Isolated Limb Infusion for Limb-Threatening Sarcomas.

BACKGROUND: Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. METHODS: A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. RESULTS: The study identified 61 patients (52.5% female; median age, 73 years; range, 20-94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR + PR + stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P < 0.0001). The responders (CR + PR) had significantly longer PFS than the non-responders (SD + PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1-12.9; P < 0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P < 0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9-12.0; P < 0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P = 0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1-6.8; P = 0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P = 0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P = 0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR + PR + SD (HR, 3.0; 95% CI 1.0-8.7; P = 0.04). CONCLUSIONS: The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS.

Predictors of amputation-free survival and wound healing after infrainguinal bypass with alternative conduits.

OBJECTIVE: Inadequate vein quality or prior harvest precludes use of autologous single segment greater saphenous vein (ssGSV) in many patients with chronic limb-threatening ischemia (CLTI). Predictors of patient outcome after infrainguinal bypass with alternative (non-ssGSV) conduits are not well-understood. We explored whether limb presentation, bypass target, and conduit type were associated with amputation-free survival (AFS) after infrainguinal bypass using alternative conduits. METHODS: A single-center retrospective study (2013-2020) was conducted of 139 infrainguinal bypasses performed for CLTI with cryopreserved ssGSV (cryovein) (n = 71), polytetrafluoroethylene (PTFE) (n = 23), or arm/spliced vein grafts (n = 45). Characteristics, Wound, Ischemia, and foot Infection (WIfI) stage, and outcomes were recorded. Multivariable Cox proportional hazards and classification and regression tree analysis modeled predictors of AFS. RESULTS: Within 139 cases, the mean age was 71 years, 59% of patients were male, and 51% of cases were nonelective. More patients undergoing bypass with cryovein were WIfI stage 4 (41%) compared with PTFE (13%) or arm/spliced vein (27%) (P = .04). Across groups, AFS at 2 years was 78% for spliced/arm, 79% for PTFE, and 53% for cryovein (adjusted hazard ratio for cryovein, 2.5; P = .02). Among cases using cryovein, classification and regression tree analysis showed that WIfI stage 3 or 4, age >70 years, and prior failed bypass were predictive of the lowest AFS at 2 years of 36% vs AFS of 58% to 76% among subgroups with less than two of these factors. Although secondary patency at 2 years was worse in the cryovein group (26% vs 68% and 89% in arm/spliced and PTFE groups; P < .01), in patients with tissue loss there was no statistically significant difference in wound healing in the cryovein group (72%) compared with other bypass types (72% vs 87%, respectively; P = .12). CONCLUSIONS: In patients with CLTI lacking suitable ssGSV, bypass with autogenous arm/spliced vein or PTFE has superior AFS compared with cryovein, although data were limited for PTFE conduits for distal targets. Despite poor patency with cryovein, wound healing is achieved in a majority of cases, although it should be used with caution in older patients with high WIfI stage and prior failed bypass, given the low rates of AFS.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.

OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. RESULTS: Fifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

Relevance of BEST-CLI trial endpoints in a tertiary care limb preservation program.

