Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery for gastric carcinoma at high risk of peritoneal carcinomatosis: short and long-term outcomes (GOETH STUDY)-a collaborative randomized controlled trial by ACOI, FONDAZIONE AIOM, SIC, SICE, and SICO.

INTRODUCTION: At the time of diagnosis, 15-20% of gastric carcinomas are in stage T4 or T4b. Furthermore, 5-20% of patients undergoing potentially curative surgery suffer from synchronous or metachronous peritoneal metastases. To date, neither surgery nor systemic chemotherapy successfully controls peritoneal dissemination, offering a limited impact on survival. Peritoneal metastases are in fact responsible for death in around 60% of gastric cancer patients. Several Eastern studies in the past have focused on hyperthermic intraperitoneal chemotherapy (HIPEC) as a prophylactic measure in patients with serosal extension, nodal involvement, and positive peritoneal fluid cytology. Therefore, a new multimodal therapeutic strategy based on aggressive surgery plus new locoregional treatment may prolong survival in this particular clinical scenario. METHODS: This study compares the efficacy of prophylactic surgery (radical gastric resection, appendectomy, resection of the round ligament of the liver, and bilateral adnexectomy) plus hybrid CO2 HIPEC system versus standard surgery in patients with T3-T4 N0-N + gastric adenocarcinoma. Patients will be randomly assigned (1:1 ratio) to the experimental arm or standard surgery. The primary endpoint is to establish the difference in disease-free survival between the groups. The secondary objective is to compare the safety and tolerability of prophylactic surgery plus HIPEC CO2 versus standard surgery. DISCUSSION: Considering the poor prognosis of patients with peritoneal dissemination from gastric cancer, a prophylactic strategy to prevent peritoneal metastases may be beneficial. In patients with gastric cancer at high risk of peritoneal carcinomatosis, we propose aggressive surgical treatment with radical gastrectomy, removal of organs at risk of harbouring tumour cells, and HIPEC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03917173. Registered on 16 April 2019. PROTOCOL VERSION: v1, March 27, 2019. Protocol number: IRFMN-GCC-7813. EudraCT number: 2019-001478-27.

Data on the design optimization, indoor characterization and outdoor testing of GaAs/Bifacial Si heterojunction four-terminal photovoltaic systems.

The development of a highly efficient multijunction technology is a key challenge for the future of photovoltaic and for the transition to more renewable energy sources. In this scenario, four-terminal architecture (4T) compared to the classic tandem design allows a large intrinsic robustness to the variations of the solar spectrum, which continuously occur under normal outdoor operation conditions. On the other hand, bifacial solar cells and modules have already proven to be able to increase the energy yield of solar farms at reduced costs. For these reasons, a thorough investigation of the compatibility between these two solutions has been performed by combining a III-V semiconductor with the silicon heterojunction technology in a four-terminal device. This work has been designed in support of the research article entitled "Outdoor performance of GaAs/Bifacial Si Heterojunction four-terminal system using optical spectrum splitting" [1], which showed, through data modeling and an accurate daily analysis of the spectral distribution of solar light, how a four-terminal architecture guarantees the consistency of the bifacial gain and more robust performances than a two-terminal system. Here additional data on the manufacturing, optimization and characterization of the device are presented.

Innovative and conventional "conservative" technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment.

BACKGROUND: To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard "conservative" procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE). METHODS: A Health Technology Assessment was conducted, assuming the payer's perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients' clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids' experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy). RESULTS: Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients' perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients' productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of - 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs. CONCLUSIONS: Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.

Should enhanced recovery after surgery (ERAS) pathways be preferred over standard practice for patients undergoing abdominal wall reconstruction? A systematic review and meta-analysis.

PURPOSE: Although many studies assessing enhanced recovery after surgery (ERAS) pathways in abdominal wall reconstruction (AWR) have recently demonstrated lower rates of postoperative morbidity and a decrease in postoperative length of stay compared to standard practice, the utility of ERAS in AWR remains largely unknown. METHODS: A systematic literature search for randomized and non-randomized studies comparing ERAS (ERAS +) pathways and standard protocols (Control) as an adopted practice for patients undergoing AWR was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and EMBASE databases. A predefined search strategy was implemented. The included studies were reviewed for primary outcomes: overall postoperative morbidity, abdominal wall morbidity, surgical site infection (SSI), and length of hospital stay; and for secondary outcome: operative time, estimated blood loss, time to discontinuation of narcotics, time to urinary catheter removal, time to return to bowel function, time to return to regular diet, and readmission rate. Standardized mean difference (SMD) was calculated for continuous variables and Odds Ratio for dichotomous variables. RESULTS: Five non-randomized studies were included for qualitative and quantitative synthesis. 840 patients were allocated to either ERAS + (382) or Control (458). ERAS + and Control groups showed equivalent results with regard to the incidence of postoperative morbidity (OR 0.73, 95% CI 0.32-1.63; I2= 76%), SSI (OR 1.17, 95% CI 0.43-3.22; I2= 54%), time to return to bowel function (SMD - 2.57, 95% CI - 5.32 to 0.17; I2= 99%), time to discontinuation of narcotics (SMD - 0.61, 95% CI - 1.81 to 0.59; I2= 97%), time to urinary catheter removal (SMD - 2.77, 95% CI - 6.05 to 0.51; I2= 99%), time to return to regular diet (SMD - 0.77, 95% CI - 2.29 to 0.74; I2= 98%), and readmission rate (OR 0.82, 95% CI 0.52-1.27; I2= 49%). Length of hospital stay was significantly shorter in the ERAS + compared to the Control group (SMD - 0.93, 95% CI - 1.84 to - 0.02; I2= 97%). CONCLUSIONS: The introduction of an ERAS pathway into the clinical practice for patients undergoing AWR may cause a decreased length of hospitalization. These results should be interpreted with caution, due to the low level of evidence and the high heterogeneity.

Could fluorescence-guided surgery be an efficient and sustainable option? A SICE (Italian Society of Endoscopic Surgery) health technology assessment summary.

BACKGROUND: Indocyanine green fluorescence vision is an upcoming technology in surgery. It can be used in three ways: angiographic and biliary tree visualization and lymphatic spreading studies. The present paper shows the most outstanding results from an health technology assessment study design, conducted on fluorescence-guided compared with standard vision surgery. METHODS: A health technology assessment approach was implemented to investigate the economic, social, ethical, and organizational implications related to the adoption of the innovative fluorescence-guided view, with a focus on minimally invasive approach. With the support of a multidisciplinary team, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaires and self-reported interviews, considering the dimensions resulting from the EUnetHTA Core Model. RESULTS: From a systematic search of literature, we retrieved the following studies: 6 on hepatic, 1 on pancreatic, 4 on biliary, 2 on bariatric, 4 on endocrine, 2 on thoracic, 11 on colorectal, 7 on urology, 11 on gynecology, 2 on gastric surgery. Fluorescence guide has shown advantages on the length of hospitalization particularly in colorectal surgery, with a reduction of the rate of leakages and re-do anastomoses, in spite of a slight increase in operating time, and is confirmed to be a safe, efficacious, and sustainable vision technology. Clinical applications are still presenting a low evidence in the literature. CONCLUSION: The present paper, under the patronage of Italian Society of Endoscopic Surgery, based on an HTA approach, sustains the use of fluorescence-guided vision in minimally invasive surgery, in the fields of general, gynecologic, urologic, and thoracic surgery, as an efficient and economically sustainable technology.

Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate 40 mg: Need for Titration?

BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events. OBJECTIVE: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40. METHODS: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied. RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059). CONCLUSIONS: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for  nocebo responses. Initial dose titration might reduce PIR frequency.

Techno-functional properties of tomato puree fortified with anthocyanin pigments.

This study investigates the effects of tomato puree fortification with several anthocyanin-rich food colorants on bioactive compound content (phenolics, isoprenoids), antioxidant capacity, in vitro biological activities and consumer acceptance. Tomato puree (tp) was added with different anthocyanin extracts from black carrot (Anthocarrot), grape fruit skins (Enocolor), elderberry fruits (Elderberry) or mahaleb cherry fruits (Mahaleb), thus obtaining a 'functional tomato puree' (ftp). The consumer acceptance (colour, flavor, taste, visual appearance) was at high level, except for Mahaleb-added ftp. Compared to the control (tp), the addition of colouring extracts increased significantly the total phenolic content, before pasteurization, in addition to the expected anthocyanin content. However, after pasteurization, mostly Anthocarrot-ftp preserved an increased phenolic (+53%) content, as well as a higher antioxidant capacity (50%), more than the other added-extracts. Consistently, against tp, Anthocarrot-ftp exhibited an increased anti-inflammatory capacity as showed by the reduced expression of vascular cell adhesion molecule (VCAM)-1 in human cultured endothelial cells, under inflammatory conditions.

Diagnostic performance of contrast-enhanced ultrasound (CEUS) and contrast-enhanced endoscopic ultrasound (ECEUS) for the differentiation of pancreatic lesions: a systematic review and meta-analysis.

PURPOSE: To evaluate CEUS for the diagnosis of pancreatic diseases and its application in the clinical routine with a focus on the value of CEUS in ductal pancreatic carcinoma and its use for the differentiation of neoplastic and non-neoplastic lesions. MATERIALS AND METHODS: All prospective and retrospective studies published in any language by March 6, 2014 were included based on the following criteria: use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced endoscopic ultrasound (ECEUS) as the imaging methods, use of histology as the reference method and availability of a complete translation. Two authors analyzed the titles and abstracts of the search results to identify all relevant publications. Two independent readers then analyzed the full articles to identify those meeting the inclusion criteria. Details regarding study design, patient characteristics, interventions, and results were then independently extracted by two radiologists and one reviewer with methodological expertise. Sensitivity, specificity and diagnostic odds ratio (DOR) were used to obtain overall estimates. RESULTS: 1293 articles were initially identified. 27 studies met the inclusion criteria. CEUS was the index test in 23 studies while ECEUS was the index test in 4 studies. The primary study objective was met by 20 studies with respect to ductal adenocarcinoma. CEUS sensitivity was evaluated in all studies. The pooled estimate of CEUS sensitivity for the diagnosis of ductal adenocarcinoma was 0.89 (95 % CI, 0.85 - 0.92). 15 out of 20 studies examined CEUS specificity. The average specificity was 0.84 (95 % CI, 0.77 - 0.89). The pooled estimate for DOR was 61.12 (95 % CI, 34.81 - 107.32). With regard to the secondary study objective, the pooled sensitivity and specificity were 0.95 (95 % CI, 0.93 - 0.96) from 14 studies and 0.72 (95 % CI, 0.58 - 0.83) from 13 studies, respectively. The pooled DOR was 57.63 (95 % CI, 33.62 - 98.78). CONCLUSION: The sensitivity, specificity, and DOR results show the high value of CEUS for the characterization and differentiation of ductal adenocarinomas from other pancreatic diseases and for cystic pancreatic lesions. For this reason and due to their noninvasive nature, CEUS and ECEUS should be used as the first methods for characterizing neoplastic pancreatic lesions, especially since these are often incidental findings. The methods improve the quality of ultrasound diagnostics and result in faster diagnosis and better disease management.

Distribution of fluoride in glass ionomer cement determined using SIMS.

The uptake by glass ionomer cement of ions (particularly fluoride) from solutions in which the cements have been immersed has been extensively reported. The concentrations within the cement often greatly exceed those in the immersing solution. The distribution of these ions has not been determined. The aim of this study is to use SIMS to investigate the levels of ions within the cement at different depths below the immersed surface of the cement. K+ and F were the ions studied and uptake was into a cement containing neither K nor F (LG30) and one containing F (AH2). The surface was analysed using a Cameca ims4f instrument employing a 14.5 keV Cs+ primary ion beam. This was calibrated on cements made from a series of glasses in which fluorine content was systematically substituted for oxygen (without other elemental changes). XPS, which is very much a surface technique, was used in confirmatory role with respect to the SIMS analysis. Cement discs were made from LG30- and AH2-based cements. After maturation for 72 h these were immersed in 0.275% KF solution for 24 h. SIMS analysis indicated appreciable surface F concentration on LG30 and on AH2 an enhanced F concentration. In contrast, K was not detected on the LG30 surface and only at a low level on AH2. These results were confirmed by XPS. Using the ion beam of the SIMS to sputter away cement enabled the F depth profile on LG30 to be measured to 10 microm. Over this distance the F content drops from 6.2 mmol/g at 0.2 microm from the surface to 0.2 mmol/g at 10 microm. No K was detected down to 13 microm from the surface. From the results of this study, it can be concluded that SIMS is an appropriate tool for further investigation of the distribution of ions uptaken by glass ionomer cements.

Purification and characterisation of a beta-glucosidase abundantly expressed in ripe sweet cherry (Prunus avium L.) fruit.

A beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was purified to homogeneity from ripe fruits of sweet cherry (Prunus avium L.) by ammonium sulphate precipitation, ion exchange and size exclusion chromatography. The enzyme is a monomer with a molecular mass of approximately 68 kDa and an acidic isoelectric point. N-terminal sequence analysis indicated that sweet cherry beta-glucosidase is related to other plant cyanogenic beta-glucosidases. Substrate specificity studies revealed that the enzyme is able to attack and hydrolyse several synthetic substrates and total cell walls purified from ripe fruit. Biochemical and immunolocalisation studies showed that sweet cherry beta-glucosidases are mainly localised in the cytosol and in the apoplast, at the unripe stage of ripening; in ripe fruit it is also associated with cell wall.

Nitridation of gate and tunnel oxides employed in CMOS-ULSI technology

Nitridation treatments are very important in CMOS technology because of their capability of improving the gate and tunnel oxide reliability. In this work we report on N2O and NO annealing of pre-oxidised samples showing physical and electrical characteristics of the thin oxides. The difference between the physical behaviours of N2O and NO oxides is evidenced and related to their different electrical properties.

Localization and expression of the alpha1A-1, alpha1B and alpha1D-adrenoceptors in hyperplastic and non-hyperplastic human prostate.

PURPOSE: To determine the expression and localization of the alpha1A-1, alpha1B and alpha1D-adrenoceptor (AR) subtypes in hyperplastic and non-hyperplastic human prostate tissue. MATERIALS AND METHODS: The expression of the alpha1-AR subtypes was examined at the mRNA level by quantitative solution hybridization, and at the protein level by immunohistochemistry using subtype selective antibodies. RESULTS: While the overall level of alpha1-AR mRNA was not significantly different between hyperplastic and non-hyperplastic tissue, there were significant differences in the ratio of the alpha1-AR subtypes expressed in the two tissue types. The most significant finding from these studies was the reduced expression of the alpha1b-AR mRNA in both glandular and stromal hyperplasia. By immunohistochemistry, the alpha1A-1-AR was detected in the stroma and not in the glandular epithelium. The alpha1B-AR was localized predominantly in the epithelium and was weakly present in the stroma. Lower levels of the alpha1B-AR were detected in the hyperplastic prostatic epithelium. The alpha1D-AR was detected in areas of stroma and was abundantly present in blood vessels. CONCLUSIONS: The alpha1A-1-, alpha1B- and alpha1D-AR subtypes are differentially localized in human prostate, and the expression levels of all three subtypes are altered in BPH. Alterations in a1-AR subtype expression (particularly the alpha1B-AR) in BPH cannot be solely attributed to changes in tissue morphometry resulting from hyperplasia and may be of significance in the pathogenesis of BPH.

Effects of thermal annealing on the optical characteristics of k(+)-na(+) waveguides.

We present a systematic study of the changes induced in the refractive-index profile of different sets of K(+)-Na(+) ion-exchanged waveguides on soda-lime and BK7 substrates because of thermal annealing in the presence or absence of salt vapors. The concentration of potassium is recovered by secondary ion mass spectrometry, and the propagation losses are measured by means of the three-prism configuration.

Effects of thermal annealing on the optical characteristics of k -na + waveguides.

We present a systematic study of the changes induced in the refractive-index profile of different sets of K -Na + ion-exchanged waveguides on soda-lime and BK7 substrates because of thermal annealing in the presence or absence of salt vapors. The concentration of potassium is recovered by secondary ion mass spectrometry, and the propagation losses are measured by means of the three-prism configuration.

Pigment production from in vitro cultures of Alkanna tinctoria Tausch.

An in vitro culture of Alkanna tinctoria Tausch cells was set up in order to investigate the possibility of producing alkannin, a red naphthoquinone naturally present in the root bark of this plant. Furthermore, an in vitro culture of callusderived roots was established and the production of alkannin evaluated. In the different experimental conditions investigated, differences in the production of alkannin derivatives as well as in the type of pigments produced, were observed. The potential use of this technology is discussed.

Alpha interferon treatment of chronic hepatitis C in beta-thalassaemia.

In this open, pilot study, interferon (IFN) alpha-2b seemed effective in the treatment of hepatitis C virus (HCV) infection in patients with beta-thalassaemia. In seven of nine patients who completed the study alanine aminotransferase activities returned to normal, and a completely stable response 24 months after treatment was seen in five. Liver biopsy specimen showed a clear reduction in portal, periportal, and lobular necroinflammation in all five cases. Three patients stopped treatment early because of side effects.

alpha-Interferon treatment of chronic hepatitis C in young patients with homozygous beta-thalassemia.

BACKGROUND: Chronic infection with the hepatitis C virus (HCV) and iron overload are the main causes of chronic liver disease in subjects with homozygous beta-thalassemia (HBT). Iron overload can be counteracted by intensive chelation. alpha-interferon reduces viremia and necroinflammation in patients with chronic HCV hepatitis. METHODS: To assess the effectiveness and safety of alpha 2b-Interferon (IFN), we enrolled in an open pilot trial of treatment 12 patients with HBT and biopsy-proven anti-HCV positive chronic hepatitis. IFN was given at a dose of 5 MU/m2 thrice weekly for 8 weeks, then 3 MU/m2 thrice weekly for 18 weeks. Patients were followed up to 24 months after stopping treatment when a second liver biopsy was performed in subjects with sustained response (normal ALT during follow-up). RESULTS: Two patients discontinued IFN at 7 weeks because of haemolytic anemia and one after 8 weeks due to persistent fever. Among 9 subjects completing the protocol, 5 normalized ALT while on treatment and a further 2 within two months after stopping IFN. A sustained response was obtained altogether in 5 patients, since ALT relapsed in 2 responders. None of the 3 subjects who discontinued IFN and of the 2 patients who did not respond to treatment normalized ALT over a 24 months follow-up. Post-treatment liver histology in long-term responders showed a reduction of portal, periportal and lobular necroinflammation, while siderosis was essentially unchanged. CONCLUSIONS: Although the pattern of response to IFN in HCV-infected subjects with HBT might differ from that of non-thalassemics, due to peculiar side effects and delayed response, the drug appears to be effective and deserves further investigation.

Retinoblastoma. The long-term appearance of radiated intraocular tumors.

A retrospective analysis of 50 patients with retinoblastoma was undertaken to determine the appearance of intraocular retinoblastoma that had received external beam radiation a minimum of 10 years previously. Of the 91 tumors found in 59 eyes, 76 (84%) continued to be ophthalmoscopically visible after 10 years. The most common ophthalmoscopic appearance was a Type III regression pattern. The type of radiation regression pattern correlated with the pretreatment volume of the tumor. The largest tumors (mean, 10.0 disc diameter [dd]) became Type I regression patterns, whereas the smallest tumors (mean, 1.0 dd) completely disappeared. This represents the first long-term follow-up of the intraocular status of radiated retinoblastoma.