Bypass surgery versus endovascular revascularization for occlusive infrainguinal peripheral artery disease: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the treatment of diabetic foot syndrome.

To report a review and meta-analysis of all randomized controlled trials (RCTs) comparing bypass surgery (BS) and endovascular treatment (ET) in infrainguinal peripheral arterial disease (PAD) for several endpoints, such as major and minor amputation, major adverse limb events (MALEs), ulcer healing, time to healing, and all-cause mortality to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS). A MEDLINE and EMBASE search was performed to identify RCTs, published since 1991 up to June 21, 2023, enrolling patients with lower limb ischemia due to atherosclerotic disease (Rutherford I-VI). Any surgical BS or ET was allowed, irrespective of the approach, route, or graft employed, from iliac to below-the-knee district. Primary endpoint was major amputation rate. Secondary endpoints were amputation-free survival major adverse limb events (MALEs), minor amputation rate, all-cause mortality, ulcer healing rate, time to healing, pain, transcutaneous oxygen pressure (TcPO2) or ankle-brachial index (ABI), quality of life, need for a new procedure, periprocedural serious adverse events (SAE; within 30 days from the procedure), hospital lenght of stay, and operative time. Twelve RCTs were included, one enrolled two separate cohorts of patients, and therefore, the studies included in the analyses were 13. Participants treated with ET had a similar rate of major amputations to participants treated with BS (MH-OR 0.85 [0.60, 1.20], p = 0.36); only one trial reported separately data on patients with diabetes (N = 1), showing no significant difference between ET and BS (MH-OR: 0.67 [0.09, 5.13], p = 0.70). For minor amputation, no between-group significant differences were reported: MH-OR for ET vs BS: 0.83 [0.21, 3.30], p = 0.80). No significant difference in amputation-free survival between the two treatment modalities was identified (MH-OR 0.94 [0.59, 1.49], p = 0.80); only one study reported subgroup analyses on diabetes, with a non-statistical trend toward reduction in favor of ET (MH-OR 0.62 [0.37, 1.04], p = 0.07). No significant difference between treatments was found for all-cause mortality (MH-OR for ET vs BS: 0.98 [0.80, 1.21], p = 0.88). A significantly higher rate of MALE was reported in participants treated with ET (MH-OR: 1.44 [1.05, 1.98], p = 0.03); in diabetes subgroup analysis showed no differences between-group for this outcome (MH-OR: 1.34 [0.76, 2.37], p = 0.30). Operative duration and length of hospital stay were significantly shorter for ET (WMD: - 101.53 [- 127.71, - 75.35] min, p < 0.001, and, - 4.15 [- 5.73, - 2.57] days, p < 0.001 =, respectively). ET was associated with a significantly lower risk of any SAE within 30 days in comparison with BS (MH-OR: 0.60 [0.42, 0.86], p = 0.006). ET was associated with a significantly higher risk of reintervention (MH-OR: 1.57 [1.10, 2.24], p = 0.01). No significant between-group differences were reported for ulcer healing (MH-OR: 1.19 [0.53, 2.69], p = 0.67), although time to healing was shorter (- 1.00 [0.18, 1.82] months, p = 0.02) with BS. No differences were found in terms of quality of life and pain. ABI at the end of the study was reported by 7 studies showing a significant superiority of BS in comparison with ET (WMD: 0.09[0.02; 0.15] points, p = 0.01). The results of this meta-analysis showed no clear superiority of either ET or BS for the treatment of infrainguinal PAD also in diabetic patients. Further high-quality studies are needed, focusing on clinical outcomes, including pre-planned subgroup analyses on specific categories of patients, such as those with diabetes and detailing multidisciplinary team approach and structured follow-up.

Chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and relatively preserved liver function. In a meta-analysis of randomized controlled trials comparing conventional TACE regimens-including the administration of an anticancer-in-oil emulsion followed by embolic agents-versus best supportive care, TACE was shown to improve median survival from 16 to 20 months. Various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. The introduction of an embolic drug-eluting bead (DEB) has been shown to substantially improve the pharmacokinetic profile of TACE, providing levels of consistency and repeatability not available with conventional regimens while concomitantly significantly diminishing systemic drug exposure. In randomized trials, DEB-TACE significantly reduced liver toxicity and drug-related adverse events compared with conventional TACE. In this article, technique, indications and contraindications, and clinical outcomes of conventional and DEB-TACE in the management of HCC are reviewed. In addition, scientific background and early clinical experience with the use of combination regimens including TACE and systemically active molecular-targeted agents with antiangiogenic properties are discussed. The combination of DEB-TACE and antiangiogenic therapy represents a potentially powerful approach that is currently undergoing clinical investigation in a phase 3 setting.

Outcomes of three years of teamwork on critical limb ischemia in patients with diabetes and foot lesions.

To evaluate the outcomes of a multidisciplinary team working on diabetic foot (DF) patients with critical limb ischemia (CLI) in a specialized center, the authors retrospectively traced all the patients admitted in their department in 3 consecutive years with a diagnosis of CLI. From January 2006 to December 2008, 245 consecutive DF patients with CLI according the TransAtlantic interSociety Consensus II criteria were included in the study. Treatment strategy was decided by a team of diabetologists, inteventional radiologists, and vascular surgeons. Technical and clinical success, mortality, and ulcer recurrence were evaluated at 6 months and at a mean follow-up of 19.5 ± 13.4 months. Percutaneous transluminal angioplasty (PTA) was performed in 189 (77%) patients, whereas medical treatment, open surgical revascularization (OSR), and primary amputation were performed in 44 (18.3%), 11 (4.3%), and 1 (0.5%) patients, respectively. Revascularization was successful in 227/233 (97.4%) patients. At follow-up, the overall clinical success rate was 60.4%; it was significantly (P = .001) higher after revascularization (75.9%) compared with medical treatment (48.3%). During follow-up, surgical interventions in the foot were 1.5 ± 0.4 in those treated with PTA, 1.6 ± 0.5 in those treated with OSR, and 0.3 ± 0.8 in those receiving medical therapy (P < .05 compared with the others). Ulcer recurrence occurred in 29 (11.8%) patients: 4 (1.6%) in PTA, 2 (0.8%) in OSR, and 23 (9.4%) in the medical therapy group (P < .05). Major amputation rate was 9.3%, being significantly (P = .04) lower after revascularization (5.2%) compared with medical therapy alone (13.8%). Cumulative mortality rate was 10.6%. In conclusion, this study confirms the positive role of a PTA-first approach for revascularizing the complex cases of DF with CLI in a teamwork management strategy.

Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS: In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS: Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.

Hepatocellular carcinoma: CT for tumor response after transarterial chemoembolization in patients exceeding Milan criteria--selection parameter for liver transplantation.

PURPOSE: To retrospectively evaluate the clinical outcome of patients with hepatocellular carcinoma (HCC) who exceeded the Milan criteria, who underwent transarterial chemoembolization (TACE) before orthotopic liver transplantation (OLT), to determine the value of computed tomography (CT)-based tumor response to TACE as a preoperative selection criterion for OLT. MATERIALS AND METHODS: The study included 33 patients with HCC who exceeded the Milan criteria and underwent OLT after TACE. Informed written consent was obtained before TACE and OLT. Institutional review board approval was not required. Tumor response to TACE was evaluated at 1 month with CT according to amended Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. In the explanted liver, degree of tumor necrosis (> or = 90%, 50%-89%, or < 50%), residual tumor stage and grade, and presence of microvascular invasion were assessed. Follow-up after OLT ranged from 1 to 143 months. RESULTS: After TACE, CT showed complete tumor response (CR) in 18 (55%) patients. On the explanted liver, tumor necrosis was rated 90% or greater in 20 (61%) patients, with a good correlation with CT. Microvascular invasion was observed in nine (27%) of 33 patients; none of them were reported to have a CR at CT. The 5-year cumulative survival rate after OLT was 72.5%; it was significantly (P = .003) higher in patients with a CR (94.4%) compared with patients with a partial response (PR) (45.4%) and stable disease (50%). The 5-year cumulative recurrence-free rate after OLT was 74.4%; it was not affected by the tumor nodule size and number, whereas it was significantly (P = .008) higher in patients with a CR (94.4%) compared with patients with a PR (46.7%) and stable disease (50%). CONCLUSION: In patients with HCC who exceeded the Milan criteria, a CR after TACE, on the basis of amended RECIST guidelines, is associated with excellent posttransplantation outcomes. Therefore, 1-month response to TACE assessed at CT may represent a valid selection criterion for OLT.

Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study.

AIM: To prospectively evaluate the short and long term clinical impact of selective transarterial chemoembolization (TACE) on liver function in patients with hepatocellular carcinoma (HCC). To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS: One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine-aminotransferase (ALT), prothrombin time (PT) and bilirubin. According to Cancer Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC) staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed "on demand". Liver function tests were checked in all patients every four months. RESULTS: After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 +/- 1.12 to 6.11 +/- 1.57 at discharge time (P < 0.0001), decreasing after four months to 5.81 +/- 0.73 (not significant). ALT, PT and bilirubin significantly (P < 0.0001) increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 +/- 6.3 mo (median: 16 mo). Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION: Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.

Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicentre study.

The purpose of this article is to present the early results of a multicentre trial using HepaSphere microspheres loaded with chemotherapeutic agents for transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma. From December 2005 to March 2007, 50 patients (36 male and 14 female, mean age 68.4 years) were treated by selective TACE using HepaSphere microspheres loaded with doxorubicin or epirubicin. The diameter of the treated lesions ranged from 20 to 100 mm (mean 42.5; maximum of 4 tumor nodules). Tumor response was evaluated by computed axial tomography according to the World Health Organization criteria as modified by the European Association for the Study of Liver Diseases. All of the procedures were technically successful, and there were no major complications. At 1-month follow-up, complete tumor response was observed in 24 of 50 (48%), partial response in 18 of 50 (36%), and stable disease in 8 of 50 (16%) patients, and there were no cases of disease progression. At 6-month follow-up (31 of 50 patients), complete tumor response was obtained in 16 of 31 (51.6%), partial response in 8 of 31 (25.8%), and progressive disease in 7 of 31 (22.6%) patients. Within the initial 9-month follow-up, TACE with HepaSphere was successfully repeated twice in 3 patients, whereas 3 patients underwent the procedure 3 times. Our initial multicentre experience demonstrates that TACE using HepaSphere is feasible, is well tolerated, has a low complication rate, and is associated with promising tumor response. When complete tumor response in not achieved, additional treatments can be performed without difficulties. Longer follow-up on larger series is mandatory to confirm these preliminary results.

Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study.

BACKGROUND/AIMS: Experimental studies have shown synergy between radiofrequency (RF) ablation and adjuvant chemotherapy in animal tumour models. We aimed to assess safety and efficacy of doxorubicin-eluting bead (DEB)-enhanced RF ablation in the treatment of human hepatocellular carcinoma (HCC). METHODS: Twenty patients with single HCC ranging 3.3-7.0 cm (mean, 5.0 cm+/-1.4) showing evidence of residual viable tumour after standard RF ablation underwent intraarterial DEB administration (50-125 mg doxorubicin; mean, 60.2 mg+/-21.8). Follow-up period ranged 6-20 months (mean, 12 months+/-5). RESULTS: No major complication occurred. No deterioration of liver function was observed. The volume of treatment-induced necrosis--as measured on imaging--increased from 48.1 cm3+/-35.7 after RF ablation to 75.5 cm3+/-52.4 after DEB administration, with an increase of 60.9%+/-39.0. The enhanced effect resulted in confirmed complete response (CR) of the target lesion in 12 (60%) of 20 patients. Incomplete response with persistence of <10% of initial tumour volume was observed in 6 (30%) of 20 patients, and local tumour progression in 2 (10%) of 20. CONCLUSIONS: Intraarterial DEB administration substantially enhances the effect of RF ablation. DEB-enhanced RF ablation is safe and results in a high rate of CR in patients refractory to standard RF treatment.

Endovascular repair of an aorto-left renal vein fistula due to a ruptured abdominal aortic aneurysm after EVAR.

PURPOSE: To report an unusual late complication of endovascular aneurysm repair: an arteriovenous fistula between the aneurysm sac and a retro-aortic left renal vein following sac expansion due to a type III endoleak. CASE REPORT: A 79-year-old man developed an arteriovenous fistula between the aneurysm sac and a retro-aortic left renal vein 67 months after endovascular aneurysm exclusion (EVAR). Aneurysm rupture was due to disconnection between the right iliac limb and an extender cuff. The problem was repaired percutaneously with another endograft bridging the two prostheses. At 16 months, the aneurysm sac diameter was decreased; there was no evidence of the AV fistula, and the patient was free from any complication related to the EVAR. CONCLUSIONS: This case emphasizes the need of close surveillance even in the late postoperative course of these patients. Moreover, this rare event confirmed that endovascular techniques can play an important role in treating emergent complications.

