Browsing by Subject "Survival"

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  • Sofou, Kalliopi; De Coo, Irenaeus F. M.; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B.; Lonnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A.; Tulinius, Mar; Darin, Niklas (2014)
  • Seibold, Petra; Schmezer, Peter; Behrens, Sabine; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Flesch-Janys, Dieter; Nevanlinna, Heli; Fagerholm, Rainer; Aittomaki, Kristiina; Blomqvist, Carl; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Lambrechts, Diether; Wildiers, Hans; Kristensen, Vessela; Alnaes, Grethe Grenaker; Nord, Silje; Borresen-Dale, Anne-Lise; Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes; Seynaeve, Caroline; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Dunning, Alison M.; Rhenius, Valerie; Shah, Mitul; Kabisch, Maria; Torres, Diana; Ulmer, Hans-Ulrich; Hamann, Ute; Schildkraut, Joellen M.; Purrington, Kristen S.; Couch, Fergus J.; Hall, Per; Pharoah, Paul; Easton, Doug F.; Schmidt, Marjanka K.; Chang-Claude, Jenny; Popanda, Odilia (2015)
    Background: Personalized therapy considering clinical and genetic patient characteristics will further improve breast cancer survival. Two widely used treatments, chemotherapy and radiotherapy, can induce oxidative DNA damage and, if not repaired, cell death. Since base excision repair (BER) activity is specific for oxidative DNA damage, we hypothesized that germline genetic variation in this pathway will affect breast cancer-specific survival depending on treatment. Methods: We assessed in 1,408 postmenopausal breast cancer patients from the German MARIE study whether cancer specific survival after adjuvant chemotherapy, anthracycline chemotherapy, and radiotherapy is modulated by 127 Single Nucleotide Polymorphisms (SNPs) in 21 BER genes. For SNPs with interaction terms showing p <0.1 (likelihood ratio test) using multivariable Cox proportional hazard analyses, replication in 6,392 patients from nine studies of the Breast Cancer Association Consortium (BCAC) was performed. Results: rs878156 in PARP2 showed a differential effect by chemotherapy (p = 0.093) and was replicated in BCAC studies (p = 0.009; combined analysis p = 0.002). Compared to non-carriers, carriers of the variant G allele (minor allele frequency = 0.07) showed better survival after chemotherapy (combined allelic hazard ratio (HR) = 0.75, 95 % 0.53-1.07) and poorer survival when not treated with chemotherapy (HR = 1.42, 95 % 1.08-1.85). A similar effect modification by rs878156 was observed for anthracycline-based chemotherapy in both MARIE and BCAC, with improved survival in carriers (combined allelic HR = 0.73, 95 % CI 0.40-1.32). None of the SNPs showed significant differential effects by radiotherapy. Conclusions: Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy. These germline SNPs could contribute towards the design of predictive tests for breast cancer patients.
  • Kostiainen, Iiro; Hakaste, Liisa; Kejo, Pekka; Parviainen, Helka; Laine, Tiina; Löyttyniemi, Eliisa; Pennanen, Mirkka; Arola, Johanna; Haglund, Caj; Heiskanen, Ilkka; Schalin-Jäntti, Camilla (2019)
    BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine carcinoma with poor 5-year survival rates of20 Hounsfield Units (HU) for all tumours (median 34 (21-45)), median size 92mm (20-196), Ki67 17% (1-40%), Weiss score 7 (4-9) and Helsinki score 24 (4-48). ACC was more often found in the left than the right adrenal (p5 to>10 years was achieved after repeated surgery of metastases. Overall 5-year survival was 67%, and 96% vs. 26% for ENSAT stage I-II vs. III-IV (p20 on nonenhanced CT but variable tumour size (20-196mm). Malignancy cannot be ruled out by small tumour size only. The 5-year survival of 96% in ENSAT stage I-III compares favourably to previous studies.
  • PERSARC Study Group; Acem, Ibtissam; Verhoef, Cornelis; Rueten-Budde, Anja J.; Grünhagen, Dirk; van Houdt, Winan; van de Sande, Michiel A. J.; Aston, Will; Bonenkamp, Han; Desar, Ingrid; Ferguson, Peter C.; Fiocco, Marta; Gelderblom, H.; van Ginkel, Robert; Van der Graaf, Winette; Griffin, Anthony; Haas, Rick; van der Hage, Jos A.; Hayes, Andrew; Jeys, Lee M; Keller, Johnny; Laitinen, Minna K.; Leithner, Andreas; Maretty-Kongstad, Katja; Ozaki, Toshifumi; Pollock, Rob; van Praag, Veroniek M.; Smith, Myles; Smolle, Maria; Styring, Emelie; Szkandera, Joanna; Tanaka, Kazuhiro; Tunn, Per-Ulf; Willegger, Madeleine; Windhager, Reinhard; Wunder, Jay S.; Zaikova, Olga (2020)
    Purpose: No studies extensively compared the young adults (YA, 18-39 years), middle-aged (40-69 years), and elderly (≥70 years) population with primary high-grade extremity soft tissue sarcoma (eSTS). This study aimed to determine whether the known effect of age on overall survival (OS) and disease progression can be explained by differences in tumour characteristics and treatment protocol among the YA, middle-aged and elderly population in patients with primary high-grade eSTS treated with curative intent. Methods: In this retrospective multicentre study, inclusion criteria were patients with primary high-grade eSTS of 18 years and older, surgically treated with curative intent between 2000 and 2016. Cox proportional hazard models and a multistate model were used to determine the association of age on OS and disease progression. Results: A total of 6260 patients were included in this study. YA presented more often after 'whoops'-surgery or for reresection due to residual disease, and with more deep-seated tumours. Elderly patients presented more often with grade III and larger (≥10 cm) tumours. After adjustment for the imbalance in tumour and treatment characteristics the hazard ratio for OS of the middle-aged population is 1.47 (95% confidence interval [CI]: 1.23-1.76) and 3.13 (95% CI: 2.59-3.78) in the elderly population, compared with YA. Discussion: The effect of age on OS could only partially be explained by the imbalance in the tumour characteristics and treatment variables. The threefold higher risk of elderly could, at least partially, be explained by a higher other-cause mortality. The results might also be explained by a different tumour behaviour or suboptimal treatment in elderly compared with the younger population. Keywords: Adolescents and young adults; Elderly; Extremities; Metastasis; Middle-aged; Recurrence; Soft tissue sarcoma; Survival.
  • Makhani, SS; Shively, D; Castro, G; de la Vega, PR; Barengo, NC (2021)
    Background: Multiple myeloma (MM) accounts for 10 % of all hematological malignancies. As recent advances in MM treatment continue to improve survival rates, socioeconomic barriers need to be identified to ensure equal treatment. This study evaluates the association between insurance status and survival in patients with MM. Methods: This study analyzed patients with MM from the 2007?2016 Surveillance, Epidemiology, and End Results (SEER) Program database. Insurance status was categorized as uninsured, Medicaid, private insurance, and other insurance. Cancer-specific survival was measured at one- and five-years post diagnosis. Results: From 2007?2016, there were 41,846 patients with MM extracted from the SEER database. Those with private insurance had a higher proportion of participants that identified as married (65.5 %), resided in metropolitan cities (90.1 %), and identified as white (76 %) and non-Hispanic (90.8 %). The uninsured group had the highest proportion of Black participants compared to other insurance groups (37.4 %). After adjustment for age, sex, race, ethnicity, marital status, and residence, the likelihood of five-year survival was significantly lower in those respondents with Medicaid (adjusted (adj) Hazard Ratio (HR): 1.44; 95 % Confidence Interval (CI): 1.36-1.53), when compared with private insurance holders. Those who were uninsured had a 26 % increased mortality hazard than those with private insurance (95 % CI 1.04-1.53). Conclusion: After adjustment, insurance status can influence the survival of adults with MM. As treatment modalities for MM continue to advance, the insurance status of a patient should not hinder their ability to receive the most effective and timely therapies.
  • Vered, Marilena; Lehtonen, Meri; Hotakainen, Lari; Pirila, Emma; Teppo, Susanna; Nyberg, Pia; Sormunen, Raija; Zlotogorski-Hurvitz, Ayelet; Salo, Tuula; Dayan, Dan (2015)
  • Irfan, Furqan B.; Consunji, Rafael I. G. D. J.; Peralta, Ruben; El-Menyar, Ayman; Dsouza, Landric B.; Al-Suwaidi, Jassim M.; Singh, Rajvir; Castren, Maaret; Djarv, Therese; Alinier, Guillaume (2022)
    Background Cardiac arrests in admitted hospital patients with trauma have not been described in the literature. We defined "in-hospital cardiac arrest of a trauma" (IHCAT) patient as "cessation of circulatory activity in a trauma patient confirmed by the absence of signs of circulation or abnormal cardiac arrest rhythm inside a hospital setting, which was not cardiac re-arrest." This study aimed to compare epidemiology, clinical presentation, and outcomes between in- and out-of-hospital arrest resuscitations in trauma patients in Qatar. It was conducted as a retrospective cohort study including IHCAT and out-of-hospital trauma cardiac arrest (OHTCA) patients from January 2010 to December 2015 utilizing data from the national trauma registry, the out-of-hospital cardiac arrest registry, and the national ambulance service database. Results There were 716 traumatic cardiac arrest patients in Qatar from 2010 to 2015. A total of 410 OHTCA and 199 IHCAT patients were included for analysis. The mean annual crude incidence of IHCAT was 2.0 per 100,000 population compared to 4.0 per 100,000 population for OHTCA. The univariate comparative analysis between IHCAT and OHTCA patients showed a significant difference between ethnicities (p=0.04). With the exception of head injury, IHCAT had a significantly higher proportion of localization of injuries to anatomical regions compared to OHTCA; spinal injury (OR 3.5, 95% CI 1.5-8.3, p
  • Kontio, R.; Hagström, J.; Lindholm, P.; Böhling, T.; Sampo, M.; Mesimäki, K.; Saarilahti, K.; Koivunen, P.; Mäkitie, A. A. (2019)
    Background: Osteosarcomas (OS) in the craniomaxillofacial (CMF) region are typically diagnosed at later age than long-bone OS, but they are reported to have better 5-year survival. Curative treatment warrants wide surgical resection, which is often not possible in the CMF region. The purpose of this article is to present a nationwide series of CMF in Finland to discuss the role of surgery. Patients and methods: All 21 CMF OS patients managed in Finland from 1992 to 2009 were included. The mean age was 40 years (range 15e72). Data on patient and tumor characteristics, treatment modalities, and survival were recorded. All patients had a minimum follow-up of 5 years or until death. Results: OS was evenly represented in the mandible and maxillary bones, which together constituted 76% of all sites. Surgery with curative intent was carried out in 20 patients. Clear margins were achieved in only five cases. Eight (40%) of these 20 patients died due to OS, and their average survival time was 1.3 years. Seven (35%) out of the 20 patients received radiotherapy due to close/intralesional surgical margins, and four of them did not develop recurrences during the follow-up. Conclusions: The results suggest that postoperative radiotherapy may alter the prognosis in CMF OS, particularly in cases with close or intralesional margins. This may increase the survival rates achieved by prompt action in performing radical surgery. (C) 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
  • Tarvasmäki, Tuukka; Lassus, Johan; Varpula, Marjut; Sionis, Alessandro; Sund, Reijo; Kober, Lars; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Cardoso, Jose Silva; Carubelli, Valentina; Di Somma, Salvatore; Mebazaa, Alexandre; Harjola, Veli-Pekka; CardShock Study Investigators (2016)
    Background: Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS. Methods: The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling. Results: Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan. Conclusion: Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.
  • Calabro, Lorenzo; Bougouin, Wulfran; Cariou, Alain; De Fazio, Chiara; Skrifvars, Markus; Soreide, Eldar; Creteur, Jacques; Kirkegaard, Hans; Legriel, Stephane; Lascarrou, Jean-Baptiste; Megarbane, Bruno; Deye, Nicolas; Taccone, Fabio Silvio (2019)
    Background Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).
  • Babini, Giovanni; Ristagno, Giuseppe; Boccardo, Antonio; De Giorgio, Daria; De Maglie, Marcella; Affatato, Roberta; Ceriani, Sabina; Zani, Davide; Novelli, Deborah; Staszewsky, Lidia; Masson, Serge; Pravettoni, Davide; Latini, Roberto; Belloli, Angelo; Scanziani, Eugenio; Skrifvars, Markus (2019)
    Aim of the study: To evaluate in an established porcine post cardiac arrest model the effect of a mild hypercapnic ventilatory strategy on outcome. Methods: The left anterior descending coronary artery was occluded in 14 pigs and ventricular fibrillation induced and left untreated for 12 min. Cardiopulmonary resuscitation was performed for 5 min prior to defibrillation. After resuscitation, pigs were assigned to either normocapnic (end-tidal carbon dioxide (EtCO2) target: 35-40 mmHg) or hypercapnic ventilation (EtCO2 45-50 mmHg). Hemodynamics was invasively measured and EtCO2 was monitored with an infrared capnometer. Blood gas analysis, serum neuron-specific enolase (NSE) and high sensitive cardiac troponin T (hs-cTnT) were assessed. Survival and functional recovery were evaluated up to 96 h. Results: Twelve pigs were successfully resuscitated and eight survived up to 96 h, with animals in the hypercapnic group showing trend towards a longer survival. EtCO2 and arterial partial pressure of CO2 were higher in the hypercapnic group compared to the normocapnic one (p <0.01), during the 4-hour intervention. Hypercapnia was associated with higher mean arterial pressure compared to normocapnia (p <0.05). No significant differences were observed in hs-cTnT and in NSE between groups, although the values tended to be lower in the hypercapnic one. Neuronal degeneration was lesser in the frontal cortex of hypercapnic animals compared to the normocapnic ones (p <0.05). Neurological recovery was equivalent in the two groups. Conclusion: Mild hypercapnia after resuscitation was associated with better arterial pressure and lesser neuronal degeneration in this model. Nevertheless, no corresponding improvements in neurological recovery were observed.
  • Salo, Silja A. S.; Ilonen, Ilkka; Laaksonen, Sanna; Myllarniemi, Marjukka; Salo, Jarmo A.; Rantanen, Tuomo (2017)
    Background: Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells in the peritoneum with poor prognosis. Earlier reports from other countries indicate an incidence of 0.2-3 new cases per million per year. No previous studies have examined the national epidemiology of MPeM in Nordic countries. This study aimed to clarify the epidemiology of MPeM in Finland over a 12-year period. Methods: The data consisted of cancer notifications, laboratory notifications, and death certificate information in the Finnish Cancer Registry (FCR) and Statistics Finland (SF) of all MPeM patients from 2000 to 2012 in Finland. We also collected data on occupational disease compensations from the Workers' Compensation Center (WCC) of Finland. Any missing information was collected from the respective patient's file of every patient obtained from health institutions that had treated the patients. Results: Between January 1, 2000 and December 31, 2012, 90 new MPeM cases (56 males, 34 females) occurred in Finland. Median annual incidence was four new cases, which corresponded to 0.74 new cases per million per year. MPeM was deemed an occupational disease in 21 patients (23.3%). 71 patients (78.9%) of whom had a known cause of death, with a median survival of 4 months. The number of deaths linked to other disease than mesothelioma was 28/74 (37.8%). Conclusions: Our study indicates that MPeM in Finland is rare and fatal, which is in accordance with previous reports from other countries. MPeM is also a fatal disease, since most of the patients died due to MPeM.
  • Lüthje, P.; Nurmi-Lüthje, Ilona; Tavast, N.; Villikka, A.; Kataja, M. (2021)
    Background Fracture liaison service (FLS) is a secondary prevention model for identification of patients at risk for fragility fractures. Aims This study was conducted to evaluate the number and costs of secondary prevention of low-energy fractures in the city of Kouvola in Finland. Methods Women aged >= 45 years and men >= 60 years treated in the emergency department with a low-energy fracture were identified. Laboratory testing, BMI, and DXA scans were performed. Fracture Risk Assessment Tool was used. The direct FLS costs were calculated. Survival was analyzed using univariate and multivariate analysis and the life-table method. Results 525 patients with 570 fractures were identified. The mean age of women was 73.8 years and of men 75.9 years. Most patients sustained wrist (31%), hip (21%) or proximal humerus (12%) fractures. 41.5% of the patients had osteoporosis according to DXA scans. 62% of patients used calcium and vitamin D daily and 38% started anti-osteoporotic medication. Protective factors for survival were: age <80 years, female sex, and S-25OHD concentration of 50-119 nmol/L. Excess mortality was highest among patients with a fracture of the femur. The total annual direct costs of FLS were 1.3% of the costs of all fractures. Discussion Many low-energy fracture types were associated with excess mortality. The use of anti-osteoporotic medication was not optimal. Conclusions FLS increased the catchment of low-energy fracture patients and was inexpensive. However, identification, evaluation and post-fracture assessment of patients should be expedited. Rehabilitation of hip fracture patients needs to be improved.
  • Fagerholm, Rainer; Faltinova, Maria; Aaltonen, Kirsi; Aittomaki, Kristiina; Heikkila, Paivi; Halttunen-Nieminen, Mervi; Nevanlinna, Heli; Blomqvist, Carl (2018)
    Long term use of postmenopausal hormone therapy (HT) has been reported to increase breast cancer risk. On the other hand, observational studies suggest that breast cancers diagnosed during HT may have a more favorable prognosis. While family history is a risk factor for breast cancer, and genetic factors also influence prognosis, the role of family history in combination with HT use has been little studied. We investigated the relationship between HT, family history, and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial breast cancer cases, using three survival end points: death from breast cancer (BCS), distant disease free survival (DDFS), and local recurrence free survival (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95% CI 0.41-0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40-0.85; p = 0.005), with a consistent but not statistically significant effect in LRFS. This effect was not seen in familial cases (HR > 1.0), and family history was found to interact with HT in BCS (p((interaction)) = 0.0067) (BC-death) and DDFS (p((interaction)) = 0.0070). There was phenotypic heterogeneity between HT-associated tumors in familial and non-familial cases, particularly on estrogen receptor (ER) status, although the interaction between HT and family history appears to be at least partially independent of these markers (p = 0.0370 after adjustment for standard prognostic factors). If confirmed by further studies, our results suggest that family history should be taken into consideration in clinical counseling before beginning a HT regimen.
  • Engström-Öst, Jonna; Barrett, Nick; Brutemark, Andreas; Vehmaa, Anu; Dwyer, Amanda; Almén, Anna-Karin; De Stasio, Bart T. (2017)
    Studying the responses of crustacean zooplankton to harmful algal blooms is important for understanding changes in lower food webs following eutrophication in the Laurentian Great Lakes and other regions around the world. Here we examine responses to toxic cyanobacteria by crustacean copepods of the genus Eurytemora from eutrophic coastal regions of Lake Michigan (Green Bay) and the Baltic Sea (Gulf of Finland). We measured grazing, survivorship, reproduction, and juvenile (nauplius) size in short-term laboratory experiments. Females were incubated with representative non-toxic food and mixtures of non-toxic food with either cyanobacteria or cyanobacteria filtrate. Eurytemora from both locations were affected negatively by cyanobacteria filtrates, even with non-toxic food available. Eurytemora carolleeae from Green Bay exhibited reduced grazing rates when exposed to filtrates, but this effect was not observed when animals were fed the cyanobacteria and filtrate along with non-toxic food. Eurytemora sp. from the Baltic Sea given filtrates and non-toxic food also exhibited decreased grazing rates, as well as decreased adult survival and nauplius size. Similarly, when cyanobacterial cells were included along with filtrate and non-toxic food these effects were not observed. Our results also demonstrated a significant trade-off between offspring quantity and quality for both groups of animals, being more pronounced when food quality was manipulated by the presence of cyanobacterial cells. These findings further our knowledge of how a widely distributed group like Eurytemora may respond in the face of changing local selection pressures from natural and anthropogenic stressors. (C) 2017 International Association for Great Lakes Research. Published by Elsevier B.V. All rights reserved.
  • Carpen, Timo; Sorsa, Timo; Jouhi, Lauri; Tervahartiala, Taina; Haglund, Caj; Syrjänen, Stina; Tarkkanen, Jussi; Mohamed, Hesham; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri S. (2019)
    Background An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. Materials and methods A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). Results High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. Conclusion Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
  • Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemstrom, Karl; Paavonen, Timo; Toppila-Salmi, Sanna (2016)
    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (aeyen80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.
  • Beilmann-Lehtonen, Ines; Hagström, Jaana; Mustonen, Harri K; Koskensalo, Selja; Böckelman, Camilla; Haglund, Caj (2021)
    Background: Colorectal cancer (CRC), the third most common cancer globally, caused 881,000 cancer deaths in 2018. Toll-like receptors (TLRs), the primary sensors of pathogen-associated molecular patterns and damage-associated molecular patterns, activate innate and adaptive immune systems and participate in the development of an inflammatory tumor microenvironment. We aimed to explore the prognostic value of TLR3, TLR5, TLR7, and TLR9 tissue expressions in CRC patients. Methods: Using immunohistochemistry, we analyzed tissue microarray samples from 825 CRC patients who underwent surgery between 1982 and 2002 at the Department of Surgery, Helsinki University Hospital, Finland. After analyzing a pilot series of 205 tissue samples, we included only TLR5 and TLR7 in the remainder of the patient series. We evaluated the associations between TLR5 and TLR7 tissue expressions, clinicopathologic variables, and survival. Using the Kaplan-Meier method, we generated survival curves, determining significance using the log-rank test. Univariate and multivariate survival analyses relied on the Cox proportional hazards model. Results: The 5-year disease-specific survival was 55.9% among TLR5-negative (95% confidence interval [CI] 50.6-61.2%) and 61.9% (95% CI 56.6-67.2%; p = 0.011, log-rank test) among TLR5-positive patients. In the Cox multivariate survival analysis adjusted for age, sex, stage, location, and grade, positive TLR5 immunoexpression (hazard ratio [HR] 0.74; 95% CI 0.59-0.92; p = 0.007) served as an independent positive prognostic factor. TLR7 immunoexpression exhibited no prognostic value in the survival analysis across the entire cohort (HR 0.97; 95% CI 0.78-1.20; p = 0.754) nor in subgroup analyses. Conclusions: We show for the first time that a high TLR5 tumor tissue expression associates with a better prognosis in CRC patients.
  • Paajanen, Juuso; Laaksonen, Sanna; Kettunen, Eeva; Ilonen, Ilkka; Vehmas, Tapio; Salo, Jarmo; Räsänen, Jari; Sutinen, Eva; Ollila, Hely; Mäyränpää, Mikko I.; Myllärniemi, Marjukka; Wolff, Henrik (2020)
    Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, where the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. In order to study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival over five years (long-term survivals [LTS]) and compared the findings with 84 tumors from a reference group with average survival (RG). We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34,90%) and a tubulopapillary growth pattern (n = 30,70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49,61%) and solid growth pattern (n = 59,70%) were more frequent in RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (p <0.001) and the presence of necrosis (p = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (p <0.001) and presence of exophytic polypoid growth (p = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.
  • Dyson, Kylie; Brown, Siobhan P.; May, Susanne; Smith, Karen; Koster, Rudolph W.; Beesems, Stefanie G.; Kuisma, Markku; Salo, Ari; Finn, Judith; Sterz, Fritz; Nuernberger, Alexander; Morrison, Laurie J.; Olasveengen, Theresa M.; Callaway, Clifton W.; Shin, Sang Do; Gräsner, Jan-Thorsten; Daya, Mohamud; Ma, Matthew Huei-Ming; Herlitz, Johan; Stromsöe, Anneli; Aufderheide, Tom P.; Masterson, Siobhan; Wang, Henry; Christenson, Jim; Stiell, Ian; Vilke, Gary M.; Idris, Ahamed; Nishiyama, Chika; Iwami, Taku; Nichol, Graham (2019)
    Introduction: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival. Methods: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n = 232). Results: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8%(range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85-0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival. Conclusions: The Utstein factors explained 51%. of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.