Nicola Carlomagno

Three submicroscopic deletions at the APC locus and their rapid detection by quantitative-PCR analysis.

We describe three unrelated kindreds, affected by familial adenomatous polyposis (FAP), with 5q submicroscopic deletions that encompass the entire adenomatous polyposis coli (APC) gene and the adjacent DP1 gene. In one family the deletion encompasses also the MCC (mutated in colon cancer) gene. Affected members of these families had dysplastic adenomatous polyps and congenital hypertrophy of the retinal pigment epithelium (CHRPE); no individual was affected by mental retardation or facial dysmorphism. The deletions were detected by linkage analysis with several intragenic and closely flanking polymorphic markers and confirmed by a quantitative PCR analysis. This procedure could have an impact on the detection of the molecular defect in FAP patients in whom mutational analysis fails to identify the specific mutation.

Familial Adenomatous Polyposis Coli: Five Novel Mutations in Exon 15 of the Adenomatous Polyposis Coli (APC) Gene in Italian Patients

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ‐line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain‐terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction‐single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.

Three Novel Germline Mutations in the Adenomatous Polyposis Coli Gene

Maria 1. Scarano, Marina De Rosa, Maurizio Gentile, Luigi Bucci, Giuseppe P. Ferulano, Nicola Carlomagno, Andrea Renda, Ginevra Guanti, Francesco Salvatore*, and Paola Izzo Dipartimento di Biochirnica e Biotecnologie Mediche, CEINGE-Biotechnologie Avanzate, Naples, Italy; Fax: + 39-81-746-3650 II Divisione di Chirurgia Generale III Divisione di Chirurgia Generale Instituto di Chirurgia Generale e Trapiand d’Organo, Medical School, University of Naples Federico 11, 80131 Naples Cattedra di Genetica Medica, Istituto di Medicina del Lavoro, Policlinico, Bari, Italy

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.

Familial adenomatous polyposis coli: five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online.

Since the identification of the BRCA1 and BRCA2 genes (MIM#s 113705 and 600185), more than hundred different mutations throughout both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. We analyzed 12 sporadic female patients with breast cancer before age 35, as well as 16 unrelated families, presenting with either (i) at least 3 first degree relatives with breast and/or ovarian cancer diagnosed at any age, or (ii) at least 2 first and/or second degree relatives with breast and/or ovarian cancer before age 45 years. We performed a protein truncation test for BRCA1 exon 11 and BRCA2 exons 10 and 11 and heteroduplex analysis for all the remaining exons of BRCA1 and 2. Presence of genomic deletions encompassing exons 13 or 22 of BRCA1, known to be Dutch founder mutations, was investigated by PCR. In 6/16 (37.5%) unrelated families the causal mutation in either the BRCA1 or BRCA2 gene was identified. Four different mutations were found in the BRCA1 gene: IVS5+3A>G (intron 5), 1191delC (exon 11), R1443X (exon 13), IVS22+5G>A (intron 22) and two in the BRCA2 gene: 6503delTT (exon 11), 6831delTG (exon 11). 1191delC (BRCA1) and 6831delTG (BRCA2) are novel mutations. IVS5+3A>G in exon 5 of BRCA1 published by Peelen et al. (1997) as a novel Belgian mutation, was identified in one additional family, not fulfilling our inclusion criteria. In the group of 12 sporadic female patients no mutations were found.

Temperature profile of ex-vivo organs during radio frequency thermal ablation by fiber Bragg gratings

Abstract. We report on the integration of fiber optic sensors with commercial medical instrumentation for temperature monitoring during radio frequency ablation for tumor treatment. A suitable configuration with five fiber Bragg grating sensors bonded to a bipolar radio frequency (RF) probe has been developed to monitor the area under treatment. A series of experiments were conducted on ex-vivo animal kidney and liver and the results confirm that we were able to make a multipoint measurement and to develop a real-time temperature profile of the area, with a temperature resolution of 0.1°C and a spatial resolution of 5 mm during a series of different and consecutive RF discharges.

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.

Intraperitoneal dedifferentiated liposarcoma showing MDM2 amplification: case report

BackgroundLiposarcoma is the most common type of soft tissue sarcoma (STS). It is divided into five groups according to histological pattern: well-differentiated, myxoid, round cell, pleomorphic, and dedifferentiated. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare. Only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We report a case initially diagnosed as undifferentiated sarcoma that was reclassified as intraperitoneal dedifferentiated liposarcoma showing an amplification of the MDM2 gene.Case presentationA 59-year-old woman with abdominal pain and constipation was referred to the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy, in November 2012. On physical examination, a very large firm mass was palpable in the meso-hypogastrium. Computed tomography (CT) scan showed a heterogeneous density mass (measuring 10 × 19 cm) that was contiguous with the mesentery and compressed the third part of the duodenum and jejunum.At laparotomy, a large mass occupying the entire abdomen was found, adhering to the first jejunal loop and involving the mesentery. Surgical removal of the tumor along with a jejunal resection was performed because the first jejunal loop was firmly attached to the tumor.Macroscopic examination showed a solid, whitish, cerebroid, and myxoid mass, with variable hemorrhage and cystic degeneration, measuring 26 × 19 × 5 cm. Microscopic examination revealed two main different morphologic patterns: areas with spindle cells in a myxoid matrix and areas with pleomorphic cells. The case was initially diagnosed as undifferentiated pleomorphic sarcoma. Histological review showed areas of well-differentiated liposarcoma. Fluorescence in situ hybridization (FISH) analysis was performed and demonstrated an amplification of the MDM2 gene. Definitive diagnosis was intraperitoneal dedifferentiated liposarcoma.No adjuvant therapy was given, but 5 months after laparotomy, the patient presented with a locoregional recurrence and chemotherapy with high-dose ifosfamide was started.ConclusionsNo guidelines are available for the management of intraperitoneal dedifferentiated liposarcoma. We report this case to permit the collection of a larger number of cases to improve understanding and management of this tumor. Moreover, this study strongly suggests that poorly differentiated sarcomas should prompt extensive sampling to demonstrate a well-differentiated liposarcoma component and, if possible, FISH analysis.

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.

What indication, morbidity and mortality for central pancreatectomy in oncological surgery? A systematic review.

Conventional pancreatic resections for pancreatic neck and body diseases include pancreaticoduodenectomy, distal pancreatectomy with or without splenectomy, and total pancreatectomy. Recent studies have reported encouraging results of non-traditional pancreatic resections, including central pancreatectomy (CP), for central pancreatic disease. This surgical approach offers the potentials of low postoperative morbidity and preservation of metabolic functions. This study performs a systematic review on CP. A comprehensive literature search was conducted, for the period 1992-2015, on three worldwide databases: PubMed, Scopus, ISI-Web of Knowledge. We focused on indications, morbidity and mortality of this surgical procedure. The review shows that CP is particularly suitable for small-medium size diseases localized into the pancreatic body. This procedure is associated with an increased postoperative morbidity but an excellent postoperative pancreatic function. CP is a safe and effective procedure when performed following the right indications.