Relevance of Advanced Plant Disease Detection Techniques in Disease and Pest Management for Ensuring Food Security and Their Implication: A Review

Plant diseases and pests present significant challenges to global food security, leading to substantial losses in agricultural productivity and threatening environmental sustainability. As the world’s population grows, ensuring food availability becomes increasingly urgent. This review explores the significance of advanced plant disease detection techniques in disease and pest management for enhancing food security. Traditional plant disease detection methods often rely on visual inspection and are time-consuming and subjective. This leads to delayed interventions and ineffective control measures. However, recent advancements in remote sensing, imaging technologies, and molecular diagnostics offer powerful tools for early and precise disease detection. Big data analytics and machine learning play pivotal roles in analyzing vast and complex datasets, thus accurately identifying plant diseases and predicting disease occurrence and severity. We explore how prompt interventions employing advanced techniques enable more efficient disease control and concurrently minimize the environmental impact of conventional disease and pest management practices. Furthermore, we analyze and make future recommendations to improve the precision and sensitivity of current advanced detection techniques. We propose incorporating eco-evolutionary theories into research to enhance the understanding of pathogen spread in future climates and mitigate the risk of disease outbreaks. We highlight the need for a science-policy interface that works closely with scientists, policymakers, and relevant intergovernmental organizations to ensure coordination and collaboration among them, ultimately developing effective disease monitoring and management strategies needed for securing sustainable food production and environmental well-being.

Beyond the gluten-free diet:Innovations in celiac disease therapeutics

Celiac disease(CD)is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals,leading to intestinal inflammation and damage.This chronic disease affects approximately 1%of the world’s po-pulation and is a growing health challenge due to its increasing prevalence.The development of CD is a complex interaction between genetic predispositions and environmental factors,especially gluten,culminating in a dysregulated immune response.The only effective treatment at present is a strict,lifelong gluten-free diet.However,adherence to this diet is challenging and often incomplete,so research into alternative therapies has intensified.Recent advances in under-standing the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effec-tive and manageable treatment options.This review examines the latest inno-vations in CD therapies.The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis.We dis-cuss both quantitative strategies such as enzymatic degradation of gluten,and qualitative approaches including immunomodulation and induction of gluten tolerance.Innovative treatments currently under investigation include transglu-taminase inhibitors,which prevent the modification of gluten peptides,and nano-particle-based therapies to recalibrate the immune response.These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions.The integration of these new therapies could revolutionize the treatment of CD and shift the para-digm from strict dietary restrictions to a more flexible and patient-friendly thera-peutic approach.This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collab-oration to integrate these advances into standard clinical practice.

The crucial role of surveillance in disease outbreak control:a comprehensive review

Surveillance systems are vital for detecting,managing,and mitigating infectious disease outbreaks.This review highlights the importance of modern technologies like AI and big data in enhancing surveillancecapabilities.It underscores the need for global collaboration and examines the role of surveillance in diseases likeinfluenza,Ebola,and COVID-19.Technological innovations such as geospatial mapping and wearable healthdevices are transforming disease control,though they raise ethical concerns about privacy.Continuousadvancements and ethical safeguards are crucial for effective surveillance and global health protection.

Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

Elastography-based liver stiffness measurement(LSM) is a non-invasive tool for estimating liver fibrosis but also provides an estimate for the severity of portal hypertension in patients with advanced chronic liver disease(ACLD). The presence of varices and especially of varices needing treatment(VNT) indicates distinct prognostic stages in patients with compensated ACLD(cACLD). The Baveno VI guidelines suggested a simple algorithm based on LSM < 20 kPa(by transient elastography, TE) and platelet count > 150 G/L for ruling-out VNT in patients with cACLD. These(and other) TE-based LSM cut-offs have been evaluated for VNT screening in different liver disease etiologies. Novel point shear-wave elastography(pSWE) and two-dimensional shear wave elastography(2D-SWE) methodologies for LSM have also been evaluated for their ability to screen for "any" varices and for VNT. Finally, the measurement of spleen stiffness(SSM) by elastography(mainly by pSWE and 2D-SWE) may represent another valuable screening tool for varices. Here, we summarize the current literature on elastography-based prediction of "any" varices and VNT. Finally,we have summarized the published LSM and SSM cut-offs in clinically useful scale cards.

