The role of glucose, insulin and NEFA in regulating tissue triglyceride accumulation: Substrate cooperation in adipose tissue versus substrate competition in skeletal muscle.

BACKGROUND AND AIMS: Metabolic factors initiating adipose tissue expansion and ectopic triglyceride accumulation are not completely understood. We aimed to investigate the independent role of circulating glucose, NEFA and insulin on glucose and NEFA uptake, and lipogenesis in skeletal muscle and subcutaneous adipose tissue (SCAT). METHODS AND RESULTS: Twenty-two pigs were stratified according to four protocols: 1) and 2) low NEFA + high insulin ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia), 3) high NEFA + low insulin (fasting), 4) low NEFA + low insulin (nicotinic acid). Positron emission tomography with [18F]fluoro-2-deoxyglucose and [11C]acetate, was combined with [14C]acetate and [U-13C]palmitate enrichment techniques to assess glucose and lipid metabolism. Hyperinsulinaemia increased glucose extraction, whilst hyperglycaemia enhanced glucose uptake in skeletal muscle and SCAT. In SCAT, during hyperglycaemia, elevated glucose uptake was accompanied by greater [U-13C]palmitate-TG enrichment compared to the other groups, and by a 39% increase in de novo lipogenesis (DNL) compared to baseline, consistent with a 70% increment in plasma lipogenic index. Conversely, in skeletal muscle, [U-13C]palmitate-TG enrichment was higher after prolonged fasting. CONCLUSIONS: Our data show the necessary role of hyperglycaemia-hyperinsulinaemia vs euglycaemia-hyperinsulinaemia in promoting expansion of TG stores in SCAT, by the consensual elevation in plasma NEFA and glucose uptake and DNL. In contrast, skeletal muscle NEFA uptake for TG synthesis is primarily driven by circulating NEFA levels. These results suggest that a) prolonged fasting or dietary regimens enhancing lipolysis might promote muscle steatosis, and b) the control of glucose levels, in association with adequate energy balance, might contribute to weight loss.

Nefropatía por mieloma múltiple / Nephropathy due to multiple myeloma

Resumen Gran parte de los pacientes con mieloma múltiple inician con signos y síntomas relacionados con la infiltración de células plasmáticas o el exceso de cadenas ligeras kappa. La enfermedad renal es común con enfermedad heterogénea que puede involucrar diferentes mecanismos. Se comunica el caso de un paciente con sospecha de mieloma múltiple debido a la existencia de lumbalgia, insuficiencia renal, anemia e hipercalcemia; con electroforesis de proteínas séricas negativa para hipergammaglobulinemia, en quien se confirmó el diagnóstico al demostrar la existencia de cadenas ligeras kappa en tejido renal; se realiza una revisión de la bibliografía actual.

Abstract Much of the patients with multiple myeloma present with signs and symptoms related to plasma cells infiltration or by the excess of kappa light chains. Kidney disease is common and has a heterogeneous pathophysiology that may involve different mechanisms. We present the case of a patient with suspected multiple myeloma because of low back pain, renal failure, anemia and hypercalcemia; without hipergammaglobulinemia in the electrophoresis, in whom the diagnosis was confirmed by the presence of kappa chains light in renal tissue; a review of current literature is made.

Post-rotavirus vaccine intussusception in identical twins: A case report.

The intussusception is one of the most frequent causes of occlusive syndrome in infants and in children. (1) The mesenteric lymphadenopathy, wich is very rare post rotavirus vaccination, can cause intussusception, (2-5) especially in genetically predisposed individuals. (6) There is an association between intussusception and some classes of genotype. (7-9) Two infants aged 3 months, vaccinated against rotavirus. After about a week, one of the 2 identical infants presented inconsolable crying, vomiting, loose stools mixed with blood, and was diagnosed with bowel obstruction with intussusception. He was operated in urgency. After a few hours, his brother presented vomiting, and was admitted to our Hospital for suspected intussusception. The controls carried out have confirmed the presence of intussusception that was treated early, before the onset of severe symptoms. The incidence of post rotavirus vaccine intussusception is very low. The determining factor hypothetically might be linked to the presence of a genotype that exposes infants to a greater risk of developing mesenteric lymphadenitis and intussusception. In our case, the diagnosis of intussusception occurred in a twin, which allowed us to recognize early symptoms which accused the brother and schedule the surgery with less urgency. Our experience may want to sensitize families and pediatricians to report cases of intussusception given a theoretical familiar association. The study of the genotype could be decisive for or not to exclude the presence of a risk of invagination, thus avoiding vaccination.

Linking surgical specimen length and examined lymph nodes in colorectal cancer patients.

AIM: The number of examined lymph nodes (NLN) was associated with survival of stages II and III colorectal cancer (CRC) patients. Guidelines recommend examining at least 12 lymph nodes. This study investigated the influence of surgical specimen length on lymph node harvest and compliance with international guidelines. MATERIALS AND METHODS: This population-based study included 4,724 cases of surgically treated CRC that were diagnosed from 2002 to 2008. Multivariate analyses were performed for the main study variables (age, gender, diagnosis at screening or in symptomatic patients, cancer site, staging, grading, number of positive nodes, neo-adjuvant treatment for rectal cancer, hospital were surgery was performed). Fractional polynomial models investigated the relationship between continuous variables and outcomes. RESULTS: The NLN increased over time reaching ≥12 NLN in 64% of cases at the end of the study period. More NLN were associated with young age, right colon cancer, pT3-T4 disease, stages II and III and high grade. Fewer NLN were associated with short surgical specimen length and neo-adjuvant treatment in rectal cancer patients. Use of laparoscopy increased sharply over time. CONCLUSIONS: NLN increased over time in accordance with international guidelines. Surgical specimen length correlated with NLN which may determine therapeutic choices, particularly in stage II colon cancer. When harvested lymph nodes are under 10 in number and all are negative, chemotherapy is always recommended. As specimen lengths <20 cm were associated with a high risk of inadequate NLN counts, patients are at risk of over-treatment.

Genetic analysis in retinoblastoma and peripheral blood correlation.

OBJECTIVE: To determine the importance of intratumoral genetic analysis in the diagnosis of germ-line mutations in patients with retinoblastoma. To underline the importance of performing these genetic tests in every case of retinoblastoma. METHOD: Intratumoral genetic analysis of RB1 mutation was performed on 17 enucleated eyes that were non-responsive to conservative treatment. Patients had no family history of retinoblastoma, and lesions were always single. The identified mutations were then also studied in peripheral blood analysis. RESULTS: There were 12 (70.6%) cases with positive results in intratumoral analysis. In 8 cases (47.1%) mutation of both RB1 alelli were detected, and in 4 (23.5%) cases only one allele was found mutated. In 5 patients (29.4%) no mutation was identified. In the first hit, mutations comprised 7 frameshift or nonsense and 2 splice, whereas in the second hit, one splice mutation, 2 nonsense and 8 loss of heterozygosity were identified. Among 6 patients where intratumoral analysis detected a single mutation associated with a loss of heterozygosity, the peripheral blood analysis was able to detect the same mutation in 3 cases (50%). CONCLUSIONS: Intratumoral genetic analysis of sporadic retinoblastoma can detect germ-line mutations. These patients are at higher risk of bilateralization and development of second tumors or trilateral retinoblastoma. Genetic screening is recommended in every patient diagnosed with retinoblastoma.

[Genetic analysis results of patients with a retinoblastoma refractory to systemic chemotherapy]. / Resultados del analisis genético de los pacientes con retinoblastoma resistente a quimioterapia sistémica.

