Mammographic density to predict response to neoadjuvant systemic breast cancer therapy.

BACKGROUND: Mammographic density (MD) is a risk factor for breast cancer (BC) development, and recurrence. However, its predictive value has been less studied. Herein, we challenged MD as a biomarker associated with response in patients treated with neoadjuvant therapy (NAT). METHODS: Data on all NAT treated BC patients prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (2009-2019) were identified. Diagnostic mammograms were used to evaluate and score MD as categorized by the Breast Imaging-Reporting and Data System (BI-RADS), which identifies 4 levels of MD in keeping with relative increase of fibro-glandular over fat tissue. Each case was classified according to the following categories a (MD < 25%), b (26-50%), c (51-75%), and d (> 75%). The association between MD and pathological complete response (pCR), i.e., absence of BC cells in surgical specimens, was analyzed in multivariable setting used logistic regression models with adjustment for clinical and pathological variables. RESULTS: A total of 442 patients were analyzed, 120 of which (27.1%) attained a pCR. BI-RADS categories a, b, c, and d accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases. Corresponding pCR were 20.5%, 26.9%, 30.5%, 23.9%, respectively. At multivariable analysis, when compared to cases classified as BI-RADS a, those with denser breast showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79, and 1.47 for b, c and d categories, respectively (p = 0.0996), independently of age, BMI [OR underweight versus (vs) normal = 3.76], clinical nodal and tumor status (OR T1/Tx vs T4 = 3.87), molecular subtype (HER2-positive vs luminal = 10.74; triple-negative vs luminal = 8.19). In subgroup analyses, the association of MD with pCR was remarkable in triple-negative (ORs of b, c and d versus a: 1.85, 2.49 and 1.55, respectively) and HER2-positive BC cases (ORs 2.70, 3.23, and 1.16). CONCLUSION: Patients with dense breast are more likely to attain a pCR at net of other predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.

Operative mortality after gastric cancer resection and long-term survival differences across Europe.

BACKGROUND: : Little is known at a population level about operative mortality after surgery for gastric cancer and whether differences between countries can explain differences in long-term survival. This study compared operative mortality recorded by ten cancer registries in seven European countries. METHODS: : Non-conditional logistic regression analysis was performed to estimate the independent effect of the studied factors on mortality within 30 days of surgery. A multivariable survival model was employed with and without operative mortality. RESULTS: : The overall operative mortality rate in 1611 patients studied was 8.9 (range 5.2-16) per cent. Country of residence was a significant prognostic factor in the multivariable analysis. The likelihood of operative mortality was lower in Italy, France and the UK than in the Netherlands, Spain, Slovenia and Poland. Age, type of gastrectomy and stage at diagnosis were also significant factors. Cancer site was not found to be significant in the multivariable analysis. The overall 5-year relative survival rate varied between 42.0 per cent (Italy) and 24 per cent (Poland); after excluding operative mortality, the 5-year survival rate was 44.3 and 28 per cent respectively. CONCLUSION: : Within Europe, the substantial differences in operative mortality after gastrectomy only partly explain marked differences in survival after gastric cancer resection.

Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?

AIM: To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). METHODS: From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). RESULTS: ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65-69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. CONCLUSIONS: In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.

Axillary nodal involvement by primary tumor features in early breast cancer: an analysis of 2600 patients.

