Impact of different tissue dissociation protocols on endothelial cell recovery from developing mouse lungs.

Flow cytometry and fluorescence-activated cell sorting are widely used to study endothelial cells, for which the generation of viable single-cell suspensions is an essential first step. Two enzymatic approaches, collagenase A and dispase, are widely employed for endothelial cell isolation. In this study, the utility of both enzymatic approaches, alone and in combination, for endothelial cell isolation from juvenile and adult mouse lungs was assessed, considering the number, viability, and subtype composition of recovered endothelial cell pools. Collagenase A yielded an 8-12-fold superior recovery of viable endothelial cells from lung tissue from developing mouse pups, compared to dispase, although dispase proved superior in efficiency for epithelial cell recovery. Single-cell RNA-Seq revealed that the collagenase A approach yielded a diverse endothelial cell subtype composition of recovered endothelial cell pools, with broad representation of arterial, capillary, venous, and lymphatic lung endothelial cells; while the dispase approach yielded a recovered endothelial cell pool highly enriched for one subset of general capillary endothelial cells, but poor representation of other endothelial cells subtypes. These data indicate that tissue dissociation markedly influences the recovery of endothelial cells, and the endothelial subtype composition of recovered endothelial cell pools, as assessed by single-cell RNA-Seq.

Clinical and psychosocial constructs for breast, cervical, and colorectal cancer screening participation: A systematic review

Research has identified a wide range of psychosocial factors associated to choosing to engage in ongoing cancer screenings. Nevertheless, a systematic review of the theoretical frameworks and constructs underpinning studies on breast, cervical, and colorectal cancer screening participation has yet to be conducted. As part of the action-research project “Miriade,” the present study aims to identifying the main theoretical frameworks and constructs adopted in the literature over the past five years to explain cancer screening participation. According to the PRISMA guidelines, a search of the MEDLINE/PubMed and PsycINFO databases was made. Empirical studies conducted from 2017 to 2021 were included. The following keywords were used: breast OR cervical OR colorectal screening AND adhesion OR participation OR engagement AND theoretical framework OR conceptual framework OR theory. Overall, 24 articles met the inclusion criteria. Each theoretical framework highlighted clinical and psychosocial constructs of cancer screening participation, focusing on the individuals (psycho-emotional functioning and skills plan) and/or the health services perspectives. Findings from the present study acknowledge the plurality of the theoretical frameworks and constructs adopted to predict or promote breast, cervical, and colorectal cancer screening adhesion and the need for new research efforts to improve the effectiveness of cancer screening promotion interventions. (AU)

Clinical and psychosocial constructs for breast, cervical, and colorectal cancer screening participation: A systematic review.

Research has identified a wide range of psychosocial factors associated to choosing to engage in ongoing cancer screenings. Nevertheless, a systematic review of the theoretical frameworks and constructs underpinning studies on breast, cervical, and colorectal cancer screening participation has yet to be conducted. As part of the action-research project "Miriade," the present study aims to identifying the main theoretical frameworks and constructs adopted in the literature over the past five years to explain cancer screening participation. According to the PRISMA guidelines, a search of the MEDLINE/PubMed and PsycINFO databases was made. Empirical studies conducted from 2017 to 2021 were included. The following keywords were used: breast OR cervical OR colorectal screening AND adhesion OR participation OR engagement AND theoretical framework OR conceptual framework OR theory. Overall, 24 articles met the inclusion criteria. Each theoretical framework highlighted clinical and psychosocial constructs of cancer screening participation, focusing on the individuals (psycho-emotional functioning and skills plan) and/or the health services perspectives. Findings from the present study acknowledge the plurality of the theoretical frameworks and constructs adopted to predict or promote breast, cervical, and colorectal cancer screening adhesion and the need for new research efforts to improve the effectiveness of cancer screening promotion interventions.

Factors promoting breast, cervical and colorectal cancer screenings participation: A systematic review.

