Search

Purpose: Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis., Methods: A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records., Results: Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm 2 (range 9-2025 mm 2 ), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm 2 (range 0-1600 mm 2 ). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7-60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009)., Conclusion: The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results., Objectives: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids., Methods: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale., Results: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection., Conclusions: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved., (© 2024. The Author(s).)

Immunotherapies have revolutionized the management of advanced cutaneous malignancies. However, some patients fail to respond to these therapies, others are ineligible because of comorbidities, and a minority of patients experience treatment-limiting systemic immune-related adverse events. To address these issues and expand treatment options for patients with early-stage disease, a variety of immunotherapies are being developed for direct intratumoral administration. Agents including oncolytic viruses, monoclonal antibodies, cytokines, peptides, and pattern-recognition receptor agonists have been engineered to evoke a local immune response while minimizing systemic toxicity and have shown favorable results in preclinical and early clinical testing. This review covers the current landscape of intratumoral immunotherapies for the treatment of cutaneous melanoma, squamous cell carcinoma, and basal cell carcinoma, highlighting the diverse array of agents being explored and their potential benefits and challenges., Competing Interests: Conflicts of interest Dr Migden serves on the advisory boards of Regeneron and Replimune and is a scientific advisor for Stamford Pharmaceuticals and a consultant for Feldan Therapeutics. He has received honoraria for scientific advisory consultation from Regeneron, Replimune, Feldan Therapeutics, and Stamford Pharmaceuticals. Dr Patel serves on the advisory boards of Regeneron, Avstera, Almirall, Sun Pharma, and Biofrontera. He has received honoraria from PhD Biosciences, Jounce Therapeutics, Sun Pharma, and Regeron. He serves on the speaker’s bureau for Regeron. The remaining authors have no disclosures., (Copyright © 2024. Published by Elsevier Inc.)

Key Points: Intralesional cidofovir injections in combination with surgery is an effective treatment for recurrent multifocal sinonasal exophytic papilloma. No malignant transformation has been observed in our experience. Anosmia is a potential side effect that patients should be aware of., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: Extensive esophageal endoscopic submucosal dissections (ESDs) without preventive measures carry a high risk of stricture. Oral steroids and local injection of triamcinolone acetonide have proven to be effective in Asia for the prevention of esophageal stricture. This study aimed to assess the efficacy of a systematic steroid administration protocol for stricture prevention in a Western center., Methods: A retrospective review was conducted of all esophageal ESDs performed at H.U.B. Erasme Hospital, Brussels between 2016 and 2022. Injection of triamcinolone was performed for mucosal defects between 50% and 89% of the circumference. We added oral corticosteroids for patients with resections of ≥90% of the circumference. The primary outcome was the incidence of symptomatic stenosis at 3 months. Secondary outcomes included the cumulative stricture rate assessed by endoscopy within 6 months of ESD. Potential risk factors of stricture were evaluated with univariate and multivariate analysis., Results: 111 patients underwent 130 esophageal ESDs, with 59 patients receiving triamcinolone acetonide local injection and eight receiving local and oral corticosteroids. The primary outcome demonstrated a stricture incidence of 8.4%. The cumulative stricture rate assessed by endoscopy within 6 months of ESD was 10.4%. A mucosal defect of ≥60 mm in length was associated with a 15-fold increased risk of stricture, with circumferential extent also identified as being an independent prognostic factor for stricture., Conclusions: Our protocol led to a low stricture rate, even after extensive resection. As a single session treatment without systemic side effects, triamcinolone injection could provide benefits as a preventive method after large esophageal resections., Competing Interests: A. Lemmers: speaker's fees to Institution from Erbe, consultancy fees to Institution for Boston Scientific, research grant to Institution from Medtronic., (Thieme. All rights reserved.)

This study arises from the need to understand the different therapies for cutaneous squamous cell carcinoma (SCC), especially in challenging clinical situations where conventional therapeutic options may not be optimal. The purpose of the study is to assess the efficacy and safety of intralesional methotrexate (MTX) as neoadjuvant therapy in the treatment of periocular SCC. The outcome of a patient after two separate intralesional MTX infiltrations 2 weeks apart is described. Therapeutic response was evaluated, achieving a significant reduction in tumor size and subsequently performing surgical excision of the residual lesion. The procedure was well tolerated, with no local or distant recurrences in the follow up. Intralesional MTX may be an effective and safe option in the neoadjuvant treatment of periocular SCC. Furthermore, we highlight the growing importance of immunotherapy in the approach to SCC and the need to familiarize specialists with these new treatments., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Vocal process granuloma (VPG) is a chronic condition resulting from a mucoperichondrial injury of vocal process. Initial conservative treatment typically involves vocal hygiene education and antireflux medication. Treatment challenges arise with refractory cases. Outcomes of second-line treatments such as surgical excision and botulinum toxin injections remain inconsistent. Thus, we propose this study to investigate the effectiveness of intralesional steroid injections for refractory VPG., Methods: We conducted a retrospective review of 23 patients with VPG who showed no improvement after 3 months of proton pump inhibitors. These patients underwent one to three courses of monthly in-office intralesional steroid injections as a second-line therapy. Treatment outcomes were evaluated by measuring the size of the VPG relative to the length of the vocal folds before and after the final injection procedure., Results: Results showed a significant reduction in VPG size from baseline of 27.74 ± 15.06 to 5.48 ± 8.95 (p < .001). 15 out of 23 patients were responsive (size reduction ≥ 75%) to intralesional steroid injection. Alcohol consumption and longer symptom duration were associated with a poor response (size reduction <75%), whereas prior intubation was associated with better response., Conclusions: For refractory VPG not responding to conservative treatment, intralesional steroid injection appears to be a promising alternative option without significant adverse effects., (© 2024 John Wiley & Sons Ltd.)

