Karolinska Institutet
  • Solna, Stockholm, Sweden
Recent publications
Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10–1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
Background The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population‐based investigation. Methods A case–control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. Results Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14–2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1–2 (OR 1.67, 95% CI 1.61–1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24–3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. Conclusions Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.
Introduction On average, people with disabilities face many difficulties in accessing healthcare and experience worse health outcomes. Yet, evidence on how to overcome these barriers is lacking. Participatory approaches are gaining prominence as they can generate low-cost, appropriate and scalable solutions. This study protocol is for the pilot testing of the co-created Participatory Learning and Action for Disability (PLA-D) groups to assess feasibility. Methods and analysis We will pilot test PLA-D in five groups in Luuka district, Uganda during 2023. Each group will include approximately 20 members (people with disabilities, family members, carers) who will meet every 2–3 weeks over a 9–11 month period. The groups, guided by a trained facilitator, will identify issues about health and healthcare access and plan and implement locally generated solutions (eg, raising awareness of rights, advocacy and lobbying, establishing health savings and financing schemes). We will collect diverse sources of data to assess feasibility: (1) in-depth interviews and focus group discussions with group participants, non-participants and group facilitators; (2) monitoring of group activities; (3) direct observation of groups and (4) quantitative survey of group participants at baseline and endline. Data analyses will be undertaken to assess feasibility in terms of: acceptability, demand, implementation and practicality. We will develop and refine evaluation tools in preparation for a future trial. Ethics and dissemination Ethical approval for the study has been received by the London School of Hygiene & Tropical Medicine and the Uganda Virus Research Institute ethics committees. Informed consent will be obtained from all study participants, making adaptations for people with disabilities as necessary. We will reach different groups for our dissemination activities, including (1) people with disabilities (eg, community meetings); (2) policy and programme stakeholders in Uganda and international (eg, individual meetings, evidence briefs) and (3) academics (journal articles, conference/seminar presentations).
Increased intrapulmonary shunt(Q S /Q t ) and alveolar dead space(V D /V T ) are present in early recovery from COVID-19. We hypothesized patients recovering from severe-critical acute illness(NIH category 3-5) would have greater and longer-lasting increased Q S /Q t and V D /V T than patients with mild-moderate acute illness(NIH 1-2). Methods: 59 unvaccinated patients (33 male, age 52[38-61] years, BMI 28.8[25.3-33.6] kg/m ² ; median[IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease), were studied 15-403 days post-acute SARS-CoV-2 infection. Breathing ambient air, steady-state mean alveolar PCO 2 and PO 2 were recorded simultaneously with arterial PO 2 /PCO 2 yielding aAPCO 2 , AaPO 2 , and from these, Q S /Q t %, V D /V T %, and relative alveolar ventilation (40 mmHg/P A CO 2 , V A rel) calculated. Results: Median PaCO 2 was 39.4[35.6-41.1] mmHg, PaO 2 92.3[87.1-98.2mmHg; P A CO 2 32.8[28.6-35.3] mmHg, P A O 2 112.9[109.4-117.0] mmHg, AaPO 2 18.8[12.6-26.8] mmHg, aAPCO 2 5.9 [4.3-8.0] mmHg, Q S /Q t 4.3 [2.1-5.9] % and V D /V T 16.6 [12.6-24.4] %. Only 14% of patients had normal Q S /Q t and V D /V T ;1% increased Q S /Q t but normal V D /V T ; 49% normal Q S /Q t and elevated V D /V T ;36% both abnormal Q S /Q t and V D /V T . Previous severe-critical COVID-19 predicted increased Q S /Q t (2.69 [0.82-4.57]% per category severity [95% CI], p<0.01), but not V D /V T . Increasing age weakly predicted increased V D /V T (1.6 [0.1-3.2]% per decade, p<0.04). Time since infection, BMI and comorbidities were not predictors (all p > 0.11). V A rel was increased in most patients. Conclusions: In our population, recovery from COVID-19 was associated with increased Q S /Q t in 37% of patients, increased V D /V T in 86%, and increased alveolar ventilation up to ~13 months post infection. NIH severity predicted Q S /Q t but not elevated V D /V T . Increased V D /V T suggests pulmonary micro-vascular pathology persists post COVID-19 in most patients.
