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Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

World Journal of Gastroenterology 2016年第34期22卷 7692-7707页

作者： Lieselotte Lemoine paul Sugarbaker Kurt van der Speeten Department of Medicine and Life Sciences Hasselt University3500 Hasselt Belglum Department of Surgical Oncology Ziekenhuis Oost-Limburg 3600 Genk Belgium Washington Cancer Institute Washington Hospital Center Washington DC 20010 United States

Colorectal cancer(CRC) is the third most common cancer and the fourth most common cause of cancerrelated death worldwide. Besides the lymphatic and haematogenous routes of dissemination,CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity,which ultimately leads to peritoneal carcinomatosis(PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However,this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements,involving several well-defined steps,together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor,gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum,subsequently invade the subperitoneal space,where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript,we review current data regarding the molecular mechanisms underlying the development of colorectal PC,with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

关键词： Peritoneal carcinomatosis Pathophysiology Peritoneal metastatic cascade Cytoreductive surgery Peritoneum Hyperthermic intraperitoneal peroperative chemotherapy

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Characteristics of viral specimens collected from asymptomatic and fatal cases of COVID-19

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The Journal of Biomedical Research 2020年第6期34卷 431-436页

作者： Andrew J.Gorzalski paul Hartley Chris Laverdure Heather Kerwin Richard Tillett Subhash Verma Cyprian Rossetto Sergey Morzunov Stephanie van Hooser Mark W.Pandori Nevada State Public Health Laboratory RenoNV 89597USA Nevada Genomics Center RenoNV 89557USA Washoe County Health District RenoNV 89512USA Nevada Institute of Personalized Medicine University of Nevada Las VegasLas VegasNV 89154-4022USA Nevada Center for Bioinformatics University of Nevada RenoRenoNV 89557USA Department of Microbiology and Immunology University of NevadaReno School of MedicineRenoNV 89557USA. Department of Pathology and Laboratory Medicine University of NevadaReno School of MedicineRenoNV 89557USA.

We sought to determine the characteristics of viral specimens associated with fatal cases,asymptomatic cases and non-fatal symptomatic cases of *** included the analysis of 1264 specimens found reactive for at least two SARS-CoV-2 specific loci from people screened for infection in Northern Nevada in March-May of *** these,30 were specimens from fatal cases,while 23 were from positive,asymptomatic *** assessed the relative amounts of SARS-CoV-2 RNA from sample swabs by real-time PCR and use of the threshold crossing value(Ct).Moreover,we compared the amount of human RNase P found on the same swabs.A considerably higher viral load was found to be associated with swabs from cases involving fatality and the difference was found to be strongly statistically *** this difference,we sought to assess whether any genetic correlation could be found in association with virus from fatal cases using whole genome *** no common genetic elements were discerned,one branch of epidemiologically linked fatal cases did have two point mutations,which no other of 156 sequenced cases from northern Nevada *** mutations caused amino acid changes in the 3′-5′exonuclease protein,and the product of the gene,orf8.

关键词： COVID-19 SARS-COV-2 real-time PCR Ct value viral load

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Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer

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World Journal of Obstetrics and Gynecology 2013年第4期2卷 143-152页

作者： Kurt van der Speeten Anthony O Stuart paul H Sugarbaker Department of Surgical Oncology Ziekenhuis Oost-Limburg 3600 Genk Belgium University Hasselt Life Sciences Faculty Oncology Research Cluster 3000 Hasselt Belgium Washington Cancer Institute Washington Hospital Center Washington DC 20010United States

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer(EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis(PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal(IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia(41-42 ℃) of the IP chemotherapy solution. Timing of the chemotherapy as a planned part of the surgical procedure to maximize expo-sure of all peritoneal surfaces is crucial to success.

关键词： Intraperitoneal chemotherapy Epithelial ovarian cancer Ifosfamide Cisplatin Carboplatin Taxanes Pharmacokinetics Pharmacodynamics

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Management of extracranial carotid artery stenosis during endovascular treatment for acute ischaemic stroke:results from the MR CLEAN Registry

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Stroke & Vascular Neurology 2023年第3期8卷 229-237,I0074-I0085页

作者： Sabine L Collette Michael P Rodgers Marianne A A van Walderveen Kars C J Compagne paul J Nederkoorn Jeannette Hofmeijer Jasper M Martens Gert J de Borst Gert Jan R Luijckx Charles B L M Majoie Aad van der Lugt Reinoud P H Bokkers Maarten Uyttenboogaart University Medical Centre Groningen University of GroningenGroningenThe Netherlands Leiden University Medical Centre LeidenThe Netherlands Erasmus MC University Medical CentreRotterdamThe Netherlands Amsterdam University Medical Centres University of AmsterdamAmsterdamThe Netherlands Rijnstate Hospital ArnhemThe Netherlands University Medical Centre Utrecht University of UtrechtUtrechtThe Netherlands

Background The optimal management of ipsilateral extracranial internal carotid artery(ICA)stenosis during endovascular treatment(EVT)is *** compared the outcomes of two different strategies:EVT with vs without carotid artery stenting(CAS).Methods In this observational study,we included patients who had an acute ischaemic stroke undergoing EVT and a concomitant ipsilateral extracranial ICA stenosis of≥50%or occlusion of presumed atherosclerotic origin,from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR CLEAN)Registry(2014-2017).The primary endpoint was a good functional outcome at 90 days,defined as a modified Rankin Scale score≤*** endpoints were successful intracranial reperfusion,new clot in a different vascular territory,symptomatic intracranial haemorrhage,recurrent ischaemic stroke and any serious adverse *** Of the 433 included patients,169(39%)underwent EVT with *** 123/168(73%)patients,CAS was performed before intracranial *** 42/224(19%)patients who underwent EVT without CAS,a deferred carotid endarterectomy or CAS was *** with and without CAS were associated with similar proportions of good functional outcome(47%vs 42%,respectively;adjusted OR(aOR),0.90;95%CI,0.50 to 1.62).There were no major differences between the groups in any of the secondary endpoints,except for the increased odds of a new clot in a different vascular territory in the EVT with CAS group(aOR,2.96;95%CI,1.07 to 8.21).Conclusions Functional outcomes were comparable after EVT with and without *** during EVT might be a feasible option to treat the extracranial ICA stenosis but randomised studies are warranted to prove non-inferiority or superiority.

关键词： stenosis carotid treatment

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Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice

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World Journal of Gastroenterology 2010年第6期16卷 703-712页

作者： Nathalie E Ruyssers Benedicte Y De Winter Joris G De Man Natacha D Ruyssers Ann J van Gils Alex Loukas Mark S Pearson Joel V Weinstock paul A Pelckmans Tom G Moreels Laboratory of Experimental Medicine and Pediatrics Division of GastroenterologyUniversity of Antwerp Division of Infectious Diseases and Immunology Queensland Institute of Medical Research 4006 Brisbane Division of Gastroenterology-Hepatology Tufts New England Medical Center

AIM:To investigate the therapeutic effect of Schistosoma mansoni(***) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with *** *** were performed 5 d after TNBS *** quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal *** activity of distal colonic segments was studied in vitro using a modified Trendelenburg *** profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe *** with *** proteins significantly ameliorated colonic inflammation after 5 *** did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of *** with *** proteins ameliorated these in vivo and in vitro motility *** addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a *** protein effect was no longer observed at this time point. CONCLUSION:Treatment with *** proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis.

关键词： Schistosoma mansoni Helminth proteins Colitis Peristalsis Crohn’s disease Gastrointestinal motility Trinitrobenzene sulphate

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Assessment and prediction of tablet properties using transmission and backscattering Raman spectroscopy and transmission NIR spectroscopy

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Asian Journal of Pharmaceutical Sciences 2016年第4期11卷 547-558页

作者： Elisabeth Peeters Ana Filipa Tavares da Silva Maunu Toiviainen Jeroen van Renterghem Jurgen Vercruysse Mikko Juuti Joao Almeida Lopes Thomas De Beer Chris Vervaet Jean-paul Remon Laboratory of Pharmaceutical Technology Ghent UniversityOttergemsesteenweg 4609000GhentBelgium Laboratory of Pharmaceutical Process Analytical Technology Ghent UniversityOttergemsesteenweg 4609000GhentBelgium REQUIMTE Department of Chemical SciencesUniversity of PortoRua de Jorge Viterbo Ferreira2284050-313PortoPortugal VTT Technical Research Centre of Finland Optical Measurement TechnologiesKaitoväylä190570 OuluFinland

This study investigated whether Raman and Near Infrared(NIR) spectroscopy could predict tablet properties. Granules were produced on a continuous line by varying granulation parameters. Tableting process parameters were adjusted to obtain uniform tablet weight and thickness. Spectra were collected offline and tablet properties determined with traditional analyzing methods. Partial Least Squares(PLS) regression was used to correlate spectral information to tablet properties, but predictive models couldn’t be established. Principal component analysis(PCA) was effectively used to distinguish theophylline concentrations and hydration levels and multiple linear regression(MLR) analysis allowed insight on how granulation parameters affect granule and tablet properties.

关键词： Continuous production PAT Granulation Tableting NIR Raman

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Trends in treatment and overall survival among patients with proximal esophageal cancer

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World Journal of Gastroenterology 2019年第47期25卷 6835-6846页

作者： Judith de Vos-Geelen Sandra ME Geurts Liselot BJ Valkenburg-van Iersel Evelien JM de Jong Vivianne CG Tjan-Heijnen Margreet van Putten Valery EPP Lemmens Heike I Grabsch Nadia Haj Mohammad Frank JP Hoebers Chantal V Hoge paul M Jeene Hanneke WM van Laarhoven Tom Rozema Marije Slingerland Grard AP Nieuwenhuijzen Department of Internal Medicine Division of Medical OncologyGROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Department of Research Netherlands Comprehensive Cancer Organization(IKNL)Eindhoven 5612 HZNetherlands Department of Pathology GROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Pathology and Data Analytics Leeds Institute of Medical Research at St James”sUniversity of LeedsLeeds LS97TFUnited Kingdom Department of Medical Oncology University Medical Center UtrechtUtrecht 3584 CXNetherlands Department of Radiation Oncology(MAASTRO clinic) GROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6229 ETNetherlands Department of Internal Medicine Division of GastroenterologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Department of Radiotherapy RadiotherapiegroepDeventer 7416 SENetherlands Department of Medical Oncology Amsterdam University Medical CentersUniversity of AmsterdamAmsterdam 1105 AZNetherlands Department of Radiotherapy Insituut VerbeetenTilburg 5042 SBNetherlands Department of Medical Oncology Leiden University Medical CenterLeiden 2333 ZANetherlands Department of Surgery Catharina Hospital EindhovenEindhoven 5623 EJNetherlands Department of Public Health Erasmus Medical Center RotterdamRotterdam 3015 GDNetherlands

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital ***-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been *** trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease *** optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life *** To establish trends in treatment and OS in patients with proximal esophageal *** In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer *** proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the *** in radiotherapy,chemotherapy,and surgery,and OS were *** were stratified by presence of distant *** Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment *** In total,2783 patients were *** the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,*** metastatic disease,the use of chemotherapy and radiotherapy increased over *** OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on ***

关键词： Esophagus Esophageal cancer Proximal Cervical Upper thoracic Trends Treatment Survival Outcome

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Self-expandable metal stents for malignant gastric outlet obstruction: A pooled analysis of prospective literature

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World Journal of Gastroenterology 2015年第43期21卷 12468-12481页

作者： Emo E van Halsema Erik AJ Rauws paul Fockens Jeanin E van Hooft Department of Gastroenterology and Hepatology Academic Medical Center

AIM: To provide an overview of the clinical outcomes of self-expandable metal stent(SEMS) placement for malignant gastric outlet obstruction(MGOO).METHODS: A systematic literature search was performed in Pub Med of the literature published between January 2009 and March 2015. Only prospective studies that reported on the clinical success of stent placement for MGOO were included. The primary endpoint was clinical success,defined according to the definition used in the original article. Data were pooled and analyzed using descriptive statistics. Subgroup analyses were performed for partially covered SEMSs(PCSEMSs) and uncovered SEMSs(UCSEMSs) using Fisher's exact ***: A total of 19 studies,including 1281 patients,were included in the final analysis. Gastric(42%) and pancreatic(37%) cancer were the main causes of MGOO. UCSEMSs were used in 76% of patients and PCSEMSs in 24%. The overall pooled technical success rate was 97.3% and the clinical success rate was 85.7%. Stent dysfunction occurred in 19.6% of patients,mainly caused by re-obstruction(12.6%) and stent migration(4.3%),and was comparable between PCSEMSs and UCSEMSs(21.2% vs 19.1%,respectively,P = 0.412). Re-obstruction was more common with UCSEMSs(14.9% vs 5.1%,P < 0.001) and stent migration was more frequent after PCSEMS placement(10.9% vs 2.2%,P < 0.001). The overall perforation rate was 1.2%. Bleeding was reported in 4.1% of patients,including major bleeding in 0.8%. The median stent patency ranged from 68 to 307 d in five studies. The median overall survival ranged from 49 to 183 d in 13 ***: The clinical outcomes in this large population showed that enteral stent placement was feasible,effective and safe. Therefore,stent placement is a valid treatment option for the palliation of MGOO.

关键词： Stents Gastric outlet obstruction Stomach neoplasm

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Evaluation of MODIS Products in the Great Australian Bight and Adjacent Coastal Waters

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Open Journal of Marine Science 2018年第4期8卷 431-449页

作者： Ana Redondo Rodriguez Edward King Mark Doubell paul van Ruth South Australian Research and Development Institute West Beach SA Australia CSIRO Oceans and Atmosphere Flagship CSIRO Hobart Australia

Satellite remote sensing data can produce global environmental data and is easily accessible and widely used by the scientific and non-scientific community. However, to use satellite data, it is important to know its limitations and how it validates against in situ measurements for the different regions. Here, field measurements of chlorophyll-a concentration and euphotic depth within the Great Australian Bight, Gulf St Vincent and Spencer Gulf were used to validate ocean colour products derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua satellite. The field data include in situ and in vivo chlorophyll-a concentration, which were compared against MODIS chlorophyll-a products derived from three algorithms (OC3M, Carder, and Garver-Siegel-Maritorena (GSM)), as well as euphotic depth measurements derived from photosynthetically active radiation (PAR) profiles, which were compared against two MODIS euphotic depth products (derived semi-analytically and from surface chlorophyll-a). The OC3M product performed well in open waters, with errors below the 35% NASA accepted limit, but it overestimated chlorophyll-a values in shallow (<50 m) waters. The GSM product produced the lowest errors, but also showed a smaller dynamic range, while the Carder product produced higher errors than GSM and it also showed small dynamic range. The relationships between the MODIS and in situ euphotic depth were robust, with errors lower than 20%. MODIS products showed weaker or no significant relationships to in situ measurements in the Eastern Great Australian Bight. This is thought to be due to the summertime subsurface upwelling pool that is characteristic of the area. Based on these results, the OC3M product provides the most reliable estimates of chlorophyll-a, and is recommended for further applications of MODIS imagery, if the limitations in shallow waters are taken into account. Alternatively, the GSM product could be a better option if the algorithm

关键词： Great Australian Bight MODIS Remote Sensing Ocean Color Chlorophyll Euphotic Depth

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Artificial intelligence in gastroenterology: A state-of-the-art review

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World Journal of Gastroenterology 2021年第40期27卷 6794-6824页

作者： paul T Kröner Megan ML Engels Benjamin S Glicksberg Kipp W Johnson Obaie Mzaik Jeanin E van Hooft Michael B Wallace Hashem B El-Serag Chayakrit Krittanawong Division of Gastroenterology and Hepatology Mayo ClinicJacksonvilleFL 32224United States Cancer Center Amsterdam Department of Gastroenterology and HepatologyAmsterdam UMCLocation AMCAmsterdam 1105The Netherlands The Hasso Plattner Institute for Digital Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Gastroenterology and Hepatology Leiden University Medical CenterAmsterdam 2300The Netherlands Division of Gastroenterology and Hepatology Sheikh Shakhbout Medical CityAbu Dhabi 11001United Arab Emirates Section of Gastroenterology and Hepatology Michael E.DeBakey VA Medical Center and Baylor College of MedicineHoustonTX 77030United States Section of Health Services Research Michael E.DeBakey VA Medical Center and Baylor College of MedicineHoustonTX 77030United States Section of Cardiology Michael E.DeBakey VA Medical CenterHoustonTX 77030United States

The development of artificial intelligence(AI)has increased dramatically in the last 20 years,with clinical applications progressively being explored for most of the medical *** field of gastroenterology and hepatology,substantially reliant on vast amounts of imaging studies,is not an *** clinical applications of AI systems in this field include the identification of premalignant or malignant lesions(e.g.,identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus,pancreatic malignancies),detection of lesions(e.g.,polyp identification and classification,small-bowel bleeding lesion on capsule endoscopy,pancreatic cystic lesions),development of objective scoring systems for risk stratification,predicting disease prognosis or treatment response[e.g.,determining survival in patients post-resection of hepatocellular carcinoma),determining which patients with inflammatory bowel disease(IBD)will benefit from biologic therapy],or evaluation of metrics such as bowel preparation score or quality of endoscopic *** objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract,including the upper,middle and lower tracts;IBD;the hepatobiliary system;and the pancreas,discussing the findings and clinical applications,as well as outlining the current limitations and future directions in this field.

关键词： Artificial intelligence Machine learning Deep learning Clinical applications Gastroenterology

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