Dietary Isoflavones Intake and Gastric Cancer.

Dietary isoflavones have been associated with a lower risk of gastric cancer (GC), but the evidence for this association is still limited. We investigated the association between isoflavone intake and GC risk using data from a case-control study including 230 incident, histologically confirmed GC cases and 547 controls with acute, non-neoplastic conditions. Dietary information was collected through a validated food frequency questionnaire (FFQ) and isoflavone intake was estimated using ad hoc databases. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) of GC using logistic regression models, including terms for total energy intake and other major confounders. The OR for the highest versus the lowest tertile of intake was 0.65 (95%CI = 0.44-0.97, p for trend = 0.04) for daidzein, 0.75 (95%CI = 0.54-1.11, p for trend = 0.15) for genistein, and 0.66 (95%CI = 0.45-0.99, p for trend = 0.05) for total isoflavones. Stratified analyses by sex, age, education, and smoking showed no heterogeneity. These findings indicate a favorable effect of dietary isoflavones on GC.

Diabetes Risk Reduction Diet and Colorectal Cancer Risk.

BACKGROUND: Diabetes has been associated with colorectal cancer. We evaluated whether adherence to a diabetes risk reduction diet (DRRD) can favorably influence the risk of colorectal cancer. METHODS: Data came from a multicentric Italian case-control study including 1,953 histologically confirmed colorectal cancer cases and 4,154 hospital controls admitted for acute nonneoplastic diseases. Diet was assessed through a validated and reproducible food frequency questionnaire. The DRRD score was computed assigning higher values for higher consumption of cereal fiber, fruit, coffee, nuts and a higher polyunsaturated/saturated fats ratio and for lower glycemic index and lower consumption of red/processed meat and sweetened beverages and fruit juices. The ORs and the corresponding 95% confidence intervals (CI) of colorectal cancer according to the DRRD score were obtained using logistic regression models adjusting for total energy intake and other major confounders. RESULTS: The DRRD was inversely related to colorectal cancer risk. The ORs of colorectal cancer were 0.77 (95% CI, 0.67-0.89) for the third versus first score tertile (Ptrend < 0.001) and 0.92 (95% CI, 0.87-0.96) for a 3-point increment in the score. Inverse associations were observed for colon and rectal cancers and were consistent in strata of sex, age, and other major covariates. CONCLUSIONS: A higher adherence to a DRRD was inversely associated with colorectal cancer risk. IMPACT: Given the high incidence and mortality rates of colorectal cancer, adherence to a DRRD can have relevant prevention and public health implications.

Dietary choline and sphingomyelin choline moiety intake and risk of colorectal cancer: a case-control study.

INTRODUCTION: Phospholipids are possible favorable agents for colorectal cancer (CRC). Choline has been inversely related to CRC risk but findings are inconsistent. We assessed the effect of dietary sphingomyelin (SM) choline moiety and total choline intake on risk of CRC. METHOD: This analysis is based on a multicenter case-control study conducted between 1992 and 1996 in Italy. A total of 6107 subjects were enrolled, including 1225 colon cancer cases, 728 rectal cancer cases and 4154 hospital-based controls. We applied data on the composition of foods in terms of SM choline moiety and choline intake on dietary information collected through a validated food-frequency questionnaire. Odds ratio (OR) for energy-adjusted tertiles of SM choline moiety and choline were estimated through logistic regression models adjusted for sex, age, center, education, alcohol consumption, body mass index, family history of CRC, and physical activity. RESULTS: Choline was inversely related to CRC risk (OR for the highest versus the lowest tertile: 0.85; 95% confidence interval [CI]: 0.73-0.99), with a significant trend in risk. The OR for an increment of one standard deviation of energy-adjusted choline intake was 0.93 (95% CI: 0.88-0.98). The association was consistent in colon and rectal cancer and also across colon subsites. SM choline moiety was not associated with CRC risk (OR for the highest versus the lowest tertile: 0.96, 95% CI 0.84-1.11). CONCLUSION: This study shows an inverse association between choline intake and CRC but not with SM choline moiety.

Dietary Choline and Betaine Intake and Risk of Colorectal Cancer in an Iranian Population.

BACKGROUND: Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We aimed to investigate the relationship between dietary betaine, choline, and choline-containing compounds and CRC risk. METHODS: We analyzed data from a case-control study, including 865 CRC cases and 3206 controls from Iran. Detailed information was collected by trained interviewers using validated questionnaires. The intake of free choline, phosphocholine (Pcho), glycerophosphocholine (GPC), phosphatidylcholine (PtdCho), and sphingomyelin (SM), as well as of betaine was estimated from food frequency questionnaires and categorized into quartiles. The odds ratios (OR) and 95% confidence intervals (CI) of CRC for choline and betaine quartiles were calculated using multivariate logistic regression by adjusting for potential confounders. RESULTS: We observed excess risk of CRC in the highest versus lowest intake of total choline (OR = 1.23, 95% CI 1.13, 1.33), GPC (OR = 1.13, 95% CI 1.00, 1.27), and SM (OR = 1.14, 95% CI 1.01, 1.28). The intake of betaine exerted an inverse association with CRC risk (OR = 0.91, 95% CI 0.83, 0.99). There was no association between free choline, Pcho, PtdCho, and CRC. Analyses stratified by gender showed an elevated OR of CRC in men for SM intake OR = 1.20, 95% CI 1.03, 1.40) and a significantly decreased CRC risk in women for betaine intake (OR = 0.84, 95% CI 0.73, 0.97). CONCLUSION: Dietary modifications leading to an increase in betaine sources and managing the use of animal products as references for SM or other choline types might contribute to decreasing the risk of CRC.

Garlic consumption in relation to colorectal cancer risk and to alterations of blood bacterial DNA.

PURPOSE: Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood. METHODS: We conducted a case-control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann-Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence. RESULTS: The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11-0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus. CONCLUSIONS: The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.

Association of prebiotic fiber intake with colorectal cancer risk: the PrebiotiCa study.

PURPOSE: To evaluate the association between the intake of specific fibers with prebiotic activity, namely inulin-type fructans (ITFs), fructooligosaccharides (FOSs) and galactooligosaccharides (GOSs), and colorectal cancer risk. METHODS: Within the PrebiotiCa study, we used data from a multicentric case-control study conducted in Italy and including 1953 incident, histologically confirmed, colorectal cancer patients and 4154 hospital controls. The amount of six prebiotic molecules [ITFs, nystose (FOS), kestose (FOS), 1F-ß-fructofuranosylnystose (FOS), raffinose (GOS) and stachyose (GOS)] in a variety of foods was quantified via laboratory analyses. Subjects' prebiotic fiber intake was estimated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. The odds ratios (OR) of colorectal cancer for quintiles of intakes were derived from logistic regression models including terms for major confounders and total energy intake. RESULTS: GOSs intake was inversely associated with colorectal cancer risk. The OR for the highest versus the lowest quintile of intake were 0.73 (95% confidence interval, CI 0.58-0.92) for raffinose and 0.64 (95% CI 0.53-0.77) for stachyose, with significant inverse trends across quintiles. No association was found with total ITFs and FOSs. The association with stachyose was stronger for colon (continuous OR = 0.74, 95% CI 0.66-0.83) than rectal cancer (OR = 0.89, 95% CI 0.79-1.02). CONCLUSION: Colorectal cancer risk was inversely associated with the intake of dietary GOSs, but not ITFs and FOSs.

Flavonoid Intake in Relation to Colorectal Cancer Risk and Blood Bacterial DNA.

Flavonoids have been inversely associated to colorectal cancer (CRC) and are plausible intermediaries for the relation among gut microbiome, intestinal permeability and CRC. We analyzed the relation of flavonoid intake with CRC and blood bacterial DNA. We conducted a case-control study in Italy involving 100 incident CRC cases and 200 controls. A valid and reproducible food-frequency questionnaire was used to assess dietary habits and to estimate six flavonoid subclass intakes. We applied qPCR and 16S rRNA gene profiling to assess blood bacterial DNA. We used multiple logistic regression to derive odds ratios (ORs) of CRC and Mann-Whitney and chi--square tests to evaluate abundance and prevalence of operational taxonomic units (OTUs) according to flavonoid intakes. Inverse associations with CRC were found for anthocyanidins (OR for the highest versus the lowest tertile = 0.24, 95% confidence interval, CI = 0.11-0.52) and flavanones (OR = 0.18, 95% CI = 0.08-0.42). We found different abundance and prevalence according to anthocyanidin and flavanone intake for OTUs referring to Oligoflexales order, Diplorickettsiaceae family, Staphylococcus, Brevundimonas, Pelomonas and Escherischia-Shigella genera, and Flavobacterium and Legionella species. The study provides evidence to a protective effect of dietary anthocyanidins and flavanones on CRC and suggests an influence of flavonoids on blood bacterial DNA, possibly through intestinal permeability changes.

Dietary intake of branched-chain amino acids and pancreatic cancer risk in a case-control study from Italy.

Circulating branched-chain amino acids (BCAAs), a subgroup of the nine essential amino acids, have been associated to pancreatic cancer risk. The aim of this study is to estimate the relation between BCAA intake from diet and pancreatic cancer risk.We analysed data from a multicentric Italian case-control study, including 326 pancreatic cancer cases and 652 controls, matched to cases by study centre, sex and age. A validated food-frequency questionnaire was used to collect the participants' usual diet before cancer diagnosis (or hospital admission for controls) and to compute dietary intakes of various nutrients, including BCAAs. Odds ratios (ORs) and corresponding confidence intervals (CIs) were computed through logistic regression models conditioned on the matching variables and adjusted for major confounding factors, including total energy intake.We found a positive association between the BCAA intake and pancreatic cancer risk (OR for the third quartile=1.88, 95% CI=1.08-3.26; OR for the fourth quartile =2.17, 95% CI=1.17-4.06), with a significant trend in risk. The association persisted after excluding subjects with diabetes and family history of pancreatic cancer, and across strata of selected covariates.These data support and quantify the association between dietary BCAAs and pancreatic cancer, previously suggested by studies on circulating BCAAs.

Diabetes risk reduction diet and the risk of pancreatic cancer.

PURPOSE: To evaluate the role of a diabetes risk reduction diet (DRRD) on pancreatic cancer risk. METHODS: We used data from a hospital-based case-control study conducted in Italy between 1991 and 2008; the study included 326 incident pancreatic cancer cases and 652 controls matched by age, gender and study center. Subjects' usual diet was collected through a valid and reproducible food frequency questionnaire. A DRRD score was derived from 8 dietary components: cereal fiber, total fruit, coffee, polyunsaturated to saturated fats ratio and nuts (higher score for higher intake), and dietary glycemic index, red/processed meat and sugar-sweetened beverages/fruit juices (higher score for lower intake). The score ranged 8-37, with higher values indicating greater DRRD adherence. Odds ratios (ORs) of pancreatic cancer according to the DRRD score were estimated using multiple conditional logistic regression models. RESULTS: After allowance for confounding factors, the DRRD score was inversely related to pancreatic cancer risk, with ORs of 0.55 (95% confidence interval, CI 0.38-0.80) for the highest versus the lowest score tertile (p for trend across tertiles = 0.002) and 0.84 (95% CI 0.75-0.95) for a 3-point score increment. The exclusion of diabetic subjects and additional adjustment for vegetable intake did not change the results. Inverse associations were observed in subgroups defined by age, gender, education, body mass index, smoking and total energy intake. CONCLUSION: Study findings suggest a protective role of high adherence to a DRRD on pancreatic cancer risk.

Diabetes risk reduction diet and the risk of breast cancer.

OBJECTIVE: Diabetes and insulin levels may increase the risk of postmenopausal breast cancer. In the present investigation, we aimed at evaluating whether adherence to a diabetes risk reduction diet (DRRD) lowers the risk of breast cancer. METHODS: We used data from an Italian, multicentric case-control study (1991-1994) including 2569 incident histologically-confirmed breast cancer cases and 2588 hospital controls. A food frequency questionnaire collected subjects' usual diet. We derived a DRRD score on the basis of eight items: intake of cereal fiber, total fruit, coffee, polyunsaturated to saturated fats ratio and nuts (higher scores for higher intakes), and dietary glycemic index, red/processed meat and sugar-sweetened beverages/fruit juices (higher scores for lower intakes). The score theoretically ranged 8-37, with higher values indicating greater DRRD adherence. Odds ratios (ORs) of breast cancer according to the DRRD score were estimated using multiple logistic regression models. RESULTS: The DRRD score was inversely related to the risk of breast cancer. The ORs were 0.93 [95% confidence interval (CI), 0.89-0.98] for a three-point score increment and 0.76 (95% CI, 0.64-0.89) for the highest versus the lowest quartile (P for trend 0.001). Inverse associations were observed in subgroups of covariates. CONCLUSIONS: Higher DRRD adherence may decrease the risk of breast cancer.

Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls.

Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.

Biochar from Pine Wood, Rice Husks and Iron-Eupatorium Shrubs for Remediation Applications: Surface Characterization and Experimental Tests for Trichloroethylene Removal.

Nowadays porous materials from organic waste, i.e., Biochar (BC), are receiving increased attention for environmental applications. This study adds information on three BCs that have undergone a number of studies in recent years. A Biochar from pine wood, one from rice husk and one from Eupatorium shrubs enriched with Iron, labelled as PWBC, RHBC and EuFeBC respectively, are evaluated for Trichloroethylene (TCE) removal from aqueous solution. Physical-chemical description is performed by SEM-EDS and BET analysis. The decrease of TCE over time follows a pseudo-second order kinetics with increased removal by the PWBC. Freundlich and Langmuir models well fit equilibrium test data. The optimized values of the maximum adsorbed amount, qmax (mg g-1), follows this order 109.41 PWBC > 30.35 EuFeBC > 21.00 RHBC. Fixed-bed columns are also carried out. Best performance is again achieved by PWBC, which operates for a higher number of pore volume, followed by EuFeBC and RHBC. Continuous testing confirms batch studies and makes it possible to evaluate the workability of materials in configurations closer to reality. Results are promising for potential environmental application. In particular, the characterization of several classes of contaminants opens the doors to possible uses in mixed contamination cases.

Dietary intake of branched-chain amino acids and colorectal cancer risk.

An adequate intake of branched-chain amino acids (BCAA) is required for protein synthesis and metabolic functions, including insulin metabolism. Emerging studies found positive associations between BCAA and the risk of various diseases sharing aetiological aspects with colorectal cancer (CRC), including type 2 diabetes, obesity and pancreatic cancer. We investigated the relation between dietary BCAA and CRC using data from a multicentric Italian case-control study, including 1953 cases of CRC (of these, 442 of sigmoid colon) and 4154 hospital controls with acute, non-neoplastic diseases. A validated FFQ was used to estimate the participants' usual diet and to assess dietary intakes of various nutrients, including energy, BCAA and Ca. OR and corresponding CI were computed by multiple logistic regression models adjusted for age, sex and other confounding factors, including total energy intake. BCAA intake was inversely related to CRC risk (OR for the highest v. the lowest quintile 0·73; 95 % CI 0·55, 0·97), but the association was attenuated after adjustment for Ca intake (OR 0·90; 95 % CI 0·65, 1·25). An inverse association with sigmoid colon cancer risk also remained after adjustment for other dietary factors, including Ca intake (OR 0·49; 95 % CI 0·27, 0·87). This study provides supporting evidence that higher levels of dietary BCAA intake are not associated with an increase of CRC risk, but confirms that they may be related to a reduced risk of sigmoid colon cancer.

Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP).

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54-0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55-0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56-0.92), flavanols (OR = 0.77, 95% CI = 0.66-0.88), flavanones (OR = 0.57, 95%CI = 0.44-0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55-0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57-0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51-1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58-1.06). Further investigations from longitudinal data are needed to confirm this association.

Malpighamoeba infection compromises fluid secretion and P-glycoprotein detoxification in Malpighian tubules.

Malpighian tubules, analogous to vertebrate nephrons, play a key role in insect osmoregulation and detoxification. Tubules can become infected with a protozoan, Malpighamoeba, which damages their epithelial cells, potentially compromising their function. Here we used a modified Ramsay assay to quantify the impact of Malpighamoeba infection on fluid secretion and P-glycoprotein-dependent detoxification by desert locust Malpighian tubules. Infected tubules have a greater surface area and a higher fluid secretion rate than uninfected tubules. Infection also impairs P-glycoprotein-dependent detoxification by reducing the net rhodamine extrusion per surface area. However, due to the increased surface area and fluid secretion rate, infected tubules have similar total net extrusion per tubule to uninfected tubules. Increased fluid secretion rate of infected tubules likely exposes locusts to greater water stress and increased energy costs. Coupled with reduced efficiency of P-glycoprotein detoxification per surface area, Malpighamoeba infection is likely to reduce insect survival in natural environments.

Flavonoids and bladder cancer risk.

PURPOSE: Flavonoids have drawn attention because of their antioxidant capacity and anti-carcinogenic effect in various types of cancer. A limited number of studies has investigated their potential effect on the risk of bladder cancer, with inconsistent results. METHODS: We analyzed data from an Italian case-control study including 690 incident bladder cancer cases and 665 controls admitted to the same network of hospitals for acute, non-neoplastic, non tobacco-related diseases. Subjects were interviewed using a reproducible and validated food-frequency questionnaire. We applied data on food and beverage composition to estimate the intake of isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones and flavonols. We estimated odds ratios (ORs) through multiple logistic regression models, including terms for potential confounding factors, including tobacco smoking and total energy intake. RESULTS: We found an inverse association between isoflavones (OR for the highest compared to the lowest quintile of intake = 0.56, 95% CI 0.37-0.84) and flavones (OR = 0.64, 95% CI 0.44-0.95) and bladder cancer. Non-significant inverse association was found for flavan-3-ols (OR = 0.70), flavonols (OR = 0.85) and total flavonoids (OR = 0.76). The results were consistent for non-muscle-invasive and muscle-invasive bladder cancers. CONCLUSIONS: Our data indicate an inverse association between isoflavones and flavones with respect to bladder cancer risk.

A cumulative meta-analysis of endoscopic papillary balloon dilation versus endoscopic sphincterotomy for removal of common bile duct stones.

BACKGROUND: Endoscopic papillary balloon dilation (EPBD) was introduced to overcome the risk of adverse events associated with endoscopic sphincterotomy in the removal of common bile duct (CBD) stones. We performed a meta-analysis of randomized controlled trials (RCTs) comparing efficacy and safety of EPBD vs. endoscopic sphincterotomy, focusing on stone size, balloon diameter, and balloon dilation time. METHODS: A multiple database search was performed, including MEDLINE, EMBASE and Cochrane Library, from their inception date until October 2017. RCTs comparing the efficacy and safety of EPBD vs. endoscopic sphincterotomy in the removal of CBD stones were included. Cumulative meta-analyses over time, and subgroup analyses according to stone size, and balloon diameter and dilation time were carried out. RESULTS: 25 RCTs met the inclusion criteria. Despite the cumulative meta-analysis showing a trend over time in favor of endoscopic sphincterotomy in studies published up to 2004, the conventional meta-analysis revealed that EPBD was equally efficacious compared with endoscopic sphincterotomy in stone removal at first attempt (odds ratio [OR] 0.95, 95 % confidence interval [CI] 0.65 - 1.38). Endoscopic sphincterotomy was superior to EPBD in terms of overall stone clearance (OR 0.65, 95 %CI 0.43 - 0.99) in studies published since 2002, but no differences emerged in studies using large ( ≥ 10 mm) balloons (OR 1.37, 95 %CI 0.72 - 2.62). No statistically significant difference in pancreatitis occurrence emerged between EPBD and endoscopic sphincterotomy (OR 1.35, 95 %CI 0.90 - 2.03). Pancreatitis was more common with EPBD than with endoscopic sphincterotomy in studies using balloons < 10 mm (OR 1.78, 95 %CI 1.07 - 2.97), whereas no difference emerged in studies using large balloons (OR 0.84, 95 %CI 0.46 - 1.53). EPBD had lower rates of bleeding and cholecystitis. CONCLUSIONS: Our latest data confirm that EPBD is currently inferior to endoscopic sphincterotomy in terms of overall stone clearance. However, EPBD using large balloons (≥ 10 mm) was as effective as endoscopic sphincterotomy, both in stone clearance and the need for endoscopic mechanical lithotripsy, without carrying an increased risk of pancreatitis.

Management and Survival of Pleural Mesothelioma: A Record Linkage Study.

BACKGROUND: Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. OBJECTIVES: To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). METHODS: Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. RESULTS: Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of surgery. Determinants of receiving chemotherapy were younger age, a more recent first diagnosis, and first diagnosis in a specialized center. OS was 45.4% at 1 year, 24.8% at 2 years, and 9.6% at 5 years (median 11 months). OS decreased with age, and was higher for those who underwent surgery, but not for those treated with chemotherapy. CONCLUSIONS: Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).