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1.
  • Maathz, Pernilla, et al. (författare)
  • Psychological Inflexibility as a Predictor of Sexual Functioning Among Women with Vulvovaginal Pain : A Prospective Investigation
  • 2020
  • Ingår i: Pain medicine (Malden, Mass.). - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637. ; 21:12, s. 3596-3602
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivePersistent vulvovaginal pain affects many women and often has adverse effects on sexual functioning. Psychological inflexibility related to pain is associated with distress and functional disability across different types of chronic pain conditions, but little is known about the role of psychological inflexibility in vulvovaginal pain. The present study examines psychological inflexibility related to pain as a predictor of sexual functioning over time among women with vulvovaginal pain.MethodsQuestionnaires including measures of psychological inflexibility, pain severity, and sexual functioning were administered to female university students at two points in time. One hundred thirty women with vulvovaginal pain responded to the questionnaire at baseline and at follow-up after 10 months. A multiple regression model was used to explore psychological inflexibility and pain severity as predictors of sexual functioning at follow-up.ResultsHigher levels of psychological inflexibility and more severe pain at baseline were associated with poorer sexual functioning 10 months later. In analysis adjusting for baseline levels of sexual functioning, psychological inflexibility was the only significant predictor of sexual functioning at follow-up.ConclusionsThe findings provide preliminary evidence that psychological inflexibility is associated with sexual adjustment over time among women with vulvovaginal pain and point to the relevance of further examinations of the psychological inflexibility model in the context of vulvovaginal pain.
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2.
  • Alfonzo, Emilia, et al. (författare)
  • 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
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 116, s. 169-177
  • Tidskriftsartikel (refereegranskat)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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3.
  • Ekdahl, Johanna, 1978-, et al. (författare)
  • Vulvovaginal pain from a fear-avoidance perspective : a prospective study among female university students in Sweden
  • 2018
  • Ingår i: International Journal of Sexual Health. - : Routledge. - 1931-7611 .- 1931-762X. ; 30:1, s. 49-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To examine how fear-avoidance influences vulvovaginal pain and sexual function over time.Method: At baseline and at 10-month follow-up, self-report measures for sexual- and fear avoidance factors were obtained from 483 female university students with and without self-reported vulvovaginal pain.Results: Individuals with pain at both times reported lower sexual function, and higher levels of fear-avoidance compared to the pain-free group. Fear-avoidance beliefs predicted the occurrence of vulvovaginal pain at follow up and the level of pain intensity.Conclusion: The results points to the relevance of the components of the fear-avoidance model in vulvovaginal pain over time.
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4.
  • Ekdahl, Linnea, et al. (författare)
  • A combination of second trimester oral metronidazole and no sexual intercourse during second and third trimester may reduce late miscarriage and premature delivery after fertility sparing radical trachelectomy
  • 2021
  • Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 265, s. 90-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Women with a previous trachelectomy have an increased risk of premature delivery and second trimester miscarriage. In this study we aim to evaluate factors and regimes possibly affecting the risk for prematurity following fertility sparing robotic radical trachelectomy (RRT) in cervical cancer. Methods: A retrospective study of the reproductive outcome following RRT with a cervical cerclage performed at one of four academic centers between 2007 and 2019. Factors possibly related to premature delivery, such as postoperative non-pregnant cervical length, previous vaginal deliveries, preservation of the uterine arteries, and the use of a second trimester oral metronidazole/no sexual intercourse regime, were assessed. Results: 109 women remained for analyses after excluding recurrences before pregnancy (n = 8), secondary hysterectomy (n = 2), and women with less than six months follow up (n = 10). 74 pregnancies occurred in 52/71 women attempting to conceive, 56 of which developed past the first trimester. Two of 22 women (9%) who were prescribed an oral metronidazole regime (400 mg × 2 from gestational week 15 + 0 to 21 + 6 and abstaining from sexual intercourse for the duration of the pregnancy) had a premature delivery, compared with 13/31 (42%) where the regime was not applied (p = 0.009). The association remained after regression analyses including possible contributing factors as of above, none of which associated with prematurity at regression analyses (p = 0.001). Conclusions: The observed four-fold reduction in premature delivery indicates that an oral metronidazole/no sexual intercourse regime may reduce second trimester miscarriage and premature deliveries following an RRT. No association was observed for other investigated factors.
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5.
  • Ekdahl, Linnea, et al. (författare)
  • Increased Institutional Surgical Experience in Robot-Assisted Radical Hysterectomy for Early Stage Cervical Cancer Reduces Recurrence Rate: Results from a Nationwide Study
  • 2020
  • Ingår i: JOURNAL OF CLINICAL MEDICINE. - : MDPI AG. - 2077-0383. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate the impact of institutional surgical experience on recurrence following robotic radical hysterectomy (RRH) for early stage cervical cancer. All women in Sweden who underwent an RRH for stage IA2-IB1 cervical cancer at tertiary referral centers from its implementation in December 2005 until June 2017 were identified using a Swedish nationwide register and local hospital registers. Registry data were controlled by a chart review of all women. Recurrence rates and patterns of recurrence were compared between early and late (<= 50 vs. >50 procedures) institutional series. Six hundred and thirty-five women were included. Regression analysis identified a lower risk of recurrence with increased experience but without a clear cut off level. Among the 489 women who did not receive adjuvant radio chemotherapy (RC-T), the rate of recurrence was 3.6% in the experienced cohort (>50 procedures) compared to 9.3% in the introductory cohort (p < 0.05). This was also seen in tumors < 2 cm regardless of RC-T (p < 0.05), whereas no difference in recurrence was seen when analyzing all women receiving RC-T. In conclusion, the rate of recurrence following RRH for early stage cervical cancer decreased with increased institutional surgical experience, in tumors < 2 cm and in women who did not receive adjuvant RC-T.
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6.
  • Ekdahl, Linnea, et al. (författare)
  • Long term oncologic and reproductive outcomes after robot-assisted radical trachelectomy for early-stage cervical cancer. An international multicenter study
  • 2022
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 164:3, s. 529-534
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Long term outcomes following fertility sparing robot-assisted radical trachelectomy (RRT). Methods: A retrospective study of consecutive women selected for RRT between 2007 and 2019 at five referral centres. Generally used selection criteria for fertility-sparing surgery were applied. Oncologic, reproductive and long-term clinical data were analysed. Results: Of the 166 included women, 149 completed a RRT. Median tumor size was 9 mm (range 3-20 mm), 111 women (75%) had FIGO 2009 stage IB1 cancer and 4.8% were node positive. At a median follow up of 58 months, 12 of all women (7.2%) and 9 of 149 women (6%) who underwent completed RRT with fertility preservation had recurred and two had died. 70 of 88 women (80%) who attempted to conceive succeeded, resulting in 81 pregnancies that progressed beyond the first trimester and 76 live births of which 54 (70%) were delivered at term and 65 (86%) delivered after gestational week 32. A short postoperative cervical length was associated with impaired fertility. A late secondary hysterectomy was necessary in four women due to persistent bleeding (n = 2), hematometra due to a cervical stenosis (n = 1) and recurrent dysplasia (n = 1). Conclusion: In this long-term follow-up of RRT the recurrence rate is comparable to larger individual studies of minimally invasive or vaginal radical trachelectomy with similar risk profile and follow up. The high pregnancy rate and low rate of premature delivery before 32 weeks GA may promote the use of robot-assisted approach.
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7.
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8.
  • Ekdahl, Linnea, et al. (författare)
  • Quality of life and long-term clinical outcome following robot-assisted radical trachelectomy
  • 2021
  • Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 267, s. 234-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Quality of Life and long-term clinical outcome following robot-assisted radical trachelectomy. Objectives: To evaluate quality of life (QoL) and long-term clinical outcome following robot-assisted radical trachelectomy (RRT). Study Design: Prospectively retrieved clinical data were rereviewed on all women planned for a fertility sparing RRT for early stage cervical cancer at Skåne University Hospital, Sweden between 2007 and 2020. QoL was assessed using the validated questionnaires EORTC QLQ-C30, QLQ-CX24 and the Swedish LYMQOL. Results: Data was analyzed from 49 women, 42 with a finalised RRT and seven with an aborted RRT due to nodal metastases (n = 3) or insufficient margins (n = 4). At a median follow-up time of 54 months one recurrence (2%) occurred (aborted RRT). According to QLQ-C30 the median global health status score was 75. The disease specific QLQ-C24 showed an impact on symptoms related to sexual function where sexual/vaginal functioning had a median score of 25 and 48% of patients reported worry that sex would cause physical pain. Despite this the functional items sexual activity and sexual enjoyment both had a median score of 66.7. Lymphoedema was reported in 45%, where 9% reported severe symptom with an impact on their QoL. No intraoperative complications and no postoperative complications ≥ Clavien Dindo grade III were observed. Twenty-two of 28 (79%) women who attempted to conceive were successful. A metronidazole/no intercourse regimen was applied between GW 15 + 0–21 + 6 in 26 of 28 pregnancies beyond first trimester resulting in a 92% term (≥GW 36 + 0) delivery rate. Conclusions: Although robot-assisted radical trachelectomy in this cohort was associated with a low recurrence rate, a high fertility rate and an exceptionally high term delivery rate, women's quality of life was affected postoperatively, particularly with regards to their sexual well-being and lymphatic side-effects.
