Subcutaneous Induration Research Articles

A jugular venous compression adjunct for surgical excision of distensible orbital venous malformations

ABSTRACT Purpose Orbital venous malformations (VM) pose challenges in complete resection due to indistinct borders and bleeding proclivity. Current methods for aiding surgical excision of distensible orbital venous malformations are inadequate. We investigated whether external neck compression could facilitate intraoperative distension of venous orbital lesions during surgical excision in patients diagnosed with VM. Methods Eighteen patients (8 males and 10 females) diagnosed with distensible venous anomalies were enrolled. Neck compression technology, was employed to distend the lesions before puncture embolization using n-butyl-2-cyanoacrylate glue under general anesthesia. The surgical process, along with preoperative to postoperative changes in ocular symptoms, were recorded. Results The average surgical duration was 95 min. A mean of 3.41 ml surgical glue was used for embolization. The compression belt maintained pressure at 35–40 mmHg. Total lesion resection was achieved in 12 patients, with 6 patients undergoing subtotal removal not requiring supplementary surgery. Symptoms were entirely alleviated in 17 patients, and signs of distensible lesions during the Valsalva maneuver were absent. One patient underwent secondary surgery for residual eyelid lesions. Minor complications included mild ocular movement restriction, residual subcutaneous induration, transiently increased orbital pressure, and lower lid ectropion in four, three, four, and one patient, respectively. Three patients experienced a mild post-operative visual acuity decrease, although none experienced vision loss. Conclusions Direct orbital embolization aided by a jugular vein compression device is safe and demonstrates satisfactory outcomes in orbital varicose vein treatment.

A comprehensive practical review of acupoint embedding as a semi-permanent acupuncture: A mini review.

Since ancient times, acupuncture has been utilized in the treatment of lots of diseases, as a part of Traditional Chinese Medicine. Acupoint embedding (AEM) therapy, known as catgut embedding, is a development of acupuncture that consists of inserting catgut or surgical threads into specific acupoints to produce continuous acupoint stimulation based on the theory of Traditional Chinese Medicine. The remaining thread in the acupoint works as a semi-permanent acupuncture needle that results in decreasing the total time of the treatment which is required for continuous manual acupuncture sessions and increasing the treatment efficacy and patients' satisfaction. In each session of AEM about twenty 1 to 2 cm-long threads-natural origin, synthetic polymer, or bioactive threads-will be inserted at the target acupoints and this process will be repeated every 3 to 4 weeks. Indications of AEM are somehow similar to manual acupuncture including obesity, pain, musculoskeletal inflammations, infertility, etc, and it cannot be performed on pregnant women and pediatrics. AEM demonstrates its therapeutic effects via modulating immune system function, alleviating body inflammatory conditions, affecting the neurohormonal system, and other mechanisms. Subcutaneous indurations, redness, bleeding, hematoma, and bruising are some adverse events reported following the AEM. In conclusion, the scientific literature suggests that AEM is a relatively safe and convenient therapy if performed by a professional skilled practitioner.

Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended-release microparticle formulation: A phase 1, dose-ascending study in male volunteers.

A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.

Giant Subcutaneous Hematoma Associated with Subcutaneous Insulin Injection in a Patient with Diabetes: a Case Report

The complications of insulin self-injection include subcutaneous bleeding, nerve damage, and subcutaneous induration due to repeated injection at the same site. However, considering the short length and thinness of the needle, it is unlikely that these complications will ever become serious. Here, we report a case of a 50-year-old man with abdominal giant hematoma due to insulin self-injection, which requires surgical treatment. The patient had obesity and took anticoagulants and steroids for 12 years. These drugs seemed to have affected the vessel wall and led to its compromise or destruction and subsequent hemorrhagic events.

Comparison of day surgery between varicose veins with and without superficial venous thrombosis below knee: a propensity score-matched analysis

ObjectivesDevelopment of endovenous treatment and sclerotherapy technology makes it feasible for clinicians to treat varicose veins (VV) through day surgery (DS). Superficial venous thrombosis (SVT) of lower extremities is a common complication of VV. This study aimed to investigate whether the existence of SVT below knee affect the safety and efficacy of DS for VV patients.MethodsThis is a single-center retrospective study. Clinical data of 593 VV patients was retrospectively analyzed. Raw data were matched by the using of propensity score matching model. Operation time, technical failure, postoperative DVT, skin burns, saphenous nerve injury, subcutaneous induration, and bleeding were compared between the groups. Also, we compared VV recurrence, SVT formation, DVT events and the change of VCSS score with 12 months.ResultsFifty-nine patients complicated with SVT below knee were matched with 118 patients had VV only. Perioperative and follow-up outcomes were similar in both groups except for the number of incisions (median = 6 [5, 7] VS median = 4 [4, 5], P < 0.001). Both groups experienced a great decrease in VCSS score.ConclusionWe systematically compared the clinical outcomes of DS in VV patients. Our results indicate DS is safe and effective for patients with VV, whether accompanied by SVT below the knee.Trial registrationThe ClinicalTrials.gov identifier for this trial is NCT05380895 (retrospectively registered).

Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis

It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50–400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60–100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.

Cutaneous arteritis: Clinicopathological study of 21 cases

AbstractObjectivesWe conducted this study to clarify the progress of cutaneous arteritis.MethodsWe examined 21 cases of cutaneous arteritis that were diagnosed at our hospital between 2005 and 2020. The male‐to‐female ratio was 1:6 with a mean age of 52.2 years.ResultsThe lower legs were involved in all cases, and the upper extremities or trunk was also involved in some cases. Cutaneous manifestations presented as indurated erythema (n = 15), subcutaneous induration (11), edema (7), livedo (6), and ulcer (3). In addition, extracutaneous conditions including numbness (10), arthritis (8), fever (2), and myalgia (1) were observed. Laboratory tests showed an increase of inflammatory markers in most cases (14). Histopathological features showed necrotizing vasculitis of small‐sized arteries at the dermo‐subcutaneous junction, and the inflammatory stages of arteritis were histopathologically divided into acute stage (5), subacute stage (5), reparative stage (7), and healed stage (1). The therapies administered were oral prednisolone (11), antiplatelet drug (14), warfarin (1), non‐steroidal anti‐inflammatory drugs (6), biological drug (1), and other drugs (14). There were no cases showing progression to systemic polyarteritis nodosa during follow‐up period. All three patients with ulceration complained of numbness, and one was revealed to have mononeuropathy multiplex. They were treated with low‐dose oral prednisolone. Three ulceration cases were histopathologically classified into the acute and subacute stages.ConclusionsIn conclusion, all 21 patients followed a chronic course with recurrent skin lesions without systemic complications. Cases with ulceration seem to reveal neurological symptoms and need systemic steroid treatment.

Treatment of mild hemifacial microsomia in children by autologous nano-fat mixed granule fat transplantation

To investigate the effectiveness of autologous nano-fat mixed granule fat transplantation in the treatment of facial soft tissue dysplasia in children with mild hemifacial microsomia (HFM). A total of 24 children with Pruzansky-Kaban type Ⅰ HFM were admitted between July 2016 and December 2020. Among them, 12 children were treated with autologous nano-fat mixed granule fat (1∶1) transplantation as study group and 12 with autologous granule fat transplantation as control group. There was no significant difference in gender, age, and affected side between groups ( P>0.05). The child's face was divided into region Ⅰ(mental point-mandibular angle-oral angle), region Ⅱ (mandibular angle-earlobe-lateral border of the nasal alar-oral angle), region Ⅲ (earlobe-lateral border of the nasal alar-inner canthus-foot of ear wheel). Based on the preoperative maxillofacial CT scan+three-dimensional reconstruction data, the differences of soft tissue volume between the healthy and affected sides in the 3 regions were calculated by Mimics software to determine the amount of autologous fat extraction or grafting. The distances between mandibular angle and oral angle (mandibular angle-oral angle), between mandibular angle and outer canthus (mandibular angle-outer canthus), and between earlobe and lateral border of the nasal alar (earlobe-lateral border of the nasal alar), and the soft tissue volumes in regions Ⅰ, Ⅱ, and Ⅲ of healthy and affected sides were measured at 1 day before operation and 1 year after operation. The differences between healthy and affected sides of the above indicators were calculated as the evaluation indexes for statistical analysis. At 1 year after operation, the parents, the surgeons, and the nurses in the operation group made a self-assessment of satisfaction according to the frontal photos of the children before and after operation. The study group and the control group were injected with (28.61±8.59) and (29.33±8.08) mL of fat respectively, with no significant difference ( t=0.204, P=0.840). After injection, 1 child in the control group had a little subcutaneous induration, and no related complications occurred in the others. All children in both groups were followed up 1 year to 1 year and 6 months, with an average of 1 year and 4 months in the study group and 1 year and 3 months in the control group. At 1 year after operation, the asymmetry of the healthy and affected sides improved in both groups; the satisfactions of parents, surgeons, and nurses in the study group were all 100% (12/12), while those of the control group were 100% (12/12), 83% (10/12), and 92% (11/12), respectively. The differences between healthy and affected sides in mandibular angle-oral angle, mandibular angle-outer canthus, earlobe-lateral border of the nasal alar, and the soft tissue volume in 3 regions of the two groups after operation were significantly smaller than those before operation ( P<0.05). There was no significant difference in the above indexes between the two groups before operation ( P>0.05). After operation, all indexes were significantly lower in study group than in control group ( P<0.05). Autologous nano-fat mixed granule fat transplantation and autologous granule fat transplantation can both improve the facial soft tissue dysplasia in children with mild HFM, and the former is better than the latter.

Local and systemic reactions associated with COVID-19 vaccines: logistic regression analysis

Objective: Universal vaccination is one of the most effective measures to control the COVID-19 epidemic. However, adverse reactions sometimes occur after vaccination. Therefore, we investigated the local and systemic adverse reactions associated with COVID-19 vaccines. Methods: We conducted a multicenter cross-sectional survey from 1 December 2021 to 28 February 2022 in Jiangsu, China to analyze skin and systemic reactions. We collected questionnaires from vaccination sites, communities, and hospitals. Participants could either complete an online survey using the WeChat-based survey program Questionnaire Star or complete a paper questionnaire. Individual participants remained anonymous both during and after data collection. Results: A total of 2136 participants successfully completed the survey. The most common symptoms were pain, swelling, and subcutaneous induration. Common systemic reactions were fatigue, muscle soreness, and dizziness and headache. The risk of reactions was associated with sex; age; history of allergy to vaccinations; history of eczema, dermatitis, or urticaria; and receiving the same type of vaccine from different manufacturers. Conclusions: Overall, our results indicated that many factors can influence the occurrence of local and systemic reactions associated with COVID-19 vaccines.

S2930 Calciphylaxis Due to Alcoholic Liver Disease

Introduction: Advanced liver disease often has multiorgan involvement, including dermatological findings. These range from spider angiomas to palmar erythema. Here we present a case of calciphylaxis as a manifestation of decompensated alcoholic liver disease. Case Description/Methods: A 38 year-old female with decompensated alcoholic cirrhosis (portal vein thrombosis, ascites, hepatic encephalopathy, and hepatic hydrothorax) reported to the emergency room complaining of new right thigh wounds. Her vital signs were unremarkable and her exam demonstrated ascites and bilateral lower extremity edema with right medial thigh erythema, induration, and superficial ulceration (Figure 1). Labs showed sodium 125 mEq/L, Creatinine 0.95 mg/dL, WBC 16.2 x109, and total bilirubin 1.6 mg/dL. CT of her thigh demonstrated bilateral, symmetric subcutaneous induration consistent with anasarca and possible superimposed cellulitis. She was admitted and treated with IV antibiotics. As the lesions became duskier and more painful dermatology was consulted who initially were concerned for a vasculopathic process versus calciphylaxis. The patient was placed on empiric treatment for calciphylaxis with sodium thiosulfate. Skin biopsies were performed and showed non-uremic calciphylaxis (Figure 2). The patient then developed an AKI thought to be from hepato-renal syndrome and was trialed on albumin, midodrine, and octreotide with no improvement in renal function. She then developed acidosis, eventually requiring a bicarb drip, and her wounds continued to progress (Figure 1). When she started becoming repeatedly hypotensive her family transitioned her to comfort care and she was discharged to hospice. Discussion: Calciphylaxis is a rare disease that was first described in 1961 by Selye et al and is largely thought to be related to uremia. Here we describe a case of calciphylaxis in a patient with alcoholic liver disease and initial normal renal function. Our review of the literature found fewer than 11 case reports of calciphylaxis associated with liver disease. The mechanism in these cases appears to be poorly understood though is believed to be connected to protein C and protein S deficiency. As in those with advanced renal disease, calciphylaxis has a poor prognosis with high mortality often reported as greater than 50% even despite treatment. Thus it is important that clinicians recognize its association with alcoholic liver disease to aid in diagnosis and ensure prompt initiation of treatment.Figure 1.: A: Right medial thigh wound B: High power of calcium deposits and thrombus (arrow) within the subcutaneous fat C: corresponding von kossa stain (arrowhead).

The Role of Jinhuang Powder to Prevent Adverse Effects of Subcutaneous Injection of Enoxaparin Sodium.

Objective To determine the role of Jinhuang Powder to prevent adverse effects of subcutaneous injection of enoxaparin sodium. Methods The clinical data of 97 patients with cervical cancer who were treated with subcutaneous injection of enoxaparin through the lower margin of the deltoid muscle of the upper arm in Zhejiang Tumor Hospital from August 2020 to August 2021 were retrospectively analyzed. All patients were divided into the control group (n = 39) and the research group (n = 58) according to the different use time periods of Jinhuang Powder. The research group was treated with Jinhuang Powder and enoxaparin sodium at the same time. The control group started to use Jinhuang Powder after the adverse reactions occurred. The induration, subcutaneous bleeding events, and pain were statistically analyzed. Results The incidence of induration (3.4% vs 15.4%, P=0.036) and subcutaneous hemorrhage (37.9% vs 76.9%, P=0.003) in the research group was significantly lower than that in the control group. The pain in the research group was lighter than that in the control group (grade 0–4 pain: 70% vs 28.2%, 19% vs 30.8%, 8.6% vs 23.1%, 1.7% vs 12.8%, 1.7% vs 5.1%, P=0.001). Conclusion Preventive use of Jinhuang Powder can significantly reduce the incidence of subcutaneous induration and subcutaneous bleeding and can effectively alleviate the local pain of injection. It is worthy of further study to clarify its role and mechanism.

Surgical management after Oxaliplatin extravasation: A case report and literature review.

This case report describes a unique case of chronic reaction after extravasation of oxaliplatin. The pain and extensive subcutaneous induration did not resolve after 9 months of conservative treatment. Surgical debridement with removal of the totally implantable venous access device (TIVAD) resulted in immediate resolution of the symptoms. Oxaliplatin has both irritant and vesicant properties that are difficult to distinguish at initial clinical presentation. In most literature cases complaints resolve within 3 months with conservative treatment yet surgical debridement should be considered if complaints persist beyond this period.

Effect of wet dressing of Chinese herbs on subcutaneous induration caused by subcutaneous injection of Azacitidine

Effect of wet dressing of Chinese herbs on subcutaneous induration caused by subcutaneous injection of Azacitidine

Clinical and penile Doppler outcomes using a modified, tourniquet free, Nesbit plication for severe Peyronie's disease.

BackgroundPenile curvature (PC) can be surgically corrected by plication techniques or Nesbit corporoplasty. These shortening techniques can be complicated by post-operative: penile shortening, recurrent PC, palpable suture knots and erectile dysfunction. Furthermore, Nesbit procedures require the use of a penile tourniquet to avoid intraoperative bleeding. This observational study aims to assess the results of Nesbit modified corporoplasty, avoiding intraoperative use of tourniquet without risk of bleeding. The objective is to reduce penile ischemic anatomical and functional damages such as long-term erectile dysfunction.MethodsBetween January 2010 and March 2019, a total of 64 patients with congenital penile curvature (CPC) and Peyronie’s disease (PD) underwent surgical correction with a Nesbit modified technique first time described by Rolle et al., with minimal technical differences. The operation notes were retrospectively reviewed. In particular, we evaluated pre- and post-operative erectile functions using IIEF-5 score, penile Doppler ultrasonography and overall patient satisfaction.ResultsDuring operations, no intraoperative bleeding was noted, and no short-term complications such as hematomas or neurovascular bundle lesions were reported. At 6 months, no palpable subcutaneous indurations and no sensory change were detected. Post-operative penile shortening was reported in 38 (59.4%) patients (mean 0.83±0.79 cm), but it did not influence the high overall satisfaction rate of 91.4%. Only 2 patients reported a slightly partial recurrence of curvature (<15%) with no need for a redo surgery. Mean IIEF-5 score increased from 17.1±5.2 to 20.8±3.9 at 6 months and 21.8±3.4 at 12 months (P<0.001 in both cases). Mean PSV also significantly increased at the end of follow-up (28.5±6.1 at baseline vs. 31.0±7.1 at 12 months, P=0.03).ConclusionsConsidering the optimal results in terms of erectile functions increasing and absence of PC recurrence (>15°), we think that Nesbit modified corporoplasty without tourniquet application during reconstruction is a safe and effective surgical procedure for all kind of shortening corporoplasty to reduce the time of penile ischemia, preventing even serious consequences for the normal physiology of erection.

Cutaneous Coinfection of Cytomegalovirus and Mycobacterium chelonae Accelerated by Immunosuppression

A mildly diabetic 58-year-old male had traumatic ulceration on the left popliteal fossa, and the lesion progressed to a painful 6 cm deep ulcer. After surgical debridement and skin grafting, ulceration recurred. Pyoderma gangrenosum was clinically diagnosed after the first biopsy, indicating a noninfective ulcer. Immunosuppressive therapy (prednisolone and cyclosporine A) induced complete epithelialization in three months. Four months later, subcutaneous nonulcerated nodules appeared on the anterior area of the left lower leg. Subcutaneous induration progressed and ulceration recurred, so that immunosuppressive therapy continued for one year. Cytomegalovirus (CMV) viremia was detected, and the second biopsy demonstrated CMV inclusions of endothelial and perivascular cells in fibrosing septolobular panniculitis. Cyclosporine A was cancelled, prednisolone was tapered, and ganciclovir started. Viremia soon disappeared, but the lesion progressed to large induration with multiple ulcers measuring up to 3 cm. The third biopsy disclosed infection of Gram-positive mycobacteria, accompanying fat droplet-centered suppurative granulomas without CMV infection. Microbial culture identified Mycobacterium chelonae. Clarithromycin with thermotherapy was effective. A review of the second biopsy confirmed coinfection of CMV and Gram-positive mycobacteria. Immunostaining using a panel of anti-bacterial antibodies visualized the mycobacteria in the lesion. Positive findings were obtained with antibodies to Bacillus Calmette-Guérin, Bacillus cereus, MPT64 (Mycobacterium tuberculosis-specific 24 kDa secretory antigen), LAM (Mycobacterium tuberculosis-related lipoarabinomannan), and PAB (Propionibacterium acnes-specific lipoteichoic acid).

Complications Following Facial Thread-Lifting

ABSTRACT Background Facial thread-lifting (FTL) is a minimally invasive facial rejuvenation technique. However, to date, no study has focused on the treatment of complications associated with FTL. The purpose of this study was to report on clinical manifestations of complications following FTL and their treatment methods. Methods We retrospectively reviewed the electronic medical records of patients who presented with complications of FTL. Patient demographics, medical history, types and clinical manifestations of complications, imaging, treatment methods, histopathological findings, and follow-up information were collected. Descriptive statistical analysis was performed. Results Our sample included 61 patients, all women, with a mean age of 36.3 ± 8.9 years. The most common reason for consultation was infection (31.2%), followed by dissatisfaction with postoperative facial contour (23%), paresthesia (19.7%), dimpling and irregularity (16.4%), subcutaneous induration (13.1%), thread extrusion (4.9%), and facial nerve injury (3.3%). Fifty-one (83.6%) patients reported alleviated symptoms after receiving pharmaceutical and physical therapies. Surgical interventions, including debridement and thread removal, were required in 10 patients (16.4%). Threads were completely or partially removed in 5 patients within 3 months of the initial FTL. During a median follow-up of 1.7 years, 9 patients recovered well and were satisfied with the clinical outcomes, whereas one patient was unsatisfied due to dimpling and scarring. Conclusions The results show that most complications after FTL can be treated non-surgically. Revision surgery is recommended for patients with recurrent infection, thread extrusion, and subcutaneous induration. Aesthetic surgeons and dermatologists should comply with the indications for FTL and optimize surgical procedures to minimize the risk of complications.

LOCAL REACTIONS OF LUTEINIZING HORMONE-RELEASING HORMONE AGENTS AND ITS EFFECTS ON CLINICAL OUTCOMES IN PROSTATE CANCER PATIENTS

(Background) Currently, luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists are used for androgen-deprivation therapy (ADT). However, they are associated with subcutaneous granuloma, rubor, dolor, calor, and eventual ulcer and/or abscess formation. The prevalence of these adverse effects, causes and mechanisms, and effects on serum testosterone levels and clinical outcomes are poorly understood. (Method) We collected the clinical records of men with pathologically diagnosed prostate cancer who were followed in our hospital. The primary aim of the study was to determine the prevalence of granuloma formation, its causes, and the mechanisms involved. The secondary aim was to analyze the effects of subcutaneous induration on serum testosterone levels and clinical outcomes. (Results) Overall, 185 men using leuprorelin (n=161; median age, 75 years), degarelix (n=21; median age, 76), or goserelin (n=3; median age, 76) were analyzed. In the leuprorelin cohort, 51 patients (33.5%) had subjective and/or objective subcutaneous induration and 2 (1.2%) had a large lesion (diameter > 3.0 cm). In the degarelix cohort, 18 patients (85.7%) developed induration and 8 (38%) had a large lesion. One month after the start of ADT, patients in the leuprorelin and degarelix cohorts had median serum testosterone levels that reached the same level as that after castration. There was no significant difference in the overall survival rate between the leuprorelin and degarelix cohorts. There was no significant difference in the serum testosterone level or overall survival rate between patients with or without induration. (Conclusions) The local adverse effects of LH-RH agents are prevalent, but we can regulate the adverse effects by understanding the mechanism involved. The formation of subcutaneous induration did not affect the serum testosterone level or clinical outcome.

Abstract CT237: A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer

Abstract Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. 10 of the 25 patients developed grade 1 local skin reactions with redness, swelling or subcutaneous indurations in the injection sites. Three patients were observed grade 2 local skin reactions in the injection sites. Four had grade 1 to 2 fever. No SAEs related to PVAC have been observed. Among median follow up time of 11.6 months (range: 7.5-24.0 months), only one patient had local recurrence at 10.5 months after surgery. The rest 24 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigens/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient's capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319. Citation Format: Qin Liu, Hanqing Qian, Jie Shao, Qiuping Xu, Huizi Sha, Yang Yang, Weifeng Wang, Lixia Yu, Baorui Liu, Jia Wei. A phase I study to assess the safety, tolerability, and immunogenicity of personalized neoantigen/cancer testis antigen nanovaccine (PVAC) for high-risk resected gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT237.

Abstract 1049: Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors

Abstract Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Nanotechnology has been reported to enhance immune responses of vaccines. Moreover, immunizing patients against such neoantigens, in combination with checkpoint inhibitor (CPI) and/or antiangiogenic drugs may elicit greater anti-tumor responses. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) is an amphiphiles nanovaccine loaded with personalized vaccine encoding multiple neoantigens designed to induce neoantigen specific T cells responses. Patients will receive PVAC in combination with PD-1 monoclonal antibody and/or antiangiogenic drugs. Primary end points include safety and tolerability. Results: 9 microsatellite stability (MSS) patients, which had relapsed from standard treatments, are enrolled in this study. 4 patients (1 gastric cancer, 1 liver cancer, 1 cervical carcinoma, 1 soft tissue sarcoma) received PVAC in combination with PD-1 mAb, and another 5 patients (2 gastric cancer, 1 colon cancer, 1 NSCLC, 1 renal carcinoma) received PVAC in combination with PD-1 mAb and antiangiogenic therapy. No DLTs were reported. Five patients developed grade 1 subcutaneous indurations in the injection sites,which collected with nanovaccine. One patient had grade 2 rash caused by antiangiogenic drug. No drug related SAEs have been observed. There are 1 CR, 4 PR, 3 SD and 1 PD. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is safe and well tolerated. Clinical responses have been observed in combination with PD-1 mAb and antiangiogenic drugs and neoantigen-specific T cell response have been observed after vaccination. Clinical trial information: ChiCTR1900022986. Citation Format: Jia Wei, Qin Liu, Hanqing Qian, Jie Shao, Lijing Zhu, Lifeng Wang, Lixia Yu, Huizi Sha, Baorui Liu. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1049.

Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors.

3134 Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Nanotechnology has been reported to enhance immune responses of vaccines. Moreover, immunizing patients against such neoantigens, in combination with checkpoint inhibitor (CPI) and/or antiangiogenic drugs may elicit greater anti-tumor responses. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) is an amphiphiles nanovaccine loaded with personalized vaccine encoding multiple neoantigens designed to induce neoantigen specific T cells responses. Patients will receive PVAC in combination with PD-1 monoclonal antibody and/or antiangiogenic drugs. Primary end points include safety and tolerability. Results: 13 microsatellite stability (MSS) patients, which had relapsed from standard treatments, are enrolled in this study. 5 patients (1 gastric cancer, 1 liver cancer, 1 cervical carcinoma, 1 soft tissue sarcoma, 1 renal carcinoma) received PVAC in combination with PD-1 mAb, and another 8 patients (3 gastric cancer, 2 colon cancer, 1 NSCLC, 1 renal carcinoma) received PVAC in combination with PD-1 mAb and antiangiogenic therapy. No DLTs were reported. Five patients developed grade 1 and one patients developed grade 2 subcutaneous indurations in the injection sites, which collected with nanovaccine. One patient had grade 2 rash caused by antiangiogenic drug. No drug related SAEs have been observed. There are 1 CR, 6 PR, 4 SD and 2 PD. Neoantigen specific T cell responses have been detected by IFN-γ ELISpot from PBMCs. Conclusions: PVAC is safe and well tolerated. Clinical responses have been observed in combination with PD-1 mAb and antiangiogenic drugs and neoantigen-specific T cell response have been observed after vaccination. Clinical trial information: ChiCTR1900022986 .