A systematic review and network meta-analysis of the effectiveness of sclerotherapy for venous malformation.

OBJECTIVE: Sclerotherapy for venous malformation has been widely used; however, no guidelines are available to assess the effectiveness of different sclerotherapy agents. We conducted a systematic review and network meta-analysis to investigate the effectiveness of sclerotherapy agents for venous malformations. METHODS: Three electronic databases were searched from their inception (1950) to April 29, 2021. Studies comparing the effectiveness of different sclerotherapy agents were included. The risk of bias within and across studies was assessed. Pairwise meta-analyses were conducted, followed by a network meta-analysis. We also assessed inconsistency and publishing bias using various approaches. RESULTS: Seven studies with 547 patients in six arms were included in the present study. We defined the response and complete response as two separate outcomes. Significant differences were observed in four comparisons with respect to the response (ethanol vs bleomycin, ethanol vs polidocanol, ethanol vs sodium tetradecyl sulfate, polidocanol vs sodium tetradecyl sulfate). No statistically significant differences were found in the other comparisons. The evidence network revealed that for the response outcome, ethanol ranked first, followed by pingyangmycin, polidocanol, sodium morrhuate, bleomycin, and, finally, sodium tetradecyl sulfate. For the complete response outcome, pingyangmycin had the best results, followed by sodium morrhuate, polidocanol, ethanol, bleomycin, and, finally, sodium tetradecyl sulfate. Major complications, such as facial nerve palsy, serious local swelling, and necrosis, had occurred mostly in the ethanol group and rarely in the other groups. Because of the limited data, no further analysis of major complications was conducted. Our confidence in the comparisons and rankings was low. We found no verified inconsistency or publishing bias in the present study using the existing approaches. CONCLUSIONS: Ethanol showed a significantly better response statistically compared with the other agents. However, ethanol had also resulted in the highest incidence of complications. Pingyangmycin showed the second-best response, best complete response, and a low rate of complications, respectively. Overall, pingyangmycin achieved excellent performance and balance in terms of the different outcomes. However, they could not be adequately recommended from the available data. More superior trials, especially randomized controlled trials, are needed in the future.

Effect of Multiple Factors on Foam Stability in Foam Sclerotherapy.

Foam sclerotherapy is a widely used treatment for varicose veins. However, complications caused by poor foam stability still remain. Most studies ignore multiple influencing factors and only study a single factor. Furthermore, a stable foam preparation using different preparation conditions has not been developed. This study aimed to explore the changing laws of foam stability under multifactorial conditions, and to determine the influence of various factors and optimal preparation conditions on the half-life of foam. A two-level orthogonal test was conducted using four factors (syringe size, surfactant, preparation temperature, and pump speed). Classifications were established as follows: syringe sizes, 2.5 mL and 5 mL; surfactant concentrations, 6% and 0%; preparation temperatures, 20 °C and 10 °C; and pump speeds, 250 mm/s and 125 mm/s, respectively. Eight experimental group (EG) multi-factor combinations were tested. Half-life and drainage time were recorded for analysis. The initial drainage time was within 200 s, but the difference between the groups was also about 200 s. The drainage rate curves of all EGs gradually increased over time. Conversely, the foam half-life extended by about 10 times for the four factors. In addition, the analyses revealed that the order of influence was surfactant >temperature >pump speed >syringe size. The most stable foam preparation was determined. Syringe size, surfactant, temperature, and pump speed had markedly observable influences on foam half-life. A combination of multiple factors can be used to prepare a more stable foam in clinical scenarios and to suitably superimpose favorable conditions to avoid unfavorable conditions.

Studies on Foam Decay Trend and Influence of Temperature Jump on Foam Stability in Sclerotherapy.

