Intramural Injection Research Articles

Effects of tramadol hydrochloride preemptive analgesia in kyphoplasty of thoracolumbar osteoporotic fractures under local anesthesia

To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty (PKP) of vertebrae following local anesthesia. From August 2019 to June 2021, 118 patients with thoraco lumbar osteoporotic fractures were treated and divided into observation group and control group, with 59 patients in each gruop. In observation group, there were 26 males and 33 females, aged from 57 to 80 years old with an average of (67.69±4.75)years old;14 patients on T11, 12 patients on T12, 18 patients on L1, 15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group. In control group, there were 24 males and 35 females, aged from 55 to 77 years old with an average of (68.00±4.43) years old;19 patients on T11, 11 patients on T12, 17patients on L1, 12 patients on L2;the same amount of normal saline was injected intramuscularly in control group. Observation indicators included operation time, intraoperative bleeding, visual analogue scale (VAS) evaluation and recording of preoperative (T0), intraoperative puncture(T1), and working cannula placement (T2) between two groups of patients, at the time of balloon dilation (T3), when the bone cement was injected into the vertebral body (T4), 2 hours after the operation (T5), and the pain degree at the time of discharge(T6);adverse reactions such as dizziness, nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery. All patients were successfully completed PKP via bilateral pedicle approach, and no intravenous sedative and analgesic drugs were used during the operation. There was no significant difference in preoperative general data and VAS(T0) between two groups (P>0.05). There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05). VAS of T1, T2, T3, T4 and T5 in observation group were all lower than those in control group(P<0.05), and there was no significant difference in T6 VAS (P>0.05). T6 VAS between two groups were significantly lower than those of T0, and the difference was statistically significant (P<0.05). There was no significant difference in incidence of total adverse reactions between two groups (P>0.05). There was a statistically significant difference in the acceptance of repeat PKP surgery (P<0.05). Half an hour before operation, intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia, which could increase the comfort of patients during operation and 2 hours after operation, and improve patients satisfaction with surgery.

Planned supportive bougienage is the basis for complex endoscopic treatment of refractory cicatricial strictures of the esophagus and anastomoses

Purpose of the study: the concept of complex endoscopic treatment of refractory benign cicatricial strictures of the esophagus and esophageal anastomoses is outlined, including the methodology of long-term planned supportive bougienage with intramural injections of glucocorticosteroids based on our own extensive experience. The results of an analysis of immediate and first long-term results in this group are presented, as well as detailed recommendations for the management of patients after interventions. Materials and methods. For the period from 2013 to 2023 in the endoscopic department of the Federal State Budgetary Institution “Petrovsky National Research Center of Surgery” 70 patients with refractory cicatricial strictures of the esophagus and anastomoses underwent complex endoscopic treatment, including the main course and long-term planned supportive bougienage, supplemented with intramural injections of Dexamethasone and triamcinolone according to the protocol we developed. Results. Of the total number of patients, 16 (23%) patients, after one or several courses of intramural steroid injections, did not have restenosis for 1 year or more, and 38 (54%) patients required no more than 3 sessions of prophylactic bougienage. In 49 (70%) patients, the duration of treatment was less than 1 year, and the average number of bougienage sessions was from 11 to 20. Conclusion. During the endoscopic treatment of patients with esophageal stenoses of various etiologies and strictures of the esophageal anastomoses, it is very important to assess the refractoriness of the narrowing at an early stage and determine the indications for intramural injections of glucocorticosteroids. Only if all recommendations and a regimen of long-term planned supportive bougienage are followed is it possible to achieve lasting stabilization of the lumen in the narrowing zone and avoid recurrence.

Endoscopic diagnosis and treatment of lichen planus of the esophagus

Purpose of the study: to attract the attention of endoscopists and doctors of other specialties to the problem of diagnosis and treatment of lichen planus of the esophagus. Materials and methods. From January 2010 to December 2023, lichen planus was the cause of dysphagia in 7 of 17 patients with unexplained cicatricial strictures of the esophagus. Our own experience and literature data on endoscopic semiotics and treatment of lichen planus of the esophagus are presented. Results of the study. Lichen planus is most often localized in the upper third of the esophagus and is accompanied by a narrowing of the esophageal lumen. The mucosa is hyperemic, dull, with areas of epithelial detachment, erosions, and fibrin deposits. All 7 patients had grade 2-3 esophageal strictures with isolated esophageal involvement (3) or oral involvement (4). Morphological changes were nonspecific: ulcerations, granulation tissue and fibrosis of the underlying layers, atrophy and thinning of the epidermis, acanthosis. Only in 2 cases apoptotic Civatte bodies were detected in the suprabasal layer, which is a characteristic feature of lichen planus of the esophagus. All patients underwent courses of endoscopic bougienage, supplemented by intramural injections of triamcinolone. This manipulations led to stabilization of the esophageal lumen at 10-15 mm without a tendency to restenosis. Conclusion. Further experience is needed to determine optimal treatment strategies, but it is critical to pay particular attention to symptom assessment in patients with skin disorders and odynophagia or dysphagia. These actions will facilitate an earlier diagnosis of lichen planus of the esophagus and increase the effectiveness of endoscopic treatment.

Layer-Specific BTX-A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement.

The rising incidence of health-endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX-A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer-specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX-A and the resulting therapeutic effects. The drug-loaded tips of the layer-specific gastric paralysis microneedles (LGP-MN) rapidly release and achieve uniform distribution of BTX-A within the designated gastric wall layers. In an obesity rat model, the LGP-MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06-fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach-derived glucagon-like peptide-1 due to the muscularis-targeting LGP-MN treatment is an important contributor to its unique glucose tolerance-improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX-A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP-MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.

A phase 1, open-label trial to evaluate feasibility and safety of intramural injection of belzupacap sarotalocan (AU-011) in non-muscle–invasive bladder cancer (NMIBC).

TPS596 Background: A high unmet medical need exists for new therapies in NMIBC to reduce common risks of recurrence, progression and, ultimately, cystectomy. Belzupacap sarotalocan, a novel investigational virus-like drug conjugate (VDC), has a dual mechanism of action designed to provide 1) selective binding to malignant cells, causing acute necrosis upon light activation, and 2) long-term anti-tumor immunity as demonstrated in pre-clinical models. This Phase 1 trial is designed to evaluate the feasibility and safety of intramural injection with or without intratumoral injection of belzupacap sarotalocan for treatment of NMIBC. The hypothesis is that after near infrared light activation, targeted distribution of belzupacap sarotalocan at high concentrations at the tumor base could necrose the tumor where it is most likely to be invasive. In turn, the tumor targeted pro-immunogenic cell death could potentially lead to an anti-tumor immune response preventing the risk for recurrence, progression and metastasis. Methods: This is an actively enrolling “window of opportunity” trial (NCT05483868) in low, medium or high risk NMIBC subjects scheduled to undergo TURBT or cystectomy per standard of care. A pre-treatment biopsy will be performed in up to 23 adult subjects enrolled in 4 cohorts, who will be given belzupacap sarotalocan +/- laser as shown in the table. The primary endpoint is incidence and severity of treatment-related adverse events, serious adverse events regardless of attribution, and incidence of dose-limiting toxicities. Each cohort will have a safety review for the injection procedure and laser (as needed), after 3 subjects have been treated and followed for 28 days. Secondary endpoints are based on histopathology and include assessment of local biodistribution of belzupacap sarotalocan measured via immunohistochemical staining, tumor necrosis, and evidence of an immune response via comparison of pre-treatment biopsy to TURBT/cystectomy samples after treatment. Statistical analysis plan includes descriptive statistics for the above endpoints. Clinical trial information: NCT05483868 . [Table: see text]

Death from Pulmonary Embolism Caused by Vaginal Injection of Hyaluronic Acid: a Case Report and a Literature Review.

A 40-year-old woman underwent vaginoplasty with intramural injection of fillers from an illegal medical practitioner. Approximately 2 h after the injection, she developed lower abdominal pain. The patient was taken to the hospital approximately 5 h later due to worsening pain. When the patient was admitted for physical examination, she suddenly experienced cardiac and respiratory arrest. She was resuscitated but remained in a coma. Unfortunately, the patient died approximately 12 h after being admitted to the hospital. The forensic autopsy revealed extensive amorphous basophilic emboli in the small interstitial vascular lumen of both lungs, and a large amount of the same type of substances were also found in the vaginal wall. Hyaluronidase digestion and Alcian blue staining confirmed that most components of the injection were hyaluronic acid (HA). HA is widely used as a cosmetic filler in the field of plastic surgery and is generally considered to have few adverse effects. This paper reports the first anatomical case of fatal pulmonary embolism caused by vaginal injection of HA. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of direct intramural injection to the bladder wall as a method for developing orthotopic tumor models.

Bladder cancer poses a great burden on society and its high rate of recurrence and treatment failure necessitates use of appropriate animal models to study its pathogenesis and test novel treatments. Orthotopic models are superior to other types since they provide a normal microenvironment. Four methods are described for developing bladder cancer models inside the animal's bladder. Direct intramural injection is one of these methods and is widely used. However, its efficacy in model development has not yet been studied. We aimed to evaluate the efficacy and success rate of the direct intramural injection method of developing an orthotopic model for the study of bladder cancer. Tumor cell lines were prepared in four microtubes. Aliquots of 200 × 103 cells were injected through a 27 gauge needle into the ventral wall of the bladders of 4 male and 4 female BALB/c mice following a midline 1cm laparotomy incision. In addition, 1 million cells from each microtube were injected into the flanks of control mice. To prevent infection and alleviate pain, 5mg/kg enrofloxacin and 2.5mg/kg flunixin meglumine, respectively, were injected subcutaneously. Tumors formed in all mice, resulting in 100% take rate and zero post-operation mortality. Surgery time was ≤15 min per mouse. In two mice, tumors were found in the peritoneal space as well. Direct intramural injection is a rapid, reliable, and reproducible method for developing orthotopic models of bladder cancer. It can be done on both male and female mice and only requires readily available surgical tools. However, needle track can result in cell spillage and peritoneal tumors.

The first experience of using autolipoaspirate in combined endoscopic treatment of severe cicatricial stricture of the esophagus

A 71-year-old patient with cicatricial stricture of the esophagus at the place of residence underwent bougienage, balloon dilatation and electric incision of the scar with a short-term effect.In March 2020, the patient applied to the Petrovsky National Research Center of Surgery with dysphagia grade 3 according to Bown. In the endoscopic department, multiple critical cicatricial strictures of presumably burn etiology were diagnosed, and therefore a long course of endoscopic bougienage was carried out, starting with Soehendra bougie with a diameter of 6 Fr to Savary bougie 45 Fr with an interval from 1–2 days to 2 weeks. Due to the tendency to rapid restenosis during this time, treatment was supplemented with 4 courses of intramural injections of dexamethasone solution. Despite the lack of a stable effect, the patient refused surgical treatment. Due to persistent restenosis, an innovative treatment was carried out—intramural injection of autologous lipoaspirate (nanofat) into the narrowed zone in order to reduce the density and rigidity of the scar tissue. At the final stage, in order to stabilize the lumen and prevent further restenosis, a course of intramural injections of triamcinolone was performed. This made it possible to successfully complete a two-year course of planned combined endoscopic treatment.

Intramural injection of pluronic gel loaded with drugs to alleviate arterial injury.

Balloon angioplasty, stent implantation, and application of an arterial clamp during surgery can induce artery injury such as elastin breaks and endothelium injury, but there is little research focused on the injury induced by these therapeutic manipulations. We established a simple and reproducible small animal aortic injury model and examined intramural injection as a potential therapeutic method to alleviate injury. The abdominal aorta of male Sprague Dawley (SD) rats or C57BL/6J mice was clamped sequentially throughout its length. Transforming growth factor β1 (TGFβ1), SB431542, lipopolysaccharide (LPS), Necrostatin-1 (Nec-1), rapamycin, or MHY1485 contained in Pluronic gel was injected intramurally at day 0 or day 7. Animals were fed with chow containing 0.25% beta-aminopropionitrile (BAPN) to evaluate the influence of BAPN. All samples were harvested and examined by immunohistochemistry and immunofluorescence. The clamped rat aorta showed luminal dilation, elastin fiber breaks, neointimal hyperplasia, and dissection (days 0-90). Intramural injection of TGFβ1, rapamycin and Nec-1 showed a protective effect on the injured aorta, whereas SB431542, MHY1485 and LPS showed more severe wall damage. The aortic lumen in rats fed with BAPN was significantly larger than in control rats (day 7). Mouse aorta showed similar injury with neointimal hyperplasia and elastin fiber breaks. The rodent arterial injury model is reproducible and may mimic early changes of arterial injury. The model accommodates intramural injection of different drugs that may show mechanisms of arterial injury. Although this is a preliminary animal model, the intramural injection method may have potential clinical application in the future.

Endoscopic Injections of Botulinum Toxin Type A in the Piglet Esophagus Is Safe and Feasible but Did Not Result in any Significant Structural Changes 3 Days after Injection.

Treatment for long-gap esophageal atresia (LGEA) aims at achieving primary anastomosis with minimal tension. Previous studies have shown that intramural injections with botulinum toxin type-A (BTX-A) from the adventitial side can increase the elongation of the piglet and rat esophagus before bursting, and that this effect is dose and time dependent. Our aim was to determine if endoscopic injections would be feasible, safe, and with an effect on the mechanical properties of the esophagus. Twenty-two male piglets (5.15 kg) were randomized into two groups, one receiving 2 units/kg BTX-A, the other equal volume 0.9% NaCl. On day 3, the esophagus was harvested and tested in a stretch-tension machine to evaluate elongation and maximum load, followed by histological examination. No adverse effects to the procedure were observed. No statistically significant difference in elongation or maximum load before bursting between the treatment and placebo group was found. In histopathological analysis, inflammation and abscess formation were observed with no statistically significant difference between the two groups. Endoscopic placement of BTX-A injections in the piglet esophagus was safe and feasible but did not result in any difference in the mechanical properties or histology of the esophagus.

Improved Healing of Colonic Anastomosis with Allotransplantation of Axillary Skin Fibroblasts in Rats.

Objective Colonic anastomosis is associated with serious complications leading to significant morbidity and mortality. Fibroblasts have recently been introduced as a practical alternative to stem cells because of their differentiation capacity, anti-inflammatory, and regenerative properties. The aim of this study was to evaluate the effects of intramural injection of fibroblasts on the healing of colonic anastomosis in rats. Materials and Methods Inbred mature male Wistar rats were used in this experimental study (n=36). Fibroblasts were isolated from the axillary skin of a donor rat. In the sham group, manipulation on descending colon was done during laparotomy. A 5 mm segment of the colon was resected, and end-to-end anastomosis was performed. In the control group, 0.5 ml of phosphate buffer saline (PBS) was injected into the colonic wall and in the treatment group, 1×106 fibroblasts were transplanted. Following euthanasia on day 7, intra-abdominal adhesion, leakage and peritonitis were evaluated by necropsy. Mechanical properties were assessed using bursting pressure and tensile tests. Inflammation, angiogenesis, and collagen deposition were examined histopathologically. Results The mean scores for adhesion and leakage were decreased in the treatment group versus control samples. Lower infiltration of inflammatory cells was observed in the treatment group (P=0.03). Angiogenesis and collagen deposition scores were significantly increased in the fibroblast transplanted group (P=0.03). Tensile mechanical properties of the colon were significantly increased in the treatment group compared to the control sample (P=0.01). There was no significant difference between the control and treatment groups in terms of bursting pressure (P=0.10). Positive weight changes were found in sham and treatment groups, but the control rats lost weight after 7 days. ConclusionThe results suggested that allotransplantation of dermal fibroblasts could improve the necroscopic, histopathological, and biomechanical indices of colonic anastomosis repair in rats.

ИНТРАМУРАЛЬНЫЕ ИНЪЕКЦИИ ТРИАМЦИНОЛОНА (КЕНАЛОГ) В ЭНДОСКОПИЧЕСКОМ ЛЕЧЕНИИ СЛОЖНЫХ РУБЦОВЫХ СТРИКТУР ПИЩЕВОДА И АНАСТОМОЗОВ

Abstract. Approximately one third of patients with complex strictures of the esophagus and esophageal anastomoses develop restenosis after a course of endoscopic bougienage. To prevent this, we have developed a tactic of long-term planned maintenance bougienage for 6-24 months, which is successfully used in the clinical practice of the endoscopy department of the Petrovsky National Research Center of Surgery for many years. Recently, to improve the results of endoscopic bougienage of refractory benign esophageal and esophageal anastomotic strictures and strictures with the tendency to restenosis or recurrence, we have been using intramural steroid injections according to our scheme. To date, the technique has been applied in 65 patients (esophageal strictures — 44, strictures of esophageal anastomoses — 21). Comparison of the immediate results of endoscopic bougienage, supplemented by the introduction of Dexamethasone and Kenalog, showed the advantage of the latter. There were no complications of intramural steroid therapy in the course of endoscopic bougienage. Our still little experience with the use of intramural injections of triamcinolone acetate (Kenalog) in the course of long-term planned endoscopic bougienage of complex recurrent and refractory strictures of the esophagus and esophageal anastomoses indicates that this technique is promising.

PD27-01 DEFINING SYNAPTOTAGMIN-1 AS THE RECEPTOR FOR BOTULINUM NEUROTOXIN B IN THE BLADDER

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-01 DEFINING SYNAPTOTAGMIN-1 AS THE RECEPTOR FOR BOTULINUM NEUROTOXIN B IN THE BLADDER Hatim Thaker, Jie Zhang, Shin-Ichiro Miyashita, Vivian Cristofaro, Maryrose Sullivan, Rosalyn Adam, and Min Dong Hatim ThakerHatim Thaker More articles by this author , Jie ZhangJie Zhang More articles by this author , Shin-Ichiro MiyashitaShin-Ichiro Miyashita More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Maryrose SullivanMaryrose Sullivan More articles by this author , Rosalyn AdamRosalyn Adam More articles by this author , and Min DongMin Dong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neurogenic and idiopathic detrusor overactivity (DO) is currently treated with onabotulinumtoxin A (BoNT/A) as third line therapy. In cases of treatment failure, alternatives to BoNT/A are limited. BoNT/B is another serotype that could serve as an alternative to BoNT/A. BoNT/B shares the same mode of action with BoNT/A, but uses different receptors. Two homologous proteins, synaptotagmin-1 and -2 (Syt-1, -2), have been identified as BoNT/B receptors. However, the dominant receptor form in bladder tissues remains unknown. Here, we aim to determine the specific Syt responsible for BoNT/B action in skeletal and smooth muscle, allowing us to engineer and improve BoNT/B efficacy in recognizing its specific receptor in the bladder. METHODS: Transgenic knock-in (KI) mice were generated by CRISPR/Cas9 approach, where a triple-residue mutation on Syt-1 and Syt-2 receptor abolishes BoNT/B binding. Wild type (WT) and KI mouse bladders were harvested, incubated with BoNT/B, and subjected to immunostaining with confocal microscopy or ex vivo nerve-evoked contraction studies via electrical field stimulation. To evaluate smooth muscle response in vivo, intramural bladder injection of BoNT/B (3.25 pg in 5 uL) via laparotomy was done. Post-op, mice underwent voiding spot assay (VSA) to assess toxin action on bladder function. RESULTS: WT bladders demonstrated high immunoreactivity to Syt-1 (Panel A), and Syt-1 KI bladders failed to bind BoNT/B in vitro (Panel B). Diaphragm skeletal muscle tissues showed a Syt-2 predominance. Ex vivo contraction studies with 0.3 nM BoNT/B showed a 90% reduction in nerve-evoked contractions in WT and Syt-2 KI, but not Syt-1 KI, bladders (Panel D). VSA after bladder injection of BoNT/B reduced voided volumes, akin to retention, in WT and Syt-2 KI mice only (Panel E). In contrast, BoNT/B produced full paralysis in hindlimb skeletal muscles in WT and Syt-1 KI mice; Syt-2 KI mice tolerated BoNT/B at 30x higher doses without paralysis (Panel C). CONCLUSIONS: We demonstrate that Syt-1 is the physiologically relevant receptor for BoNT/B in bladder tissues. The differential expression of Syt-1 vs Syt-2 provides an opportunity to engineer BoNT/B to improve its efficacy on bladder tissues and minimize its effect on skeletal muscles. Source of Funding: AUA/Urology Care Foundation Research Scholar Award and SUFU Chemodenervation Grant to H.T.R01NS080833, R01AI132387, R01AI139087, and R21NS106159 to M.D © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e443-e443 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hatim Thaker More articles by this author Jie Zhang More articles by this author Shin-Ichiro Miyashita More articles by this author Vivian Cristofaro More articles by this author Maryrose Sullivan More articles by this author Rosalyn Adam More articles by this author Min Dong More articles by this author Expand All Advertisement Loading ...

Triple intramural dexamethasone injections increase the efficiency of endoscopic bougienage of esophageal re-stenosis and anastomosis

Purpose of the study. To analyze retrospectively our own experience of using intramural dexamethasone injections during endoscopic bougienage of recurrent or very tight (refractory) benign cicatricial strictures of the esophagus and esophageal anastomoses.Materials and methods. From 2013 to March 2021, this method was applied in 43 patients (26 — men, 17 — women) with peptic (11), cicatricial (8), burn (6) esophageal strictures and strictures of anastomoses (18) prone to restenosis. Dexamethasone was injected into the constricted area with a needle passed through the endoscope biopsy channel as an addition to supportive bougienage.Results. After dexamethasone injections, 41 (95.3%) of 43 patients achieved a satisfactory lumen diameter, at which the symptoms of dysphagia disappeared for a long time without relapse. In most patients, the lumen in the stricture zone stabilized at a diameter of 8–18 mm (average 13 mm). With strictures of the esophagus, it was possible to achieve a diameter of 8–14 mm (average 11 mm), and with strictures of the anastomoses — 10–18 mm (average 14 mm).Conclusion. With the tendency of stricture to restenosis, the standard algorithm for endoscopic bougienage, developed in the endoscopy department of the “Petrovsky National Research Center of Surgery”, was supplemented with intramural injections of dexamethasone. This combined endoscopic treatment made it possible to increase the diameter of the bougie and the intervals between bougienage due to the stabilization of the scar frame and to complete the endoscopic treatment with a satisfactory result in 95.3% of patients.

Heterotopia of gastric mucosa and long segmental Barrett’ oesophagus complicated by cicatricial stricture of the upper third of the oesophagus

A 26-year-old patient with no symptoms of gastroesophageal reflux disease developed complaints of dysphagia. Endoscopic examination revealed a short grade 3 cicatricial stricture in the upper third of the oesophagus, and in the lower parts of the oesophagus mucosa was represented by a columnar epithelium for 16 cm. Histological examination verified the long segmental Barrett’ oesophagus. Above the stricture large areas of heterotopia of the gastric mucosa were determined among the regular oesophageal squamous epithelium. While taking proton pump inhibitors, the patient underwent a long course of endoscopic bougienage with intramural dexamethasone injections, which made it possible to stabilize the lumen in the stricture zone at a level of 12 mm. A precise examination of all parts of the oesophagus with the use of modern clarifying imaging techniques allows to correctly interpret the endoscopic picture and determine the further tactics of treatment and follow-up, taking into account the possible risks of neoplasia in the heterotoped area of the mucosa of the upper third of the oesophagus.

Immune checkpoint programmed death-1 mediates abdominal aortic aneurysm and pseudoaneurysm progression

PurposeThe causes and pathogenetic mechanisms underlying abdominal aortic aneurysms (AAAs) and pseudoaneurysms are not fully understood. We hypothesized that inhibiting programmed death-1 (PD-1) can decrease AAA and pseudoaneurysm formation in mouse and rat models. MethodsHuman AAA samples were examined in conjunction with an adventitial calcium chloride (CaCl2) application mouse model and an aortic patch angioplasty rat model. Single-dose PD-1 antibody (4 mg/kg) or BMS-1 (PD-1 inhibitor-1) (1 mg/kg) was administered by intraperitoneal (IP) or intraluminal injection. In the intramural injection group, PD-1 antibody was injected after CaCl2 incubation. The rats were divided into three groups: (1) the control group was only decellularized without other special treatment, (2) the PD-1 antibody-coated patch group, and (3) the BMS-1 coated patch group. Patches implanted in the rat abdominal aorta were harvested on day 14 after implantation and analyzed. ResultsImmunohistochemical analysis showed PD-1–positive cells, PD-1 and CD3, PD-1 and CD68, and PD-1 and α-actin co-expressed in the human AAA samples. Intraperitoneal (IP) injection or intraluminal injection of PD-1antibody/BMS-1 significantly inhibited AAA progression. PD-1 antibody and BMS-1 were each successfully conjugated to decellularized rat thoracic artery patches, respectively, by hyaluronic acid. Patches coated with either humanized PD-1 antibody or BMS-1 can also inhibit pseudoaneurysm progression and inflammatory cell infiltration. ConclusionPD-1 pathway inhibition may be a promising therapeutic strategy for inhibiting AAA and pseudoaneurysm progression.

Surgical ablation supplemented by ethanol injection for ventricular tachycardia refractory to percutaneous ablation.

A combination of endocardial and epicardial approaches has improved the overall success rate of ventricular tachycardia (VT) ablation in patients with cardiomyopathy. However, the origins of some VTs are truly intramural or close to coronary arteries, which makes this combined strategy either prone to failure or too risky. This observational study aimed to explore the feasibility and efficacy of direct epicardial ablation combined with intramural ethanol injection via surgical approach for inaccessible intramural VTs or VTs too close to coronary arteries. In four canines ventricular lesions produced by direct epicardial injection of ethanol were assessed. Six consecutive patients with recurrent VT refractory to catheter endocardial and epicardial RF ablation and that remained inducible after surgical epicardial mapping and RF ablation were included. Ethanol was injected by needle at the epicardial RF ablation sites. The primary outcome was freedom of sustained VT determined by device interrogation and periodical 24-h holter recordings subsequently. In an animal study, the lesions were homogenous and increased in size with the volume of ethanol injected. In all six patients, ethanol injection at the target sites in the anterior or lateral left ventricle abolished inducible VT. Over a median follow-up of 22 months (range, 6-65), all patients remained free of sustained VT. One patient died of pulmonary infection one year after the procedure. A hybrid strategy of surgical ablation combined with intramural ethanol injection is feasible and effective in patients with multiple failed percutaneous ablation attempts.

Intramural Injection of Botulinum Toxin A in Surgical Treatment of a Long Gap Esophageal Atresia-Rat Model.

