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1.  Postsurgical dysphagia: evaluation and rehabilitation 
BMC Geriatrics  2010;10(Suppl 1):L51.
PMCID: PMC3290293
2.  Comparative analysis of multilineage properties of mesenchymal stromal cells derived from fetal sources shows an advantage of mesenchymal stromal cells isolated from cord blood in chondrogenic differentiation potential 
Cytotherapy  2014;16(7):893-905.
Background aims
Cord blood (CB) and amniotic fluid (AF) could represent new and attractive mesenchymal stromal cell (MSC) sources, but their potential therapeutic applications are still limited by lack of standardized protocols for isolation and differentiation. In particular, chondrogenic differentiation has never been deeply investigated.
MSCs were obtained from CB and AF samples collected during cesarean sections at term and compared for their biological and differentiation properties, with particular interest in cartilage differentiation, in which quantitative real-time polymerase chain reaction and immunohistochemical analyses were performed to evaluate the expression of type 2 collagen, type 10 collagen, SRY-box9 and aggrecan.
We were able to isolate MSCs from 12 of 30 (40%) and 5 of 20 (25%) CB and AF units, respectively. Fluorescence in situ hybridization analysis indicated the fetal origin of isolated MSC strains. Both populations expressed mesenchymal but not endothelial and hematopoietic markers, even though we observed a lower expression of human leukocyte antigen (HLA) I in CB-MSCs. No differences in proliferation rate and cell cycle analysis could be detected. After osteogenic induction, both populations showed matrix mineralization and typical marker expression. Under chondrogenic conditions, pellets derived from CB-MSCs, in contrast with AF-MSCs pellets, were significantly larger, showed cartilage-like morphology and resulted positive for chondrocyte-associated markers, such as type 2 collagen, type 10 collagen, SRY-box9 and aggrecan.
Our results show that CB-MSCs and AF-MSCs collected at term differ from each other in their biological and differentiation properties. In particular, only CB-MSCs showed a clear chondrogenic potential and thus could represent an ideal candidate for cartilage-tissue engineering.
PMCID: PMC4062948  PMID: 24794181
amniotic fluid; chondrogenic differentiation; cord blood; mesenchymal stromal cells
3.  Chlorella for protein and biofuels: from strain selection to outdoor cultivation in a Green Wall Panel photobioreactor 
Chlorella is one of the few microalgae employed for human consumption. It typically has a high protein content, but it can also accumulate high amounts of lipids or carbohydrates under stress conditions and, for this reason, it is of interest in the production of biofuels. High production costs and energy consumption are associated with its cultivation. This work describes a strategy to reduce costs and environmental impact of Chlorella biomass production for food, biofuels and other applications.
The growth of four Chlorella strains, selected after a laboratory screening, was investigated outdoors in a low-cost 0.25 m2 GWP-II photobioreactor. The capacity of the selected strains to grow at high temperature was tested. On the basis of these results, in the nitrogen starvation trials the culture was cooled only when the temperature exceeded 40°C to allow for significant energy savings, and performed in a seawater-based medium to reduce the freshwater footprint. Under nutrient sufficiency, strain CH2 was the most productive. In all the strains, nitrogen starvation strongly reduced productivity, depressed protein and induced accumulation of carbohydrate (about 50%) in strains F&M-M49 and IAM C-212, and lipid (40 - 45%) in strains PROD1 and CH2. Starved cultures achieved high storage product productivities: 0.12 g L−1 d−1 of lipids for CH2 and 0.19 g L−1 d−1 of carbohydrates for F&M-M49. When extrapolated to large-scale in central Italy, CH2 showed a potential productivity of 41 t ha−1 y−1 for biomass, 16 t ha−1 y−1 for protein and 11 t ha−1 y−1 for lipid under nutrient sufficiency, and 8 t ha−1 y−1 for lipid under nitrogen starvation.
The environmental and economic sustainability of Chlorella production was enhanced by growing the organisms in a seawater-based medium, so as not to compete with crops for freshwater, and at high temperatures, so as to reduce energy consumption for cooling. All the four selected strains are good candidates for food or biofuels production in lands unsuitable for conventional agriculture. Chlorella strain CH2 has the potential for more than 80 tonnes of biomass, 32 tonnes of protein and 22 tonnes of lipid per year under favourable climates.
PMCID: PMC4057815  PMID: 24932216
Chlorella; Outdoor cultivation; Food; Thermotolerance; Nitrogen starvation; Sustainability; GWP-II; Biofuel
4.  Long-Term Home Noninvasive Mechanical Ventilation Increases Systemic Inflammatory Response in Chronic Obstructive Pulmonary Disease: A Prospective Observational Study 
Mediators of Inflammation  2014;2014:503145.
Background. Long-term home noninvasive mechanical ventilation (NIV) is beneficial in COPD but its impact on inflammation is unknown. We assessed the hypothesis that NIV modulates systemic and pulmonary inflammatory biomarkers in stable COPD. Methods. Among 610 patients referred for NIV, we shortlisted those undergoing NIV versus oxygen therapy alone, excluding subjects with comorbidities or non-COPD conditions. Sputum and blood samples were collected after 3 months of clinical stability and analyzed for levels of human neutrophil peptides (HNP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha). Patients underwent a two-year follow-up. Unadjusted, propensity-matched, and pH-stratified analyses were performed. Results. Ninety-three patients were included (48 NIV, 45 oxygen), with analogous baseline features. Sputum analysis showed similar HNP, IL-6, IL-10, and TNF-alpha levels (P > 0.5). Conversely, NIV group exhibited higher HNP and IL-6 systemic levels (P < 0.001) and lower IL-10 concentrations (P < 0.001). Subjects undergoing NIV had a significant reduction of rehospitalizations during follow-up compared to oxygen group (P = 0.005). These findings were confirmed after propensity matching and pH stratification. Conclusions. These findings challenge prior paradigms based on the assumption that pulmonary inflammation is per se detrimental. NIV beneficial impact on lung mechanics may overcome the potential unfavorable effects of an increased inflammatory state.
PMCID: PMC4058212  PMID: 24976687
5.  New Insights into the Steen Solution Properties: Breakthrough in Antioxidant Effects via NOX2 Downregulation 
Ex vivo lung perfusion (EVLP) allows perfusion and reconditioning of retrieved lungs for organ transplantation. The Steen solution is specifically designed for this procedure but the mechanism through which it elicits its activity is still to be fully clarified. We speculated that Steen solution may encompass antioxidant properties allowing a reestablishment of pulmonary tissue homeostasis. Blood samples from 10 healthy volunteers were recruited. Platelets and white cells were incubated with Steen solution or buffer solution as control and stimulated with suitable agonists. Reactive oxidant species (ROS), soluble NOX2 (sNOX2-derived peptide), a marker of NADPH oxidase activation, p47phox translocation to cell membrane and isoprostanes production, as marker of oxidative stress, and nitric oxide (NO), a powerful vasodilator and antioxidant molecule, were measured upon cell stimulation. The Steen solution significantly inhibited p47phox translocation and NOX2 activation in platelets and white cells. Consistent with this finding was the reduction of oxidative stress as documented by a significantly lowered formation of ROS and isoprostanes by both platelets and white cells. Finally, cell incubation with Steen solution resulted in enhanced generation of NO. Herewith, we provide the first evidence that Steen solution possesses antioxidant properties via downregulation of NADPH oxidase activity and enhanced production of NO.
PMCID: PMC4009192  PMID: 24829620
6.  RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia 
Nature genetics  2014;46(2):116-125.
The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, characterized by recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction; ~30-fold enrichment at promoters and enhancers of genes actively transcribed in B-cell development and an unexpectedly high ratio of recurrent to non-recurrent structural variants. Single cell tracking shows that this mechanism is active throughout leukemic evolution with evidence of localized clustering and re-iterated deletions. Integration of point mutation and rearrangement data identifies ATF7IP and MGA as two new tumor suppressor genes in ALL. Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, targeting the promoters, enhancers and first exons of genes that normally regulate B-cell differentiation.
PMCID: PMC3960636  PMID: 24413735
7.  Pigeons’ Choices with Token Stimuli in Concurrent Variable-Interval Schedules 
Twelve pigeons responded on concurrent variable-interval schedules that delivered token stimuli (stimulus lights for some pigeons, and white circles on the response keys for others). During exchange periods, each token could be exchanged for food on a fixed-ratio 1 schedule. Across conditions, the exchange requirements (number of tokens that had to be earned before they could be exchanged for food) varied between one and four for the two response keys. The main findings were that the pigeons’ response percentages varied as a function of the number of tokens earned at any given moment, and they were determined by both the delays to food and by the number of food deliveries in the exchange periods. In some conditions, tokens had to be earned but were not visible during the variable-interval schedules for one or both keys. When one key had visible tokens and the other did not, the pigeons showed a preference for the key without visible tokens. A model based on the matching law and a hyperbolic delay-discounting equation could account for the main patterns of choice responding, and for how response percentages changed as successive tokens were earned. The results are consistent with the view that the token stimuli served as discriminative stimuli that signaled the current delays to food.
PMCID: PMC3896056  PMID: 23460072
token stimuli; concurrent variable-interval schedules; generalized matching law; hyperbolic discounting; keypeck; pigeons
8.  Total Adiponectin Is Inversely Associated with Platelet Activation and CHA2DS2-VASc Score in Anticoagulated Patients with Atrial Fibrillation 
Mediators of Inflammation  2014;2014:908901.
Background. Adiponectin (APN) possesses anti-inflammatory and antiatherogenic effects. Atrial fibrillation (AF) is burdened by enhanced systemic inflammation and platelet activation, as documented by increased blood levels of soluble CD40L (sCD40L). The interplay between APN and platelet activation in AF is still undefined. Materials and Methods. Circulating levels of APN and sCD40L were measured in 257 anticoagulated nonvalvular AF patients. Exclusion criteria were as follows: prosthetic heart valves, cardiac revascularization in the previous year, severe cognitive impairment, chronic infectious or autoimmune diseases, and active cancer. Results. Mean age was 72.9 (±8.7) years and 41.6% were female. Serum APN and plasmatic sCD40L were inversely correlated (R −0.626, P < 0.001). A progressive increase of sCD40L across tertiles of CHA2DS2-VASc score was observed (rS 0.473, P < 0.001), whilst APN was inversely correlated (rS −0.463,  P < 0.001). A multivariable linear regression analysis showed that CHA2DS2-VASc score (B −0.227, P < 0.001) and sCD40L (B −0.524, P < 0.001) correlated to APN. Conclusions. AF patients at high risk of stroke disclose low and high levels of APN and sCD40L, respectively, suggesting a role for APN if it favors platelet activation in vivo in this clinical setting. Enhancing APN levels may be a future goal to reduce the risk of vascular outcomes in AF patients.
PMCID: PMC3955592  PMID: 24771985
9.  Tinnitus: clinical experience of the psychosomatic connection 
The connection between psychopathology and tinnitus is complex and not adequately studied. The aim of this study is to investigate the relationship between tinnitus and psychiatric comorbidities from different points of view: categorical, dimensional, temperamental, and perceived stress level.
Two hundred and thirty-nine patients affected by tinnitus were recruited between January and October 2012. Patients underwent a preliminary battery of tests including the Tinnitus Handicap Inventory (THI), Symptom Check List (SCL90-R), Temperament and Character Inventory (TCI), and Stress-Related Vulnerability Scale (VRS), and eventually a full psychiatric evaluation.
One hundred and fourteen patients (48% of the total sample) presented psychiatric comorbidity. Among these, a higher prevalence of depression, somatization, obsession, and anxiety was found. More than 41% of patients affected by decompensated tinnitus reported a family history of psychiatric disorders. Significant positive correlations between the psychopathological screening tools (SCL90-R and VRS) and THI were found. Patients affected by comorbid psychiatric disorder showed specific temperamental and characterial predispositions.
Psychiatric comorbidity in subjects affected by tinnitus is frequent. Stress can be considered as a factor leading to damage and dysfunction of the auditory apparatus. The vulnerability to neurotic disorders and the lack of coping capabilities can play a critical role in the clinical history of patients affected by severe tinnitus.
PMCID: PMC3925227  PMID: 24550676
tinnitus; psychosomatics; stress; psychopathological dimensions; personality
10.  An atypical presentation of intrahepatic perforated cholecystitis: a modern indication to open cholecystectomy. Report of a case 
BMC Surgery  2014;14:6.
Intrahepatic gallbladder perforation with chronic liver abscess formation was anecdotically reported in the literature. The aim of this work is to report a case of intrahepatic gallbladder perforation and its atypical clinical presentation.
Case presentation
A 62-year-old male patient came to our observation; his medical history showed intermittent fever up to 39-40°C of about 2 weeks and anorexia, with an overall weight loss of about 12 Kg. Physical examination of the abdomen was negative. An ultrasound of the liver and an abdominal CT angiogram detected a disomogeneous hypoechoic-hypodense area in the 5th segment of the liver. Differential diagnosis between hepatic abscess or gallbladder cancer remained open. A surgical exploration was planned. After laparoscopic exploration, a conversion to open procedure with an atypical resection of the 5th hepatic segment was performed. Histologic examination of the specimen showed an intrahepatic chronic perforation of the gallbladder with intrahepatic abscess.
To the best of our knowledge, 18 cases have been reported in the literature as a Niemeier type I perforation. Clinical presentation, even in its extreme rarity, is more often acute. Differential diagnosis between gallbladder cancer versus liver abscess remains controversial. Open approach is mandatory in such cases.
PMCID: PMC3930071  PMID: 24468118
Intrahepatic perforation; Hepatic abscess; Chronic perforation; Chronic cholecystitis
11.  Permanent draft genome sequences of the symbiotic nitrogen fixing Ensifer meliloti strains BO21CC and AK58 
Standards in Genomic Sciences  2013;9(2):325-333.
Ensifer (syn. Sinorhizobium) meliloti is an important symbiotic bacterial species that fixes nitrogen. Strains BO21CC and AK58 were previously investigated for their substrate utilization and their plant-growth promoting abilities showing interesting features. Here, we describe the complete genome sequence and annotation of these strains. BO21CC and AK58 genomes are 6,985,065 and 6,974,333 bp long with 6,746 and 6,992 genes predicted, respectively.
PMCID: PMC4062632  PMID: 24976889
Aerobic; motile; Gram-negative; mesophilic; chemoorganotrophic; chemoautotrophic; soil; plant symbiont; biological nitrogen fixation; Ensifer (Sinorhizobium) meliloti; legume yield
12.  22q11 deletion syndrome: a review of the neuropsychiatric features and their neurobiological basis 
The 22q11.2 deletion syndrome (22q11DS) is caused by an autosomal dominant microdeletion of chromosome 22 at the long arm (q) 11.2 band. The 22q11DS is among the most clinically variable syndromes, with more than 180 features related with the deletion, and is associated with an increased risk of psychiatric disorders, accounting for up to 1%–2% of schizophrenia cases. In recent years, several genes located on chromosome 22q11 have been linked to schizophrenia, including those encoding catechol-O-methyltransferase and proline dehydrogenase, and the interaction between these and other candidate genes in the deleted region is an important area of research. It has been suggested that haploinsufficiency of some genes within the 22q11.2 region may contribute to the characteristic psychiatric phenotype and cognitive functioning of schizophrenia. Moreover, an extensive literature on neuroimaging shows reductions of the volumes of both gray and white matter, and these findings suggest that this reduction may be predictive of increased risk of prodromal psychotic symptoms in 22q11DS patients. Experimental and standardized cognitive assessments alongside neuroimaging may be important to identify one or more endophenotypes of schizophrenia, as well as a predictive prodrome that can be preventively treated during childhood and adolescence. In this review, we summarize recent data about the 22q11DS, in particular those addressing the neuropsychiatric and cognitive phenotypes associated with the deletion, underlining the recent advances in the studies about the genetic architecture of the syndrome.
PMCID: PMC3862513  PMID: 24353423
22q11 deletion syndrome; microdeletion; neuropsychiatric disorders; cognitive impairments
13.  Comparison of Different Suicide-Gene Strategies for the Safety Improvement of Genetically Manipulated T Cells 
Human Gene Therapy Methods  2012;23(6):376-386.
Use of adoptive T-cell therapy (ACT) is increasing; however, T-cell therapy can result in severe toxicity. Consequently, several suicide-gene strategies that allow selective destruction of the infused T cells have been described. We compared effectiveness of four such strategies in vitro in Epstein Barr virus (EBV)-cytotoxic T lymphocytes (CTLs). Herpes simplex virus thymidine kinase (HSV-TK), human inducible caspase 9 (iCasp9), mutant human thymidylate kinase (mTMPK), and human CD20 codon optimized genes were cloned in frame with 2A-truncated codon optimized CD34 (dCD34) in a retroviral vector. Codon-optimization considerably improved CD20 expression. EBV-CTLs could be efficiently transduced in all constructs, with transgene expression similar to the control vector containing dCD34 alone. Expression was maintained for prolonged cultures. Expression of the suicide genes was not associated with alterations in immunophenotype, proliferation, or function of CTLs. Activation of HSV-TK, iCasp9, and CD20 ultimately resulted in equally effective destruction of transduced T cells. However, while iCasp9 and CD20 effected immediate cell-death induction, HSV-TK-expressing T cells required 3 days of exposure to ganciclovir to reach full effect. mTMPK-transduced cells showed lower T-cell killing all time points. Our results suggest that the faster activity of iCasp9 might be advantageous in treating certain types of acutely life-threatening toxicity. Codon-optimized CD20 has potential as a suicide gene.
Marin and colleagues compare the effectiveness of four suicide-gene strategies in a model in vitro T-cell system. Herpes simplex virus thymidine kinase (HSV-TK), human inducible caspase 9 (iCasp9), mutant human thymidylate kinase (mTMPK), and human CD20 codon-optimized genes were cloned in frame with 2A-truncated codon optimized CD34 in a retroviral vector. Suicide-gene activation ultimately resulted in equally effective destruction of transduced T cells, with iCasp9 and CD20 displaying the most immediate induction of cell death.
PMCID: PMC4015080  PMID: 23186165
14.  An inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia 
Cancer cell  2012;22(5):683-697.
To define the mutation spectrum in non-Down syndrome acute megkaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL leukemia samples. Our analysis identified a cryptic chromosome 16 inversion [inv(16)(p13.3q24.3)] in 27% of pediatric cases, which encodes a CBFA2T3-GLIS2 fusion protein. Expression of CBFA2T3-GLIS2 in Drosophila and murine hematopoietic cells induced bone morphogenic protein (BMP) signaling, and resulted in a marked increase in the self-renewal capacity of hematopoietic progenitors. These data suggest that expression of CBFA2T3-GLIS2 directly contributes to leukemogenesis.
PMCID: PMC3547667  PMID: 23153540
20.  Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia 
Blood Cancer Journal  2013;3(11):e160-.
To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59–100%) and a specificity of 87% (CI 70–96%). Positive and negative predictive values were 71% (CI 42–92%) and 96% (CI 82–100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.
PMCID: PMC3880439  PMID: 24241400
juvenile myelomonocytic leukemia; phospho-specific flow cytometry; phospho-STAT5; GM-CSF
21.  Incidence of pain after inguinal hernia repair in the elderly. A retrospective historical cohort evaluation of 18-years’ experience with a mesh & plug inguinal hernia repair method on about 3000 patients 
BMC Surgery  2013;13(Suppl 2):S19.
Chronic pain after prosthetic inguinal hernioplasty is one of the most important current issues in the current literature debate. Mechanisms related to pain development are only partially known. Influence of age as well as other factors is still unclear. The aim of this work was to evaluate whether development of chronic pain after open prosthetic plug and mesh inguinal hernioplasty is influenced by age.
Analysis was retrospectively conducted, dividing our cohort of patients (2,902) who had undergone prosthetic open plug&mesh inguinal hernioplasty from Jannuary 1994 to May 2012, following only the age criterion (cut-off 65 yrs.), into two groups (Gr.A<65 yrs, Gr.B>65 yrs.). All patients were routinely submitted to a postoperative questionnaire. Complications such as analgesic assumption were registered in both groups. Pain intensity was classified following the Visual Analogic Scale (VAS). Incidence of chronic pain, discomfort, and numbness, was assessed in both groups. Statistical significance was assessed by X2-test.
Only 0.2% of patients suffered from a recurrence in our cohort. Postoperative chronic pain was observed in Gr. A in 0.12% of patients vs Gr.B 0.09% (p>0.05). Incidence of other postoperative symptoms such as discomfort or numbness were slightly prevalent on young patients (respectively p = 0.0286 and p = 0.01), while for hyperesthesia and sensation of foreign body no statistically significant difference of incidence between groups was observed.
Real chronic pain after inguinal hernioplasty is a rare clinical entity. Other causes of chronic pain should be accurately researched and excluded. In young patients psychological factors seem to show a slight influence. There was no influence of age on chronic postoperative pain incidence after inguinal hernioplasty.
PMCID: PMC3850950  PMID: 24268023
22.  Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects 
BMC Surgery  2013;13(Suppl 2):S14.
Populations living in the area of the Mediterranean Sea suffered by decreased incidence of cancer compared with those living in the regions of northern Europe and US countries, attributed to healthier dietary habits. Nowadays, we are assisting to a moving away from the traditional Mediterranean dietary pattern, but whether this changing is influencing risk of cancers is still unclear. The aim of the study was to review recent evidence on potential relationship between the adherence to the Mediterranean diet and cancer.
The most recent pooled analyses of epidemiological studies supported strongly the hypothesis that the Mediterranean diet may play a role in preventing several types of cancers, especially those of digestive tract, whereas contrasting results were reported for hormone-dependent cancers. Specific aspects of the Mediterranean diet such as high fruit and vegetables and low red processed meat intake may explain such protective effects. Moreover, evidence regarding olive oil and whole grains increase the beneficial effects of such dietary pattern against cancer.
Literature evidence actually demonstrates that the increased adherence to the Mediterranean dietary pattern is beneficial to health across populations and may translate a protective effect with certain cancers.
PMCID: PMC3850991  PMID: 24267672
23.  Pharmacological and dietary prevention for colorectal cancer 
BMC Surgery  2013;13(Suppl 2):S16.
Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics.
The studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results.
The results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be suggested to potentiate such effects by adding them together.
PMCID: PMC3851139  PMID: 24267792
24.  Laparoscopic vs. open approach for colorectal cancer: evolution over time of minimal invasive surgery 
BMC Surgery  2013;13(Suppl 2):S12.
In the late '80s the successes of the laparoscopic surgery for gallbladder disease laid the foundations on the modern use of this surgical technique in a variety of diseases. In the last 20 years, laparoscopic colorectal surgery had become a popular treatment option for colorectal cancer patients.
Many studies emphasized on the benefits stating the significant advantages of the laparoscopic approach compared with the open surgery of reduced blood loss, early return of intestinal motility, lower overall morbidity, and shorter duration of hospital stay, leading to a general agreement on laparoscopic surgery as an alternative to conventional open surgery for colon cancer. The reduced hospital stay may also decrease the cost of the laparoscopic surgery for colorectal cancer, despite th higher operative spending compared with open surgery. The average reduction in total direct costs is difficult to define due to the increasing cost over time, making challenging the comparisons between studies conducted during a time range of more than 10 years. However, despite the theoretical advantages of laparoscopic surgery, it is still not considered the standard treatment for colorectal cancer patients due to technical limitations or the characteristics of the patients that may affect short and long term outcomes.
The laparoscopic approach to colectomy is slowly gaining acceptance for the management of colorectal pathology. Laparoscopic surgery for colon cancer demonstrates better short-term outcome, oncologic safety, and equivalent long-term outcome of open surgery. For rectal cancer, laparoscopic technique can be more complex depending on the tumor location. The advantages of minimally invasive surgery may translate better care quality for oncological patients and lead to increased cost saving through the introduction of active enhanced recovery programs which are likely cost-effective from the perspective of the hospital health-care providers.
PMCID: PMC3851244  PMID: 24267544
25.  Social disparities, health risk behaviors, and cancer 
BMC Surgery  2013;13(Suppl 2):S17.
Overall cancer incidence rates decreased in the most recent time period in both men and women, largely due to improvements in surgical therapeutic approaches (tertiary prevention) and screening programs (secondary prevention), but differences in cancer incidence and survival according to socioeconomic status are documented worldwide. Health risk behaviors, defined as habits or practices that increase an individual’s likelihood of harmful health outcomes, are thought to mediate such inequalities.
Obesity has been related with increased cancer incidence and mortality due to imbalance of leptin and adiponectin which are connected to activation of PI3K, MAPK, and STAT3 pathways and decreasing insulin/insulin-like growth factor (IGF)-1 and mTOR signaling via activation of 5 AMP-activated protein kinase (AMPK), respectively. Physical activity has been associated to prevent cancer by the aforementioned obesity-related mechanisms, but also increasing level of circulating vitamin D, which has been related to lower risk of several cancers, and increasing prostaglandin F2a and reducing prostaglandin E2, which are both related with cancer prevention and promotion, respectively. A large number of different substances may induce themselves a direct cytotoxicity and mutagenic action on cells by smoking, whereas alcohol promote immune suppression, the delay of DNA repair, inhibition of the detoxification of carcinogens, the production of acetaldehyde, and the contribution to abnormal DNA methylation. The combined smoking and alcohol drinking habits have been shown to increase cancer risk by smoke action of increasing the acetaldehyde burden following alcohol consumption and alcohol action of enhancing the activation of various procarcinogens contained in tobacco smoke.
Interventions at the social level may be done to increase awareness about cancer risks and promote changing in unhealthy behaviors.
PMCID: PMC3851246  PMID: 24267900

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