The Doctor's Channel - Ob/Gyn

Fertility-conserving surgery safe for early cervical cancer

2010-03-09T16:57:54+00:00

NEW YORK (Reuters Health) – In young women with stage IA1 cervical cancer, a fertility-preserving conization does not reduce survival compared to hysterectomy, researchers report in the March Obstetrics and Gynecology.

With either procedure, 5-year survival is excellent, approaching 100%, the findings indicate.

Small series and case control studies have suggested that conization is safe, but large studies comparing conization and hysterectomy for stage IA1 cervical cancer have been lacking until now, according to lead author Dr. Jason D. Wright, from Columbia University College of Physician and Surgeons, New York, and colleagues.

For the current analysis, the researchers used data from the Surveillance, Epidemiology, and End Results database from 1988 to 2005. They identified 1409 women, age 40 or younger, with stage IA1 cervical cancer; 841 had hysterectomy and 568 underwent conization.

On logistic regression analysis, predictors of conization included Asian ethnicity, single status, diagnosis later in the study period, and residence in the eastern United States. In addition, women younger than 30 had a 78% higher likelihood of conization compared to women above 35.

At 5 years, 98% of those treated with conization and 99% treated with hysterectomy were alive.

“Our study suggests that fertility-conserving surgery is safe for young women with stage IA1 squamous cell carcinoma of the cervix,” the authors conclude. “Young women with microinvasive cervical tumors should weigh the risks and benefits of conization in the context of individual preferences and tumor characteristics.”

Reference:
Obstet Gynecol 2010;115:585-590.

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Treatment of cervical dysplasia doesn’t increase preterm births: study

2010-03-03T16:04:38+00:00

NEW YORK (Reuters Health) – Pregnant women who’ve had abnormal cervical tissue removed with a loop electrosurgical procedure (LEEP) are not at increased risk for preterm delivery, a retrospective study suggests.

The 2006 consensus guidelines for management of cervical intraepithelial neoplasia (CIN) indicate that this procedure does increase the risk for adverse pregnancy outcomes. And the 2009 guideline for cervical cytology screening has cut back and delayed the recommended schedule, partly to avoid unnecessary interventions that could be harmful. (See Reuters Health report of November 20, 2009.)

However, researchers at the University of Texas Southwestern Medical Center in Dallas question whether “characteristics intrinsic to the woman undergoing LEEP might be associated with the adverse pregnancy effects rather than the procedure itself.”

Their study population included 241,701 women, all with singleton pregnancies, who gave birth at Parkland Hospital between 1992 and 2008. Five hundred eleven had LEEP before the index pregnancy and 842 had LEEP after the pregnancy. The mean interval from LEEP to subsequent pregnancy was 113 weeks, but 11% had an interval of no more than 90 days.

Lead author Dr. Claudia L. Werner and co-investigators note that clinicians did not modify prenatal care or surveillance for patients with a history of LEEP.

In the March issue of Obstetrics and Gynecology, the researchers report that the proportion of women delivering at 36 weeks or less was 7% in the general population, 7% among women who had LEEP prior to the pregnancy, and 9% among those who had LEEP after the pregnancy (p = ns). There was also no significant association between LEEP and perinatal mortality.

Recent studies on this topic have had conflicting results, Dr. Werner’s team points out. Two of three meta-analyses published between 2003 and 2008 suggest that LEEP does increase the risk of preterm birth.

The authors note that their study did not include information on potential confounders, such as substance use or prior preterm births, or data on LEEP depth, amount of excised tissue, or the degree of neoplasia.

They conclude, “LEEP cannot definitively be implicated as a cause of preterm birth.”

“I think the risk of premature birth is related more to the reasons that women get abnormal pap smears that lead to LEEP,” Dr. Jay Iams, an obstetrician at Ohio State University in Columbus, told Reuters Health. He explained that LEEP is performed to treat CIN that is often related to sexually transmitted viral infections, such as human papillomavirus. “People with these infections also have an increased risk for preterm birth.”

For women who’ve had any cervical procedure, Dr. Iams provides no extra surveillance other than using “ultrasound to check their cervix once or twice before 22 weeks’ gestation.”

Dr. Alan G. Waxman of the University of New Mexico, Albuquerque, who headed up the committee that developed the 2009 American College of Obstetrics and Gynecology guidelines, told Reuters Health that almost all the literature after 2003 shows an increased risk of preterm birth associated with LEEP.

“That’s why we recommend conservative surveillance for younger women,” he said. “But I’m delighted that Dr. Werner’s group is adding more evidence to what is a growing body of knowledge.”

According to Dr. Waxman, “some studies show that the extent of LEEP makes a difference, especially if it is a centimeter or more in depth,” which may account for the research team’s findings. “There may also be population differences.”

He advises that physicians should “be cognizant that most literature does show increased risk of preterm birth and should take that into account when weighing the risks and benefits of doing excision procedures.”

Reference:
Obstet Gynecol 2010;115:605-608.

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Lasofoxifene cuts fractures, breast CA, ischemic events -- but still has a down side

2010-02-26T17:14:56+00:00

[CLIN] – Lasofoxifene cuts fractures, breast CA, ischemic events -- but still has a down side

NEW YORK (Reuters Health) – In postmenopausal women with osteoporosis, the selective estrogen-receptor modulator lasofoxifene cuts the risks of fractures, estrogen-receptor-positive breast cancer, coronary disease, and stroke, the international PEARL study shows.

As do estrogen and other selective estrogen-receptor modulators, however, lasofoxifene increased the risk of venous thromboembolic events.

The findings, reported in The New England Journal of Medicine for February 25, stem from a randomized study of 8556 women who received either once-daily lasofoxifene (0.25 or 0.5 mg) or placebo for 5 years. All had bone mineral density T scores of -2.5 or less at the spine or femoral neck, lead author Dr. Steven R. Cummings, from the University of California, San Francisco, and colleagues note.

Compared with placebo, the higher dose of lasofoxifene reduced the risks of vertebral fracture (HR, 0.58), nonvertebral fracture (HR, 0.76), ER-positive breast cancer (HR, 0.19), coronary heart disease events (HR, 0.68), and stroke (HR, 0.64). The lower dose cut the risks of vertebral fracture (HR, 0.69) and stroke (HR, 0.61).

Both doses of lasofoxifene more than doubled the risk of venous thromboembolic events, the report indicates.

Two lower-dose lasofoxifene patients, two higher-dose lasofoxifene patients, and three patients given placebo developed endometrial cancer.

Mortality rates per 1000 person-years were 7.0 with lower-dose lasofoxifene, 5.7 with higher-dose lasofoxifene, and 5.1 with placebo, the report indicates.

Lasofoxifene is currently under review by the U.S. Food and Drug Administration as a treatment for postmenopausal osteoporosis in at-risk women. But while the current findings suggest that lasofoxifene is superior to placebo in many respects, the new drug may be no better than other selective estrogen-receptor modulators already on the market, according to an editorial.

“Given the plethora of drugs currently available for osteoporosis, studies of new agents should show clear benefits over existing agents,” Dr. Carolyn Becker, from Brigham and Women’s Hospital, Boston, writes.

But, she says, “On the basis of this criterion, the results of the PEARL trial suggest that lasofoxifene offers no major clinically important benefits over raloxifene for the skeleton, breast, heart, or reproductive tract.”

PEARL was funded by Pfizer, the developer of lasofoxifene.

Reference:
N Engl J Med 2010;362:686-696,752-754.

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Clinical signs at birth don’t predict survival in extreme prematurity

2010-02-24T21:39:41+00:00

NEW YORK (Reuters Health) - Survival of extremely premature infants (less than 26 weeks’ gestation) can’t be predicted by appearance at birth and early response to resuscitation, according to Australian investigators.

For these infants, the decision to resuscitate should not be based on early clinical signs, the investigators advise in the March issue of Pediatrics.

“This research was performed in response to a previous paper that suggested many neonatologists in the US would see what the baby looks likes at birth when assessing whether to commence/continue resuscitation and instigate intensive care in premature infants born at the ‘extremes of viability,’” lead author Dr. Brett J. Manley, from Royal Women’s Hospital in Melbourne, told Reuters Health by email.

Indeed, for infants born “at the border of viability,” experts generally recommend that physicians base clinical management on the condition of the infant at birth, the authors said.

