CT-guided quadratus femoris injection for ischiofemoral impingement.

OBJECTIVES: To describe the technique, efficacy, and safety of CT-guided quadratus femoris injection with corticosteroid and local anesthetic for the treatment of ischiofemoral impingement in a series of cases at our institution. METHODS: Cases of CT-guided quadratus femoris injections from 2000 to 2021 were identified in the enterprise-wide electronic medical record of our institution. Patient charts and our institutional picture archiving and communication system (PACS) were searched for demographics, pain level on a 0-10 scale before and immediately following the procedure, procedure technique, and follow-up outcomes if available. RESULTS: There were 13 cases among 12 patients with clinical and imaging findings of ischiofemoral impingement included in this study. Of the 12 patients, 10 were female and two were male. There were eight posterior approaches and five posterolateral approaches. Of the 13 cases, 11 resulted in immediate pain reduction. The median reduction in pain score was four (average 3.46, range 0-8.5). There was no statistically significant difference in pain reduction between the posterior approach cases and the posterolateral approach cases. No cases reported immediate complications or increases in pain score. Of the 12 cases, seven resulted in at least 1 month of pain relief, three had subsequent surgeries, and three had no follow-up. CONCLUSION: CT-guided quadratus femoris injection is safe and effective for treating ischiofemoral impingement. Further and larger scale study is needed to fully delineate differences in technique effectiveness. KEY POINTS: • CT-guided quadratus femoris injection is safe and effective for treating ischiofemoral impingement. • We found no statistically significant difference in pain reduction between the posterior approach and the posterolateral approach.

Different Types of Auricular Keloids and Treatment by Intralesional Cryosurgery: Best Practice for Obtaining Long-Lasting Clinical Results.

BACKGROUND: Auricular keloids belong to the most perplexing medical conditions, which have significant psychosocial impact on the patient's body image and quality of life. SUMMARY: The article is purposed to provide dermatologists and plastic surgeons with the best proven practice using intralesional cryosurgery for the treatment of the different auricular keloid types in order to obtain superior clinical results by minimizing the probability of recurrence. In the past 20 years, the authors have developed novel procedures in order to increase the effectiveness of intralesional cryosurgery on auricular keloids, including hydrodissection, warm gauze technique, and excision of dangling skin. Long-lasting clinical results with a low recurrence rate and a satisfactory aesthetic outcome are achieved with no deformation of the ear framework.

Victorian Institute of Sport Assessment-Achilles (VISA-A) Questionnaire-Minimal Clinically Important Difference for Active People With Midportion Achilles Tendinopathy: A Prospective Cohort Study.

OBJECTIVE: To determine the minimal clinically important difference (MCID) for the Victorian Institute of Sport Assessment-Achilles (VISA-A) score in patients with midportion Achilles tendinopathy (AT). DESIGN: Prospective cohort study. METHODS: We included physically active patients with midportion AT who received exercises and an injection. We measured the VISA-A score (ranging from 0 to 100 points, where 100 points represents a healthy tendon) at baseline and at 12 weeks and 24 weeks after treatment, and the 7-point Global Assessment Scale (ranging from "worse than ever" to "completely recovered") at 12 weeks and 24 weeks after treatment. We dichotomized the Global Assessment Scale to not improved ("worse than ever" to "unchanged") or improved ("moderately improved" to "completely recovered"). The area under the curve and the Youden's index value closest to 1 were determined for both MCIDs (12 and 24 weeks), with corresponding sensitivity and specificity. RESULTS: Sixty-four patients were included, and 61 patients (95%) completed the 24-week follow-up. The MCID was 14 points (95% confidence interval [CI]: 3, 19) over a 12-week period, corresponding to 57% sensitivity and 88% specificity. The MCID was 7 points (95% CI: -10, 28) over a 24-week period, with 85% sensitivity and 62% specificity. CONCLUSION: A change in VISA-A score of at least 14 points after 12 weeks or at least 7 points after 24 weeks of exercise therapy and an injection reflects a meaningful change for physically active patients with midportion AT. J Orthop Sports Phys Ther 2021;51(10):510-516. doi:10.2519/jospt.2021.10040.

Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKVBR in Mice Bearing Embryonal CNS Tumors.

The Zika virus (ZIKV) has shown a promising oncolytic effect against embryonal CNS tumors. However, studies on the effect of different administration routes and the ideal viral load in preclinical models are highly relevant aiming for treatment safety and efficiency. Here, we investigated the effect and effectiveness of different routes of administration, and the number of ZIKVBR injections on tumor tropism, destruction, and side effects. Furthermore, we designed an early-stage human brain organoid co-cultured with embryonal CNS tumors to analyze the ZIKVBR oncolytic effect. We showed that in the mice bearing subcutaneous tumors, the ZIKVBR systemically presented a tropism to the brain. When the tumor was located in the mice's brain, serial systemic injections presented efficient tumor destruction, with no neurological or other organ injury and increased mice survival. In the human cerebral organoid model co-cultured with embryonal CNS tumor cells, ZIKVBR impaired tumor progression. The gene expression of cytokines and chemokines in both models suggested an enhancement of immune cells recruitment and tumor inflammation after the treatment. These results open new perspectives for virotherapy using the ZIKVBR systemic administration route and multiple doses of low virus load for safe and effective treatment of embryonal CNS tumors, an orphan disease that urges new effective therapies.

Tumor eradicated by combination of imiquimod and OX40 agonist for in situ vaccination.

Various cancer vaccines have been developed to generate and amplify antigen-specific T cell responses against malignancy. Among them, in situ vaccination is one of the most practical types as it can trigger immune responses without previous antigen identification. Here we reported a novel in situ vaccine by intratumoral injection of imiquimod and OX40 agonist. In mice bearing hepatic carcinoma, both the injected tumor and the noninjected tumor in the distant lesion of the same mice were suppressed after vaccination. Further studies found that this in situ vaccine triggered systemic tumor-specific responses, with one-fold increase of effector memory T cells properties and stronger toxicity of lymphocytes in spleen. Besides, we found that imiquimod upregulated the expression of OX40 on CD4+ T cells and thus enhanced the effectiveness of OX40 agonist. Five immune-positive-related pathways were activated after vaccination. This in situ vaccine caused little harm to normal organs and provided long-term protection against the same syngeneic tumor rechallenge. Due to its effectiveness, feasibility and safety, this strategy could potentially be applied to various types of late-stage solid tumors and worthy of further clinical research.

The effect of botulinum toxin injection dose on the appearance of surgical scar.

Early postoperative injection of botulinum toxin type A (BTxA) can reduce surgical scar hypertrophy. BTxA injection at different time points is associated with different levels of efficacy, but the efficacy of different doses of BTxA for scar management has not investigated. The purpose of this study was to investigate the effect of different doses of BTxA administered early after surgery on scar improvement through a split-scar experiment. The study included 22 patients who underwent surgery between September 2019 and October 2020. High- and low-dose BTxA was randomly administered into each half of the surgical wound closure immediately after surgery. One half of the incision was injected with a low dose (4 U) of BTxA, and the other half was injected with a high dose (8 U). The scars were then evaluated at postoperative 6 months using the modified Stony Brook Scar Evaluation Scale (mSBSES), and patient satisfaction was evaluated using the Visual Analogue Scale (VAS). The occurrence of complications or adverse events was also recorded. Twenty patients completed the study and were analyzed. Compared with the low-dose sides, the high-dose sides had significantly better mSBSES scores and significantly higher VAS scores (p < 0.01, respectively). No serious adverse reactions or post-injection complications were observed. Immediately after the operation, high-dose BTxA (that is within the therapeutic range) injection improved the appearance of postoperative scar more than low-dose injection.

Corticosteroid Injection for Morton's Interdigital Neuroma: A Systematic Review.

