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Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease

World Journal of Gastroenterology 2007年第31期13卷 4242-4248页

作者： Silvia Sookoian Gustavo Castao Carolina Gemma tomas fernández gianotti Carlos Jose Pirola Instituto de Investigaciones Medicas A. Lanari. Universidad de Buenos Aires CONICET Combatiente de Malvinas 3150 1427-Ciudad Autonoma de Buenos Aires Argentina Consejo de Investigación GCBA Buenos Aires Argentina Consejo de Investigación GCBA Buenos Aires Argentina Instituto de Investigaciones Medicas A. Lanari. Universidad de Buenos Aires CONICET Combatiente de Malvinas 3150 1427-Ciudad Autonoma de Buenos Aires Argentina

To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease （NAFID） and their relation with the disease ***： A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency 〉 10% （rs1554483 C/G; rs11932595 A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G） encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites （P 〉 0.8） were genotyped. RESULTS： rs11932595 and rs6843722 showed significant associations with NAFLD （empiric P = 0.0449 and 0.023, respectively）. A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 （empiric P = 0.0399）, rs6843722 （empiric P = 0.0229） and rs6850524 （empiric P = 0.00899） and between fibrosis score and rs1554483 （empiric P = 0.02697）, rs6843722 （empiric P = 0.01898） and rs4864548 （empiric P = 0.02697）. Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls （empiric P = 0.0097）.CONCLUSION： Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes insusceptibility to NAFLD and disease severity.

关键词： Circadian rhythm Circadian Iocomoter outputcycles protein kaput Gene variants Haplotypes Fattyliver Liver disease Obesity Nonalcoholic steatohepatitis

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

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 265-271页

作者： Mattia Garancini Alessandro Fogliati Mauro Alessandro Scotti Cristina Ciulli Francesca Carissimi Antonio Rovere Luca gianotti Fabrizio Romano Unit of Hepatobiliopancreatic Surgery Department of SurgeryASST-MonzaSan Gerardo HospitalUniversity of Milano-Bicoccavia Pergolesi 33MonzaMB 20052Italy Interventional Radiology Department of RadiologyASST-MonzaSan Gerardo HospitalMilano-Bicocca Universityvia Pergolesi 33MonzaMB 20052Italy

Background:The superiority of anatomical resection(AR)***-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is *** are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous *** study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the ***:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was *** 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 ***:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were *** disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN ***-OUT groups were 50%vs.83%(P=0.006),20%vs.52%(P=0.003)and 16%vs.39%(P=0.020),***-OUT odds ratio for local recurrence was 4.1 at univariate regression ***-,three-,and five-year disease-free survival rates in the SegSubTe-IN ***-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.

关键词： Hepatocellular carcinoma Intraoperative ultrasound Liver surgery Computed tomography Surgical procedure

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Hyponatraemia and cirrhosis

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Gastroenterology Report 2014年第1期2卷 21-26页

作者： Robert J.gianotti Andres Cardenas Department of Gastroenterology Beth Israel Deaconess Medical CenterBoston MA GI Unit Institut Clinic de Malalties Digestives i MetaboliquesHospital ClinicUniversity of Barcelona

Hyponatraemia is a common complication of advanced cirrhosis related to an impairment in the renal capacity for eliminating solute-free water,causing a retention of water that is disproportionate to the retention of sodium,thus leading to a reduction in serum sodium concentration and *** main pathogenic factor responsible for hyponatraemia is a non-osmotic hypersecretion of arginine vasopressin(AVP)or antidiuretic hormone from the neurohypophysis,related to circulatory *** in cirrhosis is associated with increased morbidity and *** is also associated with increased morbidity and impaired short-term survival after *** current standard of care based on restricting fluids to 1-1.5 L/day is rarely *** approaches,such as albumin infusion and the use of vaptans—which act by specifically antagonizing the effects of AVP on the V2 receptors located in the kidney tubules—have been evaluated for their role in the management of *** short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatraemia;however their use in patients with end-stage liver disease is limited by hepatotoxic effects of some of these *** administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration,but the available information is still limited.

关键词： hyponatraemia cirrhosis end-stage liver disease vaptans

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Treatment of gastric varices with partial splenic embolization in a patient with portal vein thrombosis and a myeloproliferative disorder

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World Journal of Gastroenterology 2014年第39期20卷 14495-14499页

作者： Robert gianotti Hearns Charles Kenneth Hymes Hersh Chandarana Samuel Sigal Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 United States New York University School of Medicine New York NY 10022 United States

Therapeutic options for gastric variceal bleeding in the presence of extensive portal vein thrombosis associated with a myeloproliferative disorder are *** report a case of a young woman who presented with gastric variceal bleeding secondary to extensive splanchnic venous thrombosis due to a Janus kinase 2 mutation associated myeloproliferative disorder that was managed effectively with partial splenic embolization.

关键词： Gastric varices Partial splenic embolization Myeloproliferative disorder Janus kinase 2 Portal hypertension Portal vein thrombosis

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Multistage tectono-stratigraphic evolution of the Canavese Intracontinental Suture Zone:New constraints on the tectonics of the Inner Western Alps

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Geoscience Frontiers 2022年第6期13卷 91-110页

作者： Gianni Balestro Andrea Festa Sara De Caroli Edoardo Barbero Alessandro Borghi Franco gianotti Department of Earth Sciences University of TorinoTorinoItaly National Research Council of Italy Institute of Geosciences and Earth ResourcesTorinoItaly School of Earth and Environmental Sciences Cardiff UniversityCardiffWalesUK

The Canavese Intracontinental Suture Zone(CISZ) within the Inner Western Alps represents the remnant of a long-lived minor subduction zone involving a narrow, thinned continental crust/oceanic lithosphere seaway between two continental domains of the Adria microplate(i.e., the Sesia Zone and the IvreaVerbano Zone). As opposed to many suture zones, the CISZ mostly escaped pervasive tectonic deformation and metamorphism, thus preserving the original stratigraphy and allowing the relationships between tectonics and sedimentation to be defined. Through detailed geological mapping(1:5000 scale),structural analysis, stratigraphic and petrographic observations, we document evidences for the late Paleozoic to late Cenozoic tectonic evolution of the CISZ, showing that it played a significant role in the context of the tectonic evolution of the Inner Western Alps region from the early to late Permian Pangea segmentation, to the Jurassic Tethyan rifting, and up to the subduction and collisional stages,forming the Western Alps. The site of localization/formation of the CISZ was not accidental but associated with the re-use of structures inherited from regional-scale wrench tectonics related to the segmentation of Pangea, and from the subsequent extensional tectonics related to the Mesozoic rifting, as documented by crosscutting relationships between stratigraphic unconformities and tectonic features. Our findings document that evidences derived from stratigraphy, facies indicators, and relationships between tectonics and sedimentation in the shallow crustal portions of suture zones, such in the CISZ, are important to better constrain the tectonic history of those metamorphic orogenic belts around the world in which evolutionary details are commonly complicated by high-strain deformation and metamorphic transformations.

关键词： Suture zone Western Alps Structural inheritance Tectonics and sedimentation Multistage tectonic evolution

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Branching patterns of the left portal vein and consequent implications in liver surgery:The left anterior sector

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 399-402页

作者： Mattia Garancini Mauro Alessandro Scotti Luca gianotti Antonio Rovere Fabio Uggeri Marco Braga Fabrizio Romano Unit of Hepatobiliary Pancreatic Surgery Department of General Surgery 1ASST-MonzaSan Gerardo HospitalMilano-Bicocca Universityvia Pergolesi 3320900 MonzaMBItaly Unit of Interventional Radiology Department of RadiologyASST-MonzaSan Gerardo HospitalMilano-Bicocca Universityvia Pergolesi 3320900 MonzaMBItaly

To the Editor: There are still some open issues about the systematization of the knowledge of the branching of the left portal vein(LPV) and the division in anatomo-functional units within the left liver. The first controversial topic concerns the division of S4 in subsegments. The Brisbane 20 0 0 system of Nomenclature of Hepatic Anatomy and Resections(B20 0 0) [1] does not mention such subdivision, but in literature this is still a matter of discussion.

关键词： branching portal discussion

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A randomized double-blind trial on perioperative administration of probiotics in colorectal cancer patients

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World Journal of Gastroenterology 2010年第2期16卷 167-175页

作者： Luca gianotti Lorenzo Morelli Francesca Galbiati Simona Rocchetti Sara Coppola Aldo Beneduce Cristina Gilardini Daniela Zonenschain Angelo Nespoli Marco Braga Department of Surgery Milano-Bicocca University San Gerardo Hopsital Department of Microbiology Università Cattolica Sacro Cuore Department of Surgery San Raffaele University

AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for *** were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before *** same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after *** the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical ***536 was never found at any time-points *** day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ***1 was not found at day+*** observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC

关键词： Probiotic Dendritic cell Microbiota Colon cancer Lymphocyte Surgery Intestinal immunity

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Hepatic resection beyond barcelona clinic liver cancer indication:When and how

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World Journal of Hepatology 2016年第11期8卷 513-519页

作者： Mattia Garancini Enrico Pinotti Stefano Nespoli Fabrizio Romano Luca gianotti Vittorio Giardini Department of Surgery Hepatobiliopancreatic UnitSan Gerardo HospitalUniversity of Milano Bicocca

Hepatocellular carcinoma(HCC)is the main common primary tumour of the liver and it is usually associated with *** barcelona clinic liver cancer(BCLC)classification has been approved as guidance for HCC treatment algorithms by the European Association for the Study of Liver and the American Association for the Study of Liver *** to this algorithm,hepatic resection should be performed only in patients with small single tumours of 2-3 cm without signs of portal hypertension(PHT)or *** classification has been criticised and many studies have shown that multiple tumors and large tumors,as wide as those with macrovascular infiltration and PHT,could benefit from liver ***,treatment guidelines should be revised and patients with intermediate/advanced stage HCC,when technically resectable,should receive the opportunity to be treated with radical surgical ***,the surgical treatment of HCC on cirrhosis is complex:The goal to be oncologically radical has always to be balanced with the necessity to minimize organ *** aim of this review was to analyze when and how liver resection could be indicated beyond BCLC *** particular,the role of multidisciplinary approach to assure a proper indication,of the intraoperative ultrasound for intraoperative restaging and resection guidance and of laparoscopy to minimize surgical trauma have been enhanced.

关键词： Hepatocellular carcinoma Liver surgery Hepatic resection Multiple hepatocellular carcinoma Cirrhosis Barcelona clinic liver cancer Multidisciplinary approach Intraoperative ultrasound Laparoscopy Portal hypertension

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Gastric Cancer Immunotherapy: An Overview

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Journal of Cancer Therapy 2013年第5期4卷 1018-1036页

作者： Fabrizio Romano Fabio Uggeri Luca Nespoli Luca gianotti Mattia Garancini Matteo Maternini Angelo Nespoli Franco Uggeri Department of Surgery San Gerardo Hospital University of Milano-Bicocca Monza Italy

Gastric adenocarcinoma is the third most common cancer and the second most common cause of death due to cancer worldwide. Surgery is still the major prognostic factor for gastric cancer. Patients who could not be resected have a poor prognosis with survival ranging from 3 to 11 months. There is evidence that surgical operations can cause a variety of immunological disturbances in man both in vivo and in vitro. The postoperative changes in the systemic immune response are proportional to the degree of surgical trauma leading to a generalized state of immunosuppression, which is implicated in the development of septic complications and provided a “fertile soil” for tumor cell metastasis. Immunotherapy may be a potentially promising alternative strategy for gastric cancer. In early clinical trials, systemic immunotherapy included both active vaccination directed against defined tumor-associated antigens expressed in gastric carcinoma cells and passive administration of IL-2 with some evidence of regression of metastatic gastric cancer. Other studies have applied immunotherapy in the adjuvant setting with equally promising results. For example, OK-432, a streptococcal preparation, demonstrated marginal improvement in survival for patients with stage III gastric cancer and a meta-analysis of centrally randomized controlled clinical trials indicated a significant survival benefit with combination OK-432 and chemotherapy compared to chemotherapy alone (p 0.05). Additional data suggesting a biological and clinical benefit of subcutaneous, preoperative administration of low-dose IL-2 in colon cancer encouraged us to evaluate low-dose IL-2 therapy in the neoadjuvant setting for patients with gastric adenocarcinoma who undergo surgery and to evaluate its effects on systemic and tumor infiltrating lymphocyte numbers. We also sought to determine if neoadjuvant low-dose IL-2 could influence the clinical outcome for patients undergoing gastric resection for cancer. We report the b

关键词： Gastric Cancer Immunotherapy IL-2

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Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis

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World Journal of Gastroenterology 2015年第27期21卷 8366-8372页

作者： Luca Nespoli Giulia Lo Bianco Fabio Uggeri Fabrizio Romano Angelo Nespoli Davide Paolo Bernasconi Luca gianotti Department of Surgery and Translational Medicine University of Milan-Bicocca San Gerardo Hospital Department of Health Sciences Centre of Biostatistics for Clinical Epidemiology University of Milan-Bicocca

AIM: To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated ***: We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography-confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20(study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30(control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline(ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements(passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital ***: Patients characteristics and inflammatoryparameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2(mean CRP 6.0 +/- 4.2 mg/d L and 10.0 +/- 6.7 mg/d L respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1(P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3(P < 0.05 for both comparisons). Mesalamine administration was also associated with an earlier reintroduction of food intake(median 1.5 d and 3 d, study group vs controls resp

关键词： Acute diverticulitis Inflammatory boweldisease 5-ASA benign colonic disease

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