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.

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.

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.

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.

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.

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.

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.

Cost savings from emergency contraceptive pills in Canada.

OBJECTIVE: To estimate cost savings from emergency contraceptive pills in Canada. METHODS: We modeled cost savings when a single emergency contraceptive treatment was provided after unprotected intercourse and when women were provided emergency contraceptive pills in advance. RESULTS: Each dollar spent on a single treatment saved $1.19--$2.35 (in Canadian currency), depending on the regimen and on assumptions about savings from costs avoided by preventing mistimed births. The dedicated products Preven (Shire Canada, Inc., Oakville, Ontario) and Plan B (Paladin Labs, Inc., Montreal) were cost-saving even under the least favorable assumption that mistimed births prevented today occur 2 years later. Each dollar spent on advance provision of Preven saved $1.24--$12.23, depending on the regular contraception method, on how consistently emergency contraception was used when needed, and on whether mistimed births were averted forever or simply delayed. Plan B was almost always cost-saving, although less so. CONCLUSION: Emergency contraception was cost-saving whether provided when the emergency occurred or in advance to be used as needed. More extensive use of emergency contraception could save considerable medical costs by reducing unintended pregnancies.

Abortion induced with methotrexate and misoprostol: a comparison of various protocols.

Seven hundred fifty-six women had abortions induced with methotrexate and misoprostol. Various protocols were compared. In Group 1, phase 1, after receiving 50 mg/m2 methotrexate IM, 289 women were randomized to receive either 750 or 500 micrograms of vaginal misoprostol. In Group 1, phase 2, 84 women who had failed to abort after one dose of misoprostol were randomized to receive either vaginal or oral routes for the second dose of misoprostol given on Day 8. In Group 2, a cohort of 226 women who received 60 mg/m2 methotrexate were compared to the 289 women who received 50 mg/m2 in Group 1. There were no differences in rates of effectiveness in the various trial groups. Side effects were greater with 60 mg/m2 of methotrexate. In Group 3, a cohort of 241 women received the misoprostol in three vaginal doses 8 hr apart starting on Day 5, and were compared to the 289 women in Group 1 receiving one vaginal dose. In women whose medical abortion failed, fetuses were found to have limb abnormalities In the total group of 756 women, 88.8% aborted successfully without surgical aspiration, with only minor side effects, and the acceptance rate was high. This study indicates that medical abortions induced with methotrexate and misoprostol are safe and effective, but more research is needed to find a more effective protocol.

Choosing between surgical abortions and medical abortions induced with methotrexate and misoprostol.

Women phoning to request an abortion at a free-standing abortion clinic who were less than 46 days from the last menstrual period were given a choice between a surgical abortion and a medical abortion induced with methotrexate and misoprostol. Twenty-six percent (116 of 405 women) chose a medical abortion. Younger women were more likely to choose a surgical abortion. There were no other significant differences in the two groups in terms of gestational age, race, or prior pregnancies. The reasons most women listed as "very important" when making the decision to have a medical abortion were the timing (being able to have the abortion before 7 weeks), the privacy of aborting at home, and fear of surgery. The women who chose surgery gave the reasons of fear of experimental medications, the lack of emotional support at home, and wanting to avoid the extra visits and blood tests.

Comparing abortion induced with methotrexate and misoprostol to methotrexate alone.

This was a dual-cohort study performed to determine if, by using methotrexate alone, abortions could be induced with fewer side effects, without sacrificing effectiveness and patient satisfaction. The subjects were 358 consecutive patients who requested elective medical termination of pregnancy at < 7 weeks gestation. Women were given information and allowed to choose between methotrexate alone (50 mg/m2 intramuscularly) or methotrexate followed 4 days later by 800 micrograms misoprostol vaginally. The two groups were compared with respect to the number of surgical aspirations required, the number of days until the abortion was completed, side effects, and the number of women who would choose the same method again. The surgery rate for methotrexate was 17.2%, whereas for the combination it was 10.9%. The mean numbers of days until the abortion were complete was 23 and 12, respectively. Side effects, mean pain scores, total days of bleeding, and satisfaction rates were not significantly different in the two groups. The high failure rate with methotreaxate alone suggests that it should not be offered despite the high level of satisfaction.

