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The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation.Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 10All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 μm versus 643.55 IQR 560.91-733.88 μm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals.Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.

BACKGROUND There is an ongoing debate about whether neoadjuvant radiation therapy is associated with higher rates of postoperative complications after head and neck reconstruction. Herle et al. conducted a systematic review in 2014 of 24 studies, finding higher complication rates in irradiated fields. We sought to perform an exhaustive updated systematic review and meta-analysis. METHODS We conducted an updated systematic review of the literature, as outlined in our protocol, which was registered on PROSPERO. Databases included Medline, Embase, Cochrane Central, and Web of Science. There were no limits placed on the date range, place of publication, or origin. Exclusion criteria included patients less than 18 years of age, studies with less than 20 participants (n < 20), case studies, skull base reconstructions, and local tissue rearrangements. The combined results of the studies and relative risks (RR) were calculated. RESULTS 53 studies were included for analysis, including 5,086 free flaps in an irradiated field, and 9,110 free flaps in a non-irradiated field. Of the 53 studies, 21 studies overlapped with those discussed in Herle et al.'s study, with a total of 32 additional studies. Neoadjuvant radiation was found to be a statistically significant risk factor for postoperative complications (RR 1.579, P < 0.001), total flap failure (RR, 1.565; P < 0.001), and fistula (RR, 1.810; P < 0.001). Our work reaffirmed the findings of the Herle et al. STUDY CONCLUSION Preoperative radiation was associated with a statistically significant increase in the risk of total flap failure, fistula, and total complications but not partial flap failure. These high-morbidity complications must be taken into consideration when determining which patients should receive neoadjuvant radiation therapy.

Introduction: The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop drug or cell-based therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. A previously validated acute AAA swine model was treated directly with gelfoam containing human adipose-derived stem cells (h-ADSCs). Methods: Male Yorkshire swine (n=16) received periadventitial injections (type 1 collagenase and porcine pancreatic elastase) into a 4 cm segment of infrarenal aorta. Experimental group (n=7) received gel foam soaked with 10 million h-ADSCs and control group (n=9) media-soaked gel foam. Aortic diameters (AD) were monitored at post-operative day (POD) 7 and 14 using ultrasound with euthanasia on POD 21. Suprarenal (control) and infrarenal aortas (experimental) were harvested for PCR, mechanical tensiometry testing, histopathological analyses as well as immunohistochemistry (IHC). Each animal served as their own control. Groups were compared with paired t-tests and Mann Whitney U tests. Results: Twelve animals survived until POD 21. Stem cell treated AAAs, unlike controls, demonstrated no growth (-1.6 ± 8.8% vs. 34.8 ± 13.7%, p Conclusion: Stem cell therapy prevents the development of aortic aneurysms in a swine model. Stem cell treated swine with induced AAAs show more normal gross features, histologic, and biochemical properties compared to untreated controls with induced AAAs. Further investigation is merited as a possible translatable therapy for aneurysmal disease.

Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs. CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01). CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies. SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.

Introduction: Abdominal aortic aneurysms (AAA) are responsible for over 150,000 deaths worldwide annually. Attempts at producing a reliable large-animal model of AAA have proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall. Methods: A total of 9 male Yorkshire swine received periadventitial injections of type 1 collagenase (23.5 mg) and porcine pancreatic elastase (500 mg) into a 4 cm segment of infrarenal aorta. Aortic diameter growth was monitored at POD 7 and 14 using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal (treated) aorta was harvested for analysis, after gross measurement of aortic diameter under physiologic blood pressure. Sections of control and treated aorta were used to obtain tensile strength using a tensiometer. Additional segments of the aorta were collected for histopathological analysis (H&E, elastin, alpha smooth muscle actin). PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA for repeated measures, where appropriate. Results: Average percent growth of aortic diameter at POD 21 for treated segments was 27% +/- 16.5% versus 4.5% +/- 4% for control tissue. The average difference in aortic growth by subject, was 26.7% [14.6%-38.8%]; (p Conclusion: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.

There appears to be an association between preoperative opioid use and postoperative complications. We sought to determine whether patients with a history of chronic opiate use (defined as 3 months or more of sustained use) prior to undergoing free flap surgery have higher rates of 30-day complications.A retrospective review of patients undergoing free flaps from 2015 to 2020 was performed. Patient characteristics were analyzed, including daily preoperative dose of opiates, which were then converted to morphine milligram equivalents; intra-operative variables such as estimated blood loss and operating room time; and 30-day outcomes, including wound and flap complications, return to the operating room, and readmissions.One hundred fifty-five patients received 160 free flaps. Of these flaps, 50/160 (31%) were performed on patients with an opiate prescription for at least three months prior to surgery. Using multivariable analysis, morphine milligram equivalents, a surrogate for opioid dose, were significantly associated with flap complications (odds ratio (OR) 1.011, 95% confidence interval (CI) 1.003-1.020, p0.01), partial flap loss (OR 1.010, 95% CI 1.003-1.019, p0.01), and surgical site infections (OR 1.017, 95% CI 1.007-1.027, p0.01). Additionally, estimated blood loss was associated with partial flap loss (OR 4.838, 95% CI 1.589-14.728, p0.006), and operating room time was also associated with flap complications (OR 1.337, 95% CI 1.152-1.150, p0.01).Chronic preoperative opioid use is common for free flap surgery, and according to our single-center experience, higher daily doses are a risk factor for flap complications and surgical site infections. These findings add to the growing body of evidence that opioid use is a modifiable risk factor that may increase surgical morbidity.

Producing a reliable large-animal model of AAA has proven challenging. We sought to create a reproducible swine model of AAA using enzymatic degradation of the aortic wall.Twelve male Yorkshire swine received periadventitial injections of type 1 collagenase and porcine pancreatic elastase into a 4 cm segment of infrarenal aorta. Nine survived until postoperative day (POD) 21. Aortic growth was monitored at 7 and 14 days using ultrasound. The animals were euthanized on POD 21, and the suprarenal (control) and infrarenal aorta were harvested for analysis, after gross measurement of aortic diameter (AD). Tensile strength was measured and additional segments were collected for histopathological analysis. PCR of matrix metalloproteinases (MMP9) was conducted. Groups were compared with paired t-tests, or ANOVA, where appropriate.Average percent growth of AD at POD 21 for treated segments was 27% versus 4.5% for control tissue. The average difference in AD by subject, was 26.7% (P0.001). Aortic medial thickness was decreased in treated tissue; 235 μm versus 645 μm (P0.0001). Quantities of both medial elastin fibers, and smooth muscles cells were decreased in treated tissue; 1.8% compared to 9.9% (P0.0001), and 24% versus 37.4%, respectively. Tensile strength was also decreased in treated tissue; 16.7 MPa versus 29.5 MPa (P=0.0002). A 12-fold increase in expression of MMP9 mRNA was also demonstrated in aneurysmal tissue (P=0.002) CONCLUSION: A reproducible, large-animal model of AAA, with anatomical, histopathological, and biomechanical properties that are clinically translatable, can be achieved with extraluminal enzymatic degradation.

Introduction There is a paucity of data on the role of metastasectomy for metastatic anal cancer on survival outcomes. We aim to define the role of metastasectomy in stage IV anal cancer. Methods National Cancer Database (NCDB) from 2004 to 2014 was accessed to include patients with metastatic anal cancer, excluding adenocarcinoma, neuroendocrine, and ‘other’ histologies. We compared patients undergoing metastasectomy (n = 165) to those who did not have metastasectomy (n = 2093) by age, sex, cancer grade, and site of metastasis, including metastasis to bone, liver, and lung, using chi-square analysis. The primary outcome was overall survival. Results Patients had equal distribution of metastatic sites between those who underwent metastasectomy versus no metastasectomy: bone (7.64% vs 4.85%, p = 0.22), brain (0.24% vs 0%, p = 1.0), liver (23.22% vs 29.70%, p = 0.07), and lung (11.85% vs 9.09%, p = 0.38). Survival following metastasectomy was increased at one year (71% vs. 61%, p = 0.016), two years (50% vs. 38%, p = 0.014), and five years (30% vs. 19%, p = 0.025). Median overall survival was increased (23 months vs. 16 months; p = 0.015) for patients with metastasectomy. Survival increases were demonstrated only in the group with liver metastasis undergoing metastasectomy. When stratifying for liver metastases only, median overall survival time was further increased (34 months vs. 16 months; p Conclusion These results demonstrate a survival benefit for hepatic metastasectomy in stage IV anal cancer. Our findings demonstrate a potential survival benefit in highly select patients with metastatic anal cancer to the liver. These findings support further investigation in a randomized clinical trial to delineate these findings.