To study this approach, the team showed videos of 10 infants’ first 5 minutes of life to 34 neonatologists (17 attendings and 17 fellows). The recordings focused on resuscitative efforts -- which included intermittent positive-pressure ventilation and/or endotracheal intubation or nasal continuous positive airway pressure – as well as pulse oximetry displays and audio of resuscitation team discussions. The neonatologists also had details of the pregnancies and deliveries (but not birth weight).

At 20 seconds, 2 minutes and 5 minutes, the clinicians estimated the likelihood that the infant would survive to hospital discharge and whether they would continue resuscitation.

Gestational age ranged from 23 weeks, 3 days to 25 weeks, 5 days. Four infants died between ages 2 and 10 days, before hospital discharge.

The observers’ ability to predict survival was “only slightly better than chance,” with “huge” ranges of predicted survival, the authors report.

For example, estimated chances of survival for one infant ranged from 5% to 85% at 5 minutes. For all 10 babies, at 5 minutes the median predicted likelihood of survival ranged from 30% to 70%. Furthermore, one of the infants given the best chance of survival died, and the infant given the second worse prognosis survived.

Level of clinical experience was not associated with predictive accuracy.

At each time point (20 seconds, 2 minutes, and 5 minutes), the observers’ answer sheets were removed, so they couldn’t change their answers retrospectively. During the course of the 5 minutes, observers changed their minds more than half the time.

The authors note that many of the neonatologists were uncomfortable with the study design. Some felt they couldn’t predict survival based on the information they received or without being included in the discussions in the delivery room, or that the resuscitations didn’t meet their own standards.

Dr. Manley and his colleagues conclude that for extremely premature newborns, “reliance on initial appearance and early response to resuscitation in predicting survival…is misplaced.”

Instead, Dr. Manley said, “We propose that antenatal consultation with the parents (where time permits), when known survival and outcome data are presented, and a clear management plan at birth is agreed upon, is a more appropriate practice.”

Reference:
Pediatrics 2010;125:e559-e564.

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Postpartum zidovudine/didanosine prevents resistance mutations in HIV

2010-02-23T16:55:46+00:00

NEW YORK (Reuters Health) – Intra-partum nevirapine, given to prevent HIV transmission, contributes to HIV resistance mutations to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) – but a one-month postpartum course of zidovudine plus didanosine helps avoid this problem.

That’s according to results of the multicenter, open-label HIV Prevention and Treatment (PHPT)-4 trial, conducted in Thailand and reported in Clinical Infectious Diseases for March 15.

Third-trimester zidovudine and a single intra-partum dose of nevirapine are used to prevent vertical HIV transmission in resource-limited settings, lead author Dr. Marc Lallemant, from Chiang Mai University, and the study team explain.

Because blood levels of nevirapine remain elevated for weeks following the single dose, this regimen tends to select for NNRTI mutations, decreasing efficacy of subsequent NNRTI-based antiretroviral regimens. The authors theorized that by suppressing viral replication, an additional 1-month postpartum course of zidovudine/didanosine would prevent selection of resistance mutations in mothers.

The trial included 222 HIV-infected pregnant women with CD4 cell counts > 250 cells/mm3 who did not require highly active antiretroviral treatment. Enrollment began in 2005.

The women took 300 mg zidovudine twice daily starting at 28 weeks’ gestation. During labor they received 300 mg zidovudine every 3 hours, plus a single dose of nevirapine 200 mg and didanosine 400 mg. Following delivery, they took zidovudine 200 or 300 mg as well as didanosine 250 or 400 mg once daily for 1 month.

The authors compared NNRTI mutation outcomes with those in 222 women from an earlier trial (2001-2003) who had been treated with antepartum zidovudine and intra-partum nevirapine only. Women in the two trials were matched on CD4 cell count, antepartum zidovudine duration and plasma viral load.

Two different mutation assays, performed within 4 months of delivery, identified new postpartum NNRTI resistance mutations in 4 women (1.8%) in the study group and in 46 controls (20.7%) (p < 0.001), a 91% reduction.

“The 1-month postpartum regimen appeared to be safe, well tolerated, and easy to adhere to,” the investigators report.

They note that preliminary results from another study suggest that a more potent postpartum regimen of lopinavir, zidovudine, and didanosine, of shorter duration, may have similar efficacy.

“Interventions to eliminate post-exposure selection of nevirapine resistance are critical to safeguard a highly efficacious intervention for the prevention of mother-to-child transmission while preserving the mother’s future therapeutic options,” Dr. Lallemant and colleagues conclude.

A commentary by Dr. Mark F. Cotton and associates at Stellenbosch University, Tygerberg, South Africa points out that the study does not answer the question of how to protect HIV-infected infants from developing NNRTI resistance, both from single-dose nevirapine and more prolonged exposure to nevirapine during breast-feeding.

Furthermore, Dr. Cotton and his colleagues add, “This strategy needs to be replicated in Africa, where HIV-1 subtype C has a higher propensity to NNRTI resistance and where women may be sicker.”

Reference:
Clin Infect Dis 2010.

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Case finding approach misses most cases of thyroid disease during pregnancy

2010-02-11T20:29:29+00:00

NEW YORK (Reuters Health) – Limiting thyroid tests to high-risk women will miss most cases of thyroid dysfunction during pregnancy, randomized trial results show.

Furthermore, when low-risk women are identified by screening and treated, adverse outcomes are reduced.

In a February 3rd online report in the Journal of Clinical Endocrinology and Metabolism, Dr. Roberto Negro, from V. Fazzi Hospital, Lecce, Italy, and colleagues describe a study in which 4562 pregnant women were randomized either to a case finding approach or to universal screening for thyroid dysfunction by measurement of free T4, thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody

In the case finding protocol, indications for testing included a family history of autoimmune thyroid disease, presence of goiter, symptoms and signs consistent with thyroid dysfunction, a history of type 1 diabetes or other autoimmune disease, prior neck irradiation, prior miscarriage, and preterm delivery. Low-risk women in this group were screened after delivery.

In all cases, women with TSH levels > 2.5 mIU/L and thyroid peroxidase antibodies were treated with levothyroxine. Women with undetectable TSH and elevated free T4 received anti-thyroid medication at the discretion of an endocrinologist.

In the universal screening group, 91.0% of women were euthyroid without antibodies, 5.8% were euthyroid with antibodies, 2.8% were hypothyroid, and 0.4% were hyperthyroid. The corresponding percentages in the case finding group were not significantly different: 91.6%, 5.7%, 2.4%, and 0.3%.

Among the 1798 low-risk women in the universal screening group, 51 (2.8%) were diagnosed with thyroid dysfunction and treated. The number needed to screen to detect one hypothyroid or hyperthyroid woman was 36, according to the authors.

Overall, universal screening did not reduce adverse outcomes compared with the case finding approach. When the analysis was confined to low-risk women, however, adverse outcomes were significantly less likely to occur with universal screening (odds ratio, 0.43). This is presumably due to the fact that low-risk women in the case finding approach would not have received any treatment until after delivery.

“Treatment of identified thyroid hormonal abnormalities during pregnancy results in a significant decrease in adverse outcomes,” the authors conclude. “Our study confirms that case finding fails to detect the majority of pregnant women with thyroid disease.”

Reference:
J Clin Endocrinol Metab 2010.

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Simple ovarian cysts not linked to cancer in postmenopausal women

2010-02-05T20:30:13+00:00

NEW YORK (Reuters Health) - In women over 55, simple ovarian cysts are common, usually resolving or persisting without progression, according to data from the prospective Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

The presence of simple cysts, often found incidentally during transvaginal ultrasound (TVU) exams, did not affect the risk of ovarian cancer, according to lead author Dr. Robert T. Greenlee and colleagues -- bolstering recent recommendations that unilocular simple cysts in postmenopausal women be followed without intervention.

Dr. Greenlee, from the Marshfield Clinic Research Foundation, Wisconsin, and associates followed 15,735 postmenopausal women through 4 years of annual TVU screening. All were between 55 and 74 years old at enrollment, and all had CA-125 measurements and TVU studies at baseline. Both tests were repeated annually. In addition, for a woman to be included in the study, both ovaries had to be visualized at least once by TVU.

Simple cysts were defined as having a volume < 10 cm3 and with no solid areas, septae, or papillary projections within the cyst cavity.

In a paper published online January 25 in the American Journal of Obstetrics and Gynecology, the investigators report that the prevalence of at least 1 simple cyst detected during the first fully visualized TVU screening was 14.1%. Potential correlates of prevalent simple cysts were younger age (55 to 59), education past high school, and early menopause. The odds were also higher in women with a history of benign ovarian cysts, menopause before age 40, and a first pregnancy at or beyond age 30.

Among women without a cyst of any kind on their first fully visualized TVU screening, the incidence of simple cysts was approximately 8% per year, remained fairly constant, and did not vary by age.

One-third of ovaries with simple cysts were cyst-free the following year. Even when 2 or more cysts were present, all resolved a quarter of the time. Only 6% progressed in complexity from 1 year to the next.

Women with and without simple cysts were at similar risk of invasive ovarian cancer after nearly 8 years of follow-up evaluation, the authors write. Furthermore, traditional ovarian cancer risk factors, such as increasing age, family history of breast or ovarian cancer, nulliparity, and infertility, were not associated with simple cysts. Finally, changes in average CA-125 were not correlated with increases in the number or progression of simple cysts.

Thus, Dr. Greenlee and his group conclude, “Simple cysts are not likely cancer precursors or markers of increased risk and can be followed conservatively.”

Reference:
Am J Obstet Gynecol 2010.

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Internal and external tocodynamometry equivalent for monitoring contractions

2010-01-28T17:58:07+00:00

NEW YORK (Reuters Health) - It makes no difference whether internal tocodynamometry or external monitoring is used during induced or augmented labor – either way, the rate of operative deliveries is similar.

That’s according to a large randomized, controlled trial conducted at 6 hospitals in the Netherlands and reported in the New England Journal of Medicine January 28.

Internal tocodynamometry is believed to be more accurate in quantifying the frequency, duration, and magnitude of uterine activity, the authors explain. Theoretically, this information could improve oxytocin dosing, thus helping to prevent uterine hyperstimulation and fetal hypoxia, and it might also improve the interpretation of abnormal fetal heart-rate patterns.

Because data to support these theories are limited, Dr. Joris A. M. van der Post, at Amsterdam’s Academic Medical Center, and colleagues compared external monitoring and internal tocodynamometry in a randomized trial. Inclusion criteria were a singleton pregnancy, gestational age > 36 weeks, fetus in the cephalic position, and IV oxytocin required for induction (66%) or augmented labor (34%).

After randomization, 734 women were assigned to internal tocodynamometry and 722 to external monitoring.

Spontaneous vaginal delivery was achieved by 68.7% of patients in the internal monitoring group and 70.4% in the external monitoring group. Cesarean section was required by 16.3% and 15.7%, respectively, and instrument delivery by 14.9% and 14.0%, respectively. None of these differences was statistically significant.

The frequency of secondary outcomes -- complications from use of the intrauterine pressure catheter, use of analgesia or antibiotics, amount of oxytocin, time to delivery and adverse neonatal outcomes -- was also similar between groups.

Post hoc analyses showed no significant interactions between treatment and type of labor, parity, or body mass index.

The authors point out that internal tocodynamometry “has serious risks, including placental or fetal-vessel damage, infection, and anaphylactic reaction.”

They conclude, “The results of our trial do not support the routine use of internal tocodynamometry for monitoring contractions in women with induced or augmented labor.”

Reference:
N Engl J Med 2010;362:306-313.

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Treating subclinical neonatal seizures may prevent brain injury

2010-01-28T17:50:24+00:00

NEW YORK (Reuters Health) - Prompt treatment of subclinical and clinical seizures in newborns with hypoxic-ischemic encephalopathy (HIE) can potentially decrease brain injury, according to a prospective trial from Belgium and the Netherlands.

Neonatal HIE with seizures poses a high risk for death or neurologic disability, the investigators note in the February Pediatrics. They point out that a substantial proportion of neonatal seizures are subclinical, especially after the newborns have been given anticonvulsants - but the drugs themselves can also have serious adverse effects.

The question, according to senior author Dr. Linda S. de Vries, at Wilhelmina Children's Hospital, Utrecht, and her coauthors, is whether treating both subclinical and clinical seizures in newborns with HIE - as opposed to treating only clinical seizures -- would reduce the total duration of seizures and result in less-severe brain injury on magnetic resonance imaging (MRI) scans.

Neonatal HIE is diagnosed if at least three of the following are present: signs of intrauterine hypoxia, arterial cord blood pH less than 7.1, delayed onset of spontaneous breathing, Apgar score of no more than 5 at 5 minutes, or multiorgan failure.