PIP: A dual-cohort study was conducted to determine whether abortion induced by methotrexate alone produces fewer side effects than a misoprostol-methotrexate regimen without sacrificing efficacy. 358 consecutive Canadian abortion seekers with pregnancies of 7 weeks' gestation or less were given the choice of a regimen of 50 mg/sq. m of intramuscular methotrexate or methotrexate followed 4 days later by 800 mcg of vaginal misoprostol. 101 women chose the former and 257 opted for the latter regimen. Women tended to choose the methotrexate-only regimen to avoid misoprostol-related side effects; selection of the combination was motivated by a desire for a rapid pregnancy termination. 82 women (82.8%) in the methotrexate-only group and 228 (89.1%) in the combination group aborted successfully. The failure rate in both groups was significantly higher when the procedure was performed at 6 or more weeks of gestation. It took a mean of 23.1 days from injection to complete abortion in the methotrexate-only group compared with 11.7 days in the methotrexate-misoprostol group. More than half the women had medication-related side effects, primarily nausea, vomiting, and diarrhea, with no significant differences between groups. The mean number of days of bleeding was 9.0 in the methotrexate-only group and 10.1 in the combination group. The mean worst pain score (on an 11-point scale) was 6.4 in the former and 6.1 in the latter group. 91.8% of women in the methotrexate-only group and 90.7% of those in the misoprostol-methotrexate group who successfully aborted stated they would chose the same method again. Given the high failure rate, methotrexate alone should not be offered routinely to abortion seekers. Its use should be reserved for women with very early pregnancies who have relative contraindications for misoprostol.

Tamoxifen compared to methotrexate when used with misoprostol for abortion.

The purpose of this study was to compare tamoxifen to methotrexate, with respect to effectiveness, when followed by misoprostol to induce abortion. In the first phase, 198 women presenting for medical abortion at < 7 weeks gestation were randomized to receive either 40 mg of tamoxifen, followed 2 to 3 days later by 800 micrograms of misoprostol self-administered vaginally or 50 mg/m2 of methotrexate, followed 5 to 7 days later by the same dose of misoprostol. In the second phase, 200 women were randomized to receive 20 mg tamoxifen twice daily for 4 days, followed by 800 micrograms misoprostol or the same regimen of methotrexate and misoprostol as in phase 1. The main outcome measure was success rate determined by the number of women who aborted without surgery. In phase 1, the success rate was higher in the methotrexate group (93.0%) compared to the tamoxifen group (85.7%) (p = 0.045). In the tamoxifen group, nine of 98 women had incomplete abortions with symptoms requiring a surgical aspiration, compared to one of 100 women in the methotrexate group. In phase 2, the success rates were 90.9% in the methotrexate group compared to 84.7% in the tamoxifen group (p = 0.20). The side effects were less in the tamoxifen group in phase 1 but not in phase 2. When tamoxifen is given as a single dose, it is less effective than methotrexate but when it is given 20 mg twice daily for 4 days, there is no significant difference. Tamoxifen does not appear to have any benefits over methotrexate.

PIP: This study aims to compare the effectiveness of tamoxifen with that of methotrexate when each is used in combination with misoprostol for abortion. In the 1st phase of the study, 198 medical abortion cases at 7 weeks gestation were randomized to receive either 40 mg of tamoxifen followed by 800 mcg of misoprostol after 2-3 days or 50 mg/sq. m of methotrexate followed by the same dose of misoprostol after 5-7 days. In the 2nd phase, 20 mg tamoxifen twice daily for 4 days was administered to 200 women, followed by 800 mcg misoprostol or the same methotrexate and misoprostol regimen as in phase 1. The number of women who experienced abortion without surgery was determined to measure the success rate. The success rate in phase 1 was higher in the methotrexate group (93.0%) than in the tamoxifen group (85.7%) (p = 0.045). About 9 in 98 women in the tamoxifen group and 1 in 100 women in the methotrexate group had incomplete abortions, indicating surgical aspirations. In the 2nd phase, the success rates were 90.9% in the methotrexate group and 84.7% in the tamoxifen group (p = 0.20). There were fewer side effects in the tamoxifen group during the 1st phase but not in the 2nd phase. Tamoxifen was seen to be less effective than methotrexate if given in a single dose. There was no significant difference when tamoxifen was given in 20 mg doses twice daily for 4 days. There were no advantages observed in tamoxifen over methotrexate.