OBJECTIVE: To analyze the genetic alterations identified in the RB1 gene in retinoblastoma patients who do not respond to systemic chemotherapy. METHODS: A genetic analysis was performed on 115 patients with retinoblastoma, 40 of whom had received systemic chemotherapy, and 29 of them had bilateral disease. Descriptive and retrospective study. Non-responders were considered as patients who are finally enucleated. RESULTS: Patients with deletion type mutations are those with less preservation of the eyeball (Pearson Chi-square, P=.055). Patients with an impaired nonsense-frameshift type are more likely to preserve the eyeball. Of the 3 patients who had undergone bilateral enucleation, 2 of them had deletions and one missense alteration. Survival analysis (Kaplan-Meier curve) shows that patients with deletion type mutations are more resistance to chemotherapy, are suffering higher rates of enucleation, and for a shorter period of time (log rank [Mantel-Cox] with a significance level of P=.053), which are also associated with increased rate of being bilateral. CONCLUSIONS: Patients with a genotype show increased resistance to chemotherapy should be evaluated more closely and treated with various therapeutic weapons early. Patients that have deletions in the RB1 gene are at increased risk of chemoresistance. It is likely that other genetic alterations other than RB1 gene may be related to tumor aggressiveness and treatment resistance.

Seasonal variation in the month of birth in patients with skin cancer.

BACKGROUND: Month of birth influences the risk of developing several diseases. We investigated the influence of date of birth on melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC) incidence. METHODS: Enhanced cancer registry data were analysed including 1751 MSC and 15 200 NMSC. RESULTS: People born in February to April showed significantly elevated risks of NMSC compared with those born in summertime. CONCLUSIONS: We demonstrated seasonality by date of birth for skin cancer incidence. Neonatal UV exposure may explain this finding.

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge.

OBJECTIVE: Insulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering. METHODS: Forty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin. RESULTS: IR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets. CONCLUSIONS: Patients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.

[Trilateral retinoblastoma. Correlation between the genetic anomalies of the RB1 gene and the presence of pineal gland cysts]. / Retinoblastoma trilateral. Correlación de las alteraciones genéticas del gen RB1 y la presencia de quistes de la glándula pineal.

OBJETIVE: To determine the correlation between the presence of genetic anomalies identified in the RB1 gene and the development of trilateral retinoblastoma. METHOD: No patients with primitive neuroectodermal tumour (PNET) were identified out of a total of 206 patients, but there were 17 cases of pineal cysts, of which 11 had a genetic study. RESULTS: Of the 11 patients who had a genetic study performed, the anomaly in the germinal line was identified in 8 cases, which was equivalent to 100% of the bilateral retinoblastomas, and 25% of the unilateral ones. It is more common to find a germinal mutation in patients with bilateral disease (P=.024). There are no significant differences in the type of anomaly identified, although the nonsense-frameshift type is more frequent in cases with bilateral involvement. Identification of the genetic anomaly is more frequent in patients who have pineal cysts (Fisher test; P=.490). Nine of the 17 patients received systemic chemotherapy (52.29% of the cases), which could be able to prevent the development of PNET. Although a certain trend was observed in all the mentioned parameters, there was a relationship between, the presence of pineal cysts and bilateral disease (Pearson Chi X2: P=.191), a known family history (Fisher test; P=.114) and age of early diagnosis (Fisher test; P=.114). There were no significant differences in the mutation type identified. CONCLUSIONS: Considering pineal cysts as a pre-malignant form of pinealoblastoma, we found a relationship between the germinal line mutation of the RB1 gene and the cases with bilateral or unilateral retinoblastoma.

Multiple primary cancers in women with gynaecological malignancies: a cancer registry-based study in Umbria region of Italy.

To investigate the risk of developing multiple primary cancers (MPCs) in patients with previous gynaecological malignancies (cervical, uterine, and ovarian). The study's subjects included all the women on the Umbrian Cancer Registry who were first diagnosed with gynaecological cancer between 1994 and 2009. MPCs were defined according to the rules defined by International Association of Cancer Registries (IACR) and International Agency for Research on Cancer (IARC). Standardized incidence ratios (SIRs) of observed to expected cases were used as the measure of relative risk; its significance and 95% confidence intervals were determined assuming a Pois- son distribution. During the analysed period, the authors observed a total of 346 cases of MPCs in women with cervix (54 cases), corpus of uterus (196 cases), and ovarian (96 cases) malignancies. Significant SIRs were found in all of them, considering all sites combined: 2.43 (95% CI: 1.87-3.14) for cervix, 1.75 (95% CI: 1.52-2.01) for corpus of uterus, and 2.32 (95% CI: 1.90-2.84) for ovary malignancies, with different site-specific risks. Current data confirmed an excess risk of MPCs among women with gynaecological malignancies compared to the general population. The observed site-specific associations are useful to investigate shared risk factors and set up specific follow-up patients.

