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1Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation:Effects on virus replication and recurrent hepatitis显示文摘瞄准:决定 calcineurin 禁止者, cyclosporine 和 tacrolimus 的效果,在丙肝上,在病人的周期性的丙肝的病毒(HCV ) 复制和活动张贴肝移植。方法:在我们的中心为在 1999 和 2003 之间的联系 HCV 的肝肝硬化收到了肝移植的 107 个病人的一个队的数据回顾地被分析。浆液 HCV-RNA 的水平和周期性的肝炎的活动在作为主要抑制免疫力的代理人和没在移植以后在开始的 12 瞬间以内导致胆汁的复杂并发症的不那样类似的抑制免疫力的政体收到了 cyclosporine 或 tacrolimus 的 47 个病人之间被比较。结果:HCV-RNA 在移植以后在 3 瞬间以内增加了,但是 cyclosporine 组和 tacrolimus 组之间的差别是不足道的(在 12 瞬间的 P=0.49 ) 。另外,由浆液 transaminases 决定了的周期性的肝炎并且门发炎和纤维变性的组织学的分级没在 12 瞬间(P=0.34 ) 以后显示出有效差量。结论:一个主要抑制免疫力的代理人不在肝移植以后在感染 HCV 的病人影响周期性的肝炎的正式就职或严厉的 Cyclosporine 或 tacrolimus。Philip Hilgard Alisan Kahraman Nils Lehmann Cornelia Seltmann Susanne Beckebaum R Stefan Ross Hideo A Baba Massimo Malago Christoph E Broelsch Guido Gerken 2006World Journal of Gastroenterology2006,12,5:235
2The molecular machinery of regulated cell death显示文摘Cells may die from accidental cell death(ACD)or regulated cell death(RCD).ACD is a biologically uncontrolled process,whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms.A growing number of novel nonapoptotic forms of RCD have been identified and are increasingly being implicated in various human pathologies.Here,we critically review the current state of the art regarding non-apoptotic types of RCD,including necroptosis,pyroptosis,ferroptosis,entotic cell death,netotic cell death,parthanatos,lysosome-dependent cell death,autophagy-dependent cell death,alkaliptosis and oxeiptosis.The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidanee of pathogenic cell loss.Daolin Tang Rui Kang Tom Vanden Berghe Peter Vandenabeele Guido Kroemer 2019Cell Research2019,29,5:143
3Ferroptosis:molecular mechanisms and health implications显示文摘Cell death can be executed through different subroutines.Since the description of ferroptosis as an iron-dependent form of nonapoptotic cell death in 2012,there has been mounting interest in the process and function of ferroptosis.Ferroptosis can occur through two major pathways,the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway.Ferroptosis is caused by a redox imbalance between the production of oxidants and antioxidants,which is driven by the abnormal expression and activity of multiple redox-active enzymes that produce or detoxify free radicals and lipid oxidation products.Accordingly,ferroptosis is precisely regulated at multiple levels,including epigenetic,transcriptional,posttranscriptional and posttranslational layers.The transcription factor NFE2L2 plays a central role in upregulating anti-ferroptotic defense,whereas selective autophagy may promote ferroptotic death.Here,we review current knowledge on the integrated molecular machinery of ferroptosis and describe how dysregulated ferroptosis is involved in cancer,neurodegeneration,tissue injury,inflammation,and infection.Daolin Tang Xin Chen Rui Kang Guido Kroemer 2021Cell Research2021,31,2:182
4Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer显示文摘AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer.METHODS:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and fluorouracil 300 mg/m 2 per day for days 1-14),either before(Arm A)or after(Arm B)gastrectomy.Operative morbidity,overall mortality,and severe adverse events were compared by intention-to-treat analysis.RESULTS:From November 1999 to November 2005,70 patients were treated.After preoperative TCF(Arm A),thirty-two(94%)resections were performed,85% of which were R0.Pathological response was complete in 4 patients(11.7%),and partial in 18(55%).No surgical mortality and 28.5%morbidity rate were observed,similar to those of immediate surgery arm(P= 0.86).Serious chemotherapy adverse events tended to be more frequent in arm B(23%vs 11%,P=0.07),with a single death per arm.CONCLUSION:Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.Roberto Biffi Nicola Fazio Fabrizio Luca Antonio Chiappa Bruno Andreoni Maria Giulia Zampino Arnaud Roth Jan Christian Schuller Giancarla Fiori Franco Orsi Guido Bonomo Cristiano Crosta Olivier Huber 2010World Journal of Gastroenterology2010,16,7:43
