Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

[Study of lung cancer risk in the electroplating industry in Lombardy based on the OCCAM method]. / Studio del rischio cancerogeno per il polmone nell'industria galvanica in Lombardia basato sul metodo OCCAM.

BACKGROUND: The OCCAM method consists of case-control studies aimed at estimating occupational risks by cancer site, by area and by economic sector, using available archives to identify cases and controls; for exposure definition each subject is assigned to the category code of the economic sector or company where he/she worked the longest, obtained by automatic link with the Social Security Institute (INPS) files. The reference category (unexposed) consists of service industry workers. The economic sector is given by the ATECO category that INPS assigns to each firm. OBJECTIVES: In the Lombardy Region, lung cancer risk evaluated for the "metal treatment" industry as a whole was 1.32 (90% CI 1.33-3.10, 67 cases) for males and 1.33 (90% CI 0.51-3.59, 10 cases) for females. The aim of the study was to estimate lung cancer risk among metal electroplating workers only. METHODS: The metal electroplating firms were identified according to the detailed description of production, data which was also contained in INPS files, instead of using the "metal treatment" ATECO code. Lung cancer risk was evaluated using 2001-2008 incident cases identified from hospital discharge records of residents in the Lombardy Region. Controls were a sample from National Health Service files. RESULTS: For the group of firms identified as metal electroplating industries the risk was 2.03 (90% CI 1.69-8.32, 18 cases) for males and 3.75 (90% CI 1.38-9.03, 4 cases) for females. CONCLUSIONS: Focusing on the true electroplating firms increased the risk estimates. Even though these risk were due to past exposures, case histories and recent acute effects indicate that, at least in some factories, a carcinogenic hazard still exists.

High levels of women's satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study.

OBJECTIVE: To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. METHODS: Women (18-46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 µg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. RESULTS: Of the 778 participants, 36.8% (n = 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n = 334) and barrier methods (21.5%, n = 106). Of oral contraception users, 63.5% (n = 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8% (n = 260) reporting missed doses. After 3 and 6 cycles, >80% of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. CONCLUSION: Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential to offer high compliance and efficacy.

[Italian national register of low etiological fraction occupational cancer pursuant to art. 244 of legislative decree n. 81/2008]. / Il registro nazionale dei casi di neoplasia a bassa frazione eziologica con sospetta origine professionale istituito dall'art. 244 del D.Lgs. n. 81/2008.

Legislative decree No. 81/2008 in the article n. 244 states that ISPESL, now INAIL, realizes a register of occupational cancers with low etiological fraction by means of a data collection method based exclusively on voluntary reports by GPs, healthcare and social security agencies (ReNaLOC) and a surveillance cancer monitoring system (OCCAM) based on linkage of routinely available data (cancer registries, hospital discharge records, Italian Social Security archives). ReNaLOC has produced a partial picture of the situation, it includes 1.584 cases as of June 2011. With OCCAM many situations of known risks were identified and others are worthy to be deepen.

Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: a nested case-control study.

BACKGROUND AND AIMS: The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort. METHODS AND RESULTS: After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07-2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk. CONCLUSIONS: This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women.

The effect of surgery for symptomatic endometriosis: the other side of the story.

BACKGROUND: Surgery is often considered the best treatment option in women with symptomatic endometriosis. However, extent and duration of the therapeutic benefit are still poorly defined. METHODS: The best available evidence on surgery for endometriosis-associated pain has been reviewed to estimate the effect size of interventions in the most frequently encountered clinical conditions. RESULTS: Methodological drawbacks limit considerably the validity of observational, non-comparative studies on the effect of laparoscopy for stage I-IV disease. As indicated by the results of three RCTs, the absolute benefit increase of destruction of lesions compared with diagnostic only operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size tended to decrease with time and the re-operation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by approximately 70-80% of the subjects who continued the study. However, at 1 year follow-up, approximately 50% of the women needed analgesics or hormonal treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in approximately 20% of the cases, and around 25% of the women underwent repetitive surgery. CONCLUSIONS: Pain recurrence and re-operation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent.

[In-progress matrix for occupational cancer recognition]. / Matrice "inprogress" per la consultazione dei dati bibliografici relativi alle neoplasie di sospetta origine professionale.

BACKGROUND: In Italy only a small proportion of all cancers is reported to the national labour insurance board and recognized as having an occupational origin. Cancers with a lower etiological fraction such as lung or bladder cancer have a lower rate of recognition than mesotheliomas or sino-nasal tumours either because of a lack of information obtained via specific occupational anamnesis or because knowledge concerning occupational carcinogens is still uncertain. OBJECTIVES: To interpret findings and advance new working hypotheses, within the framework of an occupational monitoring survey project (OCCAM) we performed an extensive bibliographical search in the scientific literature on occupational cancer. METHODS AND RESULTS: We built an on-line "literature matrix" (www.occam.it) containing positive" results from 685 cohort, case-control and cross-sectional epidemiological studies on occupational cancer, from which 1870 citations were obtained describing risk increases by type of cancer and industry. Production cycles or type of industry (iron foundry, leather and shoe manufacturing, etc.) constitute one axis of the matrix and the other consists of type of cancer by site. CONCLUSIONS: This tool is not only useful for interpretation of evidence arising from occupational cancer surveys but was also intended to be a fast and easy-to-use working tool for occupational physicians, general practitioners and many other specialists to investigate and ascertain the possible occupational origin of a cancer case.

