3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model

Background & Aims Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. Methods Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. Results ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. Conclusions EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis.National Cancer Institute (U.S.) (CA140861)National Institutes of Health. National Institute for Biomedical Imaging and Bioengineering (EB009062)Sanofi Aventis (Firm

Liver-directed treatments of liver-dominant metastatic leiomyosarcoma

PURPOSEThe purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation.METHODSThis is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation. DEB-TACE was performed using 70–150 or 100–300 µ doxorubicin-loaded drug-eluting LC beads. Radioembolization was performed using Y90 glass microspheres. Electronic medical records were retrospectively reviewed to evaluate clinical and biochemical toxicities, tumor response on imaging, overall survival (OS), and liver progression-free survival (PFS).RESULTSA total of 24 patients with metastatic leiomyosarcoma to the liver who underwent liver-directed treatment were identified (8 males, 16 females; average age, 62.8±11.4 years). Of these patients, 13 underwent DEB-TACE, 6 underwent Y90, and 5 underwent ablation. Three patients received a combination of treatments: one received Y90 followed by DEB-TACE, one received ablation followed by DEB-TACE, and one received ablation followed by Y90. Of the 24 patients, 19 received prior chemotherapy. At 3-month follow-up, grade 1 or 2 lab toxicities were found in 20 patients; 3 patients had grade 3 toxicities. A grade 3 clinical toxicity was reported in one patient. MELD score was 7.5±1.89 at baseline and 8.8±4.2 at 3 months. Median OS was 59 months (95% CI, 39.8–78.2) from diagnosis, 27 months (95% CI, 22.9–31.0) from development of liver metastasis, and 9 months (95% CI, 0–21.4) from first liver-directed treatment. Median liver PFS was 9 months (95% CI, 1.4–16.6).CONCLUSIONTreatment with liver-directed therapies for patients with unresectable metastatic leiomyosarcoma to the liver is safe and can improve overall survival, with OS after liver-directed therapy being similar to patients who underwent surgical resection

Stress, anxiety, and illness perception in patients experiencing delay in operative care due to the COVID-19 pandemic

Background: Amid the height of the COVID-19 pandemic in the US, the US Surgeon General ordered hospitals and healthcare systems to stop all elective surgical procedures. The aim of our study was to evaluate the additional mental health impact of surgical delay on patients awaiting surgery for benign, pre-malignant and malignant conditions within the context of the COVID-19 pandemic. Study design: All patients over the age of 18 awaiting surgery for benign, pre-malignant or malignant conditions within the gynecologic oncology, surgical oncology and colorectal services across Northwell Health were eligible for participation. Upon successful enrollment, participants completed a baseline questionnaire consisting of the Generalized Anxiety Disorder Questionnaire, the Penn State Worry Questionnaire, and Brief-Illness Patient Questionnaire. Results: The surgical delay was considered moderately to extremely concerning by 72 % of survey respondents, with one third indicating the highest (10/10) level of concern. Fifty-five percent of patients with a pre-operatively suspected/confirmed cancer or pre-malignant condition demonstrated mild to severe anxiety in their completion of the GAD-7 scale. The average time awaiting surgery was 117 days (range 8–292); and 63 % of respondents indicated that the delay had a moderate to severe impact on their daily life. Conclusions: Patients awaiting surgery for confirmed, suspected or pre-malignant conditions expressed decreased sense of control and increased levels of distress compared to patients awaiting procedures for benign conditions (p < 0.05, 95 % CI [-2.65, -0.08]). Future research will focus on the effects of COVID-19 related delays in operative care on clinical outcomes, including cancer morbidity and mortality

Novel Preoperative Patient-centered Surgical Wellness Program Impacts Length of Stay Following Pancreatectomy

Background/Aim: We created a novel, preoperative wellness program (WP) that promotes recovery. This study assessed its impact on patient outcomes after pancreatectomy. Patients and Methods: Pancreatoduodenectomies (PD) and distal pancreatectomies (DP) performed from 2015 to 2018 were reviewed using our institutional NSQIP database. Patients in the WP had their medical conditions optimized and were provided with the following: chlorhexidine, topical mupirocin, incentive spirometer, and immune-nutrition supplements. Results: Out of a total of 669 pancreatectomy patients (411 PD, 258 DP), 308 were enrolled in the WP (188 PD, 120 DP). In the PD subgroup, on multivariable analysis (MVA), the WP patients had shorter lengths of hospital stay (LOS) (12 vs. 10 days, p<0.001). On MVA, WP patients had less post-op transfusion (20 vs. 10%, p=0.027). For the combined groups on MVA, LOS continued to be significant (OR=0.89, 95%CI=0.82-0.97, p<0.007). Conclusion: A preoperative patient centered WP may reduce the length of stay