Epidemiology of HPV-related female cancers in the Umbria region of Italy: pre-vaccination period.

The authors describe the incidence and mortality rates of human papillomavirus (HPV)-related female cancers in Umbria (Italy) in the pre-vaccination period from 1978-2008. Joinpoint regression was applied on age-adjusted incidence and mortality rates to evaluate temporal trends. Mouth and pharynx cancers incidence and mortality trends decreased about three percent per year. For anus and anal canal cancer, incidence and mortality trends presented a non-significant decrease. For malignant neoplasm of vulva, a significant change was found in incidence trend: the annual percentage change decreased from 2001 (- 1.8%). Mortality trend showed a non-significant decrease. Incidence and mortality rates from vaginal cancer were non-significantly decreased. For malignant neoplasm of cervix uteri, incidence rates showed a significant decrease by 2.1% per year. Mortality rates decreased as well, although non-significantly. HPV-related cancers consistently decreased in Umbria. This trend may be a consequence of safer sexual behavior. For cervical cancer, a combination of opportunistic and programmed screening led to a much-reduced disease burden. It is expected that the implementation of vaccination in the future will lead to a further decrease of HPV-related cancer incidence and mortality.

Risk of multiple primary cancers following melanoma and non-melanoma skin cancer.

BACKGROUND: The relationship between cutaneous malignancies and successive primary cancers has been studied since several years, but it still remains controversial. OBJECTIVE: The aim of this study was to evaluate the excess risk of multiple primary cancer among the population of Umbria, Italy, that survived a skin cancer. METHODS: The data registered in the Umbrian Population Cancer Registry from 1994 to 2006 were collected, recorded, and analysed in accordance to the standard methods recommended for cancer registries. Among skin cancer patients, those with multiple cutaneous and non-cutaneous cancers were selected. Only sites with a frequency of more than five cases were considered. The expected number of cases was obtained from indirect standardization with regional incidence rates in several sites that incurred in the overall period. The significance of the observed/expected ratios and the corresponding 95% CI were based on the Poisson distribution. RESULTS: In men, a significant standardized incidence ratio (SIR) was found for melanoma (2.21), non-melanoma skin cancers (1.86), Hodgkin's (4.95) and non-Hodgkin lymphoma (1.82), and tongue/mouth cancer (2.47). In women, melanoma, non-melanoma skin and breast cancer showed a significant high SIRs (4.13, 1.55 and 1.28 respectively). All other cancers showed a non-significant SIR. Considering all sites combined and all sites except skin cancers, the analysis showed a significant excess in men, whereas a significant risk was observed in women only when also skin cancers were considered. CONCLUSIONS: Data from the whole of Umbrian population revealed that skin cancer patients experience marked excess risk of further primary cancers. The main risk in both genders is skin melanoma and other skin cancers. The excess of lymphomas and tongue/mouth cancers is also significant in men, and breast cancer in women. These observations prompt us to include a screening for these cancers in the follow-up of our patients surviving a skin malignancy.

Recent trends in incidence, mortality and survival after cancer of the female breast and reproductive organs. Umbria, Italy: 1978-2005.

