Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy.

Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation-induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation-induced intestinal syndromes: urgency-tenesmus syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient-reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecal-leakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation-induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.

Remarkable effects of infliximab on severe radiation-induced side effects in a patient with uterine cervical cancer: a case report.

Pelvic radiotherapy is a powerful treatment for a broad range of cancers, including gynecological, prostate, rectal, and anal cancers. Despite improvements in the delivery of ionizing beams, damage to non-cancerous tissue can cause long-term effects that are potentially severe, affecting quality of life and daily function. There is an urgent need for new strategies to treat and reverse the side effects of pelvic radiotherapy without compromising the antitumor effect. A woman with severe radiation-induced intestinal side effects was treated with the tumor necrosis factor-alpha inhibitor infliximab with a dose of 3 mg/kg every 4 to 6 weeks. With infliximab treatment, a remarkable improvement in her bowel health was observed. The patient's late bowel toxicity was reduced from Grade 2 to Grade 0 (RTOG/EORTC Late Radiation Morbidity Scale). Although it is necessary to proceed cautiously because of the risk of serious side effects from immunosuppressants, our case suggests that infliximab can be used to treat symptoms of chronic bowel dysfunction after radiotherapy.

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors. METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection. FINDINGS: 942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration. INTERPRETATION: Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors. FUNDING: This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).

Barriers to and strategies for dealing with vaginal dilator therapy - Female pelvic cancer survivors' experiences: A qualitative study.

PURPOSE: Vaginal changes, a frequently reported late effect among women treated with pelvic radiotherapy, can result in sexual dysfunction and distress. Women are recommended vaginal dilator therapy after completed radiotherapy; however, low adoption has been recognized. This study aims to provide insight into women's difficulties with carrying out vaginal dilator therapy and their experiences of information. METHODS: Face-to-face, semi-structured interviews were undertaken with 12 pelvic cancer survivors in a selected sample of women with difficulties adopting the therapy. Interviews were audio-recorded, transcribed and analyzed using qualitative content analysis. RESULTS: One overarching theme, Being unprepared, emerged from three identified categories relating to Experience of received information, Experience of performing the therapy, and Motivation to perform the therapy. The women experienced the information as unrealistic and insufficient, and requested clearer and earlier information. Bleeding, pain, fear of cancer recurrence, and recalling memories from treatments were experienced. Women described intestinal symptoms, fatigue, and feeling that the therapy was self-harm as barriers to performing the therapy. They described creating routines, breathing exercises, relaxation, pre-warming the dilator and performing therapy together with their partner as helpful strategies. CONCLUSIONS: Careful discussion, early and clear communication, psychoeducation and supportive follow-up of vaginal changes should be integrated into cancer treatment and follow up. Healthcare professionals should be aware of potential difficulties with vaginal dilator therapy and identify women in need of extended support. Research is required to investigate interventions that suit the needs of female pelvic cancer survivors.

Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics.

Purpose: The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities. Methods and Materials: Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 × 1010 colony-forming unit/capsule twice daily) or high-dose probiotics (5 × 1010 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy. Results: Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 ± 8.92 days in the placebo and 8.65 ± 5.93 days in the high-dose probiotics group (P = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy (P = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain (P = .041) and defecation urgency (P = .08) and a reduced percentage of days with these symptoms (P = .023 and P = .042, respectively), compared with placebo. There were no differences regarding reported adverse events. Conclusions: Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer.

Sexual health and wellbeing among female pelvic cancer survivors following individualized interventions in a nurse-led clinic.

