Publications by authors named "Ryan Swan"

46 Publications

Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes.

Sci Rep 2021 03 2;11(1):4966. Epub 2021 Mar 2.

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Boulevard, Portland, OR, 97239, USA.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.
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http://dx.doi.org/10.1038/s41598-021-83552-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925531PMC
March 2021

Automated Fundus Image Quality Assessment in Retinopathy of Prematurity Using Deep Convolutional Neural Networks.

Ophthalmol Retina 2019 05 31;3(5):444-450. Epub 2019 Jan 31.

Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon; Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon. Electronic address:

Purpose: Accurate image-based ophthalmic diagnosis relies on fundus image clarity. This has important implications for the quality of ophthalmic diagnoses and for emerging methods such as telemedicine and computer-based image analysis. The purpose of this study was to implement a deep convolutional neural network (CNN) for automated assessment of fundus image quality in retinopathy of prematurity (ROP).

Design: Experimental study.

Participants: Retinal fundus images were collected from preterm infants during routine ROP screenings.

Methods: Six thousand one hundred thirty-nine retinal fundus images were collected from 9 academic institutions. Each image was graded for quality (acceptable quality [AQ], possibly acceptable quality [PAQ], or not acceptable quality [NAQ]) by 3 independent experts. Quality was defined as the ability to assess an image confidently for the presence of ROP. Of the 6139 images, NAQ, PAQ, and AQ images represented 5.6%, 43.6%, and 50.8% of the image set, respectively. Because of low representation of NAQ images in the data set, images labeled NAQ were grouped into the PAQ category, and a binary CNN classifier was trained using 5-fold cross-validation on 4000 images. A test set of 2109 images was held out for final model evaluation. Additionally, 30 images were ranked from worst to best quality by 6 experts via pairwise comparisons, and the CNN's ability to rank quality, regardless of quality classification, was assessed.

Main Outcome Measures: The CNN performance was evaluated using area under the receiver operating characteristic curve (AUC). A Spearman's rank correlation was calculated to evaluate the overall ability of the CNN to rank images from worst to best quality as compared with experts.

Results: The mean AUC for 5-fold cross-validation was 0.958 (standard deviation, 0.005) for the diagnosis of AQ versus PAQ images. The AUC was 0.965 for the test set. The Spearman's rank correlation coefficient on the set of 30 images was 0.90 as compared with the overall expert consensus ranking.

Conclusions: This model accurately assessed retinal fundus image quality in a comparable manner with that of experts. This fully automated model has potential for application in clinical settings, telemedicine, and computer-based image analysis in ROP and for generalizability to other ophthalmic diseases.
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http://dx.doi.org/10.1016/j.oret.2019.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501831PMC
May 2019

Deep Learning for Image Quality Assessment of Fundus Images in Retinopathy of Prematurity.

AMIA Annu Symp Proc 2018 5;2018:1224-1232. Epub 2018 Dec 5.

Medical Informatics & Clinical Epidemiology, and.

Accurate image-based medical diagnosis relies upon adequate image quality and clarity. This has important implications for clinical diagnosis, and for emerging methods such as telemedicine and computer-based image analysis. In this study, we trained a convolutional neural network (CNN) to automatically assess the quality of retinal fundus images in a representative ophthalmic disease, retinopathy of prematurity (ROP). 6,043 wide-angle fundus images were collected from preterm infants during routine ROP screening examinations. Images were assessed by clinical experts for quality regarding ability to diagnose ROP accurately, and were labeled "acceptable" or "not acceptable." The CNN training, validation and test sets consisted of 2,770 images, 200 images, and 3,073 images, respectively. Test set accuracy was 89.1%, with area under the receiver operating curve equal to 0.964, and area under the precision-recall curve equal to 0.966. Taken together, our CNN shows promise as a useful prescreening method for telemedicine and computer-based image analysis applications. We feel this methodology is generalizable to all clinical domains involving image-based diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371336PMC
December 2019

The genetics of retinopathy of prematurity: a model for neovascular retinal disease.

Ophthalmol Retina 2018 Sep 8;2(9):949-962. Epub 2018 Mar 8.

Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR.

Topic: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease in premature infants, and is a major cause of childhood blindness worldwide. In addition to known clinical risk factors such as low birth weight and gestational age, there is a growing body of evidence supporting a genetic basis for ROP.

Clinical Relevance: While comorbidities and environmental factors have been identified as contributing to ROP outcomes in premature infants, most notably gestational age and oxygen, some infants progress to severe disease despite absence of these clinical risk factors. The contribution of genetic factors may explain these differences and allow better detection and treatment of infants at risk for severe ROP.

Methods: To comprehensively review genetic factors that potentially contribute to the development and severity of ROP, we conducted a literature search focusing on the genetic basis for ROP. Terms related to other heritable retinal vascular diseases like "familial exudative vitreoretinopathy", as well as to genes implicated in animal models of ROP, were also used to capture research in diseases with similar pathogenesis to ROP in humans with known genetic components.

Results: Contributions across several genetic domains are described including vascular endothelial growth factor, the Wnt signaling pathway, insulin-like growth factor 1, inflammatory mediators, and brain-derived neurotrophic factor.

Conclusions: Most candidate gene studies of ROP have limitations such as inability to replicate results, conflicting results from various studies, small sample size, and differences in clinical characterization. Additional difficulty arises in separating the contribution of genetic factors like Wnt signaling to ROP and prematurity. Although studies have implicated involvement of multiple signaling pathways in ROP, the genetics of ROP have not been clearly elucidated. Next-generation sequencing and genome-wide association studies have potential to expand future understanding of underlying genetic risk factors and pathophysiology of ROP.
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http://dx.doi.org/10.1016/j.oret.2018.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150458PMC
September 2018

Retinopathy of prematurity: a review of risk factors and their clinical significance.

Surv Ophthalmol 2018 Sep - Oct;63(5):618-637. Epub 2018 Apr 19.

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP.
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http://dx.doi.org/10.1016/j.survophthal.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089661PMC
September 2018

Operative microwave ablation for hepatocellular carcinoma: a single center retrospective review of 219 patients.

J Gastrointest Oncol 2017 Apr;8(2):337-346

Division of HPB Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Background: Microwave ablation (MWA) of hepatocellular carcinoma (HCC) offers local regional treatment that can be safely and effectively performed, even in patients with advanced liver disease. We update results from our group's previous analysis of operative MWA for HCC.

Methods: Retrospective review was performed of all patients who underwent operative MWA for HCC from 2007-2014. Patient demographics, operative characteristics and complications were recorded. Follow up imaging was reviewed to determine rates of complete ablation, local, regional and metastatic recurrence.

Results: Two hundred and nineteen patients were included with a total of 340 tumors treated with operative MWA. Median tumor size was 3.2 cm (range, 1-6 cm). Cirrhosis was present in 89.5% of patients, 60.7% had hepatitis C, and 8.2% had hepatitis B. Thirty-five point nine percent were Child-Pugh class B/C. Ninety-six point eight percent of MWA procedures were performed laparoscopically. Four deaths occurred within 30 days (1.8%). Clavien-Dindo grade III complications occurred in 3.2% of patients. Complete ablation was identified in 97.1% of tumors, with local recurrence rates of 8.5% at 10.9 months median follow up (0-80 months). Regional recurrence occurred in 34.8% of patients at 10.9 months median follow up and metastatic recurrence was seen in 8.1% of patients. One year overall survival was 80.0% and 2-year survival was 61.5%.

Conclusions: We propose that laparoscopic MWA offers a low morbidity approach for treatment of HCC affording low rates of local recurrence even for patients with significant underlying liver dysfunction. This large series offers insight into outcomes of this modality as definitive treatment for patients with HCC.
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http://dx.doi.org/10.21037/jgo.2016.09.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5401852PMC
April 2017

Assessment of a Tele-education System to Enhance Retinopathy of Prematurity Training by International Ophthalmologists-in-Training in Mexico.

Ophthalmology 2017 07 3;124(7):953-961. Epub 2017 Apr 3.

Department of Ophthalmology, Weill Cornell Medical College, New York, New York; Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois; Center for Global Health, College of Medicine, University of Illinois at Chicago, Chicago, Illinois. Electronic address:

Purpose: To evaluate a tele-education system developed to improve diagnostic competency in retinopathy of prematurity (ROP) by ophthalmologists-in-training in Mexico.

Design: Prospective, randomized cohort study.

Participants: Fifty-eight ophthalmology residents and fellows from a training program in Mexico consented to participate. Twenty-nine of 58 trainees (50%) were randomized to the educational intervention (pretest, ROP tutorial, ROP educational chapters, and posttest), and 29 of 58 trainees (50%) were randomized to a control group (pretest and posttest only).

Methods: A secure web-based educational system was created using clinical cases (20 pretest, 20 posttest, and 25 training chapter-based) developed from a repository of over 2500 unique image sets of ROP. For each image set used, a reference standard ROP diagnosis was established by combining the clinical diagnosis by indirect ophthalmoscope examination and image-based diagnosis by multiple experts. Trainees were presented with image-based clinical cases of ROP during a pretest, posttest, and training chapters.

Main Outcome Measures: The accuracy of ROP diagnosis (e.g., plus disease, zone, stage, category) was determined using sensitivity and specificity calculations from the pretest and posttest results of the educational intervention group versus control group. The unweighted kappa statistic was used to analyze the intragrader agreement for ROP diagnosis by the ophthalmologists-in-training during the pretest and posttest for both groups.

Results: Trainees completing the tele-education system had statistically significant improvements (P < 0.01) in the accuracy of ROP diagnosis for plus disease, zone, stage, category, and aggressive posterior ROP (AP-ROP). Compared with the control group, trainees who completed the ROP tele-education system performed better on the posttest for accurately diagnosing plus disease (67% vs. 48%; P = 0.04) and the presence of ROP (96% vs. 91%; P < 0.01). The specificity for diagnosing AP-ROP (94% vs. 78%; P < 0.01), type 2 ROP or worse (92% vs. 84%; P = 0.04), and ROP requiring treatment (89% vs. 79%; P < 0.01) was better for the trainees completing the tele-education system compared with the control group. Intragrader agreement improved for identification of plus disease, zone, stage, and category of ROP after completion of the educational intervention.

Conclusions: A tele-education system for ROP education was effective in improving the diagnostic accuracy of ROP by ophthalmologists-in-training in Mexico. This system has the potential to increase competency in ROP diagnosis and management for ophthalmologists-in-training from middle-income nations.
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http://dx.doi.org/10.1016/j.ophtha.2017.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895299PMC
July 2017

Building the Nonuniversity, Tertiary Care Center Hepatobiliary and Pancreatic Surgery Practice: Structural and Financial Considerations.

Am Surg 2016 Dec;82(12):1196-1202

Department of General Surgery, Division of Hepato-Pancreato-Biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina, USA.

Early in their careers, many new surgeons lack the background and experience to understand essential components needed to build a surgical practice. Surgical resident education is often devoid of specific instruction on the business of medicine and practice management. In particular, hepatobiliary and pancreatic (HPB) surgeons require many key components to build a successful practice secondary to significant interdisciplinary coordination and a scope of complex surgery, which spans challenging benign and malignant disease processes. In the following, we describe the required clinical and financial components for developing a successful HPB surgery practice in the nonuniversity tertiary care center. We discuss significant financial considerations for understanding community need and hospital investment, contract establishment, billing, and coding. We summarize the structural elements and key personnel necessary for establishing an effectual HPB surgical team. This article provides useful, essential information for a new HPB surgeon looking to establish a surgical practice. It also provides insight for health-care administrators as to the value an HPB surgeon can bring to a hospital or health-care system.
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December 2016

Mixed Hepatocellular Carcinoma, Neuroendocrine Carcinoma of the Liver.

Am Surg 2016 Nov;82(11):1121-1125

Department of General Surgery, Division of Hepato-pancreato-biliary Surgery, Carolinas Medical Center, Charlotte, North Carolina, USA.