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.

Time lost from work among women choosing medical or surgical abortions.

This was a prospective cohort questionnaire study to compare the loss of ability to work in 62 women having medical and 69 having surgical abortions. Outcomes included the number of days lost from work outside the home and inside the home before and after the abortion appointment. The mean total loss from work inside the home was 10.1 days for the surgical group and 5.3 days for the medical group (P <.05). The mean total loss from work outside the home was not significant at 4.0 days for the surgical group and 2.5 days for the medical group.

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.

Pain control in abortion.

OBJECTIVE: To reduce the pain experienced during abortion. METHODS: A four-phase study was conducted at a free-standing abortion clinic. Phase 1: a double-blind, randomized, placebo-controlled trial of 600 mg ibuprofen given preoperatively was carried out in 193 women. Pain during the procedure and 30 min postoperatively was compared. Phase 2: a double-blind, randomized trial compared 1% lidocaine, buffered 1% lidocaine and 0.25% bupivacaine in terms of the pain of the injection and the pain of the procedure in 200 women. Phase 3: waiting times of 0, 3 and 10-20 min between the end of the injection and the beginning of the procedure were compared in terms of pain during the procedure in 139 women. Phase 4: local anesthetic was injected into one side of the cervix slowly and one side quickly and the pain of the injections was compared in 87 women. RESULTS: Phase 1: ibuprofen reduced pain scores more than placebo with the improvement being greatest for the postoperative period. Phase 2: buffered lidocaine was significantly less painful to inject than plain lidocaine or bupivacaine. Phase 3: waiting between the injection and the procedure did not improve pain control. Phase 4: slower injections were found to be less painful than fast injections. CONCLUSIONS: Several methods were found to improve pain control during abortions.

Arteriovenous malformations of the uterus associated with medical abortion.

Seven cases of uterine arteriovenous malformations associated with pregnancy were initially suspected by the history of prolonged bleeding after a medical abortion and then confirmed by color Doppler scanning. All cases were managed expectantly and resolved spontaneously. When AVMs required diagnosis by pathology or angiography, only the most severe cases would have been reported. Now that they can be recognized on ultrasound, it is possible that mild cases such as these will be found to be much more common.

Management of spontaneous abortion in family practices and hospitals.

BACKGROUND AND OBJECTIVES: We performed two retrospective chart surveys, the first of 200 consecutive hospital emergency visits for spontaneous abortion and the second in 33 family physicians' offices examining 245 patients with spontaneous abortions. This study determined the rate of surgical management of spontaneous abortions within family practices and hospitals, as well as the rate of referrals and complications. METHODS: In the retrospective chart surveys, the information collected included the number of spontaneous abortions, dilation and curettages (D&Cs), referrals, and complications. RESULTS: Of the women presenting to the hospitals, 92.5% had D&Cs, while 51% of the women presenting to family physicians had D&Cs. Of the women presenting to the hospitals, 99.5% were referred to gynecologists, compared with 41% of the family practice patients. Hemorrhage occurred in 4.6% of the hospital patients and 2% of the family practice patients. Infection occurred in 6% of the hospital patients and .8% of the family practice patients. CONCLUSIONS: Patients with spontaneous abortions who saw their family physicians were more likely to be managed conservatively than those seen in the hospitals. There was no increase in complications in the conservatively managed patients.

Misoprostol administration in medical abortion. A comparison of three regimens.

OBJECTIVE: To determine the best regimen for using misoprostol after methotrexate in medical abortion with respect to outcome and side effects. STUDY DESIGN: In a cohort study, we compared vaginal misoprostol in one cohort of 134 women who used 800 micrograms dry tablets with 99 women who used 600 micrograms wet and 197 women who used 800 micrograms wet. These cohorts were compared with respect to outcome and side effects. RESULTS: The "dry" group had fewer completed abortions by day 8 (55.2% as compared to 69.7% and 71.1%, P = .008) but similar surgery rates. The dry group also had fewer side effects, especially fever and chills (4.5% as compared to 25.3% and 40.6%, P = .0001) and vomiting (8.2% as compared to 16.2% and 20.3%, P = .01). CONCLUSION: Of the three methods, the one consisting of 600 micrograms of wet misoprostol is the most effective for early completion of abortion and has the fewest side effects.