BACKGROUND: Primary tumor characteristics, which are readily available to all clinicians, may aid in selecting the optimal adjuvant therapy for patients with breast cancer (BC). Herein, we investigated the relationship between tumor size, hormone receptor and HER2 status, Ki67 and age with axillary lymph node metastases (ALNM) in early-BC patients. METHODS: We analyzed data on consecutive 2600 early-BC cases collected in the registry of Fondazione IRCC Istituto Nazionale dei Tumori, Milano, Italy. Correlation between Ki67 and primary tumor size (T-size) was calculated by Spearman's rank correlation coefficient. Association of ALNM with Ki67 and other tumor characteristics was investigated by logistic regression. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in all cases, and separately analyzed according to age, T-size and BC subtype. RESULTS: Large tumor size strongly associated to ALNM, with an adjusted odds ratio (OR) for each 5-mm increase of 1.32 (95% CI 1.24-1.41), except for triple-negative BC (TNBC) cases. In tumors =10 mm, without lymphovascular invasion, representing the strongest predictor of ALNM (OR 6.09, 95% CI 4.93-7.53), Ki67 resulted particularly informative, with a fourfold increased odds of ALNM for values > 30%. CONCLUSIONS: These results raise the question whether axillary node status is redundant in cases with exceptionally good features, i.e., small tumors with low Ki67, or in those candidate to adjuvant systemic treatment/radiotherapy anyway including TNBC, and support the incorporation of primary BC tumor characteristics as stratification factors in ongoing trials aiming at de-escalating axillary surgical procedures.

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high-resolution population-based study.

PURPOSE: The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain. METHODS: A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33-C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients' hospital medical records from all public and private hospitals from two regions in southern Spain. RESULTS: There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02-0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis. CONCLUSIONS: The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.

Cancer survival in adult patients in Spain. Results from nine population-based cancer registries.

INTRODUCTION: With the aim of providing cancer control indicators, this work presents cancer survival in adult (≥15 years) patients in Spain diagnosed during the period 2000-2007 from Spanish cancer registries participating in the EUROCARE project. METHODS: Cancer cases from nine Spanish population-based cancer registries were included and analysed as a whole. All primary malignant neoplasms diagnosed in adult patients were eligible for the analysis. Cancer patients were followed until 31 December 2008. For each type of cancer, 1-, 3- and 5-year observed and relative survival were estimated by sex, age and years from diagnosis. Furthermore, age-standardized 5-year relative survival for the period 2000-2007 has been compared with that of the period 1995-1999. RESULTS: Skin melanoma (84.6 95% CI 83.0-86.2), prostate (84.6% 95% CI 83.6-85.6) and thyroid (84.2% CI 95% 82.0-86.6) cancers showed the highest 5-year relative survival, whereas the worst prognosis was observed in pancreatic (6% 95% CI 5.1-7.0) and oesophageal (9.4% 95% CI 7.9-11.1) cancers. Overall, survival is higher in women (58.0%) than in men (48.9%). The absolute difference in relative survival between 2000-2007 and 1995-1999 was positive for all cancers as a whole (+4.8% in men, +1.6% in women) and for most types of tumours. Survival increased significantly for chronic myeloid leukaemia, non-Hodgkin's lymphoma and rectum cancer in both sexes, and for acute lymphoid leukaemia, prostate, liver and colon cancers in men and Hodgkin's lymphoma and breast cancer in women. Survival patterns by age were similar in Europe and Spain. A decline in survival by age was observed in all tumours, being more pronounced for ovarian, corpus uteri, prostate and urinary bladder and less for head and neck and rectum cancers. CONCLUSION: High variability and differences have been observed in survival among adults in Spain according to the type of cancer diagnosed, from above 84% to below 10%, reflecting high heterogeneity. The differences in prognosis by age, sex and period of diagnosis reveal opportunities for improving cancer care in Spain.

Dual effects of pyrazofurin and 3-deazauridine upon pyrimidine and purine biosynthesis in mouse L1210 leukemia.