Anastomosis with minimal tension is desirable in long-gap esophageal atresia. Prior studies in piglets showed that intraesophageal injection of botulinum toxin type A (BTX-A) results in significant esophageal elongation. Our aim was to determine the BTX-A dose, number of injections, and time necessary to elicit maximal response. Adult male Wistar rats (n = 48) were randomly assorted into five groups. Four treatment groups received 2 or 4 U/kg of BTX-A, delivered using two or four injections, and a control group received 0.9% NaCl. Esophagus was removed 6 or 24-hours postinjection and tested ex vivo using a stretch tension device. Subsequently, an optimal dose and time following injection was used to study the effects of BTX-A on anastomotic healing in vivo. Rats (n = 12) received an intraesophageal injection of BTX-A or 0.9% NaCl, followed by resection of 0.5 cm of esophagus and end-to-end anastomosis. Rats were observed for 9 days, and esophagus was removed for gross and histological evaluation. The largest effect on elongation was recorded in the BTX-A (2 U/kg) 24 hour, four injection group. In the anastomosis study, stricture formation was observed in all animals in the control group. Absence of esophageal stricture was found in three out of four animals in the treatment group macroscopically and histologically. We found that BTX-A exerts a positive effect on stretch characteristics of esophageal tissue in rats at 2 U/kg via four-injection delivery and 24-hour waiting period. This study suggests that BTX-A might improve anastomotic healing.

1639 Use of High Dose Epinephrine Versus Low Dose Epinephrine to Reduce Hemorrhage During Laparoscopic Myomectomy: A Randomized Controlled Trial

Study Objective To compare the effectiveness, safety and complications of intramural injection of epinephrine in high dose versus low dose during laparoscopic myomectomy as a method to reduce blood loss. Design Forty patients undergoing laparoscopic myomectomy were allocated at random to receive either high dose or low dose epinephrine in the serosal and/or overlying myometrium. Blood loss, duration of surgery, change in Hb levels, systemic haemodynamic changes and postoperative complications were compared. Setting El-Shatby maternity hospital, Alexandria University. Patients or Participants Forty patients having single interstitial myomas ranging from 3-10 cm in diameter measured by ultrasound, complaining of abnormal uterine bleeding and/or infertility. Interventions Twenty patients received 500 μg epinephrine diluted in 200 ml saline intramural and compared to other twenty patients who received 250 μg epinephrine diluted in 200 ml saline intramural. Measurements and Main Results Patient characteristics (e.g. age, body mass index, demographic data) and average size of myomas were similar between the two study groups. The differences in intraoperative blood loss, operative time and change in Hb levels between the two groups were insignificant (p>0.05). Transient and non serious increases in systolic and diastolic blood pressure and heart rate following intramyometrial epinephrine injection occurred in 20% of cases in the low dose group and 60% of cases in the high dose group showing a significant difference (p=0.010). No significant postoperative complications were observed in either groups. Conclusion The intramyometrial injection of epinephrine in low dose leads to significantly less haemodynamic alteration than the high dose and appears to be more safe. The effectiveness of the low dose appears to be equal to the high dose regarding controlling the blood loss.

Inadequate steroid injection after esophageal ESD might cause mural necrosis

Background and study aims Locoregional triamcinolone acetonide (TAC) injection is increasingly used for prevention of stricture after extensive endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia. However, the safety of intramural TAC injection has not been elucidated. The aim of this study was to assess the clinical courses and histopathological changes after TAC injection into the muscle layer in a porcine model. Methods Three pigs were subjected to ESD under general anesthesia. Two artificial 30-mm lesions were created at the oral and anal ends of the esophagus in each pig. TAC was injected into the muscle layer of the artificial oral ulcers (TAC group) and saline was injected into the muscle layer of the artificial anal ulcers (control group). Endoscopic, macroscopic, and histopathological evaluations were performed. Results The artificial ulcers remained open at sacrifice on day 28 post-ESD in the three ulcers injected with TAC. Esophageal wall perforation and abscess spreading to the mediastinum were observed in two of the three ulcers in the TAC group. The abscesses involved the lungs, bronchi, and aortic adventitia. Severe inflammatory cell infiltration in the muscularis propria layer and significant muscularis propria degradation were observed in all three ulcers in the TAC group. Conclusions This study suggests that TAC may cause deep mural damage when it is injected into the muscularis propria. Care should be taken not to inject TAC into the muscle layer when it is used to prevent post-ESD stricture formation.