⌚ Ethanol Ablation Informative Speech

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Ethanol Ablation Informative Speech

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The study design is illustrated in Fig. Study design for assessing effects of injection rate and ethyl cellulose concentration on therapeutic efficacy in vivo. Squamous cell carcinomas were induced in the hamster cheek pouch through topical application of DMBA 3X per week until tumors formed and reached a volume of mm 3 approximately 20 weeks. After ablation, tumor volume was measured at 1, 2, 4, and 7 days after treatment.

For tumors that were still present after 7 days, repeat ablations were performed; these were treated as independent ablations if tumor volume had increased for two consecutive days after day 7. For injection volume, two-way parametric ANOVAs were performed, and the relationship between injection volume and distribution volume was fit to a linear model. Normalized tumor volume was calculated by dividing the volume at a given time point by the initial volume before treatment. Repeat injections were considered as independent injections. They did not perform significantly differently from first-time injections Supplementary Figure 1. For in vivo experiments, tumors were randomly assigned to experimental groups. Figure 2 illustrates the phase transition of ethyl cellulose-ethanol solutions from a homogenous liquid solution before addition of water to the formation of a gel-phase upon increasing the water concentration.

The density was measured to be 0. After weighing the gel, each specimen was heated until all the liquid evaporated, leaving only dried ethyl cellulose powder. This dry powder was then weighed and found to be Since ethyl cellulose is ethanol-soluble and water-insoluble, the evaporated portion of the gel was likely to be primarily ethanol. Ethyl cellulose-ethanol forms a gel upon exposure to water. Viscosity increased exponentially with ethyl cellulose concentration Fig. Ethanol viscosity increases with addition of ethyl cellulose.

The gel mass ratio is the mass of the gel divided by the mass of the ethyl cellulose powder initially in solution. This ratio Fig. This indicates that gels spontaneously degraded at physiological conditions Fig. Gel mass is a function of water concentration, ethyl cellulose concentration and time. All error bars depict standard error. An underlying design goal in developing this tumor ablation methodology is to maximize distribution volume within the tumor while minimizing injection volume. This could increase therapeutic efficacy while decreasing potential toxicities, e. Experiments with the phantoms provided biophysically relevant insights about achieving that goal. Representative images acquired from two orthogonal perspectives of a phantom are shown in Fig.

This was likely due to the increased backflow of lower viscosity ethanol around the injection needle for the latter. Backflow denotes the flow of the injection solution upwards along the needle and back out of the phantom. Distribution volume vs. Distribution volume varies with injection rate, injection volume, and ethyl cellulose concentration. Distribution volume was calculated from front and side images of each phantom, assuming that the distribution shape was an ellipsoid. The linear fits had slopes of 8.

Each injection volume was performed 5 to 7 times. Each injection rate was evaluated 7 times. All error bars depict standard error of the mean. Figure 6 shows representative images of tumor response to conventional ethanol ablation intratumoral injection of pure ethanol by hand and the average reductions in tumor volume over a 7-day period. The needle was placed approximately 4 mm deep into the center of the tumor. For most injections, some necrosis was visible and the overall tumor volume decreased, but complete response was not consistently achieved Fig.

Of the 12 tumors ablated, 4 regressed completely and had no visible lesions at day 7. High-dosage manual ethanol ablation treatment of epithelial tumors is ineffective. Scale bar is approximately 6 mm. Therapeutic efficacy is quantified as normalized tumor volume, which is tumor volume as a percentage of its Day 0 value. Gray traces represent individual tumor responses and error bars depict standard errors of the means. To evaluate the interacting effects of ethyl cellulose concentration and injection rate on therapeutic efficacy in vivo , ablations were performed on chemically-induced squamous cell carcinoma tumors in the hamster cheek pouch at injection rates of 0.

Therapeutic efficacy was again quantified as normalized tumor volume reduction which is defined as tumor volume 7 days after the treatment divided by the initial tumor volume before treatment. Thus, the injected volumes of both ethanol and ethyl cellulose-ethanol were reduced from four times the tumor volume used for ethanol, Fig. The needle was placed approximately 4 mm deep in the center of the tumor. Representative images shown in Fig. The time courses of tumor response to ethanol or ethyl cellulose-ethanol ablation are shown in Fig. Individual tumor responses are shown in Supplementary Figure 2. Normalized tumor volume at day 7 depended on both injection rate and ethyl cellulose concentration Fig.

The high variability in these average values likely reflects the varying properties of the tumors and their varying biological responses to the injection rates. These findings demonstrated that the combination of a moderate injection rate with the addition of ethyl cellulose provided the greatest treatment efficacy. To determine whether the differences in tumor regression were due to increased cytotoxicity of ethyl cellulose-ethanol, a cell viability study comparing the two different injection media was performed. No significant difference was found in the viability of HeLa cells treated with ethanol vs. Therapeutic efficacy of enhanced ethanol ablation depends on ethyl cellulose concentration and rate.

