohistochemical staining of c-erbB-2, a breast cancer prognostic factor, on cytologic FNA smears of breast cancer with that on corresponding formalin-fixed, paraffin-embedded tissue sections of the same tumor and to correlate the c-erbB-2 expression with other known breast cancer prognostic factors. FNA smears (destained, alcohol-fixed, Pap-stained direct smears) and corresponding tissue sections (formalin-fixed, paraffin-embedded, unstained sections) from 36 primary breast carcinomas were stained immunohistochemically with c-erbB-2 antibody using an avidin-biotin procedure. Ten tumors (28%) showed strong positive staining for c-erbB-2 on the FNA smear and, of those ten, seven were positive on the corresponding tissue section and three were negative. In several of the cytology and tissue positive cases, staining on the tissue section was significantly weaker than on the FNA smear. Two cases involved treatment with preoperative chemotherapy; in one of those cases, tissue staining was weaker than cytologic staining, and, in the other case, both were negative. Correlation of c-erbB-2 staining with other prognostic factors showed an association between positive c-erbB-2 staining and high nuclear grade. Our results indicate that immunohistochemical staining for c-erbB-2 can be performed on destained FNA smears of breast carcinomas and may be more sensitive on the cytologic specimens than on formalin-fixed, paraffin-embedded tissue sections.

Fine needle aspiration cytology of mycobacterial spindle cell pseudotumor. A case report.

We report a case of mycobacterial spindle cell pseudotumor (MSP) in a lymph node from an acquired immunodeficiency syndrome patient diagnosed by fine needle aspiration (FNA). The FNA cytology was characterized by spindle cell proliferation without the typical foamy histiocytes usually seen in mycobacterial infections and mimicked a mesenchymal neoplasm, particularly Kaposi's sarcoma. This case illustrates the importance of including MSP in the differential diagnosis of lymph node FNAs from immunocompromised patients, particularly those that show spindle cell proliferation suspicious for Kaposi's sarcoma or another mesenchymal neoplasm.

Specimen adequacy of ThinPrep sample preparations in a direct-to-vial study.

OBJECTIVE: To assess specimen adequacy of the ThinPrep slide preparation method in routine use. STUDY DESIGN: Two studies, a feasibility study of 299 women and a clinical study of 499 women, were conducted. A broom-type collection device was used and rinsed directly into Pre-servCyt vials. Slides were prepared with the ThinPrep 2000 device, screened and classified according to the Bethesda System. The proportion of ThinPrep slides described as "Satisfactory But Limited By: No Endocervical Component (SBLB:No ECC)" was then compared to the proportion of SBLB: No ECC slides found on conventional smears in a previously conducted clinical trial of over 7,000 patients. RESULTS: For the feasibility study the proportion of ThinPrep slides described as SBLB: No ECC was 9.36% as compared to the clinical trial combined rate of 9.4% for conventional smears. For the clinical study, 4.96% of ThinPrep slides were SBLB:No ECC as compared to the 4.4% SBLB:No ECC rate for conventional smears from the same clinical trial. The proportions were statistically equivalent for both studies. CONCLUSION: It is expected that the rate of representing endocervical component will be maintained when the ThinPrep preparation method is used routinely in place of the conventional cytologic smear method.

Gout.

In theory gout is easy to diagnose and treat. In reality gout is difficult to treat because of; the important drug and disease interactions of NSAIDs, the frequency of toxicity with colchicine and the requirement for high degrees of compliance when using hypouricaemic agents.

Melioidosis: a new disease to New Zealand.

The first case of melioidosis diagnosed in New Zealand is described. The patient presented with an abscess overlying the liver, which resolved on oral cotrimoxazole therapy, without the need for surgical drainage.

Peculiarities of PAPA syndrome.

OBJECTIVES: To describe a family from New Zealand with the pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, an autoinflammatory, variably expressed, erosive destructive form of arthritis. METHODS: Information was gained through medical records and interviews of the affected patients and wider family. DNA sequencing was performed at Seay Center for Musculoskeletal Research Texas Scottish Rite Hospital for Children. RESULTS: Five patients were affected over three generations with an E250Q mutation found on the CD2BP1 gene on chromosome 15. Common features included a severe, pauciarticular-onset, destructive peripheral arthritis, beginning at ages 5, 5, 2, 3 and 1(1/2) years. This combination marked cervical ankylosis (in two members), micrognathia and a more severe phenotype is unique. A third-generation family member treated early with DMARDs is following a less severe course. The skin involvement was variable, all with degrees of acne from puberty, though only one patient displayed pyoderma gangrenosum. A clear pattern of the arthritis switching off in adolescence and the triggering of skin disease was observed. CONCLUSIONS: Differing degrees of joint destruction, and cervical ankylosis in this family with the E250Q mutation demonstrate PAPA syndrome's variable expression. Further understanding of this rare condition and its pathway may allow better targeting of treatments, not just for families with this specific syndrome but also for other, more common, forms of arthritis.

CSF findings in 250 patients with serologically confirmed West Nile virus meningitis and encephalitis.

OBJECTIVE: To provide a large, comprehensive evaluation of the CSF findings in patients with serologically confirmed West Nile virus (WNV), CNS disease, and their correlation with outcome. METHODS: CSF samples from 334 WNV-infected hospitalized patients were analyzed. Information was available and extracted from the medical records of 250 of these patients, and CSF parameters correlated with clinical and epidemiologic features of disease (e.g., patient age, sex, outcome). RESULTS: Patients with meningitis had a mean of 226 cells/mm3, and those with encephalitis had a mean of 227 cells/mm3. Three percent of meningitis patients and 5% of encephalitis patients had fewer than 5 cells/mm3, and approximately 8% of both groups had more than 500 cells/mm3. Patients with meningitis had a mean of 41% neutrophils, and those with encephalitis had 45%. Forty-five percent of meningitis patients and 37% of encephalitis patients had at least 50% neutrophils in their initial CSF specimen. Neither the mean percent neutrophils nor their distribution differed significantly between groups. Forty-seven percent of encephalitis patients and 16% of meningitis patients had CSF protein of 100 mg/dL or greater (p < 0.01). Although specific CSF parameters, including nucleated cell count and protein concentration, correlated significantly with outcome, multivariate analysis suggested that their total predictive value was modest. Age was an additional predictor of outcome independent of CSF variables in all patients. CONCLUSIONS: Serologically confirmed West Nile virus meningitis and encephalitis produce similar degrees of CSF pleocytosis and are frequently associated with substantial CSF neutrophilia. Patients with encephalitis have higher CSF protein concentrations and are more likely to have adverse outcomes, including admission to long-term care facilities or even death after their acute illness. CSF findings were only a modest predictor of disease outcome, with patient age adding important independent prognostic information.

Inverted papilloma: an uncommon benign cause of a ureteral filling defect.

A case of inverted papilloma of the ureter in a 62-year-old man is presented along with a literature review of 14 cases. This rare benign tumor should enter the differential diagnosis of a ureteral filling defect especially when it has a smooth configuration. Preoperative consideration of this diagnosis may lead to intraoperative confirmation of pathology and conservative resection.

A retrospective review of yttrium-90 synovectomy in the treatment of knee arthritis.

We reviewed the case notes and X-rays of all patients with knee arthritis treated with yttrium-90 for the first time at a single institution from November 1981 to November 1995. Outcomes were assessed as 'improved' or 'not improved' by review of the case notes at 3, 6 and 12 months, and by the absence of further intra-articular (IA) steroid injections. Of the 121 knees treated, 87 had adequate follow-up information to allow an assessment of outcomes. Overall, 46% (95% CI 36-57) were improved at 12 months and 37% (95% CI 27-47) had no further IA injections (mean follow-up of 3.5 yr). Knees with osteoarthritis (OA) fared significantly worse with 10% (95% CI 0-29) vs 51% (95% CI 39-63) improved at 12 months (P < 0.05). Knees younger than 30 appeared to do better with 78% (95% CI 51-100) vs 28% (95% CI 17-45) having no further IA injections (P < 0.02). Knees with normal X-rays (Kellgren grade 0-1) did significantly better than those with more severe radiographic abnormalities (Kellgren grade 3-4), with 56% (95% CI 40-73) vs 24% (95% CI 8-40) improved (P < 0.01). Radiosynovectomy with yttrium-90 for knee arthritis appears to be of less value for patients with OA or with secondary OA changes on X-ray, and may be of more value for younger patients and those with spondyloarthropathies.