Predicting Individual Survival After Hepatectomy for Hepatocellular Carcinoma: a Novel Nomogram from the “HCC East & West Study Group”

Introductions

Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC.

Methods

Based on the “Hepatocellular Carcinoma: Eastern & Western Experiences Network,” data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox-regression analysis to construct a unique nomogram and contour plots to predict survival.

Results

The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59–0.69) and 0.61 (95 % CI, 0.56–0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size.

Conclusions

These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction.

     

Use of Street Methadone in Italian Heroin Addicts Presenting for Opioid Agonist Treatment

ABSTRACT

It is commonly assumed that people who are addicted to certain substances would abuse any substance. This position has never been supported by validly collected and analyzed research data. In this study, the authors examine the use of street methadone by heroin addicts seeking their first agonist opioid treatment in a clinical setting. Fifty-four heroin addicts who resorted to street methadone use were compared by socio-demographic, current clinical, and disease-related variables to 251 peers who do not use street methadone. Heroin addicts who resort to street methadone use are more likely to be females and to have a higher degree of education, are less likely to engage in polyabuse (use of more than three substances), are less severely ill, have been addicted for a shorter period of time, and have been seeking treatment sooner in the course of their disease. Also, they suffer from a wider range of psychopathological distress symptoms. In Italy, resorting to street methadone does not seem to be a surrogate form of heroin addiction, but rather represents means of harm reduction, with treatment seeking occurring shortly after its initiation. This should be accounted for when deciding on take-home policies and issues of potential methadone diversion.     

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation     

A decomposition approach for the combined master surgical schedule and surgical case assignment problems

This research aims at supporting hospital management in making prompt Operating Room (OR) planning decisions, when either unpredicted events occur or alternative scenarios or configurations need to be rapidly evaluated. We design and test a planning tool enabling managers to efficiently analyse several alternatives to the current OR planning and scheduling. To this aim, we propose a decomposition approach. More specifically, we first focus on determining the Master Surgical Schedule (MSS) on a weekly basis, by assigning the different surgical disciplines to the available sessions. Next, we allocate surgeries to each session, focusing on elective patients only. Patients are selected from the waiting lists according to several parameters, including surgery duration, waiting time and priority class of the operations. We performed computational experiments to compare the performance of our decomposition approach with an (exact) integrated approach. The case study selected for our simulations is based on the characteristics of the operating theatre (OT) of a medium-size public Italian hospital. Scalability of the method is tested for different OT sizes. A pilot example is also proposed to highlight the usefulness of our approach for decision support. The proposed decomposition approach finds satisfactory solutions with significant savings in computation time.     

Aortic Stiffness Assessed by Global Pulse Wave Velocity in Postmenopausal Women: An Ultrasonographic Study

Objective: The first goal of our study was to investigate major determinants of aortic stiffness in postmenopausal women using an echocardiographic method to calculate global pulse wave velocity (PWVg) rather than the less accurate carotid–femoral pulse wave velocity (PWVc). The second goal was to relate PWVg to the absolute risk of major cardiovascular (CV) events estimated by CV risk factors. Patients and methods: Two hundred forty‐four consecutive women who presented to our heart station were screened. One hundred twenty‐two were postmenopausal, either natural or surgical, whereas 122 were premenopausal. The mean age of the patients was 54 ± 13 years. Individuals were categorized as current smokers, former smokers, or nonsmokers and hypertensive or not. Hypercholesterolemia and diabetes mellitus were defined. Aortic stiffness was assessed by PWVg measured with pulsed Doppler, the interval between the beginning of QRS complex and the foot of the systolic upstroke in the Doppler spectral envelope was calculated at the aortic valve site and at the right common femoral artery. PWVg was calculated between the aortic valve and right common femoral artery by dividing the straight line distance between the two by the transit time. Results: There was a highly significant statistical difference (P < 0.0012) in PWVg between menstruating women and postmenopausal women. Similarly, this difference in PWVg was also noted among the menstruating population (P < 0.0014) when comparing normotensive women and hypertensive women. In postmenopausal women, PWVg was 6.8 m/sec in normotensive women and 7.56 m/sec in hypertensive women (P < 0.007). Conclusion: PWVg was increased in postmenopausal women compared with menstruating women. Systemic hypertension has an independent, but additive effect on aortic stiffness assessed by PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of CV disease and to identify subjects at risk at an early age.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism