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Management of hepatocellular carcinoma in the elderly

World Journal of Hepatology 2015年第11期7卷 1521-1529页

作者： Mauro Borzio Elena Dionigi Giancarlo Parisi Ivana Raguzzi Rodolfo Sacco Unità di gastroenterologia Azienda Ospedaliera di Melegnano Dipartimento di Medicina Ospedale Santa Maria del Prato Unità di gastroenterologia Ospedale Cisanello

Mean age of hepatocellular carcinoma(HCC) patients has been progressively increasing over the last decades and ageing of these patients is becoming a real challenge in every day clinical practice. Unfortunately, international guidelines on HCC management do not address this problem exhaustively and do not provide any specific recommendation. We carried out a literature search in MEDLINE database for studies reporting on epidemiology, clinical characteristics and treatment outcome of HCC in elderly patients. Available data seem to indicate that in elderly patients the outcome of HCC is mostly influenced by liver function and tumor stage rather than by age and the latter should not influence treatment allocation. Age is not a risk for resection and older patients with resectable HCC and good liver function could gain benefit from surgery. Mild comorbidities do not seem a contraindication for surgery in aged patients. Conversely, major resection in elderly, even when performed in experienced high-volume centres, should be avoided. Both percutaneous ablation and transarterial chemoembolization are not contraindicated in aged patients and safety profile of these procedures is acceptable. Sorafenib is a viable option for advanced HCC in elderly provided that a careful evaluation of concomitant comorbidities, particularly cardiovascular ones, is taken into account. Available data seem to suggest that in either elderly and younger, treatment is a main predictor of outcome. Consequently, a nihilistic attitude of physicians towards under- or no-treatment of aged patients should not be longer justified.

关键词： Hepatocarcinoma Epidemiology Cirrhosis Elderly Treatment

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Changes in nutritional status after liver transplantation

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World Journal of Gastroenterology 2014年第31期20卷 10682-10690页

作者： Michela Giusto Barbara Lattanzi Vincenza Di Gregorio Valerio Giannelli Cristina Lucidi Manuela Merli Ⅱ gastroenterologia Dipartimento di Medicina Clinica "Sapienza" Università di Roma00185 Roma Italy

Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades,a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the workup of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass(sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected,dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolicdisorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.

关键词： Liver transplantation Sarcopenia Malnutrition Obes

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Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

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World Journal of Gastroenterology 2008年第29期14卷 4643-4651页

作者： Anna Latiano Orazio Palmieri Maria Rosa Valvano Renata D'Incà Salvatore Cucchiara Gabriele Riegler Anna Maria Staiano Sandro Ardizzone Salvatore Accomando Gian Luigi de Angelis Giuseppe Corritore Fabrizio Bossa Vito Annese U.U. O.O. di gastroenterologia ed Endoscopia Ospedale IRCCS-CSSSan Giovanni Rotondo (Fg) 71013 Italy Cattedra di gastroenterologia Università di PadovaPadova 35122 Italy Clinica Pediatrica Università "La Sapienza" Roma 00185 Italy Cattedra di gastroenterologia Università di NapoliNapoli 80131 Italy Clinica Pediatrica Università di Napoli Napoli 80131 Italy Unità di gastroenterologia Ospedale "Sacco" Milano 20157 Italy Clinica Pediatrica Università di Palermo Palermo 90128 Italy Clinica Pediatrica Università di Parma Parma 43100 Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age 273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P 2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

关键词：肠炎肠溃疡结肠疾病遗传因素

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Pathophysiological aspects of diverticular disease of colon and role of large bowel motility

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World Journal of Gastroenterology 2003年第10期9卷 2140-2142页

作者： Gabrio Bassotti Fabio Chistolini Antonio Morelli Clinica di gastroenterologia ed Epatologia Dipartimento di Medicina Clinica e SperimentaleUniversità di PerugiaItaly

Colonic diverticular disease (diverticulosis) is one of the most common gastrointestinal disorders in Western countries. This disorder is strictly related to aging and fibre intake, and still bears a discrete amount of morbidity. Numerous etiological co-factors have to date been implicated in the pathogenesis of the disease, yet the supporting evidence is still far from absolute. The present review considers the pathophysiology of colonic diverticular disease, with a special emphasis on factors related to abnormal colonic motility.

关键词：结肠憩室胃肠功能紊乱病理特点大肠动力学

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Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 330-335页

作者： Fabiola Rabelo Jose Tadeu Stefano Ana Mercedes Cavaleiro Rodrigo Vieira Costa Lima Daniel Ferraz de Campos Mazo Flair Jose Carrilho Maria Lúcia Correa-Giannellac Claudia P.Oliveiraa Departamento de gastroenterologia Faculdade de Medicina FMUSPUniversidade de Sao PauloSao PauloSPBrazil Hospital das Clinicas HCFMUSP Departamento de GastroenterologiaLIM07Faculdade de MedicinaUniversidade de Sao PauloSao PauloSPBrazil Laboratório de Carboidratos e Radioimunensaio LIM18Hospital das Clinicas HCFMUSP(LIM07)Faculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil Programa de Pos-Graduacao em Medicina Universidade Nove de Julho(UNINOVE)Sao PauloBrazil

Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P 2). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P 2.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.

关键词： Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic polymorphism Metabolic syndrome

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Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver

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World Journal of Hepatology 2017年第8期9卷 418-426页

作者： Ana Claudia Reis Schneider Cleandra Gregório Carolina Uribe-Cruz Ranieli Guizzo Tais Malysz Maria Cristina Faccioni-Heuser Larisse Longo Themis Reverbel da Silveira La-boratório Experimental de Hepatologia e gastroenterologia Hospital de Clínicas de Porto Alegre Programa de Pós- Graduacao em Ciências Médicas Gastroenterologia e HepatologiaUniversidade Federal do Rio Grande do Sul Programa de Pós-Graduacao em Genética e Biologia Molecular(UFRGS) Instituto de Ciências Básicas da Saúde(UFRGS) Departamento de Ciências Morfológicas(UFRGS) Centro de Microscopia Eletronica(UFRGS)

AIM To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genesin zebrafish.METHODS Zebrafish(n = 104),wild type,adult,male and female,were divided into two groups:Control and ethanol(0.05 v/v).The ethanol was directly added into water;tanks water were changed every two days and the ethanol replaced.The animals were fed twice a day with fish food until satiety.After two and four weeks of trial,livers were dissected,histological analysis(hematoxilineosin and Oil Red staining) and gene expression assessment of adiponectin,adiponectin receptor 2(adipor2),sirtuin-1(sirt-1),tumor necrosis factor-alpha(tnf-a),interleukin-1b(il-1b) and interleukin-10(il-10) were performed.Ultrastructural evaluations were conducted at fourth week.RESULTS Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks,as demonstrated by oil red staining.In ethanol-treated animals,the main ultrastructural changes were related to cytoplasmic lipid particles and droplets,increased number of rough endoplasmic reticulum cisterns and glycogen particles.Between two and four weeks,hepatic mR NA expression of il-1b,sirt-1 and adipor2 were upregulated,indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses.Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol,and il-10 did not show significant difference.CONCLUSION Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

关键词： Ethanol Hepatic steatosis Inflammation Zebrafish Alcoholic fatty liver

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Prevalence of overweightedness in patients with gastro-esophageal reflux

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World Journal of Gastroenterology 2007年第34期13卷 4602-4605页

作者： Luca Piretta Federico Alghisi Fiorella Anzini Enrico Corazziari Dipartimento di Scienze Cliniche Gastroenterologia A Università di Roma "La Sapienza" Viale del Policlinico 155-00161 Roma Italy

AIM: To evaluate whether the prevalence of overweight and obese conditions is increased in gastro-esophageal reflux disease (GERD) patients (with 24-h pathological pH recordings) in comparison to general population. METHODS: A total of 196 consecutive patients (103 females, age range 18-83 years) with symptoms of gastro-esophageal reflux (GER) and 24-h pathological esophageal pH-metry. Body mass index (BMI) of the patients was calculated and its distribution (%) was compared with that of the Italian general population as assessed by National Bureau of Census (ISTAT). To evaluate the association of GERD with weight categories, the binomial test was employed. P 25-25.9) was present in 43% of GERD patients vs 41.8% of Italian population (IP) (ns), obesity (BMI ≥ 30) in 10.9% vs 9.1% (ns). In females overweight was present in 34.9% of GERD patients vs 25.7% of IP (P < 0.01), obesity in 13.6% of GERD patients vs 9.1% of IP (P < 0.01). No statistically significant differences were noted in different age classes. CONCLUSION: In comparison to the Italian general population, the prevalence of overweightedness and obesity is increased in female but not in male patients with ascertained gastro-esophageal reflux disease.

关键词：食管回流肥胖症超重体重

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Treatment of active steroid-refractory inflammatory bowel diseases with granulocytapheresis: Our experience with a prospective study

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World Journal of Gastroenterology 2006年第14期12卷 2201-2204页

作者： Bresci Giampaolo Parisi Giuseppe Bertoni Michele Mazzoni Alessandro Scatena Fabrizio Capria Alfonso U.O. di gastroenterologia U.O. di Immunoematologia Azienda Ospedaliera-Universitaria Pisana PisaItaly

瞄准：与活跃的类固醇倔强的煽动性的肠疾病(IBD ) 在 14 个病人与 granulocytapheresis (GCAP ) 的使用报导我们的经验以便在完成宽恕并且维持一个长持续没有症状的时期评估它的功效。方法：疾病的活动被临床的活动索引(蔡) 和内视镜... 详细信息

瞄准：与活跃的类固醇倔强的煽动性的肠疾病(IBD ) 在 14 个病人与 granulocytapheresis (GCAP ) 的使用报导我们的经验以便在完成宽恕并且维持一个长持续没有症状的时期评估它的功效。方法：疾病的活动被临床的活动索引(蔡) 和内视镜的索引(EI ) 在 ulcerative (UC ) 评估，当时由 Crohn 在 Crohn 的疾病(CD ) 的疾病活动索引(CDAI ) 。病人用 Adacolumn 系统被对待，有选择地绑在 granulocytes 和单核白血球的吸附列。GCAP 的一个会议 / 星期为 5 wk 被执行。类固醇在词首字母的脱落期间被停止。结果：所有病人完成了不显示出复杂并发症的五星期的功课。在最后会议的结束， 93% 病人显示出为 6 瞬间坚持了的疾病的临床的宽恕。在治疗的结束以后的九个月， 60% 案例维持了宽恕，当 23% 病人仍然在在 12 瞬间以后的临床的宽恕时。结论：就算我们有类固醇倔强的 IBD 的病人的数字不大，我们能断言 GCAP 很好被容忍并且有效特别在在治疗以后的开始的六个月内，在盒子的一个重要百分比。持续反应的率在 12 瞬间以后在 6 瞬间以后并且显著地稍微落下，然而，严重副作用的缺席能是为进一步评估治疗的新时间表的刺激。

关键词：类固醇耐火材料肠炎溃疡

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Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis:Relationship with colonic metaplasia

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World Journal of Gastroenterology 2008年第34期14卷 5290-5300页

作者： Livia Biancone Emma Calabrese Giampiero Palmieri Carmelina Petruzziello Sara Onali Giuseppe Sigismondo Sica Marta Cossignani Giovanna Condino Kiron Moy Das Francesco Pallone Cattedra di gastroenterologia Dipartimento di Medicina InternaUniversità di "Tor Vergata" Cattedra di Anatomia ed Istologia Patologica Università di "Tor Vergata" Cattedra di gastroenterologia Dipartimento di Medicina InternaUniversità di "Tor Vergata" Cattedra di Chirurgia Generale Università di "Tor Vergata" Cattedra di gastroenterologia Dipartimento di Medicina Interna Università di "Tor Vergata" GI Unit Department of Gastroenterology & Hepatology University of Medicine & Dentistry of New Brunswick

AIM:To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn’s disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identifi ed by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was investigated.RESULTS: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present fi ndings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.

关键词：溃疡性结肠炎肠阻塞回盲肠吻合术结肠组织转化

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Serum chromogranin-A in hepatocellular carcinoma: Diagnostic utility and limits

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World Journal of Gastroenterology 2005年第13期11卷 1987-1990页

作者： Aldo Spadaro Antonino Ajello Carmela Morace Agata Zirilli Graziella D'arrigo Carmelo Luigiano Francesco Martino Anna Bene Domenico Migliorato Santi Turiano Oscar Ferraù Maria Antonietta Freni Dipartimento Clinico Sperimentale di Medicina e Farmacologia Dipartimento di Statistica Dipartimento di Scienze Radiologiche Unità Operativa di gastroenterologia

AIM: The utility of serum alpha-fetoprotein (α-FP) for the detection of hepatocellular carcinoma (HCC) is questionable.High serum levels of chromogranin-A (CgA) have recently been reported in HCC. Impaired hepatic, renal, and heart functions influence circulating CgA. The aim of this study was to assess sensitivity and specificity of serum CgA as a marker of HCC in patients with liver cirrhosis (LC).METHODS: Serum CgA levels were measured by RIA in 339 patients of which 54 HCC, 132 LC, 45 chronic hepatitis (CH), 27 chronic heart failure (CHF), 36 chronic renal failure (CRF), 45 chronic inflammatory bowel disease (IBD)as disease controls and in 75 healthy controls. Patients with liver disease or IBD and concomitant renal and/or heart failure were excluded. Pearson correlation, nonparametric combination test and confidence interval analysis were used for statistical analysis.RESULTS: Serum CgA above normal values (100 ng/mL)were found in 83% of HCC patients, in 48% of LC patients,in 20% of CH patients, in 33% of IBD patients, in 92% of CRF patients, in 100% of CHF patients, and in none of the healthy controls. The mean CgA values in HCC (769±1 046), in LC (249±369), in CH (87±94), in CRF (1 390±1 401), in CHF (577±539), in IBD (146±287) were significantly higher than those in healthy controls (48±18).HCC patients had higher CgA values (P＜0.01) than LC,CH, and IBD patients but did not differ from those with CRF or CHF. The 95% CI for the mean (250-1 289 ng/mL)in HCC patients was selected as a CgA range and the lower value of such range was assumed as cut-off.Sensitivity and specificity of CgA, calculated in relation to the cut-off in patients with cirrhosis and HCC, were respectively 61% (CI 48-73%) and 82% (CI 75-88%).Serum α-FP values were ＞200 ng/mL in 21% of the HCC patients and in none of the LC patients. No significant correlation was found between α-FP and CgA in patients with HCC and in patients with cirrhosis.CONCLUSION: When HCC is suspected and α-FP is normal or ＜200 ng/mL, CgA serum values represent a co

关键词：嗜铬粒蛋白-A 血清肝细胞癌诊断方法

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