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R De Angelis

Publications and source records attributed to R De Angelis.

At least 19 recordsLinked to original sources

Estimating regional cancer burden in countries with partial registration coverage: an application to all malignant neoplasms in Italy over the period 1970-2010.

Regional epidemiological indicators of cancer burden are essential information for cancer surveillance and health resources planning, especially in countries with partial registration coverage and geographically variable risk patterns, such as Italy. This paper presents a methodology to derive cancer incidence and prevalence at the regional and national scale and illustrates its application to all malignant neoplasms in Italy for the period 1970-2010. The method, denoted as MIAMOD, is based on a back-calculation approach and derives cancer-specific morbidity measures by using official mortality data and model-based relative survival from local Cancer Registries data. The output includes time-trends and projections of a complete set of epidemiological indicators, i.e. mortality, incidence and prevalence. Results for all cancers in Italy show different incidence patterns by gender and a pronounced regional variability among men: male incidence is estimated to decrease in almost all northern-central regions, while more stable or even rising trends are estimated in the southern regions. No incidence reduction is expected for women. Prevalence increases country-wide in both sexes. The proposed approach can be applied to derive regional up-to-date time trends of cancer burden indicators in countries with local and sparse cancer registration systems. These estimates are useful for planning health services on a national and regional basis and for highlighting regional differences.

Adolescent↗

Dermoscopic observation of Bowen's disease.

BACKGROUND: In the literature no specific dermoscopic criteria have been described for the diagnosis of Bowen's disease (BD). OBJECTIVE/AIM: To assess the morphological findings of BD seen under dermoscopic observation. METHODS: Clinical and dermoscopic images of 14 patients affected by BD with various amount of pigmentation were obtained by means of Heine Dermaphot. Dermoscopic images were analysed by experienced observers applying the modified pattern analysis. RESULTS: The most frequently occurring dermoscopic features were found to be: multicomponent pattern (100%); atypical vascular structures (86.6%); absence of pigmented network (64.3%) or presence of pseudo-network (35.7%); irregular diffuse pigmentation or blotches of pigment (64.2%); irregularly distributed dots and globules (64.2%); focal/multifocal hypopigmentation (78.5%), scaly surface (64.2%) and haemorrages (26.6%). CONCLUSIONS: Dermoscopically, BD is mainly characterized by a multicomponent global pattern associated with a prominent vascular pattern (mainly dotted vessels) and a scaly surface. Although no specific dermoscopic criteria can be given for BD, epiluminescence can be a valuable aid in the diagnosis of such a mimicker lesion.

Aged↗

Diffuse scleroderma occurring after the use of paclitaxel for ovarian cancer.

Acase of diffuse scleroderma in a 56-year-old woman who received paclitaxel for the treatment of a metastatic ovarian cancer is presented. The clinical cutaneous alterations, as well as the capillaroscopic and histological findings, were indistinguishable from those encountered in definite systemic sclerosis (SSc). In contrast to SSc, Raynaud's phenomenon and cutaneous calcinosis were absent and antinuclear antibodies were negative. The temporal relationship between the onset of skin involvement and administration of the drug may indicate an effect of paclitaxel.

Antineoplastic Agents, Phytogenic↗

Cancer survival in European adolescents and young adults.

Survival of patients aged 15-24 years, diagnosed with cancer during the period of 1990-1994, is described within Europe. Data on 15101 patients, extracted from the files of the 56 adult cancer registries included in the EUROCARE-3 database, representing 20 European countries, were analysed and compared. Five-year survival for 'all cancers combined' was 75% in males (ranging from 59% in Estonia to 89% in Iceland), and 78% in females (ranging from 59% in Estonia to 89% in Norway). The Northern European countries (except Denmark) and Austria had the highest survival figures, while survival in the Eastern European countries was lower than the European average. Denmark, UK, and the pool of the central European countries, had intermediate survival figures. Haemopoietic tumours were the most common malignancies: 5-year survival was high for Hodgkin's disease (89%), intermediate for non-Hodgkin's lymphoma (68%) and lower for acute lymphoblastic leukaemia (ALL) (47%) and acute myeloblastic leukaemia (AML) (39%). Five-year survival for gonadal germ cell cancers, the second most common malignancy in young adults, was 90%. Five-year survival for the other cancers under consideration was as follows: 89% for skin melanoma, 66% for all Central Nervous System (CNS) tumours, 57% for bone tumours, 58% for osteosarcoma, 42% for Ewing's sarcoma, 57% for soft-tissue sarcomas, 99% for thyroid carcinoma, 82% for uterine cervical carcinoma, and 83% for ovarian carcinoma. For more 'adult-specific tumours', 5-year survival was good for colon (77%) and lung (60%) cancers, and less favourable, compared with adults, for breast cancer (68%). Adolescents (15-19 years) had significantly worse survival than young adults (20-24 years) for all malignancies combined. Survival for Hodgkin's lymphoma, CNS tumours, melanoma and colon cancer showed marked regional variability. Since many of the tumours occurring in young adults are curable, these results should encourage, without delay, efforts to identify obstacles to improving outcome and reducing geographical inequalities in survival for this group of patients.

Adolescent↗

Cancer prevalence in the UK: results from the EUROPREVAL study.

BACKGROUND: Cancer incidence, mortality and survival statistics for the UK are routinely available; however, data on prevalence, which is generally regarded as an important measure for health planning and resource allocation, are relatively scarce. MATERIALS AND METHODS: Eight cancer registries in the UK, covering more than half the population, provided data based on >1.5 million cases of cancer. Total prevalence was calculated using methods developed for the EUROPREVAL study, based on modelling incidence and survival trends. The prevalence of cancers of the stomach, colon, rectum, lung, breast (in females), cervix uteri, corpus uteri and prostate, melanoma of skin, Hodgkin's disease, leukaemia and all malignant neoplasms combined, was estimated for the UK for the end of 1992. RESULTS: Overall, approximately 1.5% of males and 2.5% of females in the UK population at the end of 1992 were living with a diagnosis of cancer. These proportions increased steeply with age, with approximately 7.5% (7.3% and 7.8%, in males and females, respectively) of people aged > or =65 years living with a diagnosis of cancer. Of the individual cancers, by far the highest prevalence (almost 1%) was seen for breast cancer in females; more than one in three of all living female cancer patients had been diagnosed with breast cancer. For males, around half of prevalent cases had been diagnosed >5 years previously and 30% >10 years previously; for females, these figures were both higher, at approximately 60% and 40%, respectively. CONCLUSIONS: The estimates of prevalence presented here comprise: recently diagnosed patients in need of treatment and monitoring; long-term survivors, some of whom will nevertheless eventually die from the cancer, while others may be cured of the disease; and patients in the terminal phase who are dying from the cancer. Further work should attempt to identify the proportions of patients in the different phases of care in order to optimise the use of prevalence estimates in health care planning.

Adolescent↗

The EUROCARE-3 database: methodology of data collection, standardisation, quality control and statistical analysis.

The EUROCARE database contains data on 6.5 million cancer patients diagnosed from 1978 to 1994 in populations covered by 67 cancer registries in 22 European countries. The quality-checked entries specify age, sex, diagnosis date, cancer site, morphology, microscopic confirmation and vital status, as well as containing broad indicators of stage. For EUROCARE-3, which refers to diagnoses from 1990 to 1994, 3389 cases with major data problems and 142,525 second or subsequent cancers were removed, leaving more than 2 million cases for analysis. From these data, observed and relative survival for each cancer site and country were calculated at 1, 3 and 5 years from diagnosis. Overall European survival for each cancer site and for all cancers combined were calculated combining country-specific survival figures. Overall, 1.1% of cases were lost to follow-up, 4.2% were known from death certificates only and 1.2% were known at autopsy only. The percentage of microscopically confirmed cases varied with cancer site and country, and was always higher in northern European countries. Comparison of quality indicators for the EUROCARE-3 database with earlier EUROCARE databases indicates that data quality and standardisation have improved.

Adult↗

Mininvasive abdominal aortic surgery. Early recovery and reduced hospitalization after multidisciplinary approach.

AIM: Clinical experience in gastrointestinal surgery demonstrated that a multimodal approach can improve the outcome and reduce the length of hospital stay. In this paper we investigate the impact of a multimodal clinical program, based on mininvasive surgery, epidural anesthesia and early feeding and mobilization, on postoperative morbidity and hospitalization after abdominal aortic surgery. METHODS: A 2-armed study was designed. All patients undergoing abdominal aortic surgery between May 2000 and April 2001 were enrolled in a multidisciplinary clinical program including thoracic epidural anesthesia and analgesia, left sub-costal minilaparotomy without evisceration, encouragement to feed and mobilize soon after surgery (Multidisciplinary group: n=82). For comparison purposes, a retrospective analysis was conducted using the data of all patients operated on between January and December 1997, receiving standard anesthesia care and a standard surgical and nursing program (Standard group: n=64). RESULTS: In the Multidisciplinary group we observed significantly better pain relief (p<0.01), earlier restoration of ambulation (p<0.01), earlier feeding (p<0.01) and passage of stools (p<0.01). The incidence of complications was significantly lower in the Multidisciplinary group: pulmonary (0% vs 14.1%), cardiac (2.4% vs 9.4% ) and gastrointestinal (0% vs 10.9%). None of the patients in the Multidisciplinary group required admission to Intensive Care. Median postoperative hospitalization was 3 days in the Multidisciplinary group compared to 9 days in the Standard group (p<0.01). CONCLUSION: These results suggest that a multidisciplinary intervention with review of the traditional surgical care program would enhance recovery, decrease morbidity and hospitalization after abdominal aortic surgery.

Aged↗

Measuring cancer prevalence in Europe: the EUROPREVAL project.

Cancer prevalence is the proportion of individuals in a population who at some stage during their lifetime have been diagnosed with cancer, irrespective of the date of diagnosis. Cancer prevalence statistics have generally been provided by a limited number of well established cancer registries that have been in existence for several decades. The advent of systematic follow-up of life status of incident cases and the availability of new statistical methodologies, now makes it possible for registries established during the 1970s or 1980s to provide prevalence data. The main problems encountered in the estimation of prevalence are the inclusion of: (i) cases lost to follow-up; (ii) cases known only from their death certificate; (iii) cases diagnosed before the start of registration; and (iv) the treatment of multiple tumours and migrations. The main aim of this paper was to review these problems and discuss, through the experience gained with EUROPREVAL, how they can be overcome. A method is presented for the calculation of prevalence of all cancers combined in the populations covered by the 45 cancer registries participating in EUROPREVAL. Prevalence of cancer is estimated to be 2% on average, with the highest values (3%) in Sweden and the lowest in Eastern Europe, with a minimum of approximately 1% in Poland.

Adolescent↗

Relative roles of endothelial cell damage and platelet activation in primary Raynaud's phenomenon (RP) and RP secondary to systemic sclerosis.

OBJECTIVE: To evaluate the relative roles of endothelium and platelets in the pathogenesis of primary RP and RP secondary to SSc. METHODS: Endothelial derived ET-1, t-PA, PAI-1, and platelet derived beta-TG, PDGF, TGF-beta were measured in 36 patients with primary RP, 14 patients with RP secondary to SSc and 30 age and sex matched controls. RESULTS: A significative increase of ET-1, t-PA, PAI-1, TGF-beta, and beta-TG were the most relevant changes in patients with RP secondary to SSc with respect to the controls. Less relevant increases of t-PA, PAI-1, PDGF, and beta-TG levels were observed in patients with primary RP vs controls. CONCLUSIONS: These data seem to confirm the involvement of endothelial cells and platelets in the pathogenesis of RP, with mild changes in primary RP and more relevant changes in RP secondary to SSc.

Adult↗

Vasopressin and thirst in patients with posterior pituitary ectopia and hypopituitarism.

OBJECTIVE: Partial diabetes insipidus has been documented in patients with congenital hypopituitarism and posterior pituitary ectopia, some cases being clinically silent except for enuresis. The objective of our study was to evaluate vasopressin (AVP) secretion and thirst appreciation in hypopituitary patients with posterior pituitary ectopia. PATIENTS: Twelve males and three females, aged between 13 and 38 years (median 19 years). Eleven had multiple pituitary deficiencies, adequately replaced at the time of the study, and four were only growth hormone deficient. None of the patients suffered from polyuria, polydipsia or nocturnal enuresis. We tested the patients with a 5% NaCl infusion. Five patients with abnormal vasopressin production were also tested with nitroprusside, which affects baroceptor vasopressin secretion. RESULTS: We found that only two out of 12 patients had normal AVP secretion. Thirst assessment showed severe hypodipsia in one patient, hyperdipsia in three out of 15 and more subtle abnormalities in two out of 15 patients. Concordance was found between osmotically and baroceptor-stimulated vasopressin. CONCLUSIONS: Patients with posterior pituitary ectopia showed a high prevalence of subclinical subnormal vasopressin response to the osmolar stimulus and moreover an impairment of thirst appreciation. Our data on nonosmotically stimulated AVP release suggest the existence of a damage in the hypothalamic vasopressin secreting centres.