This study analyzed the incidence, mortality and survival after cancer of the female breast and reproductive organs in the Umbria region of Italy with the aim of generating hypotheses to explain trends. Mortality data were supplied by ISTAT (1978-1993) and ReNCaM (1994-2005) and incidence (1994-2005) and survival (at 12/31/2007) data by RTUP. Joinpoint regression was applied to evaluate temporal trends of the age-adjusted incidence and mortality rates. Mortality, incidence and relative survival rates were compared with national and international data. The incidence of breast cancer increased up to 2001 and afterwards significantly decreased; mortality rates significantly decreased after 1994. Uterine corpus incidence was practically stable, and decreased over the study period; mortality from all uterine subsites significantly decreased from 1978 onwards. Trends in ovarian cancer incidence and mortality (after 1985) were constant. Trends in occurrence of breast and cervical cancer were linked to population screening of Umbrian women, noting a low compliance by younger females with cervical cancer screening and emphasizing the opportunity of starting breast cancer screening at a younger age. Trends in the incidence of cancer of the uterus and ovary, though unsteady, were probably related to modifications in risk factor exposure. Survival was better for breast and cervical cancers than in the 1978-1982 period and might be due to early diagnosis and progress in therapy.

Incidence of multiple primary malignancies in women diagnosed with breast cancer.

Using data from the Umbrian Population Cancer Registry (RTUP) we tested the hypothesis of relationships between several subsequent cancer sites in women who had had breast cancer. New patients (7,840) were collected from the RTUP between 01/01/1994 and 31/12/2006; 24 DCO cases were excluded; 332 successive multiple cancers in 320 patients were recorded. Including all second cancers, metachronous contralateral breast cancer, the observed/expected ratio (SIR) was non-significant. Excluding these cases, SIR was significantly lower whether with or without second skin carcinomas. SIR of all second metachronous contralateral cancers, excluding skin carcinomas, was non-significant. Significantly lower risk involved the colorectum, stomach, pancreas and metachronous breast with different histology. A significant excess was found of melanoma and total second breast cancers, including the contralateral. The excessive skin melanoma in breast cancer survivors was attributed to the relationship with BRCA2 and CDKN2A mutation-positive patients. The excess risk due to the CDKN2A mutation should also include pancreatic cancer which, in the present study, presented a significantly lower risk.

Epidemiological overview on the effectiveness of mass screening for female cancer in Umbria, Italy.

Using incidence, survival and mortality we tried to verify the effectiveness of mass-screening interventions for cervical uterine, breast, and colorectal cancer in females. Mortality data concern the period from 1978-2002. Incident cases derived from an ad hoc survey for 1978-1982 data and from the RTUP from 01/01/1994 to 31/12/2002. Relative survival rates were calculated for 1978-1982, 1994-1997 and 1998-2002 time intervals. All standardized mortality figures showed a steady trend. Incidence rates concerning cervical uterine cancer showed a decrease starting from the 1978-1982 period, whereas those for breast cancer had a constant increasing trend, and those for colorectal cancer increased up to 1997-1999 and later remained constant. For breast cancer the 5-year survival rate increased about 15% compared to the first period, for colon cancer there was less of an increase and the increase for cervical uterine cancer survival was only for the 1998-2002 period compared to the former ones. With constant incidence rates, improvement in survival from cervical uterine cancer may be due to a high number of cancer cases detected at an early stage. The effect of breast cancer screening on incidence is evident, though differences still did not influence mortality and survival. Colorectal cancer epidemiology can be considered as a prescreening pattern. Mortality, incidence and survival data allow a good overview for the effectiveness of screening procedures.

Urban-rural differences in gynaecological cancer occurrence in a central region of Italy: 1978-1982 and 1998-2002.