[Confounding and confusion: recognition of causative relation and identification of victims of occupational carcinogens]. / I confonditori e le confusioni: il riconoscimento del nesso causale e la identificazione delle vittime dei cancerogeni professionali.

The recognition of occupational cancers is often hampered by the confusion between the individual determinants of the disease and the effect at the group exposure. Here we propose an approach based on the evaluation of the attributable risk at group level aimed to quantify the respective role of multiple causes, and the individual rebounds of it.

Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the menstrual reflux theory.

BACKGROUND: If the menstrual reflux or implantation theory of endometriosis is true, refluxed endometrial cells could reach the right hypochondrium transported by the clockwise peritoneal fluid current and would implant more easily on the right diaphragmatic leaf as they are stuck there by the falciform ligament. METHODS: To investigate if a lateral asymmetry exists in diaphragmatic endometriotic lesion distribution, all articles on diaphragmatic endometriosis identified by MEDLINE, EMBASE and PUBMED database searches were retrieved, and additional reports were collected by systematically reviewing all references. The number of women and the side of the lesion with respect to the falciform ligament of the liver were obtained from individual studies, and the combined frequency of right- and left-side diaphragmatic endometriosis was computed. In addition, seven personal cases were described. RESULTS: There were 16 reports including 47 subjects selected. Diaphragmatic endometriosis was on the right side in 31 (66%) patients, on the left in 3 (6%) and bilateral in 13 (27%). In the personal series, lesions were on the right side in five cases, on the left in one and bilateral in one. Considering only unilateral lesions, the observed proportion of right-sided endometriotic implants (36/40) was 90% (95% CI 76-97%; chi(2)(1) 32.6, P < 0.0001). CONCLUSIONS: The observed major asymmetry in diaphragmatic endometriotic lesion distribution in favour of the right leaf supports the menstrual reflux theory.

Fibroids and female reproduction: a critical analysis of the evidence.

Observational epidemiological studies aimed at elucidating the relationship between fibroids and infertility are inconclusive due to methodological limitations. However, two main pieces of clinical evidence support the opinion that the fibroids interfere with fertility. First, in IVF cycles, the delivery rate is reduced in patients with fibroids but is not affected in patients who have undergone myomectomy. Second, even if randomized studies are lacking, surgical treatment appears to increase the pregnancy rate: approximately 50% women who undergo myomectomy for infertility, subsequently conceive. Available evidence also suggests that submucosal, intramural and subserosal fibroids interfere with fertility in decreasing order of importance. Although more limited, some data supports an impact of the number and dimension of the lesions. Drawing clear guidelines for the management of fibroids in infertile women is difficult due to the lack of large randomized trials aimed at elucidating which patients may benefit from surgery. At present, physicians should pursue a comprehensive and personalized approach clearly exposing the pros and cons of myomectomy to the patient, including the risks associated with fibroids during pregnancy on one hand, and those associated with surgery on the other hand.

Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers.

BACKGROUND: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). PATIENTS AND METHODS: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). RESULTS: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.

Endometrial bleeding.

Abnormal bleeding is a significant health problem, especially during adolescence and before menopause when anovulatory cycles are common. Curettage is rarely necessary to investigate or treat menstrual problems in adolescents, and its use should also be minimized in women younger than 40 years. In every age group, medical treatment is the initial choice, but surgical treatment by endometrial destruction or hysterectomy is sometimes required. Benign causes of bleeding include fibroids and possibly adenomyosis, but the indications for treatment in each case depend upon the extent of bleeding, not the extent of the lesion. Breakthrough bleeding (BTB) with combined oral contraceptives commonly leads to discontinuation of the method. As BTB tends to improve with time, in the first 3 months of pill use, unless there are obvious underlying causes, women should be reassured that it will likely settle. BTB is often the reason for discontinuing progestogen-only contraception, and there is a need for effective means of treating unscheduled bleeding. Bleeding occurs in approximately 3% of post-menopausal women, and the use of hormones increases the likelihood of bleeding by >5-fold. Knowledge of the underlying mechanisms of bleeding is essential to the development of effective treatment.

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.

Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.

BACKGROUND: The association between lesion type, disease stage and severity of pain was studied in a large group of women with endometriosis to verify whether endometrial implants at different sites determine specific complaints and to evaluate the validity of the current classification system in women with symptomatic disease. METHODS: A total of 1054 consecutive women with endometriosis undergoing first-line conservative or definitive surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, and type and severity of pain symptoms were collected and analysed by multiple logistic regression. RESULTS: Minimal endometriosis was present in 319 patients, mild in 139, moderate in 292 and severe in 304. A significant inverse relationship was demonstrated between age at surgery and moderate-to-severe dysmenorrhoea, dyspareunia and non-menstrual pain. A strong association was found between posterior cul-de-sac lesions and pain at intercourse [Wald chi (2) = 17.00, P = 0.0001; odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.68-4.24]. A correlation between endometriosis stage and severity of symptoms was observed only for dysmenorrhoea (Wald chi (2) = 5.14, P = 0.02) and non-menstrual pain (Wald chi (2) = 5.63, P = 0.018). However, the point estimates of ORs were very close to unity (respectively, 1.33, 95% CI = 1.04-1.71, and 1.01, 95% CI = 1.00-1.03). CONCLUSIONS: The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power.