Role of advanced glycation end products in cardiovascular disease

Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.

Magnetic resonance enterography in Crohn’s disease: Standard and advanced techniques

Crohn's disease (CD) is a chronic autoimmune disorder that affects mainly young people. The clinical management is based on the Crohn's Disease Activity Index and especially on biologic parameters with or without additional endoscopic and imaging procedures, such as barium and computed tomography examinations. Recently, magnetic resonance (MR) imaging has been a promising diagnostic radiologic technique with lack of ionizing radiation, enabling superior tissue contrast resolution due to new pulse-sequence developments. Therefore, MR enterography has the potential to become the modality of choice for imaging the small bowel in CD patients.

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

Challenges in COVID-19 drug treatment in patients with advanced liver diseases:A hepatology perspective

The global incidence of coronavirus disease 2019(COVID-19)continues to increase despite health care efforts.The disease is caused by coronavirus 2 with high transmission and mortality rates.Little is known about the management of COVID-19 in advanced liver disease.The aim of work was to propose a plan for management of this drastic disease in case of this specific population with review of medications that could be suitable for advanced liver disease.All the guidelines and medications available for treatment of COVID-19 were reviewed with selection of the less toxic medications that could be used in advanced liver disease.Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously,nitazoxanide+sofosbuvir,ivermectin,tocilizumab,convalescent plasma,and low molecular weight heparin in certain situations.Advanced liver disease is associated with portal hypertension and splenomegaly with reduction of blood elements and immune dysfunction and impaired T cell function.Thus,when confronted by cytokine storm as an immune response to COVID-19,there may be an increase in the mortality rate of these patients.Through this review,a plan to treat COVID-19 in this special group of patients with advanced cirrhosis is proposed.

Role of the advanced glycation end products receptor in Crohn's disease inflammation

AIM:To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products(RAGE)in delayed apoptosis and tumor necrosis factor(TNF)-αproduction in Crohn’s disease(CD).METHODS:Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients,respectively,and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis.Normal tissues from 21 control subjects were used for comparison.The same polyclonal anti-human RAGE antibody(R and D System)was used in all experimental conditions.RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity;cellular pattern was also described.The effects of RAGE blocking on apoptotic rate and TNF-αproduction were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus.Statistical analysis was performed via the test for trend,with regression models to account for intra-patient correlations.A 2-sided P<0.05 was considered significant.RESULTS:In inflamed areas,RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues(P=0.001 and 0.021,respectively),and a cluster of positive cells were usually found in proximity of ulcerative lesions.Similar results were obtained in the lamina propria compartment of non-inflamed areas(P=0.025).The pattern of staining was membranous and granular cytosolic at the epithelial level,while in the lamina propria it was diffuse cytosolic.When evaluating the amount of protein expression by immunoblotting,a significant increase of both surface area and band intensity(P<0.0001 for both)was observed in CD inflamed areas compared to control tissue,while in non-inflamed areas a significant increase was found only for band intensity(P<0.005).Moreover,a significantly lower expression in noninflamed areas in comparison with inflamed areas was found for both surface area and band intensity(P<0.0006 for both).Finally,RAGE blocking largely affects both the apoptotic rate of mucosal cells(towards an increase in both non-inflamed and inflamed areas of P<0.001 and<0.0001,respectively)and TNF-αsecretion(towards a decrease in both non-inflamed and inflamed areas of P<0.05 and<0.01,respectively),mainly in the presence of antigenic stimulation.CONCLUSION:RAGE is up-regulated in CD,especially in inflamed areas,and it appears to play a role in the mechanisms involved in chronic inflammation.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases:A dangerous liaison?

