Cesare Formisano

Arachidonate geometrical isomers generated by thiyl radicals: the relationship with trans lipids detected in biological samples.

The presence of trans fatty acids in mammalians is attributed to exogenous sources; nevertheless, trans isomers could be easily formed by free radical-catalyzed isomerization processes in vivo. The isomerization of methyl arachidonate (all-cis isomer) catalyzed by thiyl radical is proposed as a methodology applicable in biochemical laboratories, which produces mono- and di-trans isomers. Carbon-13 nuclear magnetic resonance spectroscopy shows that the carbon atom in position 15 is characteristic for each mono- and di-trans isomer. Antioxidants, such as alpha-tocopherol and all-trans-retinol acetate, inhibited the isomerization process. Trans phospholipids are formed in erythrocyte membranes by exposing blood to gamma-irradiation in the presence of thiols, which is in contradiction with the known role of these compounds as radioprotectors. Trans isomers are also analyzed in tissues harvested from breast cancer patients and compared to the adipose breast tissue taken a few centimeters from the edge of the tumor from the same patient. This work is generally aimed at contributing to the debate on trans fatty acids and stimulating a reconsideration of the current view on the exclusive presence of cis double bonds in cell membranes by studying radical processes that could affect or protect this natural configuration.

Laparotomic vs Laparoscopic Lap-Band: 4-year Results with Early and Intermediate Complications

Background: Adjustable banding is safe, low invasive, and effective for losing weight. Methods: 69 patients underwent this procedure by laparotomy or laparoscopy. Results: Patients operated by laparotomy lost more weight than those operated by laparoscopy, but in 4 patients we were forced to re-operate in order to remove the band (3 pouch dilatations and 1 stomach slippage), and in 9 patients a ventral hernia appeared (5 patients repaired). In the laparoscopic cases there were 4 intra-operative gastric perforations, but all were repaired and the band placed at the same time (3 conversions to open), causing an increased post-operative hospital stay.There was a lower limb deep venous thromboembolism, which was followed by fatal pulmonary embolism (although the patient had been given heparin and had been treated with elastocompression and mobilization 2 hours after surgery). The band eroded in one patient. Weight losses in these morbidly obese patients were satisfactory at 2 years and maintained beyond 3 years. Conclusion: Laparoscopic adjustable banding is an efficient, generally safe procedure.

Solitary necrotic nodule of the liver misinterpreted as malignant lesion: considerations on two cases.

In our experience, we document 2 cases of a rare and non‐tumoral lesion of the liver misinterpreted as necrotic tumor: necrotic solitary nodule. In the first clinical case, ultrasound (US) showed a polylobated lesion (35 × 35 × 38 mm) at segment 8. Color‐doppler identified a compression of celiac axis (Dunbar syndrome). Arteriography revealed a subtotal stenosis of celiac tripod soon after the emergence of the left gastric artery. FNAB‐CT showed a highly cellulated tissue with a necrotic core surrounded by a fibersclerotic tissue. The patient underwent surgery: cholecystectomy and correction of Dunbar syndrome. US follow‐up showed a progressive reduction in diameter of the lesion (24 × 25 × 25 mm at 24 months), suggesting in this case the role of ischemic injury in the pathogenesis of the lesion.

Hexadecenoic Fatty Acid Isomers in Human Blood Lipids and Their Relevance for the Interpretation of Lipidomic Profiles.

Monounsaturated fatty acids (MUFA) are emerging health biomarkers, and in particular the ratio between palmitoleic acid (9cis-16:1) and palmitic acid (16:0) affords the delta-9 desaturase index that is increased in obesity. Recently, other positional and geometrical MUFA isomers belonging to the hexadecenoic family (C16 MUFA) were found in circulating lipids, such as sapienic acid (6cis-16:1), palmitelaidic acid (9trans-16:1) and 6trans-16:1. In this work we report: i) the identification of sapienic acid as component of human erythrocyte membrane phospholipids with significant increase in morbidly obese patients (n = 50) compared with age-matched lean controls (n = 50); and ii) the first comparison of erythrocyte membrane phospholipids (PL) and plasma cholesteryl esters (CE) in morbidly obese patients highlighting that some of their fatty acid levels have opposite trends: increases of both palmitic and sapienic acids with the decrease of linoleic acid (9cis,12cis-18:2, omega-6) in red blood cell (RBC) membrane PL were reversed in plasma CE, whereas the increase of palmitoleic acid was similar in both lipid species. Consequentially, desaturase enzymatic indexes gave different results, depending on the lipid class used for the fatty acid content. The fatty acid profile of morbidly obese subjects also showed significant increases of stearic acid (C18:0) and C20 omega-6, as well as decreases of oleic acid (9cis-18:1) and docosahexaenoic acid (C22:6 omega-3) as compared with lean healthy controls. Trans monounsaturated and polyunsaturated fatty acids were also measured and found significantly increased in both lipid classes of morbidly obese subjects. These results highlight the C16 MUFA isomers as emerging metabolic marker provided that the assignment of the double bond position and geometry is correctly performed, thus identifying the corresponding lipidomic pathway. Since RBC membrane PL and plasma CE have different fatty acid trends, caution must also be used in the choice of lipid species for the interpretation of lipidomic profiles.

Automodification of PARP and fatty acid-based membrane lipidome as a promising integrated biomarker panel in molecular medicine

AIM Establishing by statistical analyses whether the analyses of auto-modified poly(ADP-ribose)polymerase and erythrocyte membrane fatty acid composition (Fat Profile(®)), separately or in tandem, help monitoring the physio-pathology of the cell, and correlate with diseases, if present. PATIENTS & METHODS Ninety five subjects were interviewed and analyzed blindly. Blood lymphocytes and erythrocytes were prepared to assay poly(ADP-ribose)polymerase automodification and fatty acid based membrane lipidome, respectively. RESULTS Poly(ADP-ribose)polymerase automodification levels confirmed their correlation with DNA damage extent, and allowed monitoring disease activity, upon surgical/therapeutic treatment. Membrane lipidome profiles showed lipid unbalance mainly linked to inflammatory states. Statistically both tests were separately significant, and correlated each other within some pathologies. CONCLUSION In the laboratory routine, both tests, separately or in tandem, might be a preliminary and helpful step to investigate the occurrence of a given disease. Their combination represents a promising integrated panel for sensible, noninvasive and routine health monitoring.

Comparison between tungsten and steel polypectomy snares: evaluation of depth of colonic thermal wall injury in a pig model.

BACKGROUND AND STUDY AIMS Thermal injury of the colonic wall during polypectomy may induce complications such as bleeding and perforation. To date, the role of the snare material in these injuries has not been examined. The aim of this study was to evaluate the depth of colonic post-polypectomy thermal wall injury induced by tungsten and steel endoscopic snares, in an effort to reduce electrosurgery-related complications. MATERIALS AND METHODS This was a single tertiary center experimental study in a porcine model. A total of 90 polypectomies where performed in three live pigs under general anesthesia, using both steel and tungsten snares by cut, coagulation, and blend current modes. The pigs were then euthanized and their colons examined histologically. RESULTS Steel snares induced significantly deeper tissue injury than tungsten snares in the pure cut mode (Pearson χ2 = 6.136, P = 0.013). The ordinal logistic regression analysis showed that the current mode and snare material were significantly associated with the ordinal score for the depth of injury. Thus, cut mode was positively associated with a lower score and coagulation mode with a higher score. In addition, tungsten was significantly associated with a lower depth of tissue injury. CONCLUSIONS Due to its inherent electrical properties, tungsten is very well suited for manufacture into electrosurgical endoscopic devices. Thus, tungsten snares may be advantageous for routine use in endoscopic polypectomy, although further studies are needed to confirm these promising findings in human patients.

Auto-Modification of Poly (ADP-Ribose) Polymerase and Membrane LipidComposition as Diagnostic Tools to Measure the Physio-Pathological Stateof the Cell

Poly(ADPribosyl)ation, catalysed by poly(ADP-ribose)polymerases, affects many cellular events and has a recognized epigenetic role. Nuclear poly(ADP-ribose)polymerases 1 and 2 are hyper activated by DNA strandbreaks. They auto-modify with large polymers of ADP-ribose and recruit DNA repair proteins. The more the DNA strand-breaks, the more poly(ADP-ribose) polymerase modifies itself. On the other hand, dietary lipids can be signaling molecules, lead to pro-(ω6)/ anti-(ω3) inflammatory compounds, and be included in biomembranes, good biomarkers of their unbalance. Here, we report the results obtained from an epidemiological study to establish whether the combination of two different analyses, i.e. detecting auto-modified poly (ADP-ribose) polymerase levels and analyzing erythrocyte membrane fatty acid composition, might help to monitor the physio-pathological state of the cell, and to correlate with lifestyle, diet or diseases. The two analyses were carried blindly on 70 subjects undergoing endoscopy. They were first interviewed, to collect anamnesis and clinical data, if present. Lymphocytes and erythrocytes were prepared from venous blood to assay poly (ADP-ribose) polymerase auto modification and membrane fatty acid content, respectively. The results were statistically evaluated. The measure of poly (ADP-ribose) polymerase automodification confirmed that its levels correlate with DNA damage extent, within the same pathology, and allowed to monitor the clinical activity of the disease, depending on ongoing therapeutic/surgical treatment. Membrane fat profile was able to evidence unbalance of lipids linked to both diet/lifestyle and inflammatory states leading to diseases. Both analyses provide possible biomarkers for sensible, non-invasive and routine monitoring.

Endoscopic Surveillance After Polypectomy

Colorectal cancer (CRC) represents the second cause of cancer mortality in Western countries after lung tumors. Its incidence is increasing in Eastern countries too, because of westernization of eating habits and aging of the population. However, since the mid-80s we are seeing a CRC incidence decline in Western countries mainly due to the screening programs. Adenomatous polyps are the most commonly found neoplastic lesions during screening colonoscopy. Patients with adenomas have an increased risk for developing metachronous adenomas or cancers compared with patients without adenomas. Modern guidelines are based on the findings of a randomized trial conducted in 1993 comparing 1-year versus 3-year surveillance intervals after polypectomy (the American National Polyp Study). Likewise, several European countries developed their own guidelines thus pushing the launch of well-organized population-based screening programs. Current American, European, and Korean guidelines for endoscopic surveillance after colorectal polypectomy were published in 2012. Japanese endoscopy society, conversely, has not yet developed specific guidelines and refers to a position statement about management of colorectal polyps, published in 2015.

Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system

Abstract The authors evaluated the role of endoscopic techniques in the diagnosis and in the potential treatment of neuroendocrine tumors (NET) localized in the gastro-entero-pancreatic system, on the basis of their experience and of the international literature. NET are rare tumors that arise from neuroendocrine cells of the gastrointestinal tract and pancreas. It is a possibility that both the digestive endoscopy and EUS play an important role in the diagnosis, staging and surveillance of this disease. In some cases, especially in the early stages, surgical endoscopy allows the treatment of such tumors.

Correction: Lobular intraepithelial neoplasia arising within breast fibroadenoma

After publication of our article [1], it has come to our attention that Professor Cesare Formisano was incorrectly excluded from the list of authors in the initial version of this manuscript. We publish this correction to update the author list to include Professor Formisano as an author. The correct author list is as follows: