Browsing by Subject "TERM-FOLLOW-UP"

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  • Baron, Frederic; Galimard, Jacques-Emmanue; Labopin, Myriam; Yakoub-Agha, Ibrahim; Niittyvuopio, Riitta; Kroeger, Nicolaus; Griskevicius, Laimonas; Wu, Depei; Forcade, Edouard; Richard, Carlos; Aljurf, Mahmoud; Helbig, Grzegorz; Labussiere-Wallet, Helene; Mohty, Mohamad; Nagler, Arnon (2020)
    We compared severe graft-versus-host-disease GyHD) free and relapse-free survival and other transplantation outcomes of acute myeloid leukemia (AML) patients given bone marrow (BM) without and-thymocyte globulin (ATG) versus peripheral blood stem cells (PBSC) with ATG after myeloablative conditioning. In the cohort of patients receiving grafts from a human leukocyte antigen (HLA)-matched sibling donor, patients given PBSC with ATG (n=1,021) and those given BM without ATG (n=1,633) presented comparable severe GvHD-free relapse-free survival (GRSF)(hazard ratio [HR]=0.9, 95% confidence interval [CI]: 0.8-1.1, P=0.5) and overall survival (HR=1.0, 95% CI: 0.8-1.2, P=0.8). They had however, a lower incidence of chronic GvHD (cGvHD) (HR=0.7, 95% CI: 0.6-0.9, P=0.01). In the cohort of patients receiving grafts from HLA-matched unrelated donor , patients given PBSC with ATG (n=2,318) had better severe GvHD-free and relapse-free survival (GRFS) than those given BM without ATG (n=303) (HR=0.8, 95% CI: 0.6-0.9, P=0.001). They also had a lower incidence of cGvHD (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) and better overall survival (HR=0.8, 95% CI: 0.6-1.0, P=0.04). In summary, these data suggest that PBSC with ATG results in comparable (in the case of sibling donor) or significantly better (in the case of unrelated donor) severe GRFS than BM without ATG in patients with AML in complete remission receiving grafts after myeloablative conditioning.
  • Sarikaya, Hakan; da Costa, Bruno R.; Baumgartner, Ralf W.; Duclos, Kathleen; Touze, Emmanuel; de Bray, Jean M.; Metso, Antti; Metso, Tiina; Arnold, Marcel; Arauz, Antonio; Zwahlen, Marcel; Jueni, Peter (2013)
  • Bryk, Saara Susanna; Färkkilä, Anniina; Butzow, Ralf; Leminen, Arto; Johanna, Tapper; Heikinheimo, Markku; Unkila-Kallio, Leila; Riska, Annika (2016)
    Objective. Adult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence. Methods. We identified all patients diagnosed with AGCT during 1956-2014 in Helsinki University Hospital, with a minimum follow-up of one year (n = 240). After a histological review supplemented with FOXL2 (402C G) mutation status analysis, we analyzed the clinical data for association with relapse. Results. The final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5 years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4 years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3 years. Premenopausal status at initial diagnosis, FIGO stage Ic versus la, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGO' in a median time of 153 years. Conclusion. Tumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15 years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations. (C) 2016 Elsevier Inc. All rights reserved.