Effect of GnRH antagonists in FSH mildly stimulated intrauterine insemination cycles: a multicentre randomized trial.

BACKGROUND: The usefulness of GnRH antagonists in mild controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) cycles is debated. METHODS: Two-hundred and ninety-nine couples with unexplained or mild male factor infertility were enrolled in this international multicentre randomized controlled trial. Women allocated to the GnRH antagonist group (n=148) received 50 IU recombinant FSH starting on day 3 of the menstrual cycle and Ganirelix 0.25 mg daily starting from the day in which a follicle with a mean diameter of 13-14 mm was visualized at ultrasound. Women allocated to the control group (n=151) were administered only 50 IU recombinant FSH starting on day 3 of the menstrual cycle. Couples were recruited only for their first treatment cycle. The primary outcome was the clinical pregnancy rate per initiated cycle. RESULTS: Baseline characteristics of the two treatment groups were similar. Clinical pregnancy rates per initiated cycle in women who did and did not receive GnRH antagonists were 12.2 and 12.6%, respectively (P=1.00). The relative risk of conception (95% confidence interval) for the use of GnRH antagonists was 1.0 (0.5-1.9). CONCLUSIONS: In mild COH and IUI cycles, any benefit of the use of GnRH antagonists in improving pregnancy rates is <2-fold increase.

[Active search of work related tumours: preliminary findings]. / La ricerca attiva deli tumori di origine professionale: primi risultati.

UNLABELLED: The OCCAM (Occupational Cancer Monitoring) project enabled the active detection of occupational cancer cases in Lombardy Region. METHODS: OCCAM is based on a record linkage with social security files to obtain occupational histories for all subjects having worked in private firms, since 1974. It provides risks by area, site and job. RESULTS: 271 incident cancer cases obtained by hospital discharge record in the period 2001-2002 where investigate to assess eventually their occupational origin. Approximately 38% where considered to be occupational cancers. CONCLUSIONS: OCCAM provides name of the firms and their economic activity completed by information coming from OCCAM risks ascertainment and deeper knowledge on productive cycle retained by local occupational health services. Thus this system can lead to detection of many cancer cases of occupational origin suitable for compensation and determine strategies for the improvement of the work environment.

[The contraceptive method that changed the world]. / La contraccezione ha cambiato il mondo.

During the past century human life expectancy doubled while the birth rate dropped. The widespread use of effective contraceptives has led to a better control of human fertility and changed the structure of modern societies: the elderly now increasingly outnumber the young. Scientifically controlled human reproduction has also resulted in fewer voluntary abortions. The choice of contraceptive strategies differs by geographic area and seems to be linked to such simple mechanisms as the ''door-to-door'' effect. In European countries where the pill is the most widely used contraceptive, interesting variations in the biological profile of oral contraceptive users can be observed; for example, women taking a hormonal contraceptive have only half the risk of developing ovarian cancer. The world is no longer the same since the advent of the pill.

Cigarette smoking and alcohol consumption as determinants of survival in non-Hodgkin's lymphoma: a population-based study.

BACKGROUND: The risk of non-Hodgkin's lymphoma (NHL) seems to be enhanced by cigarette smoking and lowered by alcohol drinking. PATIENTS AND METHODS: To assess whether cigarette smoking and alcohol drinking affect NHL survival, a population-based prospective study on 1138 Italian patients, diagnosed in 1991-1993, followed-up until 2002, was carried out. At diagnosis, clinical and socio-demographic data were recorded and lifestyle habits were assessed through a validated questionnaire. Survival analysis was performed with Kaplan-Meier methods. Hazard ratios (HR) were estimated by Cox regression. RESULTS: The mean follow-up was 6.6 years (standard deviation (SD) 4.3). The mean survival time was 7.56 years (SD 0.155). At both univariate and multivariate analysis heavy cigarette smoking and alcohol drinking were associated with poor survival. Compared with those with a lower cumulative exposure to tobacco smoking, those who had smoked>31 pack-years had a worse survival (HR=1.60, 95%CI=1.18-2.18). Drinkers had a higher risk of death compared with non-drinkers (HR=1.41, 95%CI=1.10-1.81). Considering only those who had NHL as cause of death, the HR for the higher category of pack-years smoked, compared with the lowest, was 1.63 (95% CI=1.15-2.33) and for drinkers, compared with non-drinkers, it was 1.33 (95% CI=1.01-1.80). CONCLUSIONS: cigarette smoking and alcohol drinking may influence NHL survival.

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.