Application of Irreversible Electroporation Ablation as Adjunctive Treatment for Margin Enhancement: Safety and Efficacy.

BACKGROUND: Irreversible electroporation (IRE) is a relatively new ablation technique utilized as focal therapy to target areas of significant tumor burden to ablate tumors in situ or improve margins of resection. Its application has largely been reported in the pancreas, liver, kidney, and prostate. Because locoregional therapy is becoming more common, IRE may be a reasonable alternative in additional situations if shown to be safe and efficacious. We have utilized IRE intraoperatively in highly selected patients for adjunctive treatment of primary and metastatic tumors at the time of surgical resection to achieve local control where an R1 resection is clinically felt to be likely. We hypothesize that IRE is a safe and effective adjuvant therapy. Our primary objective was to evaluate the safety of IRE with regard to the effects of other structures within the ablated zone. A secondary objective was to estimate local control rates of locally advanced tumors when IRE was used as an adjunct for margin enhancement. METHODS: This is a retrospective chart review of a prospective database at a single tertiary institution. The study included patients receiving IRE from November 2013 through May 2016 at the time of resection of tumor resection for margin enhancement. Primary tumors included liver, pancreatic, retroperitoneal, extremity, and pelvic tumors. Patients undergoing treatment for palliation or in situ ablation were excluded. RESULTS: Forty patients received IRE for margin enhancement. Median follow-up was 14 mo. Three patients (7.5%) had a local recurrence, and 12 (30%) had a distant recurrence. Adverse events possibly related to IRE are described. CONCLUSIONS: Our institution demonstrated a low local recurrence rate of only 7.5% in patients treated with intraoperative IRE for margin enhancement. This may be a useful adjunct at the time of surgical resection to help achieve local control in difficult areas where an R1 resection is likely. This topic will require further investigation with prospective trials and longer follow-up.

Cannabinoids as a Potential New and Novel Treatment for Melanoma: A Pilot Study in a Murine Model.

BACKGROUND: Malignant melanoma is a complex malignancy with significant morbidity and mortality. The incidence continues to rise, and despite advances in treatment, the prognosis is poor. Thus, it is necessary to develop novel strategies to treat this aggressive cancer. Synthetic cannabinoids have been implicated in inhibiting cancer cell proliferation, reducing tumor growth, and reducing metastasis. We developed a unique study focusing on the effects of treatment with a cannabinoid derivative on malignant melanoma tumors in a murine model. METHODS: Murine B16F10 melanoma tumors were established subcutaneously in C57BL/6 mice. Mice were then treated with intraperitoneal injections of vehicle twice per week (control-group 1, n = 6), Cisplatin 5 mg/kg/wk (group 2; n = 6), and Cannabidiol (CBD) 5 mg/kg twice per week (group 3; n = 6). Tumors were measured and volume calculated as (4π/3) × (width/2)2 × (length/2). Tumor size and survival curves were measured. Results were compared using a one-way ANOVA with multiple comparison test. RESULTS: A significant decrease in tumor size was detected in mice treated with CBD when compared with the control group (P = 0.01). The survival curve of melanoma tumors treated with CBD increased when compared with the control group and was statistically significant (P = 0.04). The growth curve and survival curve of melanoma tumors treated with Cisplatin were significantly decreased and increased, respectively, when compared with the control and CBD-treated groups. Mice treated with Cisplatin demonstrated the longest survival time, but the quality of life and movement of CBD-treated mice were observed to be better. CONCLUSIONS: We demonstrate a potential beneficial therapeutic effect of cannabinoids, which could influence the course of melanoma in a murine model. Increased survival and less tumorgenicity are novel findings that should guide research to better understand the mechanisms by which cannabinoids could be utilized as adjunctive treatment of cancer, specifically melanoma. Further studies are necessary to evaluate this potentially new and novel treatment of malignant melanoma.

Financial Analysis of Free Lung Cancer Screening Program Shows Profitability Using Broader NCCN Guidelines.

BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) chest scans in high-risk populations has been established as an effective measure of preventive medicine by the National Lung Screening Trial. However, the sustainability of funding a program is still controversial. We present a 2.5-year profitability analysis of our screening program by using the broader National Comprehensive Cancer Network criteria. METHODS: Retrospective chart review was performed on the initial 2.5-year data set of a free LDCT chest scan program that targeted the underserved Southeastern United States. Patients were selected by the National Comprehensive Cancer Network high-risk criteria, screening twice as many patients compared with Centers for Medicare and Medicaid Services criteria. LDCT scans were performed during the off-service hours of our positron emission tomography CT scanner. Analysis of fiscal years 2015 to 2017 was done to evaluate indirect cost, direct cost, and adjusted net margin per case after factoring downstream revenue from positive scans and other findings. RESULTS: A total of 705 scans were performed with 418 patients referred for subsequent procedures or specialist evaluations. The mean overhead cost over total cost was 42.3%. The adjusted net margin per case was -$212 in the first year but turned positive to $177 in the third fiscal year. The total break-even point of adjusted net margin was between 6% and 7% of indirect cost as a function of charges. Of the 60 new patients introduced to the hospital system, a gross margin per case of $211 was found. CONCLUSIONS: Free lung cancer screening can demonstrate profitability from downstream revenue with a lag time of 2 years.

Analysis of 334 Cases of Pediatric Esophageal Foreign Body Removal Suggests that Traditional Methods Have Similar Outcomes Whereas a Magnetic Tip Orogastric Tube Appears to Be an Effective, Efficient, and Safe Technique for Disc Battery Removal.

Procedures and outcomes for pediatric esophageal foreign body removal were analyzed. Traditional methods of battery removal were compared with a magnetic tip orogastric tube (MtOGT). A single institution retrospective review from 1997 to 2014 of pediatric patients with esophageal foreign bodies was performed. Balloon extraction with fluoroscopy (performed in 173 patients with 91% success), flexible endoscopy (92% success in 102 patients), and rigid esophagoscopy (95% in 38 patients) had excellent success rates. A MtOGT had 100 per cent success in six disc battery patients, when other methods were more likely to fail, and was the fastest. Power analysis suggested 20 patients in the MtOGT group would be needed for significant savings in procedural time. Thirty-two per cent of all foreign bodies and 95 per cent of batteries had complications (P = 0.002) because of the foreign body. Overall, 1.2 per cent had severe complications, whereas 10 per cent of batteries had severe complications (P = 0.04). Each technique if applied appropriately can be a reasonable option for esophageal foreign body removal. Magnetic tip orogastric tubes used to extract ferromagnetic objects like disc batteries had the shortest procedure time and highest success rate although it was not statistically significant. Disc batteries require emergent removal and have a significant complication rate.

Feasibility and Safety of Intraoperative Colonoscopy after Segmental Colectomy and Primary Anastomosis.

Patients presenting with near-obstructing colon lesions requiring segmental colectomy may benefit from intraoperative colonoscopy (IOC) after primary anastomosis for a more timely and accurate diagnosis of synchronous lesions. The aim of this study is to demonstrate the feasibility and safety of this technique. A retrospective cohort study of patients undergoing single-stage segmental colectomy and anastomosis at a single tertiary care institution from 2011 to 2013 was performed. One Hundred and sixty-eight consecutive patients underwent segmental colectomy and primary anastomosis of which 78 (46%) were unable to receive preoperative colonoscopy (POC) because of near-obstructing lesions and received IOC after the anastomosis. IOC detected synchronous adenomatous polyps in 24.4 per cent, diverticular disease in 19 per cent, and colitis/proctitis in 2.5 per cent. The IOC group was not significantly different from the POC group with regard to overall morbidity (31% vs 39% P = 0.45), anastomotic leakage (1.3% vs 0%, P = 0.46), or wound infection (5.1% vs 1.1%, P = 0.18). Operation time was 19 minutes longer in the intraoperative group, but overall length of hospital stay was not significantly different (6.4 ± 2.9 days vs 7.3 ± 4.6 days). In patients unable to receive POC because of partial obstruction, IOC after primary anastomosis is both feasible and safe for detecting proximal synchronous lesions.

Impact of cannabidiol treatment on regulatory T-17 cells and neutrophil polarization in acute kidney injury.

Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail T helper 17 (Th-17)-mediated proinflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Furthermore, cannabidiol exerts immunoregulatory effects, but its impact on Treg17 cells and neutrophil subtypes is not established. Thus, we examined the status of Treg17 cells and neutrophil subtypes in AKI and determined whether cannabidiol favors regulatory neutrophils and T cells accompanied with renoprotection. Accordingly, mice were subjected to bilateral renal ischemia-reperfusion injury (IRI), without or with cannabidiol treatment; thereafter, kidneys were processed for flow cytometry analyses. Renal IRI increased N1 and Th-17 but reduced N2 and Treg17 cells accompanied with disruption of mitochondrial membrane potential (ψm) and increased apoptosis/necrosis and kidney injury molecule-1 (KIM-1) immunostaining compared with their sham controls. Importantly, cannabidiol treatment preserved ψm and reduced cell death and KIM-1 accompanied by restoration of N1 and N2 imbalance and preservation of Treg17 cells while decreasing Th-17 cells. The ability of cannabidiol to favor development of Treg17 cells was further established using functional mixed lymphocytic reaction. Subsequent studies showed higher renal blood flow and reduced serum creatinine in cannabidiol-treated IRI animals. Collectively, our novel observations establish that renal IRI causes neutrophil polarization in favor of N1 and also reduces Treg17 cells in favor of Th-17, effects that are reversed by cannabidiol treatment accompanied with significant renoprotection.

Feasibility and Benefit of Incorporating a Multimedia Cadaver Laboratory Training Program into a Didactics Curriculum for Junior and Senior Surgical Residents.

OBJECTIVE: As operative experience in general surgery decreases and work hour limitations increase there is less exposure of surgical residents to advanced vascular and trauma exposures. Many institutions have demonstrated benefits of cadaver laboratory courses. We have incorporated a multimedia cadaver laboratory course into our general surgery residency didactics curriculum with the objective to demonstrate a benefit of the program as well as the feasibility of incorporation. STUDY DESIGN: This is a prospective study at a tertiary care institution including general surgery residents within our residency program. A curriculum was designed, requiring residents to complete multimedia learning modules before both a trauma cadaver laboratory and vascular exposure cadaver laboratory. Outcome measures included self-efficacy/confidence (precourse and postcourse 5-point Likert surveys), knowledge (net performance on precourse and postcourse multiple choice examinations), and resident perception of the curriculum (postcourse 5-point Likert survey). Data were analyzed using ANOVA paired t-tests. RESULTS: For the vascular cadaver laboratory, resident knowledge improved overall from an average of 41.2% to 50.0% of questions correct (p = 0.032) and self-efficacy/confidence improved by 0.59 from 1.52 to 2.11 out of 5 (p = 0.009). Median confidence is 1.37 out of 5 and 2.32 out of 5, before and after course, respectively. Wilcoxon nonparametric test reveals a p = 0.011. Resident's perception of the usefulness of the laboratory evaluation was 3.85 out 5. There were 85.71% agreed that the laboratory is useful and 14.29% were disagree. The Z-score is -0.1579 (means 0.1579 standard deviations a score of 3.85 below the benchmark). The percentile rank is 56.27%. The coefficient of variation is 24.68%. For the trauma cadaver laboratory, resident knowledge improved overall from an average of 55.89% to 66.17% of questions correct (p = 0.001) and self-efficacy/confidence improved by 0.75 from 1.68 out of 5 to 2.43 out of 5 (p = 0.011). Median confidence level is 1.41 out of 5 before the training course and 2.64 out of 5 after the training course. Wilcoxon signed rank test gives a p value of 0.008. Resident's perception of the usefulness of the laboratory evaluation was 3.94 out 5. There were 72.22% agreed that the laboratory is useful and 27.78% were neutral. The Z-score is -0.098 (means 0.098 standard deviations a score of 3.94 below the benchmark). The percentile rank is 53.90%. The coefficient of variation is 15.48%. CONCLUSIONS: Incorporating a multimedia cadaver laboratory into a residency education didactics curriculum was both feasible and beneficial for resident education. We demonstrate an improvement in knowledge and self efficacy/confidence following both cadaver laboratory courses.

Free Lung Cancer Screening Trends Toward a Twofold Increase in Lung Cancer Prevalence in the Underserved Southeastern United States.

OBJECTIVES: The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. METHODS: This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. RESULTS: Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. CONCLUSIONS: We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.

Development of Electronic Medical Record-Based "Rounds Report" Results in Improved Resident Efficiency, More Time for Direct Patient Care and Education, and Less Resident Duty Hour Violations.

Surgeons frequently report frustration and loss of efficiency with electronic medical record (EMR) systems. Together, surgery residents and a programmer at Augusta University created a rounds report (RR) summarizing 24 hours of vitals, intake/output, labs, and other values for each inpatient that were previously transcribed by hand. The objective of this study was to evaluate the RR's effect on surgery residents. Surgery residents were queried to assess the RR's impact. Outcome measures were time spent preparing for rounds, direct patient care time, educational activity time, rates of incorrect/incomplete data on rounds, and rate of duty hour violations. Hospital wide, 17,200 RRs were generated in the 1-month study. Twenty-three surgery residents participated. Time spent preparing for rounds decreased per floor patient (15.6 ± 3.0 vs 6.0 ± 1.2, P < 0.0001) and per intensive care unit patient (19.9 ± 2.9 vs 7.5 ± 1.2 P < 0.0001). The work day spent in direct patient care increased from 45.1 ± 5.6 to 54.0 ± 5.7 per cent (P = 0.0044). Educational activity time increased from 35.2 ± 5.4 to 54.7 ± 7.1 minutes per resident per day (P = 0.0004). Reported duty hour violations decreased 58 per cent (P < 0.0001). American Board of Surgery in Training exam scores trended up, and estimates of departmental annual financial savings range from $66,598 to $273,141 per year. Significant improvements occur with surgeon designed EMR tools like the RR. Hospitals and EMR companies should pair interested surgeons with health information technology developers to facilitate EMR enhancements. Improvements like RRs can have broad ranging, multidisciplinary impact and should be standard in all EMRs used for inpatient care at academic medical centers.

Innate lymphoid cells: a paradigm for low SSI in cleft lip repair.

BACKGROUND: Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs. MATERIALS AND METHODS: Lip tissue samples were collected from 13 subjects undergoing vermillion resection during cleft lip reconstructive surgery. Preparative, transmission electron microscopy, and analytical flow cytometry were performed. The functionality of ILCs was tested in terms of their capacity to produce type 1 (IFN-γ/TNF-α), type 2 (IL-5/IL-13), and type 3 (IL-17/IL-22) cytokines. Data were analyzed using Student t test or the analysis of variance to establish significance (P < 0.05) among groups for all other data. RESULTS: All three classes of ILCs were detected and visualized in the tissue samples. In all samples, the level of ILC2 subset was significantly higher than the other two ILC subsets (P < 0.01), followed by the ILC1 subset, which was present in significantly higher levels than the ILC3 subset (P < 0.05). CONCLUSIONS: Our data place ILCs for the first time in the interface of oral mucosal immunity, tissue microenvironment, and homeostasis during and after tissue development, possibly explaining lower infection rates in cleft lip or palate reconstructions.