Adjuvant Radiotherapy in Stage II Endometrial Cancer: Selective De-intensification of Adjuvant Treatment.

AIMS: Risk stratification, including nodal assessment, allows for selective de-intensification of adjuvant radiotherapy in stage II endometrial cancer. Patterns of treatment and clinical outcomes, including the use of reduced volume 'mini-pelvis' radiotherapy fields, were evaluated in a population-based study. MATERIALS AND METHODS: All patients diagnosed with pathological stage II endometrial cancer between 2000 and 2014, and received adjuvant radiotherapy in a regional healthcare jurisdiction were reviewed. Registry data were supplemented by a comprehensive review of patient demographics, disease characteristics and treatment details. The Charlson Comorbidity Score was calculated. Survival and recurrence data were analysed. RESULTS: In total, 264 patients met the inclusion criteria. Most patients had endometrioid histology (83%); 41% of patients had International Federation of Gynecologists and Obstetricians grade 1 disease. Half (49%) had surgical nodal evaluation; 11% received chemotherapy. Most patients (59%) were treated with full pelvic radiotherapy fields ± brachytherapy. Seventeen per cent of patients received mini-pelvis radiotherapy ± brachytherapy, whereas 24% received brachytherapy alone. Five-year recurrence-free survival was 87% for the entire cohort, with no significant difference by adjuvant radiotherapy approach. Only one patient receiving mini-pelvis radiotherapy ± brachytherapy recurred in the pelvis but outside of the mini-pelvis field. Recorded late toxicity rates were highest for full pelvis radiotherapy + brachytherapy. CONCLUSION: Risk stratification in a real-world setting allowed for selective de-intensification of adjuvant radiation with equivalent outcomes for stage II endometrial cancer. Mini-pelvis radiotherapy combined with brachytherapy is effective in highly selected patients, with the potential to decrease toxicity without compromising local control. Brachytherapy should be considered in low-risk stage II patients.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Innovation in Indian Handloom Weaving.

Handloom weaving is the second most important livelihood in rural India after farming. Improving handloom technologies and practices thus will directly affect the lives of millions of Indians, and this is similar for many other communities in the global South and East. By analyzing hand-loom weaving as a socio-technology, we will show how weaving communities are constantly innovating their technologies, designs, markets, and social organization-often without calling it innovation. This demonstration of innovation in handloom contradicts the received image of handloom as a pre-modern and traditional craft that is unsustainable in current societies and that one should strive to eliminate: by mechanization and/or by putting it into a museum.

Controlled human malaria infection trials: How tandems of trust and control construct scientific knowledge.

Controlled human malaria infections are clinical trials in which healthy volunteers are deliberately infected with malaria under controlled conditions. Controlled human malaria infections are complex clinical trials: many different groups and institutions are involved, and several complex technologies are required to function together. This functioning together of technologies, people, and institutions is under special pressure because of potential risks to the volunteers. In this article, the authors use controlled human malaria infections as a strategic research site to study the use of control, the role of trust, and the interactions between trust and control in the construction of scientific knowledge. The authors argue that tandems of trust and control play a central role in the successful execution of clinical trials and the construction of scientific knowledge. More specifically, two aspects of tandems of trust and control will be highlighted: tandems are sites where trust and control coproduce each other, and tandems link the personal, the technical, and the institutional domains. Understanding tandems of trust and control results in setting some agendas for both clinical trial research and science and technology studies.

Radiation-induced morphological changes in the vagina.

BACKGROUND AND PURPOSE: Treatment-induced chronic vaginal changes after definitive radio(chemo)therapy for locally advanced cervical cancer patients are reported as one of the most distressing consequences of treatment, with major impact on quality of life. Although these vaginal changes are regularly documented during gynecological follow-up examinations, the classic radiation morbidity grading scales are not concise in their reporting. The aim of the study was therefore to identify and qualitatively describe, on the basis of vaginoscopies, morphological changes in the vagina after definitive radio(chemo)therapy and to establish a classification system for their detailed and reproducible documentation. PATIENTS AND METHODS: Vaginoscopy with photodocumentation was performed prospectively in 22 patients with locally advanced cervical cancer after definitive radio(chemo)therapy at 3-24 months after end of treatment. All patients were in complete remission and without severe grade 3/4 morbidity outside the vagina. RESULTS: Five morphological parameters, which occurred consistently after treatment, were identified: mucosal pallor, telangiectasia, fragility of the vaginal wall, ulceration, and adhesions/occlusion. The symptoms in general were observed at different time points in individual patients; their quality was independent of the time of assessment. Based on the morphological findings, a comprehensive descriptive and semiquantitative scoring system was developed, which allows for classification of vaginal changes. A photographic atlas to illustrate the morphology of the alterations is presented. CONCLUSION: Vaginoscopy is an easily applicable, informative, and well-tolerated procedure for the objective assessment of morphological vaginal changes after radio(chemo)therapy and provides comprehensive and detailed information. This allows for precise classification of the severity of individual changes.

Voluntary exercise does not enhance long-term potentiation in the adolescent female dentate gyrus.

The hippocampus is a dynamic brain structure involved with learning and memory. Long-term potentiation (LTP) is a neuronal model of learning and memory and, in adult rodents, is enhanced by voluntary exercise (VEx). The current study sought to elucidate whether synaptic plasticity in the male and female adolescent hippocampus is augmented by VEx. Consistent with previous studies, VEx significantly enhanced LTP in adolescent males following weak and strong theta-burst stimulation. Despite running the same amount as males, however, VEx did not enhance LTP in females above non-runner females. Surprisingly, the exercise-induced enhancement to LTP in males was seen in the absence of a change in brain derived neurotrophic factor in the dentate gyrus (DG). These findings indicate that adolescent males and females are differentially sensitive to the potentiating effect of exercise on hippocampal synaptic plasticity.

The role of imaging in the pre-operative staging and post-operative follow-up of rectal cancer.

Developments in rectal cancer imaging have revolutionised the management of this condition. It has become increasingly important for oncologists and surgeons to have a working insight into radiological assessment in order to make informed clinical decisions. In this context, we discuss the role that imaging plays in the pre-operative staging, post-operative follow-up and therapy of this disease including some novel advances in the field. Rectal cancer outcomes have improved due to modern surgical techniques, namely total mesorectal excision. Meticulous pre-operative assessment remains key. Conventional TNM staging now appears less crucial compared to assessing tumour distance from the potential plane of surgical resection (particularly the circumferential margin bounded by the mesorectal fascia), and this is reliant on high-quality imaging. Those with margin threatening disease can be offered downstaging chemoradiotherapy to facilitate successful resection. Endorectal ultrasound is useful for T staging and CT for detecting metastases. Malignant lymph node identification remains a problem and the use of size and morphological criteria may lead to misdiagnosis. In the post-operative setting, intensive follow-up is associated with improved outcomes but there are many variations in protocols. Most modalities struggle to differentiate tumour from reactive or fibrotic tissue and functional imaging is being investigated as the solution. PET scanning, particularly PET/CT, has been a major recent development. It has superior utility in detecting recurrent disease, including when conventional imaging is negative, detects occult metastases and may significantly enhance our ability to deliver accurate radiotherapy. Imaging has also opened up avenues for guided therapies aimed at ablating liver metastases. Radiofrequency ablation, in particular, is being used successfully and can improve survival of stage four patients.

Imaging evaluation of potential donors in living-donor liver transplantation.

Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques.

Alternatives to mifepristone for early medical abortion.

OBJECTIVE: To review published reports of first-trimester medical abortion regimens that do not include mifepristone. METHODS: Reports listed in Pubmed and Medline on prospective and controlled trials of the efficacy of misoprostol, alone or associated with methotrexate, for first-trimester abortion were analyzed if they included more than 100 participants and were published since 1990. RESULTS: The efficacy of regimens using misoprostol alone ranged from 84% to 96%, and when misoprostol was used with methotrexate the efficacy ranged from 70% to 97%. Efficacy rates were influenced by follow-up interval. Treatment for infection, bleeding, and incomplete abortion were infrequent with both methods (0.3%-5%). CONCLUSION: Alone or in combination with methotrexate, misoprostol is an efficacious alternative to mifepristone for the medical termination of pregnancy.

Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial.

OBJECTIVE: To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion. DESIGN: Randomised nonblinded trial. SETTING: Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area. POPULATION: Women of reproductive age. METHODS: Consenting women presenting for abortion services with gestations less than 56 days and who met inclusion criteria were given 200 mg mifepristone orally and then randomised into three misoprostol study groups: (group I) 400 micrograms of oral misoprostol, (group II) 600 micrograms of oral misoprostol, and (group III) 800 micrograms of vaginal misoprostol. Misoprostol was self-administered at home 24-48 hours following mifepristone, and participants were instructed to take a second similar misoprostol dose at 24 hours after the initial dose if bleeding was less than a normal menstrual period. MAIN OUTCOME MEASURES: Successful abortion without surgery was 94.1%, with no significant differences across the three study groups (94.7% in group I, 93.4% in group II, and 94.3% in group III; P= 0.975). RESULTS: Efficacy and adverse effects did not differ significantly across the three study groups. Pain increased significantly across the study and the gestational age groups and was associated with lower acceptability. CONCLUSIONS: There appears to be a range of safe and effective options for early medical abortion with mifepristone including a choice between oral and vaginal administration of misoprostol.

Intra-cervical versus i.v. fentanyl for abortion.

BACKGROUND: The majority of abortions are performed using a para-cervical block (without general anaesthesia) and involve a significant amount of pain. If fentanyl was given with the lidocaine in the para-cervical block, it potentially could improve pain control while decreasing side effects and avoiding i.v. access for women having abortions. METHODS: This was a randomized double-blind placebo-controlled trial of two treatment arms: (i) para-cervical block with 100 microg of fentanyl i.v; or (ii) para-cervical block with 100 microg of fentanyl intra-cervically (i.c.) for first trimester abortion. The setting was a free-standing urban abortion clinic. The outcome measures were pain scores and side effects. RESULTS: A total of 104 women received the fentanyl i.v. and 98 received the fentanyl i.c. The two groups were similar with respect to age, gestational age, obstetric history, anxiety and depression. Pain scores (0-10) were 4.7 and 5.7 for dilation (P = 0.01) and 3.8 and 5.6 for suctioning (P < 0.001) in the i.v. and i.c. groups, respectively. Side effects were similar, but more women in the i.v. group received anti-emetics. More women in the i.c. group were dissatisfied with the pain control. CONCLUSION: I.v. fentanyl is more effective than i.c. fentanyl for pain control in abortion.

Anxieties and attitudes towards abortion in women presenting for medical and surgical abortions.

OBJECTIVE: To examine the differences in anxiety levels and attitudes towards abortion between women having an early medical abortion and women having a surgical (manual vacuum aspiration) abortion. METHODS: Women who presented for an early medical abortion or a surgical abortion at an urban, free-standing abortion clinic were invited to participate in this study. Fifty-nine women having a medical abortion and 43 women having a surgical abortion answered questionnaires before their scheduled abortion, and again 2 to 4 weeks after the abortion. Thirty women were interviewed about their answers. RESULTS: Anxiety levels were similar in both groups before the abortion procedure. Anti-choice views about abortion were seen in 60.5% of women having a medical abortion and in 37.3% of women having a surgical abortion (P = .027). Women who were pro-choice had a mean anxiety score of 5.0 (range, 0-10) before and 2.7 after the abortion, whereas women who were anti-choice had a mean anxiety score of 5.2 before and 4.4 after the abortion (P = .005). CONCLUSION: It is important for providers of abortion care to understand that women undergoing a medical abortion may be more ambivalent about abortion than women undergoing a surgical abortion, and women who are anti-choice but having an abortion may have unresolved anxiety after the procedure.

Pain control in medical abortion.

OBJECTIVES: In patients having medical abortions with methotrexate and misoprostol: (1) to determine if giving ibuprofen or acetaminophen plus codeine with misoprostol (prior to onset of pain) prevented severe pain; and (2) to determine if there were predictors of medical abortion pain. METHODS: A group of 281 women randomized to receive placebo, ibuprofen or acetaminophen with codeine. This was taken at home with the misoprostol 4-6 days after the methotrexate. RESULTS: There were no significant differences between the three groups with respect to age, gestational age, parity, anxiety, depression, worst period pain score, and ethnicity. There was no significant difference with respect to rates of severe pain scores. The mean pain score for the entire group was 6.2 on a scale of 0 to 10. Severe pain (scores of 9 or 10) were reported by 23.4% of women and in this group, the mean maternal age was lower (P=0.05), parity was lower (P=0.01), worst period pain scores were higher (P=0.001), anxiety scores were higher (P=0.05) and satisfaction was lower (P=0.01). CONCLUSIONS: The pain experienced in medical abortion causes significant distress and more research is needed to reduce it.

Universal screening for domestic violence in abortion.

The purpose of this study was to evaluate the policy of universal screening for domestic violence in an abortion clinic. Compliance with the policy was low, because only 254 of 499 women seen were asked the screening questions: 58% of Caucasians, 40% of East Asians, and 37% of South Asians were screened (P =.003). Of the 254 women asked about abuse, 38 said they had been abused in the past 12 months, giving a prevalence rate of domestic violence similar to that of the general population. Screening for domestic violence in women presenting for abortion is challenging, but feasible.