Scale bar is 6 mm. Normalized tumor volume is defined as tumor volume at specified time point divided by initial volume. Each cytotoxicity condition was repeated 8 times. We hypothesized that therapeutic efficacy would be strongly dependent on the distribution volume of the injected solution within the tumor, which governs the number of malignant cells contacted. There was a strong correlation between in vivo therapeutic efficacy quantified here as 1- normalized tumor volume at day 7 and injection rate for ethyl cellulose-ethanol Fig. The correlation between efficacy and distribution volume was not significant for ethanol only solution Fig.

Such vascular clearance was not embodied in the mechanical phantoms, causing divergence of the in vivo animal and in vitro phantom results shaded area in Fig. In vivo tumor ablations and in vitro tissue phantom distribution volumes have comparable results. In vivo therapeutic efficacy is defined as 1 — normalized tumor volume at day 7. In vitro tissue phantom distribution volumes were measured at rates used for the in vivo tumor ablations. The shaded area represents the injection rates that are approximately equal to the vascular clearance rates, likely reducing the accumulation rate within the tumor. This was pursued through modification of ethanol ablation, an existing tumor ablation procedure entailing direct injection of ethanol into a tumor to induce necrosis.

That technique was pioneered as a surgical alternative for treating hepatocellular carcinomas, with 5-year survival rates comparable to surgical resection It has achieved widespread success in applications to multiple tumor types 16 , 19 , 20 , 21 , Further, it has diminished efficacy in treating tumors not surrounded by fibrous capsules Our enhanced ethanol ablation strategy retains ethanol at the injection site via addition of ethyl cellulose, a water-insoluble and ethanol-soluble cellulose-derivative.

During injection into a tumor, this mixture undergoes a solution-to-gel sol-gel phase transition, as it is exposed to water. We first determined the optimal formulation based on gel formation rates as a function of water and ethyl cellulose concentration. Then we optimized the injection rate to maximize retained injection volume, using tissue-simulating phantoms. Finally we evaluated the method in vivo , using chemically-induced squamous cell carcinoma tumors in the hamster cheek pouch This animal model provides a high degree of similarity to human primary tumors, particularly those of the cervix and head and neck Historically, ethanol ablation has performed substantially worse in tumors not surrounded by fibrous capsules Thus, treatment of protruding epithelial tumors presented a challenge to our procedure, since they are not surrounded by tissue.

This renders them highly susceptible to leakage of the injected solution away from the injection site. This new approach is clearly more effective in reducing tumor volume and in reducing the overall injection volume of ethanol. The addition of ethyl cellulose significantly increased therapeutic efficacy, we suggest, for two reasons: 1 the decrease of injected liquid that leaked out of the tumor, likely due to increased viscosity of the injection medium; and 2 the increased retention within the tumor due to the formation of an ethanol-based gel upon exposure to the aqueous tumor environment.

Our tissue-mimicking mechanical phantom experiments showed that ethyl cellulose-ethanol solutions exhibited lower backflow rates up the injection pathway and out of the phantom than pure ethanol Fig. The reduction of backflow effectively increased the volume of solution delivered to the tumor. In treatment of percutaneous tumors e. Further, ethyl cellulose-ethanol gel formation in an aqueous medium enabled a lower volume of ethanol to access and treat the entire tumor volume, by increasing retention within the tumor.

Further, it is possible that this enhanced retention of ethyl cellulose-ethanol slowed clearance into the vasculature, which could diminish unintended side effects of ethanol on surrounding tissue. We analyzed the conjoint effects of injection rate and ethyl cellulose concentration on therapeutic efficacy Fig. Our data from in vitro and in vivo models extend previous reports of the non-linear relationships between intratumoral injection rate and retention Lowering injection rate decreases pressure, which may decrease both the likelihood of backflow and also of crack formation in the heterogenous tumor structure that may induce leakage into surrounding tissue Mitigating these sources of leakage will result in increased tumor retention of ethanol and, therefore, increased therapeutic efficacy.

Low-rate injections 0. A similar trend was observed for the distribution volume of ethyl cellulose-ethanol, but not pure ethanol, as measured in the tissue-mimicking phantom. A possible explanation is that low-rate ethyl cellulose-ethanol injections do not generate enough pressure to push the newly-formed gel through the porous structures of the tissue-mimicking phantom or the tumor. In contrast, since ethanol does not induce gel formation upon contact with the aqueous environment, low-rate ethanol injections had a comparable distribution volume to medium-rate injections.

