Intratumoral Injection of Immunotherapeutics: State of the Art and Future Directions.

Systemic immunotherapies have led to tremendous progress across the cancer landscape. However, several challenges exist, potentially limiting their efficacy in the treatment of solid tumors. Direct intratumoral injection can increase the therapeutic index of immunotherapies while overcoming many of the barriers associated with systemic administration, including limited bioavailability to tumors and potential systemic safety concerns. However, challenges remain, including the lack of standardized approaches for administration, issues relating to effective drug delivery, logistical hurdles, and safety concerns specific to this mode of administration. This article reviews the biologic rationale for the localized injection of immunotherapeutic agents into tumors. It also addresses the existing limitations and practical considerations for safe and effective implementation and provide recommendations for optimizing logistics and treatment workflows. It also highlights the critical role that radiologists, interventional radiologists, and medical physicists play in intratumoral immunotherapy with respect to target selection, image-guided administration, and response assessment.

CT-guided quadratus femoris injection for ischiofemoral impingement.

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

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

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

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

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

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

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

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

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

Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity.

Immune stimulation has emerged as a promising approach to the treatment of neoplastic diseases. Currently approved therapeutics, such as anti-CTLA4 and anti-PD1, are primarily aimed at blocking inhibitory signaling by immune cells. An alternative and potentially synergistic approach would involve activation of immune pathways by agonism of stimulatory receptors, such as CD40. Agonistic antibodies, while promising in principle, have encountered significant barriers in clinical trials limited by the systemic toxicity of such approaches. Using a mouse model humanized for both Fc receptors and CD40, we previously demonstrated enhanced antitumor activity with an Fc-modified antibody. We now demonstrate that this model recapitulates the platelet and hepatic toxicities seen with anti-CD40 antibodies in patients, providing a predictive measure of the dose-limiting activity of this approach. We further show that such toxicity can be circumvented and durable systemic antitumor immunity achieved by intratumoral delivery of an Fc-engineered anti-CD40 agonistic antibody.

Endoscopic ultrasound-guided cyanoacrylate injection to prevent rebleeding in hepatocellular carcinoma patients with variceal hemorrhage.

BACKGROUND AND AIM: Secondary prophylaxis (SP) of variceal rebleeding was reported to improve outcomes of hepatocellular carcinoma (HCC) patients, but the optimal endoscopic approach is not well defined. We compared outcomes in HCC patients who underwent SP by endoscopic ultrasound-guided cyanoacrylate obturation (EUS-CYA) versus no SP. METHODS: Between 2014 and 2018, 30 consecutive patients with inoperable HCC and recent endoscopically controlled variceal bleeding were prospectively recruited. Twenty-seven patients with persistent varices ≥ 3 mm on endoscopic ultrasound underwent EUS-CYA for SP. Thirty-three HCC patients treated by esophagogastroduodenoscopy-guided CYA obturation (EGD-CYA) alone for acute variceal bleeding between 2009 and 2013 were identified from a prospective gastrointestinal bleed registry as standard of care controls for comparison. Outcome measures were death-adjusted cumulative incidence of rebleeding, bleeding-free survival, technical success, and procedure-related adverse events of EUS-CYA. RESULTS: The majority of patients in both groups had advanced HCC, portal vein thrombosis, and Child-Pugh B cirrhosis. EUS-CYA was successful in all 27 patients with no radiographic evidence of cyanoacrylate-lipiodol embolization. Significantly lower 30- and 90-day death-adjusted cumulative incidence of rebleeding (14.8% vs 42.4%, P = 0.023 and 18.5% vs 60.6%, P = 0.002, respectively) and significantly higher variceal bleeding-free survival at 3 and 6 months (51.9% vs 21.2%, P = 0.009, 40.7% vs 15.2%, P = 0.010, respectively) were observed in the EUS-CYA group when compared with standard of care group. CONCLUSIONS: Secondary prophylaxis by EUS-CYA reduced rebleeding rate and improved variceal bleeding-free survival in patients with inoperable HCC and variceal bleeding when compared with no SP. Randomized studies are needed to confirm the benefits of EUS-CYA for this difficult-to-treat population.

Fiberoptic Bronchoscopic Submucosal Injection of Mitomycin C for Recurrent Bening Tracheal Stenosis: A Case Series.

BACKGROUND: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets. OBJECTIVES: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis. METHODS: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019. RESULTS: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects. CONCLUSIONS: The efficacy of MyC injection should be studied prospectively.

The injection site in the tarsal tunnel to minimize neurovascular injury for heel pain: an anatomical study.

INTRODUCTION: The aim of this study was to investigate the location and distribution patterns of neurovascular structures and determine the effective injection point in the tarsal tunnel for heel pain. METHODS: Fifteen adult non-embalmed cadavers with a mean age of 71.5 years were studied. The most inferior point of the medial malleolus of the tibia (MM) and the tuberosity of the calcaneus (TC) were identified before dissection. A line connecting the MM and TC was used as a reference line. The reference point was expressed in absolute distance along the reference line using the MM as the starting point. For measurements using MRI, the depth from the skin was measured to inferior at an interval of 1 cm from the MM. RESULTS: The posterior tibial artery, lateral plantar nerve, and medial plantar nerve were located from 29.0 to 37.3% of the reference line from the MM. The distribution frequencies of the medial calcaneal nerve on the reference line from the MM were 0%, 8.60%, 37.15%, 37.15%, and 17.10%, respectively. The mean depth of the neurovascular structures was 0.3 cm. DISCUSSION: This study recommended an effective injection site from 45.0 to 80.0% of the reference line.

Low-Dose Intralesional Recombinant Interferon-α2b in the Treatment of Mycosis Fungoides.

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is characterized by malignant CD4+ skin-homing T-cells that drive formation of cutaneous patches, plaques, and/or tumors. MF's known immunogenicity makes it an ideal candidate for local immunotherapy. Recombinant human leukocyte interferon-α2 (rIFN-α2) has well-established immunomodulatory, antiproliferative, and antitumor effects; and relatively low levels of endogenous IFN-α have been observed within MF lesions. As a systemic therapy delivered via subcutaneous (SC) or intramuscular (IM) injection, rIFN-α2 has previously shown efficacy against MF. Due to high levels of toxicity associated with the systemic dosing required for improvement of disease, rIFN-α2 has had limited use in the treatment of MF. For these reasons, we sought to deliver rIFN-2 as a local immunotherapy, and herein describe two cases of MF successfully managed with intralesional injections of low-dose rIFN-α2. With limited reporting in the medical literature, intralesional injection of rIFN-α2 has shown efficacy, but with high frequency of associated systemic side effects. Towards a better tolerated, localized immunotherapy, we initiated treatment in two MF patients with low dose (0.5 MU) rIFN-α2 per injection that led to marked responses, and subsequent dosing to 1.0 MU ultimately led to complete resolution of the treated lesions without the generalized side effects observed with systemic administration of rIFN-α2. These cases suggest that low-dose intralesional rIFN-α2 may be an efficacious and well-tolerated local immunotherapy for early stage MF, providing a therapeutic option for the management of chronic, recalcitrant lesions.

Optimizing collagenase Clostridium histolyticum therapy for Peyronie's disease using a novel approach with percutaneous needle tunnelling.

OBJECTIVES: To compare the efficacy and safety of a combined treatment of percutaneous needle tunnelling (PNT) and a modified collagenase Clostridium histolyticum (CCH) protocol (PNT/CCH) vs the modified protocol alone (CCH) in the treatment of Peyronie's disease (PD). PATIENTS AND METHODS: A prospective registry of patients treated with a modified CCH protocol was maintained between June 2014 and February 2018. The last 50 patients received PNT as an adjuvant therapy (PNT/CCH), and their data were compared with those of the other 94 patients treated previously (CCH). PNT involves the creation of multiple holes made percutaneously in the plaque before each injection. The modified protocol consisted of two collagenase injections, at 1-week intervals, followed by penile modelling. Patients used penile traction therapy, tadalafil and pentoxifylline for the next 2 months and were followed up for 6 months. The main outcome was improvement of curvature. Secondary outcomes were improvements in erectile function, PD symptoms, stretched penile length and satisfaction. RESULTS: Improvement in curvature was greater in patients in the PNT/CCH group than in the CCH group (mean ± sd 19.2 ± 6.1° vs 12.7 ± 5.0°; P < 0.001 [36.2 ± 12.5% vs 28.1 ± 14.5%; P = 0.001]). Compared with baseline, both interventions were associated with significant improvement in secondary outcomes. The main complications were ecchymosis, bruising and penile pain, with no significant differences between groups. CONCLUSIONS: Treatment of PD with CCH using our modified protocol in combination with PNT is safe and more effective than the modified protocol alone, with the potential for improved cost-effectiveness.

Ultrasonographic intraoperative monitoring and follow-up of Kaposi's sarcoma nodules under treatment with intralesional vincristine.

BACKGROUND: Intralesional vincristine is an effective treatment for Kaposi's sarcoma (KS) nodules on the skin, but there is little evidence of its action through imaging techniques. Ultrasonography can be an adjunctive tool in the diagnosis and management of KS skin lesions, but data in the literature are few. MATERIALS AND METHODS: Five patients with classic KS nodules were treated with intralesional vincristine. Ultrasonographic and color Doppler assessment were performed during vincristine injection and monitoring was repeated 1 and 3 months after the procedure. Partial response was defined as a reduction of more than 50% lesion volume and reduction of the vascular signal; complete response as a resolution of lesion associated with the absence of vascular signal. RESULTS: Six KS nodules were included in the study. On ultrasonography examination, KS nodules appeared as oval or round, hypoechoic, homogeneous structures, with intralesional vascularization, more prominent in the deepest pole of the nodule. At month 1, 4 nodules achieved a complete response, while two nodules showed a partial response and were retreated with intralesional vincristine. At month 3, all lesions achieved a complete response. CONCLUSION: Ultrasonography may be a valuable tool in assessing clinical response to intralesional vincristine therapy of cutaneous KS nodules.

Emerging Nonsteroid-Based Procedural Therapies for Alopecia Areata: A Systematic Review.

BACKGROUND: Alopecia areata (AA) is a common form of patchy, nonscarring hair loss. Although intralesional steroid injections are currently the mainstay procedural therapy for AA, other nonsteroid-based procedural therapies, including platelet-rich plasma (PRP), ultraviolet radiation (UVR), and laser-based modalities, are emerging as practical options. OBJECTIVE: To systematically review nonsteroid-based procedural therapies for AA and recapitulate the available clinical data. MATERIALS AND METHODS: A systematic review of the literature was performed searching PubMed/MEDLINE databases identifying studies investigating PRP, UVR, and laser-based modalities for AA treatment. RESULTS: Literature search yielded 644 articles encompassing PRP, UVR, and laser treatment modalities for AA. Of the 644 articles, 46 met inclusion criteria. Although numerous reports demonstrate strong potential for PRP, UVR, and laser modalities in treating AA, high-quality evidence supporting their efficacy is still lacking. CONCLUSION: There is an abundance of evidence for nonsteroid-based procedural therapies in the treatment of AA. Randomized control trials comparing these treatment options head-to-head should be performed to better understand the true efficacy of these treatments.

Treatment of male stress urinary incontinence using autologous adipose-derived regenerative cells: Long-term efficacy and safety.

OBJECTIVES: To investigate the long-term efficacy and safety of periurethral injection of autologous adipose-derived regenerative cells for the treatment of post-prostatectomy stress urinary incontinence. METHODS: A total of 13 patients with persistent stress urinary incontinence after prostate surgery (radical prostatectomy, 10 patients; holmium laser enucleation of the prostate, three patients) underwent periurethral injection of adipose-derived regenerative cells and were followed up for >4 years. A 24-h pad test was carried out for four consecutive days in each evaluation period, and changes in the mean daily leakage volume during the 4 days from baseline to 60 months after treatment were evaluated. RESULTS: The mean follow-up period was 69 months (range 55-72 months). The mean leakage volume/24 h in all patients changed from 260.7 g to 152.7 g. Urinary incontinence progressively improved up to 12 months after treatment in 10 patients, who maintained improvement up to the final assessment, with the mean daily leakage volume decreasing from 281.5 g to 119.0 g (reduction rate 57.7%). The other three patients showed no improvement at 1 year and at the final assessment. After the perioperative period, significant adverse events or prostate-specific antigen increase were not observed during long-term follow up. CONCLUSIONS: The present findings suggest that periurethral injection of autologous adipose-derived regenerative cells is a safe and feasible treatment modality with long-term efficacy for patients with male stress urinary incontinence caused by urethral sphincter deficiency.

Endoscopic Balloon Dilation Followed By Intralesional Steroid Injection for Anastomotic Strictures After Esophagectomy: A Randomized Controlled Trial.

OBJECTIVE: Endoscopic balloon dilation (EBD) is a standard treatment for anastomotic strictures after esophagectomy, and requires multiple dilations. We conducted a randomized controlled trial to assess the efficacy of adding a steroid injection to EBD to reduce restricture. METHODS: Patients were randomized to receive EBD combined with either triamcinolone or placebo injection. The primary endpoint was the number of dilations required to resolve the stricture. The secondary endpoints were restricture-free survival and adverse events. Patients with a dysphagia symptom score of ≥2 after esophagectomy with an endoscopy-confirmed anastomotic stricture were included. A total of 50 mg of triamcinolone acetonide (50 mg/5 mL) or an identical volume of normal saline solution as a placebo was injected per site using a 25-gauge needle immediately after EBD. Both the patient and treating physician were blinded to the treatment given. RESULTS: During the 4-year study period, 65 patients were randomized to either the steroid group (n = 33) or placebo group (n = 32). The median number of EBDs required to resolve strictures was 2.0 (interquartile range, 1.0-2.5) in the steroid group and 4.0 (interquartile range, 2.0-6.8) in the placebo group (p < 0.001). After 6 months of follow-up, 39% of patients who had received steroid injections remained recurrence free compared with 16% of those who had received saline injections (p = 0.002). No adverse events occurred during follow-up. CONCLUSIONS: Steroid injection shows promising results for the prevention of stricture recurrence in patients who underwent EBD for anastomotic strictures.

A Phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer.

BACKGROUND: Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study. METHODS: This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment. RESULTS: Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR). CONCLUSIONS: HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies. TRIAL REGISTRATION: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.

Fexapotide triflutate: results of long-term safety and efficacy trials of a novel injectable therapy for symptomatic prostate enlargement.

PURPOSE: These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). METHODS: Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. RESULTS: FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. CONCLUSIONS: FT 2.5 mg is a safe and effective transrectal injectable for LT treatment of BPH. FT treated patients also had reduced need for BPH intervention, and reduced incidence of PCa and AUR.

Investigational procedures in benign prostatic hypertrophy.

PURPOSE OF REVIEW: As benign prostatic hypertrophy (BPH) becomes a more common disease, there has been a dramatic rise in the number of investigational procedures being developed to manage it. We seek to present an overview of the most recently developed treatments and present clinical data related to application wherever available. RECENT FINDINGS: As a greater number of treatments become available for BPH, improved diagnostic testing could prove beneficial in helping guide patient selection. Efforts are underway to identify serum biomarkers associated with BPH as well as new classifications strategies, specifically with MRI, to determine both the anatomy of BPH as well as its histologic distribution. Outpatient-based procedures for BPH currently being developed include the temporary implantable nitinol device as well as intraprostatic injections such as Botox and PRX302. Aquablation is a novel technique that uses robotically guided high-pressured saline to ablate prostate tissue. Early data suggests noninferiority compared with TURP. Finally, efforts are underway to apply robotics to BPH with the advent of a robotic transurethral platform being designed for prostate enucleation. SUMMARY: Many new techniques are poised to be introduced to the BPH market over the coming years. The unique risk/benefit profiles as well as associated clinical outcomes of each will need to be studied in detail in order to help identify proper roles in the management of patients with symptomatic disease.

The Effects of Postoperative Intralesional Corticosteroids in the Prevention of Recurrent Earlobe Keloids: A Multispecialty Retrospective Review.

BACKGROUND: Effective treatment of keloids is challenging because the recurrence rate after surgical excision is high. Data on the best treatment practices are lacking. OBJECTIVE: To investigate the recurrence rate after surgical excision of earlobe keloids based on a postoperative intralesional corticosteroid injection protocol. MATERIALS AND METHODS: Retrospective chart review was performed from January 1, 2005, to March 31, 2016, of patients who had excision of ear keloids within the departments of dermatology, otorhinolaryngology, and plastic surgery. The number of postoperative injections was recorded, recurrence was reported by the patient, and the efficacy of an injection protocol was evaluated. RESULTS: There were 277 charts reviewed. Appropriate data were available for 184 patients. A statistically significant difference was found with recurrence associated with a lower number of injections (p < .001). Keloids were more likely to recur if they were not treated with a planned serial injection protocol (p < .001) or if they were treated outside the department of dermatology (p < .001). CONCLUSION: Intralesional corticosteroid injection after surgical excision of earlobe keloids statistically minimizes the risk of recurrence.