Differences in gynaecological cancer incidence and mortality in the urban and rural areas of the Umbria region (central Italy) were investigated. All women with primary invasive breast cancers, uterine cervix and uterine corpus, and ovarian cancers diagnosed during the periods 1978-1982 and 1998-2002 were identified and analysed according to place of residence (either urban or rural). Mortality data were supplied by the National Institute of Statistics (ISTAT) for the period 1978 to 1982, whereas for the 1994-2002 period they were supplied by the Regional Nominative Causes of Death Registry (ReNCaM). Incident cases considered were taken from an ad hoc survey for the first period and from the Umbrian Population Cancer Registry database for the second one. For each site the age-adjusted incidence (AAIR) and mortality (AADR) rates were calculated. The expected number of rural cases was obtained from indirect standardisation with urban incidence and mortality rates of several sites. The significance of the observed expected ratios (SIRs for incidence and SMRs for mortality) and the corresponding 95% confidence intervals were based on the Poisson distribution. Urbanisation levels were established following the classification of the Italian Institute of Statistics. For all sites, excluding the ovary during the most recent period, the SIR relative to rural areas was below 1, but the rates were statistically significant only for breast cancer in both periods (SIR 0.81, 95% CI 0.74-0.88 and SIR 0.82, 95% CI 0.77-0.88, respectively) and for cervix uteri in the first period (SIR 0.77, 95% CI 0.59-0.94). The lower breast cancer incidence in the rural area could also be due to lesser compliance with screening procedures which, up until 2002, were not provided in the form of mass-screenings throughout the region by the Regional Health Department. These results underscore the need for continued efforts to provide preventive health services to medically underserved women throughout Umbria, including rural communities. Underutilisation of preventive healthcare services may result in failure to identify healthcare problems that might be successfully managed with medication or lifestyle changes, as well as missed opportunities to prevent potentially life-threatening diseases.

[Survival of men with upper aerodigestive cancer in Umbria, Italy. 1978-82 and 1994-98]. / Sopravvivenza del cancro delle vie aerodigestive superiori nei maschi in Umbria. 1978-82 e 1994-98.

The aim of this study is to analyze the upper aerodigestive cancer survival in Umbria, a central Italian region, in the periods 1978-82 and 1994-98. The cases' data diagnosed in the period 1978-82 were derived from an ad hoc survey carried out in Umbria and for the years 1994-98 from Umbria Population-based Registry (RTUP). In the period 1994-98 the relative survival has lightly improved compared with the previous one. Comparison among five year relative standardized survival for head and neck, oesophagus and larynx, in Umbria region and in the other Italian registries, shows a quite high survival that could be further improved with an early diagnosis and, consequently, less destroying treatments.

[Other obstructive diseases: byssinosis, chronic bronchitis and occupational COPD and eosinophilic bronchitis]. / Otras enfermedades obstructivas: bisinosis, bronquitis crónica y EPOC de origen laboral y bronquitis eosinofílica.

Besides occupational asthma and diseases derived from acute inhalation, other obstructive diseases also have an occupational origin. Although at present byssinosis is a rare disease in Spain, we describe its characteristics because of its historical interest amongst occupational respiratory diseases and because it is still relevant in developing countries. Chronic bronchitis can also be related to exposure at work to dust and smoke, and is often referred to as "industrial bronchitis". Historically, the relation of CPOD to occupation has been subject to controversy, but nowadays this relationship is accepted; we describe the present evidence supporting this relationship. Finally, we describe eosinophilic bronchitis without asthma, an entity that was described for the first time in 1989 and that can sometimes have an occupational origin, sharing aetiological agents with occupational asthma.

A population survival model for breast cancer.

Breast cancer is a major health problem, and disease control depends on an effective healthcare system. A registry-based tool to monitor the quality of breast cancer care could be useful. The aim of this study was to develop a population survival model for breast cancer based on the Nottingham Prognostic Model (NPM). To this end, 1452 cases of breast cancer diagnosed in the Umbria Region, Italy, during the period 1994-1996 were studied. An extensive search for routinely available variants in prognosis and treatment was performed. In about 80% of cases complete information on factors included in the NPM was available. The Cox model was used to assess the prognostic value of study factors. Nodal stage was the most important prognostic factor. In women who did not undergo axillary dissection (17%) the risk of death was twice that in women with no affected nodes, but they received chemotherapy with the same frequency. Radiotherapy was also less frequently used in this group. Grading was a significant prognostic factor only when women over 80 were excluded. Population survival models based on data from cancer registries may provide a tool that can be used to evaluate healthcare systems and the effectiveness of interventions. The inclusion of older women in our models decreased the significance of many established prognostic factors because of the frequency of incomplete evaluation and less aggressive treatment in these patients. Not undergoing surgical axillary dissection was associated with a worse prognosis and with less aggressive treatment.