In vivo , these low-rate ethanol injections may have been ineffective because accumulation in the tumor decreased as the injection rate approached the vascular clearance rate. Of course, there was no vascular clearance in the phantoms. Such clearance may have contributed to poorer performance by ethanol within tumors, as seen in Fig. Ethyl cellulose has previously been used to treat venous malformations. Here, injections were performed manually and 5. This led to significantly less pain than for pure ethanol injection, without systemic side effects 38 , Our results expand on the initial success of those encouraging pilot clinical studies by focusing on solid tumors rather than vasculature.

Previous clinical studies that report spontaneous resorption of ethyl cellulose corroborate these findings 38 , Degradation and resorption of ethyl cellulose would limit vascular occlusion in other parts of the body. Such reduction in the injection volume, coupled with the linear relationship between injection volume and distribution volume in vitro Fig. In contrast, the volume of necrosis induced by thermal ablative techniques is limited by the amount of energy that can be deposited without boiling tissue and therefore reducing thermal conductivity and the loss of heat due to tissue perfusion In this context, enhanced ethanol ablation is an attractive tumor ablation modality.

Since there was a high level of agreement between in vitro distribution volume and in vivo tumor volume reduction for ethyl cellulose-ethanol injections in our study, we propose that use of mechanical phantoms can contribute to expanded optimization of enhanced ethanol ablation procedures. Although we have demonstrated the efficacy of enhanced ethanol ablation in the treatment of squamous cell carcinomas in the hamster cheek pouch, there are several limitations to this study.

First, the use of a chemically-induced tumor model in which spontaneous tumors arising in sites adjacent to a treated site would be indistinguishable from the original tumor precluded the possibility of any long-term monitoring of tumor recurrence. Second, a single animal tumor model was utilized. Further study in other tumor models is needed to investigate such recurrence, and demonstrate therapeutic efficacy more broadly. Since this study was a proof-of-concept, sample sizes were relatively low. Although other studies have shown systemic safety of ethanol ablation in a variety of applications 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , more research is needed to investigate the possibility of damage to surrounding tissue. Leakage of ethanol and nearby necrosis should be minimized, and details may be specific to tumor types.

Although ethyl cellulose-ethanol has been used in the treatment of venous malformations 38 , further safety evaluations of injections to tumors are clearly necessary. The ethanol-ethyl cellulose-water system has shown promise; but its more complete characterization will inform optimization. For example, better understanding of physicochemical details of the sol-gel transition, e. The mechanical phantoms proved helpful in this initial study. Follow up use of them can improve details of their poroelastic structures and properties, and thus improve their role in the design process for enhanced ethanol ablation. Overall, our results suggest that this enhanced version of ethanol ablation could be useful in the treatment of a number of malignancies.

Notably, breast cancer is the leading cause of cancer-related deaths in low-income countries 1 , and conventional ethanol ablation has been used to treat tumors up to 5 cm Thus, enhanced ethanol ablation might be suitable for treatment of palpable breast tumors. Application to cervical precancerous lesions is another example. Cryotherapy, the standard-of-care for cervical precancerous lesion treatment in resource-limited settings, is incapable of consistently treating advanced precancerous lesions 15 and requires hard-to-supply consumables Enhanced ethanol ablation is less expensive, does not require these consumables, and can treat a larger volume of tissue.

Given the general lack of accessibility to surgery or alternative tumor treatments in developing countries 7 and the promising results presented in this study, enhanced ethanol ablation is a promising method to meet the unmet clinical need of rising cancer mortality that challenges healthcare systems in developing countries. Ferlay, J. Int J Cancer , E—, doi: Torre, L. Global cancer statistics, CA Cancer J Clin 65 , 87—, doi: Article PubMed Google Scholar. Preker, A. Jamison et al. Kingham, T. Treatment of cancer in sub-Saharan Africa. Lancet Oncol 14 , e—, doi: Kushner, A. Addressing the Millennium Development Goals from a surgical perspective: essential surgery and anesthesia in 8 low- and middle-income countries.

Arch Surg , —, doi: Hagopian, A. The migration of physicians from sub-Saharan Africa to the United States of America: measures of the African brain drain. Hum Resour Health 2 , 17, doi: Meara, J. Global Surgery evidence and solutions for achieving health, welfare, and economic development. Lancet , —, doi: Martin, R. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol 17 , —, doi: Gervais, D. Radiofrequency ablation of renal cell carcinoma: part 1, Indications, results, and role in patient management over a 6-year period and ablation of tumors. Duncan, I. The Semm cold coagulator in the management of cervical intraepithelial neoplasia.

Clin Obstet Gynecol 26 , — Cold coagulation in the treatment of cervical intraepithelial neoplasia. Bjog-Int J Obstet Gy , —, doi: Article Google Scholar. Chen, J. Industry-academic partnerships: an approach to accelerate innovation. J Surg Res , —, doi: Tsu, V. Why the time is right to tackle breast and cervical cancer in low-resource settings. Bull World Health Organ 91 , —, doi: Mariategui, J. Comparison of depth of necrosis achieved by CO 2 - and N 2 O-cryotherapy. Int J Gynaecol Obstet , 24—26, doi: Sugiura N. Percutaneous intratumoral injection of ethanol under ultrasound imaging for treatment of small hepatocellular carcinoma. Acta Hepatol Jpn 21 Ryu, M. Therapeutic results of resection, transcatheter arterial embolization and percutaneous transhepatic ethanol injection in patients with hepatocellular carcinoma: a retrospective multicenter study.

Jpn J Clin Oncol 27 , — Sorajja, P. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation , —, doi: Solbiati, L. Percutaneous ethanol injection of parathyroid tumors under US guidance: treatment for secondary hyperparathyroidism. Radiology , —, doi: Jurgensen, C. EUS-guided alcohol ablation of an insulinoma. Gastrointest Endosc 63 , —, doi: Artifon, E. EUS-guided alcohol ablation of left adrenal metastasis from non-small-cell lung carcinoma. Gastrointest Endosc 66 , —, doi: DeWitt, J. EUS-guided alcohol ablation of metastatic pelvic lymph nodes after endoscopic resection of polypoid rectal cancer: the need for long-term surveillance.

Gastrointest Endosc 74 , —, doi: Kuang, M. Ethanol ablation of hepatocellular carcinoma Up to 5. Ebara, M. Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on year observation. J Hepatol 43 , —, doi: Huang, G. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study.

Ann Surg , 36—42 Heilo, A. Efficacy of ultrasound-guided percutaneous ethanol injection treatment in patients with a limited number of metastatic cervical lymph nodes from papillary thyroid carcinoma. J Clin Endocrinol Metab 96 , —, doi: Wang, Y. National Comprehensive Cancer Network NCCN guidelines advocate simple cholecystectomy as definitive treatment for patients with mucosal T1a disease and a negative CD margin; all other patients ie, those with involvement of muscle or beyond, a positive CD margin, or a positive cystic lymph node should undergo repeat operation for extended cholecystectomy which includes hepatic resection, lymphadenectomy and, possibly, bile duct excision Eil, et al.

Their clinical study focused on 25 women taking two TXA tablets three times a day and using a topical TXA agent twice a day, over a period of 2 months. The factors measured were pigmentation and erythema using a Mexameter to establish skin biopsies for eight volunteers before and for a period of 8 weeks post the treatment. The results of this study showed that there were no serious adverse events for the study period. However, improvements in kinematic gait parameters were not observed.

The QSE alone group showed significant improvement in all spatiotemporal parameters compared with the baseline along with improvements in kinematic gait parameters [4]. The effectiveness of Chinese massage therapy in patients with knee osteoarthritis OA was evaluated by measuring lower- limb gait parameters on A total of 20 women diagnosed with knee OA from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine in Shanghai between January and May There was no significant change in CT head imaging rates.

When examining a group of physicians who saw ten or more patients during the study, it was revealed that there was a slight significant difference in admission rate from pre-to-post. When evaluating the evidence of this article, it was stated to follow Syncope recommendations and has a high level of consensus. No patient partnerships were disclosed. This study took place at Mount Sinai Medical Center, an academic medical institution. Effectiveness of conventional treatment and herbal treatment in diabetic foot ulcer using Texas and Wagner wound scale 6. University of Texas wound classification of stage and grading scale helps to categories the wound for the purpose of treatment outcome.

This classification explains the advancement in the treatment of DFU. This scale is frequently used with good outcome with stage and grade of wounds. The wound with ischemia goes for gangrene; Charcot foot ends up with amputation. In this study there is improvement in wound healing effect in herbal treatment and in conventional treatment but the herbal treatment seems to be much better and cheaper on the economic burden of the patient. Jain, …show more content… In the conventional treatment group and in the herbal treatment group the stages were assessed in the pre-test and in the post-test, the post test 1 after 15 days and post test 2 after 30 days. There were significant changes in wound stage from ischemia and infection , and there was no ischemia and no infection.

This clearly showed that the herbal treatment was better than the conventional treatment. The Wagner scale of wound grading system the wound was classified in pre-test and post test one after 15 days and post test two after 30 days. The result showed there was no significant change in all three visits of both treatment groups. This Wagner tool result showed herbal treatment to be better but statistically not very. Show More.

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