An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring.

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05-0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24-30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.

Hematopoietic cell transplantation for Crohn's disease; is it time?

AIM: To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT) and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. METHODS: An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn's disease and inflammatory bowel disease. RESULTS: We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class III genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION: Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.

Comparative sensitivity of a simulated driving task to self-report, physiological, and other performance measures during prolonged wakefulness.

OBJECTIVES: The objectives of this study were to compare (1) the sensitivity of simulated driving to self-report measures, nocturnal sleep latency tests (SLTs), and an auditory vigilance task and (2) urban and motorway driving. METHODS: Healthy males 18 to 35 years maintained wakefulness for one night and were tested at 2400, 0230, 0500 and 0730 h. In Study 1 (n=11), the SLTs were followed by auditory vigilance and simulated driving tasks; in Study 2 (n=18), the SLTs were preceded and followed by simulated driving on motorway and urban routes. RESULTS: In Study 1, speed variability, tracking variability, and driving off the road on the driving simulator had comparable sensitivity to d' on the auditory vigilance task. In Study 2, driving performance was consistently worse on the motorway route. CONCLUSION: The driving simulator was equally sensitive to another performance measure during prolonged wakefulness and impairments were greater with motorway driving.

The use of complementary therapies by breast cancer patients attending conventional treatment.

The aim of this study was to measure the proportion and characteristics of complementary therapy (CT) users among female breast cancer patients receiving conventional treatment. 473 women who had received surgical intervention for breast cancer in the year of diagnosis were sent a questionnaire for completion, and 242 responded. CT had been used by 16.5% after cancer diagnosis, only 8.7% before. The most commonly used CTs were homeopathy, manual healing method, herbalism and acupuncture. The main reason for using CTs was physical distress. Only a minority was searching for psychological support. 24 users were satisfied with these treatments, and two-thirds would suggest them. Users were significantly younger, more educated, and previous users of CTs than non-users. Adjusting each variable for the effect of the others, only previous use had an independent effect on increasing the probability of being users after cancer diagnosis.

Female tumours in Italy: an example of quantitative assessment of disease burden and preventive strategies.

Female tumours (ie cancers of the female genital tract and breast) represent alone about 40% of new cases and 30% of cancer deaths in Italy (approximately 44,500 new cancer diagnoses and 17,800 deaths in 1991). An attempt to identify major issues in the primary and secondary prevention of these malignancies has disclosed several important points. Firstly, concerning epidemiology, excesses of mortality from cancers of the breast and ovaries exist in the northern part of Italy as compared to the centre and south, whereas mortality rates from uterine cancer are almost equally distributed. However, a tendency towards increasing similarity of various Italian regions emerges. Risk factors most amenable to intervention are overweight, contraceptive methods and dietary habits. Secondly, concerning screening, the number of mammograms (about 552) and the number of Pap smears taken every year (about 4 million) are approximately sufficient to provide a complete coverage of the target subset of the female population as concerns breast and cervical cancer screening. Still, on account of no one carrying out primary call procedures and checks, the actual situation is unsatisfactory. The present article, in addition to quantifying the present status of female cancer prevention in Italy, tries to define a framework for similar exercises in other European countries.

Progress in the fight against cancer in EC countries: changes in mortality rates, 1970-90.

The question of how much effective progress against cancer is being made has been raised repeatedly during the last decade; one approach to evaluating such progress is represented by the analysis of mortality, which has been used by several researchers. Here we report mortality trends for 1970-90 for four age-groups, calculated for each 3-year period, and presented as the percentage change of the rate of the first period examined. Detailed graphs for each country and for the European Community as a whole are presented for 'all cancers', and for cancer of the colon-rectum, lung, breast and ovary. For other cancers (stomach, melanoma, uterus, testis and Hodgkin's disease), the graphs are presented only for the whole of the European Community. Variations in mortality are discussed, in terms of changes in incidence, efficacy and diffusion of prevention, as well as improvement in diagnosis and treatment.

A case control study of lung cancer in Florence, Italy. I. Occupational risk factors.

A case control study of lung cancer in Florence, Italy was performed to investigate occupational risk factors for both men and women. The case series (n = 376) comprised all incident, histologically confirmed cases of primary lung cancer occurring in a three year period. Controls (n = 892) were patients in the same hospital of similar age, sex, date of admission, and smoking status with discharge diagnoses other than lung cancer or suicide. A detailed occupational history was collected from each subject directly. Logistic regression models were used to calculate odds ratios for specific occupations compared to all others. Among men, the lung cancer risk for bricklayers using firebrick and other refractory materials was elevated (adjusted odds ratio 6.5, 95% limits 2.1 and 20.9). Female hat makers, probably exposed to arsenic while making felt hats, had an elevated risk of lung cancer (6 cases versus 0 controls, p = 0.01). Risks in other occupations are discussed.

A case control study of lung cancer in Florence, Italy. II. Effect of migration from the south.

Risk of lung cancer related to region of birth in Italy was investigated among migrants to Florence, in a case control study of all histologically confirmed incident cases of primary lung cancer in a three year period in that city (n = 376). Controls (n = 892) were patients in the same hospital of similar age, sex, date of admission, and smoking status with discharge diagnoses other than lung cancer or suicide. Information on place of birth and year of migration to Florence was collected directly from each subject, along with a detailed occupational history. Logistic regression models were used to calculate the odds ratio for birth in the south of Italy relative to birth elsewhere. Male migrants from the south have an odds ratio of lung cancer of 0.5 (95% limits 0.3 to 0.7) relative to those born elsewhere. This "protective effect" is not explained by smoking or by any known occupational risk. The risk is lowest among those born on the island of Sicily (odds ratio 0.2 compared to those born in the centre-north).

Effect of medroxyprogesterone pretreatment on pentagastrin-induced panic symptoms in females with panic disorder.

Clinical observation, as well as epidemiological and research data, suggest that female gonadal hormones influence the course of panic disorder (PD). Panicogenic agents such as pentagastrin are useful tools with which to study the pathophysiology of panic attacks. Nine women with PD were randomly assigned to receive, in a crossover design, a 3-day pretreatment with medroxyprogesterone acetate (MP) prior to an injection of pentagastrin, and a 3-day pretreatment with a placebo prior to another injection of pentagastrin. The panic response and the anxiety response to pentagastrin were decreased after MP pretreatment. These preliminary results support the use of laboratory models for investigations of the interactions between progestins and anxiety.

Epidemiology of classic Kaposi's sarcoma, with special reference to mediterranean population.

An excess of classic Kaposi's sarcoma (KS) in individuals of southern European ancestry has long been suspected and recently quantified in terms of age-standardized rates. In Italy and most notably in southern Italy for the period 1976-84, prior to the AIDS epidemic, KS incidence rates were two-to-three-fold higher than in the United States and Sweden and many ten-fold higher than in England and Wales and Australia. A high frequency of classic KS has also been documented in Israel and, in low-risk countries, in individuals born in southern Europe and the Middle East. Many infections have been suspected to play a role in the etiology of KS, including cytomegalovirus, malaria and, most recently, a new virus of the herpes family, identified in AIDS-associated and classic KS. The present review deals with epidemiologic data concerning KS in the Mediterranean and stresses the opportunity to combine the study of KS in AIDS as well as non-AIDS patients in order to shed light on this no longer rare disease.

The accuracy of local death certificates in cancer of the lung and stomach.

The study analysed the accuracy of local death certificates (LDC) for patients with lung cancer (424 males, 36 females) and stomach cancer (99 males, 62 females) who died between 1979 and 1984. All the diagnoses were confirmed histologically. For a subgroup of lung cancer (males), we also evaluated the national death certificate (NDC) and the correspondence of LDC vs. NDC. The reliability of LDC was quite poor. This paper examines the different reasons for the underevaluation of cancer in LDC and the variables which modify the accuracy of cause of death on the death certificate.

Analysis of trends in cancer mortality in Italy 1951-1978; the effects of age, period of birth, and period of death.

We describe trends in cancer mortality in Italy between 1951 and 1978 for 6 different sites (esophagus, lung, breast, cervix uteri, testis, and bladder) as well as all cancers. This is done using a statistical model which separates the contributions associated with age, period of birth and period of death. The results are related to equivalent analyses in England and Wales and also to trends in lifestyle in Italy (alcohol consumption, cigarette consumption, birth rates).

Cell type distribution in histologic specimens of primary lung cancer.

A total of 1986 cases of primary lung cancer, observed in the Pathology Department of the University of Florence during 1971-1981, were analysed by age, sex, year of diagnosis, source of specimen, and cell type. Adenocarcinomas occurred more frequently in females and at younger ages and were diagnosed mainly from surgically obtained specimens. In contrast, squamous cell carcinomas developed more often in males and at older ages, and were chiefly diagnosed by bronchial biopsy. Over the 11-year period of study, a significant increase in the percentage of squamous cell carcinomas and a consequent decrease in the percentage of adenocarcinomas occurred both in females and in males, independent of changes in the specimen sources.

Cancer mortality in Italian migrants to Canada.

The present study reports on the analysis of cancer mortality in Italian first-generation migrants resident in Canada, deceased in the period between 1964-1985 (5,801 males: 3,267 females). Mortality in migrants is compared to that of the host population as well as to that in the migrants' country of origin. This is carried out both on a national level (Italy), and on a regional level with those regions that have made the greatest contribution to the Italian migratory flow (Southern Italy). Compared with the Canada-born population, significantly higher risks were evident for nasopharynx, stomach, liver and gallbladder tumors in migrants. Lower risks were observed for the oral cavity, esophagus, colon, rectum, pancreas (females), larynx, lung, melanoma, breast, ovary, prostate, bladder (females), and non-Hodgkin's lymphoma in migrants. This is consistent with that evidenced in the comparison between Italy and Canada. The data are discussed in relation to the results of other studies on Italian migrants and the prevalence of main risk factors.

Colorectal, lung, and breast cancer care during the three years following the diagnosis: a population-based study.

AIMS: We evaluated a number of basic parameters of care during hospitalization that contribute to the total cost of therapy during the 3 years after the first diagnosis of cancer. METHODS: The study examined a sample of cases of cancer of the colon-rectum (164 cases), lung (160 cases) and breast (144 cases) diagnosed in 1987, taken from the data base of the Tuscany Cancer Registry. All the information collected by the Registry was examined and the sample was further validated by reviewing original clinical records. The agreement between the two sources was very high, confirming the adequacy of the Registry as a source of information. The parameters evaluated for each patient were the number of cytohistologic examinations, surgery, hospital admissions and days spent in hospital during the 3 follow-up years. RESULTS: The average number of admittances in 3 years was 1.93 for colorectal, 3.39 for lung and 2.15 for breast cancer. The mean number of days spent in hospital in the 3 follow-up years was 39.9 for colorectal, 50.1 for lung and 21.1 for breast cancer. The parameters differed among subjects still alive, those deceased and those in various stages of the illness. CONCLUSIONS: The costs of the time spent in hospital, based on the number of days during the first 3 years of the illness, were higher in cases of lung cancer than of the other sites, and more so for patients diagnosed in an advanced phase of the disease.

[Mortality from malignant tumors in residents of the city of Verona in 1980]. / Mortalità per tumore maligno nei residenti della città di Verona al 1980.

Malignant tumours mortality among residents of the city of Verona (267,703 at 31-12-1980) during the year 1980 is assessed from the ISTAT individual death cards and/or municipal death certificates (especially in the case of deaths outside the municipality). The figures are broken down by site, apparatus or system (in accordance with the VIII-ICD), sex, age at death, and compared with the Italian mortality figures for 1976 (indirectly standardised) and those for the province of Verona for 1976-77 (directly standardised). Tumour mortality per site was generally higher than the Italian level. This is line with the differences noted between geographical areas and the similarity of the rates in more industrialised areas. A salient finding was that lung tumour mortality exceeded that for the province of Varese, which is among the highest in Italy entered on the Register of Tumours. Genital and breast tumours were responsible for the highest number of deaths in women, while stomach cancer was the second cause of death in both sexes. The study will be completed with an analysis of tumour deaths during 1980 and 1981 in the province of Verona as a whole.