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9.
  • Engman, Linnea, 1987-, et al. (författare)
  • Avoiding or enduring painful sex? : A prospective study of coping and psychosexual function in vulvovaginal pain
  • 2018
  • Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149. ; 22:8, s. 1388-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recurring vulvovaginal pain is common, with evident effects on affected women's lives. Little is known about how affected women cope with painful sexual activities and how coping relates to pain intensity and psychosexual functioning over time. This prospective study explored the impact of avoidance and endurance on sexual function over time. Additionally, patterns of coping were studied on an individual level to increase knowledge about coping and its relation to psychosexual functioning.Methods: One hundred and seventeen women, 18-35years old, with recurring vulvovaginal pain answered questionnaires at two measurement points, five months apart, assessing avoidance and endurance coping, pain intensity and psychosexual functioning. A multiple regression model explored the predictive value of avoidance and endurance on sexual function over time. Cluster analyses investigated patterns of coping and stability within the clusters. These subgroups were compared on psychosexual outcomes.Results: Avoidance at baseline was the only significant predictor of sexual function five months later. Distinct and stable subgroups with different patterns of coping were identified, where avoidance and endurance coping were used both separately and combined. Women who both avoided and endured had the most unfavourable outcomes in terms of psychosexual functioning.Conclusions: Avoidance of sexual activities was related to reduced sexual function over time, which calls for attention and clinical interventions targeting avoidance. Additionally, women who both avoid and endure sexual activities despite pain possibly need tailored interventions, as women with this coping pattern reported the lowest levels of psychosexual functioning.Significance: In this prospective study, avoidance of sexual activities predicted sexual function over time, when controlling for pain intensity. Subgroups of women using distinct patterns of coping were identified. Those who both avoided and endured had the lowest levels of psychosexual functioning.
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10.
  • Engman, Linnéa, 1987- (författare)
  • Vulvodynia : Understanding the Role of Pain-related Behavior
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Over the last decades, psychological mechanisms have been identified as key in the understanding of pain development and maintenance of vulvodynia. Furthermore, psychological treatments in the form of cognitive behavioral therapy (CBT) have proven helpful for those suffering. Still, prospective studies investigating psychological mechanisms over time are lacking, as are clinical studies investigating their role in treatment.The overall aim of this dissertation is to further the understanding of pain-related behavior and its role in the development and maintenance of vulvodynia by applying a fear-avoidance-endurance theoretical framework. It further aimed at consolidating the understanding of such a framework through a clinical proof of concept investigating the effect of a CBT treatment. Study I investigated the mediating role of avoidance and endurance behavior on the relationship between pain catastrophizing and pain. Study II prospectively investigated the predictive value of avoidance and endurance behavior on sexual function. Further, avoidance and endurance behavior were examined on an individual level to gain information on potential patterns of behavior. Study III investigated the effect of a CBT group treatment with partner involvement on pain and associated outcomes.Taken together, the overall findings of this dissertation further point at the importance of psychological mechanisms such as pain catastrophizing, avoidance behavior, and endurance behavior in the development and maintenance of vulvodynia. While further manifesting similarities between mechanisms involved in vulvodynia and those involved in other persistent pain conditions, the findings also verify the relevance of the Fear-avoidance model and the complementary Avoidance-endurance model for vulvodynia. Finally, a new model of understanding was proposed: the Fear-avoidance-endurance model of vulvodynia, summarizing pain-related behavior involved in the development and maintenance of vulvodynia.
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11.
  • Flink, Ida K., 1980-, et al. (författare)
  • Coping with pain in intimate situations : applying the avoidance-endurance model to women with vulvovaginal pain
  • 2017
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 17:October 2017, s. 302-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aimsChronic vulvovaginal pain is strikingly common and has a serious impact on women's lives. Nevertheless, there are few longitudinal studies focusing on mechanisms involved in the pain development. One area of interest is how women cope with sexual activities and how this affects their pain. In this study, avoidance and endurance coping behaviors were explored as possible mediators of the relation between catastrophizing and pain, cross-sectionally and longitudinally.Methods251 women (18–35 years old) with vulvovaginal pain were recruited in university settings and filled out questionnaires about their pain, catastrophizing and coping behaviors at two occasions, with five months in between. Multiple mediation models were tested, exploring avoidance and endurance as mediators of the relation between catastrophizing and pain.ResultsThe results showed that avoidance was an influential mediator of the link between catastrophizing and pain. Using multiple mediation models we found that although the indirect effects of both avoidance and endurance were significant cross-sectionally, only avoidance was a significant mediator in the combined model exploring associations over time.ConclusionsThis study indicates that the strategies women with vulvovaginal pain use for coping with sexual activities are important for the course of pain. Avoidance and, to a lesser degree, endurance strategies were identified as important mediators of the effects of catastrophizing on pain. When exploring the links over time, only avoidance emerged as a significant mediator.ImplicationsIn this longitudinal study, catastrophizing was linked to vulvovaginal pain, via avoidance and endurance of sexual activities. Hence, targeting catastrophizing early on in treatment, as well as addressing coping, may be important in clinical interventions.
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12.
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13.
  • Lindelöf, Linnea, et al. (författare)
  • 62 Acquired ficolin-3 deficiency in patients with Systemic Lupus Erythematosus
  • 2023
  • Ingår i: Immunobiology. - : Elsevier. - 0171-2985 .- 1878-3279. ; 228:5, s. 152515-152515
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Ficolin-3 is the main initiator of the lectin pathway in humans. Case reports of ficolin-3 deficient patients have suggested that ficolin-3 deficiency may be enriched in patients with Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease where complement plays an important role. Therefore, this study aimed to investigate the activity levels of ficolin-3 and to identify potential ficolin-3 deficient individuals in two Swedish SLE cohorts.Methods: Serum or plasma samples from SLE patients (n=810) and matched controls (n=566) were collected from the Karolinska Institute (KI) and Umeå University Hospital. The ficolin-3 activity levels were measured by an in-house developed functional ELISA with a pooled normal human serum sample as a reference. Serial samples were analyzed for ficolin-3 deficient patients when available. Sequencing data were analyzed for FCN3 frame-shift mutation +1637delC (rs532781899) and other potential loss-of-function (LoF) variants.Results: This screening revealed that the level of ficolin-3 activity varies largely in patients with SLE. The activity levels also show that SLE patients seem to generally have elevated ficolin-3 activity compared to the control group (p<0.0001). Out of 810 patients with SLE, four patients were determined to be ficolin-3 deficient. For two of these patients, the ficolin-3 activity was at normal levels at the time of diagnosis and thereafter depleted over time, indicating an acquired deficiency. For deficient patients, no or very low ficolin-3 protein levels and no lectin pathway-dependent complement activation could be detected. Autoantibodies against ficolin-3 were not detectable. No patients were homozygous for the +1637delC frameshift mutation, whereas in total 10 patients were determined to be heterozygous carriers. These heterozygous patients displayed lower levels of ficolin-3 activity but did not include the deficient patients. Additional possible LoF variants were analyzed but none were enriched in either patients or controls.Conclusions: Contrary to the classical pathway of the complement system we show that genetic ficolin-3 deficiency is not a risk factor for SLE. Instead, acquired ficolin-3 deficiency was observed in a subgroup of SLE patients, possibly due to a potent activation of the lectin pathway that depleted ficolin-3 plasma levels in these individuals.
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14.
  • Lindelöf, Linnea, et al. (författare)
  • A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
  • 2024
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
  • Tidskriftsartikel (refereegranskat)abstract
    • The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
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15.
