Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses.

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.

Association between parity and pregnancy-associated tumor features in high-grade serous ovarian cancer.

PURPOSE: High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer subtype. Parity is an important risk-reducing factor, but the underlying mechanism behind the protective effect is unclear. Our aim was to study if the expression of hormones and proteins involved in pregnancy were affected by the woman's parity status, and if they may be associated with tumor stage and survival. METHODS: We evaluated expression of progesterone receptor (PR), progesterone receptor membrane component 1 (PGRMC1), relaxin-2, and transforming growth factor beta 1 (TGFß1) in tumor tissue from 92 women with HGSC parous (n = 73) and nulliparous (n = 19). Key findings were then evaluated in an independent expansion cohort of 49 patients. Survival rates by hormone/protein expression were illustrated using the Kaplan-Meier method. The independent prognostic value was tested by Cox regression, using models adjusted for established poor-prognostic factors (age at diagnosis, FIGO stage, type of surgery, and macroscopic residual tumor after surgery). RESULTS: HGSC tumors from parous women were PR positive (≥ 1% PR expression in tumor cells) more often than tumors from nulliparous women (42% vs. 16%; p-value 0.04), and having more children was associated with developing PR positive tumors [i.e., ≥ 3 children versus nulliparity, adjusted for age at diagnosis and stage: OR 4.31 (95% CI 1.12-19.69)]. A similar result was seen in the expansion cohort. Parity status had no impact on expression of PGRMC1, relaxin-2 and TGFß1. No associations were seen with tumor stage or survival. CONCLUSION: Tumors from parous women with HGSC expressed PR more often than tumors from nulliparous women, indicating that pregnancies might possibly have a long-lasting impact on ovarian cancer development.

Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Risk and mortality of testicular cancer in patients with neurodevelopmental or other psychiatric disorders.

BACKGROUND: Both testicular germ cell tumours (TGCT) and neurodevelopmental disorders are associated with urogenital malformations. Few studies have investigated the association between psychiatric disorders and TGCT. We investigated whether history of any psychiatric or neurodevelopmental disorder is associated with increased risk or mortality of TGCT. METHOD: This is a nested case-control study including 6166 TGCT patients diagnosed during 1992-2014, individually matched for age and calendar period to 61,660 controls. We calculated odds ratios (ORs) for the association between type of psychiatric diagnoses and TGCT risk. Among the cases, we used a cohort design and calculated hazard ratios (HRs) of the association between psychiatric diagnose and all-cause and TGCT-specific death. RESULTS: History of a neurodevelopmental disorder (attention deficit hyperactivity disorder, autism spectrum disorder and intellectual disabilities) was associated with an increased risk of seminoma (OR: 1.54; 1.09-2.19). Seminoma patients with neurodevelopmental disorders were younger (34 versus 38 years, p = 0.004) and had more stage IV disease (5.4% versus 1.2%) than those without. Psychiatric history overall was not associated with TGCT. Patient history of any psychiatric disorder was associated with an increased all-cause and TGCT-specific death. CONCLUSIONS: We report an association between neurodevelopmental disorders and testicular seminoma, and an increased TGCT-specific mortality for TGCT patients with psychiatric disorders.

Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes.

Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype-specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer-specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox-proportional hazard models. Parity was associated with a 78% decreased risk of cause-specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07-0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38-0.95]). We found no evidence of associations between parity and cause-specific mortality among the 334 patients with sex-cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population-based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.

Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women: a registry-based study.

BACKGROUND: Non-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear. METHODS: Using data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970-2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases' birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs. RESULTS: The risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23-0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs. CONCLUSIONS: We found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman's reproductive history.

Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women.

Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) ≤30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [≥4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), pheterogeneity < 0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.

Five Facets Mindfulness Questionnaire--reliability and factor structure: a Swedish version.

Two studies were conducted to assess the Swedish version of the Five Facets Mindfulness Questionnaire (FFMQ), which was originally created by Baer et al. (2006). The aim of Study 1 was to examine the psychometric properties of the FFMQ using data from 495 individuals. Quantitative and qualitative analyses resulted in a reduction of the scale by 10 items. Psychometric properties, including internal consistency of the revised instrument, were examined. The Swedish FFMQ provides results comparable to those obtained by Baer. Cronbach's alphas were high for all the facets. The Swedish FFMQ appears to be a potentially useful tool in measuring mindfulness among Swedish participants. The aim of Study 2 was to test the suggested hierarchical five-factor solution and construct validity, using a confirmatory factor analysis (CFA). Similar to findings for the English version of the FFMQ, the CFA showed that the Observing facet was not a significant part of an overall self-reported mindfulness structure in a Swedish population with little meditation experience.

Movement-provoked muscle torque and EMG activity in longstanding motor complete spinal cord injured individuals.

Muscle resistance was evaluated by measurement of movement-provoked torque performed during simultaneous thigh muscle EMG recordings in individuals with a motor complete spinal cord injury (SCI). Fifteen men with a motor complete (ASIA grade A or B) cervical injury participated in the study. The activity started at an average of 0.11 seconds after the start of the provoking movement as evidenced by EMG recordings. However, no activity at all was found before the end of the movement provocation for 0.3 seconds in >60% of the test situations, whereas muscle torque was recorded in all cases. Significantly higher resistive muscle torque (p = 0.049) was provoked during extension movement compared with that of flexion. On the contrary, the maximum muscle activity was significantly higher (p = 0.009) during flexion movement compared with that during extension, with no differences between muscle groups. The resistive muscle torque seems to measure the passive viscoelastic component rather then the active spastic component of the movement-provoked muscle resistance in our group of motor complete SCI individuals.

Effects of functional electrical stimulation training for six months on body composition and spasticity in motor complete tetraplegic spinal cord-injured individuals.

The effect of functional electrical stimulation (FES) training on body composition, assessed by computed tomography, and the effect of spasticity, assessed by both objective and subjective measures, are evaluated. Fifteen motor-complete spinal-cord-injured men participated in the study. Eight of the 15 subjects undertook FES cycling 3 times weekly for 6 months. Whole body computed tomography scans evaluated changes in body composition. Simultaneous Modified Ashworth Scale and electromyography (EMG) measurements, resistive torque (Kin-Com) and EMG measurements, and self-ratings with Visual Analogue Scale during four consecutive days were used to evaluate changes in spasticity. Lower extremity muscle volume increased by an average of 1300 cm3 (p < 0.001) in the training group compared to the control group, who experienced no change. Otherwise no changes in body composition were seen. Significant correlations (Spearman) were found between individual EMG activity recordings and movement-provoked Modified Ashworth Scale ratings in 26% of the test situations, irrespective of group and time. The objective and subjective evaluation of movement-provoked passive (viscoelastic) and active (spasticity-related) resistance remained unchanged.

Short Form 36 assessed health-related quality of life after focal spasticity therapy.

OBJECTIVE: Analysis of the impact of an individualized comprehensive focal spasticity management on health-related quality of life. DESIGN: Prospective observational and interventional 12-week trial in a single-centre rehabilitation outpatient clinic. PATIENTS: Forty-one adult patients with upper motor neurone lesions (23 men), mean age 52 (standard deviation 13) years; 27 stroke, 7 cerebral palsy and 7 miscellaneous diagnoses. METHODS: Patients were assessed using the Short Form 36 (SF-36) Questionnaire before and after intramuscular injections of botulinum toxin type A combined with physical interventions. Spasticity was assessed with the Ashworth Scale (0-4). A verbal scale for patients' self-report of therapy effect was also used. RESULTS: Significant improvement was found in 3 of 8 SF-36 health scales: social (p = 0.008) and physical functioning (p = 0.026), and role physical (p = 0.048). Spasticity improved significantly (mean 1.1, p < 0.001). Improvement according to the verbal scale was observed for 57 (86%) indications (overall improvement in 36 patients, 88%). CONCLUSION: Comprehensive focal spasticity management with botulinum toxin type A intramuscular injections and physical interventions can improve patients' perceived health-related quality of life in addition to objectively and subjectively measured motor functions.

Reliability of a criterion-based test of athletes with knee injuries; where the physiotherapist and the patient independently and simultaneously assess the patient's performance.

UNLABELLED: A new criterion-based evaluation test method, has been developed in order to assess the functional ability of athletes with knee injuries, 'Tests for Athletes with Knee-injuries' (TAK). The physiotherapist and the patient assess independently and simultaneously the patient's performance. The TAK comprises eight demanding functional activities with emphasis on strength, stability, springiness and endurance. OBJECTIVES: To evaluate the inter-rater and intra-rater reliability of TAK between the physiotherapist's and the patient's assessments. Further, to evaluate the relation between the functional tests in TAK and the isokinetic quadriceps muscle strength. MATERIALS AND METHODS: Fifty-nine subjects were included in the study. Thirty-one were anterior cruciate ligament (ACL) reconstructed, fourteen were ACL-injured not reconstructed and fourteen were healthy athletes. The inter-rater-reliability was evaluated by assessments of 59 subjects carried out by two independent physiotherapists using visual observation. The assessment was rated on a 0-10-point scale according to five elaborate criteria drawn up for each test. Simultaneously, the subjects were asked to rate their own performance on each test using a 0-10-point scale. The intra-rater-reliability of TAK was evaluated by a test-retest of 31 patients. The relation between the physiotherapist's and the patients' ratings as well as of the patients' ratings at two different occasions were evaluated. Isokinetic quadriceps muscle strength was measured in a Biodex dynamometer on all 59 subjects in order to study the relation between quadriceps muscle strength and the results of the functional tests in TAK. RESULTS: Inter-rater-reliability showed good consistency between the assessments of the two physiotherapists in seven of eight tests (kappa = 0.62-0.78). The intra-rater-reliability was moderate to good (kappa = 0.43-0.65) in the test-retest study. The consistency of the physiotherapist and the patients' assessments differed, but showed good correlation. The consistency of the test-retest study of the patients' assessment was low. The correlation between the isokinetic quadriceps muscle strength measured in a Biodex dynamometer and the results of the functional tests was moderate in this study. CONCLUSIONS: This criterion-based test method for athletes with knee injuries showed good inter-rater reliability and acceptable intra-rater reliability for the physiotherapists' assessment. The consistency of the patients' ratings was low. The correlation between isokinetic quadriceps muscle strength and functional tests in TAK was moderate. The validity has not been evaluated in this study but will be done in the future.