BACKGROUD: This review aimed to evaluate the effects of corticosteroid injections on Morton's neuroma using an algorithmic approach to assess the methodological quality of reported studies using a structured critical framework. METHODS: Several electronic databases were searched for articles published until April 2020 that evaluated the outcomes of corticosteroid injections in patients diagnosed with Morton's neuroma. Data search, extraction, analysis, and quality assessments were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). guidelines, and clinical outcomes were evaluated using various outcome measures. RESULTS: With 3-12 months of follow-up, corticosteroid injections provided satisfactory outcomes according to Johnson satisfaction scores except in two studies. Visual analog scale scores showed maximal pain reduction between 1 week and 3 months after injection. We found that 140 subjects out of 469 (29.85%) eventually underwent surgery after receiving corticosteroid injections due to persistent pain. CONCLUSIONS: Corticosteroid injections showed a satisfactory clinical outcome in patients with Morton's interdigital neuroma although almost 30% of the included subjects eventually underwent operative treatment. Our recommendation for future research includes using more objective outcome parameters, such as foot and ankle outcome scores or foot and ankle ability measures. Moreover, studies on the safety and effectiveness of multiple injections at the same site are highly necessary.

Antireflux endoscopic injection therapy in post-pubertal patients via techniques adopted for the dilated ureteral orifice: a retrospective single-center study.

BACKGROUND: To investigate the efficacy and safety of endoscopic injection therapy for vesicoureteral reflux in post-pubertal patients with dilated ureteral orifice via modified hydrodistension implantation techniques. METHODS: We retrospectively reviewed medical records including operational procedure and clinical course of all consecutive patients over 12 years old with a history of injection therapy. Endoscopic injection of dextranomer/hyaluronic acid copolymer was performed under hydrodistension implantation technique with some modifications in order to inject through dilated ureteral orifice align with the intramural ureter. Technical selections were done according to hydrodistension grade of the ureteral orifice. Voiding cystourethrography was evaluated at 3 months postoperatively. Hydronephrosis was evaluated using ultrasonography preoperatively until 6 months postoperatively. RESULTS: From 2016 to 2019, 12 patients (all female, 16 ureteral units; median age 32 [range 15-61] years) underwent endoscopic injection therapy at one of our institutions. We have identified grade II vesicoureteral reflux in 5 ureters, grade III in 8, and grade IV in 3 ureters. Grade 3 ureteral-orifice dilation were presented in 12 ureters (75%), grade 2 in 3 and grade 1 in 1 ureter in the present cases. Postoperatively, vesicoureteral reflux was diminished to grade 0 in 12 ureteral units (75%), decreased to grade I in 3 (9%), and remained grade III in 1 (6%). Three patients reported dull flank pain for several days postoperatively and there was 1 case of acute pyelonephritis. Temporary hydronephrosis was confirmed in 3 ureteral units (19%) at 1 month postoperatively. Median follow-up duration was 23 (range 13-63) months long. Although, 3 patients were experienced f-UTI 1-2 times, repeated VCUG showed no VUR recurrence. CONCLUSIONS: According to hydrodistension grade of the ureteral orifice, endoscopic injection therapy via modified hydrodistension implantation technique is an effective and safe treatment for vesicoureteral reflux in post-pubertal female patients with dilated ureteral orifice. While ureteral deformities or a history of anti-reflux surgery may increase the risks, these can be managed with appropriate methods that ensure sufficient mound appearance and height.

Treatment of in-transit melanoma metastases using intralesional PV-10.

Melanoma in-transit metastases (ITMs) can sometimes be difficult to manage by surgical excision due to their number, size or location. Treatment by intralesional injection of PV-10, a 10% solution of rose bengal, has been reported to be a simple, safe and effective alternative, but more outcome data are required to confirm its value in the management of ITMs. Two hundred and twenty-six melanoma ITMs in 48 patients were treated with intralesional PV-10 supplied under a special-access scheme. By 8 weeks a complete response in all injected ITMs was achieved in 22 patients (46%) and a partial response in 19 patients (40%). Of 19 patients who had uninjected metastases, 3 (16%) had a response in these. The most common adverse event was transient localised pain in injected tumours. New ITMs developed in 25 patients within 8 weeks, and later in another 8 patients. Repeat injection cycles were given to 21 patients: 13 of these received repeat injection into partially responding or nonresponding tumours, 5 had new ITMs, as well as partially-responding lesions injected, and 3 received injection into new ITMs only. Twenty-two patients received subsequent systemic therapy. At 1 year 37 of the 48 patients were alive, 28 with melanoma, and at 2 years 27 were alive, and 19 with melanoma. Injection of PV-10 was simple and safe and resulted in tumour involution in most patients and sometimes in noninjected tumours. However, many patients developed new lesions; these were treated by further PV-10 injections or with alternative therapies.

The Islanding effect - a special method of percutaneous peritumor ethanol injection for hepatocellular carcinoma: 15-year follow-up outcome.

ABSTRACT: Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study.Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database.The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child-Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child-Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival.Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.

Ultrasound-guided Intralesional Injection of Talimogene laherparepvec (Imlygic) for Advanced Melanoma: Technical Note on a Preliminary Experience.

PURPOSE: To evaluate the safety and feasibility of ultrasound-guided intralesional injection of Talimogene laherparepvec (Imlygic, T-VEC) in patients with advanced non-palpable melanoma. MATERIALS AND METHODS: Fourteen consecutive patients (mean age, 67.9 years ± 13.0; range, 40-88; 12 males) with unresectable, locally advanced melanoma underwent ultrasound-guided intralesional injections of T-VEC (July 2016-March 2020) into subcutaneous lesions. Tumor response to the injection was evaluated at the last follow-up. Technical success and complication rates were recorded. RESULTS: The T-VEC injection was technically successful in all patients with all lesions successfully punctured (100%). The mean number of lesions, injection cycles, and injection volumes were 4.1 ± 2.6 (1-9), 6.5 ± 3.0 (3-12), and 2.6 mL ± 1.4 (1-4 mL), respectively. During the follow-up period (mean, 21.0 months ± 13.4; range 1-43.6 months), complete remission, partial remission, persistent disease, and disease progression were observed in 6 (42.9%), 3 (21.4%), 1 (7.1%), and 4 (28.6%) patients, respectively. Post-treatment symptoms observed in 9 patients (64.3%), including fever (n = 2), fatigue (n = 1), headache (n = 1), pain (n = 1), mouth sores (n = 1), and flu-like symptoms (n = 3). No injection-related complications occurred in all procedures. CONCLUSION: Intralesional injection of T-VEC for non-palpable metastases under ultrasound guidance is safe and feasible in patients with advanced melanoma.

T-VEC for stage IIIB-IVM1a melanoma achieves high rates of complete and durable responses and is associated with tumor load: a clinical prediction model.

BACKGROUND: Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy. METHODS: Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2020-01 with a follow-up time > 6 months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR. RESULTS: A total of 93 patients were included with a median age of 69 years, median follow-up time was 16.6 months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting > 6 months) was 51%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, prior treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving CR. The prediction model includes the predictors tumor size, type of metastases and number of lesions. CONCLUSIONS: This study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease.

Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4+ T cells, decreased numbers of regulatory T cells (Treg), and activation of the myeloid compartment. Importantly, the immunotherapy-enabling benefits of IL-12 are achieved with minimal systemic effects. Our findings thus show that local delivery of IL-12 may be an effective adjuvant for CAR-T cell therapy for GBM.

Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar.

