Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

BACKGROUND AND AIMS: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). METHODS: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). RESULTS: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). CONCLUSIONS: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. GOV NUMBER: NCT01745861. EU CLINICAL TRIALS REGISTER: EudraCT (2010-018660-16).

Morphologic Change of Flow-Related Aneurysms in Brain Arteriovenous Malformations after Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: The natural history of flow-related aneurysms after obliteration of brain arteriovenous malformations is poorly understood. The purpose of this study was to evaluate the angioarchitecture and morphologic change in flow-related aneurysms after gamma knife surgery of brain arteriovenous malformations. MATERIALS AND METHODS: During a 12-year period, 823 patients with brain arteriovenous malformations underwent gamma knife surgery at our institution with complete peritherapeutic angiographic evaluation. From this population, a series of 72 patients (8.8%) with 111 flow-related aneurysms were enrolled (1.5 aneurysms per patient). There were 43 men and 29 women; ages ranged from 18 to 72 years (mean, 43 years). The morphologic change of flow-related aneurysms was longitudinally evaluated before and after obliteration of brain arteriovenous malformations. After gamma knife surgery, angiographic follow-up varied from 26 to 130 months (mean, 58 months). RESULTS: All flow-related aneurysms were small (mean, 4.1 mm; range, 2-9 mm). There were 72 proximal flow-related aneurysms (mean size, 4.3 mm) and 39 distal flow-related aneurysms (mean size, 3.7 mm). Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms than in proximal flow-related aneurysms (P < .001). Smaller flow-related aneurysms (<5 mm) tended to spontaneously occlude after obliteration of brain arteriovenous malformations (P = .036). Two patients had ruptures of proximal flow-related aneurysms at 27- and 54-month follow-ups, respectively. CONCLUSIONS: Spontaneous thrombosis occurred more frequently in distal flow-related aneurysms due to occlusion or normalization of distal feeders. Smaller flow-related aneurysms also tended to spontaneously thrombose after obliteration of brain arteriovenous malformations. The rate of flow-related aneurysm rupture in our series was similar to that of natural intradural aneurysms.

Enhanced recovery after surgery for liver resection.

INTRODUCTION: Enhanced recovery after surgery (ERAS) reduces postoperative length of hospital stay and patient stress response to liver surgery. The aim of the present study was to evaluate the efficacy and feasibility of an ERAS programme for liver resection. METHODS: A multidisciplinary ERAS protocol was implemented for both open and laparoscopic liver resection in a tertiary hospital in Hong Kong. The clinical outcomes of patients who underwent liver resection and underwent the ERAS perioperative programme were compared with those who received a conventional perioperative programme between September 2015 and July 2016. Propensity score matching analysis was used to minimise background differences. RESULTS: A total of 20 patients who underwent liver resection were recruited to the ERAS programme. Their clinical outcomes were compared with another 20 patients who received hepatectomy under a conventional perioperative programme after propensity score matching. The ERAS programme was associated with a significantly shorter length of hospital stay (P=0.033) without an increase in complication rates in patients who underwent open liver resection. There was no such significant association in patients who underwent laparoscopic liver resection. No patients required readmission in this cohort. CONCLUSIONS: The ERAS perioperative programme for liver resection is safe and feasible. It significantly shortened the hospital stay after open liver resection but not after laparoscopic liver resection.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Application of Time-Resolved 3D Digital Subtraction Angiography to Plan Cerebral Arteriovenous Malformation Radiosurgery.

BACKGROUND AND PURPOSE: Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery. MATERIALS AND METHODS: Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18-64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA. RESULTS: Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (P = .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (P = .042 and 0.039, respectively, for measurements conducted by 2 authors). CONCLUSIONS: Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.

Quantifying the Cerebral Hemodynamics of Dural Arteriovenous Fistula in Transverse Sigmoid Sinus Complicated by Sinus Stenosis: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas. MATERIALS AND METHODS: Forty-three cases of dural arteriovenous fistula in the transverse-sigmoid sinus were reviewed and divided into 3 groups: Cognard type I, type IIa, and types with cortical venous drainage. Sinus stenosis and the double peak sign (occurrence of 2 peaks in the time-density curve of the ipsilateral drainage of the internal jugular vein) in dural arteriovenous fistula were evaluated. "TTP" was defined as the time at which a selected angiographic point reached maximum concentration. TTP of the vein of Labbé, TTP of the ipsilateral normal transverse sinus, trans-fistula time, and trans-stenotic time were compared across the 3 groups. RESULTS: Thirty-six percent of type I, 100% of type IIa, and 84% of types with cortical venous drainage had sinus stenosis. All sinus stenosis cases demonstrated loss of the double peak sign that occurs in dural arteriovenous fistula. Trans-fistula time (2.09 seconds) and trans-stenotic time (0.67 seconds) in types with cortical venous drainage were the most prolonged, followed by those in type IIa and type I. TTP of the vein of Labbé was significantly shorter in types with cortical venous drainage. Six patients with types with cortical venous drainage underwent venoplasty and stent placement, and 4 were downgraded to type IIa. CONCLUSIONS: Sinus stenosis indicated dysfunction of venous drainage and is more often encountered in dural arteriovenous fistula with more aggressive types. Venoplasty ameliorates cortical venous drainage in dural arteriovenous fistulas and serves as a bridge treatment to stereotactic radiosurgery in most cases.

Robotic surgery for thyroid disease.

While conventional open thyroidectomy techniques are the most widely performed thyroid operation, they produce an anterior neck scar that may be difficult to conceal. The endoscopic thyroidectomy was developed to decrease the cosmetic impact on the patient and has the advantage of reducing the incidence of anterior neck hypoesthesia and paresthesia. However, this procedure has some drawbacks, which motivated surgeons to develop a new operation method. Robotic thyroidectomy is a relatively new approach for treating differentiated thyroid cancer. Over the last few years, robotic thyroidectomies have become more common. Robotic thyroidectomies are a feasible, safe alternative for managing thyroid disease that has remarkable functional benefits beyond those of conventional open methods. The applications for robotic thyroidectomy have expanded to include increasingly advanced cases, which will consequently change the thyroid surgery paradigm in the future.

Early intervention in thyroidectomy scars: demographics, symptoms, and prevention.

OBJECTIVE: Although hypertrophic scars are cosmetically problematic for patients following thyroidectomy, the associated risk factors are not well defined. Our objective was to determine the factors associated with hypertrophic scar development following thyroidectomy. METHOD: A retrospective chart review was performed collecting data on sex, age, body mass index (BMI), operation site, skin characteristics (pigmentation, erythema, elasticity, and hydration), and clinical scar characteristics (itching, tightening, induration, adhesion, and oedema). It was also noted if the patient had early scar intervention with intralesional steroid injection or non-ablative fractional laser irradiation, and preventive topical treatment agents. The effects of these factors were analysed using univariate and multivariate analyses. RESULTS: Data from 1141 patients showed the incidence of hypertrophic scars was 13.9%. Significant variables in univariate analysis were combined for multivariate analysis. Young age, high BMI, itching, tightening, induration, and adhesion were associated with hypertrophic scar formation. Early scar intervention, as well as the use of preventive topical agents, were associated with decreased hypertrophic scar formation. CONCLUSION: Based on our results, we suggest that dermatologists consider using non-ablative fractional laser, intralesional steroid injection, and topical preventive agents to lower the incidence of hypertrophic scars, especially in young patients or those with high BMI and/or clinical symptoms such as itching, tightening, induration, and adhesion.

Unique features of non-obstructive emphysema and pure airway obstruction.

SETTING: Emphysema without airway obstruction or airway obstruction without emphysema are often detected clinically, although they are commonly co-existent. We therefore tested the hypothesis that non-obstructive emphysema and pure airway obstruction have unique features. METHODS: A case-control observation study was undertaken retrospectively in a patient cohort at a single centre. Among 2662 subjects who underwent chest computed tomography and pulmonary function tests, we enrolled 90 patients with non-obstructive emphysema, 119 with pure airway obstruction, 81 with obstructive emphysema and 2031 subjects as normal controls. The features of the four groups were analysed and compared. RESULTS: Higher serum homocysteine (13.4 ± 7.4 vs. 11.6 ± 4.6 mol/l), higher rate of osteoporosis (15.8% vs. 4.5%), higher leukocyte count, higher male ratio, lower serum albumin and lower body mass index were observed in subjects with non-obstructive emphysema than in controls (P < 0.05). In multiple logistic regression analysis of groups without airway obstruction, osteoporosis, hyperhomocysteinaemia, hypoalbuminaemia and higher leukocyte count were independent factors associated with non-obstructive emphysema (P < 0.05). CONCLUSION: Hyperhomocysteinaemia, hypoalbuminaemia, osteoporosis and higher leukocyte count were independent predictors of non-obstructive emphysema.

Cellular and plasma uptake of parenteral omega-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer.