We present the case of a 76-year-old male found to have a large tumor involving the left lateral lobe of the liver, presumed to be hepatocellular carcinoma (HCC). After resection, pathologic features demonstrated both high-grade HCC and high-grade neuroendocrine carcinoma (NEC). Areas of NEC stained strongly for synaptophysin, which was not present in HCC component. The HCC component stained strongly for Hep-Par 1, which was not present in the NEC component. The patient underwent genetic analysis for biomarkers common to both tumor cell types. Both tumor components contained gene mutations in CTNNB1 gene (S33F located in exon 3). They also shared mutations in PD-1, PGP, and SMO. Mixed HCC/NEC tumors have been rarely reported in the literature with generally poor outcomes. This patient has been referred for adjuvant platinum-based chemotherapy; genetic biomarker analysis may provide some insight to guide targeted chemotherapy.
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November 2016

Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability.

Ophthalmology 2016 11 31;123(11):2338-2344. Epub 2016 Aug 31.

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon. Electronic address:

Purpose: To identify patterns of interexpert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP).

Design: We developed 2 datasets of clinical images as part of the Imaging and Informatics in ROP study and determined a consensus reference standard diagnosis (RSD) for each image based on 3 independent image graders and the clinical examination results. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD.

Participants: Eight participating experts with more than 10 years of clinical ROP experience and more than 5 peer-reviewed ROP publications who analyzed images obtained during routine ROP screening in neonatal intensive care units.

Methods: Expert classification of images of plus disease in ROP.

Main Outcome Measures: Interexpert agreement (weighted κ statistic) and agreement and bias on ordinal classification between experts (analysis of variance [ANOVA]) and the RSD (percent agreement).

Results: There was variable interexpert agreement on diagnostic classifications between the 8 experts and the RSD (weighted κ, 0-0.75; mean, 0.30). The RSD agreement ranged from 80% to 94% for the dataset of 100 images and from 29% to 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and preplus disease. The 2-way ANOVA model suggested a highly significant effect of both image and user on the average score (dataset A: P < 0.05 and adjusted R = 0.82; and dataset B: P < 0.05 and adjusted R = 0.6615).

Conclusions: There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different cut points for the amounts of vascular abnormality required for presence of plus and preplus disease. This has important implications for research, teaching, and patient care for ROP and suggests that a continuous ROP plus disease severity score may reflect more accurately the behavior of expert ROP clinicians and may better standardize classification in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077639PMC
http://dx.doi.org/10.1016/j.ophtha.2016.07.026DOI Listing
November 2016

Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis.

Ophthalmology 2016 11 24;123(11):2345-2351. Epub 2016 Aug 24.

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon. Electronic address:

Purpose: To determine expert agreement on relative retinopathy of prematurity (ROP) disease severity and whether computer-based image analysis can model relative disease severity, and to propose consideration of a more continuous severity score for ROP.

Design: We developed 2 databases of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP (i-ROP) cohort study and recruited expert physician, nonexpert physician, and nonphysician graders to classify and perform pairwise comparisons on both databases.

Participants: Six participating expert ROP clinician-scientists, each with a minimum of 10 years of clinical ROP experience and 5 ROP publications, and 5 image graders (3 physicians and 2 nonphysician graders) who analyzed images that were obtained during routine ROP screening in neonatal intensive care units.

Methods: Images in both databases were ranked by average disease classification (classification ranking), by pairwise comparison using the Elo rating method (comparison ranking), and by correlation with the i-ROP computer-based image analysis system.

Main Outcome Measures: Interexpert agreement (weighted κ statistic) compared with the correlation coefficient (CC) between experts on pairwise comparisons and correlation between expert rankings and computer-based image analysis modeling.

Results: There was variable interexpert agreement on diagnostic classification of disease (plus, preplus, or normal) among the 6 experts (mean weighted κ, 0.27; range, 0.06-0.63), but good correlation between experts on comparison ranking of disease severity (mean CC, 0.84; range, 0.74-0.93) on the set of 34 images. Comparison ranking provided a severity ranking that was in good agreement with ranking obtained by classification ranking (CC, 0.92). Comparison ranking on the larger dataset by both expert and nonexpert graders demonstrated good correlation (mean CC, 0.97; range, 0.95-0.98). The i-ROP system was able to model this continuous severity with good correlation (CC, 0.86).

Conclusions: Experts diagnose plus disease on a continuum, with poor absolute agreement on classification but good relative agreement on disease severity. These results suggest that the use of pairwise rankings and a continuous severity score, such as that provided by the i-ROP system, may improve agreement on disease severity in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077696PMC
http://dx.doi.org/10.1016/j.ophtha.2016.07.020DOI Listing
November 2016

Postmarketing Analysis of a Novel, Cordless Ultrasonic Dissector.

Surg Innov 2016 Oct 2;23(5):505-10. Epub 2016 Feb 2.

Carolinas Medical Center, Charlotte, NC, USA

Introduction Tissue dissection and vessel sealing is performed using a variety of energy sources and surgical devices. We describe the postmarketing analysis of a cordless ultrasonic dissector and vessel sealer in a series of general and gynecological procedures. Methods Patients were prospectively screened and consented for participation. Data collected included demographics, device activations/seals and failures, and patient complications. Surgeons were surveyed following each case. Data was analyzed using standard statistical methods. Results A total of 110 patients were consented and participated in the study. The most frequently performed procedures were bilateral salpingo-oophorectomy (n = 48) and total laparoscopic hysterectomy (n = 36). Mean age was 54.2 years and 79.2% were female. The most frequent number of device activations per case was between 26 and 50 (36.6%). Five failed seals occurred out of 4858 total estimated seals (0.11%). Failed seals were felt to be due to thickened, scarred tissue not amenable to device compression. There were no patient intraoperative complications related to the device itself. Overall, surgeons felt the device was extremely easy to use (97.6%) and no visual obstruction due to steam from the device was encountered (95%). Ninety-five percent of surgeons felt the device was beneficial for soft tissue dissection and vessel sealing. Conclusion Sonicision is safe and effective for use in dissection of soft tissues and vessel sealing in a variety of laparoscopic and open procedures. In this study, there were no complications related to the device itself. The remarkable cordless design of this device enhances its ease of use with overall excellent effectiveness.
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http://dx.doi.org/10.1177/1553350616630141DOI Listing
October 2016

Multimodality treatment of intrahepatic cholangiocarcinoma: A review.