OBJECTIVES: This study investigated the influence of temperature jump and liquid-gas ratio on foam stability to derive the foam-decay law. METHODS: The experimental group conditions were as follows: mutation temperatures (10°C, 16°C, 20°C, 23°C, 25°C, and 27°C to >37°C) and liquid-gas ratios (1:1, 1:2, 1:3, and 1:4). The control group conditions were as follows: temperatures (10°C, 16°C, 20°C, 23°C, 25°C and 27°C) and liquid-gas ratios (1:1, 1:2, 1:3, and 1:4). A homemade device manufactured using the Tessari DSS method was used to prepare the foam. The decay process was videotape recorded. In the drainage rate curve, the temperature rose, and the liquid-gas ratio varied from 1:1 to 1:4, causing faster decay. RESULTS: In the entire process, the foam volume decreased with increasing drainage rate. The relationships were almost linear. Comparison of the experimental and control groups shows that the temperature jump results in a drainage time range of 1 to 15 seconds. The half-life ranges from 10 to 30 seconds. The maximum rate is 18.85%. Changes in the preparation temperature yields a drainage time range of 3 to 30 seconds. The half-life varies from 20 to 60 seconds. CONCLUSION: Decreasing the temperature jump range and liquid-gas ratio gradually enhances the foam stability. The foam decay time and drainage rate exhibit an exponential function distribution.

Influence of Syringe Volume on Foam Stability in Sclerotherapy for Varicose Vein Treatment.

BACKGROUND: Despite the popularity of sclerotherapy for treating varicose veins, it still exhibits various problems, such as pulmonary embolism, deep-vein thrombosis, phlebitis, and visual disorders. OBJECTIVE: To investigate syringe volume influence on foam stability, obtain the foam decay rule, and provide a reference for clinics. MATERIALS AND METHODS: Five types of syringes are used to prepare foam at room temperature with various liquid-gas ratios. Foam decay process experiments were performed 5 times and recorded by video. The stability indices used include drainage time, half-life, bubble diameter, bubble surface density, and drainage rate. RESULTS: The 30 and 2-mL syringes, respectively, recorded the highest and lowest drainage speeds. Foam drainage time and half-life, differences varied between 15 and 70 seconds, and 20 and 100 seconds, respectively. Foam bubble diameters were distributed over 0.1 to 2.0 mm with roughly 200 to 700 bubbles per square centimeter. CONCLUSION: Increased syringe volume causes the bubble diameter to increase. Thus, foam dispersion increases and foam half-life decreases; hence, foam becomes unstable. It is, thus, better to use a small syringe several times to prepare foam in clinics using segmented injections.

Delivery of sodium morrhuate to hemangioma endothelial cells using immunoliposomes conjugated with anti-VEGFR2/KDR antibody.

Hemangioma is a common benign tumor affecting infants. In this study, we prepared sodium morrhuate immunoliposomes through encapsulation of sodium morrhuate with liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the biology of human hemangioma endothelial cells (HECs). It was found that compared to the liposomal sodium morrhuate group, treatment with sodium morrhuate immunoliposomes facilitated cell detachment and apoptotic death. Confocal microscopy analysis revealed that sodium morrhuate immunoliposomes had a higher binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis further demonstrated that treatment with liposomal sodium morrhuate or sodium morrhuate immunoliposomes significantly induced apoptosis in HECs, compared to the control group. Western blot analysis revealed an induction of caspase-3 and caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with liposomal sodium morrhuate or sodium morrhuate immunoliposomes. Taken together, these results indicate that sodium morrhuate immunoliposomes have an increased capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium morrhuate immunoliposomes may represent a promising agent in the treatment of hemangiomas.

[The analysis of synovial fluid: clinical significance of derived results].

The review presents modern data concerning characteristics of drawing of synovial fluid and also informativeness of its particular indices for resolving main clinical differential diagnostic task namely - selection group of septic and micro-crystal arthritis. It is demonstrated that minimal generally available span of analysis of synovial fluid is to include: finding number of leukocytes (threshold level for diagnostic of septic arthritis is 50 000 - 100 000 kl/mkl) and percentage of ploymorpho-nuclear cells (threshold level is 90%); analysis of content of crystals, Gram's stain and culture analysis of synovial fluid using light microscopy; and all this with mandatory registration of clinical data. The common evaluation of content of glucose and protein in synovialfluid is not enough informative. The detection of concentration of procalcitonin and lactate in synovial fluid is perspective for establishing septic genesis of arthritis. The sensitivity and specificity of light microscopy are quite high. Because of it absence of polarized microscope is no obstacle for implementation of crystallographic analysis of synovial fluid.

Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: a prospective open-label trial.

OBJECTIVES: This study determined whether injection with hypertonic dextrose and morrhuate sodium (prolotherapy) using a pragmatic, clinically determined injection schedule for knee osteoarthritis (KOA) results in improved knee pain, function, and stiffness compared to baseline status. DESIGN: This was a prospective three-arm uncontrolled study with 1-year follow-up. SETTING: The setting was outpatient. PARTICIPANTS: The participants were 38 adults who had at least 3 months of symptomatic KOA and who were in the control groups of a prior prolotherapy randomized controlled trial (RCT) (Prior-Control), were ineligible for the RCT (Prior-Ineligible), or were eligible but declined the RCT (Prior-Declined). INTERVENTION: The injection sessions at occurred at 1, 5, and 9 weeks with as-needed treatment at weeks 13 and 17. Extra-articular injections of 15% dextrose and 5% morrhuate sodium were done at peri-articular tendon and ligament insertions. A single intra-articular injection of 6 mL 25% dextrose was performed through an inferomedial approach. OUTCOME MEASURES: The primary outcome measure was the validated Western Ontario McMaster University Osteoarthritis Index (WOMAC). The secondary outcome measure was the Knee Pain Scale and postprocedure opioid medication use and participant satisfaction. RESULTS: The Prior-Declined group reported the most severe baseline WOMAC score (p=0.02). Compared to baseline status, participants in the Prior-Control group reported a score change of 12.4±3.5 points (19.5%, p=0.002). Prior-Decline and Prior-Ineligible groups improved by 19.4±7.0 (42.9%, p=0.05) and 17.8±3.9 (28.4%, p=0.008) points, respectively; 55.6% of Prior-Control, 75% of Prior-Decline, and 50% of Prior-Ineligible participants reported score improvement in excess of the 12-point minimal clinical important difference on the WOMAC measure. Postprocedure opioid medication resulted in rapid diminution of prolotherapy injection pain. Satisfaction was high and there were no adverse events. CONCLUSIONS: Prolotherapy using dextrose and morrhuate sodium injections for participants with mild-to-severe KOA resulted in safe, significant, sustained improvement of WOMAC-based knee pain, function, and stiffness scores compared to baseline status.

Long-term follow-up evaluation of endoscopic sclerotherapy for dilated gastrojejunostomy after gastric bypass.

BACKGROUND: Endoscopic sclerotherapy using sodium morrhuate has been used to treat patients with weight regain after Roux-en-Y gastric bypass whose presumed etiology is loss of restriction due to gastrojejunostomy dilation. Weight loss and stability have been demonstrated in several studies with short-term follow-up evaluation. METHODS: This retrospective review evaluated all the patients who underwent sclerotherapy for a dilated gastrojejunostomy between 2007 and 2012. RESULTS: The study identified 48 patients with a mean follow-up period of 22 months (range 12-60 months). The mean age of these patients was 47.5 ± 10.5 years, and 92 % were women. The average weight loss from the primary procedure was 132.5 ± 54.82 lb, and the average weight regain from the lowest weight to the maximum weight before sclerotherapy was 46 ± 40.32 lb. The median number of sclerotherapy sessions was two (range 1-4). The pre-procedure mean gastrojejunostomy diameter was 20 ± 3.6 mm, and the mean volume of sodium morrhuate injected per session was 12.8 ± 3.7 ml. The average weight loss from sclerotherapy to the final documented weight was 3.17 ± 19.70 lb, which was not statistically significant. The following variables in the multivariate analysis were not associated with statistically significant weight loss: volume of sodium morrhuate, patient age, gastrojejunostomy diameter, number of sclerotherapy sessions, decrease in gastrojejunostomy diameter between the first and second sessions, and number of follow-up years. Weight stabilization or loss was achieved by 58 % of our cohort, with a mean weight loss of 15.9 ± 14.6 lb in this subgroup. CONCLUSION: The long-term follow-up evaluation of patients undergoing sclerotherapy of the gastrojejunostomy for weight regain after gastric bypass showed only a marginal weight loss, which was not statistically significant in our study population, although more than 50 % of the patients achieved weight loss or stabilization.

Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level, randomized controlled trial.

OBJECTIVE: Chronic lateral epicondylosis is common, debilitating, and often refractory. Prolotherapy (PrT) is an injection therapy for tendinopathy. The efficacy of two PrT solutions for chronic lateral epicondylosis was evaluated. DESIGN: This study is a three-arm randomized controlled trial. Twenty-six adults (32 elbows) with chronic lateral epicondylosis for 3 mos or longer were randomized to ultrasound-guided PrT with dextrose solution, ultrasound-guided PrT with dextrose-morrhuate sodium solution, or watchful waiting ("wait and see"). The primary outcome was the Patient-Rated Tennis Elbow Evaluation (100 points) at 4, 8, and 16 wks (all groups) and at 32 wks (PrT groups). The secondary outcomes included pain-free grip strength and magnetic resonance imaging severity score. RESULTS: The participants receiving PrT with dextrose and PrT with dextrose-morrhuate reported improved Patient-Rated Tennis Elbow Evaluation composite and subscale scores at 4, 8, and/or 16 wks compared with those in the wait-and-see group (P < 0.05). At 16 wks, compared with baseline, the PrT with dextrose and PrT with dextrose-morrhuate groups reported improved composite Patient-Rated Tennis Elbow Evaluation scores by a mean (SE) of 18.7 (9.6; 41.1%) and 17.5 (11.6; 53.5%) points, respectively. The grip strength of the participants receiving PrT with dextrose exceeded that of the PrT with dextrose-morrhuate and the wait and see at 8 and 16 wks (P < 0.05). There were no differences in magnetic resonance imaging scores. Satisfaction was high; there were no adverse events. CONCLUSIONS: PrT resulted in safe, significant improvement of elbow pain and function compared with baseline status and follow-up data and the wait-and-see control group. This pilot study suggests the need for a definitive trial.

The impact of chemical synovectomy with sodium morrhuate on human chondrocytes and cartilage in vitro.

The vessel sclerosing property of sodium morrhuate is useful in treatment of recurrent joint effusions particularly in cases of knee joint effusions. It also can be employed as an addition to surgical synovectomy. Little is known about the effects of this drug on cartilage. This study was designed to investigate the cytotoxic impact of sodium morrhuate on human chondrocytes and cartilage tissue in vitro. Primary chondrocytes from 13 patients were isolated and cultivated in three-dimensional alginate cultures. Furthermore, femoral cartilage explants of 10 patients were cultivated in vitro. Both chondrocytes and cartilage explants were exposed to mixture of sodium morrhuate and mepivacaine in different concentrations simulating chemical synovectomy. After 48 h, cell proliferation, viability, and cytotoxicity were measured. The cartilage specimens were analyzed for apoptosis by immunohistochemistry. Up to a dilution of 1:600, cells were found to be 100 % viable with a proliferation rate of 74 % compared to controls. From 1:400 onwards, a significant increase in LDH release was measured which reached at dilution of 1:200 74 % of high control, whereas histological examination showed no proof of apoptosis or necrosis in cartilage tissue. The results of this in vitro study demonstrate that the cytotoxic effects of sodium morrhuate on human chondrocytes, which lack their original extracellular matrix, manifest between dilutions of 1:500 and 1:400 and increase with higher concentrations of the drug. This effect was not found for cartilage explants, though.

Proteomic analysis of mitochondria from infantile hemangioma endothelial cells treated with sodium morrhuate and its liposomal formulation.

Hemangioma is the most common benign tumor of infancy. The aim of this study is to evaluate the biological effects of sodium morrhuate (SM) and its liposomal formulation on infantile hemangioma endothelial cells (IHECs). Morphological analysis revealed that exposure to liposomal sodium morrhuate (LSM) preferentially caused apoptotic death in IHECs, manifested as shrunken configuration and formation of apoptotic bodies. In contrast, necrotic death was prominent in IHECs treated with an equal concentration of SM. By means of proteomic analysis and confirmation experiments, we revealed that the apoptosis-inducing effects of LSM were associated with an upregulation of a set of genes involved in mitochondrial death pathway, including apoptosis-inducing factor, cytochrome c1, caspase-8, and lamin B1. In conclusion, our data highlight the proapoptotic activity of LSM in IHECs through the mitochondrial apoptotic pathway and may provide a promising avenue to treat hemangiomas of infancy.

