Giovanni Lipari

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.

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.

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.

Expansion of necrotic core and shedding of Mertk receptor in human carotid plaques: a role for oxidized polyunsaturated fatty acids?

AIMS Expansion of necrotic core (NC), a major feature responsible for plaque disruption, is likely the consequence of accelerated macrophage apoptosis coupled with defective phagocytic clearance (efferocytosis). The cleavage of the extracellular domain of Mer tyrosine kinase (Mertk) by metallopeptidase domain17 (Adam17) has been shown to produce a soluble Mertk protein (sMer), which can inhibit efferocytosis. Herein, we analysed the expression and localization of Mertk and Adam17 in the tissue around the necrotic core (TANC) and in the periphery (P) of human carotid plaques. Then we studied the mechanisms of NC expansion by evaluating which components of TANC induce Adam17 and the related cleavage of the extracellular domain of Mertk. METHODS AND RESULTS We studied 97 human carotid plaques. The expression of Mertk and Adam17 was found to be higher in TANC than in P (P < 0.001). By immunohistochemistry, Mertk was higher than Adam17 in the area of TANC near to the lumen (P < 0.01) but much lower in the area close to NC (P < 0.01). The extract of this portion of TANC increased the expression (mRNA) of Adam17 and Mertk (P < 0.01) in macrophage-like THP-1 cells but it also induced the cleavage of the extracellular domain of Mertk, generating sMer in the medium (P < 0.01). This effect of TANC extract was most evoked by its content in F(2)-isoprostanes, hydroxyoctadecadienoic acids, and hydroxytetraenoic acids. CONCLUSION Some oxidized derivatives of polyunsaturated fatty acids contained in TANC of human carotid plaques are strong inducers of Adam17, which in turn leads to the generation of sMer, which can inhibit efferocytosis.

Should current criteria for detecting and repairing arteriovenous fistula stenosis be reconsidered? Interim analysis of a randomized controlled trial

BACKGROUND The vascular access guidelines recommend that arteriovenous fistulas (AVFs) with access dysfunction and an access blood flow (Qa) <300-500 mL/min be referred for stenosis imaging and treatment. Significant (>50%) stenosis, however, may be detected in a well-functioning AVF with a Qa > 500 mL/min, too, but whether it is worth correcting or not remains to be seen. METHODS In October 2006, we began an open randomized controlled trial enrolling patients with an AVF with subclinical stenosis and Qa > 500 mL/min, to see how elective stenosis repair [treatment group (TX)] influenced access failure (thrombosis or impending thrombosis requiring access revision), or loss and the related cost compared with stenosis correction according to the guidelines, i.e. after the onset of access dysfunction or a Qa < 400 mL/min [control group (C)]. An interim analysis was performed in July 2012, by which time the trial had enrolled 58 patients (30 C and 28 TX). RESULTS TX led to a relative risk of 0.47 [95% confidence interval (CI): 0.17-1.15] for access failure (P = 0.090), 0.37 [95% CI: 0.12-0.97] for thrombosis (P = 0.033) and 0.36 [95% CI: 0.09-0.99] for access loss (P = 0.041). In the setting of our study (in which all surgery was performed as in patient procedure) no significant differences in costs emerged between the two strategies. The mean incremental cost-effectiveness ratio for TX was €282 or €321 to avoid one episode of thrombosis or access loss, respectively. CONCLUSIONS Our interim analysis showed that elective repair of subclinical stenosis in AVFs with Qa > 500 mL/min cost-effectively reduces the risk of thrombosis and access loss in comparison with the approach of the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, raising the question of whether the currently recommended criteria for assessing and treating stenosis should be reconsidered.

Bedside Screening for Fistula Stenosis Should Be Tailored to the Site of the Arteriovenous Anastomosis

BACKGROUND AND OBJECTIVES Given different sites of stenosis and access blood flow rates (Qa), the criteria for diagnosing fistula stenosis might vary according to anastomotic site. To test this, we analyzed the database of a prospective blinded study seeking an optimal bedside screening program for fistula stenosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Several methods used during dialysis (physical examination [PE], dynamic and derived static venous pressure [VAPR], dialysis blood pump flow/arterial pressure ratio, and Qa measurement) to diagnose angiographically-proven >50% stenosis were assessed in an unselected population of hemodialysis patients with mature fistulae (43 at the wrist [distal fistulae], 76 at mid-forearm or the elbow [proximal fistulae]). RESULTS Prevalence of inflow stenosis was uninfluenced by anastomotic site, whereas outflow stenoses were more prevalent in proximal fistulae. The best test for inflow stenosis was Qa <650 ml/min in distal fistulae and a combination of a positive PE and Qa <900 ml/m in proximal fistulae. In proximal fistulae, PE and VAPR >0.5 were both equally highly diagnostic of outflow stenosis. Tailoring choice of test to site of the anastomosis may also contain the screening-associated workload, by reducing the need to perform PE and measure VAPR, compared with a screening approach regardless of the access location. CONCLUSIONS Our study shows that an effective bedside screening program with ≥85% accuracy for fistula stenosis can be tailored to the site of the anastomosis, Qa being the tool of choice for the wrist, and PE alone or combined with Qa and VAPR measurements for more proximally-located accesses.