Risk factors in male infertility: a case-control study.

A case-control study was undertaken to evaluate environmental risk factors potentially involved in male infertility. One hundred twelve azoospermic or oligospermic subjects and 127 controls were interviewed, before sperm count results were available, about coffee and alcohol consumption, smoking habits, x-ray exposure, usual sitting posture, drug consumption, other nonoccupational risk factors, socioeconomic status, education level, and occupational history. An unmatched analysis was then conducted. None of the occupational risk factors appeared to be related to azoospermia or oligospermia. A high relative risk was associated with (1) occupation in the radioelectric industry, (2) nonsedentary clerical workers, (3) clerical work in the typographic industry, and (4) occupation in the textile industry, but none of these figures were statistically significant. Because of the population from which cases and controls were drawn, certain occupational risks could not be investigated in this study, e.g., exposure of agricultural workers to chemicals.

[Use of mortality data for the study of the distribution of respiratory tract tumors in Italy: characteristics and quality of the data]. / Uso dei dati di mortalità per lo studio della diffusione dei tumori dell'apparato respiratorio in Italia: caratteristiche e qualità dei dati.

This paper reviews Italian studies that deal with the accuracy of death certificates in patients with cancers of the respiratory system, particularly cancers of the larynx, lung, and pleura. These studies consider death certificates vs postmortem examinations, diagnoses histologically confirmed, and clinical and cancer registry records. The large number of cases cured by surgery is reflected in the lower levels of larynx cancers mortality vs incidence. Site misclassifications, and erroneous reports of cancer on death certificates for patients cured of the disease, lead to an overreporting of death certification vs autopsies. The death certificates for lung cancer have a high agreement with clinical diagnoses, but present underreporting when compared to autopsies, which frequently discover tumors at postmortem examination. Pleura cancer is often misclassified as lung cancer. Improvement in death certification over time could have influenced the observed increase in the mortality trend for this tumor.

[Etiological epidemiology of colorectal tumors]. / Epidemiologia eziologica dei tumori del colon-retto.

We reviewed the main results of colon cancer (CC) epidemiologic studies, according to data published in the 1973-1994 period, with a particular mention to dietary factors and to differences with Italian findings. Meat (mostly, red meat), animal fats and high energy intake not counterbalanced by sufficient physical activity seem to be the most consistent risk factors for CC. On the contrary, the vegetarian based diet seems to reduce the risk of CC. Although interestingly, the relevance to CC of other life-style and diet-related factors (alcohol intake, smoking habits, processing and cooking methods, occupation, drugs, personal medical and reproductive history) must be better defined and requests further investigations. More recently, genetic studies are clarifying the hereditary risk of CC. Several colon carcinogenesis hypotheses have been proposed, but general agreement on the most reliable is still lacking. Authors argue that in the next future, new acquirements could emerge from metabolic polymorphism studies, possibly reconciling the biological significance of individual susceptibility and environmental factors to CC incidence.

Epidemiology of lung cancer.

Primary lung cancer is now the most frequent cancer in the world. Tobacco smoking still represents its predominant cause: a recent estimate attributes 80-85% of lung cancers to smoking and the epidemic of lung cancer mortality is still ongoing, with a major contribution from East European and developing countries. The study of smoking in association with lung cancer has contributed to the understanding of the carcinogenic process in humans, especially since molecular epidemiology techniques have been developed. However, the most probable carcinogenic model, still needs to be more clearly established. Presently, it can be summarised that smoking cessation is beneficial at any age, and more so when early. The contribution of passive smoking to lung cancer risk has been widely documented; its effect in terms of attributable number of cases, however, is not easily estimated at a population level. Some authors suggest that non-smoking-related lung cancer frequency is increasing over time. Exposure to environmental carcinogens with a major emphasis on those deriving from industrial processes, among which asbestos, and on air pollution due to traffic in urban areas has been advocated. Finally, a special interest has grown in the last years on possible protective factors for lung cancer, mainly diet-related (high intake of fresh fruits and vegetables), but results from the first large randomised chemoprevention trial based on alpha-tocopherol and beta-carotene treatment, dealt with "paradoxical" results.