Pyrazofurin (NSC 143095) as the monophosphate derivative is a potent inhibitor of orotidine 5'-monophosphate (OMP) decarboxylase of the pyrimidine pathway and has been proposed to inhibit 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase (EC 2.1.2.3) of the purine pathway (J. F. Worzalla, and M. J. Sweeney, Pyrazofurin inhibition of purine biosynthesis via 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-monophosphate formyltransferase. Cancer Res., 40: 1482-1485, 1980). Measurement of levels of pyrimidine and purine intermediates in cultured mouse L1210 leukemia cells has shown that 25 microM pyrazofurin induces an 8-fold accumulation of OMP and large accumulations of intermediates proximal to the blockade with abrupt decreases in uridine and cytidine nucleotides. Considerable increases in the cellular concentrations of N-succino-AICAR (SAICAR), AICAR, 5-formamidoimidazole-4-carboxamide ribotide (FAICAR), IMP, XMP, and GMP at later times indicate that AICAR transformylase is not significantly inhibited in cultured cells; rather the purine pathway and the GMP branch are stimulated. However, addition of 25 microM 3-deazauridine (NSC 126849) to leukemia cells did result in inhibition of AICAR transformylase: AICAR and SAICAR accumulated, IMP disappeared and there was a large accumulation of guanosine nucleotides. Blockade of pyrimidine biosynthesis by derivatives of pyrazofurin or 3-deazauridine spares 5-phosphoribosyl-1-pyrophosphate and L-glutamine, elevated concentrations of which may stimulate initial reactions of purine biosynthesis and the reaction XMP----GMP.

Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.

PURPOSE: To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity. METHODS AND MATERIALS: 537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis. RESULTS: The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis. CONCLUSIONS: The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.

Survival for oesophageal, stomach and small intestine cancers in Europe 1999-2007: Results from EUROCARE-5.

BACKGROUND: European regional variation in cancer survival was reported in the EUROCARE-4 study for patients diagnosed in 1995-1999. Relative survival (RS) estimates are here updated for patients diagnosed with cancer of the oesophagus, stomach and small intestine from 2000 to 2007. Trends in RS from 1999-2001 to 2005-2007 are presented to monitor and discuss improvements in patient survival in Europe. MATERIALS AND METHODS: EUROCARE-5 data from 29 countries (87 cancer registries) were used to investigate 1- and 5-year RS. Using registry-specific life-tables stratified by age, gender and calendar year, age-standardised 'complete analysis' RS estimates by country and region were calculated for Northern, Southern, Eastern and Central Europe, and for Ireland and United Kingdom (UK). Survival trends of patients in periods 1999-2001, 2002-2004 and 2005-2007 were investigated using the 'period' RS approach. We computed the 5-year RS conditional on surviving the first year (5-year conditional survival), as the ratio of age-standardised 5-year RS to 1-year RS. RESULTS: Oesophageal cancer 1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%). Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by 2005-2007, with Ireland and the UK (3%), and Central Europe (4%) showing large improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%) and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe had the best 5-year survival (30%), though only showing an improvement of 2% by 2005-2007. Small intestine cancer 5-year RS for Europe was 48%, with Central Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year patient survival improvement for Europe was 8% by 2005-2007, with Central, Southern and Eastern Europe showing the greatest increases (⩾9%). CONCLUSIONS: Survival for these cancer sites, particularly oesophageal cancer, remains poor in Europe with wide variation. Further investigation into the wide variation, including analysis by histology and anatomical sub-site, will yield insights to better monitor and explain the improvements in survival observed over time.

Survival for retinoblastoma in Europe.

The survival of 954 cases of retinoblastoma, diagnosed between 1978 and 1989 in 28 populations belonging to 17 European countries and covered by cancer registration, is analysed in this study. Data were collected in the framework of the EUROCARE study following a common protocol and data-check procedures and were analysed centrally by the Kaplan-Meier method and by the Cox regression model. Overall 5-year survival in the European pool was 93% (95% confidence interval (CI): 91--95%), for both sexes. Five-, 10- and 18-year survival for a subset of 235 patients diagnosed in 1978--1981 was 91, 89 and 86%, respectively. Children diagnosed in their first year of age had a slightly higher survival (94%) than those diagnosed subsequently (92%). Survival rates lower than the European average were found in the Eastern European countries, Italy, England and Wales, Scotland, Spain and Denmark. Higher survival was found in the other Nordic countries and in Central European countries. However, none of these differences was statistically significant. There was statistically significant effect related to the period of diagnosis, with a 50% reduction in the relative risk (RR) for children diagnosed in 1986--1989 compared with those diagnosed in 1978-1981.

Improved survival for patients with testicular cancer in Europe since 1978. EUROCARE Working Group.

Within the framework of EUROCARE, a population-based study on survival and care of cancer patients in Europe, we analysed survival of 7426 men with testicular cancer diagnosed between 1985 and 1989 in 17 countries. For comparison between the countries, survival rates were age-standardised to the age structure of the entire study population. Among the participating countries of Northern, Western, Central and Southern Europe and the U.K., the age-standardised 5-year relative survival rate varied from 89% (Finland) to 93% (Spain, Germany). In Eastern Europe, the rate ranged from 48% (Estonia) to 84% (Slovenia). Rates in Poland, Slovakia and Estonia were significantly lower than the summary rate for Europe (P < 0.05). Relative survival generally decreased with the age of patients at diagnosis. Based on the weighted analysis of pooled European data, the 5-year relative survival rate was 91% for patients aged 15-44 years; 85% for patients aged 55-64 years; and 59% for patients aged 75 years and over. The time trend in survival by 3-year periods between 1978 and 1989 was studied on the basis of 12,084 cases provided by 12 countries. From 1978-1980 to 1987-1989, the 5-year relative survival rate for Europe increased from 79 to 93% (P < 0.05). The inequalities in survival between the more developed European countries were more notable in the 1970s than in the 1980s, suggesting that the treatment for testicular cancer became standardised in the latter period. Poorer survival in Eastern Europe and particularly in Estonia, could be related to later introduction of the effective cytotoxic treatments, but also to longer diagnostic delay and limited availability of modern staging procedures.

Survival rates for primary malignant brain tumours in Europe. EUROCARE Working Group.

In the framework of EUROCARE, a concerted action between 45 population-based cancer registries, in 17 European countries, survival of patients with primary malignant brain tumours was investigated. Survival analysis was carried out on 16,268 patients diagnosed between 1985 and 1989 and followed-up for at least 5 years. The mean European age-standardised 5-year relative survival was 17% in men and 20% in women, with minimal intercountry variations, except for markedly lower rates in Scotland, Estonia and Poland. The age-specific analysis showed a relatively uniform survival in patients aged more than 65 years at diagnosis, but there were more marked intercountry differences in younger patients. In the 15-44 year age group (25% of the total study population) 5-year relative survival ranged between 55% (Finland and Sweden) and 27% (Poland). Generally, survival decreased with increasing age at diagnosis. The analysis of a temporal trend in survival was carried out on a subset of registries with available data from 1978-1989. Overall, there was an increase in survival over the considered study period, mostly confined to 1-year survival, suggesting that it was mostly related to improved diagnostic techniques. The most important survival increase occurred in the younger patients, both for 1- and 5-year survival, suggesting that younger patients have less biologically aggressive tumours, benefiting from the combined effect of diagnostic accuracy and effective therapies. The most marked survival increase was seen in England and Denmark, countries with low survival rates at the beginning of the study period, whereas in Finland and Germany, where survival was relatively high to begin with, no important temporal trend was seen.

Substantial variation in therapy for colorectal cancer across Europe: EUROCARE analysis of cancer registry data for 1987.

To provide a quantitative description of the treatments applied to malignant colorectal cancer across Europe, we analysed all cases (11,333) of colorectal cancer registered in 1987 by 15 Cancer Registries in eight European countries. In a third of cancer registries, therapy was known for all cases, in the others 1-15% of registrations lacked treatment information. Eighty per cent of all patients received surgical resection, ranging from 58% (Estonia) to 92% (Tarn). The proportion of resections decreased with advancing age (85-73% for colon cancer; 85-70% for rectal cancer for < 65 years to > 74 years, respectively). Only 4% of colon cancer patients received adjuvant or palliative chemotherapy, range 1-12%. Sixteen per cent of rectal cancer patients received radiotherapy with great inter-registry variability (1-43%). Since the proportion of surgically resected patients correlated positively with the 5-year relative survival probability reported by the recently published EUROCARE study, this may be part of the explanation for the major differences in survival for these cancers among different European populations. The most likely determinant of this correlation is stage at diagnosis, but, quality of, and access to surgery, as well as access to endoscopy, may differ among countries and registry areas, and these may also contribute to inter-country survival differences.

Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. EUROCARE Working Group.

The EUROCARE Study is a European Union project to assemble survival data from population-based cancer registries and analyse them according to standard procedures. We investigated and compared liver, pancreatic and biliary tract cancer survival in 17 countries from 1985 to 1989. Time trends in survival over the 1978-1989 period were also investigated in 12 countries. The overall European mean 1 year relative survival was 16% for primary liver cancer, 26% for biliary tract cancer and 15% for pancreatic cancer. The corresponding 5-year relative survival was 5, 12 and 4%, respectively. Taking the European average as the reference, the relative risk (RR) of death was at least 20% higher for the three cancers in Denmark and Estonia. Survival tended to be higher in Spain for primary liver cancer and biliary tract cancer. Gender had little influence on survival whilst age at diagnosis was inversely related to prognosis. There was an improvement in 1-year relative survival rate for primary liver cancer: relative risk (RR) of 0.68 (95% confidence interval (CI) of 0.60-0.77) for 1987-1989 versus 1978-1980 and biliary tract cancer (RR 0.77, 95% CI 0.68-0.87). There was less variation in 5-year relative survival rate over time. Some intercountry survival differences for primary liver, biliary tract and pancreatic cancers exist over Europe. Differences in quality of care, in particular treatment aggressiveness, may explain some of these differences in survival. New approaches to the management of these cancers need to be found.

Incidence and prevalence of all cancerous diseases in Italy: trends and implications.

The burden of cancer in ageing populations is causing great concern, particularly in Italy with Europe's fastest growing elderly population. Studying all cancers combined in one group, although of limited medical value, is of great interest from the viewpoints of public health, epidemiology and the economy. Using mortality data and an estimate of cancer patients' survival we have estimated and projected incidence and prevalence in Italy of all cancers combined in one group. Five major phenomena are highlighted in the paper: (1) the decrease in the age-adjusted cancer mortality rates among females and the stable mortality rates among males since 1990; (2) the changing pattern of cancer incidence since 1990, it has started to decrease for females and is stabilising for males; (3) the decrease in cancer incidence among males and females born after 1940; (4) the increase in the proportion of cancer patients that are cured with calendar years of diagnosis; (5) the increase in the total and the healthy life expectancy (i.e. cancer-free) among the Italian population since 1970. The declining and flat trends in age-adjusted cancer incidence and mortality rates since 1990 is the combined effect of survival improvements and cancer risk reduction for younger cohort groups, after 1940. These favourable trends contribute to the increase in healthy life expectation, thus supporting the idea that we live longer and healthier.

Survival and age at diagnosis of breast cancer in a population-based cancer registry.

From the population covered by the Lombardy Cancer Registry, Italy, 1991 female breast cancer patients diagnosed from 1976 to 1981 were followed up until May 1987. Relative survival was 69% at 5 years and 58% at 10 years; median survival was 8.8 years. Ages 40-49 showed the best survival; ages 25-34 were 20% lower. From age 50 onwards, survival decreased progressively, with the exception of age group 65-74. We suggest that the best prognosis for ages 40-49, followed by the survival fall in subsequent ages, could be related to an anticipation of diagnosis in ages near menopause. The death hazard function showed a bimodal pattern, with a first peak in the first years after diagnosis, and a second one between the seventh and eighth years. The death hazard rate decreased by about 1% per year at each subsequent calendar year of diagnosis. When such an estimated calendar effect was taken in account, there were no considerable survival differences among Western countries covered by population-based cancer registries.

Descriptive epidemiology of colorectal cancer in Italy: the 6-year experience of a specialised registry.

