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Lynch syndrome (LS) is caused by a germline mutations in DNA mismatch repair genes and is a dominantly inherited syndrome, responsible for 2-5% of all colorectal cancer (CRC) cases. Mutation carriers have a 60-85% risk of developing CRC. With the increasing use of genetic predisposition testing, patients and health care providers must decide on cancer risk-reduction strategies. The cancers observed in families with LS are diagnosed at an unusually early age and may be multiple. The decision about which surgery is suitable should be made on the basis of patient factors and preferences, with special emphasis on age, comorbidity, sphincteric function, and the ability of the patient to cope with intensive surveillance. Colectomy decreases the risk of second CRC significantly. The estimated lifetime risk for endometrial adenocarcinoma is 40-60% in women with LS, and the mean age at diagnosis is around 50 years. This risk equals or exceeds the risk of CRC. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. Patients who are gene mutation carriers should receive counseling about colectomy, and if women, prophylactic hysterectomy and bilateral oophorectomy. [ABSTRACT FROM AUTHOR]

For a long time, the endothelial covering of the vessels has been considered an inert surface. On the contrary, the endothelial cells are active and dynamic elements in the interaction between blood and tissues. The control of the vessel basal tone is obtained by the complex balance between the relaxing and contracting endothelial factors. Previous clinical studies show that patients suffering from rheumatoid arthritis and other autoimmune rheumatologic pathologies are at high risk of death being prematurely affected by atherosclerosis and cardiovascular diseases. Blocking tumor necrosis factor (TNF)-α by biological drugs improves the endothelial function. The aim of our study was to evaluate the effects of two anti-TNF-α drugs (infliximab and etanercept) on the endothelial function by evaluating the flow-mediated dilatation (FMD), which was measured in the brachial artery before and after treatment and after 8-12 weeks. We enrolled 36 patients (average age 52 ± 9.8 years, 12 men and 24 women), 25 of them were affected by rheumatoid arthritis (RA) and 11 were affected by psoriatic arthritis (PsA) and they were divided into three groups: 10 patients were treated with etanercept, 13 patients were treated with infliximab, 13 patients were treated with DMARDs. We measured the common carotid intimal-medial thickness (ccIMT) and the endothelial function was evaluated by FMD measurement in the brachial artery, before treatment, 1 h after the beginning of treatment and after 8-12 weeks. No statistically significant difference between the three groups was found for the ultrasonographic evaluation of the carotid IMT. On the contrary, the differences between FMD values before and after the treatment in the patients treated with etanercept (13.1 ± 0.01 vs. 18.8 ± 0.01%, p < 0.01) and in the patients treated with infliximab (11.8 ± 0.09 vs. 16.7 ± 0.09%, p < 0.01) were statistically significant. Long-term evaluation for infliximab and etanercept was performed by comparing the FMD values, respectively, 8 and 12 weeks after the first treatment. After 8 weeks, FMD value was similar to the value recorded at enrollment in the infliximab group (11.9 ± 0.03 vs. 13.54 ± 0.04%, p = 0.236) and the FMD values in the etanercept group after 12 weeks showed a not statistically significant reduction of vasodilatating effect (13.01 ± 0.03 vs. 15.67 ± 0.02%, p = 0.197). In conclusion, the use of biological drugs in patients affected by autoimmune arthritis can modify the endothelial function, as indicated by the induced FMD changes, but the long-term effect tends to be considerably reduced. [ABSTRACT FROM AUTHOR]

Adiponectin is known to play a role in fatty acid and glucose metabolism through a change in insulin sensitivity and activation of fuel oxidation by AMP-activated protein kinase. Adiponectin can be considered an important factor able to modulate the adipovascular axis which, through genomic and environmental influences, affects the cardiovascular risk milieu, from the pre-metabolic syndrome-- through the metabolic syndrome--to the overt atherosclerotic process and its clinical manifestations. Hypoadiponectinaemia can be viewed as an early sign of a complex cardiovascular risk factor predisposing to the atherosclerosis process as well as a contributing factor accelerating the progress of the atherosclerotic plaque. In addition, adiponectin per se holds a protective role thanks to its anti-inflammatory and antiatherogenic properties. The early identification of patients "at cardiovascular risk" means in the current practice to search for indexes of metabolic derangements and pro-inflammatory status (adiponectin) from adolescence and childhood. [ABSTRACT FROM AUTHOR]

Background Chronic liver diseases are frequently complicated by portal hypertension, an important component of which is the increased intrahepatic vascular resistance, in part related to endothelial dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an established mediator and marker of endothelial dysfunction. We therefore investigated the possible implication of ADMA in chronic liver diseases-induced portal hypertension. Materials and methods We studied 39 consecutive patients with compensated hepatitis C virus (HCV) related chronic liver diseases. All patients underwent hepatic venous pressure gradient (HVPG) measurement, and simultaneous blood sampling from the hepatic vein and the pulmonary artery, for ADMA and nitrite/nitrate (NOx) plasma level determinations. Results A positive correlation between HVPG and ADMA concentrations in hepatic veins (ADMA- h) was found ( r = 0·77, P < 0·0001). Moreover, a negative correlation between HVPG and NOx concentrations in the hepatic veins (NO- h) ( r = −0·50, P = 0·005), and between ADMA- h and NO- h was observed ( r = −0·40, P = 0·02). ADMA concentrations in pulmonary artery (ADMA- p) (0·55 ± 0·13 µmol L−1) were significantly higher than in hepatic veins (0·47 ± 0·09 µmol L−1) ( P < 0·0001). Conclusions These results suggest that ADMA may play a pathophysiological role in portal hypertension by contributing to the relative intrahepatic NO deficiency typical of endothelial dysfunction. [ABSTRACT FROM AUTHOR]

