Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.
Hepatosplenomegaly is commonly diagnosed by radiologists based on single dimension measurements and heuristic cut-offs. Volumetric measurements may be more accurate for diagnosing organ enlargement. Artificial intelligence techniques may be able to automatically calculate liver and spleen volume and facilitate more accurate diagnosis. After IRB approval, 2 convolutional neural networks (CNN) were developed to automatically segment the liver and spleen on a training dataset comprised of 500 single-phase, contrast-enhanced CT abdomen and pelvis examinations. A separate dataset of ten thousand sequential examinations at a single institution was segmented with these CNNs. Performance was evaluated on a 1% subset and compared with manual segmentations using Sorensen-Dice coefficients and Pearson correlation coefficients. Radiologist reports were reviewed for diagnosis of hepatomegaly and splenomegaly and compared with calculated volumes. Abnormal enlargement was defined as greater than 2 standard deviations above the mean. Median Dice coefficients for liver and spleen segmentation were 0.988 and 0.981, respectively. Pearson correlation coefficients of CNN-derived estimates of organ volume against the gold-standard manual annotation were 0.999 for the liver and spleen (P < 0.001). Average liver volume was 1556.8 ± 498.7 cc and average spleen volume was 194.6 ± 123.0 cc. There were significant differences in average liver and spleen volumes between male and female patients. Thus, the volume thresholds for ground-truth determination of hepatomegaly and splenomegaly were determined separately for each sex. Radiologist classification of hepatomegaly was 65% sensitive, 91% specific, with a positive predictive value (PPV) of 23% and an negative predictive value (NPV) of 98%. Radiologist classification of splenomegaly was 68% sensitive, 97% specific, with a positive predictive value (PPV) of 50% and a negative predictive value (NPV) of 99%. Convolutional neural networks can accurately segment the liver and spleen and may be helpful to improve radiologist accuracy in the diagnosis of hepatomegaly and splenomegaly.
The coronavirus disease 2019 (COVID-19) pandemic has led to substantial disruptions in healthcare staffing and operations. Stay-at-home (SAH) orders and limitations in social gathering implemented in spring 2020 were followed by initial decreases in healthcare and imaging utilization. This study aims to evaluate the impact of subsequent easing of SAH on trauma volumes, demand for, and turnaround times for trauma computed tomography (CT) exams, hypothesizing that after initial decreases, trauma volumes have increased as COVID safety measures have been reduced.Patient characteristics, CT imaging volumes, and turnaround time were analyzed for all adult activated emergency department trauma patients requiring CT imaging at a single Level-I trauma center (1/2018-2/2022) located in the sixth most populous county in the USA. Based on COVID safety measures in place in the state of California, three time periods were compared: baseline (PRE, 1/1/2018-3/19/2020), COVID safety measures (COVID, 3/20/2020-1/25/2021), and POST (1/26/2021-2/28/2022).There were 16,984 trauma patients across the study (PRE = 8289, COVID = 3139, POST = 5556). The average daily trauma patient volumes increased significantly in the POST period compared to the PRE and COVID periods (13.9 vs. 10.3 vs. 10.1, p < 0.001), with increases in both blunt (p < 0.001) and penetrating (p = 0.002) trauma. The average daily number of trauma CT examinations performed increased significantly in the POST period compared to the PRE and COVID periods (56.7 vs. 48.3 vs. 47.6, p < 0.001), with significant increases in average turnaround time (47 min vs. 31 and 37, p < 0.001).After initial decreases in trauma radiology volumes following stay-at-home orders, subsequent easing of safety measures has coincided with increases in trauma imaging volumes above pre-pandemic levels and longer exam turnaround times.
e16548 Background: Early characterization of renal cell carcinoma (RCC) is pertinent for cancer prognosis and patient treatment. However, characterization of renal masses as benign or malignant on computed tomography (CT) remains a difficult clinical challenge. Angiogenesis plays a major role in RCC progression and assessing neovascularity in tumor-burdened kidneys with Re-VASC scoring has been shown to aptly predict tumor pathology and staging. In the current study, we evaluated if Re-VASC can reliably differentiate between malignant T1a ( < 4cm) RCC and benign T1a renal masses. Methods: All eligible patients had a diagnosis of T1a from pathologic or clinical evaluation. The inclusion criteria for malignant masses included a diagnosis of RCC by pathology after partial or radical nephrectomy. Our T1a benign group was comprised of patients with a diagnosis of a non-malignant renal mass (angiomyolipoma or oncocytoma) established via histopathology or CT imaging (fat containing lesions). Re-VASC score was calculated on axial preoperative contrast enhanced CT utilizing the system described below: 0 = No visible neovascularization 1 = visualized single new vessel < 3mm in diameter 2 = visualized single new vessel ≥3mm in diameter 3 = visualized multiple new vessels < 3mm in diameter 4 = visualized multiple new vessels and at least one vessel ≥3mm in diameter. Results: A total of 64 benign and 69 malignant T1a tumors were included. Comparison of the two groups demonstrated no significant differences with regards to age, sex, ASA, and BMI. The average Re- VASC scores was 0.159 and 0.753 for benign and malignant masses respectively (p < 0.001). Additionally, the tumor size for benign masses was 2.373 and for malignant masses was 2.546 (p = 0.210). There was no significant difference in Re-VASC score between the contralateral kidneys of malignant and benign kidney masses (p < 0.508). Additionally, the sensitivity, specificity and positive predictive values were 26%, 86% and 74% respectively, when utilizing a Re-VASC score of 1 as a cutoff for malignancy. Conclusions: Our results show a significantly higher Re-VASC score in T1a malignant tumors and T1a benign tumors. While biopsy remains the gold standard for confirmation of malignant tumors such as RCC, radiological evaluation with tumor scoring systems like Re-VASC may offer a useful clinical decision-making tool in a less-invasive manner. Because renal biopsy carries non-negligible risk of complications, reducing volume of biopsies among low-risk patients may lead to better overall care. The Re-VASC score shows potential as a confirmatory test with a specificity of 86%. We would like to apply the Re-VASC score to an expanded multi-center trial, in order to assess its translatability to the general population.
Purpose: Early characterization of small (T1a, <4 cm) renal masses is imperative for patient care and treatment planning. Renal biopsy is a sensitive and specific procedure that can accurately differentiate small renal masses as malignant or benign. However, it is an invasive procedure with a nonnegligible complication rate and is not performed routinely at most institutions. In this study, we sought to apply the Retroperitoneal Vascularity Assessment and Scoring in Carcinoma (Re-VASC) scoring system to T1a renal masses and analyzed whether it could differentiate these masses as benign or malignant. Methods: We obtained Institutional Review Board approval to retrospectively examine the records of all patients who presented to our single, urban academic referral center for surgical treatment of renal cell carcinoma (RCC). For the malignant group, patients with a diagnosis of T1a RCC from pathologic evaluation were included. Additionally, patients with a histopathological diagnosis of a T1a nonmalignant renal mass (fat poor-angiomyolipoma or oncocytoma) were included in our benign group. Results: This study includes 57 benign and 69 malignant T1a renal tumors. Average size for benign and malignant masses were 2.47 and 2.63, respectively (p = 0.267). Analysis demonstrated no significant difference between both groups in terms of sex, laterality, or size. The average Re-VASC score of benign and malignant masses was 0.175 and malignant masses was 0.784, respectively (p < 0.001). Additionally, the Re-VASC score was independently associated with malignancy with an odds ratio of 2.223 (p = 0.0109). Conclusion: The Re-VASC scoring system exhibits significantly greater values for malignant T1a renal masses when compared to benign masses. As a result, it shows promise as an adjunctive tool to renal biopsy for clinical decision-making. Further assessment of Re-VASC's true efficacy as a diagnostic marker will include prospective evaluation of a larger multicenter population.
Abstract In the era of post-COVID19, access for non-essential personnel to shadow physicians in hospitals has become increasingly difficult; combined with rapidly increasing biomedical engineering class sizes across the country, opportunities for undergraduate students to experience critically formative clinical immersion is scarce if not impossible. In order to remain competitive in the medical device landscape, biomedical engineering undergraduate students must be adequately trained to identify and unpack clinical needs through observation and experience. However, this task has become more difficult given the challenges remote learning presents to unmet clinical needs finding. Hence, there is a clear need to develop technological solutions to not only satisfy such educational demands, but also enhance the student experience by developing a more robust and effective remote learning apparatus. To address medical center accessibility issues, the Department of Biomedical Engineering (BME) at the University of California Irvine (UCI) are initiating a virtual reality (VR) clinical immersion program for undergraduate BME juniors prior to taking their senior capstone design course. Our laboratory has developed VR immersive clinical environments, physician interviews, and in class reverse engineering learning modules to give all students the opportunity to learn how to find and screen unmet clinical needs in the medical field of their interest in a hybrid course format. In collaboration with UCI School of Medicine and Medical Center, we have developed several virtual reality environments for the following procedures: colon and rectal surgeries, neurophysiological procedures, physical therapy and rehabilitation, urology, ophthalmology, plastic surgeries, cardiovascular surgeries, transplant surgeries, and orthopedic surgeries. Furthermore, we have also developed physician training immersive clinical environments for various hospital coding procedures through filming of simulation procedures during medical student training at the UCI Medical Education Simulation Center. This center provides a full-scale operating room, emergency room trauma bay, and a critical care unit; and, it is equipped with a real-time simulation dummy that can mimic real-world use cases seen in the emergency room. Employing a head-mounted camera (Sony FDR x-3000) worn by the primary physician and two 180-degree cameras (Insta360 Evo), we have combined the two recordings to create immersive virtual tours of these procedures consisting of a 360-degree panoramic view of the environment with a visualization of the physician's first-person perspective. By hosting our videos on YouTube and our interactive experiences on own website, all our students will be able to access the content through any computer, tablet, smartphone, or VR device that has access to a web browser. Additionally, students will be able to check out Oculus Quests and Google Cardboard headsets from our Science Library.
Abstract Background Patients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer. Case presentation The patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized. Conclusions Although not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation.
