Uterine Fibroid Embolization or Myomectomy: How Much Marketing Is Enough? Comparative Analysis of Public Search Trends in Google and Medical Publications in PubMed.

To compare public popularity and volume of scientific publications regarding uterine fibroid embolization (UFE) and myomectomy. Google Trends and PubMed data were queried to assess temporal variations in online public search volumes and number of research publications for UFE and myomectomy. Time series analysis was used to identify meaningful temporal trends and forecast a future trend. Compared with UFE, myomectomy had significantly higher volumes of public online search and research publications, with an increasing trend over time (P < .0001). The forecasting models predicted a continuing increase in both public search volumes and number of research publications for myomectomy and static future trends in these metrics for UFE. This study signals significantly lower public popularity and research efforts for UFE compared with myomectomy for uterine fibroids. More effective marketing strategies and further research support will be needed to fill this gap.

Peritoneal seeding of embolic beads after uterine artery embolization.

Background: Incidental identification of peritoneal nodules during laparoscopy may present a diagnostic dilemma. The differential diagnosis includes a variety of benign and malignant entities such as peritoneal carcinomatosis. Case: A 44-year-old G2P2 woman presented with recurrent menorrhagia and pelvic pain was found to have large uterine fibroids on imaging studies. Bilateral uterine artery embolization was performed with complete devascularization of the fibroid. Seven years later, she presented with similar symptoms. Imaging studies demonstrated a vascular uterine lesion. A total laparoscopic hysterectomy with bilateral salpingectomy was performed with no complications. During surgery, vesicular peritoneal implants were incidentally identified posterior to the uterus between the uterosacral ligaments. Biopsy and pathologic analysis of these nodules confirmed that they contained foreign material consistent with embolization beads. Pathologic analysis of the uterus demonstrated an intramural uterine fibroid, and presence of embolization beads in cervix, myometrium and bilateral peritubal regions. Conclusion: Non-target peritoneal implantation of embolic beads after uterine artery embolization is a rare entity that can result in vesicular appearing nodules.

Targeted Nanoparticles with High Heating Efficiency for the Treatment of Endometriosis with Systemically Delivered Magnetic Hyperthermia.

Endometriosis is a devastating disease in which endometrial-like tissue forms lesions outside the uterus. It causes infertility and severe pelvic pain in ≈176 million women worldwide, and there is currently no cure for this disease. Magnetic hyperthermia could potentially eliminate widespread endometriotic lesions but has not previously been considered for treatment because conventional magnetic nanoparticles have relatively low heating efficiency and can only provide ablation temperatures (>46 °C) following direct intralesional injection. This study is the first to describe nanoparticles that enable systemically delivered magnetic hyperthermia for endometriosis treatment. When subjected to an alternating magnetic field (AMF), these hexagonal iron-oxide nanoparticles exhibit extraordinary heating efficiency that is 6.4× greater than their spherical counterparts. Modifying nanoparticles with a peptide targeted to vascular endothelial growth factor receptor 2 (VEGFR-2) enhances their endometriosis specificity. Studies in mice bearing transplants of macaque endometriotic tissue reveal that, following intravenous injection at a low dose (3 mg per kg), these nanoparticles efficiently accumulate in endometriotic lesions, selectively elevate intralesional temperature above 50 °C upon exposure to external AMF, and completely eradicate them with a single treatment. These nanoparticles also demonstrate promising potential as magnetic resonance imaging (MRI) contrast agents for precise detection of endometriotic tissue before AMF application.

A novel multimodal nanoplatform for targeting tumor necrosis.

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Thermal Ablation Versus Stereotactic Body Radiotherapy After Transarterial Chemoembolization for Inoperable Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis.