OBJECTIVE: Major adverse limb event-free survival (MALE-FS) differed significantly by initial revascularization approach in the BEST-CLI randomized trial. The BEST-CLI trial represented a highly selected subgroup of patients seen in clinical practice; thus, we examined the endpoint of MALE-FS in an all-comers tertiary care practice setting. METHODS: This is a single-center retrospective study of consecutive, unique patients who underwent technically successful infrainguinal revascularization for chronic limb-threatening ischemia (2011-2021). MALE was major amputation (transtibial or above) or major reintervention (new bypass, open bypass revision, thrombectomy, or thrombolysis). RESULTS: Among 469 subjects, the mean age was 70 years, and 34% were female. Characteristics included diabetes (68%), end-stage renal disease (ESRD) (16%), Wound, Ischemia, and foot Infection (WIfI) stage 4 (44%), Global Limb Anatomic Staging System (GLASS) stage 3 (62%), and high pedal artery calcium score (pMAC) (22%). Index revascularization was autogenous vein bypass (AVB) (30%), non-autogenous bypass (NAB) (13%), or endovascular (ENDO) (57%). The composite endpoint of MALE or death occurred in 237 patients (51%) at a median time of 189 days from index revascularization. In an adjusted Cox model, factors independently associated with MALE or death included younger age, ESRD, WIfI stage 4, higher GLASS stage, and moderate-severe pMAC, whereas AVB was associated with improved MALE-FS. Freedom from MALE-FS, MALE, and major amputation at 30 days were 90%, 92%, and 95%; and at 1 year were 63%, 70%, and 83%, respectively. MALE occurred in 144 patients (31%) and was associated with ESRD, WIfI stage, GLASS stage, pMAC score, and index revascularization approach. AVB had superior durability, with adjusted 2-year freedom from MALE of 72%, compared with 66% for ENDO and 51% for NAB. Within the AVB group, spliced vein conduit had higher MALE compared with single-segment vein (hazard ratio, 1.8; 95% confidence interval, 0.9-3.7; P = .008 after inverse propensity weighting), but there was no statistically significant difference in major amputation. Of the 144 patients with any MALE, the first MALE was major reintervention in 47% and major amputation in 53%. Major amputation as first MALE was associated with non-AVB index approach. Indications for major reintervention were symptomatic stenosis/occlusion (54%), lack of clinical improvement (28%), asymptomatic graft stenosis (16%), and iatrogenic events (3%). Conversion to bypass occurred after 6% of ENDO cases, two-thirds of which involved distal bypass targets at the ankle or foot. CONCLUSIONS: In this consecutive, all-comers cohort, disease complexity was associated with procedural selection and MALE-FS. AVB independently provided the greatest MALE-FS and freedom from MALE and major amputation. Compared with the BEST-CLI randomized trial, MALE after ENDO in this series was more frequently major amputation, with relatively few conversions to open bypass.

Analysis of Oklahoma amputation trends and identification of risk factors to target areas for limb preservation interventions.

OBJECTIVE: Annual trends of lower extremity amputation due to end-stage chronic disease are on the rise in the United States. These amputations are leading to massive expenses for patients and the medical system. In Oklahoma, we have a high-risk population because access to care is low, the number of uninsured is high, cardiovascular health is poor, and our overall health care performance is ranked 50th in the country. But we know little about Oklahomans and their risk of limb loss. It is, therefore, imperative to look closely at this population to discover contemporary rates, trends, and state-specific risk factors for amputation due to diabetes and/or peripheral arterial disease (PAD). We hypothesize that state-specific groups will be identified as having the highest risk for limb loss and that contemporary trends in amputations are rising. To create implementable solutions to limb preservation, a baseline must be set. METHODS: We conducted a 12-consecutive-year observational study using Oklahoma's hospital discharge data. Discharges among patients 20 years or older with a primary or secondary diagnosis of diabetes and/or PAD were included. Diagnoses and amputation procedures were identified using International Classification of Disease-9 and -10 codes. Amputation rates were calculated per 1000 discharges. Trends in amputation rates were measured by annual percentage changes (APC). Prevalence ratios evaluated the differences in amputation rates across demographic groups. RESULTS: Over 5,000,000 discharges were identified from 2008 to 2019. Twenty-four percent had a diagnosis of diabetes and/or PAD. The overall amputation rate was 12 per 1000 discharges for those with diabetes and/or PAD. Diabetes and/or PAD-related amputation rates increased from 8.1 to 16.2 (APC, 6.0; 95% confidence interval [CI], 4.7-7.3). Most amputations were minor (59.5%), and although minor, increased at a faster rate compared with major amputations (minor amputation APC, 8.1; 95% CI, 6.7-9.6 vs major amputation APC, 3.1; 95% CI, 1.5-4.7); major amputations were notable in that they were significantly increasing. Amputation rates were the highest among males (16.7), American Indians (19.2), uninsured (21.2), non-married patients (12.7), and patients between 45 and 49 years of age (18.8), and calculated prevalence ratios for each were significant (P = .001) when compared within their respective category. CONCLUSIONS: Amputation rates in Oklahoma have nearly doubled in 12 years, with both major and minor amputations significantly increasing. This study describes a worsening trend, underscoring that amputations due to chronic disease is an urgent statewide health care problem. We also present imperative examples of amputation health care disparities. By defining these state-specific areas and populations at risk, we have identified areas to pursue and improve care. These distinctive risk factors will help to frame a statewide limb preservation intervention.

