Traffic-Related Air Pollution and Ground-Level Ozone Associated Global DNA Hypomethylation and Bulky DNA Adduct Formation.

Studies have indicated that air pollution, including surface-level ozone (O3), can significantly influence the risk of chronic diseases. To better understand the carcinogenic mechanisms of air pollutants and identify predictive disease biomarkers, we examined the association between traffic-related pollutants with DNA methylation alterations and bulky DNA adducts, two biomarkers of carcinogen exposure and cancer risk, in the peripheral blood of 140 volunteers-95 traffic police officers, and 45 unexposed subjects. The DNA methylation and adduct measurements were performed by bisulfite-PCR and pyrosequencing and 32P-postlabeling assay. Airborne levels of benzo(a)pyrene [B(a)P], carbon monoxide, and tropospheric O3 were determined by personal exposure biomonitoring or by fixed monitoring stations. Overall, air pollution exposure was associated with a significant reduction (1.41 units) in global DNA methylation (95% C.I. -2.65-0.04, p = 0.026). The decrement in ALU repetitive elements was greatest in the policemen working downtown (95% C.I. -3.23--0.49, p = 0.008). The DNA adducts were found to be significantly increased (0.45 units) in the municipal officers with respect to unexposed subjects (95% C.I. 0.02-0.88, p = 0.039), mainly in those who were controlling traffic in downtown areas (95% C.I. 0.39-1.29, p < 0.001). Regression models indicated an increment of ALU methylation at higher B(a)P concentrations (95% C.I. 0.03-0.60, p = 0.032). Moreover, statistical models showed a decrement in ALU methylation and an increment of DNA damage only above the cut-off value of 30 µg/m3 O3. A significant increment of 0.73 units of IL-6 gene methylation was also found in smokers with respect to non-smokers. Our results highlighted the role of air pollution on epigenetic alterations and genotoxic effects, especially above the target value of 30 µg/m3 surface-level O3, supporting the necessity for developing public health strategies aimed to reduce traffic-related air pollution molecular alterations.

Coffee consumption and risk of non-Hodgkin's lymphoma: evidence from the Italian multicentre case-control study.

PURPOSE: Several investigations have analysed the association between coffee intake and risk of cancer. Contradictory results were reported by the studies conducted in non-Hodgkin's lymphomas (NHL) few of which report results according to main NHL subgroups. The present study is aimed at evaluating the association between coffee consumption and the risk of NHL by analysing data from a large Italian multicentre case-control study that included 1,418 interviewed cases (1,301 B cell and 117 T cell NHL), diagnosed between 1990 and 1993, and 1,774 population healthy controls. METHODS: The association was evaluated by standard logistic regression analysis. Odds ratio (OR) estimates were adjusted for gender, age, residence area, educational level, previous chemotherapy treatment, smoking habit and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. RESULTS: For all B cell lymphomas, an increased risk (OR 1.6, 95% CI 1.2-2.0) was observed in the highest exposure category (consumption >4 cups per day for at least 30 years), but without a clear dose-response trend. Subgroup analyses highlighted an increased risk for drinkers of at least four cups per day for follicular lymphoma (OR 2.0, 95% CI 1.2-3.4). The risk increased with years of exposure and was more elevated among current smokers. CONCLUSIONS: Consumption of more than four cups of coffee per day enhances the risk of lymphoma, especially the follicular subtype. Further investigations based on large cohorts and accurate measures of exposure are needed to confirm the observed associations.

Metabolic evaluation in patients with infected nephrolithiasis: Is it necessary?

Fifty-four patients with infected renal lithiasis underwent complete metabolic evaluation searching for underlying factors contributing to stone formation including urine analysis and culture. Metabolic abnormalities were significantly more present in patients with mixed infected stones (struvite+/-apatite and calcium oxalate) than in patients with pure infected stones (struvite+/-carbonate apatite): hypercalciuria in 40%, hyperoxaluria in 34% and hyperuricosuria in 28% (p < 0.05). Urinary excretion of citrate was low in both groups without statistically significant difference (238+/-117 mg/24 h vs 214+/-104 mg/24/h, t = 0.72, p = 0.5). The few metabolic abnormalities present in patients with pure infected stones should suggest that urinary tract infection could change the urine chemistry in a lithogenic direction and be only cause of stone formation.