OBJECTIVE: The present study aims at systematically reviewing research conducted on factors promoting breast, cervical and colorectal cancer screenings participation. METHODS: A literature search in MEDLINE/PubMed and PsycInfo from January 2017 to October 2021 was performed. Data extraction, researchers' full agreement and the inclusion criteria produced 102 eligible studies. Data were narratively synthesized and critically interpreted. RESULTS: Multiple factors favoring or hindering breast, cervical and colorectal cancer screenings were identified and summarized as factors operating at the individual level (background information, individual characteristics, emotions related to screening procedure and to cancer, knowledge and awareness), at the relational level (relationships with healthcare staff, significant others, community members), and at the healthcare system level (systems barriers/policy, lack of staff). A critical appraisal of studies revealed a fragmentation in the literature, with a compartmentalization of studies by type of cancer screening, country and specific populations of destination. CONCLUSIONS: Overall findings indicated that greater integration of research results obtained independently for each cancer diagnosis and within the different countries/populations could foster a more comprehensive understanding of factors potentially enhancing the participation in breast, cervical and colorectal cancer screenings worldwide. This review, which is grounded in the current context of globalization and superdiversification in population, can help to enhance a better integration between research and practices, by supporting the development of more effective and inclusive evidence-based interventions and health-promotion campaigns worldwide. Research and practical implications are highlighted and discussed.

The H2S-generating enzyme 3-mercaptopyruvate sulfurtransferase regulates pulmonary vascular smooth muscle cell migration and proliferation but does not impact normal or aberrant lung development.

Along with nitric oxide (NO), the gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) are emerging as potentially important players in newborn physiology, as mediators of newborn disease, and as new therapeutic modalities. Several recent studies have addressed H2S in particular in animal models of bronchopulmonary dysplasia (BPD), a common complication of preterm birth where oxygen toxicity stunts lung development. In those studies, exogenous H2S attenuated the impact of oxygen toxicity on lung development, and two H2S-generating enzymes were documented to affect pulmonary vascular development. H2S is directly generated endogenously by three enzymes, one of which, 3-mercaptopyruvate sulfurtransferase (MPST), has not been studied in the lung. In a hyperoxia-based animal model of BPD, oxygen exposure deregulated MPST expression during post-natal lung development, where MPST was localized to the smooth muscle layer of the pulmonary vessels in developing lungs. siRNA-mediated abrogation of MPST expression in human pulmonary artery smooth muscle cells in vitro limited baseline cell migration and cell proliferation, without affecting apoptosis or cell viability. In vivo, MPST was dispensable for normal lung development in Mpst-/-mice, and MPST did not contribute to stunted lung development driven by hyperoxia exposure, assessed by design-based stereology. These data demonstrate novel roles for MPST in pulmonary vascular smooth muscle cell physiology. The potential caveats of using Mpst-/- mice to study normal and aberrant lung development are also discussed, highlighting the possible confounding, compensatory effects of other H2S-generating enzymes that are present alongside MPST in the smooth muscle compartment of developing pulmonary vessels.

E-TAN, a technology-enhanced platform with tangible objects for the assessment of visual neglect: A multiple single-case study.

Visual neglect is a frequent and disabling consequence of right brain damage. Traditional paper-and pencil tests of neglect have limited sensitivity and ecological validity. The Baking Tray Task (BTT), instead, approaches real-life situations, because it requires participants to place 16 physical objects on a board. The number of objects placed on the left and right portions of the board provides a clinical index of visual neglect. Here we present E-TAN, a technology-enhanced platform for BTT (E-BTT). E-BTT automatically determines the object locations on the board, and also records the sequence and timing of their placement. We used E-BTT to test 9 patients with right hemisphere damage and compared their performance with that obtained by 115 healthy participants. To this end, we developed a new method of analysis of participants' performance, based on the use of the convex hull described by the objects on the board. This measure provides an estimate of the portion of space processed by each participant and can effectively discriminate neglect patients from patients without neglect. E-TAN allows clinicians to assess visuospatial performance by using a convenient, fast, and relatively automatized procedure, that patients can even perform at home to follow-up the effects of rehabilitation.

Coagulopathy, thromboembolic complications, and the use of heparin in COVID-19 pneumonia.

The SARS-CoV-2 (COVID-19) is causing a pandemic and potentially fatal disease of global public health concern. Viral infections are known to be associated with coagulation impairment; thus, thrombosis, hemorrhage, or both may occur. Understanding the pathophysiologic mechanisms underlying the development of coagulation disorders during viral infection is essential for the development of therapeutic strategies. Coagulopathy in COVID-19 infection is emerging as a precipitant factor for severe respiratory complications and death. An increase in coagulation markers, such as fibrinogen and D-dimer, has been found in severe COVID-19 cases. Heparin, clinically used as an anticoagulant, also has anti-inflammatory properties, including binding of inflammatory cytokines, inhibition of neutrophil chemotaxis, and protection of endothelial cells, and a potential antiviral effect. We hypothesized that low-molecular-weight heparin may attenuate cytokine storm in COVID-19 patients; therefore, low-molecular-weight heparin could be a valid adjunctive therapeutic drug for the treatment of COVID-19 pneumopathy. In this paper, we review potential mechanisms involved in coagulation impairment after viral infection and the possible role of heparin in the treatment of COVID-19 patients.

Recent advances in our understanding of the mechanisms of lung alveolarization and bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common cause of morbidity and mortality in preterm infants. A key histopathological feature of BPD is stunted late lung development, where the process of alveolarization-the generation of alveolar gas exchange units-is impeded, through mechanisms that remain largely unclear. As such, there is interest in the clarification both of the pathomechanisms at play in affected lungs, and the mechanisms of de novo alveoli generation in healthy, developing lungs. A better understanding of normal and pathological alveolarization might reveal opportunities for improved medical management of affected infants. Furthermore, disturbances to the alveolar architecture are a key histopathological feature of several adult chronic lung diseases, including emphysema and fibrosis, and it is envisaged that knowledge about the mechanisms of alveologenesis might facilitate regeneration of healthy lung parenchyma in affected patients. To this end, recent efforts have interrogated clinical data, developed new-and refined existing-in vivo and in vitro models of BPD, have applied new microscopic and radiographic approaches, and have developed advanced cell-culture approaches, including organoid generation. Advances have also been made in the development of other methodologies, including single-cell analysis, metabolomics, lipidomics, and proteomics, as well as the generation and use of complex mouse genetics tools. The objective of this review is to present advances made in our understanding of the mechanisms of lung alveolarization and BPD over the period 1 January 2017-30 June 2019, a period that spans the 50th anniversary of the original clinical description of BPD in preterm infants.

Hyaluronic acid and metallic silver treatment of chronic wounds: healing rate and bacterial load control.

OBJECTIVE: To confirm the safety and wound healing activity of a topical spray powder containing hyaluronic acid (HA) and metallic silver (Hyalosilver, Fidia Farmaceutici S.p.A., Italy), and investigate its effect on the control of bacterial load in vascular ulcers or category I-II pressure ulcers (PU). METHODS: This is a single site, prospective, open label study involving patients with a vascular ulcer or category I-II PUs, presenting signs of critical bacterial colonisation. Patients with a wound size of ≤15cm2 were enrolled. At baseline, a swab was taken of each wound for a semi-quantitative analysis of bacterial load and the first treatment of topical spray powder was applied. The patient was then requested to self-apply the medication once a day for 28 consecutive days and to return on days one, seven and 28 for clinical and microbiological assessments. RESULTS: A total of 25 patients were enrolled in the study. Treatment with the topical spray powder enhanced the healing rate of chronic wounds in terms of a reduction of wound area as well as bacterial load (p<0.025) and the overall clinical status of wound (odour, exudate, erythema of periwound skin; p<0.017). Moreover, the spray powder increased overall patient perception of improvement in the wound (p<0.05). CONCLUSION: The data demonstrated good safety and tolerability of the topical spray powder suggesting that the product is effective not only in reducing wound area, due to the presence of HA, but in keeping the bacterial colonisation under control.

Targeting miR-34a/Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth characterized by arrested lung alveolarization, which generates lungs that are incompetent for effective gas exchange. We report here deregulated expression of miR-34a in a hyperoxia-based mouse model of BPD, where miR-34a expression was markedly increased in platelet-derived growth factor receptor (PDGFR)α-expressing myofibroblasts, a cell type critical for proper lung alveolarization. Global deletion of miR-34a; and inducible, conditional deletion of miR-34a in PDGFRα+ cells afforded partial protection to the developing lung against hyperoxia-induced perturbations to lung architecture. Pdgfra mRNA was identified as the relevant miR-34a target, and using a target site blocker in vivo, the miR-34a/Pdgfra interaction was validated as a causal actor in arrested lung development. An antimiR directed against miR-34a partially restored PDGFRα+ myofibroblast abundance and improved lung alveolarization in newborn mice in an experimental BPD model. We present here the first identification of a pathology-relevant microRNA/mRNA target interaction in aberrant lung alveolarization and highlight the translational potential of targeting the miR-34a/Pdgfra interaction to manage arrested lung development associated with preterm birth.

Promoting water intake. The persuasiveness of a messaging intervention based on anticipated negative affective reactions and self-monitoring.

The present research focused on water intake (WI) in young adults. Study 1 (N = 272) was a correlational study and showed affective attitude, perceived behavioural control, past behaviour and anticipated negative affective reactions (ANAR) to predict WI intentions. It also showed intentions, instrumental attitude, perceived behavioural control, and past behaviour to predict WI prospectively. In addition, ANAR moderates the relationship between intention and future water intake (WI). Study 2 (N = 197) was an experimental study and showed that daily text messages targeting ANAR plus a self-monitoring manipulation increased WI immediately after the intervention although this effect did not persist one month later. Mediation analysis indicated the intervention impacted WI via sequentially changing ANAR and intention.

Effect of consecutive re-synchronization protocols on pregnancy rate in buffalo (Bubalus bubalis) heifers out of the breeding season.

The combined effect of six consecutive timed artificial inseminations (TAIs) on pregnancy rates, following two different synchronization protocols on buffalo heifers, over a period of seven months typically characterized by low breeding performances, were investigated in this study. A total of 2189 TAIs were performed on 1463 buffalo heifers within a large buffalo farm in the south of Italy. Individual animals were allowed to undergo synchronization protocol (either a slightly modified Ovsynch or Progesterone treatment) and TAI until establishment of pregnancy or else for not more than six consecutive times. Semen of seven proven bulls was used throughout the study, which was carried out from March to September of the same year. Therefore, other than the effect given by consecutive TAIs over time, a monthly and a seasonal effect could also be tested, once the entire period was split into a Low Breeding Season (LBS) from March to June, and a Transition to Breeding Season (TBS) from July to September. From the data recorded in this study and the statistical analysis performed, it can be stated that the two protocols for the synchronization of ovulation were similar in efficiency in determining pregnancies with an overall fertility rate of 89.4% when the comparison was run both on a monthly basis or when months were grouped into two different seasons. In addition, an average of 1.83 AI/pregnancy was reported, slightly higher for the Ovsynch when compared to the Progesterone protocol: 1.91 vs 1.70, respectively. Finally, when considering the number of progressive synchronization treatments implemented over time as covariate, neither Ovsynch nor Progesterone treatment significantly affected pregnancy rates following the first of the six synchronization sessions. However, repeating the synchronization procedure, the progesterone based protocol resulted in significantly higher probability of success in terms of established pregnancies during the second and third re-synchronization sessions.

Perturbations to lysyl oxidase expression broadly influence the transcriptome of lung fibroblasts.

Lysyl oxidases are credited with pathogenic roles in lung diseases, including cancer, fibrosis, pulmonary hypertension, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). Lysyl oxidases facilitate the covalent intra- and intermolecular cross-linking of collagen and elastin fibers, thereby imparting tensile strength to the extracellular matrix (ECM). Alternative ECM-independent roles have recently been proposed for lysyl oxidases, including regulation of growth factor signaling, chromatin remodeling, and transcriptional regulation, all of which impact cell phenotype. We demonstrate here that three of the five lysyl oxidase family members, Lox, Loxl1, and Loxl2, are highly expressed in primary mouse lung fibroblasts compared with other constituent cell types of the lung. Microarray analyses revealed that small interfering RNA knockdown of Lox, Loxl1, and Loxl2 was associated with apparent changes in the expression of 134, 3,761, and 3,554 genes, respectively, in primary mouse lung fibroblasts. The impact of lysyl oxidase expression on steady-state Mmp3, Mmp9, Eln, Rarres1, Gdf10, Ifnb1, Csf2, and Cxcl9 mRNA levels was validated, which is interesting, since the corresponding gene products are relevant to lung development and BPD, where lysyl oxidases play a functional role. In vivo, the expression of these genes broadly correlated with Lox, Loxl1, and Loxl2 expression in a mouse model of BPD. Furthermore, ß-aminopropionitrile (BAPN), a selective lysyl oxidase inhibitor, did not affect the steady-state mRNA levels of lysyl oxidase target genes, in vitro in lung fibroblasts or in vivo in BAPN-treated mice. This study is the first to report that lysyl oxidases broadly influence the cell transcriptome.

Carnitine supplementation decreases capacitation-like changes of frozen-thawed buffalo spermatozoa.

The aim of this study was to evaluate the effect of carnitine supplementation of semen extender on fertility parameters of frozen-thawed buffalo sperm. Buffalo semen was cryopreserved in BioXcell containing 0 (control group), 2.5 and 7.5-mM carnitine. After thawing, viability, motility, membrane integrity and capacitation status (assessed by localization of phosphotyrosine-containing proteins and chlortetracycline, chlortetracycline assay) were evaluated. Furthermore, total antioxidant capacity, reactive oxygen species (ROS) and lipid peroxidation levels, as well as adenosine triphosphate (ATP) content and phospholipids concentration were assessed. Finally, in vitro-fertilizing ability was evaluated after heterologous IVF. An increased post-thawing sperm motility and membrane integrity were recorded in both treated groups compared with the control (44.4 ± 3.5, 53.1 ± 3.9, and 52.5 ± 3.6%; P < 0.05 and 48.44 ± 0.69, 55.19 ± 0.54, 59.63 ± 0.30%; P < 0.01 with 0, 2.5-mM, and 7.5-mM carnitine, respectively). Supplementation of carnitine to the freezing extender decreased (P < 0.01) the percentage of sperm displaying fluorescence at both equatorial and anterior acrosomal regions (pattern EA), corresponding to high capacitation level, compared with the control (30.3 ± 3.8, 18.8 ± 2.8, and 7.2 ± 2.9%, respectively, with 0, 2.5-mM, and 7.5-mM carnitine). In agreement with this, carnitine also decreased (P < 0.01) the percentage of sperm displaying chlortetracycline pattern B (capacitated sperm) (63.8 ± 1.8, 46.8 ± 2.2, and 37.2 ± 1.8%, respectively with 0, 2.5-, and 7.5-mM carnitine). Interestingly, carnitine increased total antioxidant capacity and ATP content of buffalo frozen-thawed sperm (1.32 ± 0.02, 1.34 ± 0.01, 1.37 ± 0.01 mM/L and 4.1 ± 0.1, 5.3 ± 0.1 and 8.2 ± 0.4 nM × 108 sperm; P < 0.01, respectively, with 0, 2.5- and 7.5-mM carnitine). Intracellular ROS decreased in carnitine-treated sperm compared with the control, as indicated by dihydroethidium (DHE) values (0.22 ± 0.01, 0.18 ± 0.01, and 0.14 ± 0.0 µM/100 µL dihydroethidium, respectively, with 0, 2.5-, and 7.5-mM carnitine; P < 0.01), whereas lipid peroxidation levels (on average 30.5 ± 0.3 nmol/mL MDA) and phospholipids concentration (on average 0.14 ± 0.00 µg/120 × 106 sperm) were unaffected. Despite the improved sperm quality, the percentage of normospermic penetration after IVF was not influenced (on average 53.5 ± 1.8). In conclusion, enrichment of extender with carnitine improved buffalo sperm quality by increasing ATP generation and modulating ROS production, without affecting in vitro fertilizing ability.

New Surfactant-based Dressing Product to Improve Wound Closure Rates of Nonhealing Wounds: A European Multicenter Study Including 1036 Patients.

OBJECTIVE: A new surfactant-based biomaterial containing the antimicrobial 1% silver sulfadiazine (SSD) was developed at the University of Virginia (Charlottesville, VA) to improve outcomes for nonhealing wounds. This study's objective was to clinically test the wound care outcomes of the new surfactant-based antimicrobial wound dressing (SAWD) in a multicenter trial. METHODS AND MATERIALS: This cohort study enrolled 1036 patients with any nonhealing wound of > 3 months duration not responding to standard-of-care treatments from 10 wound care centers in 7 European countries. The SAWD was used for all wound types at all stages of complexity, healing, and severity. Data collection ranged from 6 months to 2 years and measured the percentage of patients achieving wound closure and time to complete closure. RESULTS: Of the 1036 patients, 70% achieved wound closure, 24.6% were still in treatment at data collection, and 5.4% had a therapy change. The majority (56%) of these non-healing wounds achieved wound closure within 11 weeks. Patients were treated with the SAWD for 3 weeks to more than 1 year with no complications or adverse effects from long-term SSD antimicrobial use. CONCLUSION: Ten centers concluded that the new SAWD provided positive results (improved wound closure rates, reduction of inflammation, pain, and odor), improvements in clinical application (faster and easier dressing change), and improved patient compliance.

Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions.

INTRODUCTION: Metformin is proposed as adjuvant therapy in cancer treatment because of its ability to limit cancer incidence by negatively modulating the PI3K/AKT/mTOR pathway. In vitro, in addition to inhibiting cancer cell proliferation, metformin can also induce apoptosis. The molecular mechanism underlying this second effect is still poorly characterized and published data are often contrasting. We investigated how nutrient availability can modulate metformin-induced apoptosis in three breast cancer cell lines. MATERIAL AND METHODS: MCF7, SKBR3 and MDA-MB-231 cells were plated in MEM medium supplemented with increasing glucose concentrations or in DMEM medium and treated with 10 mM metformin. Cell viability was monitored by Trypan Blue assay and treatment effects on Akt/mTOR pathway and on apoptosis were analysed by Western Blot. Moreover, we determined the level of expression of pyruvate kinase M2 (PKM2), a well-known glycolytic enzyme expressed in cancer cells. RESULTS: Our results showed that metformin can induce apoptosis in breast cancer cells when cultured at physiological glucose concentrations and that the pro-apoptotic effect was completely abolished when cells were grown in high glucose/high amino acid medium. Induction of apoptosis was found to be dependent on AMPK activation but, at least partially, independent of TORC1 inactivation. Finally, we showed that, in nutrient-poor conditions, metformin was able to modulate the intracellular glycolytic equilibrium by downregulating PKM2 expression and that this mechanism was mediated by AMPK activation. CONCLUSION: We demonstrated that metformin induces breast cancer cell apoptosis and PKM2 downregulation only in nutrient-poor conditions. Not only glucose levels but also amino acid concentration can influence the observed metformin inhibitory effect on the mTOR pathway as well as its pro-apoptotic effect. These data demonstrate that the reduction of nutrient supply in tumors can increase metformin efficacy and that modulation of PKM2 expression/activity could be a promising strategy to boost metformin anti-cancer effect.

Surgical treatment and MRI in phyllodes tumors of the breast: our experience and review of the literature.

AIMS: To reassess the relationship between magnetic resonance imaging (MRI) findings and surgical resection margins in an attempt to address the issue of appropriate surgical management of phyllodes tumors (PT). METHODS: Three female patients with a large palpable mass suspicious for phyllodes tumors were studied by mammography (MX), ultrasound (US) and dynamic MRI and then underwent surgery. RESULTS: MRI demonstrated a rapidly and markedly enhancing multi-lobulated lesion. T1-weighted and T2-weighted sequences showed inhomogeneous signal intensity for the presence of cystic areas with internal septation and hemorrhage. Some areas of linear enhancement were present around the mass only in one case. Surgical management was mastectomy in one patient and wide excision in the other two patients. The margins in one of the latter patients were not clear, so mastectomy with immediate prosthetic reconstruction was subsequently performed. Pathological results showed 1 case of benign phylloides tumor, 1 case of borderline phylloides tumor and 1 case of malignant phylloides tumor. CONCLUSIONS: MRI enabled complete visualization of the tumor even in the region close to the chest wall, as well as clear delineation from healthy glandular tissue and may help to define the appropriate surgical management of phylloides tumor.

Breast cancer incidence in the city and province of Palermo in 1999-2002: a Breast Cancer Registry report.

The aim of this study was to assess the incidence of breast cancer in women from the city and province of Palermo (Sicily) in 1999, 2000, 2001, and 2002, using a population-based cancer registry approach. In recent years, a sharp increase of breast cancer incidence has been observed worldwide. Overall, direct age-standardized incidence rates (SIR) were 81.0 per 100,000 person-years, higher in Palermo City (89.4) than in Palermo Province (70.4). Results reported here show a highly significant difference in breast cancer incidence in different areas of Sicily, particularly in the youngest age groups; and a profound difference between the metropolitan area of Palermo and the surrounding areas. The evidence of the different breast cancer incidence in Palermo City and in the other small municipalities of Palermo Province suggests a different cancer risk pattern that seems to be related to recent changes in lifestyle and diet.

Prognostic role of sentinel lymph node biopsy in breast cancer.

Sentinel lymph node biopsy was shown to be an accurate procedure in the study of axillary lymph nodes; it allowed a marked decrease in surgery-related morbidity of breast cancer and axillary dissection could be avoided. Other parameters as molecular markers, nuclear grading, patient age, tumor size, are not able to predict the axillary lymph node status and consequent local therapeutic approach similar to those provided by sentinel lymph node biopsy. The extent of sentinel lymph node metastatic involvement, the extracapsular spread, the size of primary tumor and peritumoral lymphatic/vascular infiltration are the four characteristics shown to be significant, if considered in association and not separately as predictors of the extent of axillary involvement in presence of a positive sentinel lymph node. However, so far, specific studies did not confirm concordant and reproducible results. Therefore, apart from controlled studies, axillary dissection is always required in presence of a metastatic sentinel lymph node.