BACKGROUND. Transarterial chemoembolization (TACE) has synergistic properties when combined with ablative therapies for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to compare outcomes for inoperable HCC between TACE with percutaneous thermal ablation (TACE-TA) and TACE with stereotactic body radiotherapy (TACE-SBRT) using propensity score-weighted cohorts. METHODS. This retrospective study included 190 patients with a single inoperable HCC treated from 2007 to 2018 by either TACE-SBRT (n = 90) or TACE-TA (n = 100). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and hepatotoxicity (defined as Child-Pugh score elevation of ≥ 2 within 2-6 months after treatment). Fine-Gray competing risk models with propensity score weighting and transplant as the competing risk factor were used to model OS and PFS. RESULTS. The median follow-up time was 48.2 months. Both OS and PFS were significantly higher for TACE-TA (77% and 76%, respectively, at 2 years) than TACE-SBRT (49% and 50%, respectively, at 2 years) in the propensity score-weighted multivariate model (OS: subdistribution hazard ratio [sHR] = 2.70, p < .001; PFS: sHR = 1.71, p = .02). Treatment-related hepatotoxicity occurred in 9% of patients who underwent TACE-TA versus 27% of those who underwent TACE-SBRT (p = .01). For the subset of patients with Barcelona Clinic Liver Cancer A HCC and Child-Pugh A cirrhosis (TACE-SBRT, n = 36 patients; TACE-TA, n = 55 patients), OS (p = .11) and PFS (p = .19) were not significantly different between the two treatment modalities. CONCLUSION. Compared with TACE-SBRT, TACE-TA showed superior OS and PFS, possibly from its lesser hepatotoxicity. The two strategies did not differ in OS and PFS for patients with the earliest-stage HCC and preserved liver function. CLINICAL IMPACT. Across all patients, TACE-TA may be superior to TACE-SBRT for inoperable HCC.

Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas. MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data. RESULTS: Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was - 4.37( - 5.32, - 3.42), - 4.70( - 5.70, - 3.71), - 0.93( - 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%-100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%). CONCLUSIONS: Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation.

Correction to: Yttrium-90 Radioembolization for BCLC Stage C Hepatocellular Carcinoma Comparing Child-Pugh A Versus B7 Patients: Are the Outcomes Equivalent?

The name of one of the co-authors was slightly misspelled. Kristian Enestvedt is listed currently as "Kristian K. Enestvedt" and should be listed instead as "C. Kristian Enestvedt."

Co-presentation of pulmonary arteriovenous malformation (PAVM) and multifocal benign metastasizing leiomyoma (BML) of lungs: Diagnostic dilemma and successful endovascular treatment.

A 50-year-old female with a 20-year history of multifocal pulmonary benign metastasizing leiomyoma (BML), and asthma presented with subacute worsening of chronic dyspnea. A contrast-enhanced computerized tomography of the chest showed a single 1.4 × 1.5-cm contrast-enhancing mass in the right lower lobe among numerous non-enhancing bilateral pulmonary BML lesions. Pulmonary angiogram was not performed at that time due to clinical improvement. Four years later, the patient presented with refractory subacute worsening of her chronic dyspnea and was referred for embolization of the pulmonary arteriovenous malformation (PAVM). Two feeder arteries to the PAVM were embolized; each with a 6-mm Amplatzer-IV vascular plug and a 4-mm Nester coil. Follow-up angiograms demonstrated no flow through the PAVM. The patient's dyspnea resolved and she remained asymptomatic at one-year follow-up.

Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging.

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to perinecrotic tumor zones. Hypericin is a hydrophobic molecule with high necrosis affinity and fluorescence imaging properties. To date, the safe and effective delivery of hypericin to areas of necrosis in vivo remains a challenge because of its incompatible biophysical properties. To address this issue, we have developed a biodegradable nanoparticle (Hyp-NP) for delivery of hypericin to tumors for necrosis targeting and fluorescence imaging. The nanoparticle was developed using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) and hypericin by a modified solvent evaporation technique. The size of Hyp-NP was 19.0 ± 1.8 nm from cryo-TEM and 37.3 ± 0.7 nm from dynamic light-scattering analysis with a polydispersity index of 0.15 ± 0.01. The encapsulation efficiency of hypericin was 95.05% w/w by UV-vis absorption. After storage for 30 days, 91.4% hypericin was retained in Hyp-NP with nearly no change in hydrodynamic size, representing nanoparticle stability. In an ovarian cancer cell line, Hyp-NP demonstrated cellular internalization with intracellular cytoplasmic localization and preserved fluorescence and necrosis affinity. In a mouse subcutaneous tumor model, tumor accumulation was noted at 8 h postinjection, with near-complete clearance at 96 h postinjection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histological analysis of harvested organs demonstrated no gross abnormalities, and in vitro, no hemolysis was observed. This proof-of-concept study demonstrates the potential clinical applications of Hyp-NP for necrosis targeting.

Yttrium-90 Radioembolization for BCLC Stage C Hepatocellular Carcinoma Comparing Child-Pugh A Versus B7 Patients: Are the Outcomes Equivalent?

OBJECTIVE: To evaluate yttrium-90 (Y90) radioembolization outcomes across Child-Pugh scores in patients with advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From April 2005 to December 2018, 106 consecutive patients with BCLC Stage C HCC who underwent Y90 radioembolization were retrospectively analyzed. Exclusion criteria included additional malignancy (n = 7), death unrelated to liver disease (n = 2), metastases (n = 2), or lack of follow-up data (n = 4). Ninety-one patients were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method and compared between groups with the log-rank test. Cox regression modeling was used to evaluate the prognostic factors for survival. RESULTS: Mean age was 63 years and 85.7% were male. HCV infection was the most common etiology of liver disease (58.2%). Sixty-four (70.3%) patients were Child-Pugh A, 19 (20.9%) patients were B7, and eight (8.8%) patients were B8-9. Median OS after radioembolization was 20.2 [95% confidence interval (CI) 13.0-27.4], 6.0 (95% CI 4.4-7.6), and 5.5 (95% CI 2.5-8.5) months for Child-Pugh A, B7, and B8/9 groups, respectively (P < 0.001 for B7 vs. A; P = 0.537 for B7 vs. B8/9). The multivariable Cox regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score (P < 0.001), Child-Pugh class (P = 0.005), tumor morphology pattern (P = 0.012), and Y90 delivery location (P = 0.020) were significant independent predictors of overall survival. CONCLUSIONS: Outcomes from Y90 for BCLC C HCC for Child-Pugh B7 patients were equivalent to B8/9 patients and significantly worse compared to Child-Pugh A patients. Although further research is warranted, these results suggest continued cautious patient selection for radioembolization in advanced HCC.

Endovascular Treatment of Tracheoinnominate Artery Fistula: Case Report and Literature Review With Pooled Cohort Analysis.

To pool data from published cases of tracheoinnominate artery fistula (TIF) treated with surgical or endovascular techniques along with reporting a case of similar presentation. A total of 261 cases in 137 published case reports and case series were identified through a comprehensive systematic literature review. Data regarding patient characteristics, treatment, and follow-up were extracted. A local case of a 14-year-old boy with TIF due to longstanding tracheostomy treated with stent-graft placement was added to the data. Comparison of the complication rates between surgical vs endovascular interventions was done with the chi-square test. Factors associated with longer survival were assessed by the Cox regression analysis. Thirty-three (12.6%) of the reported cases were treated endovascularly, 137 (52.3%) were treated surgically, and 92 (35.1%) were reported with no definitive treatment. Mean age was 34 ± 22 years, and 61% were males. The mean time interval between tracheotomy placement and bleeding was 1 ± 2.5 years. A lower procedure-related complication (30% vs 50%, P = 0.045) and 30-day mortality (9% vs 23%, P = 0.008) rates had been reported with percutaneous approaches compared to surgery. No percutaneous procedure was reported prior to year 2000. In multivariate analysis stratified by publication year, a shorter tracheostomy-to-bleeding time (year) was significantly associated with higher hazards of death (hazard ratio: 1.22, P = 0.017). Type of intervention (percutaneous vs surgery) was not associated with postintervention survival (adjusted hazard ratio: 0.78, P = 0.558). Endovascular stent grafting can have a comparable postprocedural survival and lower complication rates vs open surgical repair in treatment of TIF.

Effectiveness of Thermal Ablation for Aldosterone-Producing Adrenal Adenoma: A Systematic Review and Meta-Analysis of Clinical and Biochemical Parameters.

PURPOSE: To assess the effectiveness of thermal ablation for aldosterone-producing adrenal adenoma. MATERIALS AND METHODS: A systematic search of the PubMed and CINAHL databases was performed to identify studies of thermal ablation for adrenal adenomas. Random effects meta-analysis models were used to compare pre- and post-treatment values of the following outcomes: systolic blood pressure (SBP), diastolic blood pressure (DBP), use of antihypertensive medications, and biochemical parameters (plasma aldosterone levels, aldosterone-to-renin ratio, and potassium levels). The rate of hypertension (HTN) resolution and improvement were also evaluated. RESULTS: A total of 89 patients from 7 studies were included in the analysis. The mean postablation follow-up duration was 45.8 months. Pooled data analysis revealed a statistically significant decrease in SBP (-29.06 mm Hg; 95% confidence interval [CI], -33.93 to -24.19), DBP (-16.03 mm Hg; 95% CI, -18.33 to -13.73), and the number of antihypertensive medications used (-1.43; 95% CI, -1.97 to -0.89) after ablation. Biochemical parameters had returned to normal ranges after ablation in all studies. The cumulative rate of resolution or improvement in HTN status was 75.3%. On metaregression analysis, there was no statistically significant association between postablation blood pressure changes or serum aldosterone levels and study follow-up duration. CONCLUSIONS: Thermal ablation for aldosterone-producing adrenal adenoma can be effective in controlling blood pressure, reducing the need for antihypertensive medications, and normalizing hormone secretion. Further higher-quality evidence is needed to confirm these results.

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy.

PURPOSE: To assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for in vivo localization and combinatorial phototherapy. MATERIALS AND METHODS: A VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery. Tumors were exposed via laparotomy, and nanoparticles were observed by near-infrared (NIR) fluorescence imaging. For phototherapy, a handheld NIR laser (785 nm) at 0.6 W/cm2 was used to expose tumor or background liver, and tissue temperatures were assessed with a fiberoptic temperature probe. Intratumoral reactive oxygen species formation was assessed using a fluorophore (2',7'-dichlorodihydrofluorescein diacetate). RESULTS: Nanoparticles selectively accumulated within viable tumor by NIR fluorescence. Necrotic portions of tumor did not accumulate nanoparticles, consistent with a vascular distribution. NIR-dependent heat generation was observed with nanoparticle-containing tumors, but not in background liver. No heat was generated in the absence of NIR laser light. Reactive oxygen species were formed in nanoparticle-containing tumors exposed to NIR laser light, but not in background liver treated with NIR laser or in tumors in the absence of NIR light. CONCLUSIONS: Biodegradable nanoparticle delivery to liver tumors from a transarterial approach enabled selective in vivo tumor imaging and combinatorial phototherapy.

Long-Term Toxicity after Transarterial Radioembolization with Yttrium-90 Using Resin Microspheres for Neuroendocrine Tumor Liver Metastases.

PURPOSE: To evaluate long-term effects of yttrium-90 (90Y) transarterial radioembolization (TARE) for unresectable hepatic metastases of neuroendocrine tumors (NETs). MATERIALS AND METHODS: Retrospective analysis of 93 patients (47 women, 46 men; mean age 59 y) who underwent resin-based 90Y TARE was performed. Variables associated with overall survival were analyzed using univariate and multivariate models. Changes in serologic values and imaging characteristics were assessed with long-term follow-up. RESULTS: Unilobar TARE was performed in 48 patients, and staged bilobar TARE was performed in 45 patients. In multivariate analysis, ascites (P = .002) and extrahepatic metastases (P = .038) at baseline were associated with poor survival. Among 52 patients who had > 1 year of follow-up, significant increases in alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were observed; however, only 4 patients experienced grade 3 serologic toxicities. Imaging signs of cirrhosis-like morphology and portal hypertension were observed in 15 of 52 patients, more frequently in patients treated with bilobar TARE compared with unilobar TARE. Patients treated with bilobar TARE exhibited significantly increased hepatobiliary enzymes and decreased platelet count. Sustained increases in liver enzymes were observed in patients with > 4 years of follow-up. No radioembolization-related liver failure or grade 4 toxicity was observed. CONCLUSIONS: 90Y radioembolization using resin microspheres demonstrated a high safety profile for NET liver metastases, with low-grade, although sustained, long-term liver toxicity evident > 4 years after treatment. Bilobar treatment suggested a trend for treatment-related portal hypertension. Ongoing research will help define parameters for optimizing durable safety and efficacy of radioembolization in this setting.

Tumor Dose Response in Yttrium-90 Resin Microsphere Embolization for Neuroendocrine Liver Metastases: A Tumor-Specific Analysis with Dose Estimation Using SPECT-CT.

PURPOSE: To evaluate dose-response relationship in yttrium-90 (90Y) resin microsphere radioembolization for neuroendocrine tumor (NET) liver metastases using a tumor-specific dose estimation based on technetium-99m-labeled macroaggregated albumin (99mTc MAA) single photon emission computed tomography (SPECT)-CT. MATERIALS AND METHODS: Fifty-five tumors (mean size 3.9 cm) in 15 patients (10 women; mean age 57 y) were evaluated. Tumor-specific absorbed dose was estimated using a partition model. Initial (median 2.3 months) follow-up data were available for all tumors; last (median 7.6 months) follow-up data were available for 45 tumors. Tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors (mRECIST) on follow-up CT. Tumors with complete or partial response were considered responders. Mean tumor absorbed dose was 231.4 Gy ± 184.3, and mean nontumor liver absorbed dose was 39.0 Gy ± 18.0. RESULTS: Thirty-six (65.5%) and 30 (66.7%) tumors showed response at initial and last follow-up, respectively. Mean absorbed doses in responders and nonresponders at initial and last follow-up were 285.8 Gy ± 191.1 and 128.1 Gy ± 117.1 (P = .0004) and 314.3 Gy ± 195.8 and 115.7 Gy ± 117.4 (P = .0001). Cutoff value of ≥ 191.3 Gy for tumor-specific absorbed dose predicted tumor response with 93% specificity, whereas < 72.8 Gy predicted nonresponse with 100% specificity at last follow-up. Estimated mean absorbed tumor dose per patient was significantly higher in responders versus nonresponders over the follow-up period (224.5 Gy ± 90.3 vs 70.0 Gy ± 28.0; P = .007). CONCLUSIONS: Tumor-specific absorbed dose, estimated with a partition model, was significantly associated with tumor response in NET liver metastases. An estimated dose ≥ 191.3 Gy predicted treatment response with high sensitivity and specificity.

Percutaneous renal artery revascularization after prolonged ischemia secondary to blunt trauma: pooled cohort analysis.

PURPOSE: We aimed to identify factors related to technical and clinical success of percutaneous revascularization for blunt renal arterial trauma. METHODS: All cases of percutaneous revascularization for blunt renal arterial trauma were searched in the available literature. We included a case of iatrogenic renal artery occlusion at our institution treated by percutaneous stenting 20 hours after injury. A pooled cohort analysis of percutaneous revascularization for blunt renal artery injury was then performed to analyze factors related to technical and clinical success. Clinical failure was defined as development of new hypertension, serum creatinine rise, or significant asymmetry in split renal function. RESULTS: A total of 53 cases have been reported, and 54 cases were analyzed including our case. Median follow-up was 6 months. Technical success was 88.9% and clinical success was 75%. Of 12 treatment failures (25%), 66.7% occurred during the first postprocedure month. Time from injury to revascularization was not a predictor of clinical success (OR=1.00, P = 0.681). Renal artery occlusion was significantly associated with clinical failure (OR=7.50, P = 0.017) and postintervention antiplatelet therapy was significantly associated with treatment success (OR=0.16, P = 0.043). At 37-month follow-up, the stented renal artery in our case remained patent and the patient was normotensive with preserved glomerular filtration rate. CONCLUSION: Percutaneous revascularization for blunt renal arterial injury resulted in relatively high technical and clinical success. Time-to-revascularization was independent of successful outcomes. Clinical success was significantly associated with a patent renal artery at the time of intervention and with postprocedure antiplatelet therapy.

Effect of systemic insulin treatment on diabetic wound healing.

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates.