Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance.</p> <p>Methods</p> <p>In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.</p> <p>Results</p> <p>In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106).</p> <p>The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.</p> <p>Conclusions</p> <p>The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.</p

Gestione del rischio nelle attività chirurgiche e procedure invasive

Gli autori discutono la presentazione e gestione delle principali complicanze chirurgiche in chirurgia generale

Strangulated adenoma of the liver: a unique cause of acute abdomen

Hepatic adenomas are uncommon benign tumours of the liver which may eventually present with acute onset following rupture of the lesion and haemorrhage. We present here a unique case of strangulated adenoma of the liver presenting as acute abdomen. A 27-year-old woman taking oral contraceptives, presented to the emergency department with abdominal pain, palpable abdominal mass, fever, and neutrophilia. An abdominal ultrasound showed a 3-cm hepatic nodule and an 11-cm mesogastric mass. Computed tomography of the abdomen revealed a 2.3-cm liver adenoma and a 13-cm pedunculated mass of the liver showing no contrast enhancement suggestive of pedicle torsion with ischemia of the mass. The patient underwent an emergent open resection of the strangulated liver mass, she recovered without complications, and was discharged home after three days. Final pathology confirmed an hepatocellular adenoma with areas of necrosis and hemorrhage. The clinical significance of the disease is discussed

Treatment and prognosis of endocrine tumors of gastrointestinal tract and pancreas: A retrospective study about 16 cases.

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Inflammation in venous disease.

Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated

Preoperative dexamethasone improves postoperative nausea and vomiting following laparoscopic cholecystectomy: A randomised controlled trial.

Background: Preoperative dexamethasone may reduce disabling symptoms such as pain, nausea and vomiting after laparoscopic cholecystectomy. Methods: This was a randomized, double-blind, placebo-controlled trial. Between March and December 2004, 101 patients undergoing laparoscopic cholecystectomy were randomized to receive 8 mg dexamethasone (n = 49) or placebo (n = 52) intravenously before surgery. Six patients were excluded from the study. All patients received a standardized anaesthetic, surgical and multimodal analgesic treatment. The primary endpoints were: first, postoperative nausea, vomiting and pain; second, postoperative analgesic and antiemetic requirements. The pain scores (visual analogue and verbal response scales), the episodes of nausea (verbal response scale) and vomiting were recorded at 1, 3, 6 and 24 h, respectively, after the operation. Analgesic and antiemetic requirements were also recorded. Results: No apparent drug side-effects were noted. Seven patients (14 per cent) in the treatment group reported nausea and vomiting compared with 24 (46 per cent) in the control group (P = 0·001). In the group of patients treated with dexamethasone, five (10 per cent) required antiemetics versus 23 (44 per cent) of those receiving placebo (P < 0·001). No difference in postoperative pain scores and analgesic requirements was detected between groups. Conclusion: Preoperative dexamethasone reduces postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy, with no side-effects, and may be recommended for routine us

Accuracy and reliability of sentinel node biopsy in patients with breast cancer. Single centre study with long term follow-up.

The aim of our study is to evaluate the frequency of false-negative (FN) sentinel node procedures in patients with breast cancer. A total of 791 breast cancer patients underwent sentinel lymph node (SLN) biopsy at our institution between July 1997 and February 2005. A 2-day protocol was used to localise the sentinel node with the injection of 99mTc-nanocolloid. There were two phases in the study: the learning phase (50 patients) and the application phase (741 patients). In the learning phase, a complete lymphadenectomy was always performed. In the application phase, sentinel nodes were studied postoperatively with breast cancer and lymphadenectomy was performed when considered warranted by the pathological postoperative results. The median follow-up duration in the 741 patients studied during the application phase was 32.3 months (range 6-72 months). In this phase a total of 787 sentinel nodes (719 axillary and 68 intramammary chain) were obtained (range 0-5 per patient, mean 1.01), with 153 (41 with micrometastasis) positive sentinel nodes. We observed a total of three FN SLN results (0.5%). All three presented as an axillary recurrence into 24 months from operation. After a median follow-up of 32.3 months we observed only three clinical recurrences among 741 patients. Our results indicate that the sentinel node protocol can give an adequate local control