Injection Of 5-fluorouracil Research Articles

Technique of Xen Implant Revision Surgery and the Surgical Outcomes: A Retrospective Interventional Case Series.

PurposeThe Xen® Gel Stent (Allergan, Irvine, CA, USA) is a minimally invasive glaucoma surgery device implanted to reduce intra-ocular pressure (IOP) in glaucoma. The stents can fail to drain post-operatively due to scarring of the conjunctiva around the stent opening. Data on the success rates of revision surgery in patients with Xen stent failure are scarce. We present the first detailed report of the steps, outcomes and complications of Xen revision surgery with 12 months of follow-up data.MethodsWe share our experiences on the circumstances in which to perform Xen revision surgery, the steps of the surgery and the results of a retrospective interventional case series of all Xen revisions performed at a single centre from 2013 to 2018.ResultsA total of 151 Xen implants were inserted into eyes at our tertiary centre during the study period, of which 21 eyes (patients) underwent revision surgery. Mean pre-operative IOP was 26.1 (standard deviation 8.3) mmHg with the patient on two drops of anti-glaucoma medication. Four patients were excluded from the analysis due to incomplete data (medical records were unavailable for 2 patients; 1 patient died shortly after surgery; and 1 patient moved to another area). A non-functioning Xen implant was identified in another patient during revision surgery, and the procedure was converted to a trabeculectomy. The remaining 16 patients were included in the analysis, all of whom had a minimum follow-up of 12 months, with the longest follow-up being 4 years following revision surgery. Of these 16 patients, four required needling and 5-fluorouracil injection in the first 12 months following revision surgery, three required further glaucoma drainage surgery due to the failure of the revision surgery to control IOP in the first year and one suffered bleb-related endophthalmitis at the site of previous trabeculectomy surgery. Mean IOP at 12 months following revision surgery was 16.3 (standard deviation 3.7) mmHg on 0.7 drops of anti-glaucoma medication, which equates to a 37.5% reduction in IOP and a 65% reduction in the amount of IOP-lowering drops required.ConclusionOur study shares experience on when to perform Xen revision surgery and the steps required. The results of our small cohort are the first in the literature and show that revisions can achieve promising IOP and medication reductions. Some patients still require needling in the post-operative period to optimise outcomes.

Patchouli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota

Intestinal mucositis causes great suffering to cancer patients who undergo chemotherapy and radiotherapy. Owing to the uncertain side effects of anticancer drugs to attenuate patients’ intestinal mucositis, many studies focused on traditional Chinese medicine (TCM). Patchouli alcohol (PA) is an active compound extracted from Pogostemon cablin, and has potent gastrointestinal protective effect. However, whether PA has an effect on intestinal mucositis is still unknown. Therefore, we established a rat model of intestinal mucositis via intraperitoneal injection of 5-fluorouracil, and intragastrically administrated PA (10, 20, and 40 mg/kg) to evaluate the effect of PA on intestinal mucositis. The routine observation (body weight, food intake, and diarrhea) in rats was used to detect whether PA had an effect on intestinal mucositis. Levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10, and MPO), mucosal barrier proteins (zonula occludens -1 (ZO-1), claudin-1, occludin, myosin light chain (MLC), and mucin-2) and intestinal microbiota were determined to elucidate the underlying mechanism of PA action on intestinal mucositis in rats. The results showed that PA could effectively improve body weight, food intake, and diarrhea in intestinal mucositis rats, preliminary confirming PA efficacy. Further experiments revealed that PA not only decreased the levels of TNF-α, IL-1β, IL-6, and MPO but also increased the level of IL-10 significantly. In addition, the expression of mucosal barrier proteins and microbiota community were also improved after PA treatment in diseased rats. Hence, PA may prevent the development and progression of intestinal mucositis by improving inflammation, protecting mucosal barrier, and regulating intestinal microbiota.

CLINICAL AND HISTOLOGIC EVALUATION OF LASER THERAPY IN THE TREATMENT OF ORAL MUCOSITIS: PILOT STUDY IN AN ANIMAL MODEL

The objective of this study was to evaluate the action of laser in initial events of chemo-induced oral mucositis (OM). Eight hamsters were divided into 2 groups (G): GI positive control (induction of OM) and GII Laser (induction of OM + Laser therapy). OM was induced by 2 injections of 5-fluorouracil followed by grooves in the mucosa of the cheek pouch. The laser therapy (LP) (diode laser of gallium and aluminum arsenide, λ660 nm, 40 mW, 2.4 J/cm2) was performed on day 0 of the experiment and every 48 hours until day 6. On day 7, the mucosa was photographed for clinical analysis according to Lima et al., 2005, and the animals were killed, for bag removal and histologic processing for hematoxylin and eosin (H&E) staining. After statistical analysis (Fisher exact) with a significance level 0.5%, it was concluded that the LP, according to the adopted protocol, was able to prevent OM, and most hamsters showed no visible clinical changes in the cheek pouch. Histologically, it was observed that LP reduced angiogenesis and recruitment of inflammatory cells in G2. According to the results obtained LP was effective in preventing and reducing the severity of oral mucositis. The objective of this study was to evaluate the action of laser in initial events of chemo-induced oral mucositis (OM). Eight hamsters were divided into 2 groups (G): GI positive control (induction of OM) and GII Laser (induction of OM + Laser therapy). OM was induced by 2 injections of 5-fluorouracil followed by grooves in the mucosa of the cheek pouch. The laser therapy (LP) (diode laser of gallium and aluminum arsenide, λ660 nm, 40 mW, 2.4 J/cm2) was performed on day 0 of the experiment and every 48 hours until day 6. On day 7, the mucosa was photographed for clinical analysis according to Lima et al., 2005, and the animals were killed, for bag removal and histologic processing for hematoxylin and eosin (H&E) staining. After statistical analysis (Fisher exact) with a significance level 0.5%, it was concluded that the LP, according to the adopted protocol, was able to prevent OM, and most hamsters showed no visible clinical changes in the cheek pouch. Histologically, it was observed that LP reduced angiogenesis and recruitment of inflammatory cells in G2. According to the results obtained LP was effective in preventing and reducing the severity of oral mucositis.

CURCUMA LONGA L. HAS THERAPEUTIC EFFECT IN CHEMOTHERAPY-INDUCED ORAL MUCOSITIS IN HAMSTERS DECREASING ANGIOGENESIS AND TRANSFORMING GROWTH FACTOR-β1

Objectives We explored the effects of mucoadhesive formulation with Curcuma longa L. extract (MCL) on oral mucositis induced by 5-fluorouracil in hamsters. Study Design Seventy-two golden Syrian hamsters separated into 4 groups: control group, placebo group (no active substance), positive control group (AdMuc topical chamomile), and MCL group (topical use of mucoadhesive Curcuma longa). The animals received an intraperitoneal injection of 5-fluorouracil on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched, and therapy was initiated on day 5. The animals received 2 daily applications of the product according to the experimental group. Wound area was calculated and histologic sections of 3 μm were stained by hematoxylin and eosin for semiquantitative analysis of re-epithelization and degree of tissue inflammation. Immunohistochemistry was used for transforming growth factor β1 (TGF-β1) and CD31 analysis. Results The MCL group showed a greater clinical reduction of the mucositis lesions at day 8, a higher degree of re-epithelization, and a lower inflammatory process, with a lower angiogenesis and TGF-β1 epithelial labeling compared with the placebo and control groups (P Conclusions MCL Curcuma longa L. has a therapeutic effect accelerating the healing of oral mucositis reducing the inflammatory response and increasing re-epithelization.

Establishment of patient-derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil.

BackgroundPseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient‐derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5‐fluorouracil (5‐FU) in this model.MethodsHuman PMP sample was collected to establish subcutaneous (s.c.) and i.p. model. In vivo study of i.p. injection of 5‐FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity.ResultsBoth s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal‐pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA‐S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5‐FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%).ConclusionsPDX model of PMCA‐S was established successfully, and i.p. 5‐FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect.

A comparative study of intralesional injection of Candida albicans antigen, bleomycin and 5-fluorouracil for treatment of plane warts

Background Several therapeutic modalities for the treatment of verruca plana (VP) are available, but none has achieved complete cure in all cases with associated risk of side effects. Objective To evaluate efficacy and safety of intralesional injection of Candida albicans (C. albican) antigen, bleomycin and 5-fluorouracil (5-FU) in treatment of VP. Methods Sixty patients with VP were randomly divided into three equal groups who were treated using C. albicans antigen, bleomycin or 5- FU injections every 2 weeks till complete clearance of the lesions or for a maximum of four sessions and followed up for additional 8 weeks. Results A statistically significant higher incidence of complete response was achieved with bleomycin (85%) than C. albicans antigen (60%) which was higher than 5-FU (45%) with a significantly less number of required sessions to achieve best results with bleomycin and candida antigen than 5-FU. Conclusions Candida albicans antigen, bleomycin and 5-FU are helpful modalities for treatment of VP. Bleomycin was the most effective, followed by C. albicans antigen then 5-FU (least effective). Single injection site, clearance of distant warts and decreased incidence of new lesion development – in situ or elsewhere – are additional merits of C. albicans immunotherapy. These modalities are cheap with only transient adverse effects.

Experimental study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil to treat PDX model of pseudomyxoma peritonei

Objective To evaluate the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil (5-Fu) in patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP). Methods One PMP tumor from surgery was used to establish PMP PDX models, which were equally randomized into control (no treatment), vehicle (normal saline, 0.2 ml) and treatment (5-Fu, 50 mg/kg, 0.2 ml) groups. Experimental peritoneal cancer index (ePCI) score, body weight, and pathological examination were performed to evaluate the efficacy and toxicity. Results PDX models replicating human PMP were established and diagnosed as high grade mucinous carcinoma peritonei with signet ring cells. Average ePCI score of treatment group was significantly lower than control and vehicle groups [(0.9±1.2) points vs. (3.6±1.7) points vs. (2.7±1.1) points, F=9.253, P<0.01]. Histopathological study revealed obvious tumor necrosis and reduced signet ring cells in the treatment group. The Ki-67 label index of treatment group was significantly lower than control group and vehicle group [(57.3±15.1)% vs. (72.2±15.1)% vs. (70.0±14.0)%, F=4.923, P<0.05]. The body weight of treatment group was significantly lower than control group and vehicle group [(19.7±2.8) g vs. (22.7±1.8) g vs. (21.9±1.7) g, F=4.654, P<0.05]. Major toxicities in the treatment group were animal death (10.0%), congestive splenomegaly (88.9%), lymphocyte accumulation (77.8%), bile canaliculus hyperplasia and obstruction (22.2%), cholestasis (100.0%), and acidophilic body (55.6%) in the liver. Conclusion In the PDX model of human PMP, intraperitoneal injection of 5-Fu could inhibit tumor proliferation and progression, with lowered ePCI score and reduced Ki-67, and toxicity was mainly on liver. Key words: Pseudomyxoma peritonei; PDX model; 5-Fluorouracil; Intraperitoneal injection; Organ toxicity

Efficacy of postoperative management with 5-fluorouracil injections after XEN Gel Stent implantation

PurposeTo evaluate the efficacy of postoperative management with 5-fluorouracil injections after XEN Gel Stent implantation.MethodsProspective real-world evidence study included 39 eyes (of 36 patients) with primary open-angle glaucoma without previous glaucoma surgery and with uncontrolled intraocular pressure (IOP), glaucoma progression, or intolerance to IOP-lowering therapy. Patients underwent mitomycin C-augmented XEN implantation either as a stand-alone procedure or combined with cataract extraction. 5-Fluorouracil subconjunctival injections were a first-choice therapy for bleb failure and were administered according to predetermined criteria (analogous to pro re nata regimen in age-related macular degeneration treatment). Primary outcome was unqualified success, defined as postoperative IOP < 18 mmHg and > 20% reduction from medicated baseline without any antiglaucoma medications and no detected glaucoma progression.ResultsAt median follow-up of 8 months (range 3–24 months), IOP decreased from a medicated baseline value of 23 mmHg (95% CI 21–24 mmHg) to 13 mmHg (95% CI 12–15 mmHg) and number of medications decreased from 3 (95% CI 2–3) to 0 (p < 0.0001 for both). Median number of 5-fluorouracil injections per eye was 3 (95% CI 2–3), and median time to first injection was 0.5 months (95% CI 0.25–3 months) after surgery. Thirteen eyes (33.3%) underwent ≥ 1 needling, and surgical revision was performed in three cases (7.7%). The primary outcome measure, which allows performing additional procedures, was achieved in 27 eyes (69%).Conclusions5-Fluorouracil subconjunctival injections are safe and effective in postoperative management of bleb failure after XEN implantation and represent a viable alternative to other methods.

Effect of multiple subconjunctival conbercept injections as an adjuvant to the surgical treatment of pterygium: a prospective randomised comparative 6-month follow-up study.

To evaluate the safety and efficacy of multiple subconjunctival injections of conbercept for pterygium patients after surgery. As a prospective randomised interventional trial, 96 eyes from 96 patients with a tendency to recur were collected and divided randomly into conbercept and 5-fluorouracil groups on the 5th day after pterygium. All patients received three subconjunctival injections of conbercept (0.2 ml) or 5-fluorouracil (0.2 ml) on the 5th day (baseline), and 2 and 4 weeks post-operatively. The pterygium morphology, colour intensity, recurrence, and complications were recorded and analysed pre-1st injection and 1 day, 1 week, 1 month, 3 months, and 6 months post-3rd injection. Moreover, no patient was drop-out. There were striking differences between the two groups on post-3rd injections 1 day, 1 week, 1 month, 3 months, and 6 months (p = 0.001, 0.002, 0.000, 0.000, and 0.002, respectively) with respect to colour intensity: the eyes in conbercept group were lighter than the 5-Fu group. On post-3rd injection 6 months, prominent disparities existed between the two groups with respect to pterygium morphology (p = 0.006) and recurrence (p = 0.002), occurred in the conbercept group prior to the 5-Fu group. Moreover, corneal abrasions were not noted in the conbercept group, which was significantly less than the 5-Fu group (17/48; p = 0.000). There was no conspicuous discrepancy between the two groups with respect to subconjunctival haemorrhage (p = 0.789) and persistent epithelial defects (p = 0.078). Multiple subconjunctival conbercept injections as an adjunct therapy for pterygium surgery was shown to be safe, effective, and well-tolerated.

Injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) for cancer therapy.

Niclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β-catenin, mTORC1, signal transducer and activator of transcription 3, NF-κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000-Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1 H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000-Nic was significantly increased. Niclosamide could be released from mPEG5000-Nic nanoparticles in PBS solution. mPEG5000-Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000-Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000-Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000-Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5-fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.

2018 - TRANSPOSABLE ELEMENTS ENHANCE HEMATOPOIETIC REGENERATION VIA ACTIVATION OF INNATE IMMUNE SIGNALLING

Transposable elements (TEs) are transcriptionally upregulated upon stress signals. In the hematopoietic system, stress, like myeloablation, leads to a regenerative response, where hematopoietic stem cells (HSCs) exit quiescence and differentiate. A potential role of TEs in this process is currently unknown. Here we used myeloablation by 5-fluorouracil injection as a hematopoietic regeneration system. A time course of chromatin accessibility and expression analysis revealed that during regeneration, robust chromatin rearrangement takes place in HSCs concomitant with transcriptional upregulation of TEs and activation of inflammatory signalling. We reasoned that TE upregulation could be responsible for the inflammatory signalling activation by acting as ligands for the innate immune receptor MDA5. Indeed, by sequencing the RNA that is crosslinked to MDA5 upon stress we found several TE transcripts bound to MDA5. Loss of MDA5 in HSCs did not affect TE upregulation during regeneration but led to impaired inflammatory signalling activation. Since inflammatory signalling is crucial for the quiescent status of HSCs, we then examined the ability of Mda5-/- animals to activate their HSCs. Mda5-/- HSCs were more quiescent both at steady state and during regeneration. This quiescent phenotype was validated by metabolic assays and single-cell RNA-seq analysis. Finally, overexpression of a single TE element in HSCs led to their activation in a wild type but not an Mda5-/- background. Our step-by-step model proposes that during regeneration, TE upregulation leads to binding and activation of the innate immune receptor MDA5 that in turn stimulates the inflammatory signalling necessary for HSCs to exit quiescence and regenerate the hematopoietic system. Thus, using hematopoiesis as an exemplary system, our work uncovers a novel function of TEs in tissue regeneration.

Asrij/OCIAD1 suppresses CSN5-mediated p53 degradation and maintains mouse hematopoietic stem cell quiescence

AbstractInactivation of the tumor suppressor p53 is essential for unrestrained growth of cancers. However, only 11% of hematological malignancies have mutant p53. Mechanisms that cause wild-type p53 dysfunction and promote leukemia are inadequately deciphered. The stem cell protein Asrij/OCIAD1 is misexpressed in several human hematological malignancies and implicated in the p53 pathway and DNA damage response. However, Asrij function in vertebrate hematopoiesis remains unknown. We generated the first asrij null (knockout [KO]) mice and show that they are viable and fertile with no gross abnormalities. However, by 6 months, they exhibit increased peripheral blood cell counts, splenomegaly, and an expansion of bone marrow hematopoietic stem cells (HSCs) with higher myeloid output. HSCs lacking Asrij are less quiescent and more proliferative with higher repopulation potential as observed from serial transplantation studies. However, stressing KO mice with sublethal γ irradiation or multiple injections of 5-fluorouracil results in reduced survival and rapid depletion of hematopoietic stem/progenitor cells (HSPCs) by driving them into proliferative exhaustion. Molecular and biochemical analyses revealed increased polyubiquitinated protein levels, Akt/STAT5 activation and COP9 signalosome subunit 5 (CSN5)-mediated p53 ubiquitination, and degradation in KO HSPCs. Further, we show that Asrij sequesters CSN5 via its conserved OCIA domain, thereby preventing p53 degradation. In agreement, Nutlin-3 treatment of KO mice restored p53 levels and reduced high HSPC frequencies. Thus, we provide a new mouse model resembling myeloproliferative disease and identify a posttranslational regulator of wild-type p53 essential for maintaining HSC quiescence that could be a potential target for pharmacological intervention.

Study of the chemical structure of exopolysaccharide produced from streptomycete and its effect as an attenuate for antineoplastic drug 5-fluorouracil that induced gastrointestinal toxicity in rats

Chemotherapeutic medications, including 5 – fluorouracil (5FU), are the same old technique to most cancers and are associated with numerous peripheral toxicities. We investigated exopolysaccharide (EPSST) produced from the isolated streptomycete of the Mediterranean Sea for the capability to lower the severity of mucositis in vivo. The streptomycete was isolated from Mediterranean Sea sediment from the beaches of Port Said Governorates, Egypt and identified morphologically, physiologically, and biochemically and confirmed by molecularly 16S rDNA analysis. The EPSST was extracted from the supernatant of streptomycete by using 4 volumes chilled ethanol and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), and high-performance liquid chromatography (HPLC). In addition, antioxidant activity was measured through the usage of 2, 2-diphenyl-1-picrylhydrazyl (DPPH). Thirty-two male rats (180–200 g) were randomly divided into a control group (normal saline), intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg), normal rats were treated with EPSST and 5-FU + EPSST group. These groups were continued up to the day of sacrifice (28 days post treatments). The isolated strain became recognized based totally on 16S rDNA sequence as Streptomyce sp. with accession number SAMN08349905. The chemical evaluations of EPSST were galacturonic, glucose, galactose, mannose, and arabinose with a relative ratio of 2.1: 1: 5.37: 1.62: 1.29 individually, with an average molecular weight (Mw) 9.687 × 103 g/mol. Also, the EPSST contained uronic acid (16%) and sulfate (12.149%) and no protein was detected. EPSST inhibited the DPPH radical activity. The findings of this study propose that EPSST inhibits 5-FU-induced mucositis through adjustment of oxidative stress, apoptosis, inflammatory factors, activation of antioxidant enzymes. The clinical administration of EPSST may recover the chemotherapy-induced intestinal dysfunction, consequently increasing the clinical efficiency of chemotherapy. In addition, the administration of EPSST reduced 5-FU-induced histopathological incongruities such as neutrophil infiltration, loss of cellular integrity, and villus and crypt distortion. The clinical administration of EPSST may recover the chemotherapy-induced intestinal dysfunction, consequently increasing the clinical efficiency of chemotherapy.

Ocular surface squamous neoplasia: angiographic characteristics and response to subconjunctival/perilesional 5-fluorouracil injections.

Introduction: To investigate the angiographic characteristics of ocular surface squamous neoplasia (OSSN) and to evaluate the efficacy of subconjunctival/perilesional 5-fluorouracil injections in OSSN cases.Materials and methods: Six eyes of six patients with primary OSSN, received perilesional, subconjunctival, 25-mg/mL 5-fluorouracil injections at certain intervals. Anterior segment digital photography images, anterior segment optical coherence tomography (AS-OCT), and conjunctival indocyanine green angiography (ICGA) were obtained simultaneously with fluorescein angiography.Results: The mean best-corrected vision acuity significantly improved after treatment. At baseline, the median of the largest thickness of OSSN was 905.0 (interquartile range: 492.0–1592.5) μm based on AS-OCT data. There was an abrupt transition between normal and abnormal epithelium, a thickened hyper-reflective epithelium, and a sharp plane of cleavage between the lesion and underlying tissue, all indicative of OSSN. The angiographic characteristics of OSSN included focal or seafan-shaped intratumoral and conjunctival feeding vessels visible via ICGA, and abnormal vascular leakage visible with fluorescein angiography. The median time to tumor regression after treatment was 35.0 (interquartile range: 32.0–45.5) days in five eyes without recurrence, and OSSN in one eye regressed partially 40 days after treatment.Conclusion: This is the first report of the angiographic characteristics of OSSN and its response to subconjunctival/perilesional 5-fluorouracil injections by simultaneous conjunctival angiography and AS-OCT. The improved subconjunctival/perilesional 5-fluorouracil injection was an effective therapy for OSSN in both best-corrected vision acuity gain and anatomic outcomes.

Analysis of Keloid Response to 5-Fluorouracil Treatment and Long-Term Prevention of Keloid Recurrence.

Keloids are benign fibroproliferative skin tumors that can cause disfigurement and disability. Although they frequently recur after excision or medical management and can affect 6 to 16 percent of African Americans, there is no gold standard therapy. Keloids are challenging to study because there are no animal or in vitro models of this disorder. This makes it very difficult to validate data from treated tissue samples or cells and develop targeted therapies for this disease. In this study, the authors demonstrate that intralesional 5-fluorouracil injection after keloid excision prevents recurrence for 2 years, with no reported adverse events. The authors analyze the expression of treated and untreated biopsy specimens of the same keloids in their native context to capture insights that may be missed by in vitro cell culture models and correct for intrakeloid variability. Random forest analysis of the microarray data dramatically increased the statistical power of the authors' results, permitting hypothesis-free creation of a gene expression profile of 5-fluorouracil-treated keloids. Through this analysis, the authors found a set of genes, including YAP1 and CCL-2, whose expression changes predict 5-fluorouracil therapy status and include genes that have not previously been associated with keloid biology and are of unknown function. The authors further describe keloid heterogeneity for the first time using multidimensional analysis of their microarray results. The methods and tools the authors developed in this research may overcome some of the challenges in studying keloids and developing effective treatments for this disease. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.

THE USAGE OF RADIOFREQUENCY ABLATION FOR TREATMENT OF KELOIDS AND HYPERTROPHIC SCARS.

To evaluate the effectiveness of radiofrequency ablation (RFA) for scars tissue volume reduction, and influence on the clinical manifestations of keloid and hypertrophic scars. Seventeen patients (9 males, 8 females), 19-62 years old, with some scars were enrolled into the prospective randomized controlled study: 10 with keloids, 7 with hypertrophic scars. Previous failed attempts to correct the scars were undertaken in 8 patients with keloids and in 3 patients with hypertrophic scars. The efficacy of four scar volume reduction methods was compared (12 scars in each group, 5 sessions at 10-day inter- vals): the first group - RFA, the second - intralesional 5-fluorouracil (5-FU) injections, the third - RFA followed by 5-FU injections and the fourth - RFA, injections of verapamil and then 5-FU. The scars volume reduction was faster after RFA (by 65.3 %) than after chemotherapy. Local verapamil application after RFA followed by 5-FU injections reduced scar volume after the fifth session by 78.3 %. Relieving of the associated symptoms and scars hyperaemia was faster after RFA than after cytostatic drug administration. Their simultaneous application, especially in combination with verapamil, intensified the effect. There were no infectious complications and haemorrhages. Ulcers 3-5 mm in diameter in the place of puncture on one scar in the first group, on two scars in the third and fourth groups were registered as the side effects. Seventeen scars in seven patients, who received RFA as a monotherapy or in combination with chemotherapy, were assessed 6 months after treatment. The average scars volume decreased from (3260.5 ± 2057.36) mm3 at the moment after the fifth session to (2110.6 ± 1296.16) mm3, p = 0.0033. Scars volume reduction was faster after five sessions of RFA than following local 5-FU injections. Combination of RFA with scars infiltration with verapamil and 5-FU strengthened the effect. In the same way, the above-mentioned methods influenced clinical symptomatology associated with the scars. Scars hyperaemia was also reduced by RFA. Radiofrequency ablation of excess scar tissue is advisable to use as an initial method for the treat- ment of keloids and hypertrophic scars, since it is easy to carry, is not expensive and effectively reduces the scar vol- ume, demonstrating the patient the opportunity to achieve a positive result.

Intradermal injection of Fluorouracil versus triamcinolone in localized vitiligo treatment.

Vitiligo is an autoimmune disease with a prevalence of 1.22% in Egypt. Intralesional steroids use in localized vitiligo treatment still a matter of debate. Fluorouracil was tried in vitiligo treatment after lesion dermabrasion, ablative laser, or micro-needling. The study aimed to compare the efficacy of intradermal fluorouracil and triamcinolone acetonide without any adjuvant therapy in localized vitiligo treatment. Sixty patients with localized non-segmental stable vitiligo were assigned randomly and equally into groups. Patients subjected to intradermal injection of either fluorouracil (50mg/mL), triamcinolone acetonide (3mg/mL) or an equal mixture of both drugs. All patients had four treatment sessions every 2weeks were followed up for 6months. Intradermal fluorouracil showed the best overall improvement (median 52.27, IQR 36.25-68.18) when compared with triamcinolone (median 13.86, IQR 3.83-33.32) and the drug mixture (median 17.15, IQR 7.48-41.67). During follow-up, the vitiliginous patches continued to repigment for 6months in fluorouracil and the drug mixture groups. The improvement stopped 1month after the last session in the triamcinolone group. The intradermal fluorouracil injection is an effective treatment of localized vitiligo. The intradermal steroid has a short-acting therapeutic effect, but the mixture of drugs added no therapeutic effect.

ReGAE 12: preventing glaucoma blindness in the Caribbean through implementation of the Moorfields Safer Surgery System and skills transfer from the UK to Trinidad and Tobago.

ObjectiveThe objective of the study was to present evidence of successful skills transfer of the Moorfields Safer Surgery System (MSSS) from the UK to Trinidad and Tobago and the safety and efficacy of this technique.MethodsHospital-based retrospective, consecutive, non-comparative case series study of 33 eyes (24 African-Caribbean patients; 16 male patients) with primary open-angle glaucoma undergoing trabeculectomy + mitomycin C (MSSS) by a single surgeon with UK Glaucoma Fellowship training. The clinical outcome measures included intraocular pressure (IOP), bleb morphology, postsurgical interventions, postoperative complications, and best-corrected visual acuity (BCVA) at the final follow-up.ResultsAll patients were self-identified as African-Caribbean. The median age was 56 years (range 34–79 years). The mean preoperative IOP on maximum tolerated medical treatment was 22.4 mmHg (SD=5.9 mmHg). With or without medication, IOP was ≤21 mmHg in 92.6% at 1 year and 87.5% at 5 years. At 1 year, IOP was ≤18 mmHg in 78%, ≤15 mmHg in 73% and ≤14 mmHg in 52%. Removal of scleral flap releasable suture(s) was performed in 84%, 5-fluorouracil injection(s) in 88% and bleb needling revision in 38%. The most common complication was early transient bleb leak (52%). No patient developed endophthalmitis, hypotony maculopathy, suprachoroidal hemorrhage, or malignant glaucoma. At the final follow-up, 91% had excellent or satisfactory bleb morphology, and 73% had equal or better BCVA.ConclusionSkills transfer between different geographical and economic regions contributes to the prevention of avoidable blindness through disease control – one of the core strategies of the World Health Organization’s Vision 2020 initiative. In the Caribbean (Trinidad and Tobago), the MSSS was utilized by a surgeon with Glaucoma Fellowship training and achieved outcomes similar to best-published data. This success can be reproduced in other geographic locations.

Hard palate-dermis fat composite graft for reconstruction of contracted anophthalmic socket

ABSTRACT Purpose: To describe a novel technique of using a hard palate-dermis fat composite graft (HPDFG) for reconstruction of a contracted anophthalmic socket. Methods: Retrospective, noncomparative, interventional case series of four patients who underwent HPDFG placement by one surgeon between 2010 and 2017. Results: Six harvested HPDFGs were placed in four patients with contracted anophthalmic sockets. A harvested hard palate graft (HPG) and a dermis fat graft (DFG) were adjoined with sutures to form a composite graft. All adhesions and symblephara between the eyelid and the anterior surface of the anophthalmic socket were lysed. The HPG component was attached to the tarsal margin to vertically lengthen the eyelid. The free edge of the DFG was sutured to the cut edge of the bulbar conjunctiva to simultaneously expand the anterior conjunctival surface area and fornix volume. The line of union between the two grafts formed the apex of the new fornix. Four HPDFG were used to reconstruct both the upper and lower lid fornices in two severely contracted sockets. Three patients received post-operative 5-fluorouracil (5-FU) injections. Three patients underwent additional revisions with buccal mucous membrane graft, amniotic membrane graft, full-thickness skin graft, pedicle flap, and dermal fillers. All four patients achieved excellent cosmesis and comfortable prosthesis fit. Conclusions: Composite HPDFG is an effective method of reconstructing a contracted anophthalmic socket by restoring volume, lengthening the posterior lamella, and expanding the fornix to allow for successful prosthesis retention. Adjunctive use of 5-FU injections can delay post-operative cicatrization.

The Influence of Environment Stimulation on Learning and Memory Function in Rats with Medication Chemotherapy.

To study the effect of environmental intervention on chembrain. SD rats were randomized into the experimental group and the control group. The control group was given peritoneal injection of cyclophosphamide, methotrexate and 5-fluorouracil and the experimental group received the enriched environmental intervention on the basis of the control group. The differences in learning and memory, EMG and dentate gyrus neurons were compared between the two groups. Escape latency in the experimental group was significantly shortened than that in the control group. The number of dentate gyrus NeuN (neuron-specific nuclear protein) positive cells in the experimental group was higher than that in the control group. The experimental group of action ability in the Agile and external stimuli is better than that of the control group. Enriched environmentalintervention can effectively improve the ability of chembrain in learning, memory and ability of action.