77 research outputs found

    Prognostic tumour markers in pancreatic cancer

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    Background. Pancreatic cancer is one of the major causes of cancer death in the industrialised world. The overall survival of patients with ductal pancreatic adenocarcinoma is poor: 5-year survival is only 0.2 to 4%. Tumour stage and histological grade are used as prognostic markers in pancreatic cancer. However, there are differences in survival within stages and histological grades. New, additional and more accurate prognostic tools are needed. Aims. The purpose of this study was to investigate whether the tissue expression of potential and promising tumour markers p27, tenascin C, syndecan-1, COX-2 and MMP-2 are associated with clinicopathological parameters in pancreatic cancer. The expression of p27, tenascin C and syndecan-1 was also evaluated in acute and chronic pancreatitis. The main purpose in the study was to find new prognostic markers for pancreatic adenocarcinoma. Patients. The study included 147 patients with histologically verified pancreatic adenocarcinoma treated at Helsinki University Central Hospital from 1974 to1998. Methods. The expression of tumour marker antigens was demonstrated by immunohistochemistry using monoclonal antibodies against p27, syndecan-1, tenascin C, COX-2 and MMP-2. The results were compared with clinicopathological variables, i.e. age, sex, TNM stage and histological grade. Survival analyses were performed with univariate Kaplan-Meier life-tables and the log-rank test, while multivariate analyses were performed using Cox regression. Results. Pancreatic adenocarcinomas expressed p27, syndecan-1, tenascin C, COX-2 and MMP-2 in 30, 94, 92, 36 and 50% of the samples, respectively. Loss of p27 expression was associated with poor prognosis in stage I and II pancreatic cancer. Stromal syndecan-1 expression was an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicted better prognosis only in stage I and II disease. Tenascin C expression did not correlate with survival but was associated with differentiation. COX-2 expression was associated with poor outcome and was an independent prognostic factor. Epithelial MMP-2 correlated with poor prognosis in pancreatic cancer. Conclusion: p27 and epithelial syndecan-1 are prognostic markers in early (stage I and II) pancreatic cancer. Stromal syndecan-1, COX-2 and epithelial MMP-2 are prognostic factors in ductal pancreatic adenocarcinoma.Tausta: Haiman duktaalinen syöpä on kolmanneksi yleisin mahasuolikanavan pahanlaatuisista kasvaimista paksusuolisyövän ja mahasyövän jälkeen. Vuonna 2003 Suomen syöpärekisterin mukaan uusia haimasyöpään sairastuneita potilaita oli 8,5 miestä ja 7,3 naista 100 000 asukasta kohden. Haimasyöpä on tunnettu huonon ennusteen vuoksi: lähes kaikki potilaat kuolevat viiden vuoden sisällä. Haimasyövän ensioireet ovat vähäiset ja tauti etenee nopeasti. Oireiden ilmaantuessa syöpä on usein jo levinnyt, eikä parantavaa hoitoa voida antaa. Vain joka viides kasvain todetaan varhaisvaiheessa, jolloin se voidaan poistaa leikkauksella. Haimasyövän tyyppileikkaus on pankreatikoduodenektomia, jossa poistetaan haiman pää ja pohjakaissuoli. Leikkaushoitoon voidaan yhdistää taudin kulkua hidastava solunsalpaajahoito. Valitettavasti radikaalikirurgian ja solunsalpaajahoitojen jälkeenkin taudilla on tapana uusia - joskin hoitotulokset ovat selkeästi parantuneet viimeisten 15 vuoden aikana. Haimasyöpään erikoistuneissa keskuksissa 5-vuotis ennuste on kohentunut 5:stä aina 25%:een. Taudin ennusteen määrittämiseksi on perinteisesti ollut käytössä levinneisyysluokitus (TNM-luokitus) ja kasvaimen erilaistumisaste (Grade). Näiden lisäksi kaivataan tarkempia ennustetekijöitä, joiden avulla saataisiin lisätietoa taudin tulevasta kulusta. Tutkimuksemme tarkoituksena on ollut testata uusia, mutta lupaavia biologisia syövän ennusteellisia merkkiaineita immunohistokemiallisin menetelmin. Aineistossamme on vuosina 1974 - 1998 Helsingin yliopistollisessa keskussairaalassa leikatut haimasyöpäpotilaat, joiden kasvaimesta on säilynyt kudosnäyte patologian laitoksen arkistoissa. Näytteet tutkittiin uudelleen ja aineistosta poistettiin ne potilaat joilla osoittautui olemaan väärä diagnoosi, kuten haiman kystadenokarsinooma tai insulinooma. Duktaalista haimasyöpää sairastavia potilaita aineistoon soveltui 149. Menetelmä: Potilastiedot kerättiin sairaskertomuksista, syöpärekisteristä ja väestörekisteristä. Patologi tutki kudosnäytteet, varmisti diagnoosin ja määritti erilaistumisasteen WHO:n kriteerien mukaan. Näytteet värjättiin työryhmän laboratoriossa immunohistokemiallisin menetelmin. Työssämme tutkittiin p27, syndekaani-1, tenaskiini C, syklo-oksygenaasi-2 (COX-2) ja matriksi metalloproteinaasi -2 (MMP-2) esiintyvyys haimasyöpäkasvaimissa ja verrattiin tulosta elinaikaan sekä muihin muuttujiin, kuten kasvaimen erilaistumisasteeseen, kasvaimen kokoon, imusolmukkeisiin levinneisyyteen ja etäpesäkkeisiin. Tulokset: Ennusteeseen vaikuttavia tekijöitä olivat kasvaimen erilaistumisaste, levinneisyysaste, tuumorin paikallinen levinneisyys, etäpesäkkeet, radikaalileikkaus, kasvaimen sijainti, potilaan ikä, strooman syndekaani-1, COX-2 ja epiteelin MMP-2. Potilailla, joille oli tehty parantava leikkaus, edellä olevien muuttujien lisäksi ennustetekijöitä olivat p27 ja epiteelin syndecan-1. Itsenäisiä ennustetekijöitä olivat erilaistumisaste, TNM-luokitus ja radikaalileikkaus, strooman syndekaani-2 ja COX-2 sekä radikaalileikatuilla potilailla p27. Johtopäätökset: Syndekaani-1:n, COX-2:n ja MMP-2:n esiintyvyydet syöpäkudoksessa antavat uutta ja itsenäistä tietoa aiemmin käytettyjen ja tunnettujen ennustetekijöiden lisäksi

    A Retrospective 2-Year Follow-up of Late Complications Treated Surgically and Endoscopically After Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) and Laparoscopic Sleeve Gastrectomy (LSG) for Morbid Obesity

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    The laparoscopic Roux-en-Y gastric bypass (LRYGB) has been the gold standard for bariatric surgery, but recently, the laparoscopic sleeve gastrectomy (LSG) has gained popularity. At present, limited data is available on the long-term complications of these two types of surgery. The aim of this retrospective study was to compare the 2-year data about late (more than 30 days after surgery) complications that were treated surgically or endoscopically after LRYGB and LSG operations in a large hospital area with a single patient database. This was a retrospective, non-randomized, single-center study of 760 (545 LRYGB and 215 LSG) bariatric patients surgically treated between 2008 and 2013 in the Bariatric Surgery Unit of Helsinki University Central Hospital. The patients were followed for 2 years, and late complications (more than 30 days after surgery) that were surgically and/or endoscopically treated were registered. Weight loss and the risk factors for complications were also monitored. The study found a difference between the LRYGB and LSG patients in a number of late complications treated by both intervention types: surgical intervention were required in 9.4% of LRYGB patients vs. 0.9 of LSG patients, and endoscopic intervention were required by 4.6% of LRYGB patients vs. 1.4% of LSG patients (both p <0.05). The risk of surgical complications was increased by better weight loss results in 12 months. LRYGB was found to be associated with a greater risk of late complications. If larger databases confirm these results, the trend toward LSG is justified.Peer reviewe

    Laparoskooppinen lihavuusleikkaus

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    Teema : lihavuuskirurgia. English summar

    Is preoperative gastroscopy necessary before sleeve gastrectomy and Roux-en-Y gastric bypass?

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    Background: Consensus on the necessity of esophagogastroduodenoscopy (EGD) before bariatric surgery is lacking. Recommendations and practices vary by country and unit. Several reports have expressed concerns on gastroesophageal reflux disease (GERD) and its consequences after sleeve gastrectomy (SG) and the risk of leaving a premalignant lesion in the excluded stomach after Roux en -Y gastric bypass (RYGB). Objectives: We explored the number and types of clinically significant findings in preoperative EGDs and how they associate with preexisting GERD-symptoms (SG) and premalignant lesions (RYGB). We also studied how many reoperations were performed due to postoperative GERD in SG-patients. Setting: University hospital. Methods: We investigated preoperative EGD-findings and gastrointestinal symptoms before bariatric surgery in all patients with a primary bariatric operation in our unit between December 2007 and May 2016. Results: We performed 1474 operations: 1047 (71.0%) RYGB, 407 (27.6%) SG, and 20 (1.4%) others. One thousand two hundred seventy-five (86.5%) preoperative EGD reports were analyzed: 647 (50.7%) EGDs were completely normal. Altogether, 294 patients (23.0% of total) had a clinically significant finding that was relevant for SG (hiatal hernia, esophagitis, Barrett's esophagus, esophageal dysplasia), 144 (49.0%) of whom reported gastrointestinal symptoms. Twenty patients (1.6%) had a significant finding relevant for RYGB (peptic ulcer, atrophic gastritis, gastrointestinal stromal tumor), and 6 (30%) reported gastrointestinal symptoms. Thirteen (3.2%) SGs were converted into RYGB due to GERD. Conclusions: Preoperative EGD is indicated before SG but not before RYGB for asymptomatic patients without a risk for gastric pathology. (C) American Society for Metabolic and Bariatric Surgery. All rights reserved.Peer reviewe

    Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass

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    INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.Peer reviewe

    Prospective randomized controlled trial comparing the efficacy and safety of Roux-en-Y gastric bypass and one-anastomosis gastric bypass (the RYSA trial): trial protocol and interim analysis

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    INTRODUCTION: There is a lack of prospective studies comparing Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). Also, the effects of bariatric surgery and weight loss need a deeper understanding through metabolic studies. We describe the trial protocol and interim analysis of a prospective randomized controlled study comparing RYGB and OAGB: the RYSA trial. MATERIALS AND METHODS: In total, 120 bariatric patients will be randomized between RYGB and OAGB in two academic centers. All patients will be followed up for 10 years with analysis and measurements of weight, comorbidities, blood tests, body composition and questionnaires. Extensive metabolic analyses (mixed meal tests, energy expenditure, biopsies of muscle and subcutaneous fat, urine, saliva and fecal samples) will be carried out in the Obesity Research Unit, University of Helsinki, for all patients treated at the Helsinki University Hospital (80 patients) at baseline, 6 months and 12 months. Bile reflux will be studied for the OAGB group at the Helsinki University Hospital at 6 months with gastroscopy and scintigraphy. RESULTS: At an interim analysis at 3 months (half-way) through recruitment (30 RYGB and 30 OAGB patients) there have been no deaths and no intensive care unit admittances. One patient in both groups required additional gastroscopy, with anastomosis dilatation in the RYGB group but with no additional intervention in the OAGB group. CONCLUSION: The trial can be safely carried out. Recruitment is estimated to be complete by the end of 2019. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685. Registered on August 30th 2016.Peer reviewe

    Errors-in-Variables Modeling of Personalized Treatment-Response Trajectories

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    Estimating the impact of a treatment on a given response is needed in many biomedical applications. However, methodology is lacking for the case when the response is a continuous temporal curve, treatment covariates suffer extensively from measurement error, and even the exact timing of the treatments is unknown. We introduce a novel method for this challenging scenario. We model personalized treatment-response curves as a combination of parametric response functions, hierarchically sharing information across individuals, and a sparse Gaussian process for the baseline trend. Importantly, our model accounts for errors not only in treatment covariates, but also in treatment timings, a problem arising in practice for example when data on treatments are based on user self-reporting. We validate our model with simulated and real patient data, and show that in a challenging application of estimating the impact of diet on continuous blood glucose measurements, accounting for measurement error significantly improves estimation and prediction accuracy.Peer reviewe
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