Hemoglobin A1c Levels Are Related to Patency and Adverse Limb Events in Diabetics After Revascularization.

OBJECTIVE: Poor glycemic control in the perioperative period has been reported to be associated with early and late major adverse limb events (MALE). However, these studies were mostly from large databases or lacked long-term outcomes. We examined the long-term effects of high hemoglobin A1c (HbA1c) level on patency, MALE, limb salvage (LS) and survival after lower extremity revascularization procedures in diabetic patients. METHODS: Patients with diabetes who had revascularization for Rutherford class 3-6 ischemia between May 2002 and December 2018 were identified. Patients with HbA1c≤7% were compared to HbA1c>7% for patency, MALE, survival, LS and amputation-free survival (AFS). RESULTS: Of 706 patients, 699 had HbA1c data (775 limbs), with 311 (357 limbs) in HbA1c≤7%, and 388 (418 limbs) in HbA1c>7% groups. Patients with HbA1c>7% were younger (69.9±10.2 vs 71.7±9.5, P=0.011), had higher lipid levels, insulin use (70% vs 49%, P<0.01), ASA 4, and had lower prevalence of chronic kidney disease (CKD) (32%vs41%, P=0.023). HbA1c>7% patients were more likely to present with chronic limb-threatening ischemia (CLTI) (79% vs 72%,P=0.019) and undergo infrapopliteal interventions (49% vs 42%, P=0.005), with no difference in anatomic complexity (TASC C/D, 75% vs 77%, p=0.72) or type of revascularization (24% vs 18% Open, 66% vs 70% EV, 10% vs 12% Hybrid, p=0.236). Patency and freedom from MALE were significantly lower in patients with HbA1c>7% for infra-inguinal revascularizations, whereas AFS and overall survival were similar. In patients with CLTI, LS rates at five years were significantly lower in patients undergoing open revascularization (HbA1c>7%: 64%±6%vs HbA1c<7%:86%±5%, P=0.020), whereas it was similar after endovascular interventions (HbA1c>7%:79%±4% vs HbA1c<7%:77%±3%, p=0.631). Seventy patients with HbA1c>7% lost limbs vs 38 patients with HbA1c≤7% (P=0.007). In multivariate analysis, HbA1c was significantly associated with primary patency. HbA1c, insulin use, level of intervention, and ACEI use were associated with MALE. CONCLUSIONS: Perioperative HbA1c>7% is associated with poorer patency rates, and increased MALE especially at the infra-inguinal level revascularization in diabetics, with no significant impact on survival. Limb salvage is impacted after open, but not after endovascular revascularization.

Influence of inframalleolar modifier P0/P1 on wound healing in bypass surgery vs endovascular therapy in patients with chronic limb-threatening ischemia.

OBJECTIVE: This study aimed to compare the influence of inframalleolar (IM) P0/P1 on wound healing in bypass surgery vs endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). METHODS: We retrospectively analyzed the multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. IM P represents target artery crossing into foot, with intact pedal arch (P0) and absent or severely diseased pedal arch (P1). The endpoints were wound healing, limb salvage (LS), and postoperative complications. RESULTS: We analyzed 66 and 189 propensity score-matched pairs in the IM P0 and IM P1 cohorts, respectively. In the IM P0 cohort, the 1-year wound healing rates were 94.5% and 85.7% in the bypass surgery and EVT groups, respectively (P = .092), whereas those in the IM P1 cohort were 86.2% and 66.2% in the bypass surgery and EVT groups, respectively (P < .001). In the IM P0 cohort, the 2-year LS rates were 96.7% and 94.1% in the bypass surgery and EVT groups, respectively (P = .625), and those in the IM P1 cohort were 91.8% and 81.5% in the bypass surgery and EVT groups, respectively (P = .004). No significant differences were observed between the bypass surgery and EVT in terms of postoperative complication rates in either the IM P0 or P1 cohorts. CONCLUSIONS: Bypass surgery facilitated better wound healing and LS than EVT in patients with IM P1. Conversely, no differences in wound healing or LS were observed between groups in patients with IM P0. Bypass surgery should be considered a better revascularization strategy than EVT in patients with tissue loss and IM P1 disease.

