Impact of MRI resolution for Linac-based stereotactic radiosurgery.

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. Materials/Methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume. Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001). Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.

Prostate cancer malignancy detection and localization from mpMRI using auto-deep learning as one step closer to clinical utilization.

Automatic diagnosis of malignant prostate cancer patients from mpMRI has been studied heavily in the past years. Model interpretation and domain drift have been the main road blocks for clinical utilization. As an extension from our previous work we trained on a public cohort with 201 patients and the cropped 2.5D slices of the prostate glands were used as the input, and the optimal model were searched in the model space using autoKeras. As an innovative move, peripheral zone (PZ) and central gland (CG) were trained and tested separately, the PZ detector and CG detector were demonstrated effective in highlighting the most suspicious slices out of a sequence, hopefully to greatly ease the workload for the physicians.

Bone marrow suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides.

BACKGROUND: Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides. CASE PRESENTATION: Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a bone marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myelosuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean bone marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myelosuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions. CONCLUSIONS: Both patients treated with TSHT experienced severe bone marrow suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the bone marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myelosuppression and caution used even when treating to a dose of 12 Gy.

Oral contraceptives: does formulation matter?

OCs come in a variety of formulations but verifiable differences between products are difficult to find.

Preventing injuries and illnesses in the wilderness.

Wilderness trips have become increasingly popular, especially in the adolescent population. The wilderness can be a source of rejuvenation while being mentally and physically challenging; however, it is also fraught with the potential for injury, illness, and even death. Epidemiologic studies of injuries and illnesses from hikers are not extensive, but there are sufficient data to identify the most common risk factors to offer some strategies for prevention. Many youth will have a medical visit or preparticipation physical assessment before an organized wilderness experience. This article highlights commonly seen wilderness injuries and illnesses and provides guidance for proper planning and problem solving.

Mifepristone: ten years later.

While pregnant women have sought abortifacients for thousands of years, they had no success at finding one that both worked and did not jeopardize their lives in the process. The discovery of mifepristone, with both anti-glucocorticoid and anti-progesterone properties, has had a profound effect on women's lives while weaving the abortion-related political hazards. Despite the controversies, millions of women around the world have used mifepristone for medical abortion. This review describes how researchers addressed the numerous barriers of a mifepristone abortion (i.e., gestational age limitation, lengthy process, high costs, complex regimen, failures, side effects and complications) and continue to improve upon the limited numbers and types of clinicians offering mifepristone.

Mifepristone followed in 24 hours to 48 hours by misoprostol for late first-trimester abortion.

OBJECTIVE: To investigate the efficacy of mifepristone and misoprostol for the termination of pregnancies in the late first trimester. METHODS: This was a prospective study of 321 women seeking termination of pregnancy with gestations from 64 days to 84 days (+/-3 days) by vaginal ultrasonography. Women were enrolled at three sites: University of Rochester Reproductive Health Program in Rochester, New York; Hung Vuong Hospital in Ho Chi Minh City, Vietnam; and K.E.M. Hospital in Pune, India. Eligible women received 800 mcg of misoprostol vaginally between 24 hours and 48 hours after administration of 200 mg mifepristone. Two additional doses of 400 mcg of misoprostol were administered either orally or vaginally as needed every 3 hours for a maximum of two additional doses (total 1,600 mcg). The primary study outcome measure was complete abortion without surgical intervention. RESULTS: Eighty-nine percent of women who completed the study successfully terminated their pregnancies. Most women were either satisfied (64.8%) or very satisfied (28.6%) with their experience. Ninety-four percent of women reported that they would recommend the procedure to a friend. Most women (90.4%) also agreed they would request a medical abortion if they required another abortion at this gestational age. CONCLUSION: Medical abortion is acceptable and effective in the late first trimester and offers women an acceptable alternative to surgical abortion. LEVEL OF EVIDENCE: II.

Evidence for shortening the time interval of prostaglandin after mifepristone for medical abortion.

OBJECTIVES: The aim of this study was to compare regimens that shorten the interval between mifepristone and the prostaglandin misoprostol or gemeprost for medical abortion. METHODS: The Cochrane Controlled Trials Register and MEDLINE were systematically searched for the words mifepristone and abortion. Only randomized controlled trials comparing different mifepristone regimens with either misoprostol or gemeprost were included. The outcome was a complete abortion not requiring surgical evacuation. RESULTS: Five randomized trials were identified and all were published since 1999. Four were from the United States and three had enrollments of >1000. The route of administration of the prostaglandin was used vaginally, except in one study where misoprostol was divided in two doses 2 h apart. Four studies provided information about a 1-day interval and two trials provided information about an interval of 6-8 h evaluating mifepristone 200 mg and misoprostol 800 microg vaginally. There were no significant differences noted between the current 2-day interval compared with the 1-day interval. There was one study suggesting no difference with an interval of 6-8 h. CONCLUSIONS: The interval between mifepristone and misoprostol 800 microg vaginally can be decreased from 48 to 6-8 h without loss of efficacy.

Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period.

OBJECTIVE: Mifepristone-misoprostol medical abortion has been approved in the United States since 2000. U.S. providers have preferred to use vaginal misoprostol because of evidence that such a regimen is more effective in later gestations. Buccal administration of misoprostol may be equally effective and more acceptable to some women. METHODS: This open-label, randomized trial was conducted at two sites in Rochester, NY, and involved healthy women with pregnancies through 56 days since the last menstrual period (LMP) as indicated by sonogram. Women received mifepristone 200 mg orally and were randomized to use 800 mug of misoprostol either buccally or vaginally 1 to 2 days later. They returned within 15 days for repeat sonogram. If the woman's pregnancy had not been completely aborted by day 36, a suction abortion was performed. The primary outcome was a complete abortion without surgical intervention. RESULTS: Four hundred forty-two women were enrolled in the study, and complete data were available on 429. The efficacy rate was 95% (205/216) in the buccal group and 93% (199/213) in the vaginal group (chi(2)=0.43, p=.51). Nausea was the most commonly reported side effect, affecting 70% in the buccal group and 62% in the vaginal group. There were no differences in the satisfaction with the overall procedure between the buccal (92%) and the vaginal groups (95%) (chi(2)=1.87, p=.17). CONCLUSION: Buccal administration of misoprostol after low-dose mifepristone for medical abortion appears to be a highly effective and acceptable alternative compared with vaginal administration for medical abortion in pregnancies through 56 days LMP.

Multicenter trial of a simplified mifepristone medical abortion regimen.

OBJECTIVE: To provide evidence regarding the safety, efficacy, and acceptability of 200 mg mifepristone followed by home administration of 400 mug oral misoprostol METHODS: The 376 women enrolled in this prospective, open-label, multicenter trial were administered mifepristone in the clinic and were given 2 tablets of 200 mug misoprostol to swallow at home 48 hours later. On day 15, women returned to the clinic for a gynecologic examination. Success was defined as a complete termination without surgical intervention or additional misoprostol by day 21. All participants completed an exit interview before discharge from the study RESULTS: Of the women enrolled, 58.8% had gestations of between 43 and 49 days, 54.7% had had a previous abortion, and 76% had had a previous pregnancy. Of the 354 women included in the efficacy analysis, 324 (91.5%) had a successful termination. The most common adverse effects reported by patients were pain or cramps (93.2%) and nausea (66.6%), followed by weakness (54.7%), headache (46.2%), and dizziness (44.4%). Overall acceptability of the regimen was high, with 63.3% of women reporting that it was very satisfactory and an additional 23% reporting that it was satisfactory CONCLUSION: A regimen of 200 mg mifepristone followed in 48 hours by home administration of 400 mug oral misoprostol is effective, associated with rare severe adverse effects or adverse events, and acceptable for women seeking medical abortion of pregnancies of up to 49 days duration as compared with the regimen currently approved by the Food and Drug Administration. LEVEL OF EVIDENCE: III.