  • Lührs, Oscar, et al. (författare)
  • Combining Indocyanine Green and Tc99-nanocolloid does not increase the detection rate of sentinel lymph nodes in early stage cervical cancer compared to Indocyanine Green alone
  • 2019
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether combining two independent tracers increases the SLN-detection rate in cervical cancer. Methods: Consecutive women with early stage cervical cancer planned for a robotic radical hysterectomy or a robotic radical trachelectomy with sentinel lymph node (SLN) detection were included. After cervical injections of Indocyanine green (ICG) and Tc99-nanocolloid (Tc99), near-infrared fluorescence imaging and a gamma probe were used to identify SLNs in the upper and lower paracervical pathways (UPP/LPP). A strict surgical algorithm was adhered to and the SLNs were defined as SLN-ICG, SLN-ICG+Tc99 or SLN-Tc99. In FIGO-stage ≥IA2 cancers a full pelvic lymph node dissection (PLND) was performed after detection of SLNs. The primary endpoint was the SLN detection rate per tracer and combination of tracers. Secondary endpoints were sensitivity and mapping rates of the SLN algorithm per tracer and combination of tracers. Results: In the sixty-five analyzed women, the bilateral mapping rate was 98.5% for ICG and 60% for Tc99 (p < 0.01). Combining the tracers did not increase the bilateral detection rate. In three women (5%) Tc99 identified ICG-negative non-metastatic SLNs without impact on the bilateral detection rate. Eight women (12%) had lymph node metastases (LNMs), all had at least one metastatic SLN. Seven (35%) of the 20 metastatic SLNs were detected by ICG only and 12 (60%) were ICG and Tc99 positive. Conclusion: SLN detection rate was significantly higher using ICG compared with Tc99. ICG identified all patients with LNMs. Combining ICG and Tc99 did not improve the bilateral detection rate of SLNs.
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16.
  • Lührs, Oscar, et al. (författare)
  • Resection of the upper paracervical lymphovascular tissue should be an integral part of a pelvic sentinel lymph node algorithm in early stage cervical cancer
  • 2021
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 163:2, s. 289-293
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the prevalence of lymph nodes and lymph node metastases (LNMs) in the upper paracervical lymphovascular tissue (UPLT) in early stage cervical cancer. Methods: In this prospective study consecutive women with stage IA1-IB1 cervical cancer underwent a pelvic lymphadenectomy including identification of sentinel nodes (SLNs) as part of a nodal staging procedure in conjunction with a robotic radical hysterectomy (RRH) or robotic radical trachelectomy (RRT). Indocyanine green (ICG) was used as tracer. The UPLT was separately removed and defined as “SLN-parametrium” and, as all SLN tissue, subjected to ultrastaging and immunohistochemistry. Primary endpoint was prevalence of lymph nodes and metastatic lymph nodes in the UPLT. Secondary endpoints were complications associated with removal of the UPLT. Results: One hundred and forty-five women were analysed. Nineteen (13.1%) had pelvic LNMs, all identified by at least one metastatic SLN. In 76 women (52.4%) at least one UPLT lymph node was identified. Metastatic UPLT lymph nodes were identified in six women of which in three women (2.1% of all women and 15.8% of node positive women) without lateral pelvic LNMs. Thirteen women had lateral pelvic SLN LNMs with either no (n = 5) or benign (n = 8) UPLT lymph nodes. No intraoperative complications occurred due to the removal of the UPLT. Conclusion: Removal of the UPLT should be an integral part of the SLN concept in early stage cervical cancer.
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17.
  • Lührs, Oscar, et al. (författare)
  • Similar distribution of pelvic sentinel lymph nodes and nodal metastases in cervical and endometrial cancer. A prospective study based on lymphatic anatomy
  • 2022
  • Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 165:3, s. 466-471
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Comparing the anatomical distribution of metastatic and non-metastatic pelvic sentinel lymph nodes (SLN) in cervical and endometrial cancer. Methods: Detailed SLN mapping results were prospectively retrieved in cervical (n = 145) or high-risk endometrial cancer (n = 201) patients undergoing a robotic staging procedure. Cervically injected Indocyanine Green (ICG), allowing for reinjection in case of inadequate mapping, was used as tracer. An anatomically based definition of SLNs was adhered to evaluating the upper (UPP) and lower (LPP) paracervical lymphatic pathways. The positions of SLNs were intraoperatively depicted on an anatomical chart. A completory pelvic lymphadenectomy was performed. Mapping rates and anatomical distribution of SLNs and the location of pelvic nodal metastases were compared between groups. Results: The bilateral mapping rate was 97.9% and 95.0% for cervical and endometrial cancer respectively (p = .16). The proportion of typically positioned (interiliac and proximal obturator fossa) SLNs along the UPP was similar between groups (78.1% vs 82.1%, p = .09), and the rate of metastatic SLNs in the obturator fossa was 54.1% and 48.6% respectively (p = .45). All pelvic node positive women (cervical cancer n = 19, endometrial cancer n = 37) had at least one metastatic SLN. Anatomically typical positions could not be defined along the LPP. Conclusion: The anatomical location of SLNs and SLN metastases are similar in cervical and endometrial cancer suggesting that sensitivity results for an SLN concept in endometrial cancer and cervical cancer can be accumulated.
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18.
  • Persson, Jan, et al. (författare)
  • A prospective study evaluating an optimized sentinel node algorithm in early stage cervical cancer : The PROSACC-study
  • 2024
  • Ingår i: Gynecologic Oncology. - 0090-8258. ; 187, s. 178-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: A single center prospective non-randomized study to assess a systematically developed anatomically-based sentinel lymph node (SLN) algorithm in cervical cancer. Methods: Consecutive women with FIGO 2009 stage 1A2-2A1 cervical cancer undergoing robotic radical hysterectomy/trachelectomy between September 2014 and January 2023 had cervically injected Indocyanine Green (ICG) as a tracer for detection of pelvic SLN. An anatomically based surgical algorithm was adhered to; defining SLNs as the juxtauterine mapped nodes within the upper and lower paracervical lymphatic pathways including separate removal of the parauterine lymphovascular tissue (PULT). A completion pelvic lymphadenectomy was performed. Ultrastaging and immunohistochemistry was performed on SLNs, including the PULT. Results: 181 women were included for analysis. Median histologic tumor size was 14.0 mm (range 2–80 mm). The bilateral mapping rate was 98.3%. As per protocol an interim analysis rejected H0 and inclusion stopped at 29 node positive women, all identified by at least one metastatic ICG-defined SLN. One woman awaiting histology at study-closure was node positive and included in the analysis. Sensitivity was 100% (95% CI, 88.4%–100%) and NPV 100% (95% CI, 97.6%–100%). In node positive women, the proximal obturator position harbored 46.1% of all SLN metastases representing the only position in 40% and 10% had isolated metastases in the PULT. Conclusions: Strictly adhering to an anatomically based SLN-algorithm including identification of parallell lymphatics within major pathways, partilularly the obturator compartment, assessment of the PULT, restricting nodal dissection to the removal of SLNs accurately identifies pelvic nodal metastatic disease in early-stage cervical cancer.
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19.
  • Pertesi, Maroulio, et al. (författare)
  • Essential genes shape cancer genomes through linear limitation of homozygous deletions
  • 2019
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The landscape of somatic acquired deletions in cancer cells is shaped by positive and negative selection. Recurrent deletions typically target tumor suppressor, leading to positive selection. Simultaneously, loss of a nearby essential gene can lead to negative selection, and introduce latent vulnerabilities specific to cancer cells. Here we show that, under basic assumptions on positive and negative selection, deletion limitation gives rise to a statistical pattern where the frequency of homozygous deletions decreases approximately linearly between the deletion target gene and the nearest essential genes. Using DNA copy number data from 9,744 human cancer specimens, we demonstrate that linear deletion limitation exists and exposes deletion-limiting genes for seven known deletion targets (CDKN2A, RB1, PTEN, MAP2K4, NF1, SMAD4, and LINC00290). Downstream analysis of pooled CRISPR/Cas9 data provide further evidence of essentiality. Our results provide further insight into how the deletion landscape is shaped and identify potentially targetable vulnerabilities.
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20.
  • Wenzel, H. H. B., et al. (författare)
  • A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases
  • 2023
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 185, s. 61-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.Methods: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion cri-teria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. Results: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion > 10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size 520 mm, and depth of invasion 510 mm-had a very low risk of pN + (2.4%, 95% CI, 1.7-3.3%). Conclusion: Early-stage cervical cancer without LVSI, a tumour size 520 mm and depth of invasion 510 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.& COPY; 2023 Elsevier Ltd. All rights reserved.
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