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

Advanced glycation end product:A potential biomarker for risk stratification of non-alcoholic fatty liver disease in ELSA-Brasil study

BACKGROUND Liver diseases are associated with the excess formation of advanced glycation end products(AGEs),which induce tissue inflammation and oxidative damage.However,the trend of oxidative marker levels according to the steatosis grade in non-alcoholic fatty liver disease(NAFLD)is unclear.AIM To compare serum AGE levels between participants with NAFLD accordingly to steatosis severity in the baseline ELSA-Brasil population.METHODS In 305 individuals at baseline ELSA-Brasil,NAFLD-associated steatosis was classified by ultrasound hepatic attenuation.The participants were grouped according to the severity of steatosis:mild and moderate/severe pooled.The measurement of serum fluorescent AGE concentrations was based on spectrofluorimetric detection.Serum AGE content and clinical and laboratory characteristics of the participants were compared between groups.The correlation between serum AGE levels and the grade of steatosis was analyzed.Logistic regression analysis was used to investigate the relationship between serum AGE levels and steatosis severity.A P value<0.05 was considered statistically significant.RESULTS According to the steatosis severity spectrum in NAFLD,from mild to moderate/severe,individuals with the most severe steatosis grade had a higher incidence of metabolic syndrome(63%vs 34%,P≤0.001),diabetes mellitus(37%vs 14%,P≤0.001),and high cholesterol levels(51%vs 33%,P<0.001).Moreover,individuals with increasing severity of steatosis presented increasing waist circumference,body mass index,systolic and diastolic blood pressure,fasting blood glucose,glycated hemoglobin,insulin,triglycerides,alanine aminotransferase,gamma-glutamyl transferase,C-reactive protein,and uric acid levels and lower high-density lipoprotein.Higher serum AGE content was present in the moderate/severe group of individuals than in the mild group(P=0.008).In addition,the serum AGE levels were correlated with the steatosis grade in the overall sample(rho=0.146,P=0.010).Logistic regression analysis,after adjusting for confounding variables,showed that subjects with higher serum AGE content had a 4.6-fold increased chance of having moderate or severe steatosis when compared to low levels of serum AGEs.According to the results of the receiver operator characteristic curves analyses(areas under the curve,AUC=0.83),AGEs could be a good marker of steatosis severity in patients with NAFLD and might be a potential biomarker in predicting NAFLD progression,strengthening the involvement of AGE in NAFLD pathogenesis.CONCLUSION NAFLD-associated steatosis was associated with serum AGE levels;therefore,plasmatic fluorescent AGE quantification by spectroscopy could be a promising alternative method to monitor progression from mild to severe NAFLD accordingly to steatosis grade.

Correlation between soluble receptor for advanced glycation end products levels and coronary artery disease in postmenopausal nondiabetic women

BACKGROUND The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease(CAD),especially in women.Therefore,there is a growing need for the assessment of novel biomarkers to identify women at risk.The receptor for advanced glycation end products(RAGE)and its interaction with the advanced glycation end product(AGE)ligand have been associated with atherogenesis.The soluble fraction of RAGE(sRAGE)antagonizes RAGE signaling and exerts an antiatherogenic effect.AIM The study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women.METHODS This case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups.Group I included 55 angiographically proven CAD subjects with>50%stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had<50%stenosis of the coronary arteries.Stenosis was confirmed by invasive angiography.Plasma sRAGE was determined by an enzyme-linked immunosorbent assay.RESULTS We observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls(P<0.05).Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD(P=0.01).Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL(lowest quartile)had a 6-fold increase in CAD prevalence independent of other risk factors.CONCLUSION Our findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women.Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.

Metabolomics: From liver chiromancy to personalized precision medicine in advanced chronic liver disease

Currently there is a lack of accurate biomarkers for diagnosis and prognosis in advanced liver diseases. Either the occurrence of first decompensation, or diagnosis of acute on chronic liver failure, severe alcoholic hepatitis, or hepatocellular carcinoma(HCC), none of the available biomarkers are satisfactory. Metabolomics is the newest of omics, being much closer than the others to the actual phenotype and pathologic changes that characterizes a certain condition. It deals with a much wider spectrum of low molecular weight bio-compounds providing a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication and therapy. Until now metabolomics was applied in a wide spectrum of liver conditions, but the findings were contradictory. This review proposes a synthesis of the existing evidences of metabolomics use in advanced chronic liver diseases, decompensated liver cirrhosis, severe alcoholic hepatitis and HCC.

Advanced gastrointestinal endoscopic imaging forinflammatory bowel diseases

Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn's disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection.

Compensated liver cirrhosis:Natural course and disease-modifying strategies

Compensated liver cirrhosis(CLC)is defined as cirrhosis with one or more decompensating events,such as ascites,variceal haemorrhage,or hepatic encephalopathy.Patients with CLC are largely asymptomatic with preserved hepatic function.The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors.The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis,as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years.Furthermore,early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition.With the advent of effective non-invasive tools for detecting hepatic fibrosis,more and more patients with CLC are currently being recognised.This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or,at the very least,prevent its progression.There are numerous emerging approaches for preventing or delaying decompensation in CLC patients.A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression,and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension.Additionally,address-ing various cofactors(such as obesity,diabetes,dyslipidaemia,and alcoholism)and precipitating factors(such as infection,viral hepatitis,and hepatotoxic drugs)that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC.However,high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these diseasemodifying techniques for CLC patients.This article discussed the natural history of CLC,risk factors for its progression,and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.

Advances in the relationship between apolipoprotein gene polymorphism and blood lipid and cardiovascular disease

Objective： Dyslipidemia is a leading cause of cardiovascular disease. At present, studies have shown that theincidence of cardiovascular disease in our country increased year by year. According to WHO statistics in 2013, itshowed that about 17 million people worldwide die from coronary heart disease （CHD） every year. Currently, CHDis the first cause of death in western countries and the incidence of CHD also showed a trend of increasing. Inrecent years more experts and scholars at home and abroad found gene polymorphism is closely related tohigh-density lipoprotein cholesterol （HDLC） gene and triglyceride （TG） levels. Apolipoprotein （APO） gene is akind of popular polymorphic proteins, whose genetic polymorphisms is through the impact of lipid metabolism,and then closely related to cerebrovascular diseases. But the results are different in different populations and races,or even the opposite. Methods： This review will summarize the gene polymorphism loci of commonapolipoprotein-ApoA1, ApoA5, Apo B, ApoC3, ApoE, which is associated with lipid levels and cardiovasculardisease. Conclusion： It is important for us to get a further understand and prevent the occurrence and developmentof cardiovascular disease from gene level..

早产儿视网膜病变Norrie disease基因突变研究

目的验证Norriedisease(ND)基因是否与早产儿视网膜病变有关及黄种人中是否存在较高的突变率。方法对25例进展期早产儿视网膜病变的患儿进行临床及生物分子学检查。通过外周血人基因组DNA提取,采用聚合酶链式反应(PCR)扩增,非同位素标记单链构象多态性(SSCP)分析,硝酸银染色法及直接测序法。结果2例患儿的第3外显子的非读码框架基因序列经银染后可见2条异常条带出现,并经直接测序验正发生基因的点突变由T到C,而外显子1及2以及其剪接区均未发现突变。对照组未发现相同突变。结论早产儿视网膜病变与ND基因的突变可能具有一定的联系。

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.

Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer:The debate continues

Rectal carcinoma represents the 30% of all colorectal cancers, with about 40000 new cases/years. In the past two decades, the management of rectal cancer has made important progress, highlighting the main role of a multimodality strategy approach, combining surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neoadjuvant chemoradiotherapy, based on fluoropyrimidine(5-FU) continuous infusion, is considered the standard in locally advanced rectal carcinoma. The aim is to reduce the incidence of local recurrence and to perform a conservative surgery. To improve these purposes different drugs combination have been tested in the neo-adjuvant setting. At American Society of Clinical Oncology 2014 an important abstract was presented focusing on the role of adding oxaliplatin to concomitant treatment, in patients with locally advanced rectal carcinoma. Rodel et al reported on the CAO/ARO/AIO-04 randomized phase Ⅲ trial that compared standard treatment with 5-FU and radiation therapy, to oxaliplatin plus 5-FU inassociation with radiation therapy. The addition of oxaliplatin to the neo-adjuvant treatment has been shown to improve disease-free survival from 71.2% to 75.9%(P = 0.03). This editorial was planned to clarify the optimal treatment in patients with locally advanced rectal cancer, considering the results from CAO/ARO/AIO-04 study.