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Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.

ABSTRACT: Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1-4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

SUBMITTER: Chelales E

PROVIDER: S-EPMC8526742 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.

Chelales Erika E Morhard Robert R Nief Corrine C Crouch Brian B Everitt Jeffrey I JI Sag Alan Alper AA Ramanujam Nirmala N

Scientific reports 20211019 1

Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, i ...[more]

PMID: 34667252

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Project description:PurposeTo determine whether computed tomographic (CT) attenuation values correlate with the histologic measurements of a lung cancer manifesting as a nonsolid nodule and to quantify the extent to which the tumor replaces the airspace within the nodule.Materials and methodsInformed consent was obtained to analyze images from CT and pathologic examination under an institutional review board-approved protocol. Fifteen patients who had undergone resection of nonsolid lung cancer were evaluated. On the basis of the CT attenuation values of nonsolid nodules, nonneoplastic lung, soft tissue, and air, the overall proportion of soft tissue in the nodule and nonneoplastic lung and the difference between these two measures were calculated. The analogous measures were obtained from a representative digitized histologic slide. The area of each nodule and the proportion of air within it were measured, and the proportion of soft tissue in the nodule and nonneoplastic lung and the difference between the two were calculated. The difference between the two proportions at CT and histologic examination are the proportions attributable to the cancer on the basis of CT and histologic examinations, respectively. Linear regression was performed to assess the relationship between these measures.ResultsThe average proportions of soft tissue in the nodule at CT and histologic examination were 48% and 69%, respectively, and they showed significant correlation with each other (P = .02); in addition, each showed significant correlation with the attenuation of the nodule (P < .0001 and P = .02, respectively). The difference between the proportions of soft tissue in nodule and nonneoplastic lung at CT and histologic examination were 37% and 30%, respectively, and both were independent of the tumor diameter (P = .26 and P = .41).ConclusionThe proportion of soft tissue within a nonsolid nodule is correlated with attenuation at CT. This allows for measurement of change within the nodule. An increase of 100 HU in nodule attenuation represents an approximately 10% increase in tumor volume.

Project description:ImportanceIt is currently unclear whether high-resolution computed tomography can preoperatively identify pathologic tumor invasion for ground-glass opacity lung adenocarcinoma.ObjectivesTo evaluate the diagnostic value of high-resolution computed tomography for identifying pathologic tumor invasion for ground-glass opacity featured lung tumors.Design, setting, and participantsThis prospective, multicenter diagnostic study enrolled patients with suspicious malignant ground-glass opacity nodules less than or equal to 30 mm from November 2019 to July 2021. Thoracic high-resolution computed tomography was performed, and pathologic tumor invasion (invasive adenocarcinoma vs adenocarcinoma in situ or minimally invasive adenocarcinoma) was estimated before surgery. Pathologic nonadenocarcinoma, benign diseases, or those without surgery were excluded from analyses; 673 patients were recruited, and 620 patients were included in the analysis. Statistical analysis was performed from October 2021 to January 2022.ExposurePatients were grouped according to pathologic tumor invasion.Main outcomes and measuresPrimary end point was diagnostic yield for pathologic tumor invasion. Secondary end point was diagnostic value of radiologic parameters.ResultsAmong 620 patients (442 [71.3%] female; mean [SD] age, 53.5 [12.0] years) with 622 nodules, 287 (46.1%) pure ground-glass opacity nodules and 335 (53.9%) part-solid nodules were analyzed. The median (range) size of nodules was 12.1 (3.8-30.0) mm; 47 adenocarcinomas in situ, 342 minimally invasive adenocarcinomas, and 233 invasive adenocarcinomas were confirmed. Overall, diagnostic accuracy was 83.0% (516 of 622; 95% CI, 79.8%-85.8%), diagnostic sensitivity was 82.4% (192 of 233; 95% CI, 76.9%-87.1%), and diagnostic specificity was 83.3% (324 of 389; 95% CI, 79.2%-86.9%). For tumors less than or equal to 10 mm, 3.6% (8 of 224) were diagnosed as invasive adenocarcinomas. The diagnostic accuracy was 96.0% (215 of 224; 95% CI, 92.5%-98.1%), diagnostic specificity was 97.2% (210 of 216; 95% CI, 94.1%-99.0%); for tumors greater than 20 mm, 6.9% (6 of 87) were diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas. The diagnostic accuracy was 93.1% (81 of 87; 95% CI, 85.6%-97.4%) and diagnostic sensitivity was 97.5% (79 of 81; 95% CI, 91.4%-99.7%). For tumors between 10 to 20 mm, the diagnostic accuracy was 70.7% (220 of 311; 95% CI, 65.3%-75.7%), diagnostic sensitivity was 75.0% (108 of 144; 95% CI, 67.1%-81.8%), and diagnostic specificity was 67.1% (112 of 167; 95% CI, 59.4%-74.1%). Tumor size (odds ratio, 1.28; 95% CI, 1.18-1.39) and solid component size (odds ratio, 1.31; 95% CI, 1.22-1.42) could each independently serve as identifiers of pathologic invasive adenocarcinoma. When the cutoff value of solid component size was 6 mm, the diagnostic sensitivity was 84.6% (95% CI, 78.8%-89.4%) and specificity was 82.9% (95% CI, 75.6%-88.7%).Conclusions and relevanceIn this diagnostic study, radiologic analysis showed good performance in identifying pathologic tumor invasion for ground-glass opacity-featured lung adenocarcinoma, especially for tumors less than or equal to 10 mm and greater than 20 mm; these results suggest that a solid component size of 6 mm could be clinically applied to distinguish pathologic tumor invasion.

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Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.

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Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose.

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