Predictive factors of in-stent restenosis in renal artery stenting: a retrospective analysis.

PURPOSE: To retrospectively evaluate the role of clinical and procedural factors in predicting in-stent restenosis in patients with renovascular disease treated by renal artery stenting. METHODS: From 1995 to 2002, 147 patients underwent renal artery stenting for the treatment of significant ostial atherosclerotic stenosis. Patients underwent strict clinical and color-coded duplex ultrasound follow-up. Ninety-nine patients (111 stents), with over 6 months of continuous follow-up (mean 22+/-12 months, range 6-60 months), were selected and classified according to the presence (group A, 30 patients, 32 lesions) or absence (group B, 69 patients, 79 lesions) of significant in-stent restenosis. A statistical analysis was performed to identify possible preprocedural and procedural predictors of restenosis considering the following data: sex, age, smoking habit, diabetes mellitus, hypertension, serum creatinine, cholesterol and triglyceride levels, renal artery stenosis grade, and stent type, length and diameter. RESULTS: Comparing group A and B patients (chi(2) test), a statistically significant relation was demonstrated between stent diameter and length and restenosis: the risk of in-stent restenosis decreased when the stent was >/=6 mm in diameter and between 15 and 20 mm in length. This finding was confirmed by multiple logistic regression analysis. Stent diameter and length were proved to be significantly related to in-stent restenosis also when evaluating only patients treated by Palmaz stent (71 stents). CONCLUSION: Although it is based on a retrospective analysis, the present study confirms the importance of correct stent selection in increasing long-term patency, using stents of at least 6 mm in diameter and with a length of approximately 15-20 mm.

Type II lumbar endoleaks: hemodynamic differentiation by contrast-enhanced ultrasound scanning and influence on aneurysm enlargement after endovascular aneurysm repair.

OBJECTIVE: The objective of this study was to differentiate type II lumbar endoleaks on the basis of dynamic features identified by contrast-enhanced ultrasound scanning (CUS) and to evaluate the role of this differentiation in detecting abdominal aortic aneurysm (AAA) enlargement > or =1 mL/mo. METHODS: Eighteen male patients (mean age, 71.8 years) with type II lumbar endoleak suspected at CUS underwent computed tomography angiography (CTA) and digital subtraction angiography (DSA). On CTA, AAA volumes and endoleak visualization and volume were assessed. At CUS, performed after a bolus of 1.5 to 2.4 mL of a second generation blood pool contrast agent, the following parameters were evaluated: presence of contrast material within the aneurysmal sac (endoleak), delay of endoleak detection (wash-in) and disappearance (washout) from the beginning of contrast injection, visualization of inflow and outflow vessels, and presence of cavity filling. Statistical analysis was performed regarding endoleak features at CUS, endoleak detection at CTA, and rate of AAA enlargement. RESULTS: DSA confirmed all the endoleaks. Mean +/- standard deviation wash-in and washout times were 121.9 +/- 132.6 and 337.2 +/- 193.7 seconds, respectively; a significant relation was observed between these two parameters (P < .01, analysis of variance). By Youden plots, endoleaks were classified as hyperdynamic when wash-in was <100 seconds (n = 10, 55.5%) and/or washout was <520 seconds (n = 13, 72.2%). A slower washout was associated with nonvisualized outflow (66.7%) and/or inflow arteries (66.7%) ( P < .05). Eight endoleaks (44.4%) were missed at CTA; it occurred in hypodynamic endoleaks, absence of detectable inflow or outflow vessels, and absence of cavity filling at CUS (P < .05). Overall mean AAA volume increase rate was 1.1 +/- 1.7 mL/mo. By multiple logistic regression model, the washout time > or = 520 seconds was the only independent predictor of AAA volume increase > or = 1 mL/mo (8 patients, 44.4%). CONCLUSION: Type II lumbar endoleaks show different hemodynamic features at CUS, which might influence the rate of aneurysm enlargement, addressing the need for treatment.