Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Although in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS). METHODS: Relevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016. The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method). RESULTS: A total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643). No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529). CONCLUSION: Our pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.

Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

BACKGROUND: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). METHODS: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. RESULTS: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044). CONCLUSION: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

SV40 associated miRNAs are not detectable in mesotheliomas.

BACKGROUND: Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma is widely debated. PCR based testing has been called into question, as false positives can be because of cross-reactivity with related viruses, or to laboratory contamination. The Institute of Medicine has recommended the development of more sensitive and specific tests to resolve this controversy. METHODS: We have characterized highly sensitive RT-PCR based assays that are specific for SV40-encoded microRNAs (miRNAs), as an alternative to current testing methods. RESULTS: Using this sensitive and specific detection method, we were unable to identify SV40 miRNA expression in human malignant pleural mesothelioma (MM) samples. CONCLUSION: Our work indicates that SV40 miRNAs are not likely to contribute to mesothelioma tumourogenesis, but highlights the value of this approach when compared with the relatively unspecific current testing methods.

Minimally invasive versus traditional chest surgical approach in patients with reduced renal function.

AIM: All surgical access approaches to the chest wall cause a different degree of muscle damage and freeing of substances as myogloblin into the bloodstream thus compromising kidney function. The aim of this study was to evaluate the potential kidney damage in relation to entity of muscle lesions caused by the different surgical approaches. METHODS: The hematic levels of creatine phosphokinase (CPK), myoglobin, lactate dehydrogenase (LDH), creatinine as well as the amount of the diuresis at different intervals of time were taken of 66 patients who underwent a thoracic surgical operation with diverse surgical access approaches. RESULTS: Surgery determines muscle substances to be freed into the bloodstream. Myoglo-blin levels resulted to be correlated to those of CPK (r=0.83; P<0.00005). Although serum levels of myogloblin are not determined as a routine procedure, high levels of CPK must induce to dose myogloblin. The amount of muscle substances freed depend on the width of the surgical access (r=0.7; P<0.00005) and not upon extension (r=0.36; P=0.18) or duration of surgery. (r=0.4; P=0.093). CONCLUSION: In patients with a reduced renal function or affected by kidney failure a minimally invasive or thoracoscopic approach is indicated whenever possible in order to reduce the amount of myogloblin in the bloodstream.

Incidence of pleural mesothelioma in Liguria Region, Italy (1996-2002).

In this study, incidence of pleural malignant mesothelioma (PMM) in the Liguria Region (Italy) (approximately 1.6 million inhabitants), in the presence of asbestos exposure was investigated. New PMM cases recorded by the Mesothelioma Registry of Liguria, from 1996 to 2002 and interviews reported on a standardised questionnaire were analysed according to demographical and etiological characteristics. Nine hundred and forty five PMM cases were recorded (757 males and 188 females); the age standardised (European population) incidence rates per 100,000 were 8.51 and 1.43, respectively. The rates among the four provinces ranged between 1.18 and 13.7 for males and 0.68 and 1.44 for females. The questionnaire was evaluated for 786 PMM cases (or next-of-kin). Higher incidence rates were reported in the provinces with larger industrial and harbour areas, including shipyards (construction and repair), dockyards, building activities, chemical and heavy industrial activities. Asbestos exposure was unlikely or unknown for 57.5% females and 15% males. A major role of environmental asbestos exposure in the etiology of PMM is hypothesised for females and for a minor proportion of males.

Oncological research overview in the European Union. A 5-year survey.