With the onset of COVID-19, the development of ex vivo laboratory models became an urgent priority to study host-pathogen interactions in response to the pandemic. In this study, we aimed to establish an ex vivo mucosal tissue explant challenge model for studying SARS-CoV-2 infection and replication. Nasal or oral tissue samples were collected from eligible participants and explants generated from the tissue were infected with various SARS-CoV-2 strains, including IC19 (lineage B.1.13), Beta (lineage B.1.351) and Delta (lineage B.1.617.2). A qRT-PCR assay used to measure viral replication in the tissue explants over a 15-day period, demonstrated no replication for any viral strains tested. Based on this, the ex vivo challenge protocol was modified by reducing the viral infection time and duration of sampling. Despite these changes, viral infectivity of the nasal and oral mucosa was not improved. Since 67% of the enrolled participants were already vaccinated against SARS-CoV-2, it is possible that neutralizing antibodies in explant tissue may have prevented the establishment of infection. However, we were unable to optimize plaque assays aimed at titrating the virus in supernatants from both infected and uninfected tissue, due to limited volume of culture supernatant available at the various collection time points. Currently, the reasons for the inability of these mucosal tissue samples to support replication of SARS-CoV-2 ex vivo remains unclear and requires further investigation.
Conflict between work and non-work is a bidirectional and a multidimensional construct that has garnered much attention from researchers and practitioners alike. Previously, studies with a dyadic design demonstrated that interrole conflict can cross over between partners in romantic relationships. The aim of the present study is to explore—from an individual and dyadic perspective—how partners perceive dimensions of interrole conflict (that is: time, strain, behaviour, and possibly others) and whether crossover between partners is dimension-dependent. This protocol outlines a qualitative interview study. Participants ( N = 40) will be dual-earner couples that meet two inclusion criteria: both partners need to be professionally active, and the couples need to have lived together for at least a year. Interviews will be conducted separately with each partner. To analyse the data at the individual level we will use reflexive thematic analysis. To analyse the data at the dyadic level we will apply an adapted version of the framework method. We anticipate that findings of this study will have the potential to advance theoretical models depicting crossover processes and, more generally, the interface between work and family lives. Moreover, insights into how couples experience dimension-based interrole conflict will be important for the development of targeted interventions.
We conducted a prospective cohort study to examine the associations of 21 gastroin-testinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gas-trointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.
T cells play a pivotal role in protection against various types of infections and tumours, from early childhood on and throughout life. They consist of several subsets characterised by adaptive and innate-like functions, with Vγ9Vδ2 being the largest subset in human peripheral blood. Although these cells show signs of cytotoxicity, their modus operandi remains poorly understood. Here we explore, using live single-cell imaging, the cytotoxic functions of γδ T cells upon interactions with tumour target cells with high temporal and spatial resolution. While γδ T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by γδ T cells. Thus, our data provide new insights into the cytotoxic arsenal and functions of γδ T cells, which may guide the development of more efficient γδ T cell based adoptive immunotherapies.
Background This study aims to comprehensively investigate the phenotypic and genetic relationships between four common lipids (high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; total cholesterol, TC; and triglycerides, TG), chronic kidney disease (CKD), and estimated glomerular filtration rate (eGFR). Methods We first investigated the observational association of lipids (exposures) with CKD (primary outcome) and eGFR (secondary outcome) using data from UK Biobank. We then explored the genetic relationship using summary statistics from the largest genome-wide association study of four lipids (N = 1,320,016), CKD (N case = 41,395, N control = 439,303), and eGFR(N = 567,460). Results There were significant phenotypic associations (HDL-C: hazard ratio (HR) = 0.76, 95%CI = 0.60–0.95; TG: HR = 1.08, 95%CI = 1.02–1.13) and global genetic correlations (HDL-C: $${r}_{g}$$ r g = − 0.132, P = 1.00 × 10 –4 ; TG: $${r}_{g}$$ r g = 0.176; P = 2.66 × 10 –5 ) between HDL-C, TG, and CKD risk. Partitioning the whole genome into 2353 LD-independent regions, twelve significant regions were observed for four lipids and CKD. The shared genetic basis was largely explained by 29 pleiotropic loci and 36 shared gene-tissue pairs. Mendelian randomization revealed an independent causal relationship of genetically predicted HDL-C (odds ratio = 0.91, 95%CI = 0.85–0.98), but not for LDL-C, TC, or TG, with the risk of CKD. Regarding eGFR, a similar pattern of correlation and pleiotropy was observed. Conclusions Our work demonstrates a putative causal role of HDL-C in CKD and a significant biological pleiotropy underlying lipids and CKD in populations of European ancestry. Management of low HDL-C levels could potentially benefit in reducing the long-term risk of CKD. Graphical Abstract
Background The management of alcohol-associated cirrhosis has improved in the last decades, but whether the prognosis has changed over time is uncertain. We aimed to assess time trends in mortality and life expectancy in patients hospitalized with alcohol-associated cirrhosis. Methods In this population-based cohort study, we used the Swedish national population and health registers to identify all patients with a first episode of in-hospital alcohol-associated cirrhosis from 1969 to 2019 (n = 22,658). Time trends in 1-year mortality were assessed with multivariable Cox regression. A flexible parametric model was fitted to evaluate loss in life expectancy. Results Crude mortality was similar in the 2010s and 1980s (unadjusted HR = 1.00, 95% CI = 0.93–1.08, p trend = 0.767). However, when adjusting for baseline characteristics, mortality was lower in the 2010s than in the 1980s (adjusted HR = 0.74, 95% CI = 0.68–0.80), including both liver- and nonliver-related mortalities. These results were consistent in men but not in women, where only nonliver mortality had decreased. The average loss in life expectancy for patients with alcohol-associated cirrhosis compared with the general population was similar throughout the study period (in the 2010s: 14.3 y shorter (95% CI = 13.7–14.9) in men and 15.8 years shorter (95% CI = 14.9–16.7) in women). Conclusion Mortality in patients hospitalized with alcohol-associated cirrhosis has improved somewhat when accounting for baseline characteristics, but the loss in life expectancy remains substantial. This underscores the need for new therapeutic options and health policy interventions to further improve the dismal prognosis and life expectancy of patients with alcohol-associated cirrhosis.
Importance Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.
Background Young adults entering the workforce have an almost 40% greater risk of work-related mental health problems than other working age groups. Common mental disorders (CMDs) constitute the majority of such mental health problems. Managers are crucial in promoting a good psychosocial work environment and preventing sick leave. The study aims to explore managers’ experience of 1) causes of sick leave in the personal and work-life of young employees with CMDs, and 2) prevention of such sick leave. A gender perspective is applied to examine managers’ experience of causes and prevention of sick leave in relation to male and female employees and male and female-dominated occupations. Material and methods A qualitative design was applied and 23 semi-structured interviews were conducted with Swedish managers experienced in supervising young employees with CMDs. The interviews were analysed with conventional content analysis and the managers’ experience of similarities and differences between young female and male employees and occupations were explored through reflective notes. Results Four main categories and eight subcategories describe the managers’ experience of the causes of sick leave due to CMD among young employees. The main categories are: 1) entering work life when already worn-out, 2) struggling with too high expectations at work, 3) having a challenging personal life, and 4) being unable to manage specific occupational challenges and demands. Gender differences were found in six subcategories regarding, e.g., work demands and problems in personal relationships. One main category and three subcategories describe how this type of sick leave might be prevented, with managers emphasizing the need to ease the transition into work life. Gender differences in the prevention of sick leave were found in one subcategory regarding communication about workers’ health and problems at work. Conclusion Our findings show that gender norms and the expectations of young men and women are factors of importance in managers’ experience of the development and prevention of CMDs. These results can inform their preventive work and their supervision and introduction of newly-employed young adults.
Background Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking. Aims To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics. Method Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed. Results Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8). Conclusion Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo. Trial registration EudraCT 2017-002418-30 .
Importance Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. Objective To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania. Design, Setting, and Participants In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included. Exposures The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days. Main Outcomes and Measures Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline. Results The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, −0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. Conclusion This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.
Introduction/Background The use of social media to raise awareness of gynaecological cancer is increasingly more common. Moreover, women use social media channels to share their stories and experiences of diagnosis, treatment, and survival. Influencers are using platforms such as Instagram for inspiration, motivation, and education. However, the literature on the use and engagement on Instagram to raise awareness for gynaecological cancers, particularly, vulval cancer is still lacking. In this descriptive analysis, we aim to identify the volume and themes of posts on Instagram relating to vulval cancer. Methodology We identified the volume of posts related to specific hashtags by using the Instagram search feature. We analysed results from the following hashtags from October 2010 to May 5th, 2023: #vulvarcancer, #vulvalcancer, #vulvarcancerawareness, and #vulvalcancerawareness. The top two posts were then classified and analysed by theme using the Instagram algorithm. If posts received comments, a word cloud was generated to identify the most commonly used words. Results We identified a total of 20756 posts relating to the above-mentioned hashtags. The top two posts received 11 and 23 likes, respectively, and a total of 3 comments. The central theme of the posts was sharing the patient‘s journey through treatment and general education on vulval cancer. There were not enough posts to generate a word cloud.View this table: • View inline • View popup • Download powerpoint Abstract #185 Table 1 Classification of the Top Two Instagram Posts for #vulvarcancer, #vulvalcancer, #vulvalcancerawareness and #vulvarcancerawareness: Conclusion Considering that Instagram has over one billion active users per month, the number of posts and the interaction and content are disappointingly low. In an era of digitalisation, powerful platforms such as Instagram provide enormous potential and a vast outreach to raise awareness and build communities for women with vulval cancer. Although there is a growing trend to use Instagram for this purpose, this should form an integral part in the patient‘s journey. Disclosures None
Introduction/Background To investigate time to chemotherapy (TTC) from primary debulking surgery (PDS) and relative survival (RS) in advanced epithelial ovarian cancer (EOC) in a nationwide population-based cohort. Methodology All women diagnosed with EOC, stage IIIC-IV and registered in the Swedish Quality Register for Gynecologic Cancer between 2008–2018 with PDS performed followed by chemotherapy were included. Patient and tumor characteristics including no (R0) or residual disease (RD), were retrieved. The TTC was categorized into five groups. The 2- and 5-year RS (95%CI) were calculated and uni- and multivariable Poisson regression of excess mortality rate ratios (EMRRs) analyzed with covariates; TTC, age, FIGO stage, serous and non-serous histology and residual disease. Results In total, 1710 women were included. The mean age was 64.3 years. R0 was achieved in 47.7%; 39.0% of 292 women with TTC <21 days, 46.9% of 360 with 22–28 days, 48.5% of 392 (29–35 days), 52.1% of 303 with 36–42 days and 51.0% of 363 women with TTC >42 days, respectively. In the total cohort, age <70 years, stage IIIC, serous histology and R0 were found significant prognostic factors for 5-year RS but not TTC. Two-year RS for FIGO stage IV and R0 was 92.9% (82.8–1.00) for TTC <21 days compared with 66.3% (50.8–81.8) for TTC >42 days. The corresponding figures for stage IIIC and R0 were 91.0% (84.7–97.4) and 82.4% (75.8–89.0), respectively. Five-year RS for FIGO stage IV and R0 was 67.2% (48.0–86.3) for TTC <21 days and 42.6% (25.2–59.9) for TTC > 42 days. The corresponding 5-year RS for stage IIIC and R0 were 56.4% (45.2–67.6) and 51.6% (42.8–60.5), respectively. Conclusion Our data indicate that TTC after PDS may be associated with short-term survival among stage IV disease without residual disease. Updated results with EMRR data for subgroups will be presented. Disclosures The authors declare no conflicts of interest.
Introduction/Background Sentinel node biopsy (SNB) in vulvar cancer reduces morbidity. However, the oncological safety in tumours ≥4cm and in multifocal tumours has not been systematically studied. Since 2017, vulvar cancer treatment in Sweden is centralised to four university hospitals. All cases of primary or recurrent vulvar cancer are discussed at weekly national multidisciplinary conferences.The aim of this study was to investigate the feasibility and oncological safety of SNB in vulvar squamous cell carcinoma (VSCC) with tumours ≥4cm, or multifocal disease. Methodology In this prospective nationwide pilot study, women with primary VSCC ≥4cm (group 1) or multifocal tumours (group 2) diagnosed between December 2019 and December 2022, without clinical or radiological signs of dissemination, underwent both SNB and inguinofemoral lymphadenectomy. Detection rates, negative predictive values, and the prevalence of metastases (isolated tumour cells (ITC), micro- and macrometastases) were determined for each of the two groups. • Download figure • Open in new tab • Download powerpoint Abstract #92 Figure 1 Distribution of lymph node metastases in the subgroups: A. Tumours =4cm, n=36 (58/69 groins with successful sentinel mapping) B. Multifocal tumours, n=17 (29/34 groins with successful sentinel mapping) Results 36 women were included in group 1 and 17 women in group 2. The detection rates varied between 94–100% per patient and 84–85% per groin. There were no false negative sentinel nodes, giving a negative predictive value of 100% (95% CI 91.2–100 for group 1, 95% CI 83.9–100 for group 2). 47% of the women had lymph node metastases, 15% ITC or micrometastases only. The sentinel node metastases were the only metastatic nodes in 83% of all groins. Metastatic disease was found in 4 out of 16 (25%) non-mapping groins, in all but one with extranodal growth. Conclusion In a centralised health care system with high proficiency, SNB seem to be feasible in tumours ≥4cm and multifocal disease. The procedure can be performed with high detection rates and promising oncological safety. Furthermore, SNB increases precision by detection of low-volume metastases. In non-mapping groins, an inguinofemoral lymph node dissection is mandatory to prevent undiagnosed advanced disease.
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Christopher R. Cederroth
  • Department of Physiology and Pharmacology
André Görgens
  • Department of Laboratory Medicine
Johanna Viiliäinen
  • Department of Cell and Molecular Biology
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Nobels väg 6, 17177, Solna, Stockholm, Sweden
Head of institution
Ole Petter Ottersen
Website
https://ki.se/
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+46-8-524 800 00