Umeå University's logo

Fifteen percent of patients with preoperative stage IA2-IB1 uterine cervical cancer are diagnosed with lymph node metastasis (LNM) following surgery. They must be treated with both surgery and radiotherapy, a combination associated with severe side effects. Since current diagnostic methods have limitations, biomarkers are urgently needed to improve staging. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a regulator of growth factor signaling and a prognostic factor in cervical cancer. This study investigates whether LRIG1 expression could predict LNM in cervical cancer. Sixty-seven patients were included: 31 without LNM and 36 with LNM. Tumor blocks were retrieved, and clinical data were collected. Immunohistochemical analysis of LRIG1 expression was performed, and LRIG1 immunoreactivity was correlated with lymph node status and clinicopathological prognostic factors, such as human papillomavirus status and smoking status. High LRIG1 expression (> 25% positive cells) was significantly associated with an increased risk of LNM (odds ratio 9.49, 95% CI: 1.80-50.05, P = 0.008, adjusted for age, smoking status, and BMI), suggesting the potential of LRIG1 as a biomarker. Larger, multicenter studies are needed to validate our results.

Introduction: Psychological distress is of concern among university students worldwide, more so than in a comparable working population. The impostor phenomenon (IP) describes feelings of inadequacy often experienced by individuals struggling to internalize success despite evidence to the contrary. IP is prevalent among university students and has been identified as a significant factor in understanding psychological distress within this population. This study aimed to investigate the prevalence of IP and its association with perceived stress and anxiety in dental, law, medical, nursing and psychology university students.

Methods: A web-survey consisting of the Clance Impostor Phenomenon Scale (CIPS), the Perceived Stress Scale-4 (PSS-4), the Generalized Anxiety Disorder-2 (GAD-2), and sociodemographic questions were completed by 968 university students registered at a Swedish university during 2022 and 2023. The prevalence of IP, perceived stress, and anxiety was calculated. Pearson’s correlation coefficient and multiple linear regression were used to examine the relationship between the variables.

Results: 64.0% of the participants scored above the cut off value for experiencing IP (CIPS score ≥62). According to cut-off levels developed to categorize the intensity of IP experiences 8.4% of participants had low experiences of IP, 26.0% moderate, 42.6% frequent, and 23.0% intense experiences of IP. Of all participants, 91.6% had at least moderate experiences of IP and 65.6% had frequent to intense experiences of IP. Women scored significantly higher on CIPS than men. In contrast, neither attending semester nor age group significantly impacted CIPS scores. Finally, there was a moderate correlation between the levels of perceived stress and anxiety, respectively, and the IP scores.

Conclusion: This study suggests that the majority of dental, medical, nursing, psychology and law students experience severe IP. Moreover, this study provides valuable insights into the association of IP with perceived stress and anxiety. The results underscore the significance of exploring IP and its link to psychological distress, suggesting that interventions aimed at diminishing IP may play a crucial role in enhancing the well-being of university students.

BACKGROUND: In uterine cervical cancer (UCC), tumour staging is performed according to the 2018 International Federation of Gynecology and Obstetrics (FIGO) system, where imaging is incorporated, or the more generic Tumour Node Metastasis (TNM) classification. With the technical development in diagnostic imaging, continuous prospective evaluation of the different imaging methods contributing to stage determination is warranted. The aims of this interim study were to (1) evaluate the performance of radiological FIGO (rFIGO) and T staging (rT) with 2-fluorine-18-fluoro-deoxy-glucose (2[18F]-FDG)-positron emission tomography with computed tomography (PET/CT) and with magnetic resonance imaging (PET/MRI), compared to clinical FIGO (cFIGO) and T (cT) staging based on clinical examination and conventional imaging, in treatment-naïve UCC, and to (2) identify possible MRI biomarkers for early treatment response after radiotherapy.

METHODS: Ten consecutive patients with newly diagnosed UCC from the prospective PRODIGYN (Prognostic and Diagnostic Added Value of Medical Imaging in Staging and Treatment Planning of Gynecological Cancer) study (ethical approval number 2022-04207-01; NCT05855941) were included. Study participants underwent 2[18F]FDG-PET/CT and -PET/MRI, and an additional MRI one week after radiotherapy. Agreement between rFIGO and cFIGO was analysed using Cohen's kappa. Differences in rFIGO between 2[18F]FDG-PET/CT and -PET/MRI were evaluated with Wilcoxon signed ranks test, and added value of rFIGO for metastasis assessment was demonstrated with descriptive statistics.

RESULTS: In 2/10 patients, a higher stage was obtained with rFIGO compared to cFIGO, where presence of metastases led to upstaging. In 3/10, rFIGO was lower than cFIGO, and in 5/10 rFIGO and cFIGO were similar. Degree of agreement between rFIGO and cFIGO was poor, (κ = 0.091, p < 0.005) with 2[18F]FDG-PET/CT and (κ = - 0.010, p > 0.05) with FDG/PET/MRI). There was no significant difference between 2[18F]FDG-PET/CT and -PET/MRI for rFIGO (p = 0.18), or rT stage assessment (p = 0.32). MRI-derived tumour volume and apparent diffusion coefficient (ADC) were most affected on MRI one week after radiotherapy.

CONCLUSIONS: Our results indicate that there is an added value of rFIGO staging with 2[18F]FDG-PET/CT and -PET/MRI compared to clinical examination and conventional radiology, for metastasis assessment in treatment-naïve UCC. In early treatment response evaluation with MRI, ADC and tumour volume may be predictive parameters of interest in future prognostic analyses.

TRIAL REGISTRATION: Clinical Trials, NCT05855941. Registered 02 May 2023, https://clinicaltrials.gov/study/NCT05855941?term=NCT05855941&rank=1 .

INTRODUCTION: Palliative care is an important aspect of gynaecological oncology practice. In order to successfully integrate end-of-life (EOL) care in the disease trajectory, it is crucial to incorporate systematic training in subspecialty programmes in gynaecological oncology. We aimed to evaluate the quality of training in palliative care across gynaecological oncology fellows in Europe and to provide a framework to facilitate learning opportunities.

METHODS: A web-based questionnaire was sent to members of the European Network of Young Gynae-Oncologists (ENYGO). The survey consisted of 36 items covering six domains: respondents' characteristics, quality and quantity of teaching, curriculum achievements, observation and feedback, EOL clinical practice and attitudes about palliative care.

RESULTS: Of the 703 clinicians enrolled in the study, 142 responded (20.2%). Although the majority worked in university hospitals, only half of them (47%) were in a formal subspecialty programme. The majority of respondents (60%) were trained without a mandatory rotation in palliative care units and considered the quality of EOL care teaching as 'very poor' or 'poor' (57.7%). The majority of respondents (71.6%) did not receive any supervision or feedback at the time of their first consultation on changing the goals of care.

CONCLUSION: Our study underlines lack of structured teaching and supervision in palliative care contents among European fellows in gynaecological oncology. Broad education of healthcare providers is a key factor to achieve the integration of palliative care in gynaecological oncology practice. Stakeholders like European Society of Gynaecological Oncology/ENYGO play an important role to facilitate educational activities and training programmes targeting to EOL care.

Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.

Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.

Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043).

Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.

OBJECTIVE: Both the location of primary disease and treatment side effects may have an impact on sexual function in oncogynecological patients. The aim of this study was to examine the prevalence, strategies, difficulties, and ideas for improvement in sexual counseling among specialists managing patients with gynecologic malignancies.

METHODS: This was a cross-sectional survey study performed among healthcare professionals treating patients with gynecologic malignancies. A self-prepared questionnaire included 61 questions concerning general demographic information and different aspects of sexual counseling in the gynecologic oncology practice. Analysis included attitudes, behaviors, management strategies, difficulties, and ideas for possible systemic improvements. Statistical analysis involved descriptive statistics, two-sided chi-square test, and Fisher's exact test.

RESULTS: A total of 150 respondents from 46 countries answered the survey. The majority of survey participants stated that sexual counseling of oncological patients is very important (n=73, 49%) or important (n=46, 31%). One hundred and two (68%) respondents agreed that sexual counseling of gynecologic oncology patients should be routinely provided by the specialist managing the primary disease. However, collecting information concerning sexual function is performed often or always by only 21% of respondents and 19% discuss the topic rarely or never. The most frequently indicated barriers leading to difficulties in sexual counseling include lack of time (74%), lack of specialist knowledge (55%), and patient embarrassment (48%). One hundred and seven (71%) respondents expressed interest in participating in sexual counseling workshops organized by the European Society of Gynaecological Oncology (ESGO)/European Network of Young Gynaecological Oncologists (ENYGO), 74 (49%) would like to access webinars on the topic, and 120 (80%) would be interested in materials in the ESGO online educational resources.

CONCLUSION: One of the proposed solutions to insufficient access to sexual care for women with gynecologic malignancies is providing access to specialist educational programs for both patients and healthcare specialists.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.

Primary vaginal cancer (PVC) is a rare gynae- cological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prog- nosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was signifi- cantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.

Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously.

Materials and methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses.

Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma.

Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.

INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.

MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.

RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).

CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.