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ABSTRACT: Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.
Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.
Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.
BMC Surgery 11/2012; 12 Suppl 1:S35. · 1.33 Impact Factor
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ABSTRACT: Increased life expectancy has led to elevating the mean age of the patients at the time of diagnosis of colon cancer and subsequent treatment. Differences in complication rates and outcome between elderly and younger patients have been investigated.
We retrospectively analysed a database containing the information of patients who underwent surgery for stage I-III colorectal cancer from January 2004 to January 2012 at our institution and compared demographic, cancer-related, and outcomes data of 235 elderly patients with 211 patients ≤65 years old.
Intraoperative complications did not differ between young and old patients whereas some differences have been found in postoperative and late complications: elderly patients suffered more by ileus (P = 0.024), peritonitis or septic shock (P = 0.017), pelvic abscess (P = 0.028), wound infection (P = 0.031), and incisional/port herniation (P = 0.012) compared with younger patients. Moreover, elderly patients suffered by systemic complications such as cardiovascular (4.7% vs. 1.4%, P = 0.049), renal (4.7% vs. 0.5%, P = 0.006), and respiratory (10.6% vs. 5.2%, P = 0.036). The multivariate analysis assessing the odds of having a complication revealed that older age (Odd Ratio [OR] 2.75, 95% Confidential Interval [CI]: 1.67-4.52) and open surgery (OR 1.63, 95% CI: 1.01-2.62) are significantly and independently associated with having a complication.
In our series, elderly patients have presented a slight higher incidence of comorbidities that may affect the incidence rates of postoperative complications. These results have implications in increasing the hospital stay as well as a higher rate of death.
BMC Surgery 11/2012; 12 Suppl 1:S20. · 1.33 Impact Factor
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ABSTRACT: During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages.
The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed.
The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001).
Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.
BMC Surgery 11/2012; 12 Suppl 1:S7. · 1.33 Impact Factor
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ABSTRACT: The Black Swan Theory was described by Nassim Nicholas Taleb in his book "The Black Swan". This theory refers to "high-impact, hard-to-predict, and rare events beyond the realm of normal expectations". According to Taleb's criteria, a Black Swan Event is a surprise, it has a major impact and after the fact, the event is rationalized by hindsight, as if it had been expected. For most of human history centenarians were a rare and unpredictable phenomenon. The improvements of the social-environmental conditions, of medical care, and the quality of life caused a general improvement of the health status of the population and a consequent reduction of the overall morbidity and mortality, resulting in an overall increase of life expectancy. The study of centenarians and supercentenarians had the objective to consider this black swan and to evaluate the health, welfare, social and economic consequences of this phenomenon.
BMC Surgery 11/2012; 12 Suppl 1:S36. · 1.33 Impact Factor
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ABSTRACT: Breast cancer is the most commonly diagnosed cancer among U.S. women .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these women are still alive at 15 years. When depression symptoms are present as a consequence of breast cancer treatments, they may interfere negatively with patients' quality of life. The aim of this study was to examine the effects of breast cancer treatment on the quality of life and the impact of depression on the health-related life.
We enrolled 173 women aged 65-75 years with early stage breast cancer diagnosed over the last 10 years, initially recruited to participate in a study examining heath-related quality of life in the first 5 years after breast cancer diagnosis. Participants were divided into four groups: 1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric Depression Scale was used as a routine part of a comprehensive geriatric assessment. Collection of data for the application of instruments, such as sociodemographic variables (age, educational level, social state) and clinical date (stage and time of the disease and treatment), was carried out by trained researcher assistants.
Our results demonstrated the correlation between depression and previous cancer experiences. In fact, in patients with cancer experience, the grade of depression was significantly higher compared to healthy subjects. Furthermore, we demonstrated that the patients with recurrent breast cancer were severely depressed compared to other groups.
A high percentage of participants were identified as having emotional and/or well being problems. Further investigations on the cause of depression problems cancer-related are needed.
