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| 1 | Anticancer 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 | 2015 | Cell Research2015，25，2： | 14 |
| 2 | Increased hepcidin expression in colorectal carcinogenesis显示文摘AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae- mia and whether it might have a role in colorectal car- cinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using im- munohistochemistry. RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi- tively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres- sion. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism. | Douglas G Ward Keith Roberts Matthew J Brookes Howard Joy Ashley Martin Tariq Ismail Robert Spychal Tariq Iqbal Chris Tselepis | 2008 | World Journal of Gastroenterology2008，14，9： | 12 |
| 3 | No difference in mortality among ALPPS,two-staged hepatectomy,and portal vein embolization/ligation:A systematic review by updated traditional and network meta-analyses显示文摘Background:There is an ongoing debate on the feasibility,safety,and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)technique.The aim of this study was to compare ALPPS,two-staged hepatectomy(TSH),and portal vein embolization(PVE)/ligation(PVL)using updated traditional meta-analysis and network meta-analysis(NMA).Data sources:Electronic databases were used in a systematic literature search.Updated traditional metaanalysis and NMA were performed and compared.Mortality and major morbidity were selected as primary outcomes.Results:Nineteen studies including 1200 patients were selected from the pool of 436 studies.Of these patients,315(31%)and 702(69%)underwent ALPPS and portal vein occlusion(PVO),respectively.Ninetyday mortality based on updated traditional meta-analysis,subgroup analysis of the randomized controlled trials(RCTs),and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE,PVL,and TSH cohorts.Moreover,analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts.The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters,time to operation,definitive hepatectomy,and R0 margins rates compared with the PVO cohort.In contrast,1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort.Conclusions:This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches.Furthermore,two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts. | Paschalis Gavriilidis Robert P Sutcliffe Keith J Roberts Madhava Pai Duncan Spalding Nagy Habib Long R Jiao Mikael H Sodergren | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，5： | 6 |
| 4 | Recurrence and survival following microwave, radiofrequency ablation, and hepatic resection of colorectal liver metastases: A systematic review and network meta-analysis显示文摘Background: Gold standard for colorectal liver metastases(CRLM) remains hepatic resection(HR). However, patients with severe comorbidities, unresectable or deep-situated resectable CRLM are candidates for ablation. The aim of the study was to compare recurrence rate and survival benefit of the microwave ablation(MWA), radiofrequency ablation(RFA) and HR by conducting the first network meta-analysis. Data sources: Systematic search of the literature was conducted in the electronic databases. Both updated traditional and network meta-analyses were conducted and the results were compared between them. Results: HR cohort demonstrated significantly less local recurrence rate and better 3-and 5-year diseasefree(DFS) and overall survival(OS) compared to MWA and RFA cohorts. HR cohort included significantly younger patients and with significantly lower preoperative carcinoembryonic antigen(CEA) by 10.28 ng/m L compared to RFA cohort. Subgroup analysis of local recurrence and OS of solitary and ≤3 cm CRLMs did not demonstrate any discrepancies when compared with the whole sample. Conclusions: For resectable CRLM the treatment of choice still remains HR. MWA and RFA can be used as a single or adjunct treatment in patients with unresectable CRLM and/or prohibitive comorbidities. | Paschalis Gavriilidis Keith J Roberts Nicola de’Angelis Luca Aldrighetti Robert P Sutcliffe | 2021 | Hepatobiliary & Pancreatic Diseases International2021，20，4： | 4 |
| 5 | Double-blind randomized sham controlled trial of intraperitoneal bupivacaine during emergency laparoscopic cholecystectomy显示文摘BACKGROUND: Intraperitoneal local anesthesia (IPLA) during elective laparoscopic cholecystectomy (el-LC) decreases post-operative pain. None of the studies have explored the efficacy of IPLA at emergency laparoscopic cholecystectomy (em-LC). A longer operative duration, the greater frequency of washing, and the inflammation associated with cholecystitis or pancreatitis are a few reasons why it cannot be assumed that a benefit in pain scores will be seen in em-LC with IPLA. This study was undertaken to assess the efficacy of IPLA in patients undergoing em-LC. METHODS: Double-blind randomized sham controlled trial was conducted of 41 consecutive subjects undergoing em-LC. IPLA was delivered by a combination of injection to the diaphragmatic and topical wash over the liver and gallbladder with bupivacaine or saline. The primary outcome was visual analogue scale pain scores until discharge. Secondary outcomes included pain scores in theatre recovery and analgesic consumption. RESULTS: One patient had a procedure converted to open and was excluded. There was no significant difference in pain scores in the ward or theatre recovery. Analgesic use, respiratory rate, oxygen saturation, duration to ambulation, eating, satisfaction scores, and time to discharge were comparable between the two groups. CONCLUSIONS: IPLA during em-LC does not influence postoperative pain. Other modalities of analgesia should be explored for decreasing the interval between diagnosis of acute admission and em-LC. | Keith J Roberts Jeff Gilmour Ruplay Pande James Hodson For Tai Lam Saboor Khan | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，3： | 3 |
| 6 | Pancreaticopleuralfistula:etiology,treatmentandlong-termfollow-up显示文摘BACKGROUND:Pancreaticopleural fistula(PPF) are uncommon.Complex multidisciplinary treatment is required due to nutritional compromise and sepsis.This is the first description of long-term follow-up of patients with PPF.METHODS:Eleven patients with PPF treated at a specialist unit were identified.Causation,investigation,treatment and outcomes were recorded.RESULTS:Pancreatitis was the etiology of the PPF in 9 patients,and in the remaining 2 the PPF developed following distal pancreatectomy.Cross-sectional imaging demonstrated the site of duct disruption in 10 cases,with endoscopic retrograde cholangiopancreatography identifying the final case.Suppression of pancreatic exocrine secretion and percutaneous drainage formed the mainstay of treatment.Five cases resolved following pancreatic duct stent insertion and three patients required surgical treatment for established empyema.There were no complications.In all cases that resolved there has been no recurrence of PPF over a median follow-up of 50 months(range 15-62).CONCLUSIONS:PPF is an uncommon event complicating pancreatitis or pancreatectomy;pancreatic duct disruption is the common link.A step-up approach consisting of minimally invasive techniques treats the majority with surgery needed for refractory sepsis. | Keith J Roberts Maria Sheridan Gareth Morris-Stiff Andrew M Smith | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，2： | 2 |
| 7 | RolEnact:role-basedenactable models of business processes显示文摘 | KEITH T PETER H ROBERT J | 1998 | Information and Soft-ware Technology1998，40，3： | 1 |
| 8 | Multiple pulmonary nodules in AIDS:usefulness of CT in distinguishing among potential causes显示文摘 | Keith J Edinburgh MD Robert M | 2000 | Radiology2000，214，2： | 1 |
| 9 | Placebos and paradoxes in psychiatric research: an ethics perspective显示文摘 | Roberts LW Lauriello J Geppert C Keith SJ | 2001 | Biol Psychiatry2001，49，： | 1 |
| 10 | RolEnact: role-based enactable models of business processes 显示文摘 | KEITH T P PETER H ROBERT J W | 1998 | Information and Software Technology1998，40，3： | 1 |
| 11 | Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study显示文摘 | Keith C Bible Vera J Suman Julian R Molina Robert C Smallridge William J Maples Michael E Menefee Joseph Rubin Kostandinos Sideras John C Morris Bryan McIver Jill K Burton Kevin P Webster Carolyn Bieber Anne M Traynor Patrick J Flynn Boon Cher Goh Hui Tan | 2010 | Lancet Oncology2010，，10： | 1 |
| 12 | Lymphoepithelial cysts of the pancreas:a management dilemma显示文摘Pancreatic lymphoepithelial cysts(LECs) are rare,benign lesions that are typically unexpected post-operative pathological findings. We aimed to review clinical, radiological and pathological features of LECs that may allow their preoperative diagnosis. Histopathology databases of two large pancreatic units were searched to identify LECs and notes reviewed to determine patient demographic details, mode of presentation, investigations, treatment and outcome. Five male and one female patients were identified. Their median age was 60 years. Lesions were identified on computed tomography performed for abdominal pain in two patients, and were incidentally observed in four patients. Five LECs were located in the tail and one in the body of the pancreas, with a median cyst size of 5 cm. Obtaining cyst fluid was difficult and a largely acellular aspirate was yielded. The pre-operative diagnosis was mucinous cystic neoplasm in all patients. This series of patients were treated distal pancreatectomy and splenectomy. A retrospective review of radiological examinations suggested that LECs have a relatively low signal on T2 imaging and a high signal intensity on T1 weighted images. LECs appear more common in elderly males, and are typically incidental, large, unilocular cysts. Close attention to signal intensity on MRI may allow preoperative diagnosis of these lesions. | Julie Martin Keith J Roberts Maria Sheridan Gavin A Falk Daniel Joyce R Matthew Walsh Andrew M Smith Gareth Morris-Stiff | 2014 | Hepatobiliary & Pancreatic Diseases International2014，13，5： | 1 |
| 13 | Eye tracking in human computer interaction and usability research: Ready to deliver the promise 显示文摘 | Jacob Robert J K Karn Keith S | 2003 | Computer Vision and Image Understanding2003，24，： | 1 |
| 14 | PAH refractory index as a source discriminant of hydrocarben input from crude oil and coal in Prince William Sound 显示文摘 | Frances D Hostettler Robert J Rosenbauer Keith A Kvenvolden | 1999 | Alaska Organic Geochemistry1999，30，： | 1 |
| 15 | The cloning of cattle interferon-A subtypes isolated from the gut epithelium of rotavirus-infected calves显示文摘 | Paul J C Keith R P Robert A C | 1996 | Immunogenetics1996，44，： | 1 |
| 16 | Eye tracking in human computer interaction and usability research:Ready to deliver the pormises显示文摘 | Robert J K Jacob Keith S Karn | 2003 | Computer Vision and Image Understanding2003，24，： | 1 |
| 17 | The marketing revo- lution 显示文摘 | Keith Robert J | 1960 | Journal of Marketing1960，24，3： | 1 |
| 18 | Pathogenesis of Henoch-Sch?nlein purpura nephritis显示文摘 | Keith KL Hitoshi S Robert J | 2010 | Pediatric Nephrology2010，25，1： | 1 |
| 19 | Multiple pulmonary Nodules in AIDS:usefulness of CT in Distinguishing among potential causes显示文摘 | Keith JE Robert J Laurence E | 2000 | Radiology2000，214，2： | 1 |
| 20 | Multiple pulmonary nodules in AIDS:Usefulness of CT in distinguishing among potential causes显示文摘 | Keith J Edinburgh Robert M Jasmer Laurence Huang | 2000 | Radiology2000，214，2： | 1 |
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