This study evaluates the distribution of papers published by European Union (EU) authors in oncological journals from 1996 to 2000, and compares the results with those of a previous study carried out in 1995. The impact of oncological research in the EU is compared with that of the United States (US) and the world, and research trends are highlighted through an analysis of keywords. Data on articles published in oncological journals (ISI Subject Category=ONCOLOGY) selected from Current Contents/Life Science and Current Contents/Clinical Medicine (1996-2000) on the weekly diskette version were downloaded. Mean Impact Factor (IF), source country population and gross domestic product (GDP) were analysed. A special-purpose software to determine the most commonly used keywords was utilised. From 1996 to 2000, 66021 papers were published in the world in oncological journals: 35.5% came from the EU (UK, Italy, Germany, France and The Netherlands ranking the highest) and 38.8% from the US. The total number of EU papers increased from 4063 in 1995 to 4843 in 2000. Compared with the previous study, no important changes were seen, with the top five countries in 1995 maintaining their ranking in 2000. However, some small countries (Denmark, Norway and Ireland) fared worse in 2000, while others (France, Germany and Greece) improved their position. The mean IF for the EU papers was 2.9 compared with 4.0 in the US. The mean IF increased for all of the nations. In particular, while France and Germany showed a very positive performance trend in their respective IFs, countries such as Norway, Denmark and Italy showed less improvement. The analysis of keywords appearing in articles written in 2000 showed that the leading fields of research were breast cancer in the diseases category of keywords, cisplatin and platinum compounds in the drugs category, radiotherapy in the treatment category and apoptosis in the experimental studies category. Variety in the use of keywords should be avoided, and journal editors should encourage their standardisation.

[Diabetes and bleeding in thoracic surgery]. / Diabete e sanguinamento in toraco-chirurgia.

BACKGROUND: The aim of this study is to assess the influence of diabetes over early postoperative bleeding in thoracic surgical patients. In fact, diabetes leads to hypercoagulation as well as to an alteration of microvessels that could have a negative effect on the retraction and vasoconstriction of the damaged microvessel before hemostasis coagulation phase. METHODS: Data referring to 193 typical pneumonectomies associated with extensive removal of mediastinic nodes, 19 performed in diabetic patients have been retrospectively analysed. RESULTS: Any statistically significant difference between the two groups was found. CONCLUSIONS: More studies would be necessary to confirm our conclusions, on more extensive series of patients with more severe diabetic disease, as well as on non-thoracic surgical patients, in order to avoid the consequences of the early and sudden negative pressure on wounds, that in thoracic patients could hide the effects of less evident factors.

Assessing oncological productivity. is one method sufficient?

This work analyses the distribution of oncological papers published in 1995 by authors from the European Union (EU) in any journal of all the Subject Categories of the Science Citation Index compiled by ISI (Institute for Scientific Information, Philadelphia, USA) and is based on the country of origin of all of the contributors. The study compares the results with those of a previous study dealing with publications in journals of the ISI Oncology Category based on the country of origin of the corresponding author. The aim of the study was to compare two different methods used to evaluate research productivity in order to understand the extent to which the results are influenced by the methodology adopted. Data on the number of published papers for each country, ratio between the number of occurrences of papers and country population and gross domestic product (GDP), and mean Impact Factors (IF ) were compared. While findings on the number of published papers (United Kingdom (UK), Germany and France ranking best), source country population (Sweden, Denmark and the Netherlands ranking best) and gross domestic product (Sweden, Finland and the Netherlands ranking best) showed no important changes, the mean IF value result was, for some countries, very different from the previous study. In particular, while Germany, Belgium, Portugal and France fared well, Norway, Sweden, Austria and Spain showed poorer results. Some hypotheses are advanced, and care in the scientometric interpretation of data is urged. An analysis of the journals in which EU authors published their articles was also carried out and the main SCI categories to which the journals belong are reported. As was expected, many categories other than oncology were represented (biochemistry, haematology, pathology, etc.).

Histological subtypes of Hodgkin's disease in the setting of HIV infection.

The relative incidence of Hodgkin's disease (HD) has been found to have increased approximately seven times in HIV-infected patients. We analyzed the histological distribution of HIV-associated HD with the aim of clarifying purported difference(s) from de novo HD. References on HIV/AIDS-associated HD were retrieved from the most complete databases. Nineteen articles were the subject of our analysis. Seventeen of them reported data on the histological type of HIV/AIDS-associated HD patients; the route of infection and age of the patients were also considered when available. According to the Peto's methodology, histological types were compared with those from two large studies in the United States on de novo HD: 3,245 cases from the Surveillance, Epidemiology, and End Results (SEER) and 1,140 from Stanford University. The analysis of the two groups showed statistically significant differences (p<0.001) in the percentage of all histological types and odds ratios (OR) of the pooled effect of 0.4 (95% CI: 0.3-0.6) for lymphocyte predominance (LP), 0.3 (95% CI: 0.2-0.4) for nodular sclerosis (NS), 3.2 (95% CI: 2.6-3.8) for mixed cellularity (MC), and 6.3 (95% CI: 4.5-8.8) for lymphocyte depletion (LD). Comparison with the Stanford University series yielded similar results. Whilst retrospective and based on a limited number of cases, our data confirm a higher incidence of unfavorable histological subtypes in HIV-infected patients and show a reduction in the observed cases of good prognosis subtypes. Prospective studies, with careful histological observations, are required to better evaluate the characteristics of the LP subtype in the special setting of HIV infection.

Tamoxifen in the treatment of metastatic malignant melanoma: still a controversy? (Review).

This review attempts to summarize the available preclinical and clinical evidence supporting the inclusion of tamoxifen (TAM) in the treatment of malignant melanoma, in the attempt to identify what role, if any, the antiestrogen could have in the present and future therapeutic approach to this disease. Emphasis has been given to the biological basis of the potential TAM mechanisms of action, as well as to the rational basis underlying the study design of the reported clinical experiences. Results to date show that TAM has no useful activity as a single agent in melanoma patients, most published response rates reaching less than 10%. A still controversial question is the inclusion of the antiestrogen in different active chemotherapy regimens, since clinical investigations on the role of TAM in combination therapy of advanced melanoma have produced inconclusive results. While several early trials suggested that TAM may improve the response rates when combined with different cytotoxic agents, the majority of subsequent reports, including recent randomized studies, did not show a significant benefit stemming from TAM addition to various single-agent or multi-agent combinations. Only one controlled trial showed a significant improvement in both response rate and survival for patients receiving dacarbazine plus TAM, an effect primarily noted in women, and confirmatory studies have not been reported. From a biological standpoint, why the activity of this poorly effective single-agent is potentiated when given in combination with some cytotoxic agents is not clearly understood, although preclinical and clinical experiences support a possible synergistic effect of TAM combined with cisplatin, particularly when the former is added at high doses. Of major interest is a body of experimental studies producing confirmatory data that induction of apoptosis, probably through the inhibition of protein kinase C, as well angiogenesis inhibition, at least in part mediated by TGF-beta stimulation, are alternative ways through which TAM suppresses tumor cell growth, independently of the expression of estrogen receptors. These findings also provide a model and rationale for combining TAM with agents which are able to modify cell biology in melanoma. The investigation on TAM-containing biological combinations appears to be a promising avenue to be explored in the near future. To this end, clinical research should incorporate biological studies to allow the selection of subgroups of patients who are most likely to benefit from TAM-based treatment.

Drug metabolism polymorphisms as modulators of cancer susceptibility.

Recently, several molecular genetic bases of polymorphic enzyme activities involved in drug activation and detoxification have been elucidated. Many molecular epidemiology studies based on these premises have sought to gather information on the association of genetically determined metabolic variants with different risks of environmentally induced cancer. While rare alterations of tumor suppressor genes dramatically raise cancer risk for the single affected subjects, far more common and less dramatic differences in genes encoding for drug metabolism enzymes can be responsible for a relatively small, but rather frequent increase of cancer risk at the population level. This increase could be especially important in specific cases of occupational, pharmacological or environmental exposure. Examination of the current literature reveals that the most extensively investigated metabolic polymorphisms are those of P450 1A1 and P450 2D6 cytochromes, glutathione S-transferases (GSTs; M1 and, to a lesser extent, M3, P1 and T1) and N-acetyltransferases (NATs; NAT1 and NAT2). Making reference to these enzymes, we have assayed the current knowledge on the relations among polymorphisms of human xenobiotic-metabolizing enzymes and cancer susceptibilities. We have found intriguing models of susceptibility toward different types of cancer. We have reviewed and commented these models on light of the complex balance among different enzyme activities that, in each individual, determines the degree of each cancer susceptibility. Moreover, we have found techniques of molecular genetic analysis, more suitable than previous ones on phenotypic expression, now allowing better means to detect individuals at risk of cancer. According to the models presently available, a systematic screening of individuals at risk seems to make sense only in situations of well defined carcinogenic exposures and when performed by the polymorphism analysis of coordinated enzyme activities concurring to the metabolism of the carcinogen(s) in question. Genetic polymorphism analysis can allow for the detection of patients more prone to some types of specific cancers, or to the adverse effects of specific pharmaceutical agents. Considering the increasingly confirmed double-edged sword nature of metabolism polymorphism (both wild-type and variant alleles can predispose to cancer, albeit in different situations of exposure), individual susceptibility to cancer should be monitored as a function of the nature, and mechanism of action, of the carcinogen(s) to which the individual under study is known to be exposed, and with reference to the main target organ of the considered type of exposure.

