| 1. |
- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Journal article (peer-reviewed)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 2. |
- Landén, Mikael, 1966, et al.
(author)
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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
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Journal article (peer-reviewed)abstract
- Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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| 3. |
- Akouri, Randa R., et al.
(author)
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First live birth after uterus transplantation in the Middle East
- 2020
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In: Middle East Fertility Society Journal. - : Springer Science and Business Media LLC. - 1110-5690 .- 2090-3251. ; 25:1
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Journal article (peer-reviewed)abstract
- Background The first live birth after uterus transplantation took place in Sweden in 2014. It was the first ever cure for absolute uterine factor infertility. We report the surgery, assisted reproduction, and pregnancy behind the first live birth after uterus transplantation in the Middle East, North Africa, and Turkey (MENAT) region. A 24-year old woman with congenital absence of the uterus underwent transplantation of the uterus donated by her 50-year-old multiparous mother. In vitro fertilization was performed to cryopreserve embryos. Both graft retrieval and transplantation were performed by laparotomy. Donor surgery included isolation of the uterus, together with major uterine arteries and veins on segments of the internal iliac vessels bilaterally, the round ligaments, and the sacrouterine ligaments, as well as with bladder peritoneum. Recipient surgery included preparation of the vaginal vault, end-to-side anastomosis to the external iliac arteries and veins on each side, and then fixation of the uterus. Results One in vitro fertilization cycle prior to transplantation resulted in 11 cryopreserved embryos. Surgical time of the donor was 608 min, and blood loss was 900 mL. Cold ischemia time was 85 min. Recipient surgical time was 363 min, and blood loss was 700 mL. Anastomosis time was 105 min. Hospital stay was 7 days for both patients. Ten months after the transplantation, one previously cryopreserved blastocyst was transferred which resulted in viable pregnancy, which proceeded normally (except for one episode of minor vaginal bleeding in the 1st trimester) until cesarean section at 35 + 1 weeks due to premature contractions and shortened cervix. A healthy girl (Apgar 9-10-10) weighing 2620 g was born in January 2020, and her development has been normal during the first 6 months. Conclusions This is the first report of a healthy live birth after uterus transplantation in the MENAT region. We hope that this will motivate further progress and additional clinical trials in this area in the Middle East Region, where the first uterus transplantation attempt ever, however unsuccessful, was performed already three decades ago.
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| 4. |
- Brucker, S. Y., et al.
(author)
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Living-Donor Uterus Transplantation: Pre-, Intra-, and Postoperative Parameters Relevant to Surgical Success, Pregnancy, and Obstetrics with Live Births
- 2020
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:8
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Journal article (peer-reviewed)abstract
- Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS.
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| 5. |
- Dahm-Kähler, Pernilla, 1964, et al.
(author)
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Centralized primary care of advanced ovarian cancer improves complete cytoreduction and survival - A population-based cohort study
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 142:2, s. 211-216
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Journal article (peer-reviewed)abstract
- Objective. To evaluate centralized primary care of advanced ovarian and fallopian tube cancers in a complete population cohort in relation to complete cytoreduction, time interval from surgery to chemotherapy and relative survival. Methods. A regional population-based cohort study of women diagnosed with primary ovarian and fallopian tube cancers and included in the Swedish Quality Registry (SQR) during 2008-2013 in a region where primary care of advanced stages was centralized in 2011. Surgical, oncological characteristics, outcomes, follow-ups and relative survivals were analyzed. Results. There were 817 women diagnosed with ovarian and fallopian tube cancers during 2008-2013 and 523 were classified as FIGO stage III-IV and further analyzed. Primary debulking surgery (PDS) was performed in 81% and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in 11%. Complete cytoreduction at PDS was performed in 37% before compared to 49% after centralization (p < 0.03). The chemotherapy protocols were identical in the cohorts and they received and completed the planned chemotherapy equally. The time interval between PDS and chemotherapy was 36 days (median) before compared to 24 days after centralization (p < 0.01). The relative 3-year survival rate in women treated by PDS was 44% compared to 65% after centralization and the estimated excess mortality rate ratio (EMRR) was reduced (RR 0.58; 95% CI 0.42-0.79). Comparing the complete cohorts before and after centralization, regardless primary treatment, the relative 3-year survival rate increased from 40% to 61% with reduced EMRR (RR 0.59; 95% CI 0.45-0.76). Conclusion. Centralized primary care of advanced ovarian and fallopian tube cancers increases complete cytoreduction, decreases time interval from PDS to chemotherapy and improves relative survival significantly. (C) 2016 Elsevier Inc. All rights reserved.
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| 6. |
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| 7. |
- Rosenberg, P., et al.
(author)
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Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study
- 2018
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 57:3, s. 346-353
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Journal article (peer-reviewed)abstract
- Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson's correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson's correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.
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| 8. |
- Stålberg, Karin, et al.
(author)
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Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study - On behalf of the Swedish Gynecological Cancer Group
- 2017
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:12, s. 2693-2700
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Journal article (peer-reviewed)abstract
- The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI50% (risk ratio [RR]=4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. What's new? Whether lymphadenectomy is beneficial for women with endometrial cancer remains uncertain. Moreover, additional studies are needed to explore factors that reliably predict lymph node metastasis (LNM). Here, multiple factors, including tumor histology, grade of differentiation and DNA aneuploidy, were evaluated for associations with LNM risk in women with endometrial cancer and verified lymph node status. Most significantly, deep myometrial invasion in tumors increased LNM risk fourfold, whereas DNA ploidy had essentially no impact on LNM risk. The findings confirm the predictive relevance of myometrial invasion, histology and grade reported in previous single-center and multicenter studies.
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| 9. |
- Alfonzo, Emilia, et al.
(author)
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No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study
- 2019
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 116, s. 169-177
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Journal article (peer-reviewed)abstract
- Purpose: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. Patients and methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. Results: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50–2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66–1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. Conclusion: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery. © 2019 The Authors
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| 10. |
- Andreou, Dimitrios, et al.
(author)
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Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers
- 2011
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:9, s. 700-704
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Journal article (peer-reviewed)abstract
- The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n=132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.
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| 11. |
- Ayoubi, J. M., et al.
(author)
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Evolving clinical challenges in uterus transplantation
- 2022
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In: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483. ; 45:5, s. 947-960
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Research review (peer-reviewed)abstract
- Before the first live birth following uterus transplantation (UTx) in 2014, the 1–2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.
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| 12. |
- Dahm-Kähler, Pernilla, 1964, et al.
(author)
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Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG)
- 2017
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 144:1, s. 167-173
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Journal article (peer-reviewed)abstract
- Objective. The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Methods. Nation-wide population-based study of women 18 years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Results. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulldng surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Conclusion. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. (C) 2016 Elsevier Inc. All rights reserved.
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| 13. |
- Deans, R., et al.
(author)
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The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration
- 2023
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In: Australian & New Zealand Journal of Obstetrics & Gynaecology. - 0004-8666.
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Journal article (peer-reviewed)abstract
- AimsThe aim is to report the results of Australia's first uterus transplantation (UTx). MethodsFollowing long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. ResultsThis is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. ConclusionTwenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.
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| 14. |
- Enskog, Anders, et al.
(author)
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Uterus transplantation in the baboon: methodology and long-term function after auto-transplantation.
- 2010
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In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:8, s. 1980-7
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Journal article (peer-reviewed)abstract
- Techniques for uterus transplantation (UTx) have been developed in rodent/domestic animals towards future clinical introduction of UTx to treat uterine factor infertility. The aim of this study was to extend the UTx research into a non-human primate species by developing surgical techniques for uterus retrieval and transplantation in the baboon.
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| 15. |
- Johannesson, Liza, 1976, et al.
(author)
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Uterus transplantation in a non-human primate: long-term follow-up after autologous transplantation.
- 2012
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In: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 27:6, s. 1640-8
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Journal article (peer-reviewed)abstract
- BACKGROUND Uterus transplantation (UTx) may provide the first available treatment for women affected by uterine infertility. The present study aimed to further develop a surgical technique for autologous UTx in a non-human primate species and to assess long-term function. METHODS Female baboons (n= 16) underwent autologous transplantation of the uterus with the Fallopian tubes and ovaries, performed with a previously published surgical technique (n= 6, Group 1) or using a modified technique (n= 10; Group 2). The uterine arteries were dissected to the proximal end of the anterior branch (Group 1) or the entire (Group 2) internal iliac artery, and the ovarian veins were dissected to the crossing over the ureter (Group 1) or further cranially to include greater lengths and patches of the cava/renal vein (Group 2). Back-table preparation created common venous and arterial ends with arterial anastomosis either end-to-side to the left external iliac artery (Group 1) or end-to-end to the left internal iliac artery (Group 2). RESULTS Overall short-time survival of the animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity. Regular menstruation after UTx was demonstrated only in Group 2 (60%). Menstruating animals (n= 6) were each exposed to timed mating for ≥5 menstrual cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in post-mortem analysis. CONCLUSIONS The modified UTx model of Group 2 is a safe procedure and shows resumed long-term uterine function in a majority of the animals, although pregnancy could not be demonstrated.
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| 16. |
- Johansen, G., et al.
(author)
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A Swedish Nationwide prospective study of oncological and reproductive outcome following fertility-sparing surgery for treatment of early stage epithelial ovarian cancer in young women
- 2020
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Epithelial ovarian cancer (EOC) is rare in women of reproductive age and fertility-sparing surgery (FSS) may be applied in early stages. The purpose of this study was to investigate the safety and efficacy of FSS for treatment of EOC. Methods: The Swedish nationwide population-based Quality Register for Gynecological Cancer was used to identify all women 18–40 years of age diagnosed with stage I EOC between 2008 and 2015. Detailed data on surgery, staging, histopathology, and follow-up were extracted and reviewed. Cross-linking of individuals to population-based registries allowed retrieval of data on obstetrical and reproductive outcomes after FSS. Disease-free survival (DFS) and overall survival (OS) rates were compared (Kaplan-Meier method) between women who underwent FSS vs. radical surgery (RS). Results: In total 83 women were identified; 36 who had FSS performed and 47 RS. The 5-year OS rate was 92% and no statistical differences between DFS or OS were found between women treated by FSS or RS. The recurrence rate after RS was 13% compared to 6% after FSS. Recurrences were more frequently found in women with stage IC tumor or with histologic subtypes with more aggressive behavior. In the FSS cohort, nine women gave birth to 12 healthy children, all delivered at fullterm. Only one women had received assisted reproductive technology treatment. Conclusion: In this nationwide population-based cohort study natural fertility was maintained after FSS. Specific histologic subtypes showed greater prognostic impact on the oncological outcome than the use of FSS. Recurrences occurred after FSS, but none in the uterus, which questions the need of hysterectomy in young women with EOC. Trial registration: This article reports the results of a healthcare intervention using the data prospectively registered in the Swedish population-based registries including the Quality Register for Gynecological Cancer, the National Death Register, the Swedish Medical Birth Register, and the National Quality Register for Assisted Reproduction. © 2020, The Author(s).
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| 17. |
- Johansen, G., et al.
(author)
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Fertility-sparing surgery for treatment of non-epithelial ovarian cancer: Oncological and reproductive outcomes in a prospective nationwide population-based cohort study
- 2019
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 155:2, s. 287-293
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Journal article (peer-reviewed)abstract
- Objective: To compare the oncologic outcome of women who underwent fertility-sparing surgery (FSS) vs. radical surgery (RS) for treatment of NEOC in a prospective, nationwide, population-based study and report on the reproductive outcomes in women after FSS. Methods: Using the Swedish Quality Register for Gynecological Cancer, we identified all women ages 18–40 treated with either FSS or RS for stage I NEOC between 2008 and 2015. Progression-free survival (PFS) and overall survival (OS) rates were compared using the Kaplan-Meier method. Data on use of assisted reproductive technology (ART) treatments and obstetrical outcomes after FSS were extracted from the National Quality Register for Assisted Reproduction (Q-IVF) and the Swedish Medical Birth Register. Results: During the study period, 73 women ages 18–40 received a stage I NEOC diagnosis. The majority, 78% (n = 57), underwent FSS. The 5-year OS rate, regardless of surgical approach, was 98%. There were no statistical differences between OS and PFS rates in women treated with FSS, compared to RS. Recurrences were more common after RS than FSS: 12.5% (2/16) vs. 3.5% (2/57), respectively. Following FSS, 11 women gave birth to 13 healthy children (all conceived naturally). Additionally, 12% of the women in the cohort developed infertility and received ART treatment (n = 7). Conclusion: FSS is not associated with worse oncologic outcomes than RS in young women with early stage NEOC. The prognosis was excellent in both groups, with an OS of 98%. Natural fertility was maintained in women treated with FSS, only 12% required ART treatment. © 2019
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| 18. |
- Johansen, G., et al.
(author)
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Reproductive and obstetrical outcomes with the overall survival of fertile-age women treated with fertility-sparing surgery for borderline ovarian tumors in Sweden: a prospective nationwide population-based study
- 2021
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 115:1, s. 157-163
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Journal article (peer-reviewed)abstract
- Objective: To assess the efficacy of fertility-sparing surgery (FSS) in terms of reproductive outcomes by following FSS for borderline ovarian tumors (BOTs) and comparing the safety of FSS versus radical surgery (RS). Design: Nationwide cohort study based on prospectively recorded data. Setting: Sweden. Patient (s): All women of reproductive age (18–40 years) treated in Sweden for stage I BOT with the use of FSS or RS from 2008 to 2015, identified in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Interventions (s): FSS or RS. Main Outcome Measure (s): Reproductive outcomes: natural conception, use of assisted reproductive technology (ART), live birth and obstetrical outcomes. Safety outcome: overall survival (OS) rates, comparing women undergoing FSS versus RS. The FSS cohort was linked to the Swedish Medical Birth Register to identify all women who had given birth after FSS and to obtain detailed obstetrical data. For information on ART treatment, the National Quality Registry for Assisted Reproduction was consulted. OS rate comparisons were conducted by means of Kaplan-Meier estimates. Result (s): Of the 277 women with BOTs, 213 (77%) underwent FSS, 183 (86%) unilateral salpingo-oophorectomy, and 30 (14%) cystectomy. Following FSS, 50 women gave birth to 62 healthy children, 8% of which were preterm. Only 20 (9%) of the women underwent ART treatment. OS was similar in women treated with FSS and RS. Conclusion (s): Natural fertility was maintained after FSS; only 9% required ART treatment. FSS was also deemed to be equivalent to RS regarding survival outcome. © 2020 The Authors
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| 19. |
- Jonsdottir, Björg, et al.
(author)
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Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer—A Swedish Gynecologic Cancer Group (SweGCG) study
- 2021
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:8, s. 1526-1533
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Journal article (peer-reviewed)abstract
- Introduction: Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice. Material and methods: This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I-III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard. Results: In the study population of 1401 women, 32% (n=448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively. Conclusions: In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI. © 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG)
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| 20. |
- Karam, Elias, et al.
(author)
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Outcomes of rescue procedures in the management of locally recurrent ampullary tumors : A Pancreas 2000/EPC study
- 2023
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In: Surgery (United States). - : Elsevier BV. - 0039-6060. ; 173:5, s. 1254-1262
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Journal article (peer-reviewed)abstract
- Background: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. Methods: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. Results: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. Conclusion: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.
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| 21. |
- Karlsson, Anna, 1985-, et al.
(author)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial
- 2024
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In: Acta Oncologica. - Uppsala : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 581-585
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Journal article (peer-reviewed)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 22. |
- Lindfors, Anna, et al.
(author)
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Long-term survival in obese patients after robotic or open surgery for endometrial cancer
- 2020
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 158:3, s. 673-680
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Journal article (peer-reviewed)abstract
- Objective. To evaluate surgical outcomes and survival after primary robotic or open surgery in obese women with endometrial cancer (EC). Methods. The study included obese women (BMI >= 30 kg/m(2)) with EC who underwent primary surgery before and after the introduction of robotics between 2006 and 2014. Data on complications, survival, and recurrence was obtained through the National Cancer Registry and medical files. Survival curves were calculated for overall (OS), relative (RS) and disease-free survival (DFS). Cox proportional hazards regression models to assess OS and DFS. Results. In total, 217 patients were identified, 131 robotic and 86 open surgical procedures. Significantly lower estimated blood loss, surgical time and hospital stay were found in the robotic group and the relative risk ratio of complications grades II-V, using the Clavien Dindo classification, was 0.54 (95% CI 0.31-0.93) for the robotic compared to the open group. A significant difference in OS (p = 0.029) and RS (p = 0.024) in favor of robotics was shown in the univariable survival curves, using log rank tests. No difference was seen for DFS. The 5-year RS was 96.2% (95% CI 89.7-103.3) for the robotic and 81.6% (95% CI 72.1-92.3) for the open group. Multivariable analysis showed high risk histology to be an independent risk factor, for both OS (HR 2.90; 95% CI 1.42-5.93; p < 0.05) and DFS (HR 2.74; 95% CI 1.45-5.17; p < 0.05). Robotic surgery was not found a significant independent factor for survival. Conclusions. Robotic surgery in obese women with EC had equivalent long-term and disease-free survival compared to open with significantly less complications, lower estimated blood loss, shorter surgical time and hospital stay. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 23. |
- Marcickiewicz, J., et al.
(author)
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The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study
- 2022
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 61:1, s. 30-37
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Journal article (peer-reviewed)abstract
- Background Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. Material and methods In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Results Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Conclusions Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.
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| 24. |
- Palmér, Magnus, 1980, et al.
(author)
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Accuracy of transvaginal ultrasound versus MRI in the PreOperative Diagnostics of low-grade Endometrial Cancer (PODEC) study: a prospective multicentre study.
- 2023
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In: Clinical radiology. - : Elsevier BV. - 0009-9260 .- 1365-229X. ; 78:1, s. 70-79
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Journal article (peer-reviewed)abstract
- The purpose was to investigate if the diagnostic accuracy of transvaginal ultrasound (TVUS) performed by gynaecologists is sufficient for preoperative assessment of low-grade endometrial cancer (EC) compared to magnetic resonance imaging (MRI). MRI and TVUS performed by gynaecologists were assessed at the participating centres. The MRI examinations were interpreted by two radiologists at the tertiary centre. Deep myometrial and cervical stroma invasion were visually assessed and compared to postoperative histopathology. Twohundred and fiftynine patients were included. There was a statistically significant difference in specificity assessing deep myometrial invasion between MRI and TVUS (MRI 0.88, TVUS 0.68). There was no difference in sensitivity (MRI 0.73, TVUS 0.68). When assessing cervical stroma infiltration, MRI had a higher specificity (MRI 0.96, TVUS 0.90), but there was no difference in sensitivity (MRI 0.41, TVUS 0.32). MRI has higher specificity than TVUS performed by gynaecologists for assessing deep MI and CSI in low-grade EC, but similar sensitivities. The use of TVUS as a first-line test, rather than MRI, may be supported by this study in centres where access to MRI may be limited.
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| 25. |
- Palmqvist, Charlotte, et al.
(author)
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Complications after advanced ovarian cancer surgery-A population-based cohort study
- 2022
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In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 101:7, s. 747-757
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Journal article (peer-reviewed)abstract
- Introduction Surgical complications after primary or interval debulking surgery in advanced ovarian cancer were investigated and associations with patient characteristics and surgical outcomes were explored. Material and methods A population-based cohort study including all women with ovarian cancer, FIGO III-IV, treated with primary or interval debulking surgery, 2013-2017. Patient characteristics, surgical outcomes and complications according to the Clavien-Dindo (CD) classification system <= 30 days postoperatively, were registered. Uni- and multivariable regression analyses were performed with severe complications (CD >= III) as endpoint. PFS in relation was analyzed using the Kaplan-Meier method. Results The cohort included 384 women, where 304 (79%) were treated with primary and 80 (21%) with interval debulking surgery. Complications CD I-V were registered in 112 (29%) patients and CD >= III in 42 (11%). Preoperative albumin was significantly lower in the CD >= III cohort compared with CD 0-II (P = 0.018). For every increase per unit in albumin, the risk of complications decreased by a factor of 0.93. There was no significant difference in completed chemotherapy between the cohorts CD 0-II 90.1% and CD >= III 83.3% (P = 0.236). In the univariable analysis; albumin <30 g/L, primary debulking surgery, complete cytoreduction and intermediate/high surgical complexity score (SCS) were associated with CD >= III. In the following multivariable analysis, only intermediate/high SCS was found to be an independent significant prognostic factor. Low (n = 180) vs intermediate/high SCS (n = 204) showed a median PFS of 17.2 months (95% confidence interval [CI] 15.2-20.7) vs 21.5 months (95% CI 18.2-25.7), respectively, with a significant log-rank; P = 0.038. Conclusions Advanced ovarian cancer surgery is associated with complications but no significant difference was seen in completion of adjuvant chemotherapy when severe complications occur. Importantly, our study shows that intermediate/high SCS is an independent prognostic risk factor for complications. Low albumin, residual disease and primary debulking surgery were found to be associated with severe complications. These results may facilitate forming algorithms in the decision-making procedure of surgical treatment protocols.
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