Conjugation of a therapeutic agent to a polymer for enhanced delivery into target cells followed by its intracellular triggered release has proved to be an effective drug delivery approach. This approach is applied to the delivery of the immune-stimulatory unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide for an anti-tumour immune response after intratumoral administration. On average four CpG-1668 molecules were covalently linked to a 40-kDa amino-functionalised dextran polymer via either a non-reversible (CpG-dextran) or an intracellular redox-responsive disulfide linkage (CpG-SS-dextran). Dynamic light scattering analysis showed that both conjugates had a similar particle size and surface charge of 17 nm and -10 mV, respectively. Agarose gel electrophoresis analysis showed that CpG-SS-dextran was stable in the extracellular low glutathione (GSH) concentration range (i.e. 10-20 μM) and was cleaved at the higher intracellular GSH concentration (5 mM), while CpG-dextran was stable in both GSH concentrations. Uptake and activation assays on bone-marrow-derived dendritic cells showed no significant difference between free CpG, CpG-dextran and CpG-SS-dextran. In a mouse subcutaneous colorectal tumour model the CpG-SS-dextran showed a statistically significantly greater inhibition of tumour growth (p < 0.03) and prolonged survival (p < 0.001) compared to CpG-dextran or free CpG. These results demonstrate that the redox-triggered intracellular release of CpG from a dextran polymer carrier has promise for intratumoral therapeutic vaccination against cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Greg Walker reports equipment, drugs, or supplies was provided by University of Otago. Greg Walker reports a relationship with University of Otago that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pablo Botella Asuncion reports financial support was provided by State Agency of Research. Pablo Botella Asuncion reports financial support was provided by Government of Valencia. Pablo Botella Asuncion has patent #WO2021/099662 issued to Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Cientificas. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Treatments for Dupuytren's contracture include limited fasciectomy and collagenase injection. Comparisons of the effectiveness of these treatments have been limited., Methods: We performed an unblinded, multicenter, pragmatic, two-group, randomized, controlled noninferiority trial comparing collagenase injection with limited fasciectomy in persons with moderate Dupuytren's contracture. The primary outcome was the score on the Patient Evaluation Measure-Hand Health Profile (PEM), a questionnaire for assessing hand health as reported by the patient, at 1 year after treatment. Scores on the PEM range from 0 to 100, with higher scores indicating worse outcomes. The prespecified noninferiority margin was 6 points., Results: A total of 672 persons (336 per group) were assigned to receive collagenase injection or to undergo limited fasciectomy. The primary analysis included 599 persons: 314 in the collagenase group and 285 in the limited-fasciectomy group. The mean score on the PEM at 1 year was 17.8 among the 284 patients with available data in the collagenase group and 11.9 among the 250 patients with available data in the limited-fasciectomy group (estimated difference, 5.9 points; 95% confidence interval [CI], 3.1 to 8.8; one-sided P = 0.49 for noninferiority). Among the patients with available data (229 patients in the collagenase group and 197 patients in the limited-fasciectomy group), the estimated difference in the mean score on the PEM at 2 years was 7.2 points (95% CI, 4.2 to 10.9). Moderate or severe complications of treatment occurred in 1.8% of the patients in the collagenase group and in 5.1% of those in the limited-fasciectomy group; recurrent contracture resulted in reintervention in 14.6% and 3.4%, respectively., Conclusions: Collagenase injection was not noninferior to limited fasciectomy with respect to the score on the PEM at 1 year after treatment. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme; DISC ISRCTN Registry number ISRCTN18254597.)., (Copyright © 2024 Massachusetts Medical Society.)