5Diagnosis of biliary strictures after liver transplantation:Which is the best tool?显示文摘AIM: To evaluate the diagnostic value of different indirect methods like biochemical parameters, ultrasound (US) analysis, CT-scan and MRI/MRCP in comparison with endoscopic retrograde cholangiography (ERC), for diagnosis of biliary complications after liver transplantation. METHODS: In 75 patients after liver transplantation, who received ERC due to suspected biliary complications, the result of the cholangiography was compared to the results of indirect imaging methods performed prior to ERC. The cholangiography showed no biliary stenosis (NoST) in 25 patients, AST in 27 and ITBL in 23 patients. RESULTS: Biliary congestion as a result of AST was detected with a sensitivity of 68.4% in US analysis (specificity 91%), of 71% in MRI (specificity 25%) and of 40% in CT (specificity 57.1%). In ITBL, biliary congestion was detected with a sensitivity of 58.8% in the US, 88.9%in MRI and of 83.3% in CT. However, as anastomotic or ischemic stenoses were the underlying cause of biliary congestion, the sensitivity of detection was very low. InMRI detected the dominant stenosis at a correct localization in 22% and CT in 10%, while US failed completely. The biochemical parameters, showed no significant difference in bilirubin (median 5.7; 4,1; 2.5 mg/dL), alkaline phosphatase (median 360; 339; 527 U/L) or gamma glutamyl transferase (median 277; 220; 239 U/L) levels between NoST, AST and ITBL.CONCLUSION: Our data confirm that indirect imaging methods to date cannot replace direct cholangiography for diagnosis of post transplant biliary stenoses. However MRI may have the potential to complement or precede imaging by cholangiography. Optimized MRCP-processing might further improve the diagnostic impact of this method.Thomas Zoepf Evelyn J. Maldonado-Lopez Philip Hilgard Alexander Dech■ne Massimo Malago Christoph E. Broelsch Joerg Schlaak Guido Gerken 2005World Journal of Gastroenterology2005,11,19:32
6Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstructed defecation(Part Ⅱ:Treatment)显示文摘The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation.There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation.Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre.Osmotic laxatives may be effective in patients who do not respond to fibre supplements.Stimulant laxatives should be reserved for patients who do not respond to osmotic laxatives.Controlled trials have shown that serotoninergic enterokinetic agents,such as prucalopride,and prosecretory agents,such as lubiprostone,are effective in the treatment of patients with chronic constipation.Surgery is sometimes necessary.Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coli who are resistant to medical therapy and who do not have defecatory disorders,generalised motility disorders or psychological disorders.Randomised controlled trials have established the efficacy of rehabilitative treatment in dys-synergic defecation.Many surgical procedures may be used to treat obstructed defecation in patients with acquired anatomical defects,but none is considered to be the gold standard.Surgery should be reserved for selected patients with an impaired quality of life.Obstructed defecation is often associated with pelvic organ prolapse.Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse,but the efficacy and safety of such procedures have not yet been established.Antonio Bove Massimo Bellini Edda Battaglia Renato Bocchini Dario Gambaccini Vincenzo Bove Filippo Pucciani Donato Francesco Altomare Giuseppe Dodi Guido Sciaudone Ezio Falletto Vittorio Piloni 2012World Journal of Gastroenterology2012,18,36:33
7Mitochondrial metabolism and cancer显示文摘Glycolysis 长在癌症房间为精力生产和 anabolism 的生长被看作了主要新陈代谢的过程。尽管如此的一个看法为仍然在诊所被使用的强大的成像工具的发展是有帮助的,线粒体在 oncogenesis 起一个关键作用,现在是清楚的。除施加中央 bioenergetic 函数以外,线粒体确实为肿瘤同化提供积木,控制氧化还原作用和钙动态平衡,参予 transcriptional 规定,并且管理房间死亡。因此,线粒体为新奇 anticancer 代理人的发展组成有希望的目标。然而,肿瘤产生,进行,并且回答功能依靠未经触动的 mitochondrial 新陈代谢到在有主人免疫系统,和许多免疫学的亲密串音的上下文的治疗。这里,我们考察房间内在的癌症和线粒体影响都 oncogenesis 通过走的房间外来的机制,与指向为癌症治疗的 mitochondrial 新陈代谢的治疗学的潜力的一个焦点。Paolo Ettore Porporato Nicoletta Filigheddu José Manuel Bravo-San Pedro, Guido Kroemer, Lorenzo Galluzzi José Manuel Bravo-San Pedro, Guido Kroemer José Manuel Bravo-San Pedro, Guido Kroemer José Manuel Bravo-San Pedro, Guido Kroemer José Manuel Bravo-San Pedro, Guido Kroemer Guido Kroemer Guido Kroemer Lorenzo Galluzzi Lorenzo Galluzzi 2018Cell Research2018,28,3:33
8Heparanase activates the syndecan-syntenin-ALIX exosome pathway显示文摘Bart Roucourt Sofie Meeussen Jie Bao Pascale Zimmermann Guido David 2015Cell Research2015,25,4:29
9Microwave ablation of hepatocellular carcinoma显示文摘Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgical treatment alternative,thanks to their minimal invasiveness,excellent tolerability and safety profile,proven efficacy in local disease control,virtually unlimited repeatability and cost-effectiveness.Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules.Among them,radiofrequency(RF) currents are the most used,while microwave ablations(MWA) are becoming increasingly popular.Starting from the 90s',RF ablation(RFA) rapidly became the standard of care in ablation,especially in the treatment of small HCC nodules;however,RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks.MWA,first introduced in the Far Eastern clinical practice in the 80s',showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors,resulting in a poor coagulative performance and a relatively high complication rate,nowadays shows better results both in terms of treatment controllability and of overall coagulative performance,thanks to the improvement of technology.In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems,and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications,both in absolute terms and in comparison with RFA.Guido Poggi Nevio Tosoratti Benedetta Montagna Chiara Picchi 2015World Journal of Hepatology2015,7,25:28
10Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B显示文摘AIM: To assess the performance of several non- invasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F ≥ 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB). METHODS: One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 ± 11.3) with CHB undergoing diagnostic liver biopsy were included. AST- to-Platelet ratio (APRI), Forns’ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index (GUCI), Hui’s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC). RESULTS: PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibro- test had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76, respectively). Stepwise combination algorithms of APRI, Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION: In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.Giada Sebastiani Alessandro Vario Maria Guido Alfredo Alberti 2007World Journal of Gastroenterology2007,13,4:26
11Foveal avascular zone area and parafoveal vessel density measurements in different stages of diabetic retinopathy by optical coherence tomography angiography显示文摘AIM:To investigate foveal avascular zone(FAZ) and parafoveal vessel densities(PRVD) by means of optical coherence tomography angiography(OCTA) in diabetic patients with or without diabetic retinopathy(DR) and to assess the reproducibility of FAZ and PRVD measurements.METHODS:Sixty diabetic patients(60 eyes) with different stage of DR(graded according to the International Clinical Severity Scale for DR) and 20 healthy subjects underwent FAZ area and PRVD measurements using OCTA by two experienced examiners.FAZ area in all patients was also assessed using fluorescein angiography(FA).RESULTS:In subject with proliferative DR and with moderate-severe non proliferative DR,FAZ area was significantly increased compared to healthy controls(P=0.025 and P=0.050 respectively measured with OCTA and P=0.025 and P=0.048 respectively measured with FA).OCTA showed significantly less inter-observer variability compared to FA.Concordance correlation coefficient(CCC) for FAZ area measurements was 0.829(95%CI:0.736-0.891) P<0.001 with FA and 1.000(95%CI:0.999-1.000) P<0.001 with OCTA.CCC was 0.834(95%CI:0.746-0.893) P<0.001 and 0.890(95%CI:0.828-0.930) P<0.001 for parafoveal superficial and deep vessel density measurements,respectively.CONCLUSION:OCTA shows progressive increase of FAZ area and reduction of PRVD in both superficial and deep plexus at increasing DR severity.FAZ area and PRVD measurements using OCTA are highly reproducible.Rodolfo Mastropasqua Lisa Toto Alessandra Mastropasqua Raffaella Aloia Chiara De Nicola Peter A Mattei Guido Di Marzio Marta Di Nicola Luca Di Antonio 2017International Journal of Ophthalmology(English edition)2017,10,10:26
12Interferon-α response in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment显示文摘AIM: To characterize the IFN-response and its modul- ation by the antiviral compound lamivudine in HBV- transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and HepG2 cells were stimulated with various concentrations of IFN-a2a in the presence or absence of lamivudine. Then, total RNA was extracted and analysed by customised cDNA arrays and northern blot for interferon-inducible genes (ISGs). In addition, cellular proteins were extracted for EMSA and western blot. HBV replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS: Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and 6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells. In 2 genes (IFITM1, 6-16), the response to IFN-a could be restored by treatment with lamivudine. This effect could not be explained by a direct modulation of the Jak/Stat signalling pathway since EMSA and western blot experiments revealed no suppression of Stat1 activation and ISGF3 formation after stimulation with IFN-a in HepG2.2.15 compared to HepG2 cells. CONCLUSION: These results are consistent with the assumption that chronic hepatitis B may specifically modulate the cellular response to IFN by a selective blockage of some ISGs. Antiviral treatment with lamivudine may partially restore ISG expression by reducing HBV gene expression and replication.Shi-He Guan Mengji Lu Petra Grünewald Michael Roggendorf Guido Gerken Joerg F Schlaak 2007World Journal of Gastroenterology2007,13,2:22
13Consensus statement AIGO/SICCR:Diagnosis and treatment of chronic constipation and obstructed defecation(partⅠ:Diagnosis)显示文摘Chronic constipation is a common and extremely troublesome disorder that significantly reduces the quality of life,and this fact is consistent with the high rate at which health care is sought for this condition.The aim of this project was to develop a consensus for the diagnosis and treatment of chronic constipation and obstructed defecation.The commission presents its results in a 'Question-Answer' format,including a set of graded recommendations based on a systematic review of the literature and evidence-based medicine.This section represents the consensus for the diagnosis.The history includes information relating to the onset and duration of symptoms and may reveal secondary causes of constipation.The presence of alarm symptoms and risk factors requires investigation.The physical examination should assess the presence of lesions in the anal and perianal region.The evidence does not support the routine use of blood testing and colonoscopy or barium enema for constipation.Various scoring systems are available to quantify the severity of constipation;the Constipation Severity Instrument for constipation and the obstructed defecation syndrome score for obstructed defecation are the most reliable.The Constipation-Related Quality of Life is an excellent tool for evaluating the patient's quality of life.No single test provides a pathophysiological basis for constipation.Colonic transit and anorectal manometry define the pathophysiologic subtypes.Balloon expulsion is a simple screening test for defecatory disorders,but it does not define the mechanisms.Defecography detects structural abnormalities and assesses functional parameters.Magnetic resonance imaging and/or pelvic floor sonography can further complement defecography by providing information on the movement of the pelvic floor and the organs that it supports.All these investigations are indicated to differentiate between slow transit constipation and obstructed defecation because the treatments differ between these conditions.Antonio Bove Filippo Pucciani Massimo Bellini Edda Battaglia Renato Bocchini Donato Francesco Altomare Giuseppe Dodi Guido Sciaudone Ezio Falletto Vittorio Piloni Dario Gambaccini Vincenzo Bove 2012World Journal of Gastroenterology2012,18,14:20
14Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics显示文摘交往受体的蛋白质 kinase-3 (RIP3 或 RIPK3 ) 是执行 “ 的细胞的机械的必要部分; programmed”或 “ regulated”坏死。这里,我们证明那规划坏死响应许多化学疗法的代理人被激活并且贡献导致化疗的房间死亡。然而,我们证明那 RIP3 表情经常在化学疗法的死亡期间由于它的 transcriptional 开始地点, MLKL 的这样 RIP3 依赖的激活和下游地规划的坏死附近的 genomic methylation 是在癌症房间的 silenced 大部分被镇压。不过,有 hypomethylating 代理人的治疗恢复 RIP3 表示,并且从而以一种 RIP3 依赖的方式把敏感提升到 chemotherapeutics。RIP3 表示在 85% 乳癌病人与正常织物相比在肿瘤被减少,建议那 RIP3 缺乏断然在肿瘤生长 / 发展期间被选择。因为 hypomethylating 代理人在病人是相当容忍得好的,我们建议病人们可以从收到 hypomethylating 代理人与常规 chemotherapeutics 在治疗以前导致 RIP3 表示有益于的那 RIP3 缺乏的癌症。Gi-Bang Koo Michael J Morgan Da-Gyum Lee Woo-Jung Kim Jung-Ho Yoon Ja Seung Koo Seung I1 Kim Soo Jung Kim Mi Kwon Son Soon Still Hong Jean M Mulcahy Levy Daniel A Pollyea Craig T Jordan Pearlly Yan David Frankhouser Deedra Nicolet Kati Maharry Guido Marcucci Kyeong Sook Choi Hyeseong Cho ndrew Thorbum You-Sun Kim 2015Cell Research2015,25,6:20
15Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?显示文摘Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.Anthony Davies Guido Wassink Laura Bennet Alistair J.Gunn Joanne O.Davidson 2019Neural Regeneration Research2019,14,10:20
16Cuproptosis:a copper-triggered modality of mitochondrial cell death显示文摘Various heavy metals can induce regulated cell death through different subroutines.A recent study published in Science found that intracellular copper accumulation triggers the aggregation of mitochondrial lipoylated proteins and the destabilization of Fe–S cluster proteins,leading to a unique type of cell death termed cuproptosis.Beyond classical apoptosis,several forms of regulated cell death(RCD)have been identified.These RCD subroutines differ in the initiating stimuli,intermediate activation events,and end effectors.1 Heavy metal ions are essential micronutrients,but either insufficient or excessive abundance of metals can trigger cell death.For example,ferroptosis has been defined as an iron-dependent form of oxidative cell death caused by unrestricted lipid peroxidation.2 Surprisingly,a recent study by Tsvetkov and colleagues showed that intracellular copper(Cu)induces a novel form of RCD that is different from oxidative stress-related cell death(e.g.,apoptosis,ferroptosis,and necroptosis)and has been termed“cuproptosis”.3 In contrast,mitochondrial stress,especially the aggregation of lipoylated mitochondrial enzymes and the loss of Fe–S cluster proteins,ignites cuproptosis(Fig.1).Daolin Tang Xin Chen Guido Kroemer 2022Cell Research2022,32,5:19
17Radiofrequency ablation for treatment of hypersplenism: A feasible therapeutic option显示文摘We present a case of a patient with hypersplenism secondary to portal hypertension due to hepato-splenic schistosomiasis, which was accompanied by severe and refractory thrombocytopenia. We performed spleen ablation and measured the total spleen and ablated volumes with contrast-enhanced computed tomography and volumetry. No major complications occurred, thrombocytopenia was resolved, and platelet levels remained stable, which allowed for early treatment of the patient's underlying disease. Previous work has shown that splenic radiofrequency ablation is an attractive alternative treatment for hypersplenism induced by liver cirrhosis. We aimed to contribute to the currently sparse literature evaluating the role of radiofrequency ablation(RFA) in the management of hypersplenism. We conclude that splenic RFA appears to be a viable and promising option for the treatment of hypersplenism.Guilherme Lopes P Martins Joao Paulo G Bernardes Marcello S Rovella Raphael G Andrade Publio Cesar C Viana Paulo Herman Giovanni Guido Cerri Marcos Roberto Menezes 2015World Journal of Gastroenterology2015,21,20:17
18Hepatocellular carcinoma:Surgical perspectives beyond the barcelona clinic liver cancer recommendations显示文摘The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.Alfredo Guglielmi rea Ruzzenente Simone Conci Alessro Valdegamberi Marco Vitali Francesca Bertuzzo Michela De Angelis Guido Mantovani Calogero Iacono 2014World Journal of Gastroenterology2014,20,24:16
19ERCP in acute pancreatitis:What takes place in routine clinical practice?显示文摘AIM:To evaluate the data from a survey carried out in Italy regarding the endoscopic approach to acute pancreatitis in order to obtain a picture of what takes place after the release of an educational project on acute pancreatitis sponsored by the Italian Association for the Study of the Pancreas.METHODS:Of the 1 173 patients enrolled in our survey,the most frequent etiological category was biliary forms(69.3%) and most patients had mild pancreatitis(85.8%).RESULTS:344/1 173(29.3%) underwent endoscopic retrograde cholangiopancreatography(ERCP).The mean interval between the onset of symptoms and ERCP was 6.7 ± 5.0 d;only 89 examinations(25.9%) were performed within 72 h from the onset of symptoms.The main indications for ERCP were suspicion of common bile duct stones(90.3%),jaundice(44.5%),clini cal worsening of acute pancreatitis(14.2%) and cho langitis(6.1%).Biliary and pancreatic ducts were visua lized in 305 patients(88.7%) and in 93 patients(27.0%) respectively.The success rate in obtaining a cholangio gram was statistically higher(P = 0.003) in patients with mild acute pancreatitis(90.6%) than in patients with severe disease(72.2%).Biliary endoscopic sphinc terotomy was performed in 295 of the 305 patients(96.7%) with no difference between mild and severe disease(P = 0.985).ERCP morbidity was 6.1% and mortality was 1.7%;the mortality was due to the complications of acute pancreatitis and not the endoscopic procedure.CONCLUSION:The results of this survey,as with those carried out in other countries,indicate a lack of compliance with the guidelines for the indications for interventional endoscopy.Armando Gabbrielli Raffaele Pezzilli Generoso Uomo Alessandro Zerbi Luca Frulloni Paolo De Rai Laura Castoldi Guido Costamagna Claudio Bassi Valerio Di Carlo 2010World Journal of Gastrointestinal Endoscopy2010,2,9:14
20Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel 2015Cell Research2015,25,2:14
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