Concetta Dodaro

Changes in the MicroRNA Profile Observed in the Subcutaneous Adipose Tissue of Obese Patients after Laparoscopic Adjustable Gastric Banding

Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0. Bioinformatics predicted that these miRNAs regulate genes belonging to pathways associated with the cytoskeleton, inflammation, and metabolism. Western blot analysis showed that PPAR-alpha, which is the target gene of miR-519d, increased after LAGB, thereby suggesting an improvement in SAT lipid metabolism. Accordingly, the number and diameter of adipocytes were significantly higher and lower, respectively, at T1 versus T0. Bioinformatics predicted that the decreased levels of miR-212, miR-299-5p, and miR-671-3p at T1 concur in reducing SAT inflammation. Conclusion. We show that the miRNA profile changes after LAGB. This finding, although obtained in only three cases, suggests that this epigenetic mechanism, by regulating the expression of genes involved in inflammation and lipid metabolism, could concur to improve SAT functionality in postoperative obese patients.

Total colectomy for cancer: analysis of factors linked to patients' age.

Total colectomy (TC) is a valid option for cancer treatment in selected cases. Emergency presentation, association to familial adenomatous polyposis (FAP) or intestinal bowel disease (IBD), hereditary non-polyposis cancer (HNPCC), and synchronous tumors are the common indications to TC for cancer. Despite potential high morbidity and mortality rates for worse general health conditions of the advanced age it has even suggested for elderly patients. We reviewed our experience to analyze the current role of TC comparing different results between young and elderly patients. During the period 1990-2012, 76 patients were operated on TC for cancer. Patients were divided in two groups according to the age [<65 - group A (young) and >65 years old - group B (elderly)] and were compared their systemic and surgical complication, considering the presence of comorbidities, ASA score, lifestyle habits, elective or emergency presentation. Morbidity rate was 7.7% and 38.8% in young and elderly patients respectively. 21 systemic complications (3 in group A and 18 in group B) occurred in 17 patients (22.36%) (with the coexistence of two complications in 4 patients belonging to the group B. There were 6 surgical complications (7.9%) (3 in group A and 3 in group B): anastomotic leakage 3, major wound infections 2, postoperative bleeding 1; no intra-abdominal abscess were observed. In 2 cases (2.6%) (1 anastomotic leak and 1 intra-abdominal postoperative hemorrhage) was needed a reoperation. We observed only 2 deaths in the elderly. High ASA score and emergency were associated with worst results. Systemic complications were more frequent in elderly patients cause of significant comorbidities, while the incidence of surgical complications was similar and according to literature. Besides the classic indications, it is a viable surgical option also in cancer associated with complicated diverticulitis. Our data show that TC is a safe and effective procedure providing good results even in elderly patients, when combined with a careful preoperative evaluation and age is not an absolute controindication to this procedure.

Is total colectomy for colorectal cancer contraindicated in elderly patients

Methods We reviewed our series concerning 27 patients submitted to total colectomy for CRC between January 2000 and September 2010. Indications were: synchronous tumors, cancer in FAP, HNPCC, and emergency. We divided them into two groups according to their age: 11 (40.7%) 3 days) were compared in two groups.

Rare multiple primary malignancies among surgical patients—a single surgical unit experience

Background A remarkable number of patients presents with multiple primary malignancies (MPM) over their lifetimes. In most cases inherited syndromes, iatrogenic, or viral factors are implicated, while in some cases it is not possible to ascertain a clear aetiopathogenesis. Methods Starting from a series of 315 patients with MPM, we focused our attention on those with extremely infrequent combinations of tumours. We retrospectively analysed patients’ characteristics, type of first and second tumour and the interval between the two tumours. We made a comparison between our own data and data from surveillance, epidemiology, and end results cancer registries, the largest global series on this topic. Results Six patients presented with unusual associations, namely, central nervous system (CNS)/colon, testis/stomach, colon/CNS, CNS/kidney, uterus/soft tissue, and bone/breast. The median age was 50.5 years at the diagnosis of second neoplasm and the male:female ratio was 1:1. All six patients underwent surgery for both tumours. The median interval between the first and the second tumour was 11.3 years (range 1–36 years). Five patients were given chemotherapy as adjuvant systemic treatment, and two of them with CNS tumours also received radiotherapy. Discussion We analysed the behaviour of these rare tumours as first and second neoplasms. More frequent combinations and possible aetiological factors were evaluated. Conclusions Follow-up for patients recovering from a first tumour must be strict, as there is the risk of developing MPM, even after a long time period. Advancement in biomolecular knowledge and cooperation among different specialists are strongly needed to reduce mortality related to MPM and to foresee their occurrence.

Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study

Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome, data so far are not robust enough to justify a correlation between immunodeficiency and multiple primary malignancies in transplanted patients.

Bioinformatics in MPM: Using Decision Trees To Predict a Second Tumor Site

The availability of large databases of medical data has made it possible to apply statistical methodologies designed to deal with large data sets to medical applications. One of the largest databases, comprising data on multiple primary malignancies (MPM), is that of the NCI’s Surveillance, Epidemiology and End Results (SEER) program [1]. SEER cases have been collected since 1973, with constant updates and upgrades of the program during the subsequent years. SEER thus provides an appealing source for statistical investigations of MPM.

Current Tissue Molecular Markers in Colorectal Cancer: A Literature Review

Background Colorectal cancer (CRC) is one of the most spread neoplasia types all around the world, especially in western areas. It evolves from precancerous lesions and adenomatous polyps, through successive genetic and epigenetic mutations. Numerous risk factors intervene in its development and they are either environmental or genetic. Aim of the Review Alongside common screening techniques, such as fecal screening tests, endoscopic evaluation, and CT-colonography, we have identified the most important and useful biomarkers and we have analyzed their role in the diagnosis, prevention, and prognosis of CRC. Conclusion Biomarkers can become an important tool in the diagnostic and therapeutic process for CRC. But further studies are needed to identify a noninvasive, cost-effective, and highly sensible and specific screening test for their detection and to standardize their use in clinical practice.

Ethical Issues in the Use of Suboptimal Kidneys for Transplants: an Italian Point of View

The shortage of organs leads to the need for utilizing suboptimal kidneys for transplantation. The distinction between optimal, marginal, and suboptimal kidneys leads surgeons to face not only technical problems but also ethical and legal issues related to clinical advantages offered by the transplant of a nonstandard kidney and the acquisition of consent. Between 1999 and 2015, we performed 658 transplants, 49 (7.5%) using suboptimal kidneys. All patients were alive and with vital graft throughout follow-up. We did not encounter any major surgical complications. From a technical point of view, our experience and literature review confirm that transplant of suboptimal kidney leads to good clinical results but exposes patients to a increased risks of surgical complications. Therefore, these interventions must take place in hospitals fully prepared for this type of surgery and performed by experienced transplant surgeons with proper matching between organ and recipient. Considering the insufficient resources available, from an ethical and legal point of view, doctors play an essential role in optimizing the use of these kidneys by avoiding wastage of organs, ensuring that transplants are done in suitable patients, and that patients are fully informed and aware of the risks and benefits associated with the specific suboptimal kidney being transplanted. We believe that, in highly specialized centers, the number of suboptimal kidney transplants should be increased, as their use has shown good clinical results and carries fewer ethical issues compared with marginal kidneys. Further, suboptimal kidneys may also be proposed for use in young patients with end-stage renal disease.

Characterisation of mesenchymal colon tumour-derived cells in tumourspheres as a model for colorectal cancer progression

Cellular plasticity, the ability of cells to switch from an epitheial phenotype to a mesenchymal one and vice versa, plays a crucial role in tumour progression and metastases development. In 20-25% of patients with colon cancer and in 18% of patients with rectal cancer, metastases are present at the time of the first diagnosis. They are the first cause of colorectal cancer (CRC)-related mortality, defining stage IV CRC, which is characterized by a relatively short overall survival. We previously isolated two primary colon adenocarcinoma cell cultures that had undergone epithelial-mesenchymal transition (EMT), one with a high microsatellite instability phenotype (T88) and one with a chromosomal instability phenotype (T93). The aim of this study was to establish a model with which to study EMT, stemness features and cell plasticity in cancer progression and to examine the effects of incubation with lithium chloride (LiCl), a specific glycogen synthase kinase 3 β (GSK-3β) inhibitor, on these cellular processes. Indeed, GSK3β is an important regulator of cell survival, which promotes tumourigenesis in colon cells by facilitating the crosstalk between colorectal cancer pathways. Thus, we further characterized our system of adherent primary mesenchymal colon cancer cells and their paired tumourspheres by examining the expression and localisation of a panel of markers, including E- and N-cadherin, CD133, CD44v6, aldehyde dehydrogenase 1 (ALDH1) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5). We also characterised the molecular features of these tumourspheres and examined their response to LiCl. Furthermore, we explored the effects of LiCl on cell motility and plasticity. We demonstrated that LiCl reduced cell migration, stemness features and cell plasticity. We also observed the atypical nuclear localisation of membrane proteins, including N-cadherin, CD133 and CD44v6 in mesenchymal tumour cells. Of note, CD133 and CD44v6 appeared to localise at the plasma membrane in cells with a more epithelial phenotype, suggesting that the cytoplasmic/nuclear localisation of these proteins could favour and characterize cell plasticity in colorectal cancer progression.

Geriatric day surgery: challenge or opportunity?

Given the recent advances in anesthesia, surgery, and monitoring technology, day surgery (DS) offers potential advantages for elderly patients undergoing elective surgery. Epidemiological data show a continuous expansion of elderly population, associated with an increased demand for surgical treatments by older patients. This review summarizes current selection criteria, anaesthesiology techniques and methods for perioperative management in geriatric outpatient surgery.