BACKGROUND & AIMS: Omega-3 rich fatty acids (n-3FA) have powerful anti-inflammatory and anti-neoplastic properties. Previous studies have investigated plasma and cellular uptake of oral and parenteral n-3FA regimens. These have shown that n-3FA undergo rapid uptake into cells which is sustained for the length of the treatment course. The aim of this study was to investigate long-term uptake of prolonged, regular treatment courses of parenteral n-3FA which has not been previously reported. METHODS: As part of a phase II single-arm trial, patients with advanced pancreatic cancer were treated with gemcitabine plus parenteral n-3FA rich lipid emulsion (up to 100 g) each week for three consecutive weeks with a subsequent rest week. This was repeated for up to six months in total for each patient. Pre-treatment serum and erythrocyte cell membrane (ECM) pellet samples were obtained each week for the entire treatment course of each patient. Post-treatment samples were obtained for the first two cycles only to assess rapid uptake. Fatty acid methyl esters (FAME) were produced and analysed using gas chromatography. FAME proportions as a total of sample lipid composition for each class were plotted and the results analysed using a linear regression coefficient model. RESULTS: There was rapid and significant uptake of EPA and DHA FAME into plasma Non-Esterified Fatty Acids (NEFA) and EPA into ECM pellets in post-treatment samples (median increase of 1.06%, 0.65% and 0.05% respectively). There was significant reduction in n-6 fatty acid FAMEs and DHA in ECM pellets (decrease of 0.31% and 0.8% respectively- p = 0.031 for all). There was significant sustained uptake of EPA and DHA FAME into ECM pellets over the cohort's pooled treatment course with corresponding reduction in the n-6:n-3 ratio. CONCLUSIONS: Prolonged regular parenteral n-3FA administration results in rapid and sustained cellular uptake. This regimen is appropriate for therapies aimed at increasing n-3FA content of cellular membranes and reduction of the n-6:n-3 ratio.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.

BACKGROUND: This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS: Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS: Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER: NCT01164176.

Preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anaesthesia.

BACKGROUND: Psychological factors are thought to drive inter-patient variations in anaesthetic and analgesic requirements. This cross-sectional study investigated whether preoperative psychological factors can predict anaesthetic requirements and postoperative pain. METHODS: Before total thyroidectomy, 100 consecutive women completed the Spielberger's State-Trait Anxiety Inventory (STAI) and the pain sensitivity questionnaire (PSQ). Target-controlled propofol was administered for induction of anaesthesia, and sevoflurane-oxygen-air was given to maintain equal depths of anaesthesia, as determined by bispectral index (BIS) monitoring. RESULTS: Patients with higher anxiety scores (state and trait) required greater amounts of propofol to reach light (BIS=85) and moderate (BIS=75) levels of sedation, but only trait anxiety was significantly associated with propofol requirements in reaching a deep level of sedation (BIS=65). The MAC-hour of sevoflurane was significantly correlated only with PSQ scores. The postoperative pain intensity was significantly correlated with both STAI and PSQ. CONCLUSIONS: Preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anaesthesia. Anaesthetic and analgesic doses could be modified based on the patient's preoperative anxiety and pain sensitivity.

Comparison of endoscopic and robotic thyroidectomy.

BACKGROUND: Endoscopic thyroidectomy is a technically challenging procedure. Robot-assisted thyroidectomy has been recently introduced and offers improved visualization and dexterity. The present study compared conventional endoscopic and robotic thyroidectomy for thyroid cancer patients in terms of perioperative outcomes and learning curve. All operations were performed by the same surgeon. MATERIALS AND METHODS: Between April 2007 and March 2010, 96 patients underwent endoscopic thyroidectomy (endoscopy group) and 163 patients underwent robotic thyroidectomy (robot group). A gasless transaxillary approach was used in both groups. The 2 groups were compared in terms of patient characteristics, perioperative clinical results, complications, and pathologic details. Learning curves for the 2 procedures were compared based on the number of cases required to reach a consistent operation time. RESULTS: Patient characteristics were similar for both groups. The mean total operation time for thyroidectomy with central compartment neck dissection was 142.7 ± 52.1 min in the endoscopy group and 110.1 ± 50.7 min in the robot group (P = .041). Both patient groups were similar in terms of pathological features including TNM stage, intraoperative blood loss, length of hospital stay, and complication rate. However, the mean number of retrieved central lymph nodes was 2.4 ± 1.9 for the endoscopy group and 4.5 ± 1.5 for the robot group (P = .004). The learning curve was 55-60 cases for endoscopic thyroidectomy and 35-40 cases for robotic thyroidectomy. CONCLUSION: Robotic thyroidectomy was found to be superior to endoscopic thyroidectomy in terms of operation time, lymph node retrieval, and learning curve. Complication rates and postoperative hospital stay were similar for the 2 procedures.