Transcatheter Arterialization of Deep Veins in Chronic Limb-Threatening Ischemia.

BACKGROUND: Approximately 20% of patients with chronic limb-threatening ischemia have no revascularization options, leading to above-ankle amputation. Transcatheter arterialization of the deep veins is a percutaneous approach that creates an artery-to-vein connection for delivery of oxygenated blood by means of the venous system to the ischemic foot to prevent amputation. METHODS: We conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure. RESULTS: We enrolled 105 patients who had chronic limb-threatening ischemia and were of a median age of 70 years (interquartile range, 38 to 89). Of the patients enrolled, 33 (31.4%) were women and 45 (42.8%) were Black, Hispanic, or Latino. Transcatheter arterialization of the deep veins was performed successfully in 104 patients (99.0%). At 6 months, 66.1% of the patients had amputation-free survival. According to Bayesian analysis, the posterior probability that amputation-free survival at 6 months exceeded a performance goal of 54% was 0.993, which exceeded the prespecified threshold of 0.977. Limb salvage (avoidance of above-ankle amputation) was attained in 67 patients (76.0% by Kaplan-Meier analysis). Wounds were completely healed in 16 of 63 patients (25%) and were in the process of healing in 32 of 63 patients (51%). No unanticipated device-related adverse events were reported. CONCLUSIONS: We found that transcatheter arterialization of the deep veins was safe and could be performed successfully in patients with chronic limb-threatening ischemia and no conventional surgical or endovascular revascularization treatment options. (Funded by LimFlow; PROMISE II study ClinicalTrials.gov number, NCT03970538.).

Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study.

BACKGROUND: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. METHODS: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. RESULTS: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.

A single center's 15-year experience with palliative limb care for chronic limb threatening ischemia in frail patients.

OBJECTIVE: Our institution's multidisciplinary Prevention of Amputation in Veterans Everywhere (PAVE) program allocates veterans with critical limb threatening ischemia (CLTI) to immediate revascularization, conservative care, primary amputation, or palliative limb care according to previously reported criteria. These four groups align with the approaches outlined by the global guidelines for the management of CLTI. In the present study, we have delineated the natural history of the palliative limb care group of patients and quantified the procedural risks and outcomes. METHODS: Veterans prospectively enrolled into the palliative limb cohort of our PAVE program from January 2005 to January 2020 were analyzed. The primary outcome was mortality. The secondary outcomes included overall and limb-related readmissions, limb loss, and wound healing. The clinical frailty scale (CFS) score was calculated, and the 5-year expected mortality was estimated using the Veterans Affairs Quality Enhancement Research Initiative tool. Regression analysis was performed to establish associations among the following variables: mortality, wound, ischemia, and foot infection (WIfI) score, CFS score, overall admissions, and limb-related admissions. RESULTS: The PAVE program enrolled 1158 limbs during 15 years. Of the 1158 limbs, 157 (13.5%) in 145 patients were allocated to the palliative limb care group. The overall mortality of the group was 88.2% (median interval, 3.5 months; range, 0-91 months). Of the 128 patients who had died, 64 (50%) had died within 3 months of enrollment. The predicted 5-year mortality for the group was 66%. The average CFS score for the group was 6.2, denoting persons moderately to severely frail. Using the CFS score, 106 patients were considered frail and 39 were considered not frail. No differences were found in mortality between the frail and nonfrail patients. However, a statistically significant difference was found in early (<3 months) mortality (56.2% vs 37.5%; P = .032). The 30-day limb-related readmission rate was 4.7%. Eventual major amputation was necessary for 18 limbs (11.5%). Wound healing occurred in 30 patients (20.6%). Regression analysis demonstrated no association between the CFS score and mortality (r = 0.55; P = .159) or between the WIfI score and mortality (r = 0.0165; P = .98). However, a significant association was found between the WIfI score and limb-related admissions (r = 0.97; P < .001). CONCLUSIONS: Frail patients with CLTI had high early mortality and a low risk of limb-related complications. They also had a low incidence of deferred primary amputation or limb-related readmissions. In our cohort, the vast majority of patients had died within a few months of enrollment without requiring an amputation. A comprehensive approach to the treatment of CLTI patients should include a palliative limb care option because a significant proportion of these patients will have limited survival and can potentially avoid unnecessary surgery and major amputation.

Surface osteosarcoma: Predictors of outcomes.

BACKGROUND AND OBJECTIVES: The subtypes of surface osteosarcomas include well-differentiated, low-grade parosteal osteosarcoma (POS), intermediate-grade periosteal osteosarcoma (PerOS), high-grade surface osteosarcoma (HGSO), and high-grade, dedifferentiated POS (dPOS). We aimed to determine disease progression, defined as local recurrence and metastatic disease, and overall (OS) and disease-specific survival (DSS). We identify outcome predictive factors and report functional results. METHODS: This retrospective study evaluated patients with primary surface osteosarcoma at our hospital from 1992 to 2019. Fifty-one patients had a median follow-up of 6.1 years (range: 0.1-25.2). Histologic subtypes included 32 POS, 11 PerOS, 4 HGSO, and 3 dPOS. Bone and soft tissue margins were classified using the American Joint Committee on Cancer residual tumor classification (Rx = Not evaluable; R0 = negative margin; R1 = microscopic positive margin; and R2 = macroscopic positive margin) and the modified R classification (mRx = not evaluable; mR0 = negative margin >1 mm; mR1 = negative margin ≤1 mm; mR1-dir: Positive microscopic margin locally; mR2a: Positive macroscopic margin locally; mR2b: positive macroscopic margin distally; and mR2C: positive macroscopic margin locally and distally). Forty-one patients had functional outcomes. RESULTS: Three POS patients developed recurrence: two had R0 margins and one an intralesional resection. Five patients developed lung metastases (POS: 3, dPOS: 2). Four patients died. The only significant disease progression predictor was age. OS at 10 years was 97%. 48 patients had negative bone margins (R0 or mR0 and mR1) and 47 patients had negative soft-tissue margins (R0 or mR0 and mR1). The average MSTS score was 88.43 (range: 34.29-100). CONCLUSIONS: We advocate surgery for POS and believe R0 (mR0 and mR1 resections) or planned R1 (mR1-dir) to preserve function are acceptable. We favor chemotherapy and surgery for PerOS, though a chemotherapeutic response is highly variable. High-grade tumors are the most infrequent subtype, but HGSO and dPOS seem to portend a poorer prognosis. Good function can be obtained.

"Angioplasty-First" Approach for Limb Salvage in Asian Patients with Critical Limb Ischemia: Outcomes from 3,303 Angioplasties on 2,402 Limbs in a Single Tertiary Hospital.

PURPOSE: To review outcomes of patients with critical limb ischemia (CLI) who underwent conventional percutaneous transluminal angioplasty (PTA) as first-line treatment for revascularization. MATERIALS AND METHODS: Retrospective review of 3,303 angioplasty procedures on 2,402 limbs in 1,968 patients with CLI was conducted. Mean patient age was 68 years ± 11, and 1,057 patients (54%) were male. Diabetes mellitus (DM) was present in 1,736 patients (88%), and end-stage renal disease (ESRD) in 579 (29%). A majority of patients (90%) had tissue loss. Limb salvage rates were generated by Kaplan-Meier plot. Univariate and multivariate Cox regression analysis was conducted to investigate associations between clinical predictors and time-to-event outcome. RESULTS: Limb salvage rates at 1, 3, 5, and 10 years were 75%, 73%, 72%, and 62%, respectively, and overall survival rates were 79%, 64%, 56%, and 34%, respectively. In multivariable Cox regression analysis with the outcome of major amputation, significant predictors included age < 69 years (P = .032), Malay race (P = .029), DM (P < .001), history of cerebral vascular disease (P = .003), ESRD (P < .001), Rutherford classification (P = .042), repeat intervention (P = .034), and number of straight-line flows (P < .001) and plantar arch integrity (P < .001) on completion angiography. Significant associations with mortality were age < 69 years (P < .001), male sex (P = .030), Malay race (P = .027), history of ischemic heart disease (P < .001), ESRD (P < .001), and repeat intervention (P < .001). CONCLUSIONS: PTA as first-line revascularization for patients with CLI is safe and effective. Further studies are suggested to validate the outcome predictive model.

Predictors and Survival of Patients with Osteosarcoma After Limb Salvage versus Amputation: A Population-Based Analysis with Propensity Score Matching.

BACKGROUND: Conflicting findings have been reported concerning the survival of patients treated with limb salvage and amputation for osteosarcoma. This study aimed to identify predictors associated with surgery types and survival difference. METHODS: Patients with osteosarcoma were selected from the Surveillance Epidemiology and End Results database (1975-2016). Multivariable logistic regression analysis was conducted, and a nomogram was further established. Propensity score matching (PSM)-adjusted Kaplan-Meier curves, log-rank tests, Cox proportional hazards regression analysis were performed to compare overall survival (OS) and cancer-specific survival (CSS). RESULTS: Among 3363 patients with osteosarcoma, 2447 and 916 underwent limb salvage and amputation. Predictors associated with amputation in the nomogram included age, gender, primary tumor site, tumor grade, tumor stage, tumor size and radiotherapy. Totally 900 pairs of patients treated with limb salvage and amputation were matched after PSM. Limb salvage was significantly associated with improved OS (HR, 0.773; 95% CI, 0.670-0.892; p < 0.001) and CSS (HR, 0.795; 95% CI, 0.681-0.927; p = 0.003) in PSM-adjusted cohort after adjusting for related variables. The significant treatment effect of limb salvage was consistent within most subgroups. Among patients treated with surgery for osteosarcoma, age between 41 and 60, age ≥ 61, pelvis as the primary site, high tumor grade (III/IV), regional and distant tumor stage, tumor size ≥ 92 mm and radiotherapy were independent prognostic factors in PSM cohort. CONCLUSIONS: Limb salvage exhibits significant benefit on OS and CSS compared with amputation for osteosarcoma. Predicators and survival differences should be given full consideration for the treatment of osteosarcoma.

Characteristics of high-cost inpatients with peripheral artery disease.

OBJECTIVE: Inpatient treatment of peripheral artery disease (PAD) is more than six times as costly as that of the general inpatient population. Our objective was to describe factors associated with hospital cost for patients admitted for PAD, the characteristics of high-cost patients, and their outcomes including amputations and death. METHODS: We performed a retrospective cohort study of admitted patients receiving a procedure for PAD at The Ottawa Hospital between 2007 and 2016. Demographics, comorbidity, inpatient events, and hospital cost data during the index admission were collected. We defined high-cost patients as those whose total costs of index admission were in the tenth percentile and above. Features associated with high-cost status were examined using logistic regression with elastic net regularization. We used generalized linear models to examine overall drivers of cost. RESULTS: We identified 3084 eligible patients, incurring $72.2 million in hospital costs. The mean cost of the most expensive 10% of patients was $88,076 (standard deviation, $54,720), more than five times the mean cost of $16,217 (standard deviation, $10,322) for nonhigh-cost patients. High-cost patients were more likely to present urgently (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.25; P < .01). After adjustment for preadmission factors, high-cost patients were more likely to have experienced an adverse patient safety incident (OR, 13.49; 95% CI, 6.97-24.8; P < .01), amputation (OR, 2.79; 95% CI, 1.68-4.49; P <.01), intensive care unit admission (OR, 6.42; 95% CI, 3.62-10.2; P < .01), and disposition barriers requiring alternate level of care status (OR, 10.44; 95% CI, 6.42-15.2; P < .01). The high-cost group was more likely to have received hybrid revascularization (OR, 7.07; 95% CI, 3.34-13.6; P < .01). High-cost patients had higher than predicted in-hospital mortality (18% vs 9.2% predicted) compared with the low-cost group (3.0% vs 2.7%; P < .001), and fewer than half of high-cost patients were discharged home. CONCLUSIONS: Providing hospital care for the top 10% most expensive patients in our cohort was more than five times as costly per patient than providing care for the nonhigh-cost patients. Whereas pre-existing factors may predispose a patient to require expensive care, there are potentially modifiable factors during the admission that could reduce costs of these patients.

Extra-articular resection of shoulder joint for bone sarcomas: Oncologic and limb-salvage outcomes of 32 cases compared with shoulder disarticulation and forequarter amputation.

BACKGROUND AND OBJECTIVES: We aimed to identify the overall survival (OS), surgical complications, survival of reconstruction, and functional outcome of patients who underwent extra-articular resection of the shoulder joint for primary bone sarcomas. The OS and local recurrence rates in patients who underwent an amputation were also evaluated for comparison. METHODS: Thirty-two patients treated between 1988 and 2017 were studied. The tumours were located in the humerus in 22 (69%) and scapula in 10 patients (31%). The resection types were Malawer type IV in 6 (19%), type V in 21 (66%), and type VI in 5 patients (15%). Reconstruction was performed with endoprosthesis in 23 patients (72%) while excision arthroplasty with the suspension of the humerus to the clavicle was performed in 9 patients (28%). Surgical margins were wide in 16, marginal in 8, intralesional in 3, and not available in 5 patients. During the study period, 40 patients underwent a forequarter amputation and 11 patients underwent a shoulder disarticulation. RESULTS: The 5-year OS for patients who underwent extra-articular resection of the shoulder joint was 42% which was not statistically different compared with that of patients who underwent amputation (5-year OS = 30%; P = .091). The 5-year survival of the reconstruction was 94%, similar for endoprosthesis and excision arthroplasty. Local recurrence and complications developed in 6 (19%) and 10 patients (31%), respectively. Failures of the reconstruction requiring revision surgery occurred in two patients (6%). Limb salvage was achieved in 30 patients (94%). The median Musculoskeletal Tumour Society functional score was 61% (interquartile range, 57%-70%) and was similar in the endoprosthesis and excision arthroplasty group. CONCLUSIONS: Extra-articular resection of the shoulder joint for bone sarcomas is an effective limb-salvage method. However, local recurrence remains a principal concern.

Open, percutaneous, and hybrid deep venous arterialization technique for no-option foot salvage.

OBJECTIVE: Deep venous arterialization (DVA) is a technique aimed at providing an option for chronic limb-threatening ischemia patients with no options except amputation. In patients with no outflow distal targets permitting bypass, DVA involves creating a connection between a proximal arterial inflow and a distal venous outflow in conjunction with disruption of the vein valves in the foot. This permits blood flow to reach the foot and potentially to resolve rest pain or to assist in healing of a chronic wound. We aimed to provide an up-to-date review of DVA indications; to describe the open, percutaneous, and hybrid technique; to detail outcomes of each of the available techniques; and to relay the postoperative considerations for the DVA approach. METHODS: A literature review of relevant articles containing all permutations of the terms "deep venous arterialization" and "distal venous arterialization" was undertaken with the MEDLINE, Cochrane, and PubMed databases to find cases of open, percutaneous, and hybrid DVA in the peer-reviewed literature. The free text and Medical Subject Headings search terms included were "ischemia," "lower extremity," "venous arterialization," "arteriovenous reversal," and "lower limb salvage." Studies were primarily retrospective case series but did include two studies with matched controls. Recorded primary outcomes were patency, limb salvage, wound healing, amputation, and resolution of rest pain, with secondary outcomes of complication and overall mortality. Studies were excluded if there was insufficient discussion of technical details (graft type, target vein) or lack of reported outcome measure. RESULTS: Studies that met inclusion criteria (12 open, 3 percutaneous, 2 hybrid) were identified, reviewed, and summarized to compare technique, patient selection, and outcomes between open, percutaneous, and hybrid DVA. For open procedures, 1-year primary patency ranged from 44.4% to 87.5%; secondary patency was less reported but ranged from 55.6% at 1 year to 72% at 25-month follow-up. Limb salvage rates ranged from 25% to 100%, wound healing occurred in 28.6% to 100% of cases, and rest pain resolved in 11.9% to 100% across cohorts. For the endovascular approach, primary patency ranged from 28.6% to 40% at 6-month and 10-month follow-up. Limb salvage rates ranged from 60% to 71%, with rates of major amputation ranging from 20% to 28.5%. CONCLUSIONS: This review provides an up-to-date review of DVA indications, description of various DVA techniques, patient selection associated with each approach, and outcomes for each technique.

Simultaneous Superficial Femoral Artery Angioplasty/Stent Plus Popliteal Distal Bypass for Limb Salvage.

BACKGROUND: Treatment of severe critical limb ischemia (CLI) due to superficial femoral artery (SFA) and below-the-knee (BTK) vessels' involvement could be compromised by the lack of a great saphenous vein (GSV) suitable in its entire length. The purpose of this study is to assess the efficacy of a hybrid endovascular and open lower limbs arterial reconstruction in these patients with multilevel, advanced CLI. METHODS: From 2005 to 2019, we performed hybrid endovascular and surgical treatment for limb salvage in SFA-BTK CLI. This consisted of percutaneous transluminal angioplasty (PTA) with or without stenting of the SFA, along with distal origin vein graft bypass. Inclusion criteria were Rutherford category 5 or 6, lack of a suitable GSV, patency of the popliteal artery, steno-obstructive lesions of the SFA, lesions of the 3 crural vessels >5 cm in length each. The follow-up was performed with duplex scan surveillance of both the bypass graft and PTA sites. RESULTS: The hybrid treatment could be performed in 34 patients. Fifty-six percent of the SFA steno-obstructive lesions were treated with simple PTA, except for the application of a bare metal stent in one patient (3%), while in all the SFA occlusions PTA was completed with covered stents (41%). Thirty-four popliteal-to-distal vein bypass grafts bypass grafts have been performed. There were no perioperative PTA or bypass graft failures. Clinical improvement was achieved in 26 (76%) patients. Overall, primary and secondary patency, limb salvage, and survival rates were 65%, 68%, 75%, and 75% at 5 years, respectively. CONCLUSIONS: A hybrid strategy in multilevel SFA-BTK CLI is a well-established approach. Additional studies are warranted to validate these results.

Multidisciplinary approach achieves limb salvage without revascularization in patients with mild to moderate ischemia and tissue loss.

OBJECTIVE: The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system has been validated to predict wound healing and limb salvage of patients with peripheral artery disease (PAD). Our goal was to evaluate the association between WIfI stage and wound healing, limb salvage, and survival in a select cohort of patients with PAD and tissue loss undergoing an attempt of wound healing without immediate revascularization (conservative approach) in a multidisciplinary wound program. METHODS: Veterans with PAD and tissue loss were prospectively enrolled in our Prevention of Amputation in Veterans Everywhere (PAVE) program. Limbs were stratified to a conservative, revascularization, primary amputation, and palliative limb care approach based on the patient's fitness, ambulatory status, perfusion evaluation, and validated pathway of care. Rates of wound healing, wound recurrence, limb salvage, and survival were retrospectively analyzed by WIfI clinical stages (stage 1-4) in the conservative group. Cox regression modeling was used to estimate clinical outcomes by WIfI stage. RESULTS: Between January 2006 and October 2017, there were 961 limbs prospectively enrolled in our PAVE program. A total of 233 limbs with 277 wounds were stratified to the conservative approach. WIfI staging distribution included 19.7% stage 1, 20.2% stage 2, 38.6% stage 3, and 21.5% stage 4. All ischemia scores were classified as 1 or 2. Advanced wound interventions and minor amputations were performed on 40 limbs (16.6%) and 57 limbs (23.7%), respectively. Average long-term follow-up was 41.4 ± 29.0 months. Complete wound healing without revascularization was achieved in 179 limbs (76.8%) during 4.4 ± 4.1 months. Thirty-four limbs (14%) underwent deferred revascularization because of a lack of complete wound healing. At long-term follow-up, wound recurrence per limb was 39%. Overall limb salvage at long-term follow-up was 89.3%. Stratified by WIfI stage, there was no statistically significant difference between groups for wound healing (P = .64), wound recurrence (P = .55), or limb salvage (P = .66) after adjustment for significant patient, limb, and wound characteristics. CONCLUSIONS: In select patients with mild to moderate ischemia and tissue loss, a stratified approach can achieve acceptable rates of wound healing and limb salvage, with limited need for deferred revascularization. WIfI clinical staging did not predict wound healing, limb salvage, or survival in this cohort.

Clinical Outcome and Diverse Risk Factors for Different Therapeutic Target Locations of Peripheral Artery Disease.

AIM: Previous studies on peripheral artery disease (PAD) only enrolled patients with atherosclerotic lesion limited to any one of isolated locations (aortoiliac [AI], femoropopliteal [FP], and below the knee [BTK]). However, the interventions for PAD in a real-world clinical setting are often simultaneously performed for several different locations. METHODS: We conducted a prospective multicenter study that included 2,230 patients with PAD who received intervention for lower extremity lesions in each area and across different areas. Patients were divided into 7 groups according to the combination of treatment locations. Overall survival (OS), major adverse limb events (MALEs), and risk factors for OS and MALEs were statistically analyzed. RESULTS: After adjustment for confounding factors, the attributable risk for OS was similar among isolated AI, FP, and BTK treatments. MALEs increased in correlation with the number of treatment locations. Dialysis and critical limb ischemia were the common risk factors for OS and MALEs. However, the contribution of other factors such as type of drug usage was different according to treatment locations. CONCLUSIONS: In patients with PAD, OS was largely defined by comorbidities but not by lesion location. The background risk factors, underlying comorbidities, and event rates were different according to PAD location, suggesting that stratified treatment should be established for different patient populations.

Is Treatment at a High-volume Center Associated with an Improved Survival for Primary Malignant Bone Tumors?

BACKGROUND: Centralization of cancer care to high-volume facilities has been shown to improve the overall survival of patients with soft-tissue sarcomas. Current evidence regarding the impact of increased hospital volume on treatment patterns and survival rates for patients with primary malignant bone tumors remains limited. Understanding the facility volume-outcome relationship for primary malignant bone tumors will further discussion on ways to promote delivery of quality cancer care across the nation. QUESTIONS/PURPOSES: (1) Is there a difference in overall survival for patients with primary malignant bone tumors undergoing treatment at a high-volume facility (at least 20 patients per year) versus those treated at a low-volume facility (less than 20 patients per year)? (2) Do surgical treatment patterns (limb-salvage versus amputation) and margin status (positive versus negative) vary between high-volume and low-volume facilities? METHODS: The 2004 to 2015 National Cancer Database was queried using International Classification of Disease for Oncology topographical codes to identify patients undergoing treatment (surgery, chemotherapy, and/or radiation therapy) for primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8, and C40.9) or pelvis (C41.4). Histologic codes were used to group the tumors into the following categories: osteosarcomas, Ewing's sarcomas, chondrosarcomas, chordomas, and other or unspecified. Patients who did not receive any treatment (surgery, chemotherapy, and/or radiotherapy) at the reporting facility were excluded from the study. Facility volume was calculated based on the average number of patients per year for the entire study period. A preliminary stratified Cox regression model was used to identify evidence-based thresholds or cutoffs for high-volume and low-volume facilities, while adjusting for differences in patient, tumor, and treatment characteristics. We identified high-volume facilities as those treating at least 20 patients per year and low-volume facilities as those treating fewer than 20 patients per year. A Kaplan-Meier survival analysis was used to report overall unadjusted 5-year survival rates at high-volume and low-volume facilities. Multivariate Cox regression analyses were used to assess whether undergoing treatment at a high-volume facility was associated with a lower risk of overall mortality, after controlling for differences in baseline demographics, tumor presentation, and treatment characteristics. For patients undergoing surgery, multivariate regression models were used to evaluate whether patients receiving care in a high-volume facility were more likely to receive resections with limb salvage surgery than to receive amputation and whether facility volume was associated with a patient's likelihood of having a positive or negative surgical margin. RESULTS: A total of 14,039 patients were included, 15% (2115) of whom underwent treatment in a high-volume facility. Patients undergoing treatment at a high-volume facility were more likely to be white, have tumors involving the pelvis, have larger tumor sizes, and have a higher tumor grade at presentation than those undergoing treatment at a low-volume facility. Unadjusted 5-year overall survival rates were greater for high-volume facilities than for low-volume facilities (65% versus 61%; p = 0.003). After controlling for differences in patient demographics, tumor characteristics (including histologic type, grade, stage, size, and location) and treatment factors, we found that patients treated at high-volume facilities had a slightly lower overall mortality risk than those treated at low-volume facilities (hazard ratio 0.85 [95% CI 0.77 to 0.93]; p < 0.001). Patients treated at high-volume facilities were also slightly more likely to undergo resection with limb-salvage surgery to than to undergo amputation (odds ratio 1.34 [95% CI 1.14 to 1.59]; p = 0.001). Patients undergoing surgical treatment at high-volume facilities also had a lower odds of having positive resection margins than those undergoing treatment at low-volume facilities (OR 0.56 [95% CI 0.44 to 0.72]; p < 0.001). CONCLUSIONS: Patients undergoing treatment for primary malignant bone tumors at high-volume facilities experience a slightly better overall survival than those receiving treatment at low-volume facilities. Further research questioning the value of care at high-volume facilities is required before sweeping changes in regionalization can be considered. LEVEL OF EVIDENCE: Level III, therapeutic study.

Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (ACEI/ARB) are Associated with Improved Limb Salvage after Infrapopliteal Interventions for Critical Limb Ischemia.

BACKGROUND: Angiotensin-converting enzyme Inhibitors and Angiotensin II Receptor Blockers (ACEI/ARB) reduce the risk of cardiovascular events and mortality in patients with peripheral arterial disease (PAD). However, their effect on limb-specific outcomes is unclear. The objective of this study is to assess the effect of ACEI/ARB on patency and limb salvage in patients undergoing interventions for critical limb ischemia (CLI). METHODS: Patients undergoing infrainguinal revascularization for CLI (Rutherford 4-6) between 06/2001 and 12/2014 were retrospectively identified. Primary Patency (PP), Secondary Patency (SP), Limb Salvage (LS), major adverse cardiac events (MACE), and survival rates were calculated using Kaplan-Meier. Multivariate analysis was performed using Cox regression. RESULTS: A total of 755 limbs in 611 patients (311 ACEI/ARB, 300 No ACEI/ARB) were identified. Hypertension (86% vs. 70%, P < 0.001), diabetes (68% vs. 55%, P = 0.001) and statin use (61% vs. 45%, P < 0.001) were significantly greater in the ACEI/ARB group. Interventions were performed mostly for tissue loss (83% ACEI/ARB vs. 84% No ACEI/ARB, P = 0.73). Comparing ACEI/ARB versus No ACEI/ARB, in femoropopliteal interventions, 60-month PP (54% vs. 55%, P = 0.47), SP (76% vs. 75%, P = 0.83) and LS (84% vs. 87%, P = 0.36) were not significantly different. In infrapopliteal interventions, 60-month PP (45% vs. 46%, P = 0.66) and SP (62% vs. 75%, P = 0.96) were not significantly different. LS was significantly greater in ACEI/ARB (75%), as compared to No ACEI/ARB (61%) (P = 0.005). Cox regression identified diabetes (HR 2.4 (1.4-4.1), P = 0.002), ESRD (HR 3.5 (2.1-5.7), P < 0.001), hypertension (HR 0.4 (0.2-0.6), P < 0.001), and ACEI/ARB (HR 0.6 (0.4-0.9), P = 0.03), as factors independently associated with LS after infrapopliteal interventions. Freedom from MACE (ACEI/ARB 37% vs. 32%, P = 0.82) and overall survival (ACEI/ARB 42% vs. 35% No ACEI/ARB, P = 0.84) were not significantly different. CONCLUSIONS: ACEI/ARB is associated with improved limb salvage in CLI patients undergoing infrapopliteal interventions, but not after femoropopliteal interventions. ACEI/ARB had no impact on patency rates. They were also associated with a trend toward improved survival and freedom from MACE. Our findings suggest that the use of ACEI/ARB may improve outcomes in the high-risk CLI patient population.

A propensity-score matched analysis of limb salvage vs amputation for osteosarcoma.

BACKGROUND AND OBJECTIVES: With recent advances in chemotherapy and surgical techniques, the trend in the treatment of osteosarcoma continues to progress towards limb salvage. However, studies comparing limb salvage with amputation continue to be limited by selection bias and small sample sizes. This study utilized propensity-score matching to minimize potential confounders and selection bias to compare the survival rates in patients with osteosarcoma that were treated with amputation vs limb salvage surgery. METHODS: The Surveillance, Epidemiology, and End Results Program was utilized to identify all patients with a diagnosis of extremity osteosarcoma. Patients were matched with demographics, tumor characteristics, and treatment information. These variables were then fitted in a multivariate model and hazard ratios (HR) for overall- and disease-specific mortality was calculated. RESULTS: A total of 4107 patients were identified, of which, 1538 were left after propensity-score matching. Older age, Black race, upper extremity location, and higher American joint committee on cancer (AJCC) class were associated with worse overall- and disease-specific mortality rates (P ≤ .0389). Compared with their matched counterparts, patients treated with amputation had higher overall mortality (HR 1.677; P < .0001) and higher disease-specific mortality (HR 1.678; P < .0001). CONCLUSION: Patients whose tumor characteristics preclude limb salvage have significantly higher overall- and disease-specific mortality rates.

Are Limb-sparing Surgical Resections Comparable to Amputation for Patients With Pelvic Chondrosarcoma? A Case-control, Propensity Score-matched Analysis of the National Cancer Database.

BACKGROUND: Chondrosarcoma is the second most frequent primary sarcoma of bone and frequently occurs in the pelvis. Surgical resection is the primary treatment with the two main operative modalities being limb-sparing resection and amputation. Contemporary management has trended toward limb-sparing procedures; however, whether this approach has an adverse effect on long-term survival is unclear. QUESTIONS/PURPOSES: (1) What are the 5- and 10-year survival rates after limb-sparing surgery and amputation? (2) What factors are associated with survival after contemporary surgical management of pelvic chondrosarcoma? METHODS: The 2004-2014 National Cancer Database, a nationwide registry that includes approximately 70% of all new cancers in the United States with requirement for 90% followup, was reviewed for patients diagnosed with pelvic chondrosarcoma who had undergone limb-sparing surgery or amputation. To compare survival, patient demographics, tumor attributes, and treatment characteristics were used to generate one-to-one propensity score-matched cohorts. Other factors associated with survival were determined through multivariable Cox regression. Three hundred eighty-five patients (75%) underwent limb-sparing surgery and 131 (25%) underwent amputation. Propensity score matching resulted in two balanced cohorts of 131 patients. RESULTS: With the numbers available, we could not demonstrate a difference in overall survival between limb-sparing procedures and amputation. The 5-year survivorship was 70% (95% confidence interval [CI], 62%-79%) for limb-sparing surgery versus 70% (95% CI, 62%-79%) for amputation. The 10-year survivorship was 60% (95% CI, 48%-75%) for limb-sparing surgery versus 59% (95% CI, 48%-72%) for amputation. Kaplan-Meier survival analysis did not demonstrate a difference in survival (p = 0.9). Older age (hazard ratio [HR] = 1.029, p < 0.001), higher Charlson/Deyo comorbidity score (HR = 3.039, p = 0.004), higher grade (HR = 2.547, p = 0.005 for Grade 2; HR = 7.269, p < 0.001 for Grade 3; HR = 10.36, p < 0.001 for Grade 4), and positive surgical margins (HR = 1.61, p = 0.039) were associated with decreased survival. CONCLUSIONS: Our findings support the trend toward increased use of limb-sparing surgery for patients with pelvic chondrosarcoma. Orthopaedic oncologists may use our results when counseling their patients regarding treatment options. However, the choice of limb-sparing surgery versus amputation for these challenging patients should still be a highly individualized decision with careful discussion between the patient and the surgeon. LEVEL OF EVIDENCE: Level III, therapeutic study.

Prognostic factors and survival in Ewing's sarcoma treated by limb salvage surgery.

PURPOSE: Survival in Ewing's sarcoma (ES) has increased with the use of chemotherapy. Surgical techniques such as limb salvage (LS) have been developed. Survival and adverse events have been widely studied in general series of ES, but there are few specific series of ES cases treated by LS, despite this being the most commonly used (surgical) approach. The aim of this study was to determine survival and prognostic factors in ES patients undergoing LS. PATIENTS AND METHODS: We analysed all ES patients treated between January 1984 and May 2008 and selected all those treated by systemic multimodal therapy and LS. We assessed the influence of patient characteristics, tumour parameters and therapeutic results in event-free survival (EFS). RESULTS: Ninety patients were included. Fifty of them were treated by systemic multimodal therapy and locally by LS. ean age was 20 years. Overall survival (OS) was 68.8% and EFS was 60.6% at years. In the univariate analysis, pelvic location, age and response to chemotherapy were associated with poor prognosis. After multivariate analysis, poor response to treatment, pelvis location and age between 12 and 17 years were found to be independent prognostic factors. Dissemination at diagnosis was not a prognostic factor. CONCLUSIONS: OS and EFS in ES treated by LS were similar to findings in previous ES studies. factors are no different, except for the presence of metastasis at diagnosis.

Long-Term Limb Salvage and Amputation-Free Survival After Femoropopliteal Bypass and Femoropopliteal PTA for Critical Ischemia in a Clinical Cohort.

OBJECTIVE:: This population-based retrospective cohort study investigates long-term results of femoropopliteal bypass and femoropopliteal endovascular intervention (PTA) in patients with critical ischemia, with focus on limb salvage and amputation-free survival. METHODS:: All patients who underwent femoropopliteal bypass or femoropopliteal PTA for critical ischemia without other simultaneous intervention between 1999 and 2013 were included. Stratification was according to treatment modality and symptoms, rest pain, or ischemic ulcer/gangrene. We assessed technical success, 30-day complications, length of stay, recurrent interventions, limb salvage, survival, and amputation-free survival in all patients. RESULTS:: We identified 292 operations in 264 patients, 140 bypass and 152 PTA. In 32 PTA cases, the patients were explicitly deemed unfit for bypass surgery. This group had significantly inferior technical success and limb salvage ( P = .00). In other patients, technical success was 96% for bypass and 93% for PTA, while limb salvage after 5 years was 78% for bypass and 81% for PTA. Reoperation for local complications was performed in 16% after bypass and 2% after PTA ( P = .00). Mean length of stay was 8 days after bypass and 1.9 days after PTA ( P = .00). CONCLUSIONS:: Long-term follow-up showed similar technical success and good limb salvage for both PTA and bypass patients in this clinical cohort. Patients who were unfit for bypass surgery had significantly inferior technical success and limb salvage. PTA was associated with shorter hospital stay and fewer reoperations for local complications. The findings support a PTA first strategy in all cases where technical success is likely.

Clinical Characteristics and Surgical Outcomes of Limb-Sparing Surgery with Vascular Reconstruction for Soft Tissue Sarcomas.

BACKGROUND: The standard treatment for lower extremity soft tissue sarcoma (STS) is limb-sparing surgery. For a small subset of patients, concomitant vascular reconstruction may be required to preserve limb viability and function while completely excising the tumor with an adequate resection margin. The aim of this study was to evaluate the surgical outcomes and clinical characteristics of patients with STS of the extremities requiring vascular reconstructions. METHODS: From January 2002 through December 2014, 13 patients with limb STS presenting with vascular invasion underwent surgical resection, followed by vascular reconstruction. The medical records such as demographics, histopathological findings, complications, success of vascular reconstruction, and clinical and oncological outcomes were retrospectively reviewed from a prospectively collected clinical database. RESULTS: With a mean follow-up period of 80.6 months, a total of 24 vascular reconstruction procedures (1 only arterial, 1 only venous, and 11 both arterial and venous) were performed. Contralateral great saphenous vein graft was the conduit of choice for vascular replacement. Five graft thromboses were observed in 4 patients. Arterial occlusion occurred in two cases, and venous bypasses occluded in three patients. The overall five-year patency for arterial and venous reconstructions was 84.6% and 75.2%, respectively. The mean survival period of patients was 105.5 months, with a 5-year disease-free survival rate and overall survival rate of 59.3% and 68.4%, respectively. CONCLUSIONS: Vascular resection and reconstruction for STSs of extremity can be safely performed with acceptable short- and long-term surgical and oncological outcomes. Regardless of the surgical procedure, amputation or limb-sparing surgery, the primary focus should be to adhere to strict oncological principles. In addition, because of the complexity of these tumors, an appropriate preoperative planning and meticulous multidisciplinary approach are also crucial.

Amputation-Free Survival in Patients With Diabetes Mellitus and Peripheral Arterial Disease With Heel Ulcer: Open Versus Endovascular Surgery.

BACKGROUND:: Heel ulcers in patients with diabetes mellitus (DM) and peripheral arterial disease (PAD) are hard to heal. The aim of the present study was to evaluate the difference in amputation-free survival (AFS) between open and endovascular revascularization in patients with DM, PAD, and heel ulcers. METHODS:: Retrospective comparative study of results of open versus endovascular surgery in patients with DM, PAD, and heel ulcer presented at the multidisciplinary diabetes foot clinic between 1983 and 2013. RESULTS:: Patients with heel ulcers were treated with endovascular intervention (n = 97) and open vascular surgery (n = 30). Kaplan-Meier analysis showed that the AFS was higher in patients undergoing open vascular surgery compared to the endovascular group ( P = .009). Multivariate analysis showed that open vascular surgery versus endovascular therapy (hazard ratio 2.1, 95% confidence interval 1.1-3.9; P = .025) was an independent factor associated with higher AFS. The proportion of patients undergoing endovascular therapy in the former (1983-2000) time period was 47% compared to 89% in the latter (2001-2013) time period ( P < .001). CONCLUSION:: The AFS was higher after open than endovascular surgery among patients with DM and PAD with heel ulcer. These results suggest that open vascular surgery should be offered more often as opposed to current practice.