J Surg Oncol 2016 Jan;113(1):62-83

Hepatobiliary and Pancreas Surgery, Carolinas Medical Center, Charlotte, North Carolina.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic cancer in the United States. Currently, curative treatment involves aggressive surgery. Chemotherapy and radiation treatments have been used for unresectable tumors with some success. Optimizing the use of current and developing novel multimodality treatment for iCCA is essential to improving outcomes.
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http://dx.doi.org/10.1002/jso.24093DOI Listing
January 2016

Mortality in hepatectomy: Model for End-Stage Liver Disease as a predictor of death using the National Surgical Quality Improvement Program database.

Surgery 2016 Mar 21;159(3):777-92. Epub 2015 Oct 21.

Division of Hepatopancreatobiliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, NC. Electronic address:

Background: The predictive value of the Model for End-stage Liver Disease (MELD) for mortality after hepatectomy is unclear. This study aimed to evaluate whether MELD score predicts death after hepatectomy and to identify the most useful score type for predicting mortality. We hypothesized that an increase in this score is correlated with 30-day mortality in patients undergoing hepatic resection.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for hepatectomy. Original MELD, United Network of Organ Sharing-modified MELD (uMELD), integrated MELD (i-MELD), and sodium-corrected MELD (MELD-Na) scores were calculated. Mortality was analyzed by multivariate logistic regression. MELD types were compared using receiver operating characteristic (ROC) curves.

Results: From 2005 to 2011, 11,933 hepatic resections were performed, including 7,519 partial, 2,104 right, and 1,210 left resections, and 1,100 trisectionectomies. The mean duration of stay was 8.4 ± 22.0 days, and there were 275 deaths (2.4%). The 30-day mortality rates were 1.8%, 6.9%, 15.4%, and 25% according to uMELD strata of 0-9, 10-19, 20-29, and ≥ 30, respectively. Multivariate analysis revealed that increasing MELD stratum was independently associated with higher mortality (P < .001) for all MELD types. The uMELD had the largest effect size (odds ratio [OR], 1.16; 95% CI, 1.10-1.20), whereas i-MELD had the narrowest CI (OR, 1.13; 95% CI, 1.10-1.17) and largest area under the ROC curve.

Conclusion: The postoperative 30-day mortality after hepatectomy increases with increasing MELD score across all MELD types. There is a 16% increase in the odds of mortality for each point increase in uMELD.
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http://dx.doi.org/10.1016/j.surg.2015.08.021DOI Listing
March 2016

Outcomes of surgical resection and loco-regional therapy in patients with stage 3A hepatocellular carcinoma: a retrospective review from the national cancer database.

HPB (Oxford) 2015 Nov 14;17(11):964-8. Epub 2015 Aug 14.

Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Objectives: In advanced stages, hepatocellular carcinoma (HCC) is often associated with major vascular involvement (cava, portal vein). The aim of the present study was to analyse the role of surgical resection (SR) and loco-regional therapy (LRT) in these advanced stage patients to determine if there was a survival benefit.

Methods: The study is a retrospective analysis from the Commission on Cancer's National Cancer Data Base (NCDB) from 1998 to 2011. In total, 148,882 patients with liver cancer were identified, of which 126,984 had HCC. Of these, 64,264 patients (1998-2006) had 5-year survival data available and 8825 patients had Stage 3A disease based on AJCC classification. Of these patients, 884 had SR, 771 had LRT and 7170 patients had neither intervention. Kaplan-Meier curves and log-rank tests were used for statistical analysis.

Results: Eight thousand eight hundred and twenty-five patients met analysis criteria. The mean age (years) in the SR, LRT and no intervention group were 62.5, 64.3 and 64.2, respectively. Most patients were males in all three groups (77.5%, 74.5% and 68.1%). The mean tumour size (cm) in the three groups was 9.8, 6.4 and 8.4, respectively. SR and LRT were primarily performed in major academic and comprehensive cancer programmes compared with community cancer programmes and other centres (SR: 93% versus 7%; LRT: 94.6% versus 5.4%). The median 5-year survival (months) was 26.6 in SR, 16.5 in LRT and 4.8 in the no intervention group (P < 0.0001).

Conclusion: A SR and LRT offer a survival benefit in select patients diagnosed with Stage 3A HCC.
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http://dx.doi.org/10.1111/hpb.12466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605333PMC
November 2015

Robotic pancreaticoduodenectomy for pancreatic adenocarcinoma: role in 2014 and beyond.

J Gastrointest Oncol 2015 Aug;6(4):396-405

Division of Hepato-Pancreato-Biliary Surgery, Department of General Surgery, Carolinas Medical Center, Charlotte, NC 28204, USA.

Minimally invasive surgery (MIS) for pancreatic adenocarcinoma has found new avenues for performing pancreaticoduodenectomy (PD) procedures, a historically technically challenging operation. Multiple studies have found laparoscopic PD to be safe, with equivalent oncologic outcomes as compared to open PD. In addition, several series have described potential benefits to minimally invasive PD including fewer postoperative complications, shorter hospital length of stay, and decreased postoperative pain. Yet, despite these promising initial results, laparoscopic PDs have not become widely adopted by the surgical community. In fact, the vast majority of pancreatic resections performed in the United States are still performed in an open fashion, and there are only a handful of surgeons who actually perform purely laparoscopic PDs. On the other hand, robotic assisted surgery offers many technical advantages over laparoscopic surgery including high-definition, 3-D optics, enhanced suturing ability, and more degrees of freedom of movement by means of fully-wristed instruments. Similar to laparoscopic PD, there are now several case series that have demonstrated the feasibility and safety of robotic PD with seemingly equivalent short-term oncologic outcomes as compared to open technique. In addition, having the surgeon seated for the procedure with padded arm-rests, there is an ergonomic advantage of robotics over both open and laparoscopic approaches, where one has to stand up for prolonged periods of time. Future technologic innovations will likely focus on enhanced robotic capabilities to improve ease of use in the operating room. Last but not least, robotic assisted surgery training will continue to be a part of surgical education curriculum ensuring the increased use of this technology by future generations of surgeons.
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http://dx.doi.org/10.3978/j.issn.2078-6891.2015.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502160PMC
August 2015

Implementation and evaluation of a tele-education system for the diagnosis of ophthalmic disease by international trainees.

