Autoimmune pancreatitis:Cornerstones and future perspectives

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

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.

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Non-anatomical liver resection for hepatocellular carcinoma:the SegSubTe classification to overcome the problem of heterogeneity

Background:The superiority of anatomical resection(AR)vs.non-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is debated.ARs are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous outcomes.This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor.Methods:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted.The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section(segmental,subsegmental or terminal next to the tumor)of vascular pedicles feeding the HCCs;then,the population was divided in“SegSubTe-IN”or“SegSubTe-OUT”groups,and the tumor recurrence and survival were analyzed.Results:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were SegSubTe-OUT.Total disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN vs.SegSubTe-OUT groups were 50%vs.83%(P=0.006),20%vs.52%(P=0.003)and 16%vs.39%(P=0.020),respectively.SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis.One-,three-,and five-year disease-free survival rates in the SegSubTe-IN vs.SegSubTe-OUT groups were 81%,58%and 35%vs.46%,21%and 11%,respectively(P<0.001).Conclusions:The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC,aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

Later-Life Marital Dissolution in Italy:An Emerging Phenomenon?

The phenomenon of marital dissolution in later life,also referred to as“gray divorce”,is described on the rise in contemporary Western societies.This article contributes to the study of marriage breakdown in older age,with a specific focus on Italian society.First,the temporal trends of this phenomenon are reconstructed using official statistics.The data reveal that,although still relatively rare,the dissolution of marriage in later life is expanding in Italy.The analysis of the period from 1974 to 2015 indicates a rise in the average age at separation,a higher percentage of spouses over 50 years on the total number of couples obtaining legal separation,and an increase in the proportion of Italian spouses separating after many years of marriage.Furthermore,data from the national survey“Family and Social Subjects”,conducted in 2016 by the Italian National Institute of Statistics,are utilized to explore the relationship between specific traits of those who separated and their tendency to dissolve marriages before or after the age of 50.The data suggest that individuals with characteristics such as lower educational attainment,residence in the South and Islands,and adherence to more traditional family models are more likely to experience separation in later life.

Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis:Insights into mechanisms,pathophysiology,and treatment options

BACKGROUND Autoimmune gastritis(AIG)is a progressive,chronic,immune-mediated inflammatory disease characterized by the destruction of gastric parietal cells leading to hypo/anacidity and loss of intrinsic factor.Gastrointestinal symptoms such as dyspepsia and early satiety are very common,being second in terms of frequency only to anemia,which is the most typical feature of AIG.AIM To address both well-established and more innovative information and knowledge about this challenging disorder.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 10 years.RESULTS A total of 125 records were reviewed and 80 were defined as fulfilling the criteria.CONCLUSION AIG can cause a range of clinical manifestations,including dyspepsia.The pathophysiology of dyspepsia in AIG is complex and involves changes in acid secretion,gastric motility,hormone signaling,and gut microbiota,among other factors.Managing dyspeptic symptoms of AIG is challenging and there are no specific therapies targeting dyspepsia in AIG.While proton pump inhibitors are commonly used to treat dyspepsia and gastroesophageal reflux disease,they may not be appropriate for AIG.Prokinetic agents,antidepressant drugs,and non-pharmacological treatments may be of help,even if not adequately evidence-based supported.A multidisciplinary approach for the management of dyspepsia in AIG is recommended,and further research is needed to develop and validate more effective therapies for dyspepsia.

Radiological findings in non-surgical recurrent hepatocellular carcinoma:From locoregional treatments to immunotherapy

Since hepatocellular carcinoma(HCC)represents an important cause of mortality and morbidity all over the world.Currently,it is fundamental not only to achieve a curative treatment but also to manage in the best way any possible recurrence.Even if the latest update of the Barcelona Clinic Liver Cancer guidelines for HCC treatment has introduced new locoregional techniques and confirmed others as well-established clinical practices,there is still no consensus about the treatment of recurrent HCC(RHCC).Locoregional treatments and medical therapy represent two of the most widely accepted approaches for disease control,especially in the advanced stage of liver disease.Different medical treatments are now approved,and others are under investigation.On this basis,radiology plays a central role in the diagnosis of RHCC and the assessment of response to locoregional treatments and medical therapy for RHCC.This review summarized the actual clinical practice by underlining the importance of the radiological approach both in the diagnosis and treatment of RHCC.

