Superficial Injection Research Articles

Simulating Upper Eyelid Ptosis During Neuromodulator Injections-An Exploratory Injection and Dissection Study.

Aesthetic neuromodulator injections of the upper face are frequently performed to temporarily block muscular actions of the periorbital muscles to ultimately reduce skin rhytids. However, the adverse event rate in the literature for toxin-induced blepharoptosis ranges from 0.51% to 5.4%. To identify access pathways by which injected neuromodulator product can travel from extra- to intra-orbital and therefore affect the levator palpebrae superioris muscle. Nine non-embalmed human body donors were investigated in this study with a mean age at death of 72.8 (16.1) years. The 18 supraorbital regions were injected in 28 times (14 for supratrochlear and 14 for supraorbital) with 0.5 cc, whereas eight cases (four for supratrochlear and four supraorbital) were injected with 0.1 cc of colored product. Anatomic dissections were conducted to identify structures stained by the injected color. The results of this injection- and dissection-based study revealed that both the supratrochlear and the supraorbital neurovascular bundles are access pathways for injected neuromodulator products to reach the intra-orbital space and affect the levator palpebrea superioris muscle. Out of 36 conducted injection passes, seven (19.44%) resulted in affection of the sole elevator of the eyelid of which 100% occurred only at an injection volume of 0.5 cc and not at 0.1 cc. Clinically, the results indicate that a low injection volume, a superficial injection for the supraorbital location, and angling the needle tip away from the supratrochlear foramen (toward the contralateral temple) when targeting the corrugator supercilii muscles, can increase the safety profile of an aesthetic toxin glabellar treatment.

The efficacy and safety of neubotulinumtoxinA for the treatment of forehead horizontal lines in Asians - A clinical, prospective, interventional, split-face study.

Botulinum toxin injections are widely sought after in the field of medical aesthetics, offering consumers a variety of brand choices. Two commonly available botulinum toxin products, onabotulinumtoxinA and neubotulinumtoxinA, are featured in numerous clinics, leading many to question whether there are discernible differences in results, given their varying price ranges. To evaluate the efficacy and safety of neubotulinumtoxinA for the treatment of forehead horizontal lines. A 12-week prospective, single-centre, interventional split-face study was conducted, including 30 subjects. These enrolled subjects received a single treatment session, with neubotulinumtoxinA applied to the left side of the forehead and onabotulinumtoxinA to the right side. A superficial injection was performed in all individuals, where the product was injected subdermally in the frontalis muscle. Evaluation was conducted at baseline, 7 days, 14, days and 4, 8, and 12weeks after treatment, both when the eyebrows were at maximum lift and in a resting position. Treatment efficacy was assessed by two physicians and self-assessed by the patients, using the Fitzpatrick Wrinkle Classification system. Adverse events were documented to evaluate safety. The study found no statistically significant difference in the efficacy of neubotulinum and onabotulinum for treating forehead wrinkles, as indicated by p-values above 0.05 for both static and dynamic conditions. No safety and adverse events were observed in both formulations. This study has demonstrated that neither formulation is inferior to each other in the treatment of forehead horizontal lines.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

ObjectiveThe purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer.MethodsA 26 question survey was emailed to international...

Efficacy and safety of botulinum toxin for rosacea with positive impact on quality of life and self-esteem.

Rosacea is a prevalent chronic inflammatory skin disease with a multifactorial pathophysiology. It compromises several skin structures, including the proliferation and dilation of dermal blood vessels, primarily in the central areas of the face, accompanied by significant psychosocial impairment, leading to reduced quality of life (QoL) and self-esteem. There are consensus guidelines for its treatment, but few options for the erythema. This study hypothesizes that treating rosacea skin lesions with botulinum toxin (BTX) could improve signs and symptoms, resulting in enhanced QoL and self-esteem. This interventional, open, uncontrolled, and prospective study, conducted at a single center, included 33 individuals diagnosed with rosacea, treated with standard therapeutic options according to the rosacea subtype plus superficial injections of BTX, and followed up for 90 days. Botulinum toxin injections were applied on Days 1 and 14. Clinical features and side effects were assessed at each visit; QoL, self-esteem, and medication adherence questionnaires were administered on Days 1 and 90. Treatment with BTX yielded improvement in the clinical signs of rosacea, registered by the investigators, and reported by 94% of the participants. Improved QoL scores (P < 0.05) and a notable increase in self-esteem scores (P < 0.001) were demonstrated. Rare adverse events were observed. The utilization of BTX superficial injections in patients with rosacea was safe and effective, improving the clinical appearance of the lesions. Despite some limitations, to our knowledge, this is the first study that showed the positive impact of this treatment modality on both QoL and self-esteem.

What Is the Role of a Periarticular Injection for Knee Arthroplasty Patients Receiving a Multimodal Analgesia Regimen Incorporating Adductor Canal and Infiltration Between the Popliteal Artery and Capsule of the Knee Blocks? A Randomized Blinded Placebo-Controlled Noninferiority Trial.

Optimal analgesic protocols for total knee arthroplasty (TKA) patients remain controversial. Multimodal analgesia is advocated, often including peripheral nerve blocks and/or periarticular injections (PAIs). If 2 blocks (adductor canal block [ACB] plus infiltration between the popliteal artery and capsule of the knee [IPACK]) are used, also performing PAI may not be necessary. This noninferiority trial hypothesized that TKA patients with ACB + IPACK + saline PAI (sham infiltration) would have pain scores that were no worse than those of patients with ACB + IPACK + active PAI with local anesthetic. A multimodal analgesic protocol of spinal anesthesia, ACB and IPACK blocks, intraoperative ketamine and ketorolac, postoperative ketorolac followed by meloxicam, acetaminophen, duloxetine, and oral opioids was used. Patients undergoing primary unilateral TKA were randomized to receive either active PAI or control PAI. The active PAI included a deep injection, performed before cementation, of bupivacaine 0.25% with epinephrine, 30 mL; morphine; methylprednisolone; cefazolin; with normal saline to bring total volume to 64 mL. A superficial injection of 20 mL bupivacaine, 0.25%, was administered before closure. Control injections were normal saline injected with the same injection technique and volumes. The primary outcome was numeric rating scale pain with ambulation on postoperative day 1. A noninferiority margin of 1.0 was used. Ninety-four patients were randomized. NRS pain with ambulation at POD1 in the ACB + IPACK + saline PAI group was not found to be noninferior to that of the ACB + IPACK + active PAI group (difference = 0.3, 95% confidence interval [CI], [-0.9 to 1.5], P = .120). Pain scores at rest did not differ significantly among groups. No significant difference was observed in opioid consumption between groups. Cumulative oral morphine equivalents through postoperative day 2 were 89 ± 40 mg (mean ± standard deviation), saline PAI, vs 73 ± 52, active PAI, P = .1. No significant differences were observed for worst pain, fraction of time in severe pain, pain interference, side-effects (nausea, drowsiness, itching, dizziness), quality of recovery, satisfaction, length of stay, chronic pain, and orthopedic outcomes. For TKA patients given a comprehensive analgesic protocol, use of saline PAI did not demonstrate noninferiority compared to active PAI. Neither the primary nor any secondary outcomes demonstrated superiority for active PAI, however. As we cannot claim either technique to be better or worse, there remains flexibility for use of either technique.

Dynamic changes in some facial muscles after superficial versus deep hyaluronic acid injection: An electromyographic study

Dynamic changes in some facial muscles after superficial versus deep hyaluronic acid injection: An electromyographic study

Superficial versus deep parasternal intercostal plane blocks: cadaveric evaluation of injectate spread

BackgroundDeep and superficial parasternal intercostal plane blocks provide anterior chest wall analgesia for both breast and cardiac surgery. Our primary objective of this cadaveric study was to describe the parasternal spread of deep and superficial parasternal intercostal plane blocks. Our secondary objectives were to describe needle proximity to the internal mammary artery when performing deep parasternal intercostal plane blocks, and compare lateral injectate spread and extension into the rectus sheath. MethodsWe performed ultrasound-guided deep and superficial parasternal intercostal plane blocks 2 cm from the sternum at the T3–4 interspace in four fresh frozen cadavers as described in clinical studies. ResultsParasternal spread of injectate was greater with the deep parasternal intercostal plane injection than with the superficial parasternal intercostal plane injection. The internal mammary artery was ∼3 mm away from the needle trajectory in cadaver #1 and ∼5 mm from the internal mammary artery in cadaver #2. Lateral spread extended to the midclavicular line for all deep parasternal intercostal plane blocks and beyond the midclavicular line for all superficial parasternal intercostal plane blocks. Neither block extended to the rectus sheath. ConclusionsA greater number of parasternal interspaces were covered with the deep parasternal intercostal plane block than with the superficial parasternal intercostal plane block when one injection was performed at the T3–4 interspace. However, considering proximity to the internal mammary artery, and potential devastating consequences of an arterial injury, we propose that the deep parasternal intercostal plane block be classified as an advanced block and that future studies focus on optimising superficial parasternal intercostal plane parasternal spread.

Case Report: Lip Augmentation with Injection of a Novel PEG-crosslinked Hyaluronic Acid Hydrogel

BACKGROUND: Lip augmentation with hyaluronic acid (HA) hydrogels is one of the most common esthetic procedures worldwide, but requires products with an optimal balance of elasticity and cohesivity to volumize while integrating with the surrounding tissue. This case report describes the results of lip augmentation with a novel, 24 mg/mL HA hydrogel cross-linked with poly (ethylene glycol) diglycidyl (PEGDE-HA 24), and supplemented with l-proline and glycine to limit post-injection swelling. METHODS: In three separate treatment sessions (Weeks 0, 2, and 10), a 29-year-old woman requesting lip augmentation was injected with PEGDE-HA 24 as multiple superficial injections using a tenting technique. Photographs were taken before treatment and at 2-weeks, 1-month, and 5-months after the initial injection. The subject provided post-treatment updates on her experience with the hydrogel in terms of the results achieved and any adverse events experienced. RESULTS: A total of 1.0 mL PEGDE-HA 24 was injected: treatment session 1 (0.3 mL); session 2 (0.4 mL); and session 3 (0.3 mL). The day after each injection the subject reported that her lips were sensitive, but not painful. The level of post-injection bruising and swelling diminished with each subsequent injection and healed rapidly. No other adverse events were reported. The subject was very satisfied with the results describing them as attractive and natural looking for up to 5 months. CONCLUSIONS: This case report demonstrated that 1 mL of PEGDE-HA 24 was effective and well tolerated for volume augmentation of the lip. The subject was very satisfied with her experience of the hydrogel and natural-looking results were achieved.

Superficial versus deep injections of the upper midface-A prospective interventional split-face study.

Various injection algorithms have been proposed in the past which are in line with the three aesthetic principles: upper face first, lateral face first, and deep regions first. However, increasing evidence is provided that the upper midface can be targeted with superficial soft tissue filler injections alone too. To investigate in a prospective split-face study design whether superficial or deep upper midfacial injections provide superior aesthetic outcomes. A total of n = 20 study participants (100% females; age 43.95 (11.7) years; BMI 22.92 (2.6) kg/m2 ) were treated with superficial soft tissue filler injections on side of their face and deep injections on the contralateral side with a mean volume of 0.78 cc. Outcome was evaluated at 7 weeks follow-up for midfacial, and lower facial volume, for medial and lateral facial skin vector displacement, and for improvement of nasolabial, crow's feet, and upper cheek fullness severity scores. No adverse events related to safety or product tolerability were observed during the entire study period. All semiquantitative scores improved statistically significantly after the observational period (p < 0.001) but displayed no difference between the two applied injection techniques (p > 0.05). The results of this split-face study revealed that both the superficial and the deep cannula injection technique for midface volumization statistically significantly improve the midfacial volume, reduce nasolabial fold and crow's feet severity. No statistically significant difference was observed between the two injection techniques when compared via semiquantitative and objective outcome evaluation after 7 weeks follow-up.

Outcome of ganglion impar block in chronic coccydynia

Background: Chronic coccydynia is an annoying condition and is characterized by pain in the tail bone. Most cases are treated conservatively initially but failed conservative management calls for interventions of various type. One of the interventions in the armamentarium of the orthopaedic surgeon is a ganglion impar block. The present study aimed at assessing the outcome of ganglion impar block in chronic coccydynia. Methods: This prospective study of five years duration included 27 patients with chronic coccydynia with failed conservative treatment. Visual analogue score (VAS) and Oswestry disability index (ODI) were used to quantify pain and the improvement in symptoms. Minimum final follow-up was two years. Results: The mean VAS and ODI scores pre-injection were 5.98±1.86 and 52.13±2.13, respectively. The mean VAS and ODI scores at final follow-up were 2.47±1.65 and 23.59±2.34, respectively. The improvement in the above objective scores was found to be statistically significant with a p=0.00257 for VAS score and 0.00425 for ODI score. One patient developed syncope post-injection and one patient complained of superficial injection site pain which persisted for three weeks. No significant or major complication was encountered. Conclusions: Ganglion impar block appears to be a very impressive modality of treatment for chronic coccydynia in view of the simplicity, ease and reproducibility of the technique along with minimal complication rates. However, randomized control trials with large sample size are recommended.

PARODOXICAL BULGING PHENOMENA AFTER MASSETER BOTOX INJECTIONS; CASE SERIES AND THE REVIEW OF THE LITERATURE

Aim: The temporomandibular joint (TMJ), also known as the mandibular joint; is a nearby the synovial joint that connects the mandible to the temporal bone the external auditory canal. Although TMJ disorders are frequently seen; they can be caused by many reasons such as disorders caused by masticatory muscles, condyle and articular disc incompatibility, inflammatory joint diseases, chronic mandibular hypomobility, and congenital or acquired muscle and bone disorders.&#x0D; Case reports: In our study, the diagnosis and treatment process of 4 patients who applied to the Gazi University Faculty of Dentistry Department of Oral and Maxillofacial Surgery clinic with complaints of TMJ pain were presented. All of the cases had masseter hypertrophy due to bruxism. Botulinum toxin-A (BTA) was injected to the masseter muscles bilateraly after written informed consents were obtained from each patients before the procedure. In the control examinations an unexpected paradoxical masseteric bulging was detected. A more superficial BTA injection was applied to the superficial lobe of the masseter muscles that was not affected by BTA in presented patients and the complaints were dissolved in ten days.&#x0D; Conclusions: The cases presented in our article have a rare complication of BTA injections and can be treated easily after a correct diagnosis by the physician. Physicians who perform BTA injections for bruxism and masseter hypertrophy should be aware of the possible complications and should have sufficient knowledge and experience to overcome it.

Impact of Glabellar Injection Technique With DaxibotulinumtoxinA for Injection on Brow Position.

Precise injection technique is vital for avoiding suboptimal eyebrow position when treating glabellar lines with botulinum toxin type A. The aim of this study was to evaluate the impact of glabellar injection technique on eyebrow position in patients treated with DaxibotulinumtoxinA for Injection (DAXI). This retrospective post hoc analysis involved 60 adults who received a single treatment with DAXI 40 U to the glabella and had standardized facial photography. Median vertical and horizontal displacement of the brows (at rest) at baseline and 2 weeks after glabellar injection were measured. Brow position outcomes were evaluated by an oculoplastic surgeon and expert anatomist. Investigators were interviewed to ascertain individual injection techniques. Precise injection location and depth, and median resting brow position following treatment varied between investigators. Positive brow outcomes were achieved with deep DAXI injections into the medial corrugator, superficial lateral corrugator injections placed between the midpupil and lateral limbus, and deep midline procerus injections. Glabellar injection technique that more precisely targeted the corrugator muscles resulted in longer glabellar line treatment duration compared to a less targeted technique. Medial corrugator injections above the medial brow; lateral corrugator injections administered deeply or more medially, toward the medial third of the brow; and procerus injections superior to the inferomedial brow tended to be associated with suboptimal outcomes that were more apparent during dynamic expression. Aesthetically pleasing brow outcomes and greater duration of efficacy can be achieved with an injection pattern that precisely treats the anatomic location of the corrugator supercilii and procerus muscles, avoiding the frontalis.

Efficacy of Percutaneous Superficial Temporal Arterial Hyaluronidase Injection for Hyaluronic Acid Filler-Induced Necrosis of Frontotemporal Skin and/or the Ipsilateral Scalp With Subsequent Alopecia.

Necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after hyaluronic acid (HA) filler injection into the temple is rare complications with superficial temporal artery embolization are suspected as the major pathological mechanism. The main treatment currently is intralesional hyaluronidase (HAase) injection, but the effectiveness of percutaneous superficial temporal arterial HAase injection still lacks consensus. To investigate the effectiveness of superficial temporal arterial HAase injection in dissolving HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia. Five recent clinical cases with necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after HA filler injection into the temple were analyzed retrospectively. The patients underwent HAase injection via superficial temporal artery combined with adjunctive treatments, and the clinical progress was observed. Significant improvement was observed in terms of necrosis of frontotemporal skin and the ipsilateral scalp after treatment, and the patients were relieved of their clinical symptoms. Alopecia occurred approximately 1 to 2 weeks after HA filler injection, and the well-defined alopecia areas were formed 15 to 20 days after HAase injection. Patients were followed for 3 to 6 months. During follow-up, the skin lesions of all patients were restored to near normal appearance. Hair regrowth was observed 2 to 3 months after HAase treatment, and hair density nearly reached the normal level 3 to 4 months later. Percutaneous superficial temporal arterial HAase injection is an effective treatment option for HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia.

Clinical and histological comparative outcomes after injections of poly-L-lactic acid and calcium hydroxyapatite in arms: A split side study.

Although much has been published on the use of poly-L-lactic acid (PLLA) and calcium hydroxyapatite (CaHA) for off-face indications, questions remain regarding their exact mechanisms of action in subcutaneous tissue and their comparative efficacy. To present the clinical and histological results of the PLLA and CaHA injections into the opposing arms of the same patients. Five women received superficial subcutaneous injections of PLLA into the left arm and CaHA into the right arm. After three sessions, the clinical and histological outcomes were analyzed. After the first session, three patients showed improvement in the right arm (CaHA), but at the end of study, two patients showed better results in the left arm (PLLA). Histologically, moderate to intense lymphocytic and giant cell infiltrate, as well as collagen and elastic fiber neoformation, were observed equally near the particles of both products. Dermis had no inflammatory or fiber alterations. In this study, there were no clinical differences between these two fillers. Despite current thinking and previous histological studies, we found both products produced moderate to intense inflammatory reaction, as well as collagenic/elastogenic fiber neoformation, only in the subcutaneous tissue of the immediate vicinity and surrounding the individual filler particles.

Trapezius Muscle and the Cutaneous Branches of Spinal Nerves: Sonographic/Anatomic Discussion of Myofascial Pain and Superficial Injections.

Trapezius Muscle and the Cutaneous Branches of Spinal Nerves: Sonographic/Anatomic Discussion of Myofascial Pain and Superficial Injections.

Effect of intratumoral INT230-6 on tumor necrosis and promotion of a systemic immune response: Results from a multicenter phase 1/2 study of solid tumors with and without pembrolizumab (PEM) [Intensity IT-01; Merck KEYNOTE-A10

2520 Background: INT230-6 is a new product with a unique dual anti-cancer mechanism. The drug is comprised of cisplatin (CIS) and vinblastine (VIN) co-formulated with an amphiphilic molecule that enables drug dispersion throughout a tumor and passive diffusion into cancer cells following intratumoral (IT) delivery. A neoadjuvant study in breast cancer confirms that a single injection can kill 95% of an injected tumor and recruit TILs. Methods: INT230-6 treatments are Q2W for up to 5 treatments followed by maintenance dosing every 9 weeks. Dose is set by the tumor’s longest diameter or volume. One arm received INT230-6 plus PEM 200mg IV Q3W. Biopsies from injected tumor are taken pretreatment and Day 28 for immunohistochemistry (IHC) analysis. Results: Sixty-two subjects received INT230-6 alone (median age 61, with 4 prior treatments), and 21 INT230-6 + PEM (median age 70, with 3 prior treatments). To these subjects over 575 image guided INT230-6 IT injections were given (320 to visceral tumors such as lung, liver, pancreas). Doses ranged from 0.14 to 175mL (87.5 mg of CIS, 17.5 mg VIN - higher than typical IV doses). Pharmacokinetic data shows &gt; 95% of the INT230-6 active agents remain in the tumor. The most common ( &gt; 25%) adverse events (AEs) related to INT230-6 were localized pain (58%), nausea (40%), and fatigue (29%). The most common AEs attributed to the PEM combination were nausea (62%), localized pain (57%), vomiting (57%), decreased appetite (43%), fatigue (43%) and constipation (29%). The incidence of grade 3 AEs for the INT230-6 arm was 11% and for the PEM combination was 14%. There were no related grade 4 or 5 AEs in the INT230-6 arm; and one grade 4 neutrophil count decrease was seen on the PEM combination. There were no dose limiting adverse events. No patient discontinued therapy due to toxicities related to either drug or injection procedure. The monotherapy arm enrolled patients from 17 tumor types; while the PEM combo recruited primarily pancreatic, CRC, triple negative breast, or bile duct cancer. IHC results confirm a marked reduction in proliferating tumor cells with influx of CD4 and CD8 T-cells. Seven of the INT230-6 monotherapy patients had non injected tumor shrinkage in 9 visceral/deep lesions. Estimated median overall survival (mOS) was over 1 year for both arms. Conclusions: In this clinical trial, deep and superficial tumor injections into patients with widely metastatic disease was feasible and well tolerated. Biopsies confirm the dual anti-cancer mechanism, and study patients live longer than would be expected for these refractory populations. INT230-6’s rapid tumor killing and immune activation properties may offer an alternative to control refractory patients (even those that are chemotherapy refractory) and the product is moving into randomized controlled registration trials. Clinical trial information: NCT03058289.

Efficacy and safety of two hyaluronic acid fillers withdifferent injection depths for the correction of moderate-to-severe nasolabial folds: A 52-week, prospective, randomized, double-blinded study in a Chinese population.

Hyaluronic acid (HA) fillers are known to be effective for the correction of facial wrinkles and folds, but there is no clinical study that compares the efficacy of small-to-medium-particle HA fillers and large-particle HA fillers for the correction of nasolabial folds (NLFs). Moreover, injection depth also plays an important role in the correction of NLFs as well as improvement of facial aesthetics. To assess the efficacy, safety, and durability of a small-to-medium-particle HA filler, Restylane, and a large-particle HA filler, Yishumei, as well as the effect of injection depth in the correction of moderate-to-severe NLFs and facial aesthetics in a Chinese population. This 52-week, prospective, randomized, double-blind study enrolled 100 participants with moderate-to-severe NLFs. The participants were randomized to receive either Restylane (Group A) or Yishumei (Group B). Group A and Group B were further randomly divided into a superficial injection group (Group A1 & B1) and a deep injection group (Group A2&B2) according to injection depth. Improvement in the Wrinkle Severity Rating Scale (WSRS) score and Global Aesthetic Improvement Scale (GAIS) and participants' satisfaction were evaluated as endpoints. All adverse events were monitored throughout the study. The treatments were well tolerated by all the participants. All four groups showed a reduction in their mean WSRS scores and GAIS scores by week 12. At week 24, the WSRS and GAIS scores did not change in Group A1 and A2, while participants in Group B1 and Group B2had higher WSRS and GAIS scores than those in the previous weeks. By week 52, the WSRS scores in all the groups returned to almost baseline levels. The mean FACE-Q scores increased compared with the baseline scores in all groups through week 24. Most participants were satisfied with their treatment, and no meaningful differences were found between the fillers in terms of participant satisfaction. The most common adverse events were swelling, redness, and tenderness at the injection site, but they resolved spontaneously without treatment. The two HA fillers had good therapeutic effect on NLFs in the early stage of treatment, but Restylane had a more prolonged effect. Moreover, compared with the superficial injection, the deep injection provided slight midface lifting and improved facial aesthetics.

Creatine Derivatives: Rapid Complete Relief of Pain by Topical or Transcutaneous Administration

Our research reveals that non-toxic creatine derivatives, especially N-acetyl-creatine ethyl ester, to be therapeutically effective on topical application or by superficial subcutaneous injection over sites of pain to rapidly alleviate or eliminate pain associated with various inflammatory conditions including arthritis, acute common headache, osteoarthritis, psoriatic arthritis, rheumatoid arthritis and various other pains associated with inflammation.

Endoscopic submucosal dissection: How to be more efficient?

Endoscopic submucosal dissection (ESD) allows an “en bloc” resection with safety margins (R0 resection) regardless of the size of the lesion. However, while R0 brings a real benefit for the patient, it is not considered sufficient by many experts to justify the technical difficulties and the longer procedure time compared to piecemeal mucosectomy. The aims of this review are to provide several technical and strategical tips to help you save time and become comfortable during ESD procedures. ESD is divided into several intertwined phases: injection, incision, access to the submucosae, and submucosal dissection itself. During injection there are some mistakes that should not be made: a superficial injection, or on the contrary, a too deep injection. A good needle and good injection technique are mandatory. Some techniques, such as repeated injection or prolonged lifting solution, can help maintain the lift. After this step, mucosal incision can be made, taking care to have a good margin to allow an R0 resection. Starting the mucosal incision from a small point allows calibration of the depth of the incision and then obtaining a nice incision. Trimming is also very important to widen submucosal access. Then comes the submucosal dissection itself. Strategies such as the tunnel strategy or the pocket creation method can help to facilitate dissection, but more importantly, traction systems have become unavoidable, especially in the stomach and colon. Most common complications are bleeding and perforation, and they usually can be managed endoscopically.

Optimization of pig models for translation of subcutaneous pharmacokinetics of therapeutic proteins: Liraglutide, insulin aspart and insulin detemir

Prediction of human pharmacokinetics (PK) from data obtained in animal studies is essential in drug development. Here, we present a thorough examination of how to achieve good pharmacokinetic data from the pig model for translational purposes by using single-species allometric scaling for selected therapeutic proteins: liraglutide, insulin aspart and insulin detemir. The predictions were based on non-compartmental analysis of intravenous and subcutaneous PK data obtained from two injection regions (neck, thigh) in two pig breeds, domestic pig and Göttingen Minipig, that were compared with PK parameters reported in humans. The effects of pig breed, injection site and injection depth (insulin aspart only) on the PK of these proteins were also assessed. Results show that the prediction error for human PK was within two-fold for most PK parameters in both pig breeds. Furthermore, pig breed significantly influenced the plasma half-life and mean absorption time (MAT), both being longer in Göttingen Minipigs compared to domestic pigs (P <0.01). In both breeds, thigh vs neck dosing was associated with a higher dose-normalized maximum plasma concentration and area under the curve as well as shorter MAT and plasma half-life (P <0.01). Finally, more superficial injections resulted in faster absorption, higher Cmax/dose and bioavailability of insulin aspart (P <0.05, 3.0 vs 5.0 mm injection depth). In conclusion, pig breed and injection region affected the PK of liraglutide, insulin aspart and insulin detemir and reliable predictions of human PK were demonstrated when applying single-species allometric scaling with the pig as a pre-clinical animal model.