Comparison of misoprostol plasma concentrations following buccal and sublingual administration.

BACKGROUND: New indications for misoprostol include medical abortion, cervical softening, induction of labor and treatment of postpartum hemorrhage. Various routes of misoprostol administration under study include oral, vaginal, buccal, sublingual and rectal. MATERIALS AND METHODS: This was an open-label, randomized, cross-over study of the pharmacokinetic differences of buccal vs. sublingual misoprostol 800 mug in 10 healthy women. RESULTS: Of the 10 women enrolled, 2 withdrew after experiencing excessive cramping from the sublingual route of misoprostol. The mean misoprostol plasma concentration-time curves at 4 h [area under the curve (AUC)0-4)] and the maximum concentration (C(max)) showed that levels were significantly higher for sublingual administration than the buccal route. Buccal misoprostol administration resulted in fewer symptoms and was found to be more acceptable. CONCLUSIONS: Sublingual administration of misoprostol had a higher AUC and C(max) compared with buccal administration. The pharmacokinetics may help to determine the best application of misoprostol depending on the indication.

Low-dose mifepristone for contraception: a weekly versus planned postcoital randomized pilot study.

In this randomized pilot study, we compared the contraceptive efficacy, safety and side effect profiles of weekly versus planned postcoital regimens of low-dose mifepristone. Forty participants were randomized to receive mifepristone 10 mg weekly or planned postcoitally (to be used no more frequently than once every 5 days), for 12 consecutive months. Participants were evaluated monthly to determine pregnancy, ovulation status and acceptability of physical side effects. We ended this pilot study prematurely due to low efficacy and predetermined stopping rules. Three pregnancies during 56 woman-months occurred in the weekly group and three pregnancies during 68 woman-months occurred in the planned postcoital group. Almost half of the participants ovulated monthly on either regimen. The majority of the participants found the physical side effects of these regimens acceptable. Participants in the planned postcoital group, however, found adhering to the regimen more difficult than those in the weekly group. Mifepristone 10 mg used weekly or planned postcoitally did not adequately prevent pregnancy in our pilot study population. Although the concept of intermittent low-dose mifepristone is appealing, the contraceptive effectiveness was disappointing.

A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion.

OBJECTIVE: To demonstrate equivalence between mifepristone 200 mg followed 6 to 8 hours later and 24 hours later by misoprostol 800 microg vaginally for abortion in women up to 63 days of gestation. METHODS: Mifepristone 200 mg was swallowed by 1,080 women after which they were randomly assigned to self-administer misoprostol intravaginally 6 to 8 hours later (group 1) or 23 to 25 hours later (group 2) at home. Participants returned for an evaluation, including transvaginal ultrasonography, 7 +/- 1 days after initiating treatment. Subjects who had not aborted were offered a second dose of misoprostol. All participants returned approximately 2 weeks after receiving mifepristone. Telephone contact was also attempted approximately 5 weeks after treatment. Treatment was considered a failure if a suction aspiration was performed for any indication. RESULTS: Complete abortion rates for groups 1 and 2 were 503 of 525 (95.8%, 95% confidence interval 93.7%, 97.3%) and 521 of 531 (98.1%, 95% confidence interval 96.6%, 99.1%), respectively, which were statistically equivalent. Side effects were significantly more common after mifepristone administration for women in group 2. Nausea, vomiting, and heavy bleeding were also significantly greater for women in group 2 after misoprostol treatment. Pain and subject acceptability were similar between groups. CONCLUSION: Mifepristone 200 mg followed 6 to 8 hours later by misoprostol 800 microg vaginally is as effective for abortion and has significantly fewer side effects as compared with regimens using a 24-hour dosing interval. Women receiving mifepristone and vaginal misoprostol for abortion can have the flexibility to administer the misoprostol as soon as 6 hours after using the mifepristone.