Incidence and prevalence of gastric neuroendocrine tumors in patients with chronic atrophic autoimmune gastritis

BACKGROUND The incidence of type I gastric neuroendocrine neoplasms(gNENs)has increased significantly over the past 50 years.Although autoimmune gastritis(AIG)increases the likelihood of developing gNENs,the exact incidence and prevalence of this association remain unclear.AIM To evaluate the incidence and prevalence of type I gNENs in a cohort of patients with a histological diagnosis of AIG.METHODS Patients with a histological diagnosis of AIG were enrolled between October 2020 and May 2022.Circulating levels of CgA and gastrin were assessed at enrollment.Included patients underwent regular endoscopic follow-up to detect gastric neoplastic lesions,enterochromaffin-like(ECL)cell hyperplasia,and the development of gNEN.RESULTS We included 176 patients[142 women(80.7%),median age 64 years,interquartile range(IQR)53–71 years]diagnosed with AIG between January 1990 and June 2022.At enrollment.One hundred and sixteen patients(65.9%)had ECL hyperplasia,of whom,29.5%had simple/linear,30.7%had micronodular,and 5.7%had macronodular type.The median follow-up time was 5(3–7.5)years.After 1032 person-years,33 patients developed a total of 50 type I gNENs,with an incidence rate of 0.057 person-years,corresponding to an annual cumulative incidence of 5.7%.Circulating CgA levels did not significantly differ between AIG patients who developed gNENs and those who did not.Conversely,gastrin levels were significantly higher in AIG patients who developed gNENs[median 992 pg/mL IQR=449–1500 vs 688 pg/mL IQR=423–1200,P=0.03].Calculated gastrin sensitivity and specificity were 90.9%and 1.4%,respectively,with an overall diagnostic accuracy of 30%and a calculated area under the gastrin receiver operating characteristic curve(AUROC or AUC)of 0.53.CONCLUSION Type I gNENs are a significant complication in AIG.Gastrin’s low diagnostic accuracy prevents it from serving as a marker for early diagnosis.Effective strategies for early detection and treatment are needed.

Molybdenum disulfide as hydrogen evolution catalyst:From atomistic to materials structure and electrocatalytic performance

Hydrogen production via water electrolysis defines the novel energy vector for achieving a sustainable society.However,the true progress of the given technology is hindered by the sluggish and complex hydrogen evolution reaction(HER)occurring at the cathodic side of the system where overpriced and scarce Pt-based electrocatalysts are usually employed.Therefore,efficient platinum group metals(PGMs)-free electrocatalysts to carry out HER with accelerated kinetics are urgently demanded.In this scenario,molybdenum disulfide(MoS_(2))owing to efficacious structural attributes and optimum hydrogen-binding free energy(ΔG_(H*))is emerging as a reliable alternative to PGMs.However,the performance of MoS_(2)-based electrocatalysts is still far away from the benchmark performance.The HER activity of MoS_(2)can be improved by engineering the structural parameters i.e.,doping,defects inducement,modulating the electronic structure,stabilizing the 1 T phase,creating nanocomposites,and altering the morphologies using appropriate fabrication pathways.Here,we have comprehensively reviewed the majority of the scientific endeavors published in recent years to uplift the HER activity of MoS_(2)-based electrocatalysts using different methods.Advancements in the major fabrication strategies including hydrothermal synthesis methods,chemical vapor deposition,exfoliation techniques,plasma treatments,chemical methodologies,etc.to tune the structural parameters and hence their ultimate influence on the electrocatalytic activity in acidic and/or alkaline media have been thoroughly discussed.This study can provide encyclopedic insights about the fabrication routes that have been pursued to improve the HER performance of MoS_(2)-based electrocatalysts.

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

MR with Gd-EOB-DTPA in assessment of liver nodules in cirrhotic patients

To date the imaging diagnosis of liver lesions is based mainly on the identification of vascular features, which are typical of overt hepatocellular carcinoma(HCC), but the hepatocarcinogenesis is a complex and multistep event during which, a spectrum of nodules develop within the liver parenchyma, including benign small and large regenerative nodule(RN), low-grade dysplastic nodule(LGDN), high-grade dysplastic nodule(HGDN), early HCC, and well differentiated HCC. These nodules may be characterised not only on the basis of their respective different blood supplies, but also on their different hepatocyte function. Recently, in liver imaging the introduction of hepatobiliary magnetic resonance imaging contrast agent offered the clinicians the possibility to obtain, at once, information not only related to the vascular changes of liver nodules but also information on hepatocyte function. For this reasons this new approach becomes the most relevant diagnostic clue for differentiating low-risk nodules(LGDN-RN) from highrisk nodules(HGDN/early HCC or overt HCC) and consequently new diagnostic algorithms for HCC have been proposed. The use of hepatobiliary contrast agents is constantly increasing and gradually changing the standard of diagnosis of HCC. The main purpose of this review is to underline the added value of Gd-EOB-DTPA in early-stage diagnoses of HCC. We also analyse the guidelines for the diagnosis and management of HCC, the key concepts of HCC development, growth and spread and the imaging appearance of precursor nodules that eventually may transform into overt HCC.

Hepatocellular carcinoma treated with transarterial chemoembolization: Dynamic perfusion-CT in the assessment of residual tumor

AIM: To asses the value of computed tomography (CT)-perfusion in the detection of residual hepatocellular carcinoma (HCC) vascularization after transarterial chemoembolization (TACE). METHODS: Thirty-two consecutive patients were pro-spectively included in this study. All patients had liver cirrhosis and a conf irmed HCC lesion which was treated with TACE. One month after treatment, perfusion measurements of treated lesions were carried out. The CTperfusion (CT-p) protocol was performed with 16 slice multidetector computed tomography which included the following parameters: 8 dynamic slices/scan per 40 scans after iv injection of 50 mL of iodinated contrast (350 mg/mL) at a flow rate of 6 mL/s. Treated lesions were evaluated using dedicated perfusion software, which generated a quantitative colour map of perfusion. The following parameters were considered: hepatic perfusion (HP), arterial perfusion (AP), blood volume (BV), hepatic perfusion index (HPI), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution and statistically analyzed. RESULTS: Perfusion parameters of the treated lesions could be quantitatively assessed using CT-p analysis. The presence of residual tumor tissue was observed in 13 of the 32 patients. The values of the perfusion parameters measured within the relapse tissue were: HP (mL/100 g per minute): median = 44.4 (1stqt = 31.3, 3rdqt = 55.8); BV (mL/100 g): median = 18.7 (1stqt = 11.5, 3rdqt = 22.5); AP (mL/min): median = 39.0 (1stqt = 36.5, 3rdqt = 61.3); HPI (%): median = 34.0 (1stqt = 30.4, 3rdqt = 38.9); TTP (s): median = 17.3 (1stqt = 15.8, 3rdqt = 26.5). With the use of the univariate paired Wilcoxon signed rank test, HP, AP and HPI were shown to be significantly higher (P<0.001) in the relapse site than in the primary lesion. The BV and TTP parameters showed a tendency to be greater and lower, respectively, in the relapse site than in the primary lesion. CONCLUSION: In patients with HCC treated with TACE, CT-p provides measurement of flow parameters related to residual arterial structures in viable tumor, thus helping in the assessment of therapeutic response.

Recent advances in non-invasive magnetic resonance imaging assessment of hepatocellular carcinoma

Magnetic resonance(MR) imaging of the liver is an important tool for the detection and characterization of focal liver lesions and for assessment of diffuse liver disease,having several intrinsic characteristics,represented by high soft tissue contrast,avoidance of ionizing radiation or iodinated contrast media,and more recently,by application of several functional imaging techniques(i.e.,diffusion-weighted sequences,hepatobiliary contrast agents,perfusion imaging,magnetic resonance(MR)-elastography,and radiomics analysis). MR functional imaging techniques are extensively used both in routine practice and in the field of clinical and pre-clinical research because,through a qualitative rather than quantitative approach,they can offer valuable information about tumor tissue and tissue architecture,cellular biomarkers related to the hepatocellular functions,or tissue vascularization profiles related to tumor and tissue biology. This kind of approach offers in vivo physiological parameters,capable of evaluating physiological and pathological modifications of tissues,by the analysis of quantitative data that could be used in tumor detection,characterization,treatmentselection,and follow-up,in addition to those obtained from standard morphological imaging. In this review we provide an overview of recent advanced techniques in MR for the diagnosis and staging of hepatocellular carcinoma,and their role in the assessment of response treatment evaluation.

Rectal cancer staging: Multidetector-row computed tomography diagnostic accuracy in assessment of mesorectal fascia invasion

AIM: To assess the diagnostic accuracy of multidetectorrow computed tomography(MDCT) as compared with conventional magnetic resonance imaging(MRI), in identifying mesorectal fascia(MRF) invasion in rectal cancer patients.METHODS: Ninety-one patients with biopsy proven rectal adenocarcinoma referred for thoracic and abdominal CT staging were enrolled in this study. The contrast-enhanced MDCT scans were performed on a 256 row scanner(ICT, Philips) with the following acquisition parameters: tube voltage 120 KV, tube current 150-300 m As. Imaging data were reviewed as axial and as multiplanar reconstructions(MPRs) images along the rectal tumor axis. MRI study, performed on 1.5 T with dedicated phased array multicoil, included multiplanar T2 and axial T1 sequences and diffusion weighted images(DWI). Axial and MPR CT images independently were compared to MRI and MRF involvement was determined. Diagnostic accuracy of both modalities was compared and statistically analyzed.RESULTS: According to MRI, the MRF was involved in 51 patients and not involved in 40 patients. DWI allowed to recognize the tumor as a focal mass with high signal intensity on high b-value images, compared with the signal of the normal adjacent rectal wall or with the lower tissue signal intensity background. The number of patients correctly staged by the native axial CT images was 71 out of 91(41 with involved MRF; 30 with not involved MRF), while by using the MPR 80 patients were correctly staged(45 with involved MRF; 35 with not involved MRF). Local tumor staging suggested by MDCT agreed with those of MRI, obtaining for CT axial images sensitivity and specificity of 80.4% and 75%, positive predictive value(PPV) 80.4%, negative predictive value(NPV) 75% and accuracy 78%; while performing MPR the sensitivity and specificity increased to 88% and 87.5%, PPV was 90%, NPV 85.36% and accuracy 88%. MPR images showed higher diagnostic accuracy, in terms of MRF involvement, than native axial images, as compared to the reference magnetic resonance images. The difference in accuracy was statistically significant(P = 0.02). CONCLUSION: New generation CT scanner, using high resolution MPR images, represents a reliable diagnostic tool in assessment of loco-regional and whole body staging of advanced rectal cancer, especially in patients with MRI contraindications.

Role of dynamic perfusion magnetic resonance imaging in patients with local advanced rectal cancer

BACKGROUND The management of rectal cancer patients is mainly based on the use of the magnetic resonance imaging(MRI)technique as a diagnostic tool for both staging and restaging.After treatment,to date,the evaluation of complete response is based on the histopathology assessment by using different tumor regression grade(TRG)features(e.g.,Dworak or Mandard classifications).While from the radiological point of view,the main attention for the prediction of a complete response after chemotherapy treatment focuses on MRI and the potential role of diffusion-weighted images and perfusion imaging represented by dynamiccontrast enhanced MRI.The main aim is to find a reliable tool to predict tumor response in comparison to histopathologic findings.AIM To investigate the value of dynamic contrast-enhanced perfusion-MRI parameters in the evaluation of the healthy rectal wall and tumor response to chemo-radiation therapy in patients with local advanced rectal cancer with histopathologic correlation.METHODS Twenty-eight patients with biopsy-proven rectal adenocarcinoma who underwent a dynamic contrast-enhanced MR study performed on a 1.5 T MRI system(Achieva,Philips),before(MR1)and after chemoradiation therapy(MR2),were enrolled in this study.The protocol included T1 gadolinium enhanced THRIVE sequences acquired on axial planes.A dedicated workstation was used to generate color permeability maps.Region of interest was manually drawn on tumor tissue and normal rectal wall,hence the following parameters were calculated and statistically analyzed:Relative arterial enhancement(RAE),relative venous enhancement(RVE),relative late enhancement(RLE),maximum enhancement(ME),time to peak and area under the curve(AUC).Perfusion parameters were related to pathologic TRG(Mandard’s criteria;TRG1=complete regression,TRG5=no regression).RESULTS Ten tumors(36%)showed complete or subtotal regression(TRG1-2)at histology and classified as responders;18 tumors(64%)were classified as non-responders(TRG3-5).Perfusion MRI parameters were significantly higher in the tumor tissue than in the healthy tissue in MR1(P<0.05).At baseline(MR1),no significant difference in perfusion parameters was found between responders and nonresponders.After chemo-radiation therapy,at MR2,responders showed significantly(P<0.05)lower perfusion values[RAE(%)54±20;RVE(%)73±24;RLE(%):82±29;ME(%):904±429]compared to non-responders[RAE(%):129±45;RVE(%):154±39;RLE(%):164±35;ME(%):1714±427].Moreover,in responders group perfusion values decreased significantly at MR2[RAE(%):54±20;RVE(%):73±24;RLE(%):82±29;ME(%):904±429]compared to the corresponding perfusion values at MR1[RAE(%):115±21;RVE(%):119±21;RLE(%):111±74;ME(%):1060±325];(P<0.05).Concerning the time-intensity curves,the AUC at MR2 showed significant difference(P=0.03)between responders and non-responders[AUC(mm2×10-3)121±50 vs 258±86],with lower AUC values of the tumor tissue in responders compared to nonresponders.In non-responders,there were no significant differences between perfusion values at MR1 and MR2.CONCLUSION Dynamic contrast perfusion-MRI analysis represents a complementary diagnostic tool for identifying vascularity characteristics of tumor tissue in local advanced rectal cancer,useful in the assessment of treatment response.

Hepcidin modulation in human diseases: From research to clinic

By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.

Rethinking the Barcelona clinic liver cancer guidelines:Intermediate stage and Child-Pugh B patients are suitable for surgery?

According to Barcelona Clinic Liver Cancer recommendations,intermediate stage hepatocellular carcinomas(stage B)are excluded from liver resection and are referred to palliative treatment.Moreover,Child-Pugh B patients are not usually candidates for liver resection.However,many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection,maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function.Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification,and this treatment gives good results in the setting of multinodular,large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis.In this review we explore this controversial topic,and we show through the literature analysis how liver resection may improve the short-and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients.However,other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.

Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer

AIM:To assess the clinical diagnostic value of functional imaging,combining quantitative parameters of apparent diffusion coefficient(ADC) and standardized uptake value(SUV)max,before and after chemo-radiation therapy,in prediction of tumor response of patients with rectal cancer,related to tumor regression grade at histology.METHODS:A total of 31 patients with biopsy proven diagnosis of rectal carcinoma were enrolled in our study.All patients underwent a whole body ^(18)FDG positron emission tomography(PET)/computed tomography(CT) scan and a pelvic magnetic resonance(MR)examination including diffusion weighted(DW) imaging for staging(PET1,RM1) and after completion(6.6 wk)of neoadjuvant treatment(PET2,RM2).Subsequently all patients underwent total mesorectal excision and the histological results were compared with imaging findings.The MR scanning,performed on 1.5 T magnet(Philips,Achieva),included T2-weighted multiplanar imaging and in addition DW images with b-value of 0 and 1000 mm^2/s.On PET/CT the SUVmax of the rectal lesion were calculated in PET1 and PET2.The percentage decrease of SUVmax(△SUV) and ADC(△ADC) values from baseline to presurgical scan were assessed and correlated with pathologic response classified as tumor regression grade(Mandard's criteria;TRG1 = complete regression,TRG5 = no regression).RESULTS:After completion of therapy,all the patients were submitted to surgery.According to the Mandard's criteria,22 tumors showed complete(TRG1) or subtotal regression(TRG2) and were classified as responders;9tumors were classified as non responders(TRG3,4 and5).Considering all patients the mean values of SUVmax in PET 1 was higher than the mean value of SUVmax in PET 2(P < 0.001),whereas the mean ADC values was lower in RM1 than RM2(P < 0.001),with a △SUV and △ADC respectively of 60.2%and 66.8%.The best predictors for TRG response were SUV2(threshold of4.4) and ADC2(1.29 × 10^(-3) mm^2/s) with high sensitivity and specificity.Combining in a single analysis both the obtained median value,the positive predictive value,in predicting the different group category response in related to TRG system,presented R^2 of 0.95.CONCLUSION:The functional imaging combining ADC and SUVmax in a single analysis permits to detect changes in cellular tissue structures useful for the assessment of tumour response after the neoadjuvant therapy in rectal cancer,increasing the sensitivity in correct depiction of treatment response than either method alone.

Neural plasticity and adult neurogenesis: the deep biology perspective

The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology.

Impact of the COVID-19 pandemic on liver donation and transplantation:A review of the literature

The coronavirus disease 2019(COVID-19)pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation(LT)activity.During the first pandemic wave,administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a lifesaving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients.Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients,design COVID-safe clinical pathways,and promote telehealth to prevent nosocomial transmission.Despite the ever-growing literature on COVID-19,the amount of high-quality literature on LT remains limited.This review will provide an updated view of the impact of the pandemic on LT programs worldwide.Donor and recipient screening,strategies for waitlist prioritization,and posttransplant risk of infection and mortality are discussed.Moreover,a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients.