[Furuncular myiasis caused by Dermatobia hominis. Fortuitous diagnosis on extemporaneous macroscopic analysis of an excised cutaneous nodule]. / Myiase furonculoïde à Dermatobia hominis: diagnostic fortuit sur la coupe macroscopique extemporanée d'un nodule cutané.

BACKGROUND: Furuncular myiasis is a parasitic disease caused by the development of human botfly larva in the skin. It affects people living in tropical countries and travelers returning from these countries and concerns a number of medical specialties. One form of treatment involves surgical extraction of the parasites. PATIENTS AND METHODS: We report the case of a 47-year-old man returning from Guyana presenting two furuncle-like nodules of the skin on the right buttock and on the right shoulder blade. Extemporaneous intraoperative macroscopic examination of the buttock nodule resulted in diagnosis of myiasis caused by the human botfly, Dermatobia hominis. DISCUSSION: The diagnosis of furuncular myiasis is made primarily on clinical grounds and should be suspected on observation of an abscess in subjects returning from a tropical region. It is consequently rare to find D. hominis in biopsy specimens. In the present case, macroscopic examination showed an extremely rare image of the edge of the intact larva in a longitudinal cut, which to our knowledge has never been published to date.

Antidepressants and risk of prostate cancer: a nested case-control study.

Although the association between antidepressant drug use and risk of cancer has received considerable attention in the past years, no work has been done specifically on prostate cancer. We carried out a population-based case-control study to assess the risk of prostate cancer in association with exposure to tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). 7767 prostate cancer cases diagnosed between 1981 and 2000 were accrued through the Saskatchewan Cancer Agency. Saskatchewan Health identified a total of 31,068 male controls who were matched on age and calendar time. Data on exposure to TCAs and SSRIs were compiled from the Saskatchewan outpatient prescription drug database, and covered a period upto 24 years. A positive significant association was found between TCA use and risk of prostate cancer, when exposure took place 2-5 years before diagnosis, with rate ratios of 1.31, 1.58, and 2.42 at the low, medium and high average daily dose levels, respectively. Exposure to SSRIs was not found to be significantly associated with the risk of prostate cancer. TCA use 2-5 years in the past was associated with a small dose-dependent increase in the risk of prostate cancer. Nevertheless, detection bias could have contributed to the observed association.

The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study.

OBJECTIVE: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. METHODS: A case-cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. RESULTS: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50-1.36). Age > or = 65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02-5.15). CONCLUSIONS: In our SLE sample, age > or = 65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.

Lung cancer in systemic lupus erythematosus.

BACKGROUND: Evidence points to a link between systemic lupus erythematosus (SLE) and an increased risk of lung cancer. Our objective was to provide a brief report of the lung cancer cases from an SLE cohort, with respect to demographics, histology, and exposures to smoking and immunosuppressive medications. METHODS: Data were obtained from a multi-site international cohort study of over 9500 SLE patients from 23 centres. Cancer cases were ascertained through linkage with regional tumor registries. RESULTS: We analyzed information on histology subtype for 30 lung cancer cases that had occurred across five countries. Most (75%) of these 30 cases were female, with a median age of 61 (range 27-91) years. In eight cases, the histological type was not specified. In the remainder, the most common histological type reported was adenocarcinoma (N=8; two of the adenocarcinomas were bronchoalveolar carcinoma) followed by small cell carcinoma (N=6), and squamous cell carcinoma (N=6) with one case each of large cell carcinoma and carcinoid tumor. Most (71%) of the lung cancer cases were smokers; only the minority (20%) had been previously exposed to immunosuppressive agents. CONCLUSIONS: The histological distribution of the lung cancers from the SLE sample appeared similar to that of lung cancer patients in the general population, though the possibility of a higher proportion of more uncommon tumors (such as bronchoalveolar and carcinoid) cannot be excluded. A large proportion of the cancer cases were smokers, which is also not surprising. However, only a minority appeared to have been exposed to immunosuppressive agents. A large case-cohort study currently in progress should help shed light on the relative importance of these exposures in lung cancer risk for SLE patients.

Hodgkin's lymphoma in systemic lupus erythematosus.

OBJECTIVE: In systemic lupus erythematosus (SLE), there is a well-documented increased risk of non-Hodgkin's lymphoma (NHL), but little is known about the risk of Hodgkin's lymphoma (HL). The purpose of our work was to describe the phenomenon of HL in SLE. METHODS: A multi-site cohort of 9547 SLE subjects was assembled; HL cases were ascertained through cancer registry linkage, and the standardized incidence ratio (SIR) for HL was determined. We also performed a literature search for HL cases in SLE, and compared these with our sample. Finally, we pooled results from our cohort study with two large population-based cohort studies providing SIR estimates for HL in SLE. RESULTS: Five cases of HL occurred in our SLE cohort during the observation interval, for an SIR of 2.4 (95% CI 0.8, 5.5). The literature review documented 13 HL case reports developing in patients with SLE. A pooled analysis combining our data with the other large cohort studies yielded a standardized incidence ratio of 3.16 (95% CI, 1.63-5.51) for HL in SLE. CONCLUSIONS: Data suggest that risk in SLE is increased not only for NHL, but also for other malignancies arising from B-lymphocytes, including HL.

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Breast cancer stage at time of detection in women with systemic lupus erythematosus.

Mounting evidence suggests an increased cancer risk in several autoimmune diseases, including systemic lupus erythematosus (SLE). However, greater scrutiny for cancer in subjects with chronic disease (compared to the general population) might explain this apparent association. If so, one would expect cancers in SLE to be diagnosed at earlier stages than in the general population. This might be particularly evident in cancers where screening is available, such as breast cancer. We linked the University of Pittsburgh lupus cohort with the Pennsylvania Cancer Registry to determine the frequency distribution for stage at diagnosis of invasive breast cancers in the SLE subjects. Data on staging of cancers occurring in the general population of Pennsylvania were obtained from The US Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. A lower percentage of women with SLE presented with localized breast cancer (nine of the 16, 56.2%) compared to the general population of women (63.5%). Although not definitive, this evidence suggests that cancers in SLE are not necessarily diagnosed at earlier stages than in the general population.

Factors associated with abnormal Pap results in systemic lupus erythematosus.

OBJECTIVE: Previous studies have suggested that women with systemic lupus erythematosus (SLE) are at greater risk for cervical dysplasia than are women in the general population. However, the factors associated with abnormal Pap test results in SLE have not been well studied. We therefore aimed to determine the factors associated with lifetime occurrence of an abnormal Pap test in women with SLE, and the influence of immunosuppressive exposure on the odds of abnormal Pap test results occurring after diagnosis of SLE. METHODS: Data were pooled from SLE cohorts from three centres. Self-report data were available on smoking, reproductive history, use of oral contraceptives (OC), history of sexually transmitted diseases (STDs) and whether the subjects had had cervical dysplasia on Pap testing. Logistic regression was used to examine the effect of these variables on the lifetime odds of cervical dysplasia. We then generated the adjusted odds ratio (OR) for the effect of immunosuppressive exposure on cervical dysplasia occurring after diagnosis of SLE. RESULTS: History of STDs and use of OCs were positively associated with reports of cervical dysplasia in adjusted analyses. The ORs for the effect of immunosuppressives on abnormal Pap test occurrence (adjusted for race, age, smoking, nulliparity, OC use and history of STDs) after diagnosis of SLE was 1.6 (95% CI 1.0, 2.7). CONCLUSIONS: A history of STDs and use of OCs were associated with abnormal Pap reports in this SLE sample. Immunosuppressive exposure may confer further risk to women with SLE.

Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus.

OBJECTIVES: To determine if breast cancer risk in women with SLE is modified by a history of exposure to hormone replacement therapy (HRT) or oral contraceptives (OC), after adjusting for other risk factors. METHODS: Data were pooled from SLE cohorts at three centres. For each female cohort member (n = 871), the probability of developing breast cancer was estimated from factors (age, parity, age at first live birth, age of menarche, personal history of benign breast disease, family history) in the Gail model, an established tool for predicting breast cancer risk. From these probabilities, the expected number of breast cancers for the cohort was estimated. Actual occurrence of cases was determined by linkage with regional cancer registries. Standardized incidence ratios (SIRs; ratio of cancers observed to expected) were calculated, with subgroup analyses according to HRT and OC exposure. RESULTS: In the cohort, 15 breast cancers occurred vs 7.2 predicted [SIR 2.1, 95% confidence interval (CI) 1.1, 3.5]. When controlling for Gail model risk factors, estimates were similar for women never exposed to HRT vs those exposed to HRT. Adjusted SIR estimates appeared similar also for women exposed or not exposed to OC. CONCLUSIONS: Although not definitive, the data suggest that the breast cancer experience in this sample is not completely explained by factors such as reproductive and family history, or by exogenous hormonal exposures. Other determinants, including medication exposures or genetic factors (possibly related to oestrogen receptors or metabolism) may be important. Variations in these factors might explain why an elevated risk of breast cancer has not been apparent in all SLE populations.

The effects of transdermal and oral oestrogen replacement therapy on colorectal cancer risk in postmenopausal women.

The aim of this study was to examine the effects of oral and transdermal oestrogen replacement therapy on the risk of colorectal cancer. Data from a nested case-control study, designed to investigate the effect of hormone replacement therapy (HRT) on colorectal cancer were analysed. New cases of colorectal cancer, diagnosed between 1992 and mid-1998 (N=1197), were identified using the Saskatchewan Cancer Agency cancer registry. Women >/=50 years of age, eligible for coverage by the Saskatchewan Prescription Drug Plan, were included in the study. Four controls per case were age matched to cases, using incidence density sampling. The outpatient prescription drug plan database was used to ascertain oestrogen prescriptions. Women were classified according to history of transdermal (TDE) and oral (OE) oestrogen use. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women who had never used HRT, ORs for <3 and >/=3 years of TDE use and colorectal cancer were 0.69 (95% CI: 0.43-1.10) and 0.33 (95% CI: 0.12-0.95), and for OE use were 0.90 (95% CI: 0.73-1.01) and 0.75 (95% CI: 0.60-0.93), respectively. The risk reduction for colorectal cancer with TDE may be greater in magnitude than that which has been reported for oral HRT.

[Colorectal spirochetosis, a possible but unusual cause of chronic diarrhea?]. / Spirochétose colo-rectale, une cause possible mais inhabituelle de diarrhée chronique?

INTRODUCTION: Human intestinal spirochetosis has been known since the end of the nineteenth century. OBSERVATION: We report one case of intestinal spirochetosis revealed by chronic diarrhoea and diagnosed on colonic biopsies. The chronic diarrhoea disappeared with antibiotherapy. COMMENTARIES: The prevalence of intestinal spirochetosis in rectal and colonic biopsies, among patients with digestive disorders, varies in occidental countries from 2% to 7%. Presently, the pathogenic role of intestinal spirochetosis is controversial.

The effects of tricyclic antidepressants on breast cancer risk.

To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case-control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged 35 years from 1981-995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23,517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11-15 years later (2.02, 95% confidence interval: 1.34-3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use.

Functional outcome and satisfaction after photorefractive keratectomy. Part 1: development and validation of a survey questionnaire.

OBJECTIVE: The aim of this study was to develop a valid, reliable, and easy-to-administer instrument to assess patient satisfaction and perceived outcome after bilateral excimer laser photorefractive keratectomy. DESIGN: Development and validation of a psychometric questionnaire. PARTICIPANTS: Consecutive patients who underwent bilateral excimer laser photorefractive keratectomy from May 1994 through May 1997 by 12 surgeons from four collaborating centers. To be eligible, a minimum of 4 months since the last surgery and a maximum of 30 months since the first surgery was required. METHODS: The new instrument was derived in part from the Prospective Evaluation of Radial Keratotomy (PERK) study 10-year psychometric questionnaire and the Visual Functional Index (VF-14), an index of functional impairment in patients with cataract. Questions were grouped in seven scales, each covering a specific aspect of quality of vision. These included global satisfaction, quality of uncorrected vision, quality of corrected vision, quality of night vision, glare, daytime driving, and night driving. MAIN OUTCOME MEASURES: Acceptability, reliability, validity, and interpretability of the instrument, as well as its ease of administration. RESULTS: The instrument scale structure was examined and scale scores were created. Item-discriminant validity ensured that questions belonged to their hypothesized scale, based on multitrait correlation analysis. The instrument was shown to be reliable by a high level of internal consistency, and all Cronbach's alpha coefficients were superior or equal to 0.83. Construct-related validity and interpretability were assessed based on correlations between scale scores and clinically recognized success criteria such as visual acuity and refraction. Respondent burden was shown to be minimal. Acceptability of the instrument was shown to be very good, with a participation rate of 74.3% (690 of 929 patients). The instrument is available in English and in French and the translation was shown to be reliable. CONCLUSIONS: The acceptability, reliability, and interpretability of the instrument, as well as its ease of administration, were shown to be adequate. This questionnaire appears clinically useful to document patient satisfaction after excimer laser photorefractive keratectomy.

Functional outcome and satisfaction after photorefractive keratectomy. Part 2: survey of 690 patients.

PURPOSE: To document patient satisfaction and self-perceived quality of vision after bilateral photorefractive keratectomy (PRK). DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Consecutive patients who underwent bilateral PRK from May 1994 through May 1997 by the 12 surgeons of four collaborating centers with a minimum of 4 months since the last surgery and up to 30 months since the first surgery. METHODS: A questionnaire with known psychometric properties was self-administered by the patients. MAIN OUTCOME MEASURES: Responses to individual questions and scale scores. RESULTS: A total of 929 questionnaires were sent, of which 690 were answered and returned (74.3% response rate). The preoperative spherical equivalent ranged from -0.38 diopters [D] to -27.75 D (mean, -5.32 D; standard deviation, 2.85 D). Although 91.8% of the patients were satisfied or very satisfied with their surgery, 96.3% considered that their main goal had been reached, and 95.7% would still choose to have surgery if they had it to do over. The degree of satisfaction was proportional to the postoperative uncorrected visual acuity in the best eye expressed in LogMAR (r = -0.18, P: = 0. 0001) and was negatively correlated with the importance of the corneal haze (r = -0.23, P = 0.0001). Daytime glare was reported to be greater than before surgery by 55.1% of patients. A decrease in night vision was reported by 31.7% of patients, and 31.1% of patients reported increased difficulty driving at night because of their vision. CONCLUSIONS: Overall satisfaction after PRK for low to severe myopia appears to be very good. Glare and night vision disturbance, particularly bothersome for night driving, seem to constitute significant secondary effects that deserve further investigation and should be kept in mind for future improvements in the technique.