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Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery

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World Journal of Gastroenterology 2013年第21期19卷 3272-3280页

作者： Maija Piekkala Jaana Hagstrm Maarit Tanskanen Risto Rintala Caj Haglund Kaija-Leena Kolho Children's Hospital University of HelsinkiFIN-00029 HUSHelsinkiFinland Department of Pathology Haartman InstituteUniversity of HelsinkiFIN-00029 HUS HelsinkiFinland Department of Surgery Helsinki University Central HospitalFIN-00029 HUS HelsinkiFinland

AIM: To investigate whether matrix metalloproteinases-9 (MMP-9) or trypsinogens could serve as histological markers for an aggressive disease course in pediatric ulcerative colitis (UC). METHODS: We identified 24 patients with pediatric onset (≤ 16 years) UC who had undergone surgery during childhood/adolescence a median of 2.1 years (range 0.1-7.4 years) after the diagnosis (between 1990 and 2008) in Children's Hospital, Helsinki, Finland. We also identified 27 conservatively treated UC patients and matched them based on their age at the time of diagnosis and follow-up at a median of 6 years (range 3-11 years) to serve as disease controls. Twenty children for whom inflammatory bowel disease (IBD) had been excluded as a result of endoscopy served as non-IBD controls. Colon biopsies taken by diagnostic endoscopy before the onset of therapy were stained using immunohistochemistry to study the expression of MMP-9, trypsinogen-1 (Tryp-1), Tryp-2, and a trypsin inhibitor (TATI). The profiles of these proteases and inhibitor at diagnosis were compared between the surgery group, the conservatively treated UC patients and the non-IBD controls. RESULTS: The proportions of Tryp-1 and Tryp-2 positive samples in the colon epithelium and in the inflammatory cells of the colon stroma were comparable between the studied groups at diagnosis. Interestingly, the immunopositivity of Tryp-1 (median 1; range 0-3) was significantly lower in the epithelium of the colon in the pediatric UC patients undergoing surgery when compared to that of the conservatively treated UC patients (median 2; range 0-3; P = 0.03) and non-IBD controls (median 2; range 0-3; P = 0.04). For Tryp-2, there was no such difference. In the inflammatory cells of the colon stroma, the immunopositivities of Tryp-1 and Tryp-2 were comparable between the studied groups at diagnosis. Also, the proportion of samples positive for TATI, as well as the immunopositivity, was comparable between the studied groups in the colon epithelium. In the stromal inflammatory cells of t

关键词： Children Ulcerative colitis Inflammatory bowel disease Matrix metalloproteinase-9 resection Trypsin inhibitor

Quality of life following laparoscopic Nissen fundoplication: Assessing short-term and long-term outcomes

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World Journal of Gastroenterology 2013年第24期19卷 3810-3818页

作者： Ilmo Kellokumpu Markku Voutilainen Caj Haglund Martti Frkkil Peter J Roberts Hannu Kautiainen Department of Surgery Central Hospital of Central Finland40620 Jyvskyl Finland Department of Gastroenterology Central Hospital of Central Finland40620 Jyvskyl Finland Department of Surgery Helsinki University Central Hospital Division of Gastroenterology Department of Internal Medicine Helsinki University Central Hospital Department of Surgery Turku University Hospital Biostatistician Unit of Primary Health Care Helsinki University Hospital Department of General Practice Primary Health Care Unit Turku University Hospital

AIM: To investigate the quality of life following lapa-roscopic Nissen fundoplication by assessing short-term and long-term outcomes. METHODS: From 1992 to 2005, 249 patients under-went laparoscopic Nissen fundoplication. Short-term outcome data including symptom response, side effects of surgery, endoscopy, and patient's perception of over-all success were collected prospectively. Long-term out-comes were investigated retrospectively in patients witha median follow-up of 10 years by assessment of reflux symptoms, side effects of surgery, durability of antire-flux surgery, need for additional treatment, patient's perception of success, and quality of life. Antireflux sur-gery was considered a failure based on the following criteria: moderate to severe heartburn or regurgitation; moderate to severe dysphagia reported in combination with heartburn or regurgitation; regular proton pump inhibitor medication use; endoscopic evidence of erosive esophagitis Savary-Miller grade 1-4; pathological 24-h pH monitoring; or necessity to undergo an additional surgery. The main outcome measures were short-and long-term cure rates and quality of life, with patient sat-isfaction as a secondary outcome measure. RESULTS: Conversion from laparoscopy to open sur-gery was necessary in 2.4% of patients. Mortality was zero and the 30-d morbidity was 7.6% (95%CI: 4.7%-11.7%). The median postoperative hospital stay was 2 d [interquartile range (IQR) 2-3 d]. Two hundred and forty-seven patients were interviewed for short-term analysis following endoscopy. Gastro-esophageal reflux disease was cured in 98.4% (95%CI: 95.9%-99.6%) of patients three months after surgery. New-onset dysphagia was encountered postoperatively in 13 patients (6.7%); 95% reported that the outcome was better after antireflux surgery than with preopera-tive medical treatment. One hundred and thirty-nine patients with a median follow-up of 10.2 years (IQR 7.2-11.6 years) were available for a long-term evalu-ation. Cumulative long-term cure rates were 87.7% (81.0%-92.2%)

关键词： Laparoscopy Nissen fundoplication Long-term outcome Antireflux Gastrointestinal symptom rating scores RAND-36

Carbonic anhydrase enzymes Ⅱ, Ⅶ, Ⅸ and Ⅻ in colorectal carcinomas

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World Journal of Gastroenterology 2016年第36期22卷 8168-8177页

作者： Pia Viikil? Antti J Kivel? Harri Mustonen Selja Koskensalo Abdul Waheed William S Sly Jaromir Pastorek Silvia Pastorekova Seppo Parkkila Caj Haglund School of Medicine University of Tampere and Fimlab Ltd Tampere University Hospital Department of Surgery University of Helsinki and Helsinki University Hospital Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine Centre of Molecular Medicine Institute of Virology Slovak Academy of Sciences Research Programs Unit Translational Cancer Biology University of Helsinki

AIM To investigate expression of four alpha-carbonic anhydrases(CAs) in colorectal carcinomas(CRC) and compare the results with patients' survival.METHODS Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA Ⅱ, CA Ⅶ, CA Ⅸ, and CA Ⅻ. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients' survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients' age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data. RESULTS CA Ⅱ and CA Ⅻ staining intensities correlated with patients' survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA Ⅱ intensity increased the hazard ratio to 1.19 fold(CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA Ⅻ staining intensity with survival of CRC patients(HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA Ⅻ immunostaining did not correlate to the patients' survival(P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA Ⅱ staining was found. Increased extent of CA Ⅱ had a significant hazard ratio among patients 65 years and older(1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA Ⅶ(intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA Ⅸ(intensity P = 0.879, extent P = 0.315, KaplanMeier analysis) immunostaining results and survival, or the other parameters. CONCLUSION The present findings indicate that CA Ⅱ and CA Ⅻ could be useful in predicting survival in CRC.

关键词： Biomarker Carbonic anhydrase Colorectal cancer Immunohistochemistry Prognosis Survival

美国临床生化科学院检验医学实践指南:睾丸、前列腺、结直肠、乳腺及卵巢癌肿瘤标志物的应用

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临床检验杂志 2012年第2期30卷 116-160页

作者：鄢盛恺 Ulf-Hkan Stenman Rolf Lamerz Leendert H.Looijenga Nils Brünner Michael J.Duffy Caj Haglund Mads Holten-Andersen Hans JФrgen Nielsen Francisco J.Esteva Nadia Harbeck Daniel F.Hayes Rafael Molina Daniel W.Chan Robert C.Bast Jr Ie-Ming Shih Lori J.Sokoll Gyrgy Slétormos 刘洋梁红艳姜晓峰田亚平薛丽林文涛顾兵潘世扬沈文梅郑磊李江卫生部中日友好医院检验科北京100029 北京豪迈生物工程有限公司北京100028

经美国临床生化科学院(NCAB)授权,由鄢盛恺教授组织学者、专家翻译审定2009年NCAB检验医学实践指南:睾丸、前列腺、结直肠、乳腺及卵巢癌中肿瘤标志物的应用单行本(Catharine M.Sturgeon教授和Eleftherios P.Diaman-dis教授编辑)。该指... 详细信息

经美国临床生化科学院(NCAB)授权,由鄢盛恺教授组织学者、专家翻译审定2009年NCAB检验医学实践指南:睾丸、前列腺、结直肠、乳腺及卵巢癌中肿瘤标志物的应用单行本(Catharine M.Sturgeon教授和Eleftherios P.Diaman-dis教授编辑)。该指南包含第1至6章共6部分内容,参加指南制订的专家阵容强大,分别从临床及检验角度对睾丸、前列腺、结直肠、乳腺及卵巢癌中肿瘤标志物的检测与临床应用方面的问题进行了详细阐述与说明,是目前国内外在肿瘤实验诊断方面的纲领性应用文件。不仅适合广大检验人员、临床医护人员学习使用,也非常适合相关仪器试剂生产厂商研发应用。本指南由刘洋、薛丽、林文涛、李江、梁红艳、顾兵、潘世扬、郑磊等翻译,姜晓峰、沈文梅、田亚平、鄢盛恺审校,最后由鄢盛恺统稿审定。本指南的翻译出版,不仅有助于我国检验人员和医护人员合理的检测和应用睾丸、前列腺、结直肠、乳腺及卵巢癌肿瘤标志物,对我国检验医学指南的编写与应用也有一定的借鉴作用。本刊特在本期刊发,以飨广大读者。

关键词：肿瘤标志物临床应用实践指南检验医学临床生化前列腺结直肠卵巢癌