In 138 such newborns, the authors used amplitude-integrated electroencephalography (aEEG) to monitor for seizures. Infants with clinical seizures were treated with antiepileptic drugs (AEDs). As soon as an infant had a subclinical seizure, he or she was randomized either to be treated for both clinical and subclinical seizure patterns (group A, n = 19) or for clinical seizures only (group B, n = 14).

There was a nonsignificant trend to decreased median duration of seizure patterns in group A (196 vs 503 min).

MRI was performed for 14 patients in group A and 11 in group B when they were 4 to 10 days old. In linear regression analysis, the authors found a significant relationship between the duration of seizure patterns and MRI scores (and degree of brain injury) in group B.

The authors also analyzed the appropriateness of treatment, that is, whether AEDs were given within 2 hours after the onset of seizures and whether another AED was given if no effect was seen in 1 to 2 hours.

In group A, treatment was appropriate for 8 infants, leading to a significant difference in seizure duration compared to the babies who did not receive appropriate treatment (37 vs 248 minutes, p = 0.02). Infants treated appropriately for both clinical and subclinical seizure patterns received more AEDs within a relatively short period.

In group B, 6 infants were treated with AEDs for clinical seizures that could not be confirmed on aEEG. Four babies had seizure patterns for several hours before clinical signs were observed, and in 5, seizure patterns persisted after AEDs were given, even though clinical signs had resolved. One infant with subclinical seizures received no further treatment after assignment.

Six patients in group A (32%) and 7 in group B (50%) died in the neonatal period. Although recording time was shorter in the babies who died, they had longer duration of seizures than survivors (428 vs 164 min).

According to Dr. de Vries and her associates, "recognition and treatment of neonatal (clinical and subclinical) seizures in infants with HIE can reduce brain injury."

Pediatrics 2010;125:e358-e366.

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Radiotherapy for cervical cancer increases pelvic fracture risk

2010-01-27T23:14:59+00:00

NEW YORK (Reuters Health) - A substantial proportion of women with cervical cancer who receive curative-intent radiotherapy will soon develop pelvic fractures, clinicians from the University of Texas M. D. Anderson Cancer Center in Houston have found.

Therefore, “bone mineral density screening and pharmacologic intervention should be considered in these women,” lead author Dr. Kathleen M. Schmeler commented in an email to Reuters Health.

As Dr. Schmeler and her colleagues note in the January 5th online issue of Cancer, earlier studies showed that radiation to the pelvis “results in demineralization of bone matrix, with a pelvic fracture rate of 2% to 89%” in women with gynecologic malignancies.

Because of certain limitations in these studies, Dr. Schmeler’s group examined the incidence of pelvic fractures and associated risk factors in 300 women who underwent curative-intent radiotherapy for cervical cancer between 2001 and 2006. The median follow-up for all patients was 20.9 months, and the median interval from the end of treatment to the last imaging study (either CT or MRI) was 7.4 months.

None of the women had bony metastases or a pelvic fracture history at baseline. During follow-up, 29 women (9.7%) developed pelvic fractures; 23 had received primary radiotherapy and 27 had also been treated with cisplatin or cisplatin plus 5-fluorouracil.

“Given that our median age was 47.4 years and 40% of our patients were premenopausal at the start of treatment, it is estimated that an age-matched population of women not receiving radiation therapy would have a background fracture rate of less than 5%,” Dr. Schmeler noted.

Only 13 women had fracture symptoms, most commonly pain. Fracture sites included the sacrum (83%), sacrum and pubis (10%), iliac crest (3.5%), and sacrum and acetabulum (3.5%).

Older age at cancer diagnosis, postmenopausal status and lower body mass index were associated with higher fracture risks.

It’s important to note, Dr. Schmeler said, that the median interval from the end of radiation therapy to the fracture diagnosis was only 14 months, with 38% of fractures diagnosed within 1 year and 83% of fractures diagnosed within 2 years after treatment.

“Because radiation therapy cures many of these patients, the long-lasting effects such as osteoporosis and pelvic fractures need further attention,” Dr. Schmeler concludes.

To better assess the effects of radiation on bone, she and her colleagues are currently measuring changes in bone mineral density and serum markers of bone turnover in women undergoing pelvic radiation therapy for gynecologic cancers.

Cancer 2010.

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