  • Seppänen, H.; Puolakkainen, P. (2020)
    Background: Acute pancreatitis is a common disease, the incidence of which is 75-100/100,000/year in Finland. The worldwide incidence of acute pancreatitis is increasing. The identified mildcases usually show rapid recovery with conservative treatment allowing early discharge. Severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. The revised Atlanta classification of acute pancreatitis was introduced in 2012-2013. A recurrent acute pancreatitis is defined as two or more well-documented separate attacks of acute pancreatitis with complete resolution in between. Alcoholic pancreatitis is the most common recurrent acute pancreatitis type. Methods: In this review current severity classifications and literature on the prevention of recurrent acute pancreatitis are analyzed. Results: The severity of the disease is classified as mild, moderately severe, and severe acute pancreatitis. Novel entities include acute peripancreatic fluid collections in mild acute pancreatitis and acute necrotic collections in necrotizing acute pancreatitis lesser than 4 weeks after the onset and pancreatic pseudocyst in mild acute pancreatitis and walled-off necrosis in necrotizing acute pancreatitis more than 4 weeks after the onset of the disease. After the first attack of alcohol-induced acute pancreatitis, 46% of the patients develop at least one recurrence within 10- to 20-year follow-up. With repeated intervention against alcohol consumption, it is possible to reduce the recurrences. Removing the gall bladder after biliary pancreatitis is the key preventing recurrences. In mild cases, even during the index admission; in severe cases, it is recommended to wait until the inflammatory changes have resolved. Of total, 59% of the idiopathic pancreatitis had sludge of stones in the gall bladder. In other etiologies, addressing the etiological factor may prevent recurrent acute pancreatitis. Conclusions: This review describes current use of novel severity classifications and also different possibilities to prevent recurrent acute pancreatitis with different etiologies including idiopathic.
  • Friedmacher, Florian; Pakarinen, Mikko P.; Rintala, Risto J. (2018)
    Despite a growing interest to clinicians and scientists, there is no comprehensive study that examines the global research activity on congenital diaphragmatic hernia (CDH). A search strategy for the Web of Science (TM) database was designed to identify scientific CDH publications. Research output of countries, institutions, individual authors, and collaborative networks was analyzed. Semi-qualitative research measures including citation rate and h-index were assessed. Choropleth mapping and network diagrams were employed to visualize results. A total of 3669 publications were found, originating from 76 countries. The largest number was published by the USA (n = 1250), the UK (n = 279), and Canada (n = 215). The USA combined the highest number of cooperation articles (n = 152), followed by Belgium (n = 115) and the Netherlands (n = 93). The most productive collaborative networks were established between UK/Belgium (n = 53), Belgium/Spain (n = 47), and UK/Spain (n = 34). Canadian publications received the highest average citation rate (22.8), whereas the USA had the highest country-specific h-index (72). Eighty-five (2.3%) articles were published by international multicenter consortiums and national research networks. The most productive institutions and authors were based in North America and Europe. Over the past decades, CDH research has increasingly become multidisciplinary and numerous innovative therapeutic strategies were introduced. CDH-related research has constantly been progressing, involving today many disciplines with main research endeavors concentrating in a few high-income countries. Recent advances in prenatal interventions and regenerative medicine therapy hold the promise of improving CDH outcome in the 21st century. International collaborations and translational research should be strengthened to allow further evolution in this field.
  • Koenig, J.; Siebenhaar, A.; Hoegenauer, C.; Arkkila, P.; Nieuwdorp, M.; Noren, T.; Ponsioen, C. Y.; Rosien, U.; Rossen, N. G.; Satokari, R.; Stallmach, A.; de Vos, W.; Keller, J.; Brummer, R. J. (2017)
    Background Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. Aim To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. Methods Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. Results Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. Conclusions Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
  • Enders, Felicitas Bellutti; Bader-Meunier, Brigitte; Baildam, Eileen; Constantin, Tamas; Dolezalova, Pavia; Feldman, Brian M.; Lahdenne, Pekka; Magnusson, Bo; Nistala, Kiran; Ozen, Seza; Pilkington, Clarissa; Ravelli, Angelo; Russo, Ricardo; Uziel, Yosef; van Brussel, Marco; van der Net, Janjaap; Vastert, Sebastiaan; Wedderburn, Lucy R.; Wulffraat, Nicolaas; McCann, Liza J.; van Royen-Kerkhof, Annet (2017)
    Background In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile dermatomyositis (JDM) is a rare disease within the group of paediatric rheumatic diseases (PRDs) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. Consequently, treatment regimens differ throughout Europe. Objectives To provide recommendations for diagnosis and treatment of JDM. Methods Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was constituted, consisting of 19 experienced paediatric rheumatologists and 2 experts in paediatric exercise physiology and physical therapy, mainly from Europe. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using nominal group technique. Recommendations were accepted if > 80% agreement was reached. Results In total, 7 overarching principles, 33 recommendations on diagnosis and 19 recommendations on therapy were accepted with > 80% agreement among experts. Topics covered include assessment of skin, muscle and major organ involvement and suggested treatment pathways. Conclusions The SHARE initiative aims to identify best practices for treatment of patients suffering from PRD. Within this remit, recommendations for the diagnosis and treatment of JDM have been formulated by an evidenceinformed consensus process to produce a standard of care for patients with JDM throughout Europe.
