Intralesional therapies for vascular malformations of the head and neck.

Vascular malformations of the head and neck represent a spectrum of complex vascular anomalies, requiring a multidisciplinary approach toward diagnosis and treatment. Several intralesional therapeutic agents have been devised and pioneered over the years, some of which are now primary and standard of care for the management of these lesions. In this article, the authors discuss the currently available intralesional therapeutic agents for the management of vascular malformations in the head and neck region.

A comparative evaluation of therapeutic response in warts to intralesional vitamin D3 versus intralesional measles, mumps, and rubella vaccine.

The infection of keratinocytes by human papilloma virus (HPV) causes warts. These are of different types based on morphological and anatomical grounds. This has led to the development of strategies involved in the treatment of warts by induction of delayed hypersensitivity reactions. The current study aims to compare the therapeutic response and side effect profile of intralesional vitamin D3 and measles, mumps, and rubella (MMR). The aim of this study is to study the therapeutic response of two intralesional immunotherapies in warts and compare their efficacies and side effects. A single-blind randomized control trial was conducted over 12 months on 100 patients using the purposive sampling technique. Randomly, half of the participants received one of the two immunotherapies. The clinical response was evaluated on the basis of decrease in wart size, wart number, wart distribution, and photographic comparison. The mean size of the largest wart in the vitamin D3 group was found to be 0.70 cm, and in the MMR group, it was 0.79 cm in breadth. The mean onset of first response was 3.55 weeks in the vitamin D3 group and 3.85 weeks in the MMR group. Complete response was seen in 54% and 62% of study participants in the vitamin D3 and MMR groups respectively. The study recommends that both intralesional vitamin D3 and MMR are efficacious in treating cutaneous warts, with MMR agents being moderately better compared to vitamin D3 in terms of warts clearance and side effects profile.

Debulking followed by intralesional 5-fluorouracil for the treatment of cutaneous squamous cell carcinoma and keratoacanthoma: A retrospective analysis.

Debulking followed by intralesional 5-fluorouracil (deb-IL5FU) is a nonsurgical modality which has been used to treat skin cancer anecdotally for many years. There are few in depth studies examining this technique and success rate of intralesional 5-fluorouracil (IL5FU) for the treatment of cutaneous squamous cell carcinoma (cSCC). To evaluate the response rate of deb-IL5FU for the treatment of cSCC and to determine which patient factors were associated with tumor clearance or treatment failure. A retrospective chart analysis of patients with the diagnosis of cSCC or keratoacanthoma (KA) and subsequent deb-IL5FU treatment. Sixty-one patients with a total of 315 tumors (cSCC and KA), were treated using deb-IL5FU. The overall tumor clearance rate was 89%. This was highest for well-differentiated SCC, SCC, KA-type SCC, and KA. Tumors on the trunk and extremities showed high clearance rates while tumors on the scalp/face/neck/ears showed lower clearance rates. Immunocompetent patients cleared more tumors compared to immunocompromised patients. Limitations included the retrospective nature of this analysis as well as a small sample size. Treatment of cSCC and KA with deb-IL5FU demonstrated high tumor clearance rates. Lower rates of clearance were seen in males, immunosuppressed patients, tumors located on the scalp and face/neck/ears.

Conservative Therapy for Peyronie's Disease: a Contemporary Review of the Literature.

PURPOSE OF REVIEW: To analyze the literature on current conservative treatment options for Peyronie's disease (PD). RECENT FINDINGS: Conservative therapy with intralesional collagenase clostridium histolyticum (CCH) is safe and efficacious in either the acute or chronic phases of PD. Combination treatment with penile traction therapy (PTT) can produce even better results. While most PTT devices require extended periods of therapy up to 8 h per day, the RestoreX® device can be effective at 30-90 min per day. A variety of conservative therapies are available for treatment of PD. The available literature does not reveal any treatment benefit of oral therapies. Intralesional therapy is the mainstay conservative treatment of PD. Intralesional CCH therapy is the first Food and Drug Administration-approved intralesional therapy and represents the authors' preference for medical therapy. The most effective conservative management of PD likely requires a combination of therapies.

Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Medical treatment of Peyronie's disease (PD) in terms of intralesional therapy is still a matter of debate. AIM: To compare the efficacy of different classes of intralesional therapy with a network meta-analysis (NMA) method. METHODS: The search was conducted using documents published in PubMed, Scopus, and Web of Science databases until September 30, 2017. We included randomized controlled trials comparing at least 1 intralesional therapy with a placebo therapy or with another drug for the treatment of PD. All intralesional therapies have been considered: collagenase Clostridium histolyticum (CCH), hyaluronic acid, verapamil, and interferon α-2b. MAIN OUTCOME MEASURE: Outcomes of the study are the mean change in penile curvature (PC) and in erectile function (EF) assessed with the International Index of Erectile Function questionnaire. RESULTS: In total, 8 comparisons matched with the inclusion criteria, which includes 1,050 patients. With regard to PC (degree) improvement, hyaluronic acid and verapamil showed worse outcomes when compared with CCH (-6.66 and -2.30) and interferon α-2b (-6.75 and -2.38). When considering improvement in EF, hyaluronic acid, verapamil and interferon α-2b showed a slight increase in mean change when compared with CCH (+2.39, +1.77, and +0.65). Moreover, verapamil and interferon α-2b showed slightly worse mean change in comparison to hyaluronic acid (+0.62 and +1.74), whereas interferon α-2b was worse than verapamil (-1.12). CLINICAL IMPLICATIONS: Based on this NMA, empirical therapy for PD should be avoided to offer the patients the best treatment in terms of level of evidence. STRENGTHS & LIMITATIONS: In this NMA, we have provided, for the first time, evidence of the efficacy between different intralesional therapies for the treatment of PD. We were not able to compare all specific outcomes (ie, pain, plaque size, patient satisfaction) of PD, because of the lack of homogeneity across relevant studies. Moreover, because of the few included studies, a meta-regression analysis of predictive factors of treatment response was not calculated. CONCLUSION: This is the first meta-analysis comparing all available intralesional treatments for PD. CCH and interferon α-2b showed the best outcome in terms of PC, whereas hyaluronic acid was most efficient in relation to EF. Russo GI, Cacciamani G, Cocci A, et al. Comparative Effectiveness of Intralesional Therapy for Peyronie's Disease in Controlled Clinical Studies: A Systematic Review and Network Meta-Analysis. J Sex Med 2019;16:289-299.

Management of local or regional non-nodal disease.

Some melanomas develop a striking avidity for lymphatic spread. In spite of multiple recurrences, patients can remain years without visceral metastasis. There is clearly a biologic reason for this lymphotrophic pattern of growth and dissemination, which we have yet to uncover. In-transit metastases have widely diverse clinical presentations and can be a stubborn disease to cure. As a result, a host of treatments exist that should be tailored to the individual patient.

Neo-DREAM study investigating Daromun for the treatment of clinical stage IIIB/C melanoma.

High-risk resectable melanoma poses therapeutic challenges as this subgroup remains most vulnerable for disease recurrence. Immunotherapy has established its efficacy in cases of advanced melanoma, and now is actively being investigated in the multimodal management of resectable disease. Daromun, an intralesional immunocytokine, has emerged as a unique immunotherapy in its ability to preferentially target tumor cells, resulting in direct destruction, while generating a bystander effect that leads to a distant treatment effect. On the basis of its mechanism of action, there is growing interest in delivering immune-based therapies in a neoadjuvant setting. In this review, the neo-DREAM study, a Phase III trial comparing the safety and efficacy of neoadjuvant Daromun for resectable stage IIIB/C melanoma will be described. Clinical Trial Registration Number: NCT03567889.

Intralesional therapy for the treatment of keratoacanthoma.

Keratoacanthoma (KA) is a common epidermal tumor that originates from the hair follicle of the skin. It is generally considered as a benign neoplasm, but in rare cases, it can also transform into squamous cell carcinoma. Although surgical excision with a safety margin is considered to be the gold standard treatment for most subtypes of KA, several other treatment options are also available. Intralesional therapy is one of these options, which could be cosmetically and functionally a better alternative to surgical removal, while it provides similar outcomes. It is more effective than topical treatments, yet fewer side effects may be seen than in systemic treatments. Based on the literature, the most commonly used intralesional agent is methotrexate, followed by 5-fluorouracil and interferon alpha. Regardless of the advantages, which make intralesional therapy a desirable treatment alternative, guidelines for the intralesional treatment of KA are not yet established. A histopathological confirmation before the start of treatment is still recommended to prevent any possible misdiagnosis of KA for SCC. In our present study, we set out to review the current state of the art of the intralesional treatment of KA.

A snapshot of intralesional verapamil injection in the treatment of Peyronie's disease today.

Studies assessing the efficacy of intralesional verapamil injection in the treatment of Peyronie's disease have yielded mixed results. The purpose of this meta-analysis is to systematise the existing literature on the efficacy of intralesional verapamil injection when used in the treatment of Peyronie's disease. The treatment outcomes of seven different study groups identified by computerised literature search were compared with natural history outcomes and data from control groups of three studies involving placebo saline injection. An exploratory meta-analysis was performed on the data due to differing patient populations, treatment protocols, and inconsistent selection and reporting of outcomes. Intralesional verapamil injection significantly improved sexual function (p < .0005) and penile curvature (p < .005) in individuals with Peyronie's disease. Decreases in pain may be significant after therapy but are questionable. The effect of verapamil on plaque size remains less impressive (p > .05). Intralesional verapamil injection has promise to positively impact a number of clinical outcomes of Peyronie's disease; however, a large, multicentre, randomised, controlled study with reliable protocols is needed to confirm the efficacy of treatment.

Plasma antimony determination during cutaneous leishmaniasis treatment with intralesional infiltration of meglumine antimoniate.

OBJECTIVES: To evaluate the antimony (Sb) in plasma of patients who underwent a standardised meglumine antimoniate (MA) intralesional infiltration protocol for cutaneous leishmaniasis treatment. METHODS: The level of Sb in plasma was determined by atomic absorption spectroscopy, before and 1, 2, 4 and 6 hours after the first intralesional infiltration of MA to determine the parameters peak concentrations (C1 h ), area under curve of drug concentration in plasma from zero to 6 h (AUC0-6 h ) and elimination half-life (t½) of Sb. Blood samples were also collected weekly during the treatment period, always before infiltration. RESULTS: Fourteen patients underwent MA intralesional infiltration with doses ranging from 0.8 to 9 mg Sb/kg at the first infiltration. The C1 h ranged from 3850 to 47 095 mg × h/L and was the highest concentration obtained for 11 of 14 patients after the first intralesional infiltration of MA. A rapid initial phase of distribution lasting up to 4 h (2.6 ± 0.34 h) was followed by a slower elimination phase. Total skin lesion area, C1 h and AUC(0-6 h) were related to the dose of Sb infiltered (P < 0.05). Plasma Sb in samples collected weekly before the infiltration revealed antimony concentrations below the quantification limit (15.0 µg Sb/l) during the treatment period. CONCLUSIONS: Sb is quickly absorbed and eliminated after intralesional administration of MA, in a pattern similar to that reported with the Sb systemic administration. Using a therapeutic schedule limited to weekly intralesional infiltration of doses <10 mg Sb/kg does not result in plasma Sb accumulation.

Intralesional therapy with PV-10 (Rose Bengal) for in-transit melanoma.

Rose Bengal is a novel injectable agent that has been evaluated as a rational treatment strategy for melanoma patients with recurrent unresectable local/regional metastases accessible for intralesional injection. PV-10 (10% Rose Bengal) has completed phase 1 and phase 2 multi-center clinical trials demonstrating significant local/regional disease control and also responses in non-injected regional bystander lesions and distant metastases. The published results of studies that have assessed PV-10 are presented, and the rationale for combining its use with recently approved immunotherapeutic agents is discussed.

Intralesional immunotherapy for melanoma.

Intralesional immunotherapy of melanoma has two complementary aims. One is to cause regression of the injected metastasis. The other is to incite or modulate systemic immune responses in such a way that non-injected metastases will also undergo regression. A number of phase 1 and phase II studies with cytokines, viral, or bacterial agents have been conducted but their use has remained sporadic and has not progressed to become established treatments. Two treatments have progressed to randomized phase III studies. The most promising of these is based on intralesional injection of a genetically modified herpes simplex virus (HSV) (T-Vec). Initial results have shown a significant effect on durable response rates (DRR) but effects on overall survival remain under study. The second involved injection of plasmids coding for the HLA B7 antigen (Allovectin). Despite encouraging early results the treatment did not reach its endpoints and its use has been discontinued. A phase II study involving intralesional injection of oncolytic A21 coxsackie virus (Cavatak) is also under way and is showing promise.

Safety and Effectiveness of Percutaneous Ultrasound-Guided Galvanic Current in Tunnels of Patients with Hidradenitis Suppurativa: A Pilot Study.

INTRODUCTION: The recurrent nature of hidradenitis suppurativa (HS), even under maintained systemic treatment, makes it necessary to have effective local treatments; however, the response to these therapies is variable (44-81%). The application of galvanic current (GC) has demonstrated its utility in humans in treating lesions structurally similar to those of HS. With this background, the main objective of this study was to evaluate the efficacy and safety of ultrasound-guided percutaneous GC in inflamed and/or draining tunnels of HS. METHODS: This was an open study (one-way repeated measures design over time). Patients were evaluated at 4 and 12 weeks after receiving GC. A combined clinical response at week 12 (absence of suppuration/inflammation on examination and clinical interview) was considered the principal variable of efficacy. Adverse effects potentially associated with GC were reported by telephone and at each visit. RESULTS: Twenty-six patients were included, with a male/female ratio of 5:8. The mean age was 35.84 (13.14) years. At 12 weeks after the administration of GC, a complete response was achieved in 77% (20/26) of the treated lesions. No serious adverse effects were observed, and the mean procedural pain assessed by the numeric rating scale was 0.03 (0.2). CONCLUSION: GC has proven to be effective and well tolerated in inflamed and draining tunnels of patients with HS.

Systematic Review of Intralesional Therapies for Cutaneous Warts.

Intralesional therapies are used for recalcitrant warts, but no Food and Drug Administration-approved treatment exists nor is there consensus regarding the most efficacious therapy. Therefore, this systematic review aims to summarize efficacy and adverse events reported in 62 randomized controlled trials (RCTs) of intralesional therapies for cutaneous warts. The most studied intralesional therapies included measles, mumps, rubella (MMR) vaccine (n = 24 studies), purified protein derivative (PPD) (n = 19 studies), vitamin D3 (n = 15 studies), and Candida antigen (n = 14 studies). Most studies included adult and pediatric patients or adults alone, with only 4 studies on pediatric patients alone. MMR vaccine was the most studied treatment (n = 853 patients). MMR had a complete response rate of 27-90%. The next most common treatment, PPD, had a complete response rate of 45-87%. Other treatments included Candida antigen and vitamin D3, with complete response rates of 25-84% and 40-96%, respectively. The most frequent side effects were injection-site reactions and flu-like symptoms. This systematic review represents a useful summary of intralesional therapy RCTs for clinician reference. This study also highlights the lack of large multi-institutional RCTs, despite many patients being treated for this widespread problem.

Intratumoral therapies in head and neck squamous cell carcinoma: A systematic review and future perspectives.

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.

Enhanced Insights into Frontal Fibrosing Alopecia: Advancements in Pathogenesis Understanding and Management Strategies.

Frontal fibrosing alopecia (FFA) represents a distinctive form of primary lymphocytic scarring alopecia characterized by fronto-temporal hair recession and eyebrow hair loss. While predominantly affecting postmenopausal women, FFA also occurs in women of reproductive age and men, with variations observed across different ethnic groups. Genetic predisposition, environmental factors and inflammatory pathways contribute to its pathogenesis, with evolving diagnostic criteria enhancing accuracy. FFA treatment lacks standardization, encompassing topical, systemic and physical therapies, while hair transplantation remains a temporary solution. This article reviews the current understanding of FFA, aiming to provide clinicians with updated insights for its management.

Surgical pearl: Modified hypodermic needle and its cap for guarded prick incision.

There are many instruments to prick the comedone before its extraction and scalp during hair transplantation. These instruments are not well guarded, and it can cause deep injury and fear in the patients. Here we described how to guard these needle for safety during procedure.

Intralesional cidofovir for the management of refractory cutaneous verrucae: a review of applications and opportunities.

Viral warts - manifestations of cutaneous infection by human papilloma virus - can be a significant physical and emotional burden for patients when common treatments fail, particularly for individuals who are immunocompromised or with multiple lesions. Cidofovir, an antiviral agent typically used for the treatment of cytomegalovirus infection, has emerged as an alternative treatment option for viral warts when administered topically or intralesionally. In this review, we highlight the scientific rationale, published evidence, and practical clinical uses of intralesional cidofovir for the management of cutaneous warts as well as ongoing questions requiring further research and exploration of this emerging therapy for refractory verrucae.

Sealing of Follicular Openings in Keloid with Cyanoacrylate Glue for Effective Intralesional Therapy.

Intralesional therapy is a common treatment for keloid. However, because of some follicular openings and comedones on the surface of the keloid on the hairy chest and acne keloidalis, there is a risk of drug leakage, and sometimes ejection of drugs like a jet spray leads to therapy being ineffective. The authors describe a novel and effective method for preventing drug loss from follicular openings during intralesional therapy. To prevent drug loss during intralesional injection, cyanoacrylate glue is applied to the follicular and comedone openings on the keloid's surface.

Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress.

Locoregionally advanced and metastatic melanoma are complex diagnoses with a variety of available treatment options. Intralesional therapy for melanoma has been under investigation for decades; however, it has advanced precipitously in recent years. In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma. There has been significant progress since that time with other oncolytic viruses, toll-like receptor agonists, cytokines, xanthene dyes, and immune checkpoint inhibitors all under investigation as intralesional agents. Further to this, there has been exploration of numerous combinations of intralesional therapies and systemic therapies as various lines of therapy. Several of these combinations have been abandoned due to their lack of efficacy or safety concerns. This manuscript presents the various types of intralesional therapies that have reached phase 2 or later clinical trials in the past 5 years, including their mechanism of action, therapeutic combinations under investigation, and published results. The intention is to provide an overview of the progress that has been made, discuss ongoing trials worth following, and share our opinions on opportunities for further advancement.