Sophie C. Hofferberth

The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. METHODS Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). RESULTS At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). CONCLUSIONS Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.

Left thoracoscopic sympathectomy for cardiac denervation in patients with life-threatening ventricular arrhythmias

BACKGROUND We reported the outcomes of a single-institution experience using video-assisted thoracoscopic left cardiac sympathetic denervation as an adjunctive therapeutic technique in pediatric and young adult patients with life-threatening ventricular arrhythmias. METHODS We conducted a retrospective clinical review of all patients who underwent left cardiac sympathetic denervation by means of video-assisted thoracoscopic surgery at our institution. From August 2000 to December 2011, 24 patients (13 with long QT syndrome, 9 with catecholaminergic polymorphic ventricular tachycardia, and 2 with idiopathic ventricular tachycardia) were identified from the cardiology database and surgical records. RESULTS There were no intraoperative complications. The median postoperative length of stay was 2 days (range, 1-32 days). There were no major perioperative complications. Longer-term follow-up was available in 22 of 24 patients at a median follow-up of 28 months (range, 4-131 months). Sixteen (73%) of the 22 patients experienced a marked reduction in their arrhythmia burden, with 12 (55%) becoming completely arrhythmia free after sympathectomy. Six (27%) of the patients were nonresponsive to treatment; each had persistent symptoms at follow-up. CONCLUSIONS Video-assisted thoracoscopic left cardiac sympathetic denervation can be safely and effectively performed in most patients with life-threatening ventricular arrhythmias. This minimally invasive procedure is a promising adjunctive therapeutic option that achieves a beneficial response in most symptomatic patients. These results support the inclusion of thoracoscopic cardiac sympathetic denervation among the treatment armamentarium in all patients with ventricular arrhythmias refractive to conventional medical therapy.

Combined Proximal Endografting With Distal Bare-Metal Stenting for Management of Aortic Dissection

BACKGROUND Established endovascular treatments for aortic dissection often result in incomplete aortic repair, potentially leading to late complications involving the distal aorta. To address the problems of incomplete true lumen reconstitution and late aneurysmal change, we report the midterm results of combined proximal endografting with distal true lumen bare-metal stenting (STABLE: Staged Total Aortic and Branch vesseL Endovascular reconstruction) in Stanford type A and B aortic dissection. METHODS Between January 2003 and January 2010, 31 patients underwent staged total aortic and branch vessel endovascular reconstruction for management of acute (type A, 13; type B, 11) and chronic (type B, 7) aortic dissection. Proximal endografting was combined with bare-metal Z stent implantation in the distal true lumen. Patients with type A dissection underwent adjunctive treatment at operation. Computed tomography angiography was performed at baseline, 1 year, and annually thereafter to assess aortic remodelling. RESULTS Primary technical success was 97%. Thirty-day rates of death, stroke, and permanent paraplegia/paresis were 3% (n=1), 0%, and 0%, respectively. Mean follow-up was 57.3 months (range, 5 to 100 months). Overall survival was 60% at 100 months. Aortic-specific survival was 93%. Four patients (13%) underwent device-related reintervention. One (3%) late aortic-related death occurred. Thoracic (p=0.64) and abdominal (p=0.14) aortic dimensions were stable. The true lumen index increased significantly at follow-up. CONCLUSIONS Staged total aortic and branch vessel endovascular reconstruction is a feasible ancillary endovascular technique to address the problems of distal true lumen collapse, incomplete aortic remodelling, and late aneurysm formation in aortic dissection.

Management of Congenital Tracheal Stenosis

Congenital tracheal stenosis (CTS) is a serious and rare condition. In most cases, stenotic lesions are composed of complete tracheal rings of cartilage. The severity of symptoms correlates with the length of affected trachea, the presence of concomitant respiratory conditions, degree of luminal narrowing, and any bronchial involvement. Critically, CTS is a disorder that can lead to life-threatening respiratory insufficiency in children. Thus, it is a clinical entity that demands timely diagnosis and treatment. This review will firstly discuss the anatomy and pathophysiology of CTS and outline the various clinical presentations associated with the disorder. In addition, methods of diagnosis and treatment strategies will be reviewed, with a focus on contemporary surgical techniques. Finally, postoperative care of patients with CTS will be reviewed, and a contemporary multidisciplinary management approach will be presented.

Aortic False Lumen Thrombosis Induction by Embolotherapy (AFTER) Following Endovascular Repair of Aortic Dissection

Purpose To report the use of a technique (AFTER: aortic false lumen thrombosis induction by embolotherapy) to achieve false lumen (FL) thrombosis and aortic remodeling in patients with residual FL patency after initial endovascular repair of aortic dissection. Methods Between January 2003 and January 2010, 31 patients underwent staged total aortic and branch vessel endovascular reconstruction (STABLE) of type A (n = 13) and type B (n = 18) dissection. Of these, 10 patients (5 men; mean age 61 years) who had undergone repair of 4 acute type A, 3 acute type B, and 3 chronic type B dissections demonstrated re-entry tear(s) and FL patency associated with aortic expansion ≥5 mm or flow into a persistently dilated aortic segment. Catheter-directed embolization using coils, glue, or occlusion balloons was performed via a transfemoral approach to the true lumen at a mean of 7 months (range <1 to 26) after initial repair. Results Technical success was achieved in all patients, with no intraoperative complications. Thirty-day morbidity and mortality was nil. Mean follow-up was 63 months (range 13–96). Reversal or stabilization (<5-mm increase) of thoracoabdominal aortic growth occurred in 9 patients. Complete thrombosis of the thoracic and abdominal FL occurred in 2 patients. In 4, FL occlusion and subsequent thrombosis of the upstream thoracic segment was achieved. Four demonstrated partial FL thrombosis in the thoracic and abdominal aorta. One patient with chronic aneurysmal type B dissection died 4 months post-embolization from aortic rupture. Conclusion The AFTER strategy appears to be a safe and promising adjunctive endovascular approach to treat residual FL patency or aortic enlargement post endovascular repair of aortic dissection. Elimination of FL flow and stabilization of aortic expansion may reduce the risk of late distal aortic complications.

Impact of pacing on systemic ventricular function in L-transposition of the great arteries

OBJECTIVE(S) To assess the impact of univentricular versus biventricular pacing (BiVP) on systemic ventricular function in patients with congenitally corrected transposition of the great arteries (ccTGA). METHODS We performed a retrospective review of all patients with a diagnosis of ccTGA who underwent pacemaker insertion. From 1993 to 2014, 53 patients were identified from the cardiology database and surgical records. RESULTS Overall mortality was 7.5% (n = 4). One patient required transplantation and 3 late deaths occurred secondary to end-stage heart failure. Median follow-up was 3.7 years (range, 4 days to 22.5 years). Twenty-five (47%) underwent univentricular pacing only, of these, 8 (32%) developed significant systemic ventricular dysfunction. Twenty-eight (53%) received BiVP, 17 (26%) were upgraded from a dual-chamber system, 11 (21%) received primary BiVP. Fourteen (82%) of the 17 undergoing secondary BiVP demonstrated systemic ventricular dysfunction at the time of pacer upgrade, with 7 (50%) demonstrating improved systemic ventricular function after pacemaker upgrade. Overall, 42 (79%) patients underwent univentricular pacing, with 22 (52%) developing significant systemic ventricular dysfunction. In contrast, the 11 (21%) who received primary BiVP had preserved systemic ventricular function at latest follow-up. CONCLUSIONS Late-onset systemic ventricular dysfunction is a major complication associated with the use of univentricular pacing in patients with ccTGA. All patients with ccTGA who develop heart block should undergo primary biventricular pacing, as this prevents late systemic ventricular dysfunction. Preemptive placement of BiVP leads at the time of anatomical repair or other permanent palliative procedure will facilitate subsequent BiVP should heart block develop.

Paclitaxel-loaded expansile nanoparticles enhance chemotherapeutic drug delivery in mesothelioma 3-dimensional multicellular spheroids

OBJECTIVES Intraperitoneal administration of paclitaxel-loaded expansile nanoparticles (Pax-eNPs) significantly improves survival in an in vivo model of malignant mesothelioma compared with conventional drug delivery with the clinically utilized Cremophor EL/ethanol (C/E) excipient. However, in vitro monolayer cell culture experiments do not replicate this superior efficacy, suggesting Pax-eNPs utilize a unique mechanism of drug delivery. Using a mesothelioma spheroid model, we characterized the mechanisms of enhanced tumor cytotoxicity leveraged by Pax-eNPs. METHODS Human malignant mesothelioma (MSTO-211H) spheroids were co-incubated for 24 hours with Oregon Green-conjugated paclitaxel dissolved in C/E or loaded into eNPs. Oregon Green-paclitaxel uptake was measured as Oregon Green intensity via confocal microscopy and kinetics of tumor cytotoxicity were assessed via propidium iodide staining. Pharmacologic endocytotic inhibitors were used to elucidate mechanisms of eNP uptake into spheroids. RESULTS Increased drug penetration and a 38-fold higher intraspheroidal drug concentration were observed 24 hours after MSTO-211H spheroids were treated with Oregon Green-conjugated paclitaxel loaded into eNPs compared with Oregon Green-conjugated paclitaxel dissolved in C/E (P < .01). Macropinocytosis was the dominant endocytotic pathway of eNP uptake. Spheroids were more susceptible to paclitaxel when delivered via eNP, exhibiting more than twice the propidium iodine intensity compared with an equivalent paclitaxel-C/E dose. CONCLUSIONS Compared with monolayer cell culture, the in vitro 3-D tumor spheroid model better reflects the superior in vivo efficacy of Pax-eNPs. Persistent tumor penetration and prolonged intratumoral release are unique mechanisms of Pax-eNP cytotoxicity. 3-D spheroid models are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.

Takedown of cavopulmonary shunt at biventricular repair

OBJECTIVE With advances in valve repair and ventricular recruitment strategies, patients initially palliated with single ventricle physiology have been increasingly brought to biventricular circulation. Few data are available on the technical aspects and outcomes after takedown of the superior cavopulmonary anastomosis (bidirectional Glenn [BDG]). We reviewed a single-institutional experience in BDG takedown. METHODS The demographic, procedural, and outcome data were obtained for all children who had undergone BDG takedown at our institution from 2000 to 2012. The primary outcome measures were achievement of biventricular circulation, reoperation, and mortality. The secondary outcome measures were postoperative arrhythmias, superior vena cava (SVC)-right atrium (RA) or pulmonary artery stenosis at the BDG takedown site. RESULTS A total of 40 patients were included during the study period, with a mean age of 4.4 years (range, 7 months to 22 years). Primary SVC-RA anastomosis was performed in 7 patients (18%), and an anterior patch was used in 33 patients (82%). Of the 40 patients, 38 were discharged with biventricular physiology (98%) and mild or less ventricular dysfunction. During a mean follow-up period of 3.4±2.9 years, 3 patients died and 1 required heart transplantation; 2 patients developed more than mild SVC stenosis requiring reintervention and 1 developed pulmonary artery stenosis. Finally, 34 patients were in normal sinus rhythm and 4 had heart block (1 pacemaker placement). CONCLUSIONS BDG takedown can be undertaken with a low operative risk and a low incidence of SVC or pulmonary artery stenosis or sinus node dysfunction. Additional follow-up is required to see how the reconstructed SVC grows.

Valve-sparing repair with intraoperative balloon dilation in tetralogy of Fallot: Midterm results and therapeutic implications

Objectives: The significant morbidity of long‐term pulmonary regurgitation (PR) has driven the development of pulmonary valve (PV) sparing repair strategies in patients with tetralogy of Fallot (ToF). We assessed mid‐term PV function in patients who underwent primary ToF repair with valve‐sparing intraoperative balloon dilation (IBD) technique. Methods: We evaluated 162 consecutive patients with ToF and pulmonary stenosis (ToF‐PS) who underwent valve‐sparing repair with IBD under 1 year of age. Results: Median age at surgery was 98 days (interquartile range [IQR], 72‐126) and median follow‐up was 2.5 years (IQR, 0.6‐4.9). Median preoperative PV annulus z score was −2.2 (IQR, −2.5 to −1.8). Twenty‐five patients (15.4%) required reintervention for residual valvular stenosis. Multivariable analysis demonstrated preoperative annulus z score less than −2.45 (P = .036) and younger age at surgery (P = .001) were independent risk factors for early reintervention for stenosis. Freedom from at least moderate PR was 77%, 61%, and 43% at 1, 3, and 5 years postrepair. Right ventricular dimensions were not significantly different compared with a matched cohort of patients undergoing transannular patch repair at midterm follow‐up. Conclusions: Patients with ToF‐PS who undergo valve‐sparing repair with IBD develop progressive PR. Compared with transannular patch repair, the extent of RV dilation at midterm follow‐up is not significantly different. Patients younger than 3 months of age and those with an annulus z score less than −2.45 experience higher rates of early reintervention for PV stenosis. In these patient subgroups, alternative strategies should be considered. This study suggests valve‐sparing repair with IBD does not preserve long‐term PV function in patients with ToF‐PS.

From Diagnosis to Treatment: Clinical Applications of Nanotechnology in Thoracic Surgery

Nanotechnology is an emerging field with potential as an adjunct to cancer therapy, particularly thoracic surgery. Therapy can be delivered to tumors in a more targeted fashion, with less systemic toxicity. Nanoparticles may aid in diagnosis, preoperative characterization, and intraoperative localization of thoracic tumors and their lymphatics. Focused research into nanotechnologys ability to deliver both diagnostics and therapeutics has led to the development of nanotheranostics, which promises to improve the treatment of thoracic malignancies through enhanced tumor targeting, controlled drug delivery, and therapeutic monitoring. This article reviews nanoplatforms, their unique properties, and the potential for clinical application in thoracic surgery.