Recent studies that examined the treatment efficacy of Candida antigen injection for both non-genital and genital warts yield inconsistent results. To address this, a systematic review and meta-analysis was conducted, comparing the treatment response between Candida antigen injection therapy and other intralesional immunotherapies across all types of warts. PubMed, Cochrane Library, and Embase were searched for relevant randomized controlled trials (RCTs) from inception to 16 September 2023, and 24 eligible RCTs were identified. A protocol was developed using the PRISM A-P checklist. In terms of complete clearance, intralesional Candida injection therapy demonstrated a significant improvement compared with saline (risk ratio [RR] 5.39; 95% confidence interval [CI] 3.49-8.33; I2=0%). However, no statistically significant differences were observed when compared with other therapies such as mumps-measles-rubella vaccines, purified protein derivative, vitamin D3, bivalent human papillomavirus vaccine, and zinc sulphate. Adverse effects associated with intralesional Candida therapy were generally reported as mild and manageable. In conclusion, intralesional Candida injection therapy for cutaneous warts may exhibit a superior complete and distant response rate. Nevertheless, owing to a limited sample size and other limitations, future research should aim for larger studies to provide more conclusive evidence.

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting.

Recent studies have shown that local injection of secukinumab can achieve positive therapeutic effects when applied in the treatment of nail psoriasis. At present, there have been no other studies on the use of biological agents in the treatment of pediatric nail psoriasis. Three children were included in the study to evaluate the efficacy and safety of periungual injection and long-term injection of secukinumab in the treatment of nail psoriasis in children. It was found that local injection did not achieve a remarkable therapeutic effect. The nail lesions were improved continuously by subcutaneous injection once a month., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Sun, Xie, Liu and Liu.)

The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345)., (© 2024. The Author(s).)

Aims: A local injection may be used as an early option in the treatment of Morton's neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition., Methods: A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications., Results: Both groups showed significant improvement in VAS and AOFAS scores (p < 0.05) after 12 months. The corticosteroid group had a significantly greater reduction in VAS and increase in AOFAS scores compared with the hyaluronic acid group, at one, three, and six months, but with no significant difference at 12 months. There were no complications in the hyaluronic acid group. There were minor local complications in six patients (six feet) (25.0%) in the corticosteroid group, all with discolouration of the skin at the site of the injection. These minor complications might have been due to the three weekly injections of a relatively high dose of corticosteroid. No patient subsequently underwent excision of the neuroma., Conclusion: An ultrasound-guided corticosteroid injection showed statistically significantly better functional and pain outcomes than an ultrasound-guided injection of hyaluronic acid for the treatment of a Morton's neuroma at many timepoints. Thus, a corticosteroid injection should be regarded as a primary option in the treatment of these patients, and the only indication for an injection of hyaluronic acid might be in patients in whom corticosteroid is contraindicated., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Objective: Recurrent respiratory papillomatosis (RRP) is a rare disease of the airway for which there is no known cure. Treatment involves the surgical removal or destruction of these lesions. There has been a long-standing debate over the effectiveness of the adjuvant intralesional injection of the immune modifying agent bevacizumab. This study is a systematic review investigating the effect of adjuvant intralesional bevacizumab on patients with laryngeal papillomatosis. The main objective was to assess functional outcomes and efficacy., Data Sources: Pubmed, Google Scholar, and Web of Science., Review Methods: Search words were "intralesional bevacizumab" AND "recurrent respiratory papillomatosis." Sources were systematically identified using inclusion and exclusion criteria (ie, study publication must post-date 2000, must be peer-reviewed, investigate patients with RRP, apply bevacizumab intralesionally, not systemically). Findings were then collected and analyzed., Results: Ten studies were included for analysis. The majority of these studies found an increase in the surgical interval, voice outcomes, and a decrease in tumor burden in most patients. No studies reported side effects or lasting complications related to the bevacizumab injection., Conclusion: This systematic review provides further evidence for the safety of intralesional bevacizumab injections and their likely positive effect on disease control. Future research would benefit from the implementation of standardized documentation of RRP outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the efficacy of intralesional rituximab injection for the management of idiopathic orbital inflammation (IOI) involving the lacrimal gland, which is the most common subtype., Method: Eighteen consecutive patients with biopsy-proven IOI involving the lacrimal gland were included. Rituximab (50 mg/5 mL) was injected intralesionally at monthly intervals., Results: Clinically, all patients presented with upper eyelid swelling and ptosis. Most patients (56%) had periocular pain and a palpable superotemporal mass. Biopsies showed chronic inflammation without fibrosis in 14 patients (78%) and chronic inflammation and fibrosis in 4 patients (22%). Intralesional rituximab was injected once in 1 patient (6%) because of complete response after the first injection, twice in 11 patients (61%), and 3 times in 6 patients (33%) because of partial response after 2 injections. After a mean follow-up of 33 months (median, 33 months; range, 11-59 months), 16 patients (89%) showed a clinical response, including 14 patients (78%) a complete response (i.e., disappearance of all lesions) and 2 patients (11%) with a partial response (i.e., ≤30% decrease in lesion diameter). Two patients (11%) did not respond after 3 injections and were placed on systemic corticosteroid and methotrexate therapies. Two patients (11%) with a complete response developed subsequent recurrence 12 and 49 months after their last injections. Both were treated with 2 additional rituximab injections, 1 month apart, and showed complete response when examined 27 and 11 months after treatment, respectively., Conclusion: Intralesional rituximab injection may be an effective treatment for IOI involving the lacrimal gland, achieving a 78% complete response rate in this series. Local treatment with rituximab has the potential to avoid the ocular and systemic side effects of corticosteroid and systemic immunosuppressive treatment., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Actinic granuloma (AG) is a rare dermatological condition with only a few dozen cases reported worldwide. Initially classified as a variant of granuloma annulare, it is now recognized as a distinct entity characterized by asymptomatic annular plaques in sun-exposed areas of the skin. The exact pathogenesis remains unclear, but it is believed to be an inflammatory response to sun damage, possibly involving injured elastic fibers. Numerous local and systemic therapeutic options exist, but no specific treatment guidelines have been established. We present a case of AG treated with intralesional application of triamcinolone acetonide in a 64-year-old male patient. We also discuss the most important clinical and histological characteristics and various treatment options.

Peyronie's disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie's plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Intratumoral delivery of mRNA encoding immunostimulatory molecules can initiate a robust, global antitumor response with little side effects by enhancing local antigen presentation in the tumor and the tumor draining lymph node. Neoantigen-based mRNA nanovaccine can inhibit melanoma growth in mice by intratumoral injection. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune responses by secreting immunosuppressive agents, such as reactive oxygen species (ROS). Suppression of STAT3 activity by stattic may reduce MDSC-mediated immunosuppression in the TME and promote the antitumor immune responses. In this study, in vitro transcribed mRNA encoding tumor antigen survivin was prepared and injected intratumorally in BALB/c mice bearing subcutaneous colon cancer tumors. In vivo studies demonstrated that intratumoral survivin mRNA therapy could induce antitumor T cell response and inhibit tumor growth of colon cancer. Depletion of CD8 + T cells could significantly inhibit survivin mRNA-induced antitumor effects. RT-qPCR and ELISA analysis indicated that survivin mRNA treatment led to increased expression of receptor activator nuclear factor-κB ligand (RANKL). In vitro experiment showed that MDSCs could be induced from mouse bone marrow cells by RANKL and RANKL-induced MDSCs could produce high level of ROS. STAT3 inhibitor stattic suppressed activation of STAT3 and NF-κB signals, thereby inhibiting expansion of RANKL-induced MDSCs. Combination therapy of survivin mRNA and stattic could significantly enhance antitumor T cell response, improve long-term survival and reduce immunosuppressive tumor microenvironment compared to each monotherapy. In addition, combined therapy resulted in a significantly reduced level of tumor cell proliferation and an obviously increased level of tumor cell apoptosis in CT26 colon cancer-bearing mice, which could be conducive to inhibit the tumor growth and lead to immune responses to released tumor-associated antigens. These studies explored intratumoral mRNA therapy and mRNA-based combined therapy to treat colon cancer and provide a new idea for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

Background: Treatment of scarring has long been a problem due to high incidence and recurrence. Despite many existing treatment therapies, the efficacy remains unstable., Objectives: To determine the efficacy and safety of skin biopsy punch in combination with corticosteroid injection (BPCI) in treating keloids., Approach: This was a retrospective study. In total, 16 patients with keloids received BPCI. Changes in scar appearance, accompanied symptoms, and Vancouver Scar Scale (VSS) were analyzed. Patient satisfaction, VAS scores, and adverse effects were also evaluated., Results: Scar appearance, accompanied symptoms, and VSS scores improved significantly after the treatment. The total effective rate was 93.75% at an 18-month follow-up on average. The mean reduction rate of VSS score was 58.44% (p < 0.0001), especially in height and pliability (84.44% and 78.19%, p < 0.0001). The recurrence rate in this study was 12.5% (n = 2) at an 18-month follow-up on average. Mild adverse effects of pain, pruritus, hypopigmentation, and telangiectasia were recorded., Conclusions: This study demonstrated BPCI might be an effective and safe therapy in keloids with a low long-time recurrence rate and well tolerance for patients., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

In-transit metastasis (ITM) develop in approximately 1 in 10 patients with melanoma and the disease course can vary widely. Surgical resection is the gold-standard treatment; however, ITM are often surgically unresectable due to size, distribution, and/or anatomic involvement. Oncolytic viral therapies are one category of non-surgical treatment options available for ITM. They induce tumor cell lysis and systemic anti-tumor activity through selective infection of tumor cells by naturally occurring or genetically modified factors. While there are numerous oncolytic viral therapies in various stages of development for the treatment of ITM, this discussion focuses on the mechanism and available literature for the two most established herpes virus-based therapies., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Keloid scars are a particularly challenging fibroproliferative wound healing disorder with a variety of proposed management approaches including concurrent surgery and intralesional steroid injection. We aimed to identify the optimum time for triamcinolone injection of keloids, by comparing the recurrence and complication occurrence in patients who received pre-, intra- or post-operative injection. Studies reporting on the rate of recurrence and complication occurrence following treatment of keloid scarring with concurrent surgical excision and intralesional steroid injection were identified from the PubMed, Web of science and Embase databases. The I-squared (I 2 ) statistic was used to quantify the variability in study estimates due to heterogeneity and to determine whether the fixed or random effect models will be employed. Publication bias was visualized through funnel plots and tested with the Egger's test. We found that the recurrence rate was significantly lower with post-operative injection compared to intra-operative injection (p < 0.001) and pre-operative injection (p = 0.009). A significant difference between intra-operative and pre-operative injection was not found (p = 0.46). In conclusion, post-operative steroid injection after surgical excision results in lower keloid recurrence compared to pre- and intra-operative injection.Level of Evidence IV "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .", (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Electrochemotherapy (ECT) combines the reversible electroporation (rEP) with intravenous (i.v.) or intratumoral (i.t.) administration of chemotherapeutic drugs. We conducted this study to compare the efficacy of i.v., i.t., and i.v. + i.t. injection of bleomycin (BLM) in ECT treatment of colorectal hepatic metastases in a rat model. WAG/Rij rats were randomized into three groups and underwent ECT with i.v., i.t., or i.v. + i.t. injection of BLM. Tumor volumes and oxygenation were measured by means of ultrasound and photoacoustic imaging. Moreover, liver and tumor tissue were analyzed by histology and immunohistochemistry. The i.v. and i.v. + i.t. groups exhibited a 44.0% and 46.6% reduction in oxygen saturation of the tumor tissue when compared to pretreatment values, whereas the i.t. group only showed a reduction of 35.2%. The extent of tumor tissue necrosis did not statistically differ between the groups. However, the i.t. group showed a tendency towards a lower necrosis rate. Cell proliferation, apoptotic cell death, vascularization, and immune cell infiltration were comparable in the treated tumors of the three groups. ECT with i.v. administration of BLM should be preferred in clinical practice, as the combined i.v. + i.t. therapy did not show superior oncological outcomes in the present study., (© 2024. The Author(s).)

Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment., (© 2024. The Author(s).)

In 2022, the Pan American Health Organization recommended the intralesional application (IL) of pentavalent antimonials in adult patients with localized cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis. Other guidelines differ from that recommendation, considering that infections caused by a Leishmania species that can be associated with increased risk for mucosal leishmaniasis, in particular L. (V.) braziliensis, should not be eligible for intralesional treatment. This was a prospective interventional study carried out with eight patients diagnosed with CL residing in northeast Brazil during the period from 2019 to 2022. To our knowledge, this is the first prospective study on the subject conducted in the northeast region, which has the second-highest number of cases in the country. In our sample, clinical cure was achieved with the use of intralesional treatment in all cases, and there were no serious adverse events or mucosal involvement during the 1-year follow-up period. We emphasize the importance of using the right criteria for choosing this therapeutic modality and highlight the advantages of intralesional treatment due to the lower risk of adverse events and cost reduction to health services.

Objective: To analyze the efficacy of intralesional steroid treatment in refractory caustic esophageal stricture., Materials and Methods: An analytical, retrospective study of patients receiving intralesional steroid treatment with triamcinolone acetonide as a result of refractory caustic esophageal stricture was carried out. Demographic variables, stricture characteristics, number of dilations, steroid injections, and dilation score (no. of dilations/follow-up period in months) pre- and post-treatment were collected. Stricture characteristics (diameter and length) and dilation score pre- and post-treatment were compared using the T-Test or Wilcoxon test., Results: N= 5. Median age: 5 years (17 months-7 years). Follow-up: 6.60 ± 2.70 years. Swallowed products included NaOH, KOH, and ClH. Zargar classification at follow-up initiation was IIb (n= 2), IIIa (n= 1), and two chronic strictures. 6.6 ± 9.23 esophageal dilations were carried out before steroid treatment initiation. The mean number of intralesional therapy sessions was 11.20 ± 6.14. Stricture length decreased by 3.60 ± 2.63 cm (t= 3.06; p= 0.019). No differences were found in terms of diameter increase: -1.60 ± 3.58 mm (t= -1.00; p= 0.187). The dilation score diminished from 1.47 ± 0.86 to 0.47 ± 0.18 dilations per month of follow-up (Z= -2.02; p= 0.043)., Conclusions: Even though there is limited evidence available in the pediatric population, intralesional triamcinolone treatment is seemingly useful in the treatment of refractory caustic esophageal stricture, since it reduces length and dilation score.

Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been employed for the treatment of keloids; however, there is no one gold standard approach. Five-fluorouracil, a potent chemotherapeutic agent, has emerged as a promising therapeutic option. Therefore, this systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focused on providing a broad overview of the use of 5-fluorouracil for the management of keloids. Forty studies (2325 patients) met inclusion criteria and investigated 5-fluorouracil for keloid management, with 19 studies (1043 patients) including a 5-fluorouracil monotherapy group. Five-fluorouracil monotherapy demonstrated consistent keloid improvement with >254 keloids injected across various anatomical regions. Five-fluorouracil monotherapy was most often compared to intralesional triamcinolone acetonide, utilizing the Patient and Observer Scar Assessment Scale and the Vancouver Scar Scale. The most common keloid parameters assessed were height, size, volume, width, length, induration, pruritus, and erythema. Five-fluorouracil monotherapy exhibited substantial improvements, with weight averages of 73% of patients experiencing >25% improvement and 67% achieving >50% improvement. Relapse rate was 16% at 27 weeks after 5-fluorouracil monotherapy treatment. Limitations included potential selection bias, language restrictions, and heterogenous data analysis among studies. Overall, our findings underscore the potential effectiveness of 5-fluorouracil monotherapy in the management of keloids, with an encouraging safety profile. Larger prospective trials are needed to determine optimal therapy or combination therapy for the management of keloids. This detailed compilation of treatment protocols, outcomes, and relapse rates stand as a valuable resource for further research and clinical applications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nail psoriasis is associated with significant disease burden, negative impact on quality of life, and potential progression to psoriatic arthritis. Initiating timely and appropriate treatment is of the utmost importance, especially because nail disease may be more resistant to therapies than cutaneous psoriasis. This article reviews available intralesional, topical, and systemic treatment options for nail psoriasis, and discusses efficacy and safety of studied agents. Also reviewed are consensus treatment guideline recommendations. An updated algorithm to aid physicians in selection of specific treatment options is provided., Competing Interests: Disclosure Mr J.K. Hwang and Dr S.R. Lipner have no conflicts of interest to disclose. Dr S.R. Lipner has served as a consultant for Ortho-Dermatologics, BelleTorus Corporation, Eli Lilly, and Moberg Pharmaceuticals. Mr J.K. Hwang has no financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The application of Botulinum toxin (Masport) in urology has a long history. We aimed to assess the effect of local Masport on improvement in patients with urethral stricture by reducing the recurrence of urethral stricture. This pilot study conducted was a double-blind randomized clinical trial with code IRCT20191222045852N1 on patients suffering from urethral stricture. Finally, 28 patients were allocated to intervention and control groups. Twelve patients received intralesional injection with Masport in addition to internal urethrotomy, while 16 patients underwent internal urethrotomy with normal saline. The Cox regression hazard model was used to evaluate the effect of treatment status on recurrence time adjusted for the age, length, and location of the stenosis, cause of the stenosis, and history of previous operations. The effect of treatment type was significant at the .05 level. The past medical history and cause of urethral stricture had a significant impact on relapse-free survival. Also, the improvement in the mean score of the EuroQol Visual Analogue Scale (EQ-VAS), International Prostate Symptom Score (IPSS), and Q-max in the group with Masport was significantly different from the group with normal saline. The internal urethrotomy with intralesional injection of Masport has a better survival prognosis than internal urethrotomy with normal saline group. Therefore, the authors suggest that, given this successful initial clinical trial, consideration be given to future studies involving the use of botox in the management of urethral strictures in conjunction with internal urethrotomy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Recent approaches for recurrent respiratory papillomatosis including local injection of bevacizumab and HPV vaccination show promise in reducing the need for frequent surgeries. In this study we propose a new combined approach of surgery, intralesional injection of 25 mg bevacizumab and HPV vaccine that can lead to resolution of RRP., Material and Methods: Our study involved 5 patients treated with a combination of transoral microsurgery, intralesional injection of 25 mg bevacizumab, and HPV vaccination with Gardasil 9 between April 2020 and May 2023. Standard video laryngoscopy was performed to assess the presence of papilloma and Derkay score was used to assess the severity of disease., Results: All 5 patients completed the study successfully and a complete response was achieved by all. The follow-up ranged from 8 to 45 months. The mean total Derkay score before treatment was 41 (range 25 to 52) and after the combined approach was 0 both anatomically and clinically in all patients., Conclusions: This study demonstrates the effectiveness of a combined treatment approach for RRP involving surgical intervention, intralesional injection of bevacizumab, and HPV vaccination., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Collagenase Clostridium histolyticum (CCH) remains the only Food and Drug Administration-approved medical treatment for Peyronie's disease (PD). The initial IMPRESS I and II trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety), which led to Food and Drug Administration approval, revealed a rate of treatment-related adverse events as high as 84%. Studies fail to provide clear definitions of complications., Objectives: To review complications, provide a CCH complication atlas, and propose management strategies for commonly encountered complications., Methods: We performed a literature review using PubMed. A photographic atlas was provided regarding complications in patients in a high-volume CCH center for PD., Results: Complications were identified and classified by nature and severity. We followed a standardized previously published grading system for hematomas. Complications include bruising, swelling, hematoma formation, back pain, and, rarely, corporal rupture. Complications were discussed, and hematomas were graded by penile surface area. Complication photographs were graded and displayed. Treatment-related adverse effects do not affect overall results., Conclusion: Recognizing and grading complications associated with CCH therapy for PD is crucial for effective patient management and informed decision making. A standardized grading system allows for consistency in reporting and comparing hematoma complication rates across studies and patient populations. Herein we provide images that will help clinicians identify and confidently manage common complications that may occur in any CCH program., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and "bathes" the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor. When MS ~ SN-38 was injected locally, tissues showed high levels of SN-38 with a long half-life of ~ 1 week. IT MS ~ SN-38 was ~ tenfold more efficacious as an anti-tumor agent than systemic SN-38. We also propose and provide an example that long-acting IT therapy might enable safe use of two drugs with overlapping toxicities. Here, long-acting IT MS ~ SN-38 is delivered with concurrent systemic PARP inhibitor. The tumor is exposed to both drugs whereas other tissues are exposed only to the systemic drug; synergistic anti-tumor activity supported the validity of this approach. We propose use of this approach to increase efficacy and reduce toxicities of combinations of immune checkpoint inhibitors such as αCTLA-4 and αPD-1., (© 2024. The Author(s).)

Background: Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and usually disfiguring. Thus, non-operative modalities represent good alternatives., Objective: To assess and compare the efficacy of intralesional methotrexate (MTX) and 5-flurouracil (5-FU) in the treatment of KA., Patients and Methods: Randomized controlled trial included 20 patients with biopsy proven KA divided into 2 equal groups; group (A) received intralesional MTX, 25 mg/ml and group (B) received intralesional 5-FU, 50 mg/ml every 2 weeks till complete clearance or for a maximum 5 sessions., Results: In the MTX group, complete clearance was observed in 7 patients (70%) compared to 8 patients (80%) in the 5- FU group with no statistically significant difference. However, the median number of injections needed to achieve complete response in the MTX group was 3 sessions versus only 2 sessions in the 5-FU group., Limitations: the small sample size due to the relatively low incidence of KAs in our population., Conclusion: Intralesional therapy is a good alternative to surgery in selected cases of KA. Both drugs showed comparable efficacy, but 5-FU may give faster results, hence increasing patient satisfaction and compliance., (© 2024. The Author(s).)

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts., (© 2024. The Author(s).)

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids., (© 2024. The Author(s).)

Background: Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC., Patients and Methods: A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported., Results: After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review., Conclusion: This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PJL: research funding from Roche, Merck; speakerś bureau from MSD Merck Sharp & Dohme, travel and accommodation expenses from MSD, and Novartis; and stockholding from Elli Lilly outside the current work. AHC: travel and accommodation expenses from Merck Serono and Kyowa Kirin International and research grant from Gilead (Inst) outside the current work. IB received personal fees from Merck sharp & Dohme, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert Now, Boehringer Ingelheim as a Speakers’ Bureau: Bristol Myers Squibb, Merck Serono, Roche, MSD. Lastly, as a research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Gliknik (Inst), GlaxoSmithKline (Inst), Janssen Oncology (Inst), Kura Oncology (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Shattuck labs (Inst), Nanobiotix (Inst), Seattle Genetics (Inst), Immutep (Inst), Debiopharm Group (Inst), Regeneron (Inst), Boehringer Ingelheim (Inst), ISA Pharmaceuticals (Inst), Merck Serono (Inst), Seattle Genetics (Inst), Northern Biologics (Inst), VCN Biosciences (Inst), and for travel, accommodations and expenses: MSD Oncology. VM: Consulting or Advisory Role: Roche (Inst), Bayer (Inst), Pieris (Inst), BMS (Inst), Janssen (Inst), Basilea (Inst), Regeneron/Sanofi (Inst), BMS (Inst), Bayer (Inst), Nanobiotix (Inst). Research Funding: AbbVie (Inst), Achilles (Inst), AbbVie (Inst), AceaBio (Inst), Adaptimmune (Inst), ADC Therapeutics (Inst), Arcus (Inst), Ascendis Pharma (Inst), Aduro (Inst), Agenus (Inst), Amcure (Inst), Amgen (Inst), Astellas (Inst), AstraZeneca (Inst), Bayer (Inst), Beigene (Inst), Biomea (Inst), BioInvent International AB (Inst), BMS (Inst), Boehringer (Inst), Boston Therapeutics (Inst), Celgene (Inst), Daiichi Sankyo (Inst), Debiopharm (Inst), Eisai (Inst), e-Terapeutics (Inst), Exelixis (Inst), Forma Therapeutics (Inst), Genmab (Inst), GSK (Inst), Harpoon (Inst), Hutchison (Inst), Immutep (Inst), Incyte (Inst), Inovio (Inst), Iovance (Inst), Janssen (Inst), Kyowa Kirin (Inst), Lilly (Inst), Loxo (Inst), Monta Bioscience (Inst), MedSir (Inst), Menarini (Inst), Merck (Inst), Merus (Inst), Millennium (Inst), MSD (Inst), Nanobiotix (Inst), Nektar (Inst), Novartis (Inst), Odonate Therapeutics (Inst), Pfizer (Inst), Pharma Mar (Inst), PharmaMar (Inst), Principia (Inst), PsiOxus (Inst), Puma (Inst), Regeneron (Inst), Relay Therapeutics (Inst), Revolution Medicines (Inst), Rigontec (Inst), Roche (Inst), Sanofi (Inst), Sierra Oncology (Inst), Synthon (Inst), Taiho (Inst), Takeda (Inst), Tesaro (Inst), Transgene (Inst), Turning Point Therapeutics (Inst), Upsher-Smith (Inst). BD: Principal Investigator – Institutional Funding: AbbVie, Achilles, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Arcus, Ascendis Pharma, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer, Beigene, Biomea, BioInvent International AB, BMS, Boheringer, Boston Therapeutics, Celgene, Daichii Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, Monta Bioscience, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Relay Therapeutics, Revolution Medicines, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. KJH received honoraria from Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys Biopharma (Inst), Pfizer (Inst), Replimune (Inst), Inzen Therapeutics (Inst) and Codiak Biosciences (Inst). Consulting or Advisory Role: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys BioPharma (Inst), Replimune (Inst), Inzen Therapeutics (Inst) Speakers’ Bureau: BMS (Inst), Merck Serono (Inst), MSD (Inst) Research Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Replimune (Inst), Boehringer Ingelheim (Inst). All other authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Treating plantar warts is still a challenging problem with a long list of diverse treatment options that none of them seems to be definitive. To evaluate the effectiveness of intralesional acyclovir versus intralesional Hepatitis-B vaccine (HBV) in treatment of multiple resistant plantar warts. Forty-eight patients with resistant plantar warts completed the study with no dropouts. They were randomized into 3 groups; group(A) receiving intralesional HBV, group (B) receiving intralesional acyclovir and group (C) receiving intralesional saline as a control group over 5 biweekly sessions or until wart clearance. Clinical outcome was assessed through sequential digital lesion photographing upon each visit. Treatment related adverse reactions were recorded. 43.8%, 37.5% & 18.7% of Groups A, B &C respectively showed a complete response. pain was obvious in 100% and 56.3% of cases receiving intralesional acyclovir and HBV respectively. Up to the 6 month follow up period, none of the complete responders in all groups returned with a recurrence. Both acyclovir and HBV showed comparable efficacy and seem to be promising options for treating plantar warts being safe, affordable, and theoretically safe in immunocompromised cases., (© 2024. The Author(s).)

Background: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy., Methods: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital., Results: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence., Conclusions: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest and received no funding to conduct this study. Because this is a retrospective review, this article does not contain any studies with human or animal subjects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration., Methods: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations., Results: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail., Conclusions: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the treatment of pathologic scars, although the evidence base is limited. The authors compared the efficacy and complication rates of combination intralesional TAC and 5-FU with those of monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars., Methods: Embase, MEDLINE, and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using the Cochrane risk of bias tool., Results: Of 277 articles screened, 13 studies were included, comprising 12 randomized control trials and one nonrandomized study. Six studies compared combination intralesional therapy versus monotherapy 5-FU, and nine studies compared combination intralesional therapy versus monotherapy TAC. The combined group demonstrated superior objective treatment efficacy compared with the monotherapy TAC group (OR, 3.45; 95% CI, 2.22 to 5.35; I 2 = 0%; P < 0.00001) and monotherapy 5-FU group (OR, 4.17; 95% CI, 2.21 to 7.87; I 2 = 0%; P < 0.0001). Telangiectasia was less frequent in combination therapy (OR, 0.24; 95% CI, 0.11 to 0.52; I 2 = 0%; P = 0.0003) compared with monotherapy TAC., Conclusions: Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared with monotherapy TAC or 5-FU. Patient-reported outcome measures should be incorporated in the design of future research to justify clinical recommendations., Clinical Relevance Statement: Combined TAC and 5-FU has demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU in the treatment of hypertrophic scars and keloids., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Introduction: Recalcirant warts are resistant to conventional therapeutic option with high recurrence rate. In recent year, treatment of warts with different immunotherapeutic agent has shown good results, as it regulate epidermal cell proliferation and are involved in the formation of anti microbial peptides. Hence, this study was undertaken to evaluate the efficacy of immunotherapy with intralesional vitamin D in wart., Methods: A descriptive cross-sectional study was conducted from 1 January 2021 to 2 February 2023 at Kathmandu Medical College after approval from the Institutional Review Committee (Reference number: 0110202002). Ninety - two patients with recalcitrant wart of varying sizes and duration were included in the study. Injection vitamin D ( 600000 IU, 15mg/ ml) was injected about (0.2-0.5 ml) to the base of the wart. Maximum of five warts were injected per month, and was repeated after 4 weeks for 3 sessions., Results: Among 92 patient, complete response was seen in 70 patient (76.08%), partial response was seen in 17 patients ( 18.47%) and 5 patient(5.43%)showed no response. Mild pain as observed at the time of injection. Signs of hypervitaminosis D was not observed., Conclusions: Intralesional administration of Vitamin D is an effective treatment option for reclacitrant warts and is, highly effective, cost-efficient, with minimal adverse effects, and can be perfomed in our clinical set up.