PURPOSE: Treatment-induced sexual and intestinal dysfunctions coexist among women after pelvic radiotherapy. We aimed to explore if sexual health and wellbeing may be improved after radiotherapy following nurse-led interventions and if an association exists between improved intestinal health and sexual health. METHODS: A population-based cohort of women treated with pelvic radiotherapy underwent interventions at a nurse-led clinic at Sahlgrenska University Hospital, Sweden, from 2011 to 2017. Self-reported questionnaires were used, pre- and post-intervention, to compare self-reported changes in sexual health and wellbeing. A regression model was performed to explore the association between intestinal and wellbeing variables. RESULTS: Among the 260 female pelvic cancer survivors included in the study, more women reported increased than decreased satisfaction with overall sexual health post-intervention (26.0% vs. 15.3%, p = 0.035). They also reported significantly reduced superficial genital pain (25.8% vs. 13.1%, p ≤ 0.025), reduced deep genital pain (23.1% vs. 8.0%, p ≤ 0.001), increased QoL (42.7% vs. 22.4%, p < 0.001), and reduced levels of depression (43.1% vs. 28.0%, p = 0.003) or anxiety (45.9% vs. 24.4%, p < 0.001) post-intervention. We found a significant association between reduced urgency to defecate and improved satisfaction with overall sexual health (RR 3.12, CI 1.27-7.68, p = 0.004) and between reduced urgency to defecate with fecal leakage and reduced anxious mode (RR 1.56, CI 1.04-2.33, p = 0.021). CONCLUSION: Sexual health and wellbeing can be improved by interventions provided in a nurse-led clinic focusing on physical treatment-induced late effects. Further research to optimize treatment strategies in female pelvic cancer survivors is needed.

Astatine-211 based radionuclide therapy: Current clinical trial landscape.

Astatine-211 (211At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.

A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy.

Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.

Cohort profile: an observational longitudinal data collection of health aspects in a cohort of female cancer survivors with a history of pelvic radiotherapy-a population-based cohort in the western region of Sweden.

PURPOSE: The study 'Health among women after pelvic radiotherapy' was conducted in response to the need for more advanced and longitudinal data concerning long-term radiotherapy-induced late effects and chronic states among female cancer survivors. The objective of this paper is to detail the cohort profile and the study procedure in order to provide a sound basis for future analyses of the study cohort. PARTICIPANTS: Since 2011, and still currently ongoing, participants have been recruited from a population-based study cohort including all female patients with cancer, over 18 years of age, treated with pelvic radiotherapy with curative intent at Sahlgrenska University Hospital in Gothenburg, in the western region of Sweden, which covers 1.7 million of the Swedish population. The dataset presented here consists of baseline data provided by 605 female cancer survivors and 3-month follow-up data from 260 individuals with gynaecological, rectal or anal cancer, collected over a 6-year period. FINDINGS TO DATE: Data have been collected from 2011 onwards. To date, three studies have been published using the dataset reporting long-term radiation-induced intestinal syndromes and late adverse effects affecting sexuality, the urinary tract, the lymphatic system and physical activity. These projects include the evaluation of interventions developed by and provided in a nurse-led clinic. FUTURE PLANS: This large prospective cohort offers the possibility to study health outcomes in female pelvic cancer survivors undergoing a rehabilitation intervention in a nurse-led clinic, and to study associations between demographics, clinical aspects and long-term late effects. Analysis focusing on the effect of the interventions on sexual health aspects, preinterventions and postinterventions, is currently ongoing. The cohort will be expanded to comprise the entire data collection from 2011 to 2020, including baseline data and data from 3-month and 1-year follow-ups after interventions. The data will be used to study conditions and treatment-induced late effects preintervention and postintervention.

Sexual health and wellbeing after pelvic radiotherapy among women with and without a reported history of sexual abuse: important issues in cancer survivorship care.

AIMS: Sexual abuse is a women's health concern globally. Although experience of sexual abuse and cancer may constitute risk factors for sexual dysfunction and low wellbeing, the effects of sexual abuse have received little attention in oncology care. This study aims to explore sexual health and wellbeing in women after pelvic radiotherapy and to determine the relationship between sexual abuse and sexual dysfunction, and decreased wellbeing. METHODS: Using a study-specific questionnaire, data were collected during 2011-2017 from women with gynaecological, anal, or rectal cancer treated with curative pelvic radiotherapy in a population-based cohort and a referred patient group. Subgroup analyses of data from women with a reported history of sexual abuse were conducted, comparing socio-demographics, diagnosis, aspects of sexual health and wellbeing. RESULTS: In the total sample of 570 women, 11% reported a history of sexual abuse and among these women the most common diagnosis was cervical cancer. More women with than without a history of sexual abuse reported feeling depressed (19.4% vs. 9%, p = 0.007) or anxious (22.6% vs. 11.8%, p = 0.007) and suffering genital pain during sexual activity (52% vs. 25.1%, p = 0.011, RR 2.07, CI 1.24-3.16). In the total study cohort, genital pain during sexual activity was associated with vaginal shortness (68.5% vs. 31.4% p ≤ 0.001) and inelasticity (66.6% vs. 33.3%, p ≤ 0.001). CONCLUSIONS: Our findings suggest that a history of both sexual abuse and pelvic radiotherapy in women are associated with increased psychological distress and sexual impairment, challenging healthcare professionals to take action to prevent retraumatisation and provide appropriate interventions and support.

Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy.

BACKGROUND: The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the 'excessive mucus discharge' syndrome after pelvic radiotherapy for gynaecological cancer. METHODS AND MATERIALS: From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as 'excessive mucus discharge' syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. RESULTS: The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ50: 1.28, 1.23, 1.32, D50: 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. CONCLUSION: An association was found between the mean dose to the small intestine and the occurrence of 'excessive mucus discharge'. When trying to reduce and even eliminate the incidence of 'excessive mucus discharge', it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.

Lifestyle and Long-Term Smoking Cessation.

BACKGROUND: Since smoking is the leading cause of preventable death, discouraging smoking initiation, encouraging smoking cessation, and exploring factors that help individuals to stay smoke free are immensely important. One such relevant factor may be the impact of lifestyle for long-term smoking cessation. METHOD: A representative sample of successful quitters was recruited for a study about smoking cessation. These respondents are now part of a 7-year follow-up with the overall aim of revealing factors affecting long-term smoking cessation. Descriptive analyses were carried out at baseline and at follow-up, as well as a further two-step cluster analysis to explore profiles of long-term smoke-free individuals. RESULTS: A majority did not make any particular lifestyle changes, but among those who did, most adopted a healthier lifestyle and/or increased their quota of physical training, where permanent changes in this direction seem to promote a more enduring smoke-free life. CONCLUSIONS: Individuals who want to quit smoking should be encouraged to increase their level of physical activity. Swedish health care institutions should be able to provide support for this both initially and over time to promote the long-term maintenance of a smoke-free lifestyle.

Problematic internet use: A scoping review - longitudinal research on a contemporary social problem, 2006-2017.

Background and aims: Problematic internet use (PIU), and kindred concepts such as internet addiction (IA), make up a growing research field, partly due to the suggested inclusion of internet gaming disorder in a future DSM-6 as well as the fact that gaming disorder is on its way to being included in the ICD-11. Conclusions from research are far from unified. This study aims to synthesise the research field of problematic internet use/internet addiction/gaming disorder, with a focus on the reporting of prevalence and change. Methods: Longitudinal studies of PIU/IA formed the basis for a scoping review. Systematic searches of Web of Science, Scopus and Proquest, for peer-reviewed and published articles based on empirical data collected at a minimum of two time points for studies, and with an end point set at 2017, led to the inclusion of 97 studies. Endnote X7 was used to organise the results and NVivo 11 was used for synthesising the results. Results: Analyses focused on prevalence and change. Findings show variation among measures and prevalence as well as in reported outcomes relating to social life and other problems. Most studies reported relations between PIU/IA and other problems in life, but no specific time order could be established. Furthermore, many studies did not present data on prevalence or change even though using a longitudinal survey design. Discussion and conclusions: In summary, the research field is plagued by a lack of consensus and common understanding, regarding both measures, perceptions of the problem, and findings.

Persistence in Problematic Internet Use-A Systematic Review and Meta-Analysis.

Background and Aims: Problematic internet use, internet addiction, and internet gaming disorder all describe a global phenomenon where individuals have trouble limiting their use of internet to such an extent that their use has negative consequences. Past systematic reviews and meta-analyses have focused on estimating prevalence, but there has been no comprehensive research synthesis of the trajectory of the problem. The research objective was to create a pooled estimate of the persistence of problematic internet use. This review included studies using a longitudinal panel data design with a follow-up of at least a year. Studies had to be published before the end of the year 2017, in peer-reviewed academic journals, using English language. Samples from populations in any country were accepted, given they were of acceptable quality. Methods: A literature search was conducted in Web of Science, Pro Quest, and Scopus. Several definitions of problematic internet use were included. Inverse-variance, random-effect meta-analysis was used to estimate weighted summary means of persistence. Attrition and selection bias was investigated using pre-specified tools, and heterogeneity was assessed in subgroup analysis. Results: Nine studies fit the criteria, all using samples from Asian or Western countries. The aggregate estimate for 1-year persistence it was 50% (CI: 40-61%), but results were heterogeneous. Prevalence and persistence estimates were correlated and generally higher in Asian countries. Methodological differences only explain part of the heterogeneity. Conclusion: All included studies found individuals with persistent problems, but the between-studies variation is substantial.

Sex steroid hormone receptor expression in the vaginal wall in cervical cancer survivors after radiotherapy.

Background: Sex steroid hormones and their receptors are important in female sexual function. The aim of this study was to investigate the expression and distribution of estrogen receptor (ER)α, ERß, G-protein-coupled ER-1 (GPER), androgen receptor (AR), progesterone receptor (PR)A, PRB and connective tissue growth factor (CTGF) in the vaginal wall among women who had been treated for cervical cancer with radiotherapy. Material and methods: We included cervical cancer survivors treated with radiotherapy and premenopausal control women of the same age scheduled for benign gynecological surgery. We analyzed the expression and distribution of sex steroid hormone receptors and CTGF in biopsies from the vaginal wall, by real-time PCR and immunohistochemistry (IHC). Serum samples were analyzed for hormone levels and radiation dose at biopsy site were calculated and correlated to levels of the sex steroid hormone receptors. Results: In the cervical cancer survivors (n = 34), we found a lower expression of ERα at both mRNA and protein levels, compared to the control women (n = 37). In the survivors with high radiation dose at biopsy site, the immunostaining of ERα and AR was lower in the epithelium and the stroma, compared to survivors with minimal radiation dose. The later group showed expression of ERα comparable to the control women. The cancer survivors were sufficiently substituted with systemic estradiol with no difference in the serum estradiol levels compared to control women. Conclusions: We found that external radiation reduces the ERα and AR protein expression in the vaginal mucosa, indicating that the vaginal changes in irradiated cervical cancer survivors and the lack of response to hormonal treatment could be due to the decreases in sex steroid hormone receptor expression.

Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations.

Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle-emitting 211At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using 211At conjugated to MX35, the antigen-binding fragments-F(ab')2-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of 211At-MX35 F(ab')2.Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.

Intake of citrus fruits and vegetables and the intensity of defecation urgency syndrome among gynecological cancer survivors.

BACKGROUND: Despite the experimental evidence that certain dietary compounds lower the risk of radiation-induced damage to the intestine, clinical data are missing and dietary advice to irradiated patients is not evidence-based. MATERIALS AND METHODS: We have previously identified 28 intestinal health-related symptoms among 623 gynaecological-cancer survivors (three to fifteen years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five radiation-induced survivorship syndromes: defecation-urgency syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge and blood discharge. The grouping was based on factor scores produced by Exploratory Factor Analysis in combination with the Variable Cutoff Method. Frequency of food intake was measured by a questionnaire. We evaluated the relationship between dietary intake and the intensity of the five syndromes. RESULTS: With the exception of excessive mucus discharge, the intensity of all syndromes declined with increasing intake of citrus fruits. The intensity of defecation-urgency and fecal-leakage syndrome declined with combined intake of vegetables and citrus fruits. The intensity of excessive mucus discharge was increased with increasing intake of gluten. CONCLUSION: In this observational study, we found an association between a high intake of citrus fruits and vegetables and a lower intensity of the studied radiation-induced cancer survivorship syndromes. Our data suggest it may be worthwhile to continue to search for a role of the diet before, during and after radiotherapy to help the cancer survivor restore her or his intestinal health after irradiation.

Long-term fertility, oncological, and quality-of-life outcomes after trachelectomy in early stage cervical cancer.

PURPOSE: Our aim was to evaluate fertility-sparing surgery of early stage cervical cancer after the introduction of vaginal trachelectomy (VT) and pelvic lymph node dissection (PLND). The objectives were to assess surgical, long-term oncological, fertility, and obstetric outcomes together with self-assessed quality of life (QoL). METHODS: All women ≤ 40 years diagnosed with early stage cervical cancers IA1-IB1 and ≤ 2 cm treated by VT and PLND between 2000 and 2014 were included. All successful fertility-sparing surgeries were identified. Medical records were reviewed and analyzed for surgical, oncological, fertility, and obstetric outcomes. Postal questionnaires were collected to further evaluate and validate the fertility and obstetric outcomes and QoL was assessed using the QLQ-C30 and QLQ-CX24 instruments. RESULTS: Thirty-nine patients fulfilled the inclusion criteria, where 28 patients (71.8%) had successful VT performed with preserved fertility according to the oncological guidelines. Mean follow-up after VT was 95.0 months (range 26.5-182.4). There were 2 recurrences (7.1%) registered. All together, 24 pregnancies were identified and 17 children born; 76.5% after gestational week (gw) ≥ 34 + 0 and 23.5% preterm (gw < 34 + 0). The questionnaires revealed an overall high level of self-assessed QoL with global health status scores of 91.7 (median) and physical, role, emotional, cognitive, and social functioning all had median scores of 100 and a low incidence of "symptom experience scores" of urogynecological morbidity, although 38.9% experienced lymphedema. CONCLUSIONS: Early stage cervical cancers treated by VT and PLND are associated with acceptable long-term oncological outcomes, relatively high rate of successful pregnancies, and a high long-term QoL.

Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.

PURPOSE: To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future. MATERIAL AND METHODS: From a larger group of gynecological cancer survivors followed-up 2-14 years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models. RESULTS: The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3 Gy, γ50 = 1.19 for all models, s was 7.0e-09 for RS and n was 9.9 × 107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5 Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB. CONCLUSIONS: Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.

A weak scientific basis for gaming disorder: Let us err on the side of caution.

We greatly appreciate the care and thought that is evident in the 10 commentaries that discuss our debate paper, the majority of which argued in favor of a formalized ICD-11 gaming disorder. We agree that there are some people whose play of video games is related to life problems. We believe that understanding this population and the nature and severity of the problems they experience should be a focus area for future research. However, moving from research construct to formal disorder requires a much stronger evidence base than we currently have. The burden of evidence and the clinical utility should be extremely high, because there is a genuine risk of abuse of diagnoses. We provide suggestions about the level of evidence that might be required: transparent and preregistered studies, a better demarcation of the subject area that includes a rationale for focusing on gaming particularly versus a more general behavioral addictions concept, the exploration of non-addiction approaches, and the unbiased exploration of clinical approaches that treat potentially underlying issues, such as depressive mood or social anxiety first. We acknowledge there could be benefits to formalizing gaming disorder, many of which were highlighted by colleagues in their commentaries, but we think they do not yet outweigh the wider societal and public health risks involved. Given the gravity of diagnostic classification and its wider societal impact, we urge our colleagues at the WHO to err on the side of caution for now and postpone the formalization.