Impact assessment of oncology research in the European Union.

In this study the distribution of papers published by authors from the European Union (EU) in oncological journals was analysed, as was the impact of oncological research in the EU compared with that produced in other countries. Papers published during 1995 in the oncological journals listed by ISI (Institute for Scientific Information, Philadelphia, U.S.A.) were downloaded. The parameters of impact factor (IF), source country population and gross domestic product (GDP) were considered. An analysis of the key words, both those reported by the authors and those attributed by ISI, was carried out using a special purpose program. 36.5% of papers published in oncological journals come from the EU (the U.K., Italy, Germany and France ranking at the top) and 40.7% from the U.S.A. The mean IF was 2.4 for EU papers, 3.3 for the US and 2.4 for other countries. Our data confirm that smaller countries performed better than larger ones. The key words analysis shows that the leading fields of research were breast cancer for diseases, cisplatin for drugs and p53 for experimental studies. A standardisation of key words on behalf of journal editors is proposed.

Electronic biomedical journals: how they appear and what they offer.

This study, prompted by a number of articles presaging the imminent demise of biomedical journals due to the rise of their electronic spread, analysed 54 Web sites of the journals included in the Oncology section of the Science Citation Index, Journal Citation Reports (1994) and the sites of 10 other leading digitised biomedical journals. The aim was to determine quantitative and qualitative differences in terms of information content existing between the two media. The analysis confirmed that there are limits to the information contained in the scientific journals currently on the Internet and upholds the authors' conclusion that, in the oncology field, the printed journal will continue to have an important role for most individual users for some time.

Assessing research productivity in an oncology research institute: the role of the documentation center.

An evaluation method used to assess the quality of research productivity and to provide priorities for budget allocation purposes is presented. This method, developed by a working group of the National Institute for Research on Cancer (IST), Genoa, Italy, is based on the partitioning of categories of the Science Citation Index and Journal Citation Reports (SCI-JCR) into deciles, which normalizes journal impact factors in order to gauge the quality of the productivity. A second parameter related to the number of staff of each institute department co-authoring a given paper has been introduced in order to guide departmental budget allocations. The information scientists of the IST Documentation Center who participated in the working group played a pivotal role in developing the computerized database of publications, providing and analyzing data, supplying and evaluating literature on the topic, and placing international bibliographic databases at the working group's disposal.

Sustaining Oncology Studies--SOS: information and support for training, research and exploitation in cancer and related biomedical disciplines.

This paper outlines the development of the Sustaining Oncology Studies Information Resources (SOS Europe), a multimedia World Wide Web (WWW) prototype providing support to experimental and clinical cancer researchers, general practitioners, industry personnel, and university students in the field of oncology in Europe and Italy. The system utilizes applications developed for the WWW and is designed in the most easily understandable approaches possible. The prototype now structures oncology-related information available on the Internet and also places resources maintained locally at users' disposal. The system utilizes a WWW browser as a design platform and HTML to build its Home and subpages and to create hyperlinks to internal and external resources.

[Surgical staging of pulmonary carcinoma. Probability of error]. / Stadiazione chirurgica del carcinoma polmonare. Probabilità di errore.

234 patients with lung cancer and operated in Thoracic and Cardiovascular Surgery Department of Careggi Hospital in Florence have been evaluated in order to examine surgical staging accuracy in comparison with pathological staging. There is a statistically significative difference between surgical and pathological staging as a datum point. Surgeon is inclined to over-estimate the lymph-nodes involvement and the primitive tumor extension. It is important to bear in mind this bent whenever decisions of surgical strategy have to be taken.