BMC Surgery 11/2012; 12 Suppl 1:S14. · 1.33 Impact Factor
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ABSTRACT: Studies on experimental animals have shown liver is a common target of chemical carcinogens; this might suggest that occupational exposure to chemicals is another risk factor for HCC. However, the relationship between occupation and liver cancer has not been extensively studied, with the exception of the known association between vinyl chloride and angiosarcoma of the liver.
A MEDLINE and conventional search of the past 50 years of the medical literature was performed to identify relevant articles on incidence and mechanisms of HCC due to occupational exposure to chemicals. Several important edited books and monographs were also identified and reviewed.
While laboratory data clearly indicate that the liver is an important target of chemical carcinogenesis, epidemiological studies provide very limited evidence on occupational risk factors for HCC. Nevertheless, we found some case reports and epidemiological data showing a moderately increased risk of HCC development in people exposed to vinyl chloride, organic solvents, pesticides, polychlorinated biphenyls, and arsenic.
Occupational exposure to chemicals may be another risk factor for HCC development, but the interpretation of currently available findings is limited by the small number of studies, questionable accuracy of the diagnosis of liver cancer, and potential confounding or modifying factors such as chronic hepatitis virus infection and alcohol consumption. Further relevant investigations are required for clarifying the actual contribution of occupational exposure to chemicals in HCC development.
Hepatitis Monthly 10/2012; 12(10 HCC):e5943. · 2.19 Impact Factor
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ABSTRACT: Osteoblastoma is a rare benign tumor of bone that accounts for approximately 1% of primary skeletal neoplasms, with around 90% of cases diagnosed in the second and third decades of life. Cervical spine is an usual localization of osteoblastoma. The main clinical manifestation in case of cervical spine location is a progressive and resistant pain, possibly accompanied by stiffness, scoliosis or other ailments, including severe neurological deficits. Owing to a non-specific clinical presentation of osteoblastoma, the delay in diagnosis is common. Osteoblastomas may have an aggressive behavior, tend to enlarge and damage the bone and adjacent structures. The treatment of choice is, therefore, a wide and complete surgical excision of the lesion in order to achieve full recovery and prevent recurrence or, in some cases, malignant transformation. In the case of persistent neck pain, not readily relieved by aspirin and possibly accompanied by stiffness, scoliosis or neurological deficits, especially in young subjects, osteoblastoma of cervical spine may be one of the diagnostic options to be considered, in order to avoid delay in diagnosis. We report the case of a 41-year-old male affected by cervical spine osteoblastoma causing a lasting neck pain.
European review for medical and pharmacological sciences 10/2012; 16 (4 Suppl):17-20. · 1.04 Impact Factor
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Marco Ragusa,
Luisa Statello,
Marco Maugeri,
Alessandra Majorana,
Davide Barbagallo,
Loredana Salito,
Mariangela Sammito,
Manuela Santonocito,
Rosario Angelica,
Andrea Cavallaro, [......],
Antonio Biondi,
Maria Di Vita,
Alessandro Cappellani,
Enrico Vasquez,
Salvatore Lanzafame,
Elisabetta Tendi,
Salvatore Celeste,
Cinzia Di Pietro, Francesco Basile,
Michele Purrello
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ABSTRACT: The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has a master control role in various cancer-related biological processes as cell growth, proliferation, differentiation, migration, and apoptosis. It also regulates many transcription factors that control microRNAs (miRNAs) and their biosynthetic machinery. To investigate on the still poorly characterised global involvement of miRNAs within the pathway, we profiled the expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after blocking the pathway with three different inhibitors. This allowed the identification of two classes of post-treatment differentially expressed (DE) miRNAs: (1) common DE miRNAs in all CRC lines after treatment with a specific inhibitor (class A); (2) DE miRNAs in a single CRC line after treatment with all three inhibitors (class B). By determining the molecular targets, biological roles, network position of chosen miRNAs from class A (miR-372, miR-663b, miR-1226*) and class B (miR-92a-1*, miR-135b*, miR-720), we experimentally demonstrated that they are involved in cell proliferation, migration, apoptosis, and globally affect the regulation circuits centred on MAPK/ERK signaling. Interestingly, the levels of miR-92a-1*, miR-135b*, miR-372, miR-720 are significantly higher in biopsies from CRC patients than in normal controls; they also are significantly higher in CRC patients with mutated KRAS than in those with wild-type genotypes (Wilcoxon test, p < 0.05): the latter could be a downstream effect of ERK pathway overactivation, triggered by KRAS mutations. Finally, our functional data strongly suggest the following miRNA/target pairs: miR-92a-1*/PTEN-SOCS5; miR-135b*/LATS2; miR-372/TXNIP; miR-663b/CCND2. Altogether, these results contribute to deepen current knowledge on still uncharacterized features of MAPK/ERK pathway, pinpointing new oncomiRs in CRC and allowing their translation into clinical practice and CRC therapy.
Journal of Molecular Medicine 06/2012; · 4.67 Impact Factor
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The Lancet 06/2012; 379(9831):2116. · 38.28 Impact Factor
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Massimiliano Berretta,
Arben Lleshi,
Rossella Fisichella,
Salvatore Berretta, Francesco Basile,
Giovanni Li Volti,
Antonio Bolognese,
Antonio Biondi,
Paolo De Paoli,
Umberto Tirelli,
Alessandro Cappellani
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ABSTRACT: Cancer of the esophagus is the eighth most common cancer by incidence worldwide and ranks sixth as the most common cause of cancer death. It is unique among the gastrointestinal tract malignancies because it embodies two distinct histopatologic types, squamous cell carcinoma and adenocarcinoma. Which type of cancer occurs in a given patient or predominates in a given geographic area depends on many variables, including individual lifestyle, socioeconomic pressures, environmental factors and diet and nutrition. Generally for both squamous cell carcinoma and adenocarcinoma of the esophagus case-control studies provide evidence of a protective effect of fruits and vegetables. Here we review the role of nutrition in the etiology of esophageal cancer.
Frontiers in bioscience (Elite edition) 01/2012; 4:351-7.
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ABSTRACT: Pancreatitis is a diffuse systemic immuno-inflammatory response to a localized process of auto-digestion within the pancreatic gland, caused by premature activation of proteolytic digestive enzymes. According to the ATLANTA criteria (1992) we recognized a mild and a severe acute pancreatitis (SAP ) . Mortality rate in SAP account up to the 20 percent and most complications and deaths are due to an inflammatory immune response to pancreatic necrosis and/or infection. Patients affected by SAP rapidly incur accelerated catabolism and thus nutritional support is essential, especially in the earliest period of the disease. Recent observations show that the route of nutritional support may also affect disease severity and its course. In this view several important questions about nutritional support need to be addressed : indication , timing, enteral vs parenteral and composition . With this review we analyze the state-of-the-art and we present a decisional flow chart to better manage the nutritional support in SAP.
Frontiers in bioscience (Elite edition) 01/2012; 4:1999-2006.
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ABSTRACT: The elevated variety of procedures proposed for surgical treatment of obesity in the last few years suggests the necessity to find an ideal operation. Laparoscopic mini-gastric bypass (LMGB) was developed to obtain better results with lesser morbidity and mortality. LMGB was introduced by Rutledge, in 1997, and it consists of a long lesser-curvature tube with a terminolateral gastroenterostomy 180 cm distal to the Treitz ligament. From July 1995 to May 2011 we have performed 552 bariatric operations, among them we have operated 197 laparoscopic mini-gastric bypass (Fig. 1). There were 147 female (75%) and 50 male (25%) with the mean age of 37.9 years (range 20-55) and the mean BMI of 52.9 kg/m(2). All procedures were completed laparoscopically, without conversion and the mean operative time was 120 min (range from 90 to 170 min). The average postoperative stay was 5.0 days. We report one case of mortality for pulmonary septic complications. Major complications were two cases of pulmonary embolism (treated in ICU), six cases of melena on seventh postoperative day and three cases of anastomotic ulcers resolved with high doses of PPI. We registered a significant reduction of BMI and percentage of excess weight after surgery with a significant improvement in obesity-related comorbidities including blood pressure, hyperglycemia, blood lipid, uric acid, and liver function. An ideal weight loss operation should be effective, easy to perform and safe. Laparoscopic Roux-en-Y Gastric Bypass is actually the "gold-standard" technique but LMGB seems to be an attractive alternative: shorter operative time, with less morbidity and mortality, easier to teach and to perform. Another advantage could be the presence of a single anastomosis alone reducing the possibility of leaks.
