Evidence and research perspectives for surgeons in the European Rectal Cancer Consensus Conference (EURECA-CC2)

PURPOSE: Although surgery remains the most important treatment of rectal cancer, the management of this disease has evolved to become more multidisciplinary to offer the best clinical outcome. The International Conference on Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) had the due to identify the degree of consensus that could be achieved across a wide range of topics relating to the management of rectal cancer helping shape future programs, investigational protocols and guidelines for staging and treatment throughout Europe. MATERIALS AND METHODS: Consensus was achieved using the Delphi method. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by topic, and a series of statements were developed. Each committee member commented and voted, sentence by sentence three times. Sentences which did not reach agreement after voting round # 2 were openly debated during the Conference in Perugia (Italy) December 2008. The Executive Committee scored percentage consensus based on three categories: 'large consensus', 'moderate consensus', 'minimum consensus'. RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of members. All chapters were voted on by at least 75% of the members, and the majority was voted on by 85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. In spite of substantial progress, many research challenges remain

Assessment of “Sugranineteen” Table Grape Maturation Using Destructive and Auto-Fluorescence Methods

The optimal harvesting of table grapes is commonly determined based on technological and phenolic indices analyzed over the course of its maturity. The classical techniques used for these analyses are destructive, time-consuming, and work for a limited number of samples that may not represent the heterogeneity of the vineyard. This study aimed to follow the ripening season of table grapes using non-destructive tools as a rapid and accurate alternative for destructive techniques. Grape samples were collected from a Sugranineteen vineyard during the ripening season to measure the basic maturity indices via wet chemistry, and total polyphenols, anthocyanins, and flavonoids were evaluated by spectrophotometry. Fluorescent readings were collected from intact clusters with a portable optical sensor (Multiplex® 3, Force-A, France) that generates indices correlated to different maturity parameters. Results revealed strong relationships between the Multiplex® indices ANTH_RG and FERARI and the skin anthocyanin content, with R2 values equal to 0.9613 and 0.8713, respectively. The NBI_R index was also related to total anthocyanins (R2 = 0.8032), while the SFR_R index was linked to the titratable acidity (R2 = 0.6186), the sugar content (R2 = 0.7954), and to the color index of red grapes (CIRG) (R2 = 0.7835). Results demonstrated that Multiplex® 3 can be applied on intact clusters as an effective non-destructive tool for a rapid estimation of table grapes’ anthocyanin content

BASEL III: Long-term impact on economic performance and fluctuations

We assess the long-term economic impact of the new regulatory standards (the Basel III reform), answering the following questions. (1) What is the impact of the reform on long-term economic performance? (2) What is the impact of the reform on economic fluctuations? (3) What is the impact of the adoption of countercyclical capital buffers on economic fluctuations? The main results are the following. (1) Each percentage point increase in the capital ratio causes a median 0.09 percent decline in the level of steady state output, relative to the baseline. The impact of the new liquidity regulation is of a similar order of magnitude, at 0.08 percent. This paper does not estimate the benefits of the new regulation in terms of reduced frequency and severity of financial crisis, analysed in Basel Committee on Banking Supervision (BCBS, 2010b). (2) The reform should dampen output volatility; the magnitude of the effect is heterogeneous across models; the median effect is modest. (3) The adoption of countercyclical capital buffers could have a more sizeable dampening effect on output volatility. These conclusions are fully consistent with those of the reports by the Long-term Economic Impact group (BCBS, 2010b) and Macro Assessment Group (MAG, 2010b).Basel III, countercyclical capital buffers, financial (in)stability, procyclicality, macroprudential policy.