OBJECTIVES/HYPOTHESIS: Vocal fold atrophy, scar, and sulcus reduce the vibratory function of the vocal fold mucosa, which causes severe refractory dysphonia. We have reported encouraging preliminary results using an intracordal injection of basic fibroblast growth factor (bFGF) and showed improvement in phonatory parameters and voice. The present study summarizes our experience with 100 cases of stiffened vocal folds that were treated with bFGF injections. STUDY DESIGN: Retrospective chart review with Interstitial Review Board (IRB) approval. METHODS: Local injection of bFGF was performed in 100 cases of vocal fold pathology, which included 43 cases of vocal fold atrophy, 41 cases with scar, and 16 cases with sulcus. Ten micrograms of bFGF were injected into the vocal folds under topical anesthesia 4 times in each patient. Therapeutic outcomes were examined with maximum phonation time (MPT), voice handicap index-10 (VHI-10), and GRBAS scale. RESULTS: MPT, VHI-10, and GRBAS scores significantly improved in all pathology groups. An improvement on the VHI-10 greater than five points was observed in 82% of atrophy cases, 78% of scar cases, and 67% of sulcus cases. Improvement on the VHI-10 was significantly better in the atrophy group than the scar or sulcus groups. The mild/moderate cases of scar and sulcus showed better improvement than severe cases. CONCLUSIONS: The current large case series indicates positive effects of intracordal injection of bFGF for improvement of voice with no severe adverse events. The effects appeared best for cases of atrophy, while the treatment of severe scar and sulcus requires further improvement. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2059-2064, 2021.

Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile.

PURPOSE: Cervical cancer represents the fourth most frequent malignancy in the world among women, and mortality has remained stable for the past 4 decades. Intravenous cisplatin with concurrent radiation therapy is the standard-of-care for patients with local and regional cervical cancer. However, cisplatin induces serious dose-limiting systemic toxicities and recurrence frequently occurs. In this study, we aimed to develop an intracervical drug delivery system that allows cisplatin release directly into the tumor and minimize systemic side effects. METHODS AND MATERIALS: Twenty patient biopsies and 5 cell lines treated with cisplatin were analyzed for platinum content using inductively coupled plasma mass spectrometry. Polymeric implants loaded with cisplatin were developed and evaluated for degradation and drug release. The effect of local or systemic cisplatin delivery on drug biodistribution as well as tumor burden were evaluated in vivo, in combination with radiation therapy. RESULTS: Platinum levels in patient biopsies were 6-fold lower than the levels needed for efficacy and radiosensitization in vitro. Cisplatin local delivery implant remarkably improved drug specificity to the tumor and significantly decreased accumulation in the blood, kidney, and other distant normal organs, compared with traditional systemic delivery. The localized treatment further resulted in complete inhibition of tumor growth. CONCLUSIONS: The current standard-of-care systemic administration of cisplatin provides a subtherapeutic dose. We developed a polymeric drug delivery system that delivered high doses of cisplatin directly into the cervical tumor, while lowering drug accumulation and consequent side effects in normal tissues. Moving forward, these data will be used as the basis of a future first-in-human clinical trial to test the efficacy of localized cisplatin as adjuvant or neoadjuvant chemotherapy in local and regional cervical cancer.

Potentiating Antitumor Efficacy Through Radiation and Sustained Intratumoral Delivery of Anti-CD40 and Anti-PDL1.

PURPOSE: Mounting evidence demonstrates that combining radiation therapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study was to investigate a minimally invasive therapeutics delivery approach to improve clinical response while attenuating toxicity. METHODS AND MATERIALS: We used a nanofluidic drug-eluting seed (NDES) for sustained intratumoral delivery of combinational antibodies CD40 and PDL1. To enhance immune and tumor response, we combined the NDES intratumoral platform with RT to treat the 4T1 murine model of advanced triple negative breast cancer. We compared the efficacy of NDES against intraperitoneal administration, which mimics conventional systemic treatment. Tumor growth was recorded, and local and systemic immune responses were assessed via imaging mass cytometry and flow cytometry. Livers and lungs were histologically analyzed for evaluation of toxicity and metastasis, respectively. RESULTS: The combination of RT and sustained intratumoral immunotherapy delivery of CD40 and PDL1 via NDES (NDES CD40/PDL1) showed an increase in both local and systemic immune response. In combination with RT, NDES CD40/PDL1 achieved significant tumor burden reduction and liver inflammation mitigation compared with systemic treatment. Importantly, our treatment strategy boosted the abscopal effect toward attenuating lung metastatic burden. CONCLUSIONS: Overall, our study demonstrated superior efficacy of combination treatment with RT and sustained intratumoral immunotherapy via NDES, offering promise for improving therapeutic index and clinical response.