Updates in surgery. 11/2011; 63(4):239-42.
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Roberto Ciuni,
Antonio Biondi,
Giuseppe Grosso,
Giuseppe Nunnari,
Ettore Panascia,
Lisa Randisi,
Riccardo Volpes,
Antonio Arcadipane, Francesco Basile,
Bruno Gridelli,
Salvatore Gruttadauria
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ABSTRACT: In the past two decades, hepatic surgery has achieved important technical breakthroughs resulting in a drastic reduction of the onset of complications and in an improved post-resective survival. Pre-operative nutritional status is one of the key points for the success of a liver resection. Modern surgical achievement such as the development of living-related liver donation, and the possibility to perform more laparoscopic liver resection gave us the opportunity to extend post-operative protocol focused on early intestinal feeding to tumor patients. The aims of this review were to report the current status of the knowledge regarding nutritional aspects in liver resection patients.
Updates in surgery. 11/2011; 63(4):249-52.
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ABSTRACT: We aimed to determine whether education level and socioeconomic status in a cohort of liver transplant recipients in the south of Italy were potential predictors of graft and patient survival.
This retrospective study included 221 liver transplant recipients at Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione between January 2006 and September 2009. Donor gender and age, cold ischaemic time, extended criteria donors, recipient age, gender, body mass index, primary aetiology, Model for End-Stage Liver Disease score, co-morbidities, patient health score assessed on the basis of clinical follow-up, highest level of education achieved, and socioeconomic status were collected and analysed.
Kaplan-Meier analysis of survival measured by education level and socioeconomic status showed a higher survival rate in patients with higher education level (p=0.04) and socioeconomic status (p=0.01). After adjusting for all covariables, results of the multivariate Cox regression analyses showed that only socioeconomic status remained an independent and significant predictor of overall survival (Hazard Ratio=0.16, p=0.03).
Patient survival after liver transplantation was influenced by low income, low educational level, and lack of access to quality health care. Prospective clinical studies are necessary to fully identify the impact of socioeconomic status on long-term health outcomes, and to propose an evidence-based guide to clinical intervention.
Digestive and Liver Disease 07/2011; 43(11):893-8. · 3.05 Impact Factor
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ABSTRACT: Nerve growth factor (NGF) is a pleiotropic member of the neurotrophin family. Beside its neuronal effects, NGF plays a role in various processes, including angiogenesis. Mast cells release NGF and are among elements contributing to angiogenesis, a process regulated by arrays of factors, including the inhibitory cannabinoids. The possible inhibitory role of cannabinoids on mast cell-related NGF mitogenic effect on endothelial cells was then investigated. Human mastocytic cells HMC-1, challenged with PMA to yield release of NGF, were preincubated with the endocannabinoid PEA. Then, conditioned media were added to HUVEC cultures. PMA-activated HMC-1 cells released substantial amounts of NGF, whereas PEA inhibited PMA-induced NGF release. HUVEC proliferation increased after treatment with media from activated HMC-1 cells, while was reduced with media from HMC-1 cells treated with PEA. To characterize receptors mediating such effects of PEA, RT-PCR and western blot analysis were performed on HMC-1 cells. None of the two cannabinoid CB1 and CB2 receptors was expressed by HMC-1 cells, which on the other hand expressed the orphan receptor GPR55. PEA was ineffective in inhibiting NGF release from HMC-1 cells treated with PMA and transfected with positive GPR55 RNAi, whereas it induced significant reduction of NGF in cells transfected with the corresponding negative control RNAi. Results indicate that NGF released from inflammatory mast cells induces angiogenesis. Cannabinoids attenuate such pro-angiogenic effects of NGF. Finally, cannabinoids could be considered for antiangiogenic treatment in disorders characterized by prominent inflammation.
Biochemical pharmacology 05/2011; 82(4):380-8. · 4.25 Impact Factor
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Sebastiano Cavallaro,
Sabrina Paratore,
Femke de Snoo,
Edvige Salomone,
Loredana Villari,
Calogero Buscarino,
Francesco Ferraù,
Giuseppe Banna,
Marco Furci,
Angela Strazzanti,
Rosario Cunsolo,
Salvatore Pezzino,
Santi Gangi, Francesco Basile
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ABSTRACT: Breast cancer is a clinically heterogeneous and complex disease that can affect differently individuals with seemingly identical clinicopathologic parameters. This heterogeneity is strictly linked to individuals and tumors genetic variability. Currently, the development of high-throughput technologies are proving novel tools to tackle this complexity. By DNA microarray technology, genomic analysis has been used successfully for breast carcinomas stratification into molecular subgroups with relevant implications for clinical outcomes, and detection of prognostic/treatment predictive signatures. Indeed, DNA microarray has rapidly improved becoming a powerful diagnostic tool. Information derived from these assays allows clinicians to estimate the risk for distant recurrence, and predict accurately which patients are likely to benefit from adjuvant therapy. This review will describe the state-of-the-art of genomic analysis in breast cancer and introduce the clinicians to a genomic approach to cancer management, illustrating how it can help in defying a better diagnosis, prognosis and therapeutic treatment.
Critical reviews in oncology/hematology 04/2011; 81(3):207-23. · 5.27 Impact Factor
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ABSTRACT: Biliary tract carcinomas are relatively rare, representing less than 1% of cancers. However, their incidence has increased in Japan and in industrialized countries like the USA. Biliary tract tumors have a poor prognosis and a high mortality rate because they are usually detected late in the course of the disease; therapeutic treatment options are often limited and of minimal utility. Recent studies have shown the importance of serum and molecular markers in the diagnosis and follow up of biliary tract tumors. This review aims to introduce the main features of the most important serum and molecular markers of biliary tree tumors. Some considerable tumor markers are cancer antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen, chromogranin A, mucin 1, mucin 5, alpha-fetoprotein, claudins and cytokeratins.
World journal of gastrointestinal oncology. 04/2011; 3(4):49-59.
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ABSTRACT: The residual liver function is a major clinical index in hepatocellular carcinoma (HCC) patients. As the liver plays a crucial role in lipid and lipoprotein metabolism, the significant impairment of the hepatic function occurring during chronic liver diseases, such as HCC, can influence plasma lipoprotein profiles. Although, lipoprotein(a) (Lp(a)) circulating concentrations are mostly determined by genetic factors, in the majority of reports they have shown a correlation with the hepatic status and a significant decrease in HCC and liver cirrhosis patients than among the controls. In such a way, Lp(a) may represent a new additional and useful marker for a more complete assessment and monitoring of the liver function in patients with HCC and liver cirrhosis. Further studies are needed in order to evaluate the clinical significance of Lp(a) in HCC.
Indian journal of medical and paediatric oncology 04/2011; 32(2):71-5.
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Mario Testini,
Angela Gurrado,
Nicola Avenia,
Rocco Bellantone,
Antonio Biondi,
Paolo Brazzarola,
Filippo Calzolari,
Giuseppe Cavallaro,
Giorgio De Toma,
Pietro Guida,
Germana Lissidini,
Michele Loizzi,
Celestino Pio Lombardi,
Giuseppe Piccinni,
Piero Portincasa,
Lodovico Rosato,
Nora Sartori,
Chiara Zugni, Francesco Basile
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ABSTRACT: To compare the outcome in patients with cervical goiters and cervicomediastinal goiters (CMGs) undergoing total thyroidectomy using the cervical or extracervical approach.
This was a retrospective study conducted at six academic departments of general surgery and one endocrine-surgical unit in Italy. The study population consisted of 19,662 patients undergoing total thyroidectomy between 1999 and 2008, of whom 18,607 had cervical goiter (group A) and 1055 had CMG treated using a cervical approach (group B, n = 986) or manubriotomy (group C, n = 69). The main parameters of interest were symptoms, gender, age, operative time, duration of drain, length of hospital stay, malignancy and outcome.
A split-sternal approach was required in 6.5% of cases of CMG. Malignancy was significantly more frequent in group B (22.4%) and group C (36.2%) versus group A (10.4%; both P < .001), and in group C versus group B (P = .009). Overall morbidity was significantly higher in groups B + C (35%), B (34.4%) and C (53.5%) versus group A (23.7%; P < .001). Statistically significant increases for group B + C versus group A were observed for transient hypocalcemia, permanent hypocalcemia, transient recurrent laryngeal nerve (RLN) palsies, permanent RLN palsies, phrenic nerve palsy, seroma/hematoma, and complications classified as other. With the exception of transient bilateral RLN palsy, all of these significant differences between group B + C versus group A were also observed for group B versus group A.
Symptoms, malignancy, overall morbidity, hypoparathyroidism, RLN palsy and hematoma are increased in cases of substernal goiter.
Annals of Surgical Oncology 02/2011; 18(8):2251-9. · 4.17 Impact Factor
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Marco Ragusa,
Alessandra Majorana,
Luisa Statello,
Marco Maugeri,
Loredana Salito,
Davide Barbagallo,
Maria Rosa Guglielmino,
Laura R Duro,
Rosario Angelica,
Rosario Caltabiano,
Antonio Biondi,
Maria Di Vita,
Giuseppe Privitera,
Marina Scalia,
Alessandro Cappellani,
Enrico Vasquez,
Salvatore Lanzafame, Francesco Basile,
Cinzia Di Pietro,
Michele Purrello
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ABSTRACT: The relationship between therapeutic response and modifications of microRNA (miRNA) transcriptome in colorectal cancer (CRC) remains unknown. We investigated this issue by profiling the expression of 667 miRNAs in 2 human CRC cell lines, one sensitive and the other resistant to cetuximab (Caco-2 and HCT-116, respectively), through TaqMan real-time PCR. Caco-2 and HCT-116 expressed different sets of miRNAs after treatment. Specifically, 21 and 22 miRNAs were differentially expressed in Caco-2 or HCT-116, respectively (t test, P < 0.01). By testing the expression of differentially expressed miRNAs in CRC patients, we found that miR-146b-3p and miR-486-5p are more abundant in K-ras-mutated samples with respect to wild-type ones (Wilcoxon test, P < 0.05). Sixty-seven percent of differentially expressed miRNAs were involved in cancer, including CRC, whereas 19 miRNA targets had been previously reported to be involved in the cetuximab pathway and CRC. We identified 25 transcription factors putatively controlling these miRNAs, 11 of which have been already reported to be involved in CRC. On the basis of these data, we suggest that the downregulation of let-7b and let-7e (targeting K-ras) and the upregulation of miR-17* (a CRC marker) could be considered as candidate molecular markers of cetuximab resistance. Global network functional analysis (based on miRNA targets) showed a significant overrepresentation of cancer-related biological processes and networks centered on critical nodes involved in epidermal growth factor receptor internalization and ubiquitin-mediated degradation. The identification of miRNAs, whose expression is linked to the efficacy of therapy, should allow the ability to predict the response of patients to treatment and possibly lead to a better understanding of the molecular mechanisms of drug response.
Molecular Cancer Therapeutics 09/2010; 9(12):3396-409. · 5.23 Impact Factor
