Giancarlo Mansueto

Increased Oxidative Stress and Platelet Activation in Patients With Hypertension and Renovascular Disease

Background—Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system. Methods and Results—We measured the urinary excretion of 8-iso-prostaglandin (PG) F2&agr; and 11-dehydro-thromboxane (TX) B2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF2&agr; was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients , urinary 8-iso-PGF2&agr; correlated with 11-dehydro-TXB2 (rs=0.48;P <0.05) and renal vein renin (rs=0.67;P <0.005) and angiotensin II (rs=0.65;P =0.005) ratios. A reduction in 8-iso-PGF2&agr; after angioplasty was observed in RVD patients with high baseline levels of lipid peroxidation. Changes in 8-iso-PGF2&agr; were related to baseline lipid peroxidation (rs=−0.73;P <0.001), renal vein angiotensin II (rs=−0.70;P <0.01) and renin (rs=−0.63;P <0.05) ratios. Conclusions—Lipid peroxidation is markedly enhanced in hypertensive patients with RVD and is related to activation of the renin-angiotensin system. Moreover, persistent platelet activation triggered or amplified by bioactive isoprostanes may contribute to the progression of cardiovascular and renal damage in this setting.

A Prospective Controlled Trial on Effect of Percutaneous Transluminal Angioplasty on Functioning Arteriovenous Fistulae Survival

Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P < 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P < 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.

Neuroendocrine pancreatic tumor: value of contrast enhanced ultrasonography.

The recently introduced contrast-enhanced ultrasonography (CEUS) has led to a great development in the diagnostic abilities of US. Second-generation contrast media, characterized by harmonic responses at low acoustic pressures (low mechanical index) of the US beam, have proved their usefulness in the study of the liver, but other abdominal organs can benefit from the dynamic study that derives from the nonlinear response during continuous US scans. The study of the pancreas is a new and promising application of CEUS, especially in the evaluation of hypervascular lesions, such as neuroendocrine pancreatic tumors. Neuroendocrine tumors, or islet cell tumors, of the pancreas originate from multipotential stem cells that have retained the ability to proliferate and differentiate into various cellular lines that make up this group of neoplasms. They account for about 1% to 2% of all pancreatic tumors [1]. Most of these tumors can be clinically diagnosed because they secrete one or more active peptides that produce clinical symptoms. These neuroendocrine tumors are called functioning islet cell tumors. The clinical manifestations of these tumors appear early, when very small in dimension, so that preoperative localization with noninvasive imaging can be difficult to obtain. Conversely, when not symptomatic because of the lack of active peptide secretion, neuroendocrine tumors of the pancreas can grow slowly, without significant or specific clinical manifestations. These neuroendocrine tumors are called nonfunctioning islet cell tumors (NEFTs). Because they are not specifically symptomatic, the characterization of these pancreatic tumors is often entrusted to imaging and results from the identification of their hypervascular architecture. Moreover, an accurate differential diagnosis is needed because of the favorable responses to surgery and specific chemotherapy of these tumors, with a better prognosis than with ductal adenocarcinoma. We discuss the possibilities of CEUS in the study of neuroendocrine pancreatic tumors.

Diagnostic accuracy of ultrasound dilution access blood flow measurement in detecting stenosis and predicting thrombosis in native forearm arteriovenous fistulae for hemodialysis

BACKGROUND Vascular access surveillance by ultrasound dilution blood flow rate (Qa) measurement is widely recommended; however, optimal criteria for detecting stenosis and predicting thrombosis in arteriovenous fistulae (AVFs) are still not clearly defined. METHODS In a blinded trial, we evaluated the accuracy of single Qa measurement, Qa adjusted for mean arterial pressure (Qa/MAP), and decrease in Qa over time (dQa) in detecting stenosis and predicting thrombosis in an unselected population of 120 hemodialysis subjects with native forearm AVFs (91 AVFs, located at the wrist; 29 AVFs, located at the midforearm). All AVFs underwent fistulography, which identified greater than 50% stenosis in 54 cases. RESULTS Receiver operating characteristic curve analysis showed that dQa, Qa, and Qa/MAP have a high stenosis discriminative ability with similar areas under the curve (AUCs), ie, 0.961 +/- 0.025, 0.946 +/- 0.021, and 0.912 +/- 0.032, respectively. In the population as a whole, optimal thresholds for stenosis were Qa less than 750 mL/min alone and in combination with dQa greater than 25% (efficiency, 90%); however, the best threshold depended on anastomotic site; it was Qa less than 750 mL/min for an AVF at the wrist and Qa less than 1,000 mL/min for an AVF in the midforearm. Qa was the best predictor of incipient thrombosis (AUC, 0.981 +/- 0.013) with an optimal threshold at less than 300 mL/min (efficiency, 94%). Pooled intra-assay and interassay variation coefficients were 8.2% for MAP, 7.9% for Qa, and 11.2% for Qa/MAP. CONCLUSION Our study shows that ultrasound dilution Qa measurement is a reproducible and highly accurate tool for detecting stenosis and predicting thrombosis in forearm AVFs. Neither Qa/MAP nor dQa improve the diagnostic performance of Qa alone, although its combination with dQa increases the tests sensitivity for stenosis.

Endovascular versus Surgical Preemptive Repair of Forearm Arteriovenous Fistula Juxta-Anastomotic Stenosis: Analysis of Data Collected Prospectively from 1999 to 2004

Surgery is the traditional treatment for juxta-anastomotic stenoses in forearm arteriovenous fistulas (AVF), but percutaneous transluminal angioplasty (PTA) is a suitable alternative. No prospective comparative trials between the two have been reported to date, however. A retrospective analysis of prospectively, concurrently collected data was performed to compare the outcome and cost of surgery and PTA in the preemptive repair of juxta-anastomotic stenosis in lower forearm AVF. Sixty-four AVF with >50% venous juxta-anastomotic stenosis were considered: 21 were treated surgically (11 proximal neo-anastomosis and 10 polytetrafluoroethylene interposition graft) and 43 by PTA. After treatment, AVF were monitored by quarterly ultrasound dilution access blood flow measurement. End points were restenosis and procedure failure rate (re-intervention by another technique or access loss), and determinants were analyzed using Cox hazard model. Initial procedural success was 100% for surgery and 95% for PTA (P = 0.539). Restenosis rate was 0.168 and 0.519 events/AVF-year for surgery and PTA, respectively (P = 0.009). The type of procedure was the only variable that was significantly associated with restenosis, the adjusted relative risk being 2.77-fold higher (95% confidence interval 1.07 to 7.17; P = 0.036) after PTA than surgery. The procedure failure rate was 0.110 and 0.097 events/AVF-year for surgery and PTA, respectively (P = 0.736). The cost profile also was similar for the two procedures. This prospective comparative study confirms a higher restenosis rate after PTA than surgery, but with strict surveillance for restenosis, the two procedures show similar assisted primary patency and cost, suggesting that they should be considered equally valid, complementary alternatives in the preemptive treatment of juxta-anastomotic stenosis in forearm AVF.

Contrast-enhanced ultrasonography better identifies pancreatic tumor vascularization than helical CT.

Background: Contrast-enhanced ultrasonography (CEUS) is a recently introduced field of ultrasonography (US). To assess the ability of CEUS to identify the vascularization of solid pancreatic tumors in comparison to helical CT. Methods: Forty-two resected pancreatic tumors, found at US, were studied with CEUS and helical CT. The tumor enhancement at CEUS was scored in comparison to the baseline aspect of the lesion and/or the extralesional pancreatic parenchyma together with the adjacent vessels during the dynamic study. All the lesions underwent pathological examination using H&E stains and CD34 markers with an evaluation of the microvessel density (MVD). The correlation of CEUS and helical CT with the MVD of the lesions was established with Spearman’s test. Results: The correlation of CEUS with the MVD of the lesions was significantly superior (Rs = 0.914; p < 0.0001) to that of helical CT (Rs = 0.635; p < 0.0001). Conclusions: CEUS is better than helical CT in the identification of the vascularization of solid pancreatic tumors. CEUS, when the pancreatic gland is optimally visualized, should be therefore considered a complementary imaging modality in the characterization of pancreatic tumors. CEUS can be a valid onco-imaging modality for quantifying tumoral vascularization in a noninvasive and accurate way.

Adding access blood flow surveillance to clinical monitoring reduces thrombosis rates and costs, and improves fistula patency in the short term: a controlled cohort study

BACKGROUND Access blood flow (Qa) measurement is the recommended method for fistula (AVF) surveillance for stenosis, but whether it may be beneficial and cost-effective is controversial. METHODS We conducted a 5-year controlled cohort study to evaluate whether adding Qa surveillance to unsystematic clinical monitoring (combined with elective stenosis repair) reduces thrombosis and access loss rates, and costs in mature AVFs. We prospectively collected data in 159 haemodialysis patients with mature AVFs, 97 followed by unsystematic clinical monitoring (Control) and 62 by adding Qa surveillance to monitoring (Flow). Indications for imaging and stenosis repair were clinically evident access dysfunction in both groups and a Qa < 750 ml/min or dropping by >20% in Flow. RESULTS Adding Qa surveillance prompted an increase in access imaging (HR 2.96, 95% CI 1.79-4.91, P < 0.001), stenosis detection (HR 2.55, 95% CI 1.48-4.42, P = 0.001) and elective repair (HR 2.26, 95% CI 1.16-4.43, P = 0.017), and a reduction in thromboses (HR 0.27, 95% CI 0.09-0.79, P = 0.017), central venous catheter placements (HR 0.14, 95% CI 0.03-0.42, P = 0.010) and access losses (HR 0.35, 95% CI 0.11-1.09, P = 0.071). In the Kaplan-Meier analysis, adding Qa surveillance only extended short-term cumulative patency (P = 0.037 in the Breslow test). Mean access-related costs were 1213 Euro/AVF-year in Control and 743 in Flow (P < 0.001). CONCLUSIONS Our controlled cohort study shows that adding Qa surveillance to monitoring in mature AVFs is associated with a better detection and elective treatment of stenosis, and lower thrombosis rates and access-related costs, although the cumulative access patency was only extended in the first 3 years after fistula maturation. We are aware of the limitations of our study (non-randomization and the possible centre effect) and that further, better-designed trials are needed to arrive at a definitive answer concerning the role of Qa surveillance for fistulae.

Contrast-Enhanced Ultrasonographic Detection of Small Pancreatic Insulinoma

Endocrine tumors of the pancreas originate from multipotential stem cells that have retained the capacity to proliferate and differentiate themselves in the various cellular lines that make up this group of neoplasms. Insulinomas represent the most frequently found functioning endocrine tumors of the pancreas and are benign in most cases (85%-99%), are single (93%-98%), and have diameters of less than 2.5 cm. 1,2 When malignant, their diameters are generally greater than 3 cm, and about one third of these have metastases at the moment of diagnosis. 1,2 They appear early with signs and symptoms linked to hypoglycemia due to the hypersecretion of insulin; they are almost exclusively located at the pancreatic level with no preferential sites. Preoperative ultrasonographic detection of insulinomas is generally difficult but possible in 25% to 60% of cases. 3 The main difficulty in detecting a pancreatic insulinoma lies in the organs anatomic structure and the tumors small dimensions at clinical appearance. The use of second-generation contrast-enhanced imaging can increase the capacity to detect pancreatic insulinomas in preoperative ultrasonography, as the following case confirms.

Gastroduodenal artery stump haemorrhage following pylorus-sparing Whipple procedure: treatment with covered stents.

Background/Aims: To report a case of bleeding after pancreatoduodenectomy in a patient with pancreatic leak and portal thrombosis who was successfully treated with an endovascular approach. Methods: A 58-year-old male, suffering from neoplasm of the distal bile duct, underwent a pylorus-preserving Whipple procedure. On the 18th day, following a sudden drop in pressure and low haematocrit values, the patient underwent surgery. The source of the bleeding was not found. Six days later, following the appearance of bleeding from the abdominal drainage and haematemesis with shock, the patient had an immediate angiography. Bleeding from the gastroduodenal artery stump was evident, the portography showed no portal flow. With respect to the shortness of the stump, safe embolisation with coils, while preserving the common hepatic artery patency, was difficult to obtain. Results: By transcatheter placement of covered stents into the hepatic artery and thereby occluding the origin of the gastroduodenal artery, the bleeding was stopped. After 2 months, CT angiography showed patency of both the common and proper hepatic arteries. Nine months after the procedure the patient is in good health. Conclusions: Percutaneous placement of covered stents can be the solution in cases where transcatheter embolisation is not recommendable because of portal vein thrombosis.

Role of chemoembolization in synchronous liver metastases from pancreatic endocrine tumours.

Endocrine tumours of the pancreas, even in case of liver involvement, are generally characterized by a slower evolution and a better prognosis, if compared with ductal carcinoma. This fact gives reason to a radical surgical approach, whenever possible, and to the research of any effective adjuvant treatment. For this purpose, hepatic transarterial chemoembolization (TACE) has been proposed in recent years for the treatment of metastatic endocrine tumours. Out of 80 patients suffering from endocrine tumours of the pancreas, observed between January 1985 and December 1996, 28 (35%) presented liver metastases at the time of diagnosis. Twelve of these patients were submitted to palliative resection of pancreatic tumour and one or more cycles of TACE. Overall survival was 50% (6/12); median survival was 35.4 months (range 4–75). These results suggest that chemoembolization, combined with surgical resection of primary malignancy, appears to be able to control the disease for a certain time and to increase the survival rate.