Real-World Vein Mapping Practice Patterns Before Endovascular Treatment of Limb Ischemia.

INTRODUCTION: The Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial results suggest that in patients with chronic limb-threatening ischemia (CLTI) and adequate single-segment great saphenous vein (SSGSV) by preoperative duplex ultrasonography, a surgical-first treatment strategy is superior to an endovascular-first strategy. However, the utilization of vein mapping prior to endovascular-first revascularization for CLTI in actual clinical practice is not known. METHODS: Data from a multicenter clinical data warehouse (2008-2019) were linked to Medicare claims data for patients undergoing endovascular-first treatment of infra-inguinal CLTI. Only patients who would have otherwise been eligible for enrollment in BEST-CLI were included. Adequate SSGSV was defined as healthy vein >3.0 mm in diameter from the groin through the knee. Logistic regression was used to estimate associations between preprocedure characteristics and vein mapping. Survival methods were used to estimate the risk of major adverse limb events and death. RESULTS: A total of 142 candidates for either surgical or endovascular treatment underwent endovascular-first management of CLTI. Ultrasound assessment for SSGSV was not performed in 76% of patients prior to endovascular-first revascularization. Of those who underwent preprocedure vein mapping, 44% had adequate SSGSV for bypass. Within one year postprocedure, 12.0% (95% confidence interval 7.4-18.0%) of patients underwent open surgical bypass and 54.7% (95% confidence interval 45.3-62.4%) experienced a major adverse limb event or death. CONCLUSIONS: In a real-world cohort of BEST-CLI-eligible patients undergoing endovascular-first intervention for infra-inguinal CLTI, three-quarters of patients had no preprocedure ultrasound assessment of great saphenous vein conduit. Practice patterns for vein conduit assessment in the real-world warrant reconsideration in the context of BEST-CLI trial results.

Below-the-Ankle Antegrade Teleferic Technique: New Approach for Below-the-Ankle Revascularization in Challenging Cases of Chronic Limb-Threatening Ischemia.

PURPOSE: To describe a novel bailout technique to approach below-the-ankle (BTA) chronic total occlusions or plantar-arch severe disease where the balloon/catheter is unable to follow the crossing guidewire and no other described recanalization approach is feasible. TECHNIQUE: When facing a complex BTA revascularization, if the guidewire crosses but the balloon cannot progress due to a lack of pushability, an antegrade puncture of the infrapopliteal vessel where the tip of the guidewire lays is performed. The guidewire is then carefully navigated through this distal BTA vessel into the needle to achieve its rendezvous and externalization. A low-profile balloon is inserted through the femoral access and advanced till the non-crossable point of the BTA vessels. A torque device is then attached to the proximal hub of the balloon, and the through-and-through guidewire is subsequently pulled from the new distal access, allowing the balloon to be dragged across the lesion together with the wire. CONCLUSION: The below-the-ankle antegrade teleferic (BAT) technique may be considered for highly complex BTA revascularization procedures where the wire crosses the lesion, but no other device can be tracked over it. CLINICAL IMPACT: The clinical impact of this article lies in the description of a bailout technique for BTA revascularization where the guidewire crosses, but no device can be advanced. This technique can be helpful in scenarios where failure to achieve success could result in limb loss. The BAT technique provides a solution in extremely challenging cases, enhancing technical success, improving outcomes and potentially preserving the limbs of patients who would otherwise face amputation, if not revascularized.The video shows the BAT technique performed with a support catheter under fluoroscopy: antegrate puncture of the DP, advancement of the support catheter over the wire, rendezvous of the guidewire in the catheter and subsequent externalization of the wire.

Tips and Tricks for Simple and Complex Below-the-Ankle Punctures.

CLINICAL IMPACT: When the standard endovascular crossing maneuvers have failed during CLTI recanalization procedures and the distal below-the-knee or proximal below-the-ankle retrograde access is not possible due to chronic occlusion of the vessels, mastering the more distal and complex retrograde BTA punctures may be advantageous.There are scanty reports regarding the retrograde puncture of the mid and forefoot vessels. The aim of this article is to review different tips and tricks related to these techniques to help operators to apply them in specific scenarios to eventually improve procedural success rate.