Munuaisensiirto elävältä luovuttajalta

Teema : elinsiirrotMunuaisensiirtoja elävältä luovuttajalta on Suomessa perinteisesti tehty vain vähän, mutta niiden määrää on viime vuosina pyritty lisäämään. Uusi kudoslaki mahdollistaa yhä useamman toimimisen elävänä luovuttajana. Munuaisluovuttajan riskit ovat vähäiset ja nykyään erittäin hyvin tunnetut

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Teema : elinsiirro

High TKTL1 expression as a sign of poor prognosis in colorectal cancer with synchronous rather than metachronous liver metastases : Cancer Biology & Therapy

ABSTRACT Colorectal cancer (CRC) is the third most common cancer in the world. More than half of all affected patients develop liver metastases during the course of the disease, and over half experience recurrence despite radical primary surgery. Transketolase-like protein 1 (TKTL1) is a key enzyme in the glucose metabolism of cancer cells, and its expression in tumor tissue was previously shown to indicate a poor prognosis in colorectal cancer. In this study, we investigated the prognostic significance of TKTL1 in 111 patients with surgically resected colorectal liver metastases, with a minimum follow-up time of 10.3 years. TKTL1 expression was examined in tissue samples of both primary tumors and liver metastases, and compared to clinicopathological parameters, disease-free survival, and overall survival. We show that a high expression of TKTL1 in primary tumor tissue associated with poor disease-free survival in patients with synchronous liver metastases (P = .026, Kaplan-Meier log-rank test), but with better disease-free survival in patients with metachronous metastases, although not statistically significantly (P = .073). We found similar tendencies for TKTL1 expression in liver metastases. Thus, TKTL1 could serve as a candidate marker to identify patients who benefit from liver resection or who need more aggressive perioperative chemotherapy.Peer reviewe

Atrial Fibrillation and Adverse Outcomes in Patients Undergoing Simultaneous Pancreas-Kidney Transplantation

Background. There are no published data on atrial fibrillation (AF) in patients receiving simultaneous pancreas-kidney transplantation (SPKT). We explored the epidemiology and adverse outcomes of AF in SPKT recipients in this retrospective observational cohort study. Materials and Methods. All 200 SPKT recipients in Finland to date between March 2010 and April 2021 were included in the present study. Demographics, comorbidities, medications, and transplantation data were collected from the electronic patient records. Outcome measures included new-onset AF (NOAF), ischemic stroke, and death. Results. Median age was 42 years (interquartile range [IQR] 35-49), 69 (35%) were female, and median dialysis vintage was 13 months (IQR 9-19). Altogether 7 patients (4%) had a previous diagnosis of AF at baseline, and heart failure was independently associated with prior AF in the age-adjusted multivariable logistic regression analysis. After a median follow-up of 3 years (IQR 1-5), 2 patients (1%) were observed with incident NOAF, 4 (2%) with ischemic stroke, and 7 patients (4%) died. Prior AF or NOAF were not associated with cardiovascular adverse outcomes, mortality or graft outcomes. Conclusions. We demonstrate a low prevalence and incidence of AF for the first time in this large observational study comprising all SPKT recipients in Finland to date.Peer reviewe

TKTL1 as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma and Its Correlation with FDG-PET-CT

Introduction: Glucose metabolism in cancer cells differs from noncancerous cells. The expression of transketolase-like protein 1 (TKTL1), a key enzyme in the glucose metabolism of cancer cells, predicts poor prognosis in several cancer types. We studied TKTL1 as a prognostic tool and whether TKTL1 expression correlates with 18F-FDG-PET-CT among patients with pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective study examined two PDAC patient cohorts: 168 patients operated on at Helsinki University Hospital between 2001 and 2011, and 20 patients with FDG-PET-CT results available from the Auria Biobank. We used immunohistochemistry for TKTL1 expression, combining results with clinicopathological data. Results: Five-year disease-specific survival (DSS) was slightly but not significantly better in patients with a high versus low TKTL1 expression, with DSS of 28.0 versus 17.3%, respectively (p = 0.123). TKTL1 served as a marker of a better prognosis in patients over 65 years old (p = 0.012) and among those with TNM class M1 (p = 0.018), stage IV disease (p = 0.027), or perivascular invasion (p = 0.008). Conclusions: Our study shows that TKTL1 cannot be used as a prognostic factor in PDAC with the exception of elderly patients and those with advanced disease. The correlation of TKTL1 with 18F-FDG-PET-CT requires further study in a larger patient cohort.Peer reviewe

Global practice variation in pharmacologic thromboprophylaxis for general and gynaecological surgery : systematic review

Peer reviewe

Atrial Fibrillation and Adverse Outcomes in Patients Undergoing Simultaneous Pancreas-Kidney Transplantation

BackgroundThere are no published data on atrial fibrillation (AF) in patients receiving simultaneous pancreas-kidney transplantation (SPKT). We explored the epidemiology and adverse outcomes of AF in SPKT recipients in this retrospective observational cohort study.Materials and MethodsAll 200 SPKT recipients in Finland to date between March 2010 and April 2021 were included in the present study. Demographics, comorbidities, medications, and transplantation data were collected from the electronic patient records. Outcome measures included new-onset AF (NOAF), ischemic stroke, and death.Results Median age was 42 years (interquartile range [IQR] 35-49), 69 (35%) were female, and median dialysis vintage was 13 months (IQR 9-19). Altogether 7 patients (4%) had a previous diagnosis of AF at baseline, and heart failure was independently associated with prior AF in the age-adjusted multivariable logistic regression analysis. After a median follow-up of 3 years (IQR 1-5), 2 patients (1%) were observed with incident NOAF, 4 (2%) with ischemic stroke, and 7 patients (4%) died. Prior AF or NOAF were not associated with cardiovascular adverse outcomes, mortality or graft outcomes.ConclusionsWe demonstrate a low prevalence and incidence of AF for the first time in this large observational study comprising all SPKT recipients in Finland to date.</p

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) : introduction and methodology

Funding Information: The Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) project was conducted by the Clinical Urology and Epidemiology (CLUE) Working Group and supported by the Academy of Finland (309387, 340957), Sigrid Jusélius Foundation and Competitive Research Funding of the Helsinki University Hospital (TYH2019321; TYH2020248). The sponsors had no role in the analysis and interpretation of the data or the manuscript preparation, review, or approval. Funding Information: KMA received a research grant from Astra Zeneca, and is consultant for Gedeon Richter, and received reimbursement for attending a scientific meeting from GSK (Tesaro Bio). RMT received reimbursement for attending a scientific meeting from Olympus. LIL, GHG, YL, RC, ALL, VJS, IEJK, PJK, RJC, RLA, KA, KMA, IB-L, MHB, JLC, SC, PJG, HAG-P, FZG, HAG, LH, MLI-K, KMJ, PKK, NK, TPK, AJK, TK, HL, AKM, BTN, TPN, CN, SMO, SP, NP, CBBR, ARR, TS, RMT, RWMV, YW, YX, LY, JH, and KAOT have no financial conflicts of interest. GHG and RC were panel members of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery. KAOT was chair of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery and panel member of the American Society of Hematology (ASH) Guideline Panel on Prevention of Venous Thromboembolism (VTE) in Surgical Hospitalized Patients. Publisher Copyright: © 2021, The Author(s).Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119Peer reviewe

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology

Background: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries.Methods: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty.Discussion: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach.Systematic review registration: PROSPERO CRD42021234119</p

The prognostic significance of transketolase-like protein 1 in gastrointestinal malignancies

Background: Cancer is the second most common cause of death nowadays. Gastrointestinal malignancies account for over 20% of cancer deaths globally. The prognosis in colorectal cancer has improved over the years while that of pancreatic and stomach has remained poor for the past decade. Biochemical tumor markers help in subtyping cancers to aim in choosing the best possible treatment for each individual. They are also helpful in follow-up and in determining prognosis. Cancer cells have metabolic features that differ from non-cancerous cells. One of these is the ability to use glycolysis as an energy source. Transketolase-like protein 1 (TKTL1) is a protein that catalyses cancer cells’ glucose production via the pentose phosphate pathway. This thesis consists of four studies that aimed to investigate the potential of TKTL1 as a prognostic marker in gastrointestinal cancers. Materials and methods: Study I included 840 colorectal patients treated in 1989-2000. The second study comprised 111 patients with colorectal cancer and liver metastases thereof. These patients were operated on in 1988-2007. Formalin-fixed samples were obtained from the primary tumor and liver metastases in 60 patients, the primary tumor only in 21 patients and liver metastases only in 30 patients. Study III included 313 patients with gastric cancer surgically treated in 2000-2009. Study IV on pancreatic ductal adenocarcinoma (PDAC) comprised 168 patients who were treated surgically in 2001-2011. All patients were treated at the Department of Surgery at Helsinki University Hospital. Clinicopathological data was gathered from patient records and causes of death from Statistics Finland. For all patients, tissue micro array (TMA) series were constructed including 3-6 tumor spots per patient. For study IV whole tissue samples were used in addition to TMA blocks. All tissue samples were stained for TKTL1 using immunohistochemistry. In study III also Glucose transporter 1 (GLUT1) staining was done. Results: TKTL1 immunostaining occurs mostly in cytoplasm although nucleus staining can also be seen. TKTL1 positivity is typical for cancer cells, but weak expression can occur in normal cells. In study I on colorectal cancer, TKTL1 associated with Dukes stage B through D, with left-sided disease, and with adenocarcinoma. Patients with high tissue expression of TKTL1 had poor prognosis but TKTL1 was not an independent prognostic factor. In study II, in the subgroup of patients with synchronous liver metastasis, the prognosis was poor in those with a high expression of TKTL1 in primary tumor tissue. In gastric cancer (study III), positive TKTL1 immunostaining associated with positive immunostaining of GLUT1, higher age, male gender, and advanced stage disease (stage II-IV and pT2-4). GLUT1 associated with intestinal type of cancer. TKTL1 served as a marker of poor prognosis in gastric cancer, but not independent, but GLUT1 did not have any prognostic value. Contradictory to previous findings in other cancer types, study IV showed that high expression of TKTL1 in PDAC was a marker of better prognosis in patients over 65 years old and those with distant metastasis, perivascular invasion and stage IV disease, but had no prognostic value in general. Conclusions: TKTL1 was a marker of poor prognosis among patients with colorectal cancer and also among those with synchronous liver metastases and those with intestinal or diffuse gastric cancer. TKTL1 cannot be used as a general prognostic marker in pancreatic ductal adenocarcinoma.Tausta: Syöpä on nykyisin maailman toiseksi yleisin kuolinsyy. Vatsan alueen syövät ovat syynä noin viidennekseen syöpäkuolemista. Paksu- ja peräsuolisyövän ennuste on parantunut, mutta maha- ja haimasyövän ennuste on pysynyt huonona viimeisten vuosikymmenten ajan. Biokemialliset kasvainmerkkiaineet eli biomarkkerit auttavat syövän alaluokittelussa. Alaluokat auttavat valitsemaan parhaan mahdollisen hoiton yksilötasolla sekä syövän seurannassa ja ennusteen määrittämisessä. Syöpäsolujen aineenvaihdunta eroaa normaalien solujen aineenvaihdunnasta. Syöpäsolut pystyvät hyödyntämään glykolyysia eli glukoosisokerin hajoittamista energian saamiseksi. Transketolase-like protein 1 (TKTL1) on biomarkkeri, joka katalysoi syöpäsolujen sokeriaineenvaihduntaa pentoosi-fosfaatti reitin kautta. Tämä väitöskirja koostuu neljästä osatyöstä, joiden tarkoituksena oli tutkia TKTL1:n käytettävyyttä ennusteellisena biomarkkerina vatsan alueen syövissä. Potilaat ja menetelmät: Ensimmäisessä osatyössä perehdyttiin 840 paksusuolisyöpää sairastavaan potilaaseen, jotka leikattiin vuosina 1989-2000. Toisessa osatyössä tutkittiin maksaan levinnyttä paksusuolisyöpää. Vuosina 1988-2007 leikattuja potilaita oli yhteensä 111, joista 60:llä oli näytteet sekä suolen syöpäkasvaimesta, että maksan etäpesäkkeestä, 21:llä ainoastaan paksusuolisyöpäkasvaimesta ja 30:llä ainoastaan maksan etäpesäkkeestä. Kolmannessa osatyössä tutkittiin 313 mahasyöpään sairastunutta potilasta, jotka leikattiin vuosina 2000-2009. Neljännessä osatyössä tutkittiin haimasyöpänäytteitä 168 potilaasta, jotka leikattiin 2001-2011. Kaikki potilaat leikattiin Helsingin yliopistollisessa sairaalassa. Kliinis-patologiset tiedot kerättiin potilastietojärjestelmästä sekä Väestörekisterikeskuksesta ja Tilastokeskuksesta. Kaikista näytteistä valmistettiin kudossirublokkisarjat, joissa oli 3-6 näytettä kustakin kasvaimesta. Kaikissa osatöissä kudossirublokkisarjat värjättiin TKTL1:llä, mahasyöpätyössä myös GLUT1:llä. Tulokset: TKTL1 ilmeni pääasiassa solun sytoplasmassa, mutta myös tumailmenemistä oli havaittavissa joissain syöpätyypeissä. Vaikka TKTL1 ilmeni syöpäsoluissa, oli ilmentymistä myös normaaleissa soluissa. Paksusuolisyövässä TKTL1 oli huonon ennusteen tekijä, joka lisäksi assosioitui adenokarsinooma kasvaintyyppiin, Dukes B-D taudin asteeseen sekä vasemman puolen tautiin. Toisessa osatyössä todettiin lisäksi, että potilailla, joilla maksametastasointi ilmeni diagnoosivaiheessa tai viimeistään 6 kk kuluessa diagnoosista, TKTL1 oli huonon ennusteen tekijä. Mahasyövässä positiivinen TKTL1-värjäys liittyi positiiviseen Glucose transporter 1 (GLUT1) -värjäykseen, iäkkäämpiin potilaisiin, miessukupuoleen sekä edenneeseen tautiin (luokat II-IV sekä pT2-4). GLUT1 assosioitui intestinaaliseen mahasyöpätyyppiin. TKTL1 oli mahasyövässä huonon ennusteen merkkiaine, mutta GLUT1:llä ei ollut ennusteellista merkitystä. Muista syöpätyyppien löydöksistä poiketen TKTL1 oli positiivisen ennusteen merkkiaine haimasyövässä iäkkäämillä potilailla sekä potilailla, joilla on etäpesäkkeitä, perivaskulaarinen invaasioa ja luokan IV tauti, mutta näitä ryhmiä lukuun ottamatta TKTL1:llä ei ollut ennusteellista merkitystä haimasyövässä. Päätelmät: TKTL1 oli huonon ennusteen syöpämerkkiaine paksu- ja peräsuolisyövässä, intestinaalisessa ja diffuusissa mahasyövässä sekä niissä maksaan levinneissä paksu- ja peräsuolisyövässä, joissa maksapesäkkeet ilmenivät viimeistään 6 kk sisällä syöpädiagnoosista. Haimasyövässä TKTL1:llä ei ollut ennusteellista arvoa