Transient, Image-Guided Gel-dissection for Percutaneous Thermal Ablation.

Image-guided tumor ablative therapies are mainstay cancer treatment options, but often require intra-procedural protective tissue displacement to reduce the risk of collateral damage to neighboring organs. Standard of care (SoC) strategies, such as hydrodissection (fluidic injection), are limited by rapid diffusion of fluid and poor retention time, risking injury to adjacent organs, increased cancer recurrence rates from incomplete tumor ablations, and limited patient qualification. Herein, we developed "gel-dissection," a technique leveraging injectable hydrogels for longer-lasting, shapeable, and transient tissue separation, empowering clinicians with improved ablation operation windows and greater control. A rheological model was designed to understand and tune gel-dissection parameters. In swine models, gel-dissection achieved 24 times longer-lasting tissue separation dynamics compared to saline, with 40% less injected volume. Gel-dissection achieved anti-dependent dissection between free-floating organs in the peritoneal cavity and clinically significant thermal protection, with the potential to expand minimally invasive therapeutic techniques, especially across locoregional therapies including radiation, cryoablation, endoscopy, and surgery. This article is protected by copyright. All rights reserved.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.

Individualized Ultrasound-Guided Intervention Phantom Development, Fabrication, and Proof of Concept.

Commercial ultrasound vascular phantoms lack the anatomic diversity required for robust pre-clinical interventional device testing. We fabricated individualized phantoms to test an artificial intelligence enabled ultrasound-guided surgical robotic system (AI-GUIDE) which allows novices to cannulate deep vessels. After segmenting vessels on computed tomography scans, vessel cores, bony anatomy, and a mold tailored to the skin contour were 3D-printed. Vessel cores were coated in silicone, surrounded in tissue-mimicking gel tailored for ultrasound and needle insertion, and dissolved with water. One upper arm and four inguinal phantoms were constructed. Operators used AI-GUIDE to deploy needles into phantom vessels. Two groin phantoms were tested due to imaging artifacts in the other two phantoms. Six operators (medical experience: none, 3; 1-5 years, 2; 5+ years, 1) inserted 27 inguinal needles with 81% (22/27) success in a median of 48 seconds. Seven operators performed 24 arm injections, without tuning the AI for arm anatomy, with 71% (17/24) success. After excluding failures due to motor malfunction and a defective needle, success rate was 100% (22/22) in the groin and 85% (17/20) in the arm. Individualized 3D-printed phantoms permit testing of surgical robotics across a large number of operators and different anatomic sites. AI-GUIDE operators rapidly and reliably inserted a needle into target vessels in the upper arm and groin, even without prior medical training. Virtual device trials in individualized 3-D printed phantoms may improve rigor of results and expedite translation.Clinical Relevance- Individualized phantoms enable rigorous and efficient evaluation of interventional devices and reduce the need for animal and human subject testing.

Preventing inadvertent drain removal using a novel catheter securement device.

Percutaneous drains have provided a minimally invasive way to treat a wide range of disorders from abscess drainage to enteral feeding solutions to treating hydronephrosis. These drains suffer from a high rate of dislodgement of up to 30% resulting in emergency room visits, repeat hospitalizations, and catheter repositioning/replacement procedures, which incur significant morbidity and mortality. Using ex vivo and in vivo models, a force body diagram was utilized to determine the forces experienced by a drainage catheter during dislodgement events, and the individual components which contribute to drainage catheter securement were empirically collected. Prototypes of a skin level catheter securement and valved quick release system were then developed. The system was inspired by capstans used in boating for increasing friction of a line around a central spool and quick release mechanisms used in electronics such as the Apple MagSafe computer charger. The device was tested in a porcine suprapubic model, which demonstrated the effectiveness of the device to prevent drain dislodgement. The prototype demonstrated that the miniaturized versions of technologies used in boating and electronics industries were able to meet the needs of preventing dislodgement of patient drainage catheters.

Evaluation of paravertebral blocks in improving post-procedural pain and decreasing hospital admission after microwave ablation of liver tumors.

Although ablations are performed with conscious sedation or general anesthesia, microwave ablations can be painful post procedure. Newer analgesic modalities, including regional blocks, have promoted the proliferation of less invasive anesthesia care for ablative procedures. This study evaluates whether bilateral paravertebral blocks reduce the need for additional analgesics in comparison to unilateral blocks in microwave ablations. In this retrospective study, individuals undergoing microwave ablation who underwent unilateral versus bilateral nerve blocks at a single institution from 2017 to 2019 were compared. Categorical variables were analyzed using Pearson's chi-squared tests. Comparisons of means were completed using multiple T-tests corrected using the Holm-Sidak method with α = 0.05. Regression modeling was used to identify factors related to increased MME (milligram morphine equivalent) usage and post-procedure admission rates. A total of 106 patients undergoing 112 liver MWA procedures were included in this analysis, with patients receiving either a bilateral or unilateral block. Pre-procedural characteristics demonstrated no significant differences in age or gender. Bilateral blocks were associated with decreased usage of gabapentin (14% vs. 0%, p = 0.01) and a lower rate of post-procedure admissions (OR 0.23, p = 0.003). Therefore, when using paravertebral blocks, bilateral blocks are superior to unilateral blocks, as demonstrated by decreased rates of hospital admission and reduced use of systemic neuropathic pain medication. Additionally, reducing post-procedural MME may reduce the rate of admission to the hospital.

Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation.

BACKGROUND: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. METHODS: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. FINDINGS: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). CONCLUSION: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. FUNDING: This work was supported by K. Lisa Yang Center for Bionics at MIT.

Rate of True-Positive Findings of COVID-19 Typical Appearance at Chest CT per RSNA Consensus Guidelines in an Increasingly Vaccinated Population.

Background RSNA consensus guidelines for COVID-19-related chest CT are widely used but, to the knowledge of the authors, their rate of true-positive findings for COVID-19 pneumonia in vaccinated patients has not been assessed. Purpose To assess the rate of true-positive findings of typical appearance for COVID-19 at chest CT by using RSNA guidelines in fully vaccinated patients with polymerase chain reaction (PCR)-confirmed COVID-19 infection compared with unvaccinated patients. Materials and Methods Included were patients with COVID-19 who had typical appearance on chest CT images and one PCR test for COVID-19 with a positive result or two tests with negative results within 7 days of undergoing chest CT between January 2021 and January 2022 at a quaternary academic medical center. True-positive findings were defined as chest CT images interpreted as COVID-19 typical appearance and PCR-confirmed COVID-19 infection within 7 days. Logistic regression models were constructed to quantify the association between PCR results and vaccination status, vaccination status and COVID-19 variants, and vaccination status and number of months. Results Included were 652 patients (median age, 59 years; IQR, 48-72 years; 371 men [57%]) with CT scans classified as typical appearance. Of those patients, 483 (74%) were unvaccinated and 169 (26%) were fully vaccinated. The overall rate of true-positive findings on CT images rated as typical appearance was lower in vaccinated versus unvaccinated patients (70 of 169 [41%; 95% CI: 34, 49] vs 352 of 483 [73%; 95% CI: 69, 77]; odds ratio [OR], 3.8 [95% CI: 2.6, 5.5]; P < .001). Unvaccinated patients were more likely to have true-positive findings on CT images compared with fully vaccinated patients during the peaks of COVID-19 variants Alpha (OR, 16; 95% CI: 6, 42; P < .001) and Delta (OR, 8; 95% CI: 4, 16; P < .001), but no statistical differences were found during the peak of the Omicron variant (OR, 1.7; 95% CI: 0.3, 11; P = .56). Conclusion Fully vaccinated patients with confirmed COVID-19 breakthrough infections had lower rates of true-positive findings of COVID-19 typical appearance at chest CT. © RSNA, 2022 Supplemental material is available for this article.

Intubation and mortality prediction in hospitalized COVID-19 patients using a combination of convolutional neural network-based scoring of chest radiographs and clinical data.

Objective: To predict short-term outcomes in hospitalized COVID-19 patients using a model incorporating clinical variables with automated convolutional neural network (CNN) chest radiograph analysis. Methods: A retrospective single center study was performed on patients consecutively admitted with COVID-19 between March 14 and April 21 2020. Demographic, clinical and laboratory data were collected, and automated CNN scoring of the admission chest radiograph was performed. The two outcomes of disease progression were intubation or death within 7 days and death within 14 days following admission. Multiple imputation was performed for missing predictor variables and, for each imputed data set, a penalized logistic regression model was constructed to identify predictors and their functional relationship to each outcome. Cross-validated area under the characteristic (AUC) curves were estimated to quantify the discriminative ability of each model. Results: 801 patients (median age 59; interquartile range 46-73 years, 469 men) were evaluated. 36 patients were deceased and 207 were intubated at 7 days and 65 were deceased at 14 days. Cross-validated AUC values for predictive models were 0.82 (95% CI, 0.79-0.86) for death or intubation within 7 days and 0.82 (0.78-0.87) for death within 14 days. Automated CNN chest radiograph score was an important variable in predicting both outcomes. Conclusion: Automated CNN chest radiograph analysis, in combination with clinical variables, predicts short-term intubation and death in patients hospitalized for COVID-19 infection. Chest radiograph scoring of more severe disease was associated with a greater probability of adverse short-term outcome. Advances in knowledge: Model-based predictions of intubation and death in COVID-19 can be performed with high discriminative performance using admission clinical data and convolutional neural network-based scoring of chest radiograph severity.

Image-guided intratumoral immunotherapy: Developing a clinically practical technology.

Immunotherapy has revolutionized the contemporary oncology landscape, with durable responses possible across a range of cancer types. However, the majority of cancer patients do not respond to immunotherapy due to numerous immunosuppressive barriers. Efforts to overcome these barriers and increase systemic immunotherapy efficacy have sparked interest in the local intratumoral delivery of immune stimulants to activate the local immune response and subsequently drive systemic tumor immunity. While clinical evaluation of many therapeutic candidates is ongoing, development is hindered by a lack of imaging confirmation of local delivery, insufficient intratumoral drug distribution, and a need for repeated injections. The use of polymeric drug delivery systems, which have been widely used as platforms for both image guidance and controlled drug release, holds promise for delivery of intratumoral immunoadjuvants and the development of an in situ cancer vaccine for patients with metastatic cancer. In this review, we explore the current state of the field for intratumoral delivery and methods for optimizing controlled drug release, as well as practical considerations for drug delivery design to be optimized for clinical image guided delivery particularly by CT and ultrasound.

Predictors for Nonhome Patient Discharge following Lower Extremity Arterial Interventions.

PURPOSE: To identify the variables associated with patient discharge disposition to optimize postprocedural care and discharge planning following lower extremity arterial interventions for peripheral artery disease (PAD). MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried using current procedural terminology codes for endovascular infrainguinal interventions for PAD. The main outcome variable of interest was nonhome discharge. Covariates included patient sociodemographic variables, age quartile (upper quartile, ≥77 years), comorbidities (diabetes, renal disease, bleeding disorder, congestive heart failure [CHF], and chronic obstructive pulmonary disease), presence of an open wound before a procedure, type of procedure, operative time, symptom severity, American Society of Anesthesiologists class, and baseline functional status. Univariate analysis and multivariate logistic regression were performed on Stata/SE 15.1. RESULTS: A total of 3,190 patients met the inclusion criteria, of whom 664 (20.8%) had nonhome discharge. Multivariate regression revealed that age (odds ratio [OR], 1.9 for the upper age quartile [>77 years]; 95% confidence interval [CI], 1.46-2.50), operative time (OR, 1.2 per increase in quartile; 95% CI, 1.09-1.30), preoperative wound (OR, 1.5; 95% CI, 1.24-1.90), renal failure (OR, 1.7; 95% CI, 1.30-2.14), CHF (OR, 2.2; 95% CI, 1.51-3.24), symptom severity (OR, 1.7; 95% CI, 1.46-1.98), and independent functional status (OR, 0.74; 95% CI, 0.59-0.92; P = .007) were associated with nonhome discharge. All P values were ≤.001 unless otherwise stated. CONCLUSIONS: Prolonged procedural time, the presence of preprocedural wound and patient comorbidities, symptomatology, and baseline functional status may be used to identify patients who will require a nonhome discharge and early discharge planning.

Utility of the RENAL Nephrometry Scoring System in Predicting Adverse Events and Outcomes of Percutaneous Microwave Ablation of Renal Tumors.

PURPOSE: To assess the utility of the radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines (RENAL) nephrometry scoring system at predicting adverse events and outcomes in percutaneous microwave ablation (MWA) of renal tumors. MATERIALS AND METHODS: A retrospective review of 116 patients who underwent MWA from 2004 to 2018 at 2 large university hospitals was conducted. Patient demographics and tumor characteristics were collected. The RENAL nephrometry scores were calculated, and procedure-related adverse events were stratified into minor and major (the Society of Interventional Radiology classification of class C or higher). Technical and oncologic outcomes were based on follow-up magnetic resonance imaging and computed tomography scans after ablation. RESULTS: The mean RENAL score was 6.6 (range, 4-11), and the mean tumor size was 24 mm. Follow-up ranged between 16 and 161 weeks (median, 50 weeks; mean, 65 weeks). Oncologic control was achieved in 96% (n = 111) of patients. The major and minor adverse event rates were 8.6% (n = 10) and 17% (n = 19), respectively. The mean RENAL score for patients with recurrent and/or residual tumor (8.2 ± 2.7) was higher than that for patients without disease recurrence (6.5 ± 3.5, P = .05). However, in a multivariate analysis, the RENAL score was not found to be an independent predictor of oncologic outcomes (odds ratio, 1.548; P = .092). CONCLUSIONS: The RENAL nephrometry score has minimal utility for predicting outcomes and adverse events in MWA of renal tumors. The inconsistent nature of RENAL nephrometry scoring in percutaneous ablation procedures underscores the need for an ablation-specific risk stratification system.

Lung-RADS Category 3 and 4 Nodules on Lung Cancer Screening in Clinical Practice.

BACKGROUND. Lung-RADS category 3 and 4 nodules account for most screening-detected lung cancers and are considered actionable nodules with management implications. The cancer frequency among such nodules is estimated in the Lung-RADS recommendations and has been investigated primarily by means of retrospectively assigned Lung-RADS classifications. OBJECTIVE. The purpose of this study was to assess the frequency of cancer among lung nodules assigned Lung-RADS category 3 or 4 at lung cancer screening (LCS) in clinical practice and to evaluate factors that affect the cancer frequency within each category. METHODS. This retrospective study was based on review of clinical radiology reports of 9148 consecutive low-dose CT LCS examinations performed for 4798 patients between June 2014 and January 2021 as part of an established LCS program. Unique nodules assigned Lung-RADS category 3 or 4 (4A, 4B, or 4X) that were clinically categorized as benign or malignant in a multidisciplinary conference that considered histologic analysis and follow-up imaging were selected for further analysis. Benign diagnoses based on stability required at least 12 months of follow-up imaging. Indeterminate nodules were excluded. Cancer frequencies were evaluated. RESULTS. Of the 9148 LCS examinations, 857 (9.4%) were assigned Lung-RADS category 3, and 721 (7.9%) were assigned category 4. The final analysis included 1297 unique nodules in 1139 patients (598 men, 541 women; mean age, 66.0 ± 6.3 years). A total of 1108 of 1297 (85.4%) nodules were deemed benign, and 189 of 1297 (14.6%) were deemed malignant. The frequencies of malignancy of category 3, 4A, 4B, and 4X nodules were 3.9%, 15.5%, 36.3%, and 76.8%. A total of 45 of 46 (97.8%) endobronchial nodules (all category 4A) were deemed benign on the basis of resolution. Cancer frequency was 13.1% for solid, 24.4% for part-solid, and 13.5% for ground-glass nodules. CONCLUSION. In the application of Lung-RADS to LCS clinical practice, the frequency of Lung-RADS category 3 and 4 nodules and the cancer frequency in these categories were higher than the prevalence and cancer risk estimated for category 3 and 4 nodules in the Lung-RADS recommendations and those reported in earlier studies in which category assignments were retrospective. Nearly all endobronchial category 4A nodules were benign. CLINICAL IMPACT. Future Lung-RADS iterations should consider the findings of this study from real-world practice to improve the clinical utility of the system.

Assessing Public Interest in Elective Surgery During the COVID-19 Pandemic: A Google Trends Analysis.

Objective: To determine trends in internet search volume for elective surgery terms during the first peak of the coronavirus disease 2019 (COVID-19) pandemic using Google Trends data. Background: Postponement of much-needed elective and urgent oncologic surgeries takes a toll on patients and the health care system. The COVID-19 pandemic has led to a decline in elective surgery volume, partially due to the cancellation of elective surgeries at the start of the pandemic. Methods: We performed a cross-sectional analysis of internet search volume trends for elective surgery terms during the first peak of the COVID-19 pandemic using Google Trends data and compared to a control group of terms representing common urgent and oncologic surgeries. Results: Search volume for elective surgery terms ("knee replacement," "spinal fusion," "hip replacement," "laminectomy," "cataract surgery") revealed a decrease of up to 54% compared to the prepandemic period, a significantly greater decrease than search volume for urgent and oncologic surgery terms ("C-section," "cholecystectomy," "CABG," "colectomy," "lobectomy," and "mastectomy"). Conclusions: The first phase of the COVID-19 pandemic led to sharp declines in search volume for essential elective surgical procedures, which may have been partially due to the cancellation of elective surgeries, but patient factors such as a temporary decline in interest in elective surgery might have also played a role. Attention to internet search volume may be used during future public health crises to monitor public engagement and interest in important health topics, including preventive health measures such as cancer screening.

Microwave Ablation as Bridging Therapy for Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: A Single Center Experience.

PURPOSE: To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests. RESULTS: The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively). CONCLUSIONS: Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma. CEBM LEVEL OF EVIDENCE: Level 3, non-randomized controlled cohort study/follow-up study.