The Colorectal Cancer Registry of Modena recorded 838 malignancies of the large bowel between 1984 and 1989. Crude Incidence rates were 59.5 new cases per 100,000 per year in men and 47.4 in women (age-standardised values 33.1 and 20.6, respectively). 35 incident cases (4.2%) had multiple colorectal tumours, whereas 42 (5.1%) had extraintestinal malignancies (mainly breast, endometrium and stomach). Although 90.5% of the patients underwent surgery, this was "curative" in 634 (77.6% of the total), while 105 individuals (12.8%) had palliative operations; 78 patients (9.5%) were not operated, mainly because of metastatic disease or poor clinical condition. Finally, emergency operations--due to intestinal obstruction, perforation or massive bleeding--were carried out in 46 patients (6.1%). A total of 659 tumours (79%) were accurately staged. Among first-degree relatives of the registered patients a significant excess of cases of colorectal cancer was found in each year of the study. 5-year survival was evaluated in 132 (out of 140) patients registered in 1984 and followed-up until 1989. Overall 5-year survival was 37%, but rose to 43% when only colorectal cancer related deaths were taken into consideration. As expected, survival was strongly influenced by stage (P < 0.0001 by log-rank test). In conclusion, this study confirms previously reported data about incidence and mortality rates for colorectal cancer in northern Italy. The particular approach--limited to the large bowel--allowed the evaluation of the frequency of multiple tumours and of the marked aggregation of cancer among first-degree relatives. Finally, survival figures are comparable to those of many other studies and confirm that the clinical outcome of this neoplasm remains unfavourable in more than 50% of the affected patients.

Cancer survival increases in Europe, but international differences remain wide.

The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

Estimation and projections of colorectal cancer trends in Italy.

BACKGROUND: Occurrence of and prognosis for tumours of the colon and rectum are thought to be changing rapidly due to simultaneous changes in risk factor prevalence, early diagnosis and treatment. In this paper time trends of morbidity, survival and mortality for colorectal cancer during the period 1970-1990 are estimated and analysed. METHODS: Mortality trends were obtained from official death certificates. Relative survival rates were computed from population-based cancer registries. Incidence and prevalence rates were estimated from mortality and survival data. RESULTS: Incidence rates were increasing during the period considered, with a lower rate of increase for the youngest birth cohorts. Relative survival rates of both colon and rectum cancers were higher for women, and for younger age groups, and were positively associated with period of diagnosis. No significant survival difference among the cancer registries used was found. A total of about 155,000 prevalent cases, 40% of which had been diagnosed > or = 7 years before, were estimated in the Italian population for the year 1990. Mortality rates were slightly increasing for men and stable for women. Projections of colorectal cancer trends to the year 2000 indicate major expected rises in both incidence and prevalence. CONCLUSION: Colorectal cancer represents a problem of growing impact for health services in Italy. This conclusion can probably be extended to many developed countries.

Does arterial PCO2 interfere with hypoxia in muscular metabolism in man?

To answer the question whether PCO2 affects the muscular metabolism, PO2, PCO2, pH, lactic acid concentration and hemoglobin were measured in the efferent muscular venous blood from common flexor digitorum, during forearm rhythmic exercise corresponding to VO2max. Exercise was carried out either in hypocapnic hypoxia i.e. in permanent high altitude residents and translocated lowlanders, or in hypercapnic hypoxia i.e. in chronic obstructive lung disease (COLD) patients. The results show that, during exercise: i) PO2 in muscular venous blood remains around 20 Torr in normoxia and hypocapnic hypoxia and even higher (25 torr) in COLD patients, despite low arterial PaO2, and ii) arterial and/or local PCO2 play a role in the control of the muscular blood flow. But we cannot conclude that a change in PaCO2 affects muscular metabolism itself, because lactic acid in the muscular venous blood, that we used to check this effect, is likely dependent on mechanisms other than anaerobic glycolysis, such as a change in lactic acid efflux from the myocytes. The increase in muscular venous PCO2 may enhance the myocyte permeability to lactic acid during exercise.