  • Lim, Soo; Taskinen, Marja-Riitta; Boren, Jan (2019)
    Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed.
  • Taskinen, Seppo; Suominen, Janne; Mäkelä, Eija (2020)
    OBJECTIVE To evaluate to what extend urinary continence develops during puberty in patients with classic bladder exstrophy (CBE) and epispadias. METHODS The operative database was reviewed for surgical procedures and urinary continence in all 65 CBE and epispadias patients born in 1976-2005. Excluded were 2 patients who had insufficient data for evaluation. RESULTS Thirty-five patients with volitional voiding were incontinent at the age of 10 years, 27 had daily incontinence, and 8 had rare incontinence. Sixteen patients (46%) became later fully continent without any major surgery (except Deflux injections in 3 patients) or CIC treatment. Among these 16 fully continent patients there were 7/8 with rare incontinence, 9/23 with daily incontinence (P = .04); 3/9 males with CBE, 10/13 males with epispadias, 3/5 females with CBE, and 0/4 females with epispadias (P = .25 between sex and P =.48 between diagnosis). Of the 15 patients remaining incontinent, 10 had daily and 5 had rare incontinence episodes. The latest control was at the median age of 19 years (interquartile range 17-21 years). Twenty-five patients (40% of the whole material) were fully continent (11/38 (29%) with CBE and 14/25 (56%) with epispadias, P =.04) and 8 (13%) had rare incontinence with volitional voiding (1/38 [3%] with CBE and 7/25 [28%] with epispadias). CONCLUSION Almost half of the incontinent CBE and epispadias patients with volitional voiding achieved continence after the age of 10 without major surgery. Prognosis for pubertal development of continence was best in patients with rare incontinence and in males with epispadias. UROLOGY 144: 194-197, 2020. (c) 2020 Elsevier Inc.
  • Cammarota, Giovanni; Ianiro, Gianluca; Tilg, Herbert; Rajilic-Stojanovic, Mirjana; Kump, Patrizia; Satokari, Reetta; Sokol, Harry; Arkkila, Perttu; Pintus, Cristina; Hart, Ailsa; Segal, Jonathan; Aloi, Marina; Masucci, Luca; Molinaro, Antonio; Scaldaferri, Franco; Gasbarrini, Giovanni; Lopez-Sanroman, Antonio; Link, Alexander; De Groot, Pieter; de Vos, Willem M.; Hoegenauer, Christoph; Malfertheiner, Peter; Mattila, Eero; Milosavljevic, Tomica; Nieuwdorp, Max; Sanguinetti, Maurizio; Simren, Magnus; Gasbarrini, Antonio; European FMT Working Grp (2017)
    Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
  • Fokkens, Wytske J.; Lund, Valerie J.; Hopkins, Claire; Hellings, Peter W.; Kern, Robert; Reitsma, Sietze; Toppila-Salmi, Sanna; Bernal-Sprekelsen, Manuel; Mullol, Joaquim; Alobid, Isam; Anselmo-Lima, Wilma Terezinha; Bachert, Claus; Baroody, Fuad; von Buchwald, Christian; Cervin, Anders; Cohen, Noam; Constantinidis, Jannis; De Gabory, Ludovic; Desrosiers, Martin; Diamant, Zuzana; Douglas, Richard G.; Gevaert, Philippe H.; Hafner, Anita; Harvey, Richard J.; Joos, Guy F.; Kalogjera, Livije; Knill, Andrew; Kocks, Janwillem H.; Landis, Basile N.; Limpens, Jacqueline; Lebeer, Sarah; Lourenco, Olga; Matricardi, Paolo M.; Meco, Cem; O'Mahony, Liam; Philpott, Carl M.; Ryan, Dermot; Schlosser, Rodney; Senior, Brent; Smith, Timothy L.; Teeling, Thijs; Tomazic, Peter Valentin; Wang, De Yun; Wang, Dehui; Zhang, Luo; Agius, Adrian M.; Ahlstrom-Emanuelsson, Cecilia; Alabri, Rashid; Albu, Silviu; Alhabash, Saied; Aleksic, Aleksandra; Aloulah, Mohammad; Al-Qudah, Mohannad; Alsaleh, Saad; Baban, Muaid Aziz; Baudoin, Tomislav; Balvers, Tijmen; Battaglia, Paolo; Bedoya, Juan David; Beule, Achim; Bofares, Khaled M.; Braverman, Itzhak; Brozek-Madry, Eliza; Byaruhanga, Richard; Callejas, Claudio; Carrie, Sean; Caulley, Lisa; Chussi, Desderius; de Corso, Eugenio; Coste, Andre; El Hadi, Usama; Elfarouk, Ahmed; Eloy, Philippe H.; Farrokhi, Shokrollah; Felisati, Giovanni; Ferrari, Michel D.; Fishchuk, Roman; Grayson, Jessica W.; Goncalves, Paulo M.; Grdinic, Boris; Grgic, Velimir; Hamizan, Aneeza W.; Heinichen, Julio V.; Husain, Salina; Ping, Tang Ing; Ivaska, Justinas; Jakimovska, Frodita; Jovancevic, Ljiljana; Kakande, Emily; Kamel, Reda; Karpischenko, Sergei; Kariyawasam, Harsha H.; Kawauchi, Hideyuki; Kjeldsen, Anette; Klimek, Ludger; Krzeski, Antoni; Barsova, Gabriela Kopacheva; Kim, Sung Wam; Lal, Devyani; Letort, Jose J.; Lopatin, Andrey; Mahdjoubi, Abdelhak; Mesbahi, Alireza; Netkovski, Jane; Tshipukane, Dieudonne Nyenbue; Obando-Valverde, Andres; Okano, Mitsuhiro; Onerci, Metin; Ong, Yew Kwang; Orlandi, Richard; Otori, Nobuyoshi; Ouennoughy, Kheir; Ozkan, Muge; Peric, Aleksandar; Plzak, Jan; Prokopakis, Emmanuel; Prepageran, Nerayanan; Psaltis, Alkis; Pugin, Benoit; Raftopulos, Marco; Rombaux, Philippe; Riechelmann, Herbert; Sahtout, Semia; Sarafoleanu, Caius-Codrut; Searyoh, Kafui; Rhee, Chae-Seo; Shi, Jianbo; Shkoukani, Mahdi; Shukuryan, Arthur K.; Sicak, Marian; Smyth, David; Snidvongs, Kornkiat; Kosak, Tanja Soklic; Stjarne, Par; Sutikno, Budi; Steinsvag, Sverre; Tantilipikorn, Pongsakorn; Thanaviratananich, Sanguansak; Thuy Tran,; Urbancic, Jure; Valiulis, Arunas; de Aparicio, Carolina Vasquez; Vicheva, Dilyana; Virkkula, Paula M.; Vicente, Gil; Voegels, Richard; Wagenmann, Martin; Wardani, Retno S.; Welge-Lussen, Antje; Witterick, Ian; Wright, Erin; Zabolotniy, Dmytro; Zsolt, Bella; Zwetsloot, Casper P. (2020)
    The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.
  • Rossen, Noortje G.; MacDonald, John K.; de Vries, Elisabeth M.; D'Haens, Geert R.; de Vos, Willem M.; Zoetendal, Erwin G.; Ponsioen, Cyriel Y. (2015)
    AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. RESULTS: We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome.
  • Arbyn, Marc; Redman, Charles W. E.; Verdoodt, Freija; Kyrgiou, Maria; Tzafetas, Menelaos; Ghaem-Maghami, Sadaf; Petry, Karl-Ulrich; Leeson, Simon; Bergeron, Christine; Nieminen, Pekka; Gondry, Jean; Reich, Olaf; Moss, Esther L. (2017)
    Background Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. Methods We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. Findings 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23.1% (95% CI 20.4-25.9) overall and varied by treatment procedure (ranging from 17.8% [12.9-23.2] for laser conisation to 25.9% [22.3-29.6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6.6% (95% CI 4.9-8.4) and was increased with positive compared with negative resection margins (relative risk 4.8, 95% CI 3.2-7.2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55.8% (95% CI 45.8-65.5) and 84.4% (79.5-88.4), respectively, for the margin status, and 91.0% (82.3-95.5) and 83.8% (77.7-88.7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0.8%, whereas this risk was 3.7% when margins were free. Interpretation The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status.
  • Siironen, Päivi; Hagstrom, Jaana; Maenpaa, Hanna O.; Louhimo, Johanna; Arola, Johanna; Haglund, Caj (2016)
    Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n = 54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p = 0.004), lymph node metastases (p <0.001), distant metastases (p <0.001), stage (p <0.001), and elevated postoperative calcitonin (p <0.001) significantly associated with survival. Conclusions Lymph node metastasis and elevated postoperative calcitonin are important prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis.
  • Kyrklund, Kristiina; Pakarinen, Mikko P.; Rintala, Risto J. (2017)
    Aims: To compare anorectal manometry (AM) in patients with different types of anorectal malformations (ARMs) in relation to functional outcomes. Methods: A single-institution, cross-sectional study. After ethical approval, all patients >= 7 years old treated for anterior anus (AA), perineal fistula (PF), vestibular fistula (VF), or rectourethral fistula (RUF) from 1983 onwards were invited to answer the Rintala bowel function score (BFS) questionnaire and to attend anorectal manometry (AM). Patients with mild ARMs (AA females and PF males) had been treated with minimally invasive perineal procedures. Females with VF/PF and males with RUF had undergone internal-sphincter saving sagittal repairs. Results: 55 of 132 respondents (42%; median age 12 (7-29) years; 42% male) underwent AM. Patients with mild ARMs displayed good anorectal function after minimally invasive treatments. The median anal resting and squeeze pressures among patients with mild ARMs(60 cm H2O and 116 cm H2O respectively) were significantly higher than among patients with more severe ARMs (50 cm H2O, and 80 cm H2O respectively; p Conclusions: Our findings support the appropriateness of our minimally invasive approaches to the management of mild ARMs, and IAS-saving anatomical repairs for patients with more severe malformations. (C) 2017 Elsevier Inc. All rights reserved.
  • Saraceni, Francesco; Labopin, Myriam; Gorin, Norbert-Claude; Blaise, Didier; Tabrizi, Reza; Volin, Liisa; Cornelissen, Jan; Cahn, Jean-Yves; Chevallier, Patrice; Craddock, Charles; Wu, Depei; Huynh, Anne; Arcese, William; Mohty, Mohamad; Nagler, Arnon (2016)
    Background: Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT), especially mismatched UD-HSCT. Methods: We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT) or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT) to autologous transplantation in patients with AML in first complete remission (CR1). A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups. Results: Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, rho = 0.0016). Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, rho = 0.2). Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, rho = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, rho = 0.49). Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, rho = 0.049), while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, rho = 0.88). In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively. Conclusions: Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML.
  • Dang, Kien Xuan; Ho, Tho; Sistonen, Saara; Koivusalo, Antti; Pakarinen, Mikko; Rintala, Risto; Stenman, Ulf-Hakan; Orpana, Arto; Stenman, Jakob (2018)
    Background Previous studies have reported an association among esophageal atresia (EA), Barrett's esophagus, and esophageal adenocarcinoma later in life. Objective The objective of the article is to evaluate KRAS and BRAF mutations as potential genetic markers for early detection of malignant transformation, we used an ultrasensitive technique to detect tissue expression of KRAS and BRAF mutations in endoscopic biopsies from 61 adult patients under follow-up after treatment for EA. Materials and Methods RNA was extracted from 112 fresh-frozen endoscopic tissue biopsies from 61 adult patients treated for EA in early childhood. RNA was reverse transcribed using the extendable blocking probe reverse transcription method. KRAS codons 12 and 13, as well as BRAF mutations were detected by quantitative polymerase chain reaction. Results No mutations of KRAS codon 12, KRAS codon 13, or BRAF were found in 112 endoscopic biopsy samples from 61 patients. Conclusion Despite the presence of histological findings indicating long-standing gastroesophageal reflux in 25%, as well as symptomatic gastroesophageal reflux in more than 40%, there was no detectable tissue expression of KRAS or BRAF mutations in this cohort of patients.
  • Holmer, Magnus; Melum, Espen; Isoniemi, Helena; Ericzon, Bo-Göran; Castedal, Maria; Nordin, Arno; Schultz, Nicolai Aagaard; Rasmussen, Allan; Line, Pal-Dag; Stål, Per; Bennet, William; Hagström, Hannes (2018)
    Background & Aims Nonalcoholic fatty liver disease(NAFLD) is the second most common cause of liver transplantation in the US. Data on NAFLD as a liver transplantation indication from countries with lower prevalences of obesity are lacking. We studied the temporal trends of NAFLD as an indication for liver transplantation in the Nordic countries, and compared outcomes for patients with NAFLD to patients with other indications for liver transplantation. MethodResultsPopulation-based cohort study using data from the Nordic Liver Transplant Registry on adults listed for liver transplantation between 1994 and 2015. NAFLD as the underlying indication for liver transplantation was defined as a listing diagnosis of NAFLD/nonalcoholic steatohepatitis, or cryptogenic cirrhosis with a body mass index 25kg/m(2) and absence of other liver diseases. Waiting time for liver transplantation, mortality and withdrawal from the transplant waiting list were registered. Survival after liver transplantation was calculated using multivariable Cox regression, adjusted for age, sex, body mass index and model for end-stage liver disease. A total of 4609 patients listed for liver transplantation were included. NAFLD as the underlying indication for liver transplantation increased from 2.0% in 1994-1995 to 6.2% in 2011-2015 (P=.01) and was the second most rapidly increasing indication. NAFLD patients had higher age, model for end-stage liver disease and body mass index when listed for liver transplantation, but overall survival after liver transplantation was comparable to non--NAFLD patients (aHR 1.03, 95% CI 0.70-1.53 P=.87). ConclusionNAFLD is an increasing indication for liver transplantation in the Nordic countries. Despite more advanced liver disease, NAFLD patients have a comparable survival to other patients listed for liver transplantation.
  • Wickberg, Asa; Liljegren, Goran; Killander, Fredrika; Lindman, Henrik; Bjöhle, Judith; Carlberg, Michael; Blomqvist, Carl; Ahlgren, Johan; Villman, Kenneth (2018)
    Purpose: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and Methods: Eligibility criteria were: consecutive patients with age >= 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. Results: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). Conclusion: BCS and ET without RT seem to be a safe treatment option in women >= 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.