The effect of dietary estimates calculated using food frequency questionnaires on micronuclei formation in European pregnant women: a NewGeneris study.

The use of biomarkers of early genetic effects, predictive for cancer, such as micronuclei (MN) in lymphocytes, may help to investigate the association between diet and cancer. We hypothesised that the presence of mutagens in the diet may increase MN formation. A 'pooled' standardised analysis was performed by applying the same experimental protocol for the cytokinesis block micronucleus assay in 625 young healthy women after delivery from five European study populations (Greece, Denmark, UK, Spain and Norway). We assessed MN frequencies in mono- and binucleated T-lymphocytes (MNMONO and MNBN) and the cytokinesis blocked proliferation index using a semi-automated image analysis system. Food frequency questionnaires (FFQs) were used to estimate intake of fatty acids and a broad range of immunotoxic and genotoxic/carcinogenic compounds through the diet. Pooled difference based on delivery type revealed higher MNMONO frequencies in caesarean than in vaginal delivery (P = 0.002). Statistical analysis showed a decrease in MNMONO frequencies with increasing calculated omega-6 PUFA concentrations and a decrease in MNBN frequencies with increasing calculated omega-3 PUFA concentrations. The expected toxic compounds estimated by FFQs were not associated with MN formation in mothers after delivery. In pregnant women, an omega-3 and -6 rich diet estimated by FFQ is associated with lower MN formation during pregnancy and delivery.

Urolithiasis in renal transplantation: diagnosis and management.

OBJECTIVES: To report our experience of diagnosis and multimodal management of urolithiasis in renal transplantation. PATIENTS AND METHODS: From January 1995 to December 2012, 953 patients underwent renal transplantation in the Kidney Transplant Unit of Treviso General Hospital. Ten (10%) of them developed urinary calculi and were referred at our institution. Their mode of presentation, investigation and treatment were recorded. RESULTS: Seven had renal and 3 ureteral calculi. Urolithiasis was incidentally discovered on routine ultrasound in 6 patients, 1 presented with oliguria, 1 with anuria and acute renal failure and in 2 urolithiasis was found at removal of the ureteral stent. Nephrostomy tube was placed in 5 patients. Hypercalcemia with hyperparathyroidism (HPT) was present in 5 patients and hyperuricemia in 3. Two patients were primary treated by shock wave lithotripsy (SWL) and one of them was stone-free after two sessions. Two patients, one with multiple pielocaliceal calculi and the other with staghorn calculus in the lower calyx, were treated with percutaneous nephrolitothotomy (PCNL). Three patients were treated by ureteroscopy (URS) and in one of them two treatments were carried out. One patient had calculus impacted in the uretero-vesical anastomosis and surgical ureterolithotomy with re-do ureterocystoneostomy was performed after failure of URS. Two patients with calculi discovered at removal of the ureteral stent were treated by URS. CONCLUSIONS: The incidence of urolithiasis in renal transplantation is uncommon. In the most of patients the condition occurs without pain. Metabolic anomalies and medical treatment after renal transplantation may cause stone formation. Advancements in endourology and interventional radiology have influenced the management of urolithiasis that can be actually treated with a minimal incidence of risk for the renal allograft.

CINSARC in high-risk soft tissue sarcoma patients treated with neoadjuvant chemotherapy: Results from the ISG-STS 1001 study.

BACKGROUND: The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001). PATIENTS AND METHODS: Patients with available pre-treatment samples, treated with 3 cycles of either standard (ST) preoperative or histotype-tailored (HT) chemotherapy, were scored according to CINSARC (low-risk, C1; high-risk, C2). The 10-year overall survival probability (pr-OS) according to SARCULATOR was calculated, and patients were classified accordingly (low-risk, Sarc-LR, 10-year pr-OS>60%; high-risk, Sarc-HR, 10-year pr-OS<60%). Survival functions were estimated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Eighty-six patients were included, 30 C1 and 56 C2, 49 Sarc-LR and 37 Sarc-HR. A low level of agreement between CINSARC and SARCULATOR was observed (Cohen's Kappa = 0.174). The 5-year relapse-free survival in C1 and C2 were 0.57 and 0.55 (p = 0.481); 5-year metastases-free survival 0.63 and 0.64 (p = 0.740); 5-year OS 0.80 and 0.72 (p = 0.460). The 5-year OS in C1 treated with ST and HT chemotherapy was 0.84 and 0.76 (p = 0.251) respectively; in C2 treated it was 0.72 and 0.70 (p = 0.349). The 5-year OS in Sarc-LR treated with S and HT chemotherapy was 0.80 and 0.82 (p = 0.502) respectively; in Sarc-HR it was 0.70 and 0.61 (p = 0.233). CONCLUSIONS: Our results, although constrained by the small size of the series, suggest that CINSARC has weak prognostic power in high-risk, localized STS treated with neoadjuvant chemotherapy.

Nephrolithiasis in medullary sponge kidney.

Seventy-one patients with documented Medullary Sponge Kidney (MSK) and nephrolithiasis underwent complete metabolic evaluation. These patients constituted 7.3% of our calcium stone-forming population Metabolic anomalies (hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria) were observed in 82% of patients. No patient was hypercalcemic and none had hyperparathyroidism. Thus the patients with medullary sponge kidney and renal stones had the same spectrum of metabolic anomalies as the overall population of idiopathic stone formers. Although these patients may have anatomic anomalies which determine stasis of urine and infection causing stone formation, they should be evaluated and treated appropiately for any metabolic defect.

Stenting after ureteroscopy for ureteral lithiasis: results of a retrospective study.

OBJECTIVES: Routine ureteral stenting after ureteroscopy for stone removal is common. However ureteral stent negatively impact quality of life and can cause significant morbidity. This study was carried out to report our experience. MATERIALS AND METHODS: A total of 529 patients underwent ureteroscopy for the treatment of ureteral stones. In 436 pts (82%) a stent was placed, in 281 double J (removed within 2-4 weeks) and in 155 mono J (removed within 24 h). Ninethy-three did not received stenting. At 24 hour the mesaured outcomes were post operative pain, fever and hematuria, at 4 weeks need for hospital care (readmission or visit in the clinic) for lower urinary tract symptoms (LUTS), hematuria, fever or pain. RESULTS: No significant difference was observed between two groups regarding the complications at 24 hour after the treatment ( pain p = 0.6, fever = 0.7, hematuria p = 0.8). At 4 weeks after the ureteroscopy the incidence of LUTS, hematuria, pain and fever requiring the need for hospital care (readmission or visit in the clinic) was higher in the group with double J stent respect to the group with mono J stent (p < 0.05). At 3 months follow-up no difference was oberved between the two groups regarding stone-free rate and incidence of ureteral stricture formation. CONCLUSIONS: Routine stenting is necessary after ureteroscopy for ureteral lithiasis to prevent pain and fever without difference in stone free rate and incidence of stricture formation rate between the two groups. LUTS, hematuria and/or pain needing for hospital care were more frequent in the group with double J stent in spite of high stone free rate and low incidence of stricture formation. Further prospective randomized studies are needed to assess the role of using "short" and "long-term" stenting after ureteroscopy lithotripsy, considering that the choice actually depends on the surgeon's intraoperative judgment.

Simultaneous surgical management of chronic grade-2 valgus instability of the knee and anterior cruciate ligament deficiency in athletes.

We report on 22 patients with chronic grade-2 valgus laxity of the knee combined with chronic anterior cruciate ligament (ACL) insufficiency, in whom the two lesions were addressed at the same surgical setting. At a minimum follow-up of 24 months, clinical and functional variables had improved significantly (P < 0.001), and 20 of the 22 patients (91%) had returned to sport at pre-injury level. There were no operative complications in this series. In selected athletes with chronic symptomatic valgus laxity of the knee combined with ACL insufficiency, surgical repair of the MCL in association with ACL reconstruction is a suitable and reliable option to restore knee stability and allow return to pre-injury activity level.

Urinary alkalization for the treatment of uric acid nephrolithiasis.

Three major conditions control the potential for uric acid stones: the quantitative excretion of uric acid, the volume of urine as it affects the urinary concentration of uric acid and the urinary pH. However, the most important factor for uric acid stone formation is acid urinary pH that is a prerequisite for uric acidic stone formation. Indeed the goal standard of urinary alkalization is to achieve a pH of 6-6.5. Administration of alkali should be titrated appropriately by pH paper to record urinary pH until a steady state is achieved. Alkali therapy such as sodium bicarbonate and potassium citrate has been advocated on the basis of established clinical experience, although potassium citrate should be preferred because it may avoid the complication of calcium salt precipitation. Recently it has been reported the clinical efficacy of therapy with potassium citrate/potassium bicarbonate for dissolution of radiolucent stones respect to control study period (only water daily intake of 1500 ml). Furthermore, mean urinary pH was significantly continuously higher during the alkali treatment study in comparison to the control study period, even though the mean of urinary volumes were similar in the two periods. In conclusion urinary alkalization with maintaining continuously high urinary pH values, could be the treatment of choice for stone dissolution and prevention of uric acid stones.

Early palliative care in haematological patients: a systematic literature review.

BACKGROUND: Early palliative care together with standard haematological care for advanced patients is needed worldwide. Little is known about its effect. The aim of the review is to synthesise the evidence on the impact of early palliative care on haematologic cancer patients' quality of life and resource use. PATIENTS AND METHODS: A systematic review was conducted. The search terms were early palliative care or simultaneous or integrated or concurrent care and haematological or oncohaematological patients. The following databases were searched: PubMed, Embase, Cochrane, CINHAL and Scopus. Additional studies were identified through cross-checking the reference articles. Studies were in the English language, with no restriction for years. Two researchers independently reviewed the titles and abstracts, and one author assessed full articles for eligibility. RESULTS: A total of 296 studies titles were reviewed. Eight articles were included in the synthesis of the results, two controlled studies provided data on the comparative efficacy of PC interventions, and six one-arm studies were included. Since data pooling and meta-analysis were not possible, only a narrative synthesis of the study results was performed. The quality of the two included comparative studies was low overall. The quality of the six non-comparative studies was high overall, without the possibility of linking the observed results to the implemented interventions. CONCLUSIONS: Studies on early palliative care and patients with haematological cancer are scarce and have not been prospectively designed. More research on the specific population target, type and timing of palliative care intervention and standardisation of collected outcomes is required. PROSPERO REGISTRATION NUMBER: CRD42020141322.

Genetic susceptibility to benzene toxicity in humans.

Human metabolism of benzene involves pathways coded for by polymorphic genes. To determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active personal sampling, were studied. The frequency of DNA single-strand breaks (DNA-SSB) was determined by alkaline elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NAD(P)H:quinone oxidoreductase 1 (NQO1) variant had significantly twofold increased DNA-SSB levels compared to wild-type individuals. The same result was observed for subjects with microsomal epoxide hydrolase (EPHX) genotypes that predict the fast catalytic phenotype. Deletion of the glutathione S-transferase T1 (GSTT1) gene also showed a consistent quantitative 35-40% rise in DNA-SSB levels. Neither glutathione S-transferase M1 (GSTM1) nor myeloperoxidase (MPO) genetic variants exerted any effect on DNA-SSB levels. Combinations of two genetic polymorphisms showed the same effects on DNA-SSB as expected from the data on single genotypes. The three locus genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5-fold higher level of DNA-SSB than did the genotype predicted to yield the least genotoxicity.

Management of residual fragments after SWL.

Residual fragments after shock wave lithotripsy (SWL) represent a common and still controversial problem. These fragments can be important risk factors for stone growth and recurrence, may lead to symptomatic events and need further urologic treatment. The term "Clinically Insignificant Residual Fragments" (CIRF) is therefore a misnomer and should be abandoned. Although the goal of urolithiasis treatment is stone-free status, that the presence or non-infected, non-obstructive, asymptomatic residual fragments after SWL should be managed metabolically in order to prevent stone growth and recurrence. Further urologic treatment is warranted if the clinical indications for stone removal are present.

The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene.

S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below. It has been suggested that S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of S-PMA have been found in control subjects. We have evaluated the use of S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects). S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite trans,trans-muconic acid (t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1 ppm benzene), whereas t,t-MA and S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765 microg/m3 (0.55 ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).

Simian virus 40 and malignant mesothelioma (Review).

Simian virus 40 (SV40) was recognized as a contaminant of early poliovirus vaccines that were provided to millions of individuals in Europe and in the USA between 1955 and 1963. SV40, a DNA virus of the family of papovaviridae, was proven to be oncogenic in rodents and able to transform human and animal cells in vitro. In 1993 SV40 was accidentally discovered to produce mesotheliomas in hamsters when it was injected in visceral cavities. Afterwards, SV40 DNA sequences were detected with significative frequency in human pleural mesotheliomas by using polymerase chain reaction (PCR) and then SV40 DNA oncogenicity was associated with its large T antigen (Tag). This finding was confirmed by many laboratories, while a few research groups failed to replicate these data and argued that the SV40 DNA detection might be a PCR contamination artefact. In this review the dispute is examined in the light of recent experiments performed to identify molecular and cellular aspects of carcinogenicity and/or co-carcinogenicity of SV40 in human mesothelioma.

Micronuclei frequency in children exposed to environmental mutagens: a review.

Cytogenetic monitoring has been traditionally used for the surveillance of populations exposed to genotoxic agents. In recent years sensitivity problems emerged in surveys of populations exposed to low levels of mutagens, and therefore alternative approaches have been explored. Biomonitoring studies in children are a promising field, since because of evident differences in the uptake, metabolism, distribution and excretion of mutagens this population seems to be more susceptible than adults. Further, the effect of major confounders such as cigarettes smoking, occupation, life-style, and dietary factors plays a minor role. Among cytogenetic assays, the micronucleus assay (MN) has several advantages and is increasingly used. A review was then carried out to synthesize the published data on the occurrence of MN in children and adolescents (age range 0-18 years), and to assess the impact of genotoxic exposure on MN frequency. Overall, 20 papers from international literature and 8 Russian papers were included. An effect of age was found within this age range, while the influence of gender on MN frequency was irrelevant. These results were confirmed by the re-analysis of data for 448 children selected from the HUMN database. An effect of chronic and infectious diseases on MN levels has been reported by various authors. Most studies describing the effect of exposure to genotoxic agents (ionizing radiation, chemicals, drugs, environmental tobacco smoke) found an increase of MN in exposed children. The limited number of published papers indicates that the conduct of properly designed studies on the effect of environmental pollutants in children may be difficult. This review confirmed the usefulness of MN assay in biomonitoring studies conducted in children, revealing that in many circumstances investigating children increases the sensitivity of the study, even with low dose exposures.

[Prostatic tumor: how many biopsies?]. / Tumore prostatico: quante biopsie?

INTRODUCTION: Ultrasound-guided prostatic biopsy is usually performed by sextants according to Hodge, but the authors feel that 6 biopsies are insufficient. It has been suggested that the number of prostatic biopsies be increased and the mapped areas extended, but this causes discomfort to patients and increases effective costs. The authors suggest repetition of biopsies in "risk" cases, routinely selecting patients taking into account the best cost-benefit ratio. MATERIALS AND METHODS: From January 2000 to December 2001, 682 first series biopsies were performed on as many patients. A Stamey modified sextant technique was used: 6 biopsies, 3 on each side carried out more posterolaterally than the original technique. The biopsy procedure was repeated within 4 months in 11 patients with high risk clinical parameters (PSA > 10 or high PSA and prostatic nodule). During the period of observation, 25 patients had over 0.75 ng/year increase in their PSA and so biopsies were repeated. RESULTS: After the first biopsy series, 277 were positive. Of the 11 repeated biopsies, 3 were positive. Of the 25 patients with altered PSA velocity, 9 were positive. DISCUSSION AND CONCLUSIONS: It has been shown that only 10-12% of biopsies are false negative in the sextant biopsy series when taken posterolaterally. The techniques that increase the number of biopsies have around 3-5% false negatives, but this involves more discomfort for the patient, local anaesthesia and a possible increase in complications. The procedure whereby biopsies were only repeated in patients with high risk clinical elements, saved 3852 biopsies from being carried out, with an economic saving (just on the histological exam that was not carried out) assessed at 59.681,80 Euro (115,560,000 Lire) for our Local Health Service.

Management of Clinically Insignificant Residual Fragments following Shock Wave Lithotripsy.

Clinically insignificant residual fragments (CIRFs) are small fragments (less than 5 mm) that are present in upper urinary tract at the time of regular post-SWL followup. The term is controversial because they may remain silent and asymptomatic or become a risk factor for stone growth and recurrence, leading to symptomatic events, and need further urologic treatment. Although a stone-free state is the desired outcome of surgical treatment of urolithiasis, the authors believe that the presence of noninfected, nonobstructive, asymptomatic residual fragments can be managed metabolically in order to prevent stone growth and recurrence. Further urologic intervention is warranted if clinical indications for stone removal are present.

Maternal and gestational factors and micronucleus frequencies in umbilical blood: the NewGeneris Rhea cohort in Crete.

BACKGROUND: The use of cancer-related biomarkers in newborns has been very limited. OBJECTIVE: We investigated the formation of micronuclei (MN) in full-term and preterm newborns and their mothers from the Rhea cohort (Crete), applying for the first time in cord blood a validated semiautomated analysis system, in both mono- and binucleated T lymphocytes. METHODS: We assessed MN frequencies in peripheral blood samples from the mothers and in umbilical cord blood samples. We calculated MN in mononucleated (MNMONO) and binucleated (MNBN) T lymphocytes and the cytokinesis block proliferation index (CBPI) in 251 newborns (224 full term) and 223 mothers, including 182 mother-child pairs. Demographic and lifestyle characteristics were collected. RESULTS: We observed significantly higher MNBN and CBPI levels in mothers than in newborns. In newborns, MNMONO and MNBN were correlated (r = 0.35, p < 0.001), and we found a moderate correlation between MNMONO in mothers and newborns (r = 0.26, p < 0.001). MNMONO frequencies in newborns were positively associated with the mother's body mass index and inversely associated with gestational age and mother's age, but we found no significant predictors of MNBN or CBPI in newborns. CONCLUSIONS: Although confirmation is needed by a larger study population, the results indicate the importance of taking into account both mono- and binucleated T lymphocytes for biomonitoring of newborns, because the first reflects damage expressed during in vivo cell division and accumulated in utero, and the latter includes additional damage expressed as MN during the in vitro culture step.

The last three months of life of Italian cancer patients. Methods, sample characteristics and response rate of the Italian Survey of the Dying of Cancer (ISDOC).

STUDY OBJECTIVE: The Italian Survey of the Dying of Cancer (ISDOC) was undertaken to evaluate the experiences of Italian people dying from cancer during their last three months of life in all settings of care. STUDY DESIGN: A two-stage probability sample was used to estimate end-of-life outcomes of about 160 000 Italian cancer deaths. In the first stage, 30 of the 197 Italian Local Health Districts (LHD) were randomly selected after stratification. In the second stage, a fixed proportion of cancer deaths was randomly drawn from each LHD, and 2000 death certificates of patients who died of cancer were identified. The non-professional caregivers were identified and interviewed using a semi-structured questionnaire derived from the Views of Informal Carers--Evaluation of Services (VOICES). RESULTS: Caregivers were successfully identified for 95% of the sample (n=1900). The caregiver was the child (42.7%), the spouse (36.5%), another family member (17.3%), or a friend (1.5%). Only 3% of the sample had no non-professional support. An interview was obtained for 1289 (64.5%) of the sample, at a median time of 234 days after death (range: 103-374). Higher response rates were associated with home death (67.7%) and with a higher education (>70%). Conversely, a lower response rate was observed when the caregiver was the spouse (56.2%). Response rates ranged from about 80% for letters sent four to six months after the patients' death to about 60% for letters sent after eight months or more. A descriptive analysis of refusals, based on the transcripts of the telephone calls, allowed classification of 61% of refusals for at least one of the two dimensions examined: caregiver psychological suffering and quality of care received by the patient. Psychological suffering was present in 99% of refusals examined for this dimension (48%). Conversely, a poor quality of care was reported by 63% of the refusals examined for this dimension (23%). CONCLUSION: The ISDOC survey provides a representative picture of the needs and problems associated with the last three months of life of Italian cancer patients.