AMIA Annu Symp Proc 2015;2015:366-75. Epub 2015 Nov 5.

Department of Ophthalmology, Weill Cornell Medical College, New York, NY.

Tele-education systems are increasingly being utilized in medical education worldwide. Due to limited human resources in healthcare in low and middle-income countries, developing online systems that are accessible to medical trainees in underserved areas potentially represents a highly efficient and effective method of improving the quantity and quality of the health care workforce. We developed, implemented, and evaluated an interactive web-based tele-education system (based on internationally accepted, image-based guidelines) for the diagnosis of retinopathy of prematurity among ophthalmologists-in-training in Brazil, Mexico, and the Philippines. We demonstrate that participation in this tele-education program improved diagnostic accuracy and reliability, and was preferred to standard pedagogical methods. This system may be employed not only in training, but also in international certification programs, and the process may be generalizable to other image-based specialties, such as dermatology and radiology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765571PMC
February 2017

Laparoscopic microwave ablation of human liver tumours using a novel three-dimensional magnetic guidance system.

HPB (Oxford) 2015 Jan 17;17(1):87-93. Epub 2014 Sep 17.

Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Background: Accurate antenna placement is essential for effective microwave ablation (MWA) of lesions. Laparoscopic targeting is made particularly challenging in liver tumours by the needle's trajectory as it passes through the abdominal wall into the liver. Previous optical three-dimensional guidance systems employing infrared technology have been limited by interference with the line of sight during procedures.

Objective: The aim of this study was to evaluate a newly developed magnetic guidance system for laparoscopic MWA of liver tumours in a pilot study.

Methods: Thirteen patients undergoing laparoscopic MWA of liver tumours gave consent to their participation in the study and were enrolled. Lesion targeting was performed using the InnerOptic AIM™ 3-D guidance system to track the real-time position and orientation of the antenna and ultrasound probe.

Results: A total of 45 ablations were performed on 34 lesions. The median number of lesions per patient was two. The mean ± standard deviation lesion diameter was 18.0 ± 9.2 mm and the mean time to target acquisition was 3.5 min. The first-attempt success rate was 93%. There were no intraoperative or immediate postoperative complications. Over an average follow-up of 7.8 months, one patient was noted to have had an incomplete ablation, seven suffered regional recurrences, and five patients remained disease-free.

Conclusions: The AIM™ guidance system is an effective adjunct for laparoscopic ablation. It facilitates a high degree of accuracy and a good first-attempt success rate, and avoids the line of site interference associated with infrared systems.
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http://dx.doi.org/10.1111/hpb.12315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266445PMC
January 2015

Survival analysis of patients with stage I and II hepatocellular carcinoma after a liver transplantation or liver resection.

HPB (Oxford) 2014 Dec 25;16(12):1102-9. Epub 2014 Jun 25.

Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Introduction: Liver transplantation (LT) is a treatment option in select patients with hepatocellular carcinoma (HCC). The aim of the present study was to compare survival in Stage I or II HCC patients undergoing either liver transplant (LT) or a liver resection (LR).

Method: The study is a retrospective analysis of the National Cancer Data Base (1998-2011). In total, 148,882 patients with liver cancer were identified, of which 5-year survival data (1998-2006) were available for 64,227 patients. Patients were stratified by the American Joint Committee on Cancer (AJCC) clinical stage I and II. Kaplan-Meier curves and log-rank tests were used for statistical analysis.

Results: 3340 HCC patients met analysis criteria. Among stage I HCC, 860 had LT and 871 had LR. Among stage II HCC, 833 had LT and 776 LR. In stage I patients the median survival for LT and LR were 127.9 and 56.7 months, respectively, (P < 0.0001) and in stage II patients the median survival was 110.8 and 42.8 months (P < 0.0001). Unlike LT patients, LR patients with Stage I HCC had a longer median survival compared with Stage II patients (P = 0.0002).

Conclusion: Liver transplantation offers a survival advantage compared with a liver resection among patients with Stage I and II HCC. LT is the best surgical treatment for early stage (I/II) HCC in patients with advanced fibrosis or cirrhosis, whereas LR provides equivalent outcomes to LT in patients without advanced fibrosis and should be considered as the first surgical option.
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http://dx.doi.org/10.1111/hpb.12300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253334PMC
December 2014

Outcomes of pancreatic debridement in acute pancreatitis: analysis of the nationwide inpatient sample from 1998 to 2010.

Am J Surg 2014 Sep 29;208(3):350-62. Epub 2014 Mar 29.

Carolinas Medical Center, Charlotte, NC, USA. Electronic address:

Background: The objective of this study was to perform a national review of patients with acute pancreatitis (AP) who undergo pancreatic debridement (PD) to evaluate for risk factors of in-hospital mortality.

Methods: The Nationwide Inpatient Sample was used to identify patients with AP who underwent PD between 1998 and 2010. Risk factors for in-hospital mortality were assessed with multivariate logistic regression.

Results: From 1998 to 2010, there were 585,978 nonelective admissions with AP, of which 1,783 (.3%) underwent PD. From 1998 to 2010, the incidence of PD decreased from .44% to .25% (P < .01) and PD in-hospital mortality decreased from 29.0% to 15% (P < .05). Of patients undergoing PD, independent factors associated with increased odds of mortality were increased age (odds ratio [OR] 1.04, confidence interval [CI] 1.03 to 1.05; P < .01), sepsis with organ failure (OR 1.76, CI 1.24 to 2.51; P < .01), peptic ulcer disease (OR 1.83, CI 1.02 to 3.30; P < .05), liver disease (OR 2.27, CI 1.36 to 3.78; P < .01), and renal insufficiency (OR 1.78, CI 1.14 to 2.78; P < .05).

Conclusions: The incidence and operative mortality of PD have decreased significantly over the last decade in the United States with higher odds of dying in patients who are older, with chronic liver, renal, or ulcer disease, and higher rates of sepsis with organ failure.
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http://dx.doi.org/10.1016/j.amjsurg.2013.12.030DOI Listing
September 2014

Optimal ablation volumes are achieved at submaximal power settings in a 2.45-GHz microwave ablation system.

Surg Innov 2015 Feb 3;22(1):41-5. Epub 2014 Jun 3.

Carolinas Medical Center, Charlotte, NC, USA.

Introduction: Local ablative therapies, including microwave ablation (MWA), are common treatment modalities for in situ tumor destruction. Currently, 2.45-GHz ablation systems are gaining prominence because of the shorter application times required. The aims of this study were to determine optimal power and time to ablation volume (AbV) ratios for a new 1.8-mm-2.45-GHz antenna using ex vivo tissue models.

Methods: The 1.8-mm-2.45-GHz Accu2i MWA system was employed to perform ablations in bovine liver, porcine muscle, and porcine kidney ex vivo. Whole tissues were prewarmed (35°C) and multiple ablations performed at power settings of 60 to 180 W for 2- to 6-minute time intervals. Postablation, tissues were dissected, AbVs calculated, and correlations to power and time settings made.

Results: Significant increases in AbV were measured between each of the time points for a constant power setting in all 3 tissues. Increasing power settings led to significant increases in AbV at power settings ≤140 W. However, no significant increase in AbV was obtained at power settings >140 W.

Conclusions: Optimal efficiency for MWA using a new 1.8-mm-2.45-GHz system is achieved at settings of ≤140 W for 6 minutes in a range of ex vivo tissue and no additional benefit occurs by increasing the power setting to 180 W in these tissues.
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http://dx.doi.org/10.1177/1553350614532535DOI Listing
February 2015

The impact of regionalization of pancreaticoduodenectomy for pancreatic Cancer in North Carolina since 2004.

Am Surg 2014 Jun;80(6):561-6

Division of Hepato-Pancreato-Biliary Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina, USA.

Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers (HVCs) provide improved outcomes and regionalization is advocated. Rapid regionalization could, however, have detrimental effects. North Carolina has multiple HVCs, including an additional HVC added in late 2006. We investigated regionalization of PD and its effects before, and after, the establishment of this fourth HVC. The North Carolina Hospital Discharge Database was queried for all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and high (20/year or more). Mortality and major morbidity was assessed by comparing volume groups across time periods. Number of PDs for cancer increased 91 per cent (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium-volume centers (P < 0.001). Mortality was significantly less at HVCs (2.8%) compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to 2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per cent (P = 0.31). Major morbidity was not significantly different between groups within either time period; however, there was a significant increase in major morbidity at low-volume centers (P = 0.018). Regionalization of PD for cancer is occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid regionalization has not detracted from the superior outcomes at HVCs.
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June 2014

Fibrin sealants and topical agents in hepatobiliary and pancreatic surgery: a critical appraisal.

Langenbecks Arch Surg 2014 Oct 2;399(7):825-35. Epub 2014 Jun 2.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Carolinas Medical Center, 1025 Moorehead Medical Drive, Suite 600, Charlotte, NC, 28204, USA.

Introduction: Fibrin sealants and topical hemostatic agents have been used extensively in hepatobiliary and pancreatic (HPB) surgery to promote coagulation and clot formation decreasing the need for allogeneic blood transfusion and to act as tissue sealants, ideally preventing biliary, enteric, and pancreatic leaks.

Results: Current literature has demonstrated some favorable outcomes using many different products for application in the field of HPB surgery. However, critical findings exist demonstrating lack of reproducible efficacy or benefit. In all, many clinical trials have demonstrated effectiveness of fibrin sealants and other agents at reducing the need for intraoperative and postoperative blood transfusion. Ability to effectively seal tissues providing biliostatic effect or preventing postoperative fistula formation remains debated as definitive evidence is lacking.

Conclusions: In the following invited review, we discuss current literature describing the use of topical agents and fibrin sealants in liver and pancreas surgery. We summarize major contemporary clinical trials and their findings regarding the use of these agents in HPB surgery and provide evidence from the preclinical literature as to the translation of these products into the clinical arena.
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http://dx.doi.org/10.1007/s00423-014-1215-5DOI Listing
October 2014

Laparoscopic transgastric endolumenal cystogastrostomy and pancreatic debridement.

Surg Endosc 2014 May 27;28(5):1465-72. Epub 2014 Mar 27.

Section of Hepatobiliary and Pancreas Surgery, Department of General Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Background: Cystogastrostomy is commonly performed for internal drainage of pancreatic pseudocysts (PP) and concomitant debridement of walled-off pancreatic necrosis (WOPN). While an open approach to cystogastrostomy is well established, an optimal minimally invasive technique continues to evolve. This laparoscopic transgastric endolumenal cystogastrostomy presented here allows for a large cystogastrostomy with complete debridement of necrosis and internal drainage through a minimally invasive approach.

Methods: We performed a retrospective review of 22 patients with symptomatic PP/WOPN treated with attempted laparoscopic transgastric endolumenal cystogastrostomy (Lap-TEC) and pancreatic debridement. Short- and long-term outcomes were assessed.

Results: From November 2006 to March 2013, a total of 22 Lap-TEC/pancreatic debridement procedures were attempted; 15 were completed laparoscopically. The median age of the cohort was 49.5 ± 12 years (range = 18-71), average body mass index = 29.1 kg/m(2), 77 % had an ASA score ≥ 3, and 10 were female. Gallstones were the most common etiology (50 %), and median time between initial presentation and surgery was 86 days (range = 0-360). Median operative time and estimated blood loss were 213 min and 100 cc, respectively. Forty-one percent of the patients were admitted to the ICU postoperatively and the average length of stay was 14 days (range = 4-50). Median follow-up was 2 months (range = 0-62.5), with one patient having a procedure-related complication. No other reoperations, late complications, or mortalities occurred. All patients had resolution of their symptoms and fluid collections.

Conclusion: This technique of internal drainage via Lap-TEC and pancreatic debridement has been successful in achieving primary drainage and relieving symptoms of PP/WOPN with no mortality and minimal morbidity.
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http://dx.doi.org/10.1007/s00464-013-3317-5DOI Listing
May 2014

Regionalization and outcomes of hepato-pancreato-biliary cancer surgery in USA.

J Gastrointest Surg 2014 Mar 16;18(3):532-41. Epub 2014 Jan 16.

Division of Gastrointestinal and Minimally Invasive Surgery, Carolinas Laparoscopic and Advanced Surgery Program, Carolinas Medical Center, 1025 Morehead Medical Drive, Suite 300, Charlotte, NC, 28204, USA.

Background: Recent publications demonstrate regionalization of complex operations to high-volume centers (HVCs) in the USA. We hypothesize that this pattern applies to hepato-pancreato-biliary (HPB) cancer resections and improved outcomes.

Methods: The Nationwide Inpatient Sample (NIS) data were analyzed from 1995-1999(T1) to 2005-2009(T2) for all HPB oncologic resections. Division of hospitals into high-, mid-, and low-volume centers (HVC, MVC, LVC) was performed. Multivariate regression was utilized to identify predictors of LVC resection. Outcomes were compared in both eras.

Results: A total of 45,815 cases met the inclusion criteria (19,250 from T1 and 25,565 from T2). At T1, 32.5% of resections were performed at HVCs and 34.9% at LVCs. At T2, 60.8% were performed at HVCs versus 18.5% at LVCs. In T1, inpatient mortality at HVCs versus LVCs was 3.3% versus 8.67% (p < 0.0001) and 2.7% versus 6.5% (p < 0.0001) in T2. LOS and routine discharge were improved in HVCs, but total charges were higher. All outcomes significantly differed between HVCs and LVCs in multivariate analysis, except for LOS and total charges in T2.

Conclusion: The most recent NIS data demonstrate better outcomes in HVCs for HPB oncologic resections. These trends reflect alignment with national recommendations to centralize complex cancer surgery, as well as improved outcomes in all centers.
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http://dx.doi.org/10.1007/s11605-014-2454-zDOI Listing
March 2014

Microwave ablation for hepatic malignancies: a multiinstitutional analysis.

Ann Surg 2014 Jun;259(6):1195-200

*Department of Surgery, Medical College of Wisconsin; Milwaukee, WI †Department of General Surgery, Carolinas Medical Center; Charlotte, NC ‡Division of Surgical Oncology, Ohio State University Wexner Medical Center; Columbus, OH §Department of Radiology, Ohio State University Wexner Medical Center; Columbus, OH ¶Department of Surgery, University of Louisville; Louisville, KY ∥Department of Radiology, Medical College of Wisconsin; Milwaukee, WI.

Objective: This study hypothesized that tumor size, number of tumors, surgical approach, and tumor histology significantly affected microwave ablation (MWA) success and recurrence-free survival.

Background: Although many hepatobiliary centers have adopted MWA, the factors that influence local control are not well described.

Methods: Consecutive patients with hepatic malignancy treated by MWA were included from 4 high-volume institutions (2003-2011) and grouped by histology: hepatocellular carcinoma (HCC), colorectal liver metastases, neuroendocrine liver metastases, and other cancers. Independent significance of outcome variables was established with logistic regression and Cox proportional hazards models.

Results: Four hundred fifty patients were treated with 473 procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18 months. Concurrent hepatectomy was performed in 178 patients (38%), and when performed was associated with greater morbidity. Complete ablation was confirmed for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no significant impact on complication rates, recurrence, or survival. The local recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size 3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95% CI: 1.02-2.50, P = 0.039).

Conclusions: In this large data set, patients with 3 cm or more tumors showed a propensity for early recurrence, regardless of histology. Higher rates of local recurrence were noted in HCC patients, which may reflect underlying liver disease. There were no significant differences in morbidity or survival based on the surgical approach; however, local recurrence rates were highest for percutaneously ablated tumors.
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http://dx.doi.org/10.1097/SLA.0000000000000234DOI Listing
June 2014

Microwave ablation using 915-MHz and 2.45-GHz systems: what are the differences?

HPB (Oxford) 2013 Dec 14;15(12):991-6. Epub 2013 Mar 14.

Section of Hepatobiliary and Pancreas Surgery, Carolinas Medical Center, Charlotte, NC, USA.

Objectives: This study was conducted to evaluate differences between 915-MHz and 2.45-GHz microwave ablation (MWA) systems in the ablation of hepatic tumours.

Methods: A retrospective analysis of patients undergoing hepatic tumour MWA utilizing two different systems over a 10-month period was carried out.

Results: Data for a total of 48 patients with a mean age of 58 ± 1.24 years were analysed. A total of 124 tumours were ablated; 72 tumours were ablated with a 915-MHz system and 52 with a 2.45-GHz system. Mean tumour diameters were 1.7 ± 0.1 cm in the 915-MHz group and 2.5 ± 0.2 cm in the 2.45-GHz group (P < 0.01). Mean ablation time per burn was 8.1 ± 0.3 min in the 915-MHz group and 4.0 ± 0.1 min in the 2.45-GHz group (P < 0.01). The mean number of burns per lesion was 2.0 ± 0.1 in the 915-MHz group and 1.7 ± 0.1 in the 2.45-GHz group (P < 0.05). The mean ablation time per lesion was 9.7 ± 0.7 min in the 915-MHz group, and 6.6 ± 0.6 min in the 2.45-GHz group (P < 0.01). The 2.45-GHz system demonstrated a better correlation between ablation time and tumour size (r(2) = 0.6222) than the 915-MHz system; (r(2) = 0.0696). Mean total energy applied per lesion, and energy applied per cm, were greater with the 915-MHz system (P < 0.05 and P < 0.01, respectively). Total energy applied per lesion was similarly correlated for the 2.45-GHz (r(2) = 0.6263) and 915-MHz (r(2) = 0.7012) systems. Mean total energy applied per cm/min was greater with the 2.45-GHz system (P < 0.05).

Conclusions: Both 915-MHz and 2.45-GHz MWA systems achieve reproducible hepatic tumour ablation. The 2.45-GHz system achieves equivalent, but more predictable and faster ablations using a single antenna system.
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http://dx.doi.org/10.1111/hpb.12081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843618PMC
December 2013

Obesity, but not ethanol, promotes tumor incidence and progression in a mouse model of hepatocellular carcinoma in vivo.

Surg Endosc 2013 Aug 7;27(8):2782-91. Epub 2013 Mar 7.

Department of General Surgery, Hepatobiliary and Pancreatic Surgery, Carolinas Medical Center, 1025 Morehead Medical Drive, Suite 300, Charlotte, NC 28203, USA.

Background: Hepatocellular carcinoma (HCC) is a major global health burden. Although chronic, heavy alcohol abuse is an established risk factor for HCC, obesity is emerging as an increasingly important factor in HCC development. Given that other risk factors for HCC act synergistically to promote tumorigenesis, we investigated the effects of diet-induced obesity and chronic ethanol consumption on tumor progression.

Methods: A diethylnitrosamine (DEN) mouse model of HCC was established and mice randomized to control (CD; 10 % kcal% fat) or high fat (HFD; 60 % kcal% fat diet) at 5 weeks of age. At 35 weeks, mice were randomized to 10/20 % ethanol (EtOH) in drinking water (alternate days), or drinking water (H2O) alone. Tumor incidence/size were measured and confirmed. Liver tissue was analyzed for oxidative stress and EtOH-metabolizing enzymes and serum analyzed for liver function and nutritional status.

Results: DEN treatment induced HCC formation in 60 % CD-H2O mice (6 of 10), an effect exacerbated by HFD (89 %). Tumors in HFD animals occupied significantly more of the liver than mice on CD. EtOH-feeding did not impact HCC incidence or tumor size. HFD resulted in increased liver injury and liver:body weight ratio regardless of EtOH consumption. Increased tumor incidence was associated with elevated hepatic oxidative stress in the absence of changes in intrinsic antioxidant (glutathione) levels.

Conclusions: Obesity independently promoted HCC formation in the absence or presence of a known hepatocarcinogen (DEN), and enhanced both number and size of hepatic tumors independent of chronic EtOH consumption in mice.
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http://dx.doi.org/10.1007/s00464-013-2808-8DOI Listing
August 2013

Operative microwave ablation for hepatocellular carcinoma: complications, recurrence, and long-term outcomes.

J Gastrointest Surg 2013 Apr 13;17(4):719-29. Epub 2013 Feb 13.

Hepato-Pancreato-Biliary Surgery, Department of General Surgery, Carolinas Medical Center, 1025 Morehead Medical Drive, Suite 300, Charlotte, NC 28204, USA.

Background: Treatment of hepatocellular carcinoma (HCC) in the setting of cirrhosis is limited by tumor size/location and underlying liver disease. Radiofrequency ablation is utilized in selected patients; however, local recurrence remains a concern. Microwave ablation (MWA) delivers energy to tissue in a unique fashion, reducing local recurrence. A minimally invasive operative approach allows for mobilization/protection of adjacent structures, intra-operative ultrasound, and assessment of ablation progress.

Study Design: Retrospective review of operative MWA performed for HCC in patients with cirrhosis over a 4-year period at a single center. Complications were stratified by Clavien-Dindo classification. Incomplete ablation and local, regional, and metastatic recurrence was assessed on follow-up imaging. Survival was assessed in months.

Results: Fifty-four patients with 73 tumors underwent MWA. Median tumor size was 2.6 cm (range 0.5-8.5 cm). Cirrhosis was present in 92.6 % of patients, with a Child-Pugh score of B/C in 27.8 % and hepatitis C present in 59.3 %. A minimally invasive approach was used in 94.5 % of patients. There were no deaths within 30 days. Thirty-day morbidity was 28.9 %, with grade III complications present in 11.5 %. Delayed complications occurred in 7.8 % of patients, with a 5.6 % 90-day mortality. Incomplete ablation was identified in 5.9 % of tumors with local recurrence of 2.9 % at 9 months median follow-up. Regional and metastatic recurrence occurred in 27.5 and 11.8 % at 9 months median follow-up. Median survival was not reached at 11 months median follow-up. One- and 2-year survival was 72.3 and 58.8 %.

Conclusion: Operative, preferably minimally invasive, MWA can be performed in cirrhotic patients with HCC with acceptable morbidity and low recurrence rates. High regional and metastatic recurrence rates in these patients underscore the need for minimally invasive, low morbidity approaches to liver-directed therapy.
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http://dx.doi.org/10.1007/s11605-013-2164-yDOI Listing
April 2013

Evaluation of an innovative, cordless ultrasonic dissector.

Surg Innov 2013 Oct 8;20(5):524-9. Epub 2013 Jan 8.

1Carolinas Medical Center, Charlotte, NC, USA.

Ultrasonic thermal energy is commonly used for dissection and vessel ligation. This study compared HARMONIC ACE and Sonicision Cordless Ultrasonic Dissector (SCUD). The devices were used in an in vivo porcine model to coagulate 189 arteries up to 5 mm. Seal times were similar: SCUD, 5.2 ± 1.7 s; ACE, 4.9 ± 1.5 s (P = .20). Burst pressures for SCUD and AVE were 578 ± 284 and 605 ± 288 mm Hg, respectively (P = .48). Stratification by vessel diameter yielded similar results. In all, 17 applications resulted in seal failure on either the proximal or distal side, with no difference between SCUD (4.4%) and ACE (6.6%; P = .37). Histological examination of 48 specimens showed similar thermal spreads: 1.06 ± 0.05 versus 1.08 ± 0.05 mm for SCUD and ACE, respectively (P = .82). In 41 timed mesenteric transections, SCUD required 24.8 ± 4.9 s, which was significantly less than the 33.8 ± 5.4 s for ACE (P < .0001), with no bleeding in either group. SCUD and ACE showed similar vessel seal times, burst pressures, thermal spreads, and seal failure rates. SCUD was more efficient than ACE in mesenteric transection.
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http://dx.doi.org/10.1177/1553350612471206DOI Listing
October 2013
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