The effects of oral supplements with sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (H122), Arabinogalactans, Vitamin D, vitamin E and Vitamin C in otitis media with effusion in children: a randomized controlled trial

– OBJECTIVE: To evaluate the ability of oral supplements with immune-stimulating molecules (Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (H122), Arabinogalactans, vitamin D, vitamin E and vitamin C) to reduce the inflammation of the upper airway tract and improve the outcome of otitis media with effusion (OME) in children. PATIENTS AND METHODS: Randomized controlled trial. One-hundred ninety-eight children (CI 95%: 12-96 months) were divided into four groups. Group 1 (48 subjects) received 10 ml of oral supplements (OS) with immune-stimulating molecules for three months (20 days consecutively, then 10 days of suspension – the therapeutic scheme was repeated three times); Group 2 (54 children) underwent treatment with 10 ml of OS for 90 consecutive days; Group 3 (48 subjects) received 15 ml of OS for 45 consecutive days; a control group (48 children) underwent the standard treatment for rhinitis and OME. Outcome measures included otoscopy, tympanometry, fibroendoscopy, and the pure tone audiometry (PTA) at T0 (before treatment), T1 (45 days after treatment), and T2 (90 days after treatment). RESULTS: All children treated with OS showed a reduction of Upper Airway Infection (UAI) episodes and OME compared to the control group independent of the administration method and posology. The three groups treated with OS showed statistically significant differences between T0 and T2 for otoscopy, tympanometry, fibroendoscopy, and PTA. In Group 2, the otoscopy and the tympanometry scores improved at T1. Group 2 and 3 had better PTA results than Group 1. CONCLUSIONS: OS with immune-stimulating molecules should be considered as a supporting therapy in children affected by recurrent episodes of UAI associated with OME due to their capacity to improve the immune response and reduce the inflammatory phenomena. OS can improve the fibroendoscopic findings by restoring middle ear ventilation, in addition to their ability to reduce inflammation in the middle ear

Phenols, volatiles and sensory properties of primitivo wines from the "Gioia Del Colle" PDO area

The aim of this study was to characterise the phenol, anthocyanin, volatile and sensory profiles of Primitivo wines. The wines were produced in three wineries located in the Gioia del Colle PDO (Protected Designation of Origin) area (Southern Italy - Apulia Region). The grapes came from three vineyards of different ages and were grown according to different training systems. The winemaking techniques applied also differed in some technological variables. The results obtained showed that all wines had a high alcohol content (15 to 16% v/v) and were rich in total phenols and proanthocyanidins. The anthocyanin profile was characterised by the prevalence of non-acylated forms, of which malvidin-3-O-monoglucoside accounted for 62 to 67% of the total anthocyanin, followed by the coumarate, acetate and caffeate forms. The volatile fraction was constituted mainly alcohols and esters, the latter having concentrations above the odour threshold. From a sensory point of view, all wines were judged positively, and presented high olfactory and gustatory persistence. The main odour attributes found were soft fruits, cherry and cloves

Trimethoxylated halogenated chalcones as dual inhibitors of mao-b and bace-1 for the treatment of neurodegenerative disorders

Six halogenated trimethoxy chalcone derivatives (CH1–CH6) were synthesized and spec-trally characterized. The compounds were further evaluated for their inhibitory potential against monoamine oxidases (MAOs) and β-secretase (BACE-1). Six compounds inhibited MAO-B more effectively than MAO-A, and the 2′,3′,4′-methoxy moiety in CH4–CH6 was more effective for MAO-B inhibition than the 2′,4′,6′-methoxy moiety in CH1–CH3. Compound CH5 most potently inhibited MAO-B, with an IC50 value of 0.46 µM, followed by CH4 (IC50 = 0.84 µM). In 2′,3′,4′-methoxy derivatives (CH4-CH6), the order of inhibition was –Br in CH5 >-Cl in CH4 >-F in CH6 at the para-position in ring B of chalcone. CH4 and CH5 were selective for MAO-B, with selectivity index (SI) values of 15.1 and 31.3, respectively, over MAO-A. CH4 and CH5 moderately inhibited BACE-1 with IC50 values of 13.6 and 19.8 µM, respectively. When CH4 and CH5 were assessed for their cell viability studies on the normal African Green Monkey kidney cell line (VERO) using MTT assays, it was noted that both compounds were found to be safe, and only a slightly toxic effect was observed in concentrations above 200 µg/mL. CH4 and CH5 decreased reactive oxygen species (ROS) levels of VERO cells treated with H2 O2, indicating both compounds retained protective effects on the cells by antioxidant activities. All compounds showed high blood brain barrier permeabilities analyzed by a parallel artificial membrane permeability assay (PAMPA). Molecular docking and ADME prediction of the lead compounds provided more insights into the rationale behind the binding and the CNS drug likeness. From non-test mutagenicity and cardiotoxicity studies, CH4 and CH5 were non-mutagenic and non-/weak-cardiotoxic. These results suggest that CH4 and CH5 could be considered candidates for the cure of neurological dysfunctions

Nomograms to predict survival and the risk for developing local or distant recurrence in patients with rectal cancer treated with optional short-term radiotherapy

Surgical oncolog

Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives

External beam radiotherapy boost versus surgical debulking followed by radiotherapy for the treatment of metastatic lymph nodes in cervical cancer: A systematic review and meta-analysis.

We aimed to assess disease-free survival (DFS), overall survival (OS) and treatment-related toxicity of two therapeutic strategies for treating bulky lymph nodes on imaging in patients with locally advanced cervical cancer (LACC): radiotherapy boost versus surgical debulking followed by radiotherapy. We performed a systematic review of studies published up to October 2023. We selected studies including patients with LACC treated by external beam radiotherapy (EBRT) boost or lymph node debulking followed by EBRT (with or without boost). We included two comparative (included in the meta-analysis) and nine non-comparative studies. The estimated 3-year recurrence rate was 28.2% (95%CI:18.3-38.0) in the EBRT group and 39.9% (95%CI:22.1-57.6) in the surgical debulking plus EBRT group. The estimated 3-year DFS was 71.8% and 60.1%, respectively (p = 0.19). The estimated 3-year death rate was 22.2% (95%CI:11.2-33.2) in the EBRT boost group and 31.9% (95%CI:23.3-40.5) in the surgical debulking plus EBRT group. The estimated 3-year OS was 77.8% and 68.1%, respectively (p = 0.04). No difference in lymph node recurrence between the two comparative studies (p = 0.36). The meta-analysis of the two comparative studies showed no DFS difference (p = 0.13) but better OS in the radiotherapy boost group (p = 0.006). The incidence of grade≥3 toxicities (ranging 0-50%) was not different between the two approaches in the two comparative studies (p = 0.31). No DFS and toxicity difference when comparing EBRT boost with surgical debulking of enlarged lymph nodes and EBRT in patients with cervical cancer was evident. Radiotherapy boost had better OS. Further investigation is required to better understand the prognostic role of surgical lymph node debulking in light of radiotherapy developments

Timing to achieve the highest rate of pCR after preoperative radiochemotherapy in rectal cancer: a pooled analysis of 3085 patients from 7 randomized trials

Purpose: Optimal timing of surgery after neoadjuvant chemoradiotherapy (Nad-CRT) is still controversial in locally advanced rectal cancer (LARC). The primary goal of this study was to determine the best surgical interval (SI) to achieve the highest rate of pathological complete response (pCR) and secondly to evaluate the effect on survival outcomes according to the SI.Patients and methods: Patients data were extracted from the international randomized trials: Accord12/0405, EORTC22921, FFCD9203, CAO/ARO/AIO-94, CAO-ARO-AIO-04, INTERACT and TROG01.04. Inclusion criteria were: age &gt;= 18, cT3-T4 and cN0-2, no clinical evidence of distant metastasis at diagnosis, Nad-CRT followed by surgery.Pearson's Chi-squared test with Yates' continuity correction for categorical variables, the MannWhitney test for continuous variables, Mann-Kendall test, Kaplan-Meier curves with log-rank test, univariate and multivariate logistic regression model was used for data analysis. Results: 3085 patients met the inclusion criteria. Overall, the pCR rate was 14% at a median SI of 6 weeks (range 1-31). The cumulative pCR rate increased significantly when SI lengthened, with 95% of pCR events within 10 weeks from Nad-CRT.At univariate and multivariate logistic regression analysis, lengthening of SI (p&lt; 0.01), radiotherapy dose (p&lt; 0.01), and the addition of oxaliplatin to Nad-CRT (p&lt; 0.01) had a favorable impact on pCR. Furthermore, lengthening of SI was not impact on local recurrences, distance metastases, and overall survival.Conclusion: This pooled analysis suggests that the best time to achieve pCR in LARC is at 10 weeks, considering that the lengthening of SI is not detrimental concerning survival outcomes. (C) 2020 Elsevier B.V. All rights reserved.</p