Adolescent↗

Identification of a novel partner of RNA polymerase II subunit 11, Che-1, which interacts with and affects the growth suppression function of Rb.

hRPB11 is a core subunit of RNA polymerase II (pol II) specifically down-regulated on doxorubicin (dox) treatment. Levels of this protein profoundly affect cell differentiation, cell proliferation, and tumorigenicity in vivo. Here we describe Che-1, a novel human protein that interacts with hRPB11. Che-1 possesses a domain of high homology with Escherichia coli RNA polymerase final sigma-factor 70 and SV40 large T antigen. In addition, we report that Che-1 interacts with the retinoblastoma susceptibility gene (Rb) by two distinct domains. Functionally, we demonstrate that Che-1 represses the growth suppression function of Rb, counteracting the inhibitory action of Rb on the trans-activation function of E2F1. These results identify a novel protein that binds Rb and the core of pol II, and suggest that Che-1 may be part of transcription regulatory complex.

Amino Acid Sequence↗

PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE, treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabilitation, and may be easily used in a larger number of nonspecialized units.

Aged↗

Superficial vein valve repair with a new external valve support (EVS). The IMES (International Multicenter EVS Study).

The aim of this international multicenter trial was to evaluate the effects of a new surgical device (Gore External Valve Support-EVS) and technique for external valvuloplasty of the long saphenous vein (LSV). Patients with superficial venous disease and venous hypertension due to pure superficial venous incompetence were randomized into two treatment groups, the first treated with "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with the EVS. Patients with uncomplicated varicose veins within the age range of 35-65 years were included. Incompetence with presence of functional cusps at the saphenofemoral junction (SFJ), with vein dilatation were the main inclusion criteria. The EVS comprised of a GORE-TEX patch material (including a nitinol frame) that is placed around the vein, producing a reduction in the caliber of the vein. Also the vein section becomes elliptical. These combined actions are aimed to reduce incompetence, allowing a better closure of the cusps. The EVS was placed at the SFJ after limited dissection of the vein and ligation of collaterals. The procedure was randomized as an alternative to simple ligation or stripping (according with the procedure commonly used in the center). The associated ligation of distal incompetent veins was allowed. The main outcome measures of the study were evaluated by color-duplex (morphologic findings and evaluation of reflux) and with ambulatory venous pressure (AVP) or air-plethysmography (APG). Main endpoints of the first year of the study and main subject of this report (mainly concerning safety within the first year of follow-up) were considered presence/absence of reflux; patency of the veins; mobility/function of vein cusps; occurrence of thrombosis; tolerability of the device; and increased complexity and operating time needed for the EVS. At 1 year 30 patients had been randomized (14 EVS implanted, 16 controls). Reflux was absent in all EVS patients, all treated veins were patent, and all cusps were mobile. No thrombosis had been observed and the tolerability of the device was very good. The increased complexity required by placing the EVS was limited (5-12 minutes more). In conclusion results of the first year show efficacy and tolerability of the EVS. In selected patients (superficial LSV incompetence, reflux-dilatation, functional SFJ cusps, incompetence mainly due to enlargement of the vein), the EVS could be an effective alternative to "destructive" ligation and/or stripping of the vein. Prolonged follow-up will indicate the clinical potentials of the EVS.

Adult↗

Interaction between the pRb2/p130 C-terminal domain and the N-terminal portion of cyclin D3.

An association between cyclin D3 and the C-terminal domain of pRb2/p130 was demonstrated using the yeast two-hybrid system. Further analysis restricted the epitope responsible for the binding within the 74 N-terminal amino acids of cyclin D3, independent of the LXCXE amino acid motif present in the D-type cyclin N-terminal region. In a coprecipitation assay in T98G cells, a human glioblastoma cell line, the C-terminal domain of pRb2/p130 was able to interact solely with cyclin D3, while the corresponding portion of pRb interacted with either cyclin D3 or cyclin D1. In T98G cells, endogenous cyclin D3-associated kinase activity showed a clear predisposition to phosphorylate preferentially the C-terminal domain of pRb2/p130, rather than that of pRb. This propensity was also confirmed in LAN-5 human neuroblastoma cells, where phosphorylation of the pRb2/p130 C-terminal domain and expression of cyclin D3 also decreased remarkably in the late neural differentiation stages.

Adenovirus E1A Proteins↗

The RNA polymerase II core subunit 11 interacts with keratin 19, a component of the intermediate filament proteins.

We have previously cloned the human RNA polymerase II subunit 11, as a doxorubicin sensitive gene product. We suggested multiple tasks for this subunit, including structural and regulatory roles. With the aim to clarify the human RNA polymerase II subunit 11 function, we have identified its interacting protein partners using the yeast two-hybrid system. Here, we show that human RNA polymerase II subunit 11 specifically binds keratin 19, a component of the intermediate filament protein family, which is expressed in a tissue and differentiation-specific manner. In particular, keratin 19 is a part of the nuclear matrix intermediate filaments. We provide evidence that human RNA polymerase II subunit 11 interacts with keratin 19 via its N-terminal alpha motif, the same motif necessary for its interaction with the human RNA polymerase II core subunit 3. We found that keratin 19 contains two putative leucine zipper domains sharing peculiar homology with the alpha motif of human RNA polymerase II subunit 3. Finally, we demonstrate that keratin 19 can compete for binding human RNA polymerase II subunit 11/human RNA polymerase II subunit 3 in vitro, suggesting a possible regulatory role for this molecule in RNA polymerase II assembly/activity.

Amino Acid Sequence↗

Mixture models for cancer survival analysis: application to population-based data with covariates.

The interest in estimating the probability of cure has been increasing in cancer survival analysis as the curability of many cancer diseases is becoming a reality. Mixture survival models provide a way of modelling time to death when cure is possible, simultaneously estimating death hazard of fatal cases and the proportion of cured case. In this paper we propose an application of a parametric mixture model to relative survival rates of colon cancer patients from the Finnish population-based cancer registry, and including major survival determinants as explicative covariates. Disentangling survival into two different components greatly facilitates the analysis and the interpretation of the role of prognostic factors on survival patterns. For example, age plays a different role in determining, from one side, the probability of cure, and, from the other side, the life expectancy of fatal cases. The results support the hypothesis that observed survival trends are really due to a real prognostic gain for more recently diagnosed patients.

Age Factors↗

The cure for colon cancer: results from the EUROCARE study.

The interpretation of time trends and geographical differences of population-based survival rates is generally not easy, due to the difficulty in disentangling the effects of observational biases, diagnostic and therapeutic procedures and their interactions. Whereas descriptive analysis of relative survival is generally based on survival levels estimated at fixed time since diagnosis, interpretation issues can take advantage from the analysis of the shape of the considered relative survival. Parametric survival models allowing the estimation of the fraction of cured patients are applied here to analyze and discuss the differences in colon cancer relative survival between European countries, according to age and period of diagnosis. The survival curves of colon cancer patients are described according to 2 parameters: the proportion of cured patients and the mean survival time of fatal cases. These parameters are estimated by least square nonlinear regression of relative survival values derived from the EUROCARE Project publication. Exponential and Weibull survival functions are used to model the relative survival curve for the fraction of fatal cases. The Weibull model gives generally a better fit with respect to the exponential model, thus indicating that the mortality rate for fatal cases is decreasing with time since diagnosis. For the youngest patients, however, the 2 survival functions give practically overlapping estimates. The overall proportion of colon cancer patients in Europe that are estimated to be cured was 38.6%. This proportion increased from 36% to 40% for patients diagnosed in 1978-1980 and in 1983-1985, respectively. Accordingly, mean survival time of fatal cases increased from 1.18 to 1.52 years. According to age, the proportion of cured patients present a marked decrease from young (48.4% at age 15-44 years) to middle-aged patients (38.6% at age 5564 years) and only a mild decrease from these to the oldest patients (34.4% at age 75 or more). The opposite effect was shown by survival time of fatal cases, i.e., 1.71, 1.75 and 0.77 years for the same age classes, respectively. Proportion of cured cases and mean survival time of fatal cases tended to be positively correlated with each other across countries. Our results are consistent with the hypothesis that a real improvement in colon cancer survival took place in Europe during the years 1978-1985 and also suggest that the well-known decrease of relative survival with age at diagnosis could be mostly due to a decreasing efficacy of early diagnosis for patients under 60 years old and to less effective therapies for older patients.

Adult↗