Pancreatectomy with venous resection for pT3 head adenocarcinoma: Perioperative outcomes, recurrence pattern and prognostic implications of histologically confirmed vascular infiltration

BACKGROUND The outcomes of pancreatectomy with superior mesenteric vein (SMV) or portal vein (PV) resection have been mixed. This study investigated the morbidity and mortality profile after SMV-PV resection in comparison with standard pancreatectomy. Furthermore, we assessed whether tumors with histologically proven SMV-PV infiltration differ from other pT3 neoplasms in terms of recurrence pattern and survival. METHODS All patients with a pT3 head adenocarcinoma resected from 2000 to 2013 were analyzed retrospectively. In the SMV-PV resection group, information on venous wall status was obtained through pathologic reports. Standard statistical methods were used for data analysis. RESULTS The study population consisted of 651 patients, of whom 81 (12.4%) underwent synchronous SMV-PV resection. Venous resection was not associated with a higher rate of postoperative complications (60.5% versus 50.2%) and mortality (1.2% versus 1.1%) in comparison with standard pancreatectomy. Vascular infiltration was confirmed pathologically in 56/81 patients (69.1%). The median disease-specific survival of the entire population was 27 months (95% CI 24.6-29.3), with a 5-year survival rate of 20.5%. The median recurrence-free survival was 18 months (95% CI 15.0-20.9). On multivariate analysis, ASA score, preoperative pain, Ca 19-9 levels, tumor grade, R-status, lymph-vascular invasion, N-status, and adjuvant therapy resulted to be survival predictors. Similarly, Ca 19.9 levels, R-status, and N-status were predictors of recurrence. SMV-PV infiltration was not a significant prognostic factor. CONCLUSION Morbidity and mortality rates of pancreatectomy with SMV-PV resection are comparable with standard pancreatectomy. Pancreatic head adenocarcinoma with histologically confirmed SMV-PV infiltration does not segregate prognostically from other pT3 tumors.

Treatment of an aneurysm of the celiac artery arising from a celiomesenteric trunk. Report of a case

Introduction Visceral artery aneurysms (VAA) are rare, frequently present as a life-threatening emergency and are often fatal. The celiacomesenteric trunk (CMT), a common origin of the celiac trunk (CT) and the superior mesenteric artery (SMA) from abdominal aorta, is quite rare. Aneurysms that involve this celiomesenteric anomaly are even rarer and in the last 32 years have been reported in only 20 cases in the literature. Presentation of case We describe a case with 30 mm aneurysm arising from a CMT. In general, an aneurysm that is 20 mm or greater in size is considered to be significant enough to warrant treatment. Abdominal VAA sometimes can be treated with low-invasive procedures: our patient required open surgical repair with the celiac artery replanted on to the aorta. Discussion The clinical course was complicated only by an increase of hepatic cytolysis enzymes, and by a low output pancreatic fistula, treated conservatively. The patient was discharged on the fifteenth postoperative day. One month after discharge, imaging revealed a good patency of all reconstructed arteries. In the subsequent 36-month follow-up period, the patient reported no clinical episodes. Conclusion Our finding of a very rare case of a celiomesenteric anomaly with a concurrent aneurysm is extremely rare (20 cases in word literature in the last 32 years). The feasibility of the endovascular approach for aneurysms originating from the common celiomesenteric trunk depends mainly on aneurysmal location, diameter and neck size. In case of specific unfit anatomy, a careful surgical treatment can ensure the best results.

Anévrismes de l’artère carotide interne extra-crânienne : à propos de 2 cas

Resume Introduction Bien qu’ils constituent un evenement rare (0,1-2% de toutes les procedures chirurgicales concernant l’artere carotide interne, 0,4-1% de tous les anevrismes arteriels et 4% de tous les anevrismes arteriels peripheriques), les anevrismes du segment extra-crânien de l’artere carotide interne (ACI) revetent une signification clinique importante en raison du risque eleve de thromboembolisme cerebral. Vu la rarete de cette pathologie, nous jugeons opportun de signaler l’observation de deux anevrismes de l’ACI extra-crânienne, d’etiologie, respectivement, atherosclerotique et fibrodysplasique. Malades et methodes Notre experience se limite a deux patientes, traitees dans le Departement de Sciences Chirurgicales et Gastro-enterologiques du C.H.U. G.B. Rossi de Verone. Ces deux patientes se sont presentees avec des tableaux cliniques et instrumentaux tres differents et n’ont par consequent pas recu le meme type de traitement chirurgical. Dans le premier cas, on a procede a la resection de l’anevrisme et a la reconstruction termino-terminale ; dans le deuxieme, a une transposition carotidienne avec internalisation de la carotide externe. Resultats Les deux patientes n’ont pas presente de complications neurologiques majeures ou mineures, ni pendant l’intervention ni pendant le suivi, au cours duquel la permeabilite de l’axe carotidien extra-crânien a pu etre confirmee. Conclusions Sur la base de cette experience limitee et de l’analyse des donnees de la litterature, nous avons defini quelques points concernant l’approche diagnostique —qui se revele differente de celle ayant trait aux lesions carotidiennes stenosantes —les indications et le type de traitement. (J Mal Vasc 2006; 31: 152-158)