Prognostic factors for survival in patients with colorectal liver metastases: experience of a single brazilian cancer center

CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients showed similar results to those pointed in international series. The occurrence of major postoperative complications appears to be able to compromise overall survival and further investigation in needed in this topic.

Early development, survival and growth rates of the giant clam Tridacna crocea (Bivalvia: Tridacnidae)

Tridacnid clams are conspicuous inhabitants of Indo-Pacific coral reefs and are traded and cultivated for the aquarium and food industries. In the present study, daily growth rates of larvae of the giant clam Tridacna crocea were determined in the laboratory during the first week of life. Adults were induced to spawn via intra-gonadal serotonin injection through the byssal orifice. After spawning oocytes were collected, fertilized and kept in 3 L glass beakers and raceways treated with antibiotics to avoid culture contamination. Larvae were fed twice with the microalga Isochrysis galbana and zooxanthellae were also offered twice during the veliger stage (days 4 and 6). Larval length was measured using a digitizing tablet coupled to a microcomputer. Larval mortality was exponential during the first 48 hours of life declining significantly afterwards. Mean growth rate was 11.3 μm day-1, increasing after addition of symbionts to 18.0 μm day-1. Survival increased to ca. 75% after the addition of zooxanthellae. The results describe the growth curve for T. crocea larvae and suggest that the acquisition of symbionts by larvae may be useful for larval growth and survival even before larvae have attained metamorphosis.

Tiller population density and tillering dynamics in marandu palisade grass subjected to strategies of rotational stocking management and nitrogen fertilization

The objective of this experiment was to evaluate tiller population density and the dynamics of the tillering process in marandu palisade grass subjected to strategies of rotational stocking management and nitrogen fertilization. Treatments corresponded to combinations between two targets of pre-grazing conditions (sward surface height of 25 and 35 cm) and two rates of nitrogen application (50 and 200 kg ha-1 year-1), and were allocated to experimental units according to a 2 x 2 factorial arrangement in a randomised complete block design, with four replications. The following response variables were studied: initial (TPDi), intermediate (TPDm) and final (TPDf) tiller population density as well as the rates of tiller appearance (TAR) and death (TDR) and the tiller population stability index (SI). TPDi was similar to all treatments, with differences in tiller population density becoming more pronounced as the experiment progressed, resulting in larger TPDf on swards managed at 25 cm pre-grazing height. Tiller death was larger on swards managed at 35 cm, with differences in tiller appearance being recorded only from February 2010 onwards. Stability of tiller population was higher on swards managed at 25 cm pre-grazing height. Overall, there was no effect of nitrogen on the studied variables, and the most adequate grazing strategy corresponded to the pre-grazing height of 25 cm, regardless of the nitrogen application rate used.

The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas

Abstract: Background Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors. Methods Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant. Results In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival. Conclusions Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive. Virtual slides. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514

Adipose tissue-derived mesenchymal stem cells increase skin allograft survival and inhibit Th-17 immune response

Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4(+) regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation.

Effect of sex ratio on growth and survival in Octopus vulgaris (Cuvier, 1797) reared in floating cages

[EN]Octopus vulgaris is a potential candidate to diversify European aquaculture for its rapid growth and high market prices (Vaz Pires et al. 2004). One factor affecting industrial development of octopus culture is sexual maturation under rearing conditions. Octopus females can lose up to 30-60% of their initial body weight during egg-laying (Iglesias et al., 2000) and die after the paralarvae hatch (Guerra,1992), while a correlation between males death and spermatic sac depletion has being recently reported by Estefanell et al. (2010b). The present experiment discusses the effect of three different sex ratios on growth, sexual maturation and survival in O. Vulgaris. Conclusions: Discarded bogue from fish farms could be used as alternative diet for the final stage of O. vulgaris ongrowing ; Male segregation would maximize biomass increment ; Under the conditions described, sex ratios close to 1:1 produced higher biomass increment than 4:1

Use of different commercial Artemia sp. Enrichements in Octopus Vulgaris, paralarval rearing at initial planctonic phase: effects on growth, survival and fatty acid composition of the paralarvae

[EN] Octopus "paralarvae", are planktonic, swim actively and have high metabolic rates, requiring large quantities of live prey of adequate motility and nutritional quality ( Iglesias et al., 2000; Navarro and Villanueva, 2000, 2003). During the planktonic phase, they undergo strong morphological changes, after which the octopuses start settling to the bottom. The potential of Octopus vulgaris as candiadate for diversification of marine aquacultures are mainly due to its high food conversion rate and fast growth.( Iglesias et al 2006). Despite the research effort taken until now, paralarval rearing of O. vulgaris still suffers high mortalities which limited the industrial culture of this species. The main problems in the paralarval rearing stages are the high mortality rates and poor growth. These are attributed to the lack of standardized culture techniques and nutritional deficiencies in the diet of paralarvae, especially in n-3 highly unsaturated fatty acids (n-3 HUFA). The objective if this experience was to test different commercial live prey enrichment to improve nutritional quality of the artemia.

Effect of different rotifers enrichment formula feed on growth and survival of sea bream larvae ("Sparus aurata")

Universidad de Las Palmas de Gran Canaria. Facultad de Ciencias del Mar. Final assignment for the Marine Science Degree ; 2013-2014

Effect of rearing techniques over, survival growth and skeletal abnormalities development in red porgy (Pagrus Pagrus) larvae

[EN] Red porgy is one of the most interested new species for Spanish and other Mediterranean countries. Although no industrial procedures for fry production has been yet developed. The aim of this work was to develop an industrial scale larval rearing protocols testing the viability of two different rearing techniques (semi-intensive vs intensive) in pilot scale facilities. The second objective was to obtain information about the contribution of rearing system to the apparition of morphological abnormalities such as lordosis, opercular deformities and upper/lower jaws shortening which are considered as quality descriptors in commercial marine fish fry production and seem to be related with larval culture conditions in early larval stages. For that purpose, two different larval rearing systems semi-intensive and intensive were compared using the same live feed enrichments. Biochemical composition of larvae, preys and commercial products was analysed. At 50 days post hatching six hundred fish per treatment was individually studied under stereoscope and abnormalities frequency recorded. At 95 days post hatching fry were soft X ray monitored as well. Survival and abnormalities frequency were similar between treatments although a better growth in terms of total length was obtained in the semi-intensive system.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

ATG based combination therapy - a novel clinically relevant approach to promote regulation and induce long-term allograft survival

Regulatory T cells (Treg) actively regulate alloimmune responses and promote transplantation tolerance. Polyclonal anti-thymocyte globulin (ATG), a widely used induction therapy in clinical organ transplantation, depletes peripheral T cells. However, resistance to tolerance induction is seen with certain T cell depleting strategies and is attributed to alterations in the balance of naïve, memory and regulatory T cells. Here we report a novel reagent, murine ATG (mATG), depletes T cells but preferentially spares CD25+ natural Tregs which limit skewing of T cell repertoire toward T-effector-memory (Tem) phenotype among the recovering T cells. T-cell depletion with mATG combined with CTLA4Ig and Sirolimus synergize to prolong graft survival by tipping the Treg/Tem balance further in favor of Tregs by preserving Tregs, facilitating generation of new Tregs by a conversion mechanism and limiting Tem expansion in response to alloantigen and homeostatic proliferation. These results provide the rationale for translating such novel combination therapies to promote tolerance in primate and human organ transplantation.