Social context and the experience of a sample of U.S. women taking RU-486 (mifepristone) for early abortion.

Of 50 women seeking an abortion in Rochester, New York, between November 1999 and January 2001, 35 went on to complete an in-depth interview from 1 to 6 weeks after their follow-up clinical visit. A higher proportion of women who defined their pregnancy as a baby indicated emotional distress during their in-depth interview compared to those who saw their pregnancy as only having the potential to become a baby. The authors conclude that abortion might be made less difficult through public education about the different views of pregnancy and abortion throughout U.S. history. It might be important for abortion counselors to first ask a woman how she defines her pregnancy. A larger study is warranted.

Which cannulae fit the Ipas manual vacuum aspiration syringe?

BACKGROUND: The Ipas double-valve manual vacuum aspiration (MVA) syringe is an alternative to electrical vacuum aspiration. METHODS: This study determines which US cannulae (flexible, rigid-straight and rigid-curved) work with the Ipas MVA syringe. Cannulae from Ipas, MedGyn, Berkeley and Milex, in sizes 6-12 mm, were randomized and affixed to the MVA syringe. A pressure gauge was attached to the cannula with rubber tubing. Pressure readings were recorded initially and over 30 s. RESULTS: Milex cannulae were not compatible. For the remaining brands, initial vacuum pressures ranged from 55 to 65 mmHg. Flexible cannulae from Ipas, Berkeley and MedGyn maintained initial pressures without leaks, as did the 6-12-mm straight- and curved-rigid cannulae by Berkeley. Eight of the 13 tested MedGyn rigid cannulae lost >10% pressure over 30 s. CONCLUSION: Several US manufacturers produce cannulae that fit on the Ipas MVA syringe without a leak, including Ipas flexible cannula; Berkeley flexible, rigid-straight and rigid-curve cannulae and MedGyn flexible cannula, but not their rigid cannulae.

Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy.

This prospective, open-label, randomized trial of healthy adult women up to 9 weeks pregnant compared mifepristone 200 mg followed 2 days later with misoprostol 400 microg orally versus misoprostol 800 microg vaginally. The study was interrupted after the oral misoprostol group experienced a higher than expected failure rate. This treatment was discontinued and another substituted consisting of oral misoprostol 800 microg divided into two doses two hours apart. Women returned for a follow-up visit from Day 4 to 8. All women with a continuing pregnancy received a repeat dose of misoprostol vaginally and returned before Day 15. The primary outcome measure was a complete medical abortion without surgical intervention at the first visit. Of the 1045 women enrolled, 1011 had complete data: Group 1 (220) used oral misoprostol 400 microg, Group 2 (269) used oral misoprostol 800 microg, and Group 3 (522) used vaginal misoprostol 800 microg. At first follow-up visit, the primary outcome, that is, a complete abortion, was 84% for Group 1, 92% for Group 2, and 96% for Group 3, p < 0.001. After a second dose of vaginal misoprostol in women with on-going pregnancies at their first follow-up visit, the complete abortion rates were 91%, 95%, and 98%, respectively, p < 0.001. There were minimal differences in side effects, onset of bleeding and overall acceptability in the three groups. Mifepristone 200 mg followed by vaginal misoprostol 2 days later was more effective at inducing an abortion up to 9 weeks of pregnancy than the same dose of mifepristone followed by oral misoprostol.

Clinicians' perception of sonogram indication for mifepristone abortion up to 63 days.

One barrier in the US to wider acceptance of mifepristone for abortion is the additional cost of the routine use of two sonograms, that is, for pregnancy dating and confirmation of a complete abortion. The purpose of this study is to document how the accuracy of medical abortion clinicians experienced with pelvic exams and dating pregnancies in assessing gestational age at the first visit compared with sonograms, and to identify the factors influencing whether they perceive that sonograms are desired or indicated at the first and follow-up visits. This was a prospective study of 1016 women wanting to participate in a medical abortion trial. After informed consent, clinicians (1) dated the pregnancy before routine sonography and (2) determined whether a sonogram was indicated. Women with sonographic pregnancies of less than 63 days were eligible for mifepristone followed by misoprostol 48 h later. Women returned on Day 4 to Day 8, and clinicians performed a clinical assessment of whether the abortion was complete and determined whether a sonogram was indicated. Fifteen sites participated. Advanced-level providers performed 56% of the assessments. When clinicians assessed a pregnancy under 43 days gestation, they perceived that a sonogram was "not indicated" in 60% of these women. This percentage increased to 66% at 43-49 days gestation, and declined to 46% of women assessed at more than 49 days. Clinicians correctly assessed gestational age as no more than 63 days in 87% of women. In only 1% (14/1013) of their assessments did clinicians underestimate gestational age. In 7/24 (29%) women with a persistent gestational sac, clinicians did not indicate the need for sonography when it was likely indicated. We conclude that the clinicians in our study felt confident in not using sonography in most cases. If clinicians monitor hCG levels to identify any ectopic or continuing pregnancies, medical abortion can be safely performed without sonography.

Randomized trial of a Slip-Coat cannula for early abortion.

The objective of the study was to determine the effectiveness of a 6-mm coated cannula with Slip-Coat lubrication to avoid mechanical dilatation for abortion up to 712 weeks gestation. A blinded, randomized control trial of 50 healthy women, > or =18 years old, up to 54 days pregnant by ultrasound, requesting a surgical abortion was conducted. A successful outcome was defined as a completed abortion without the need for mechanical cervical dilatation. Of the 50 women, 29 received a Slip-Coat cannula, and 21 received a standard cannula. There were no overall differences in efficacy of the Slip-Coat cannula (17/29 or 59%) compared with the control group (12/21 or 57%, p = 0.91), or the acceptability of the procedure (93% versus 91%, respectively, p = 0.74), the level of pain (48 vs. 35, respectively, p = 0.052), acceptability of pain (66% vs. 67%, respectively, p = 0.93), or acceptability of bleeding (90% vs. 86%, respectively, p = 0.67). It was concluded that Slip-Coat cannulae were more effective than standard control cannulae for women who had no prior live births (6/10 or 60% vs. 0/7 or 0%, respectively, p = 0.01). This finding warrants further study.

Having an abortion using mifepristone and home misoprostol: a qualitative analysis of women's experiences.

CONTEXT: Women choose medical over surgical abortion because it is more natural, more private and less painful. Whether their perceptions change during the medical abortion process has not been explored. METHODS: A nonprobabilitysample of 43 participants in a clinical trial of abortion using mifepristone completed two open-ended questionnaires about this method, one before taking mifepristone and the second during their follow-up clinic visit 4-8 days after taking misoprostol. Thirty women participated in in-depth interviews 1-6 weeks following their abortion. Researchers analyzed transcripts to identify common themes. RESULTS: On the first visit to the clinic, women expressed anxiety and uncertainty about the effectiveness of medical abortion, guilt or ambivalence, and a desire to avoid surgery. For most women, emotional distress decreased after their abortion. Control was the overarching theme women expressed regarding the meaning of the procedure: Women stressed the importance of being able to select the type of abortion procedure, to maintain control over their future and to preserve their family's quality of life, given the constraints of time, finances and emotional resources. In in-depth interviews, eight women remained concerned about long-term health effects; 18 said that having an abortion at home was a comfortable experience. CONCLUSIONS: Learning whether women are concerned about personal control may help clinicians identify appropriate candidates for medical abortion. In addition, clinicians could help allay women's anxiety at their first abortion visit by explaining that the uncertainties posed by any medical procedure create similar feelings. Clinicians also should reemphasize at the follow-up visit that there are no long-term health effects related to abortion.