Endoscopic sclerotherapy for the treatment of weight regain after Roux-en-Y gastric bypass: outcomes, complications, and predictors of response in 575 procedures.

BACKGROUND: Weight regain after Roux-en-Y gastric bypass (RYGB) is common. Endoscopic sclerotherapy is increasingly used to treat this weight regain. OBJECTIVES: To report safety, outcomes, durability, and predictors of response to sclerotherapy in a large prospective cohort. DESIGN: Retrospective analysis of a prospective cohort study of patients with weight regain after RYGB. PATIENTS: A total of 231 consecutive patients undergoing 575 sclerotherapy procedures between September 2008 and March 2011. INTERVENTIONS: Single or multiple sclerotherapy procedures to inject sodium morrhuate into the rim of the gastrojejunal anastomosis. MAIN OUTCOME MEASUREMENTS: We report weight loss, complications, and predictors of response. We also used Kaplan-Meier survival analysis and log-rank test to compare time to continuation of weight regain after sclerotherapy in patients undergoing a single versus multiple sclerotherapy procedures. RESULTS: At 6 and 12 months from the last sclerotherapy procedure, weight regain stabilized in 92% and 78% of the cohort, respectively. Those who underwent 2 or 3 sclerotherapy sessions had significantly higher rates of weight regain stabilization than those who underwent a single session (90% vs 60% at 12 months; P = .003). The average weight loss at 6 months from the last sclerotherapy session for the entire cohort was 10 lb (standard deviation 16), representing 18% of the weight regained after RYGB. A subset of 73 patients (32% of the cohort) had greater weight loss at 6 months (26 lb, standard deviation 12), representing 61% of the weight regained. Predictors of a favorable outcome included greater weight regain and the number of sclerotherapy procedures. Bleeding was reported in 2.4% of procedures and transient diastolic blood pressure increases in 15%, without adverse health outcomes. No GI perforations were reported. CONCLUSIONS: Endoscopic sclerotherapy appears to be a safe and effective tool for the management of weight regain after RYGB.

Chemical synovectomy with sodium morrhuate in the treatment of symptomatic recurrent knee joint effusion.

The aim of this study was to assess the efficacy and safety of intra-articular sodium morrhuate injections in the treatment of recurrent knee joint effusions. Ninety-eight knees of 92 patients (f = 59, m = 33) with knee arthritis of heterogeneous etiology were treated with chemical synovectomy (CSO). Of those, 39 patients suffered from rheumatoid arthritis (RA). The mean follow-up was 29.8 months. Clinical outcome was evaluated by analyzing subjective patient satisfaction, activity level, pain severity on the basis of the Visual Analogue Pain Scale (VAS), Lysholm and Gillquist score, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Fifty-seven percent of all patients and 67% of patients diagnosed with RA were satisfied with CSO. No significant effects on patient satisfaction by CSO were noted in patients older than 40 years. Overall, VAS, Lysholm and Gillquist score, and KOOS improved significantly at final review. The intra-articular application of sodium morrhuate is an effective and safe measure in the treatment of recurrent symptomatic knee joint effusions in young patients suffering from recurrent knee joint effusions.

Subtotal excision with adjunctive sclerosing therapy for the treatment of severe symptomatic orbital lymphangiomas.

Orbital lymphangiomas are congenital malformations with abnormal and dead-end lymphatic channels and present management challenges to ophthalmologists and orbital surgeons. Recurrent hemorrhage and expansion can lead to vision loss and disfigurement. We report our technique that uses adjunctive intraoperative injection of sodium morrhuate, 5%, under direct visualization into lymphangioma channels prior to excision. We believe that in the hands of experienced orbital surgeons, and with appropriate preoperative evaluation and careful surgical technique, this procedure is useful in saving vision and avoiding complications from orbital lymphangiomas.

Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of prolotherapy versus corticosteroid injection for the treatment of chronic lateral epicondylosis. DESIGN: A prospective, randomized controlled, double-blinded study. SETTING: Academic, tertiary, outpatient, rehabilitation hospital. PARTICIPANTS: Twenty-four subjects with clinically determined chronic (ie, lasting 3 months or longer) lateral epicondylosis were recruited. All subjects noted pain intensity levels significant enough to prevent the participation in activities, such as playing racquet sports or lifting heavy objects. METHODS: Subjects were assigned to receive either prolotherapy or corticosteroid injection for treatment of chronic lateral epicondylosis. Each subject underwent injection at baseline followed by a second injection 1 month later. OUTCOME MEASUREMENTS: Visual analog scale (VAS) self-rating of pain, quadruple visual analog scale (QVAS), and the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) were measured at baseline and at 1, 3, and 6 months' follow-up. RESULTS: Within each group, the analysis demonstrated statistically significant improvements in both VAS and DASH within the prolotherapy group with significant changes noted from baseline to 3 months (VAS: Δ2.38; 95% confidence interval [95% CI] 1.04-3.71, P = .004 and DASH: Δ19.89; 95% CI 5.73-34.04, P = .01), and baseline to 6 months (VAS: Δ2.63; 95% CI 0.61-4.62, P = .017 and DASH: Δ21.76; 9% CI 7.43-36.09, P = .009) after initial treatment, as well as in the QVAS from baseline to 3 months. The steroid group demonstrated a clinically and statistically significant change for DASH only at both 3-month (Δ13.33; 95% CI 0.68-25.99, P = .04) and 6-month (Δ15.56; 95% CI 1.30-29.81, P = .04) follow-up. Comparison of the subjects completing the study revealed no significant differences between the prolotherapy and the corticosteroid group for change in VAS, QVAS, or DASH, although the study lacked sufficient power to draw conclusions from this finding. Eighty-three percent of the subjects were satisfied with their overall improvement during the course of the study, without significant differences revealed between groups. Aside from injection-associated pain, no adverse reactions were reported. Seventeen subjects completed study protocol. CONCLUSIONS: Both prolotherapy and corticosteroid therapy were generally well tolerated and appeared to provide benefit of long duration. Small sample size precludes determining whether one therapy is superior to the other. Larger, controlled trials appear feasible and warranted on the basis of these findings.

Targeted long-term venous occlusion using pulsed high-intensity focused ultrasound combined with a pro-inflammatory agent.

Esophageal and gastric varices are associated with significant morbidity and mortality for cirrhotic patients. The current modalities available for treating bleeding esophageal and gastric varices, namely endoscopic band ligation and sclerotherapy, require frequent sessions to obtain effective thrombosis and are associated with significant adverse effects. A more effective therapy that results in long-term vascular occlusion has the potential to improve patient outcomes. In this study, we investigated a new potential method for inducing long-term vascular occlusion by targeting segments of a rabbit's auricular vein in vivo with low-duty-cycle, high-peak-rarefaction pressure (9 MPa), pulsed high-intensity focused ultrasound in the presence of intravenously administered ultrasound microbubbles followed by local injection of fibrinogen and a pro-inflammatory agent (ethanol, cyanoacrylate or morrhuate sodium). The novel method introduced in this study resulted in acute and long-term complete vascular occlusions when injecting a pro-inflammatory agent with fibrinogen. Future investigation and translational studies are needed to assess its clinical applicability.

Ultrasonography in regenerative injection (prolotherapy) using dextrose, platelet-rich plasma, and other injectants.

Recent advances in ultrasound technology are leading physiatrists to new understandings of pain sources, new treatment options, and the ability to guide soft tissue interventions. This article examines the role of imaging ultrasound in diagnosing soft tissue injury and disease that may respond to regenerative medicine techniques (known as prolotherapy) using injectants such as dextrose, morrhuate sodium, or platelet-rich plasma. The current state of ultrasound evidence for these interventions is reviewed. Case examples assist in understanding clinical applications that currently outpace the evidence base. Development of quantitative ultrasound measures to objectively evaluate soft tissue organization is discussed.