To investigate diurnal profile of leptin and β-endorphin circulating levels and to assess any possible influence between these two peptides, 24-h serum concentrations of leptin and β-endorphin were examined in 24 obese (BMI 32.1 ± 1.3) women and in 12 controls (BMI 21 ± 0.5). Blood samples for leptin and β-endorphin determinations were drawn every four hours for 24 hours beginning at 8.00 am. Data were analyzed by unpaired t-test, linear regression and by inferential statistical procedures. We found a significant circadian rhythm for both peptides, either in obese or in controls. The 24-h mean leptin levels were significantly (p < 0.0001) higher (32.1 ± 2.8 ng/ml; mean ± SE) in obese women than controls (13.6 ± 1.1), with a peak time located after midnight in obese and controls. The 24-h β-endorphin mean levels were significantly (p < 0.0001) higher in obese than controls (30.6 ± 2 vs 22 ± 1.9 pg/ml), with acrophase located in the early morning hours in both groups. Finally, we found a positive relationship (R² = 0.303; p = 0.0005) between leptin and β-endorphin circadian mean levels. These results show that the time course of 24-h rhythm of leptin and β-endorphin are similar in obese and lean women. The positive relationship between 24-h leptin and β-endorphin mean levels allow us to speculate that leptin may be a likely candidate to increase β-endorphin levels in obese subjects. [ABSTRACT FROM AUTHOR]

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02±2.9 pg/ml vs 4.4±1.1 pg/ml and 3.08±0.7 pg/ml, respectively; P<0.001). No difference was demonstrated between diabetic patients without angiopathy and controls. These findings suggest that ET-1 may be a marker for arterial vascular disease only in patients with overt angiopathy. It is unclear whether it participates in the endothelial injury process or it is merely released from damaged endothelial cells. [ABSTRACT FROM AUTHOR]

The use of polytetrafluoroethylene (PTFE)-covered prostheses improves trans-jugular intrahepatic porto-systemic shunt (TIPS) patency and decreases the incidence of clinical relapses and re-interventions. Therefore, the improvement provided by covered stents might expand the currently accepted recommendations for TIPS use. Stent-related occlusion of the hepatic vein with consequent ischaemia of the corresponding liver parenchyma emerges as a novel complication reported in at least 5% of patients implanted with coated stents. However, this complication was reported to be mild, without signs or symptoms of liver failure, and self-limiting. We report a case of segmental liver ischaemia following PTFE-covered stent placement resulting in a marked impairment in liver function in a patient with hepatitis C virus cirrhosis implanted because of refractory oesophageal bleeding, thus expanding the severity range of this new procedural complication. Moreover, we discuss the possible involvement of additional pathogenetic mechanisms other than out-flow obstruction in the onset of coated-stent induced congestive liver ischaemia. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy of gastric cancer after curative resection is still subject to discussion. In this study 137 patients with gastric adenocarcinoma, all with positive nodes, were randomized after curative resection so that 69 received epidoxorubicin (EPI), leucovorin (LV) and 5-fluorouracil (5-FU) on days 1-3 every 3 weeks for 7 months, whereas the remaining 68 did not. After a follow-up period of 5 years, 21 of the 69 treated patients (30%) and nine controls (13%) were still alive; median survival time was 18 months for the controls and 31 months for the patients treated with adjuvant chemotherapy (P < 0.01). [ABSTRACT FROM AUTHOR]

The abundance of endothelial cells in bone marrow and the proximity of these cells to osteoclasts and osteoblasts suggest a role for endothelin-1 (ET-1) on bone metabolism. In vitro, the direct contact with bone endothelial cells induces osteoclastic progenitors to differentiate into mature elements. Recently it has been reported that ET-1 inhibits osteoclastic bone resorption and cell mobility through a specific receptor on osteoclasts; other authors demonstrated that ET-1 exerts a mitogenic activity on osteoblast-like cells (MC3T3) by stimulating tyrosin phosphorylation. We measured ET-1 circulating levels in patients with active Paget's bone disease, a condition with accelerated bone turnover. For the study we recruited 11 patients with Paget's bone disease (5F, 6M; mean age 68.2 +/- 3.6) in the acute stage of the disease; 10 healthy subjects (7F, 3M; mean age 66.5 +/- 3.9) were also enrolled as controls. Plasma ET-1 levels were measured with RIA kits provided by Nichols Institute. Patients showed significantly (P < 0.01) higher ET-1 circulating levels than controls (6.35 +/- 1.9 versus 3.4 +/- 1.2 pg/ml) with a positive correlation (r = 0.63; P = 0.038) with serum alkaline phosphatase (ALP), but not with urinary hydroxyproline. The higher levels of ET-1 in our patients suggest a physiopathological role for this peptide in the disease and, could perhaps represent a new useful marker of Paget's bone disease activity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Management of presacral hemorrhage has always been a challenge for surgeons because such bleeding can rapidly destabilize the patient. Traditional methods like electric cauterization and suture ligation often fail and can aggravate bleeding. METHODS: We report the case of a severe presacral hemorrhage that occurred during an ultra low rectal resection for cancer in a male patient. RESULTS: After failing of electric cauterization and suture ligation the hemorrhage was successfully treated with pelvic packing. CONCLUSIONS: Coagulation and suturing should be avoided because they can aggravate bleeding resulting in significant blood loss. Pelvic packing is the treatment of choice in our experience. [ABSTRACT FROM AUTHOR]