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1.
Sci Rep ; 11(1): 4966, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33654115

ABSTRACT

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.


Subject(s)
Exome Sequencing , Retinal Neovascularization/genetics , Retinopathy of Prematurity/genetics , Female , Humans , Infant, Newborn , Infant, Premature , Male
2.
Ophthalmol Retina ; 3(5): 444-450, 2019 05.
Article in English | MEDLINE | ID: mdl-31044738

ABSTRACT

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.


Subject(s)
Neural Networks, Computer , Ophthalmoscopy/methods , Retinopathy of Prematurity/diagnostic imaging , Algorithms , Female , Humans , Image Processing, Computer-Assisted/methods , Infant, Newborn , Male , ROC Curve
3.
Ophthalmol Retina ; 2(9): 949-962, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30250936

ABSTRACT

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.

4.
Surv Ophthalmol ; 63(5): 618-637, 2018.
Article in English | MEDLINE | ID: mdl-29679617

ABSTRACT

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.


Subject(s)
Retinopathy of Prematurity/etiology , Birth Weight , Diet , Female , Gestational Age , Humans , Infant, Premature , Oxygen/adverse effects , Pregnancy , Pregnancy Complications , Risk Factors , Smoking/adverse effects
5.
AMIA Annu Symp Proc ; 2018: 1224-1232, 2018.
Article in English | MEDLINE | ID: mdl-30815164

ABSTRACT

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.


Subject(s)
Algorithms , Deep Learning , Fundus Oculi , Neural Networks, Computer , Retina/diagnostic imaging , Retinopathy of Prematurity/diagnostic imaging , Area Under Curve , Humans , Infant, Newborn , Infant, Premature , ROC Curve , Reproducibility of Results , Telemedicine/methods
6.
J Gastrointest Oncol ; 8(2): 337-346, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28480072

ABSTRACT

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.

7.
Ophthalmology ; 124(7): 953-961, 2017 07.
Article in English | MEDLINE | ID: mdl-28385303

ABSTRACT

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.


Subject(s)
Clinical Competence , Education, Medical, Graduate/methods , Internet , Ophthalmologists/education , Ophthalmology/education , Retinopathy of Prematurity/diagnosis , Telemedicine/methods , Follow-Up Studies , Humans , Mexico , Prospective Studies , Reproducibility of Results
8.
Ophthalmology ; 123(11): 2338-2344, 2016 11.
Article in English | MEDLINE | ID: mdl-27591053

ABSTRACT

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 R2 = 0.82; and dataset B: P < 0.05 and adjusted R2 = 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.


Subject(s)
Neonatal Screening/methods , Retina/diagnostic imaging , Retinal Vessels/diagnostic imaging , Retinopathy of Prematurity/diagnosis , Diagnosis, Differential , Female , Humans , Infant, Newborn , Male , Photography , ROC Curve , Reproducibility of Results , Retinopathy of Prematurity/classification
9.
Ophthalmology ; 123(11): 2345-2351, 2016 11.
Article in English | MEDLINE | ID: mdl-27566853

ABSTRACT

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.


Subject(s)
Clinical Competence , Diagnostic Techniques, Ophthalmological/trends , Image Processing, Computer-Assisted/methods , Retina/diagnostic imaging , Retinopathy of Prematurity/diagnosis , Humans , Infant, Newborn , ROC Curve , Reproducibility of Results , Retinopathy of Prematurity/classification , Severity of Illness Index
10.
Surg Innov ; 23(5): 505-10, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26839213

ABSTRACT

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.


Subject(s)
General Surgery/instrumentation , Gynecologic Surgical Procedures/instrumentation , Patient Safety , Product Surveillance, Postmarketing , Surgical Instruments , Ultrasonics/instrumentation , Dissection/instrumentation , Equipment Design , Equipment Safety , Female , General Surgery/methods , Gynecologic Surgical Procedures/methods , Humans , Male , Minimally Invasive Surgical Procedures/instrumentation , Minimally Invasive Surgical Procedures/methods , Prospective Studies
11.
J Surg Oncol ; 113(1): 62-83, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26797780

ABSTRACT

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.


Subject(s)
Bile Duct Neoplasms/therapy , Cholangiocarcinoma/therapy , Combined Modality Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/epidemiology , Catheter Ablation , Cholangiocarcinoma/epidemiology , Embolization, Therapeutic/methods , Humans , Immunotherapy/methods , Prognosis , Proton Therapy , Radiosurgery , United States/epidemiology , Yttrium Radioisotopes/therapeutic use
12.
Surgery ; 159(3): 777-92, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26474653

ABSTRACT

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.


Subject(s)
Cause of Death , End Stage Liver Disease/mortality , End Stage Liver Disease/surgery , Hepatectomy/mortality , Hospital Mortality/trends , Quality Improvement/standards , Age Factors , Aged , Cohort Studies , Confidence Intervals , Databases, Factual , End Stage Liver Disease/etiology , Female , Follow-Up Studies , Hepatectomy/methods , Humans , Liver Neoplasms/complications , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Sex Factors , Time Factors , United States
13.
Am Surg ; 82(12): 1196-1202, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-28234184

ABSTRACT

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.


Subject(s)
Gastroenterology/organization & administration , Practice Management, Medical/organization & administration , Specialties, Surgical/organization & administration , Tertiary Care Centers/organization & administration , Clinical Coding , Delegation, Professional , Gastroenterology/economics , Humans , Liver Diseases/surgery , Marketing of Health Services/methods , Marketing of Health Services/organization & administration , Operating Rooms/organization & administration , Pancreatic Diseases/surgery , Population Density , Practice Management, Medical/economics , Professional Practice Location , Referral and Consultation/organization & administration , Research , Salaries and Fringe Benefits/economics , Specialties, Surgical/economics , Tertiary Care Centers/economics , United States
14.
Am Surg ; 82(11): 1121-1125, 2016 Nov 01.
Article in English | MEDLINE | ID: mdl-28206942

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Neuroendocrine/pathology , Liver Neoplasms/pathology , Neoplasms, Complex and Mixed/pathology , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/genetics , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/genetics , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/genetics , Male , Neoplasms, Complex and Mixed/diagnostic imaging , Neoplasms, Complex and Mixed/genetics , Tomography, X-Ray Computed
15.
HPB (Oxford) ; 17(11): 964-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26271743

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/therapy , Hepatectomy/methods , Liver Neoplasms/therapy , Neoplasm Staging , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Combined Modality Therapy , Databases, Factual , Disease Progression , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Puerto Rico/epidemiology , Retrospective Studies , Survival Rate/trends , United States/epidemiology
16.
J Gastrointest Oncol ; 6(4): 396-405, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26261726

ABSTRACT

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.

17.
AMIA Annu Symp Proc ; 2015: 366-75, 2015.
Article in English | MEDLINE | ID: mdl-26958168

ABSTRACT

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.


Subject(s)
Internship and Residency , Ophthalmology/education , Retinopathy of Prematurity/diagnosis , Telemedicine/methods , Adult , Brazil , Female , Humans , Internet , Male , Mexico , Ophthalmology/standards , Philippines , Reproducibility of Results
18.
HPB (Oxford) ; 17(1): 87-93, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25231167

ABSTRACT

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.


Subject(s)
Ablation Techniques , Imaging, Three-Dimensional , Laparoscopy/methods , Liver Neoplasms/surgery , Magnetics/methods , Microwaves/therapeutic use , Surgery, Computer-Assisted/methods , Ultrasonography, Interventional/methods , Ablation Techniques/instrumentation , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Equipment Design , Female , Humans , Image Interpretation, Computer-Assisted , Imaging, Three-Dimensional/instrumentation , Laparoscopy/instrumentation , Liver Neoplasms/pathology , Magnetics/instrumentation , Male , Materials Testing , Middle Aged , Neoplasm Recurrence, Local , Pilot Projects , Predictive Value of Tests , Prospective Studies , Surgery, Computer-Assisted/instrumentation , Time Factors , Transducers , Treatment Outcome , Ultrasonography, Interventional/instrumentation
19.
Surg Innov ; 22(1): 41-5, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24899579

ABSTRACT

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.


Subject(s)
Catheter Ablation/methods , Microwaves/therapeutic use , Animals , Cattle , Kidney/surgery , Liver/surgery , Muscle, Skeletal/surgery , Surgery, Computer-Assisted , Swine , Time Factors
20.
HPB (Oxford) ; 16(12): 1102-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24964271

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Liver Transplantation , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Databases, Factual , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Staging , Patient Selection , Proportional Hazards Models , Retrospective Studies , Time Factors , Treatment Outcome , United States/epidemiology
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