Predicting liver-related events in NAFLD: A predictive model.

BACKGROUND AND AIMS: Management of NAFLD involves noninvasive prediction of fibrosis, which is a surrogate for patient outcomes. We aimed to develop and validate a model predictive of liver-related events (LREs) of decompensation and/or HCC and compare its accuracy with fibrosis models. APPROACH AND RESULTS: Patients with NAFLD from Australia and Spain who were followed for up to 28 years formed derivation (n = 584) and validation (n = 477) cohorts. Competing risk regression and information criteria were used for model development. Accuracy was compared with fibrosis models using time-dependent AUC analysis. During follow-up, LREs occurred in 52 (9%) and 11 (2.3%) patients in derivation and validation cohorts, respectively. Age, type 2 diabetes, albumin, bilirubin, platelet count, and international normalized ratio were independent predictors of LRE and were combined into a model [NAFLD outcomes score (NOS)]. The NOS model calibrated well [calibration slope, 0.99 (derivation), 0.98 (validation)] with excellent overall performance [integrated Brier score, 0.07 (derivation) and 0.01 (validation)]. A cutoff ≥1.3 identified subjects at a higher risk of LRE, (sub-HR 24.6, p < 0.001, 5-year cumulative incidence 38% vs 1.0%, respectively). The predictive accuracy at 5 and 10 years was excellent in both derivation (time-dependent AUC,0.92 and 0.90, respectively) and validation cohorts (time-dependent AUC,0.80 and 0.82, respectively). The NOS was more accurate than the fibrosis-4 or NAFLD fibrosis score for predicting LREs at 5 and 10 years ( p < 0.001). CONCLUSIONS: The NOS model consists of readily available measures and has greater accuracy in predicting outcomes in patients with NAFLD than existing fibrosis models.

Primary Tumour Detection in Carcinoma of Unknown Primary with Transoral Robotic Surgery (TORS) Tongue Base Mucosectomy: A Meta-analysis.

BACKGROUND: Head and neck carcinoma of unknown primary (CUP) represents a challenging diagnostic process when standard work-up fails to identify the primary tumour site. The aim of this systematic review and meta-analysis was to evaluate the diagnostic utility and complication profile of transoral robotic surgery (TORS) tongue base mucosectomy (TBM) in the management of CUP. PATIENTS AND METHODS: An electronic database search was performed in the EMBASE, MEDLINE, PubMed and Cochrane databases. A meta-analysis of proportions was performed to obtain an estimate of the overall proportion for the detection and complication rates. RESULTS: Nine studies representing 235 patients with CUP who had TORS TBM were included in the final analysis. The overall pooled tumour detection rate was 66.2% [95% confidence interval (CI) 56.1-75.8]. The incidence of tumour detection in human papilloma virus (HPV)-positive cases (81.5%, 95% CI 60.8-96.4) was significantly higher than HPV-negative cases (2.3%, 95% CI 0.00-45.7). Weighted overall complication rate was 11.4% (95% CI 7.2-16.2). The majority were grade I or II (80%) according to the Clavien-Dindo classification. CONCLUSIONS: This meta-analysis suggests TORS to be safe and effective in localising the primary tumour site in patients with CUP. While the current data supports the use of TORS in patients who are HPV positive, larger numbers of HPV-negative cases are required to determine the true diagnostic effect with TORS before any valid conclusions can be inferred in this particular subgroup. Further research should focus on high quality prospective trials with stringent methodological work-up to minimise heterogeneity and allow for more accurate statistical analysis.

Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. METHODS: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3-4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. RESULTS: In 271 NAFLD patients, 83 (31%) had F3-4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). CONCLUSIONS: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.

Serum Fibrosis Tests Guide Prognosis in Metabolic Dysfunction-Associated Fatty Liver Disease Patients Referred From Primary Care.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is managed predominately in primary care, however, there is uncertainty regarding how to best identify patients for specialist referral. We examined the accuracy of noninvasive tests as screening tools for the prediction of outcomes in MAFLD patients referred from primary care. METHODS: Patients with MAFLD referred by primary care for specialist review to Sir Charles Gairdner Hospital (cohort 1, n = 626) or tertiary centers within Western Australia (cohort 2, n = 246) were examined. Hepascore, aspartate aminotransferase to platelet ratio, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score performed at baseline were examined for their accuracy in predicting liver-related death (LRD), decompensation, and hepatocellular carcinoma. Outcomes were collected from hospital records and data linkage. RESULTS: The median follow-up period was 5.0 years (range, 0.1-13.0 y) and 3.8 years (range, 0.1-10.0 y) in cohorts 1 and 2, respectively. In both cohorts, Hepascore and FIB-4 had the highest area under the curve for the prediction of LRD (0.90-0.95 and 0.83-0.94, respectively), decompensation (0.86-0.91 and 0.86-0.87, respectively), and hepatocellular carcinoma (0.75-0.90 and 0.67-0.85, respectively). The sensitivity and negative predictive values were high (>90%) for Hepascore (cut-off value, 0.60), FIB-4 (cut-off value, 1.30), and nonalcoholic fatty liver disease fibrosis score (cut-off value, -1.455) for all outcomes in cohort 1, and for predicting LRD in cohort 2. Hepascore had the highest specificity, classified the greatest proportion of patients as low risk, and was favored by decision curve analysis as providing the greatest net benefit. CONCLUSIONS: Serum noninvasive tests accurately stratify risk of liver-related outcomes in MAFLD patients and can be used as a screening tool for patients referred for specialist review by primary care.

Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS).

Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

Which Electronic Health Record System Should We Use? A Systematic Review.

The UK government had intended to introduce a comprehensive Electronic Health Record (EHR) system in England by 2020. These EHRs would run across primary, secondary, and social care, linking data in a single digital platform. The objectives of this systematic review were to identify studies that compare EHR in terms of direct comparison between systems and to evaluate them using System and Software Quality Requirements and Evaluation (SQuaRE) ISO/IEC 25010. A systematic review was performed by searching Embase and Ovid MEDLINE databases between 1974 and April 2021. All original studies that appraised EHR systems and their providers were included. The main outcome measures were EHR system comparison and the eight characteristics of SQuaRE: functional suitability, performance efficiency, compatibility, usability, reliability, security, maintainability, and portability. A total of 724 studies were identified using the search criteria. After a review of titles and abstracts, this was filtered down to 40 studies as per the exclusion and inclusion criteria set out in our study. Seven studies compared more than one EHR. The following number of studies looked at the various aspects of the SQuaRE, respectively - 19 studies: functional suitability, performance efficiency: 18 studies, compatibility: 12 studies, usability: 25 studies, reliability: 6 studies, security: 2 studies, maintainability: 16 studies, portability: 13 studies. Epic was the most studied EHR system and one of the most implemented systems in the US market and one of the top ten in the UK. It is difficult to assess which is the most advantageous EHR system when they are assessed by SQuaRE's 8 characteristics for software evaluation.

Surgical Innovation in the Era of Global Surgery: A Network Analysis.

OBJECTIVE: To present a novel network-based framework for the study of collaboration in surgery and demonstrate how this can be used in practice to help build and nurture collaborations that foster innovation. BACKGROUND: Surgical innovation is a social process that originates from complex interactions among diverse participants. This has led to the emergence of numerous surgical collaboration networks. What is still needed is a rigorous investigation of these networks and of the relative benefits of various collaboration structures for research and innovation. METHODS: Network analysis of the real-world innovation network in robotic surgery. Hierarchical mixed-effect models were estimated to assess associations between network measures, research impact and innovation, controlling for the geographical diversity of collaborators, institutional categories, and whether collaborators belonged to industry or academia. RESULTS: The network comprised of 1700 organizations and 6000 links. The ability to reach many others along few steps in the network (closeness centrality), forging a geographically diverse international profile (network entropy), and collaboration with industry were all shown to be positively associated with research impact and innovation. Closed structures (clustering coefficient), in which collaborators also collaborate with each other, were found to have a negative association with innovation (P < 0.05 for all associations). CONCLUSIONS: In the era of global surgery and increasing complexity of surgical innovation, this study highlights the importance of establishing open networks spanning geographical boundaries. Network analysis offers a valuable framework for assisting surgeons in their efforts to forge and sustain collaborations with the highest potential of maximizing innovation and patient care.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia.

BACKGROUND & AIMS: Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. METHODS: We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. RESULTS: In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P < .001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. CONCLUSIONS: In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.

The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium-90 resin microsphere radioembolization.

BACKGROUND AND AIM: Yttrium-90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre-treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials. METHODS: Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child-Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups. RESULTS: One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2 months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End-Stage Liver Disease score (≤ 7), lower Alpha-fetoprotein (≤ 150 IU/L), higher serum Albumin (> 37 g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group = 0). Three survival prognostic groups were identified: good (median overall survival 25.0 months), average (15.3 months), and poor (6.3 months) (overall log-rank test, P < 0.001). CONCLUSION: The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy.

BACKGROUND AND AIMS: 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) is an emerging functional imaging technique in the diagnosis and management of hepatocellular carcinoma (HCC). The aim of this study was to assess the ability of a pre- and post-treatment 18F-FCH PET/CT to predict prognosis and treatment response in early-stage HCC. METHODS: Patients with early- or intermediate-stage HCC planned for locoregional therapy were prospectively enrolled. Baseline demographic and tumor information was collected and baseline and post-treatment 18F-FCH PET/CT performed. Maximum standardized uptake values (SUVmax) were determined for each HCC lesion, and the difference between baseline and post-treatment SUVmax values were compared with progression-free survival outcomes. RESULTS: A total of 29 patients with 39 confirmed HCC lesions were enrolled from a single clinical center. Patients were mostly men (89.7%) with hepatitis C or alcohol-related cirrhosis (65.5%) and early-stage disease (89.7%). Per-patient and per-lesion sensitivity of 18F-FCH PET/CT was 72.4% and 59.0%, respectively. A baseline SUVmax < 13 was associated with a superior median progression-free survival compared with an SUVmax of > 13 (17.7 vs. 5.1 months; p = 0.006). A > 45% decrease in SUVmax between baseline and post-treatment 18F-FCH PET/CT ("responders") was associated with a superior mean progression-free survival than a percentage decrease of < 45% ("non-responders," 36.1 vs. 11.6 months; p = 0.034). CONCLUSIONS: Baseline and post-treatment 18F-FCH PET/CT predicts outcomes in early-stage HCC undergoing locoregional therapy. This technique may identify patients with an objective response post-locoregional therapy who would benefit from further therapy.

The role of allied healthcare professionals in head and neck cancer surveillance: A systematic review.

OBJECTIVES: The roles of Allied Health Care Professionals (AHPs) in Head and Neck Cancer (HNC) are wide ranging but not clearly defined. Inter-regional variability in practice results from a lack of standardisation in approaches to the Multidisciplinary Team (MDT) make-up and structure. Traditionally, the follow-up of HNC patients is clinician led with multiple scheduled follow-up appointments. The increasing population of HNC patients provides logistical, monetary and efficiency challenges. This systematic review presents the roles of the multiple AHP sub-groups in HNC with the aim of presenting how their differing skill sets can be integrated to modernise our approach in follow-up. DESIGN: We searched MEDLINE, Embase, the Cochrane Library, NIHR Dissemination Centre, The Kings Fund Library, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify multiple subgroups of AHPs (Dentists, Speech and Language Therapists, Dieticians, Physiotherapists, Psychologists, Clinical Nurse Specialists) and evidence of their role in HNC follow-up. Evidence not directly relating to HNC follow-up was excluded. SETTING AND PARTICIPANTS: This Systematic Review was undertaken online by the Integrate (UK ENT Trainee National Collaborative) Head and Neck Subcommittee. MAIN OUTCOME MEASURES: Most evidence was of low-quality, and the broad nature of the protocol provided a wide variety of study models. Two authors screened the articles for relevance to the topic before final analysis. RESULTS: The main role identified was improvement in Quality of Life and symptom control rather than detecting recurrence. We also demonstrate that it is possible to stratify HNC follow-up patients using their received treatment modality and Distress Thermometers to identify groups who will require more intensive AHP input. CONCLUSIONS: HNC follow-up covers a broad group of patients with differing needs. As such, a blanket approach to this phase of treatment is likely to be less effective than a patient-led model where the group of AHPs are employed on a needs basis rather than at set time points. This will likely lead to greater patient satisfaction, earlier detection of recurrence and efficiency savings.

Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial.

Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors, regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets (Mediterranean [MD] or low fat [LF]) on hepatic steatosis (HS) and cardiometabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs. LF). HS was determined by magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat, but lower carbohydrate and sodium, intakes compared to LF subjects (P < 0.01). At week 12, HS had reduced significantly in both groups (P < 0.01), and there was no difference in liver fat reduction between groups (P = 0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups (-1.6 [±2.1] kg in LF vs -2.1 [±2.5] kg in MD; P = 0.52). Within-group improvements in Framingham Risk Score (FRS), total cholesterol, serum triglyceride (TG), and glycated hemoglobin (HbA1c) were observed in the MD (all P < 0.05), but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%; P = 0.048). Conclusion: Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree.

Type and Pattern of Alcohol Consumption is Associated With Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced. RESULTS: Among 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3-60) g over an average of 18 years. Modest consumption (1-70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14-0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a binge-type fashion. Exclusive wine drinkers but not exclusive beer drinkers, had lower mean fibrosis stage and lower odds of advanced fibrosis (OR 0.20, 95% CI 0.06-0.69, p = 0.01), compared to lifetime abstinent subjects. No interaction between gender and alcohol quantity, type, or binge consumption on fibrosis was observed. DISCUSSION: Modest (1-70 g per week) alcohol consumption, particularly wine in a non-binge pattern, is associated with lower fibrosis in patients with NAFLD. Prospective longitudinal studies into fibrosis progression, cardiovascular outcomes, and mortality are required before clinical recommendations can be made.

Induced Bias Due to Crossover Within Randomized Controlled Trials in Surgical Oncology: A Meta-regression Analysis of Minimally Invasive versus Open Surgery for the Treatment of Gastrointestinal Cancer.

BACKGROUND: Randomized controlled trials (RCTs) inform clinical practice and have provided the evidence base for introducing minimally invasive surgery (MIS) in surgical oncology. Crossover (unplanned intraoperative conversion of MIS to open surgery) may affect clinical outcomes and the effect size generated from RCTs with homogenization of randomized groups. OBJECTIVES: Our aims were to identify modifiable factors associated with crossover and assess the impact of crossover on clinical endpoints. METHODS: A systematic review was performed to identify all RCTs comparing MIS with open surgery for gastrointestinal cancer (1990-2017). Meta-regression analysis was performed to analyze factors associated with crossover and the influence of crossover on endpoints, including 30-day mortality, anastomotic leak rate, and early complications. RESULTS: Forty RCTs were included, reporting on 11,625 patients from 320 centers. Crossover was shown to affect one in eight patients (mean 12.6%, range 0-45%) and increased with American Society of Anesthesiologists score (ß = + 0.895; p = 0.050). Pretrial surgeon volume (ß = - 2.344; p = 0.037), composite RCT quality score (ß = - 7.594; p = 0.014), and site of tumor (ß = - 12.031; p = 0.021, favoring lower over upper gastrointestinal tumors) showed an inverse relationship with crossover. Importantly, multivariate weighted linear regression revealed a statistically significant positive correlation between crossover and 30-day mortality (ß = + 0.125; p = 0.033), anastomotic leak rate (ß = + 0.550; p = 0.004), and early complications (ß = + 1.255; p = 0.001), based on intention-to-treat analysis. CONCLUSIONS: Crossover in trials was associated with an increase in 30-day mortality, anastomotic leak rate, and early complications within the MIS group based on intention-to-treat analysis, although our analysis did not assess causation. Credentialing surgeons by procedural volume and excluding high comorbidity patients from initial trials are important in minimizing crossover and optimizing RCT validity.

Diabetes impacts prediction of cirrhosis and prognosis by non-invasive fibrosis models in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) patients with diabetes are at increased risk of cirrhosis and liver-related death, and thus accurate fibrosis assessment in these patients is important. We examined the ability of non-invasive fibrosis models to determine cirrhosis and outcomes in NAFLD patients with and without diabetes. METHODS: Non-alcoholic fatty liver disease patients diagnosed between 2006 and 2015 had Hepascore, NAFLD fibrosis score (NFS), APRI and FIB-4 scores calculated at baseline and were followed up for outcomes of overall and liver-related mortality/liver transplantation, hepatic decompensation and hepatocellular carcinoma (HCC). Model accuracy was determined by Harrell's C-index and by Kaplan-Meier analysis. RESULTS: A total of 284 patients (53% diabetic, 15% cirrhotic) were followed up for a median of 51.4 months, (range 6.1-146). During follow-up, diabetic patients had a greater risk of liver-related death/transplantation, HR 3.4 (95% CI 1.2-9.1) decompensation, HR 4.7 (95% CI 2.0-11.3) and HCC, HR 2.9 (95% CI 1.2-7.3). Among 241 subjects with a baseline liver biopsy, the accuracy of Hepascore, APRI and FIB-4 for predicting cirrhosis was lower amongst diabetics compared to non-diabetics (P < .005 for all). Model accuracy apart from Hepascore, was also significantly lower for predicting liver death/transplantation in patients with diabetes. No patient with a low fibrosis score and without diabetes developed liver decompensation or HCC, whereas up to 21% of diabetic patients with a low fibrosis score developed liver decompensation and up to 27% developed HCC at 5 years. CONCLUSIONS: Non-invasive scoring systems are less accurate at predicting cirrhosis and liver-related outcomes in patients with NAFLD and diabetes.

Rate of Nonsurveillance and Advanced Hepatocellular Carcinoma at Diagnosis in Chronic Liver Disease.

AIMS: Ultrasound surveillance for hepatocellular carcinoma (HCC) is recommended in cirrhotic patients to allow early diagnosis. This study investigated risk factors for nonsurveillance and advanced HCC at diagnosis and their effect on survival. MATERIALS AND METHODS: Two hundred seventy HCC patients were included. Clinical data were collected from hospital databases. RESULTS: One hundred twenty-eight (47.1%) patients had 6-monthly ultrasound surveillance before HCC diagnosis. Ninety-two (34.1%) patients had advanced HCC (multifocal or total diameter ≥6 cm) at diagnosis. The nonsurveillance rate was significantly higher in nonalcoholic fatty liver disease (NAFLD) (79%) compared with other causes of chronic liver disease (31.6% to 58.1%, P<0.001). Nonrecognition of NAFLD was significantly higher (68.4%) compared with other causes of chronic liver disease (0% to 23.2%, P<0.001). In NAFLD HCC patients, 23.7% were noncirrhotic and smoking was significantly associated HCC in this noncirrhotic group (P=0.041). No-surveillance for HCC was significantly associated with advanced HCC at diagnosis with an odds ratio (OR) of 8.1. Compared with nondrinkers, heavy alcohol consumption was significantly associated with advanced HCC (OR=7.6). In the surveillance group, diagnosis using computed tomography rather than magnetic resonance imaging was significantly associated with advanced HCC (OR=3.36). Patients without HCC surveillance had a significantly shorter median survival compared with those who had HCC surveillance (27.4 vs. 52.0 mo, P=0.0006). CONCLUSIONS: The lack of HCC surveillance is associated with advanced HCC at diagnosis and decreased survival. NAFLD patients with HCC have a significantly lower rate of diagnosis of chronic liver disease and HCC surveillance compared with the other causes of chronic liver disease.

The Prognostic Ability of Major Hepatocellular Carcinoma Staging Systems Is Improved by Including a Treatment Variable.

BACKGROUND AND AIMS: There has been significant debate regarding which hepatocellular carcinoma (HCC) staging system is best able to predict survival. We hypothesized that the prognostic ability of the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) systems would be improved with the addition of an explicit treatment variable. METHODS: We performed an analysis of a prospectively enrolled cohort of 292 patients undergoing 532 treatment episodes for HCC from 2006 to 2014. BCLC, standard nine-stage HKLC (HKLC9), and modified five-stage HKLC (HKLC5) for each treatment episode were assessed. Overall survival and time to disease progression were calculated for the initial treatment, re-treatment, and overall treatment cohorts. We compared the performance of various prognostic models including staging system alone, treatment alone, and staging system plus treatment using the corrected Akaike information criterion and Harrell's C statistic. RESULTS: The BCLC, HKLC5, and HKLC9 systems were significant predictors of survival and time to progression for all treatment cohorts (log rank test, p < 0.001). The addition of a treatment variable significantly improved (p < 0.01) the prognostic ability of the survival and time to progression models compared with those containing only the BCLC or HKLC stage across all treatment cohorts other than survival in re-treatment for BCLC (p = 0.094). CONCLUSIONS: Adding a treatment variable to major HCC staging systems improves their ability to predict survival and time to progression in initial treatment, re-treatment, and overall.

Prevalence of restless legs syndrome in a tertiary cohort of ambulant patients with chronic liver disease.

A cross-sectional survey of 188 ambulant patients with chronic liver disease was performed to determine the prevalence of restless legs syndrome (RLS) using a validated patient completed questionnaire. Patient responses were verified by standardised telephone interview. RLS was identified in 64 (34%) patients. Significantly, more patients with cirrhosis had RLS than patients without RLS (43.9 vs 23.3%, P = 0.003, respectively). Cirrhotic patients with a history of hepatic encephalopathy were also more likely to have RLS than patients without hepatic encephalopathy (odds ratio = 4.33, 95% confidence interval = 1.40-13.37, P = 0.011). Patients with chronic liver disease may be at risk for RLS; early detection and treatment may improve patient outcomes.

Robotic Head and Neck Surgery: History, Technical Evolution and the Future.

The first application of robotic technology in surgery was described in 1985 when a robot was used to define the trajectory for a stereotactic brain biopsy. Following its successful application in a variety of surgical operations, the da Vinci® robot, the most widely used surgical robot at present, made its clinical debut in otorhinolaryngology and head and neck surgery in 2005 when the first transoral robotic surgery (TORS) resections of base of tongue neoplasms were reported. Subsequently, the indications for TORS rapidly expanded, and they now include tumours of the oropharynx, hypopharynx, parapharyngeal space, and supraglottic larynx, as well as obstructive sleep apnoea (OSA). The da Vinci® robot has also been successfully used for scarless-in-the-neck thyroidectomy and parathyroidectomy. At present, the main barrier to the wider uptake of robotic surgery is the prohibitive cost of the da Vinci® robotic system. Several novel, flexible surgical robots are currently being developed that are likely to not only enhance patient safety and expand current indications but also drive down costs, thus making this innovation more widely available. Future directions relate to overlay technology through augmented reality/AR that allows real-time image-guidance, miniaturisation (nanorobots), and the development of autonomous robots.