Tools and methods for cell ablation and cell inhibition in Caenorhabditis elegans.

To understand the function of cells such as neurons within an organism, it can be instrumental to inhibit cellular function, or to remove the cell (type) from the organism, and thus to observe the consequences on organismic and/or circuit function and animal behavior. A range of approaches and tools were developed and used over the past few decades that act either constitutively or acutely and reversibly, in systemic or local fashion. These approaches make use of either drugs or genetically encoded tools. Also, there are acutely acting inhibitory tools that require an exogenous trigger like light. Here, we give an overview of such methods developed and used in the nematode Caenorhabditis elegans.

A Hospital-Based Longitudinal Study of Rubber Band Ligation and Sclerotherapy Treatment for Internal Hemorrhoids From South India.

Background Hemorrhoids are an extremely common surgical condition affecting millions of individuals worldwide. Treatment options for hemorrhoids vary depending on the severity of symptoms and the type of hemorrhoids. The common non-surgical procedures for grade one and two hemorrhoids include rubber band ligation and sclerotherapy. The present study aims to compare the efficiency of rubber band ligation and sclerotherapy for the treatment of symptomatic grade one and two internal hemorrhoids in a tertiary care hospital. Methodology We conducted a one-year longitudinal survey among 200 patients with internal hemorrhoids in a tertiary care center in Madurai. We gathered data on demographic profiles, symptoms, postoperative complications, intraoperative pain, and treatment outcomes. Data analysis was done using the Pearson chi-square test to assess the difference between rubber band ligation and sclerotherapy treatment groups. A p-value <0.05 was considered statistically significant. Results A total of 200 patients were studied, of whom 100 belonged to the rubber band ligation treatment group and 100 belonged to the sclerotherapy treatment group. The preoperative symptoms were similarly distributed between both treatment groups. Intraoperative and immediate postoperative pain was higher in the rubber band ligation group than in the sclerotherapy group. Post-procedure complications were more commonly seen in the rubber band ligation group than in the sclerotherapy group at various weeks of the procedures. Conclusions Postoperative complications such as bleeding, prolapse, and infection/discharge were significantly different between the two treatment groups. The treatment outcome was significantly different between the two treatment groups after three, six, and nine weeks postoperatively. Overall, the sclerotherapy group was associated with fewer postoperative complications, more excellent patient response, and a more complete response to treatment than the rubber band ligation group.

Mechanisms of Vein of Marshall-Related Tachyarrhythmias and the Impact of Ethanol Infusion.

The Ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and the left cardinal vein, containing a combination of fat, fibrous tissue, blood vessels, muscle bundles, nerve fibers, and ganglia. Various muscular connections exist between the LOM and the left atrium (LA) and the coronary sinus (CS). The LOM is richly innervated by autonomic nerves, with ganglion cells distributed around it. The unique characteristics of the LOM are responsible for generating focal electrical activities and enable it to serve as a substrate for micro- and macro-reentrant circuits. This, in turn, leads to the initiation and perpetuation of atrial fibrillation (AF) and atrial tachycardia (AT). Endocardial ablation in this region does not consistently succeed due to anatomical constraints within the left lateral LA, including the presence of a thicker and longer mitral isthmus (MI), anatomical variations between the MI and epicardial structures such as the CS and vein of Marshall (VOM) and circumflex artery, and the presence of fibrofatty tissue insulating the LOM. Furthermore, epicardial ablation is challenging for inexperienced institutions because of its invasive nature. Ethanol infusion into the VOM (EI-VOM) represents an effective and safe approach that can be employed in conjunction with radiofrequency ablation to eliminate this arrhythmogenic structure.

Chemical ablation of the left ventricular endocardium reduces ventricular fibrillation inducibility in acute ischemic canine heart.

Objective: Ventricular fibrillation remains as the major cause of death in patients with acute myocardial infarction. Effects of trans-atrial chemical ablation of the left ventricular (LV) endocardium with Lugol's solution on ventricular fibrillation inducibility and ventricular conduction were examined in canines with acute myocardial ischemia. Materials and Methods: Chemical ablation of the LV endocardium with Lugol's solution or normal saline was preformed through a left atrial appendage in 14 canines 30 min after occlusion of the left anterior coronary artery. Results: Ventricular fibrillation threshold decreased after the coronary artery occlusion and increased after endocardial chemical ablation. There was a significant difference in the ventricular fibrillation threshold after chemical ablation between with Lugol's solution and with normal saline (25.9 ± 9.2 mA vs. 11.3 ± 2.7 mA, p < .01). QRS width significantly increased from 88 ± 4msec to 116 ± 5msec (p < .01) after the chemical ablation with Lugol's solution, and the activation map of the ventricles demonstrated a left bundle branch block ventricular conduction pattern. Histological examination of the LV endocardium showed lymphocyte infiltration for a depth of 1 mm. Conclusions: Chemical ablation of the LV endocardium with Lugol's solution injures endocardial conduction system and increases ventricular fibrillation threshold in the early phase of myocardial ischemia in canines. The procedure may be useful in suppressing intractable ventricular tachyarrhythmias in patients with acute myocardial ischemia.

Effect of different retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules.

OBJECTIVE: To assess the influence of varying retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules. METHODS: A retrospective study was conducted from December 2019 to January 2022, including 78 patients with benign cystic-solid thyroid nodules, of which 31 received polidocanol chemical ablation alone, 23 received polidocanol chemical plus thermal ablation, and 24 received open surgery. Patients who received polidocanol chemical ablation were assigned into groups based on the retention dose of polidocanol: 0 %, 10 %, 20 %, 30 %, and 50 %. Follow-ups were done at 1, 3, 6, and 12 months postoperatively. The volume of the nodules, postoperative complications, and recurrence of the nodules were examined before treatment and during follow-up visits. RESULTS: Total operation time and intraoperative bleeding volume for patients who received ablation were substantially lower than those for patients who received open surgery (P < 0.001). Among patients in the polidocanol chemical ablation group, volume shrinkage rate of thyroid nodules in the 10 % retention dose group was significantly lower than that in the 0 % retention dose group at 1, 3, and 6 months postoperatively (P < 0.05). The 30 % retention dose group had the highest nodule shrinkage rate (98.46 ± 1.55 %) at 12 months postoperatively, which was significantly higher than that in the 50 % retention dose group (P < 0.05). Among patients in the polidocanol chemical and thermal ablation group, the volume shrinkage rate of thyroid nodules in the 10 % and 30 % retention dose groups at 1 month postoperatively was significantly lower than that in the 0 % retention dose group (P < 0.05). Although volume shrinkage rate in the 20 % retention dose group after thermal ablation was higher than that in the 0 % retention dose group, the difference was not statistically significant (P > 0.05). In terms of adverse reactions, the incidence of hoarseness and coughing was higher in the open surgery group than in the polidocanol chemical ablation and polidocanol chemical and thermal ablation groups, but there was no significant difference (P > 0.05). CONCLUSION: Chemical ablation with polidocanol was safe and effective for therapy of benign cystic-solid thyroid nodules, and the optimal retention dose may be between 20 % and 30 %. Patients with poor efficacy from chemical ablation alone can receive safe and effective treatment through thermal ablation.

Optimal treatment of biatrial tachycardia diagnosed by one-chamber mapping within an ultrahigh-resolution mapping system.

Biatrial tachycardia (BiAT) is a rare arrhythmia, and identification of the re-entry circuit is often complicated. By creating an activation map of the right atrium, left atrium, and coronary sinus as a single chamber, the LUMIPOINT module of the Rhythmia mapping system (Boston Scientific, Marlborough, MA, USA) can be used in real time to make an accurate diagnosis. Ablation of the Bachmann bundle is a feasible way to terminate BiAT, but might cause interatrial conduction delay and electrical isolation of the left atrial appendage. Chemical ablation into the vein of Marshall might be the more beneficial treatment, avoiding any potential interatrial conduction delay.

Endoscopic Ultrasound-Guided Local Ablative Therapies for the Treatment of Pancreatic Neuroendocrine Tumors and Cystic Lesions: A Review of the Current Literature.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

Aggressive angiomyxoma of the pelvis and abdominal wall: Dramatic response to chemical ablation therapy.

Objective: Aggressive angiomyxoma (AAM) is a rare, locally aggressive soft tissue neoplasm with a marked tendency for local recurrence after surgery. Although hormone therapy, radiation therapy, and vascular embolization can be performed, we investigated the safety and efficacy of a new chemical ablation protocol for AAM. Methods: This study included two female AAM patients from 2012 to 2016. The patients' clinical and imaging data were collected. The amount of anhydrous ethanol and glacial acetic acid used for chemical ablation was documented, and the management of any complications was detailed. Results: The maximum dimensions of the residual tumor were 12.6 cm and 14.0 cm. In one case, the lesion was in the pelvis and protruded into the vulva. Eighty milliliters of liquid with a mixture of glacial acetic acid, anhydrous ethanol, and iohexol (10:9:1) was used for chemical ablation therapy via multipoint injections with a single needle. However, a pelvic fistula developed 1 month later. In another case, the lesion was located in the abdominal wall. The ablation procedure was improved by performing chemical ablation therapy with multiple needles for multi-point injections of smaller than 30 ml injections for each procedure. To date, no recurrence or metastasis has been observed in the two cases. Conclusion: The preferred treatment for AAM is complete resection. Chemical ablation therapy is a novel adjuvant therapy for AMM. Nonetheless, more research is needed to confirm these findings.

VIEW-VLU observational study of the effect of Varithena on wound healing in the treatment of venous leg ulcers.

OBJECTIVE: Chronic venous hypertension, triggered by venous reflux and/or obstruction, leads to skin changes and venous leg ulcers (VLUs). Compression therapy is the standard of care, but many wounds remain unhealed. The objectives of this study were to observe the effects of endovenous chemical ablation with commercially available 1% polidocanol injectable microfoam on VLU healing and recurrence rates. METHODS: The VIEW VLU study was a multicenter, open-label, phase IV registry of patients with active VLUs resulting from venous insufficiency of the great saphenous vein and/or anterior accessory saphenous vein systems who underwent ablation with 1% polidocanol microfoam. Primary outcomes included wound healing rate (change in wound perimeter), wound closure at 12 weeks after treatment, and time to wound closure. Secondary outcomes included VLU recurrence, numeric pain score at the ulcer location, EuroQol five-dimension five-level questionnaire quality-of-life index, and the Venous Clinical Severity Score. Patients were followed for 12 months. RESULTS: We enrolled 76 patients (80 ulcers) from 14 sites across the United States and Canada (mean age 63.6 ± 13.7 years, 39.5% female, mean body mass index 36.3). Of the enrollees, 96.3% presented with great saphenous vein incompetence. The mean baseline wound perimeter was 117.2 ± 107.4 mm and 26.3% of wounds (21/80) were circumferential. The mean ulcer age was 34.8 ± 51.8 weeks at first presentation and the mean compression therapy duration was 26.4 ± 35.9 weeks. The median wound perimeter decreased by 16.3% from baseline in the first 2 weeks after the procedure and by 27.0% at 12 weeks. By 12 weeks, 53.8% of wounds (43/80) were healed. The median time to ulcer closure by Kaplan-Meier analysis was 89 days (95% confidence interval, 62.0-117.0). In a Kaplan-Meier analysis of initially healed wounds, 88.9% (95% confidence interval, 76.9-94.8) remained closed at 12 weeks after closure. The mean numeric pain scores (ulcer site) improved by 41.0% and 64.1% at 12 weeks and 12 months after the procedure, respectively. The health-related quality-of-life index (scale of 0-1) improved from 0.65 ± 0.27 at baseline to 0.72 ± 0.28 at 12 weeks and 0.73 ± 0.30 at 12 months. By 12 weeks after treatment, the mean target leg Venous Clinical Severity Score had significantly decreased by 5.8 points, and by 12 months it had decreased by 10.0 points. CONCLUSIONS: Treatment with 1% polidocanol microfoam was associated with promising wound healing rates and low recurrence rates for VLUs, despite a challenging patient population with recalcitrant ulcers, a large percentage of which were circumferential, in patients with high body mass indexes.

[Minimally invasive catheters in varicose vein treatment : New gold standard?] / Minimal-invasive Katheterverfahren in der Varizentherapie : Neuer Goldstandard?

BACKGROUND: Endovenous procedures are commonly used for varicose vein treatment. OBJECTIVES: Types, functionality, and significance of endovenous devices. METHODS: To describe the different endovenous devices, their mode of action, inherent risks and efficacy according to the literature. RESULTS: Long-term data confirm that endovenous procedures are equally effective as open surgery. Postoperative pain is minimal and downtime shorter after catheter interventions. CONCLUSION: Catheter-based endovenous procedures increase the diversity of varicose vein treatment options. They are preferred by patients due to less pain and shorter downtime.

CT-guided percutaneous chemical ablation combined with radiofrequency ablation for hepatocellular carcinomas in high-risk locations: lobaplatin vs. ethanol.

To retrospectively compare the clinical efficacy and safety of CT-guided percutaneous injection of lobaplatin vs. ethanol for chemical ablation combined with radiofrequency ablation (RFA) in patients with hepatocellular carcinomas (HCCs) in high-risk locations. From January 2017 to June 2018, a total of 41 patients with HCCs in high-risk locations were enrolled and divided into two groups: percutaneous lobaplatin injection (PLI+RFA) group and percutaneous ethanol injection (PEI+RFA) group. The mixture of lobaplatin or ethanol was accurately injected into the high-risk part of the tumors, while RFA ablated the non-high-risk part. The efficacy and safety were compared between the two groups. 41 patients had 51 lesions in high-risk locations, including 24 cases with 30 lesions in PLI+RFA group and 17 cases with 21 lesions in PEI+RFA group. The complete ablation rate was 93.3% (28/30) in PLI+RFA group and 90.5% (19/21) in PEI+RFA group (P=1.000). The 2-year local tumor progression rate of PLI+RFA group and PEI+RFA group was 20.0% (6/30) and 19.0% (4/21), respectively (P=1.000). No significant differences were found in time to progression and overall survival between the two groups (P=0.501 and P=0.424, respectively). The incidence and severity of adverse events between the two groups were similar (P > 0.05). No severe complications were observed in both groups. Percutaneous lobaplatin injection combined with RFA in the treatment of HCC in high-risk locations may achieve the complete ablation rate similar to percutaneous ethanol injection combined with RFA, but further research is needed to confirm.

Klippel-Trenaunay Syndrome: Employment of a New Endovascular Treatment Technique-Mechanochemical Ablation Using the Flebogrif System.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is characterized by a triad of symptoms; varicose veins and venous malformations (VMs), capillary malformations (port-wine stain), and soft tissue and bone hypertrophy. Herein, we retrospectively studied six patients with KTS who underwent treatment with the Flebogrif system and evaluated their outcomes. METHODS: Six KTS patients aged 16-22 years who had undergone 18 non-thermal ablations using the Flebogrif system were enrolled. All patients underwent multistage foam sclerotherapy with 3% polidocanol at 3-4-week intervals. RESULTS: Venous clinical severity score (VCSS) analysis showed improvement in the patients' clinical condition. All patients reported a significant improvement in aesthetic outcomes. One patient presented with recanalization of ablated marginal veins during the 24-month follow-up period. Patients could return to full activity within 7-10 days after the procedure. None of the patients experienced serious systemic complications. CONCLUSION: The use of the Flebogrif system in treating various forms of chronic venous insufficiency, including in patients with KTS, provides a high success rate with a high closure rate.

Distribution of atrial low voltage induced by vein of Marshall ethanol infusion.

INTRODUCTION: Systematic and quantitative descriptions of vein of Marshall (VOM)-induced tissue ablation are lacking. We sought to characterize the distribution of low voltage observed in the left atrium (LA) after VOM ethanol infusion. METHODS AND RESULTS: The distribution of ethanol-induced low voltage was evaluated by comparing high-density maps performed before and after VOM ethanol infusion in 114 patients referred for atrial fibrillation ablation. The two most frequently impacted segments were the inferior portion of the ridge (82.5%) and the first half of the mitral isthmus (pulmonary vein side) (92.1%). Low-voltage absence in these typical areas resulted from inadvertent ethanol infusion in the left atrial appendage vein (n = 3), initial VOM dissection (n = 3), or a "no branches" VOM morphology (n = 1). Visible anastomosis of the VOM with roof or posterior veins more frequently resulted in low-voltage extension beyond typical areas, toward the entire left antrum (19.0% vs. 1.9%, p = .0045) or the posterior LA (39.7% vs. 3.8%, p < .001) but with a limited positive predictive value ranging from 29.4% to 43.5%. Ethanol-induced low voltage covered a median LA surface of 3.6% (1.9%-5.0%) and did not exceed 8% of the LA surface in 90% of patients. CONCLUSION: VOM ethanol infusion typically locates at the inferior ridge and the adjacent half of the mitral isthmus. Low-voltage extensions can be anticipated but not guaranteed by the presence of visible anastomosis of the VOM with roof or posterior veins.

Physical & Chemical Microwave Ablation (MWA) Enabled by Nonionic MWA Nanosensitizers Repress Incomplete MWA-Arised Liver Tumor Recurrence.

Ionic liquid (IL)-loaded or metal ions-enriched nanoparticles have been witnessed to assist microwave ablation (MWA) and heighten heat utilization for tumor treatment, which, however, inevitably brings about cell dys-homeostasis and severely endangers normal cells or tissues. In this report, a nonionic MWA sensitizer that encapsulates ethyl formate (EF) and doxorubicin (DOX) in liposomes (EF-DOX-Lips) was constructed to reinforce MWA and combined therapy against incomplete MWA-induced tumor recurrence. EF in EF-DOX-Lips as the nonionic liquid can perform like IL to accelerate energy transformation from electromagnetic energy to heat for strengthening MWA. More significantly, EF metabolite, that is, ethanol, also enables chemical ablation, which further enhances MWA. As well, the EF gasification-enhanced lipid rupture and cavitation can promote DOX delivery into a liver tumor for magnifying MWA & chemotherapy combined therapy. By virtue of these contributions, this nonionic MWA nanosensitizer exerts robust antitumor effects to inhibit tumor proliferation and angiogenesis for repressing tumor growth and recurrence or metastasis via downregulating the Epha2 gene and unconventional PI3K/Akt & MAPK signal pathways that the incomplete MWA activated, which provides an avenue to elevate an MWA-based antitumor outcome.

Clinical outcome of intravitreal gentamicin injection for the treatment of end-stage glaucoma in five rabbits (eight eyes).

Background: Glaucoma is a painful and blinding condition that occurs in many species, including rabbits. When medication is no longer effective in maintaining intraocular pressure (IOP), enucleation is the recognized treatment for rabbits with end-stage glaucoma. However, this procedure carries risks relating to the procedure and the anesthesia. Aim: The aim of this retrospective study was to report the efficacy of intravitreal gentamicin injection in controlling IOP in blind eyes of rabbits with end-stage glaucoma. Ocular and non-ocular complications were retrospectively assessed. Methods: Medical record review was performed to identify five client-owned rabbits (eight eyes) that were treated by intravitreal injection of 6-20 mg of gentamicin per eye (median 7.18 mg/kg) for chronic, end-stage glaucoma. Treatment was unilateral in two and bilateral in three rabbits. IOP control was assessed via rebound tonometry readings performed approximately 2 weeks, 1 month, 3 months, and 6 months after injection. Total follow-up was between 313 and 1,111 days. Ocular complications were recorded and systemic health was estimated by the owner-answered questionnaire and changes in body weight. Results: IOP was <25 mmHg in 87.5% of eyes 3 months post-injection. The most common ocular complications were cataracts (62.5%), anterior uveitis (25%), retinal detachment (12.5%), and corneal erosion (12.5%). There were no behavioral or body weight changes suggestive of systemic complications. Conclusion: 87.5% of rabbit eyes treated with intravitreal gentamicin had controlled IOP 3 months after injection. All eyes were blind at the time of injection. Ocular side effects were common. Investigation of the safety and systemic effects of intravitreal gentamicin injection is required; however, no overt complications were identified in treated rabbits in this study.

Durability of mitral isthmus ablation with and without ethanol infusion in the vein of Marshall.

INTRODUCTION: Ethanol infusion in the vein of Marshall (EIVOM) effectively creates a linear ablation lesion in the mitral isthmus (MI). However, data on the long-term success rates of MI ablation is limited. METHODS AND RESULTS: Our cohort consisted of 560 patients with nonparoxysmal atrial fibrillation (AF) who underwent an initial MI ablation. Ablations were performed by only radiofrequency (RF) in 384 (RF group) or by RF and EIVOM in 176 (EIVOM/RF group) patients; 5 ml anhydrous ethanol was used to perform EIVOM in advance of RF. Following EIVOM, RF pulses were delivered to the lateral MI line. Bidirectional MI block was fully achieved in 353/384 (92%) (First 318, Re-do 35) patinents in the RF group and 171/176 (97%) (First 128, Re-do 43) patients in the EIVOM/RF group (p = .09 in the first, p = .10 in the re-do ablation cases). In cases with complete MI line block, recurrent AF or atrial tachycardia was observed in 130/353 (37%) patients in the RF group and in 64/171 (37%) patients in the EIVOM/RF group (log-rank p = .12 in the first, and p = .30 in the re-do ablation cases). Of the total 560 patients, 123 proceeded to the subsequent ablation session. Reconduction across MI line block was observed in 39/80 (49%) patients in the RF group and 25/43 (58%) patients in the EIVOM/RF group (p = .32). CONCLUSION: EIVOM effectively ensures MI line block; however, the reconduction rate was similar between the two groups.

Chemical Ablation for Treating Anal Fistulas without Surgical Intervention: Long-Term Results.

Purposes. This study aimed to evaluate long-term outcomes after the application of a corrosive chemical agent for ablation of epithelial tissue as a non-surgical treatment of anal fistulas. Methods. Adult patients with symptomatic perianal fistula were prospectively included in the study. The fistula tract was irrigated with a 5% silver nitrate solution. The primary outcome measured in this study was the rate of clinical healing after long-term follow-up. Factors that may affect healing were also analysed. Results. A total of 186 patients with anal fistula were analysed. After irrigation with silver nitrate, 82 (44%) patients had complete clinical healing during a median follow-up time of 50 (7-64) months. Patients with intermittent discharge had a significantly higher rate of complete clinical healing than those with continuous discharge (P < .04). Fistulas without abscesses or secondary tracts had a significantly higher rate of complete clinical healing than the other types (P = .007). Conclusion. Chemical ablation of the epithelium of the anal fistula yields promising long-term outcomes in the management of anal fistulas without surgical intervention.

Outcomes following minimally invasive imagine-guided percutaneous ablation of adrenal glands.

Whilst surgery represents the gold standard for the treatment of adrenal primary malignant tumors, metastatic involvement of the adrenal glands is generally approached conservatively; however, surgery for local control has been controversial, and several reports have described the utility of surgical removal in terms of prolonged survival in selected patients. Different techniques, including radiofrequency ablation (RFA), microwave ablation (MWA), laser induced thermal therapy (LITT), cryoablation (CRA), and chemical ablation, are employed in percutaneous image-guided ablation for primary and metastatic malignancies of the adrenal glands, in case of patients with multiple comorbidities or who refuse surgery. Technical success, clinical success and safety were analysed and discussed in this systematic review. Tumor size was found a significant determinant for local disease control; histology of the primary malignancy and coexistence of tumor elsewhere were correlated with prognosis. These procedures resulted to be feasible and safe, with hypertensive crisis representing the most common complication. Although there is lack of evidence in the literature concerning outcomes compared with surgery, percutaneous ablation may represent a useful therapeutic option for controlling unresectable adrenal metastases, offering patients opportunities for improved survival.