Should We Be Concerned About Jaw Osteonecrosis with Oral Bisphosphonates?
BRONJ probably occurs rarely with oral bisphosphonate therapy, but the true incidence isn’t clear yet.
Increasingly, patients are asking physicians about bisphosphonate-related osteonecrosis of the jaw (BRONJ). Some patients are researching the topic themselves on the Internet before starting bisphosphonate drugs that are recommended by their physicians. In other cases, dentists are reluctant to perform invasive dental procedures in patients who are taking these drugs. How should primary care physicians respond to these patients or their dentists?
First, some background: BRONJ is defined as exposed, necrotic bone in the maxillofacial region that persists for more than 8 weeks in current or past recipients of bisphosphonate therapy.1,2 The condition can occur spontaneously or after invasive dental procedures. These lesions often expand — sometimes involving large areas of the alveolar bone — and no treatment has been proven to be effective. Reports of BRONJ first surfaced about 5 years ago, primarily in cancer patients who had received IV bisphosphonates for hypercalcemia and bone metastases. Experts generally accept the association between jaw osteonecrosis and IV bisphosphonates, which are often given repetitively in high doses.2,3
The data are less compelling for oral bisphosphonates. Based on case reports and surveys, jaw osteonecrosis has been described in relatively few patients who have received oral bisphosphonates to treat osteoporosis. For example, in a recent review of the literature, 11 published reports, comprising 26 cases, were identified.4 In a survey mailed to oral surgeons in Australia, 94 clinicians reported 36 cases.5 In contrast, no cases of BRONJ were identified in one large New York dental practice where 468 implants were placed in 115 patients who took oral bisphosphonates.6 And no cases were reported in the FLEX trial, in which 1099 women took oral alendronate for 5 to 10 years.7
Researchers recently attempted an analysis of this problem that was somewhat more population-based: They analyzed medical claims in the database of a large health insurance plan.8 No association was found between oral bisphosphonates and jaw osteonecrosis among 180,000 patients with osteoporosis who filled prescriptions for oral bisphosphonates. However, the study had an important limitation: No ICD-9 code exists for jaw osteonecrosis, so the researchers had to use other codes (e.g., diagnostic codes for inflammatory conditions of the jaw and procedure codes for jaw surgery) as surrogate markers for jaw osteonecrosis.
We have spoken to dentists and oral surgeons who occasionally have encountered oral bisphosphonate–treated patients with alveolar bone exposure that arose either after invasive procedures or without apparent trauma. Although these anecdotal unpublished observations hardly prove cause and effect, they should not be dismissed out of hand for at least two reasons. First, if we accept that IV bisphosphonates can cause jaw osteonecrosis, we can reasonably assume that oral therapy occasionally might cause the same complication in highly susceptible people. And second, biopsy-proven severe suppression of bone turnover — resulting in spontaneous fractures of the femur, pelvis, and ribs — has been described in several patients after long-term oral bisphosphonate therapy.9
The American Association of Oral and Maxillofacial Surgeons (AAOMS) has published a position paper on BRONJ.1 The authors recognize limitations in the published data, but they believe that jaw osteonecrosis occasionally occurs in patients who have received oral bisphosphonates. They recommend no alteration to or delay in necessary dental surgery for patients who have taken oral bisphosphonates for fewer than 3 years and have none of the characteristics that are thought to be risk factors (which can be found in the report1). However, for patients who have taken oral bisphosphonates for longer than 3 years, the statement urges prescribing physicians to stop the drug 3 months before oral surgery and to restart it only after osseous healing has occurred. The authors acknowledge that these recommendations are consensus judgments that are not yet evidence-based.
Now let’s return to our original question: How should primary care physicians respond to patients and dentists who are concerned about BRONJ? In our view, patients who are considering oral bisphosphonate therapy should be told that a small risk — which cannot be quantified yet and which probably emerges only after several years of treatment — is plausible. For most patients with documented osteoporosis and for those with osteopenia plus multiple risk factors for fracture, the potential benefits of bisphosphonate therapy outweigh the risks. However, some clinicians are prescribing bisphosphonates to patients with marginal indications (e.g., to recently postmenopausal healthy women with mild osteopenia). For relatively young patients, delaying bisphosphonate therapy seems prudent: We simply don’t know whether years or decades of exposure to bisphosphonates might result in unanticipated harms.
What about the patient who is already taking an oral bisphosphonate and whose dentist recommends stopping it because an invasive procedure is necessary? Although the AAOMS recommendations admittedly are based on opinion and not hard data, stopping the drug temporarily is reasonable. On the one hand, no proof exists to show that interruption of bisphosphonate therapy will make the dental procedure safer; but, on the other hand, a 6- or 12-month "drug holiday" is unlikely to alter fracture risk substantially in a patient who has already taken a bisphosphonate for several years.2 Indeed, the FLEX data suggested that a 5-year drug holiday after 5 years of active treatment is reasonable for many patients.7
Practitioners and patients often are forced to make clinical decisions under conditions of uncertainty; the situation with BRONJ is no exception. Although bisphosphonates are extraordinarily valuable drugs with proven benefits, recent developments with cyclooxygenase (COX)-2 inhibitors, recombinant erythropoietins, rosiglitazone, and postmenopausal hormone therapy should remind us to remain open-minded about unexpected effects of drug therapies.
— Allan S. Brett, MD, and Peter B. Lockhart, DDS
Dr. Lockhart is Chair of the Department of Oral Medicine and Director of the Oral Medicine Institute at Carolinas Medical Center in Charlotte, North Carolina.
Published in Journal Watch General Medicine April 8, 2008
Citation(s):
1. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007 Mar; 65:369. (http://www.aaoms.org/docs/position_papers/osteonecrosis.pdf)
Medline abstract (Free)
2. Khosla S et al. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007 Oct; 22:1479. (http://dx.doi.org/10.1359/JBMR.0707ONJ)
Medline abstract (Free)
3. Bilezikian JP. Osteonecrosis of the jaw — Do bisphosphonates pose a risk? N Engl J Med 2006 Nov 30; 355:2278.
Original article (Subscription may be required)
Medline abstract (Free)
4. Pazianas M et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: Prevalence, risk factors, and clinical characteristics. Clin Ther 2007 Aug; 29:1548.
Medline abstract (Free)
5. Mavrokokki T et al. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 2007 Mar; 65:415.
Medline abstract (Free)
6. Grant B-T et al. Outcomes of placing dental implants in patients taking oral bisphosphonates: A review of 115 cases. J Oral Maxillofac Surg 2008 Feb; 66:223.
Medline abstract (Free)
7. Black DM et al. Effects of continuing or stopping alendronate after 5 years of treatment. The Fracture Intervention Trial Long-term Extension (FLEX): A randomized trial. JAMA 2006 Dec 27; 296:2927.
Original article (Subscription may be required)
Medline abstract (Free)
8. Cartsos VM et al. Bisphosphonate use and the risk of adverse jaw outcomes: A medical claims study of 714,217 people. J Am Dent Assoc 2008 Jan; 139:23.
Original article (Subscription may be required)
Medline abstract (Free)
9. Odvina CV et al. Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab 2005 Mar; 90:1294.
Original article (Subscription may be required)
Medline abstract (Free)
Monday, April 14, 2008
Wednesday, February 20, 2008
Epidemiology of Polymorphic Eruption of Pregnancy
Some of our assumptions about this condition have been mistaken.
An eruption occurring in the third trimester of pregnancy, primarily in primigravid women, was first described in 1979 and given the designation pruritic urticarial papules and plaques of pregnancy (PUPPP). Later investigation linked the syndrome to twin pregnancies and excessive weight gain. Several subsequent studies found greater frequency when the fetus was male, but one other study found greater frequency with female fetal sex. Researchers have suggested that all eruptions of pregnancy be categorized together as polymorphic eruption of pregnancy (PEP).
These authors performed a retrospective, case-control study of 200 pregnancies: 40 women with PEP and 4 matched healthy controls each. The researchers noted a number of factors that were statistically associated with PEP in univariate analysis, including primigravidas, multiple-gestation pregnancy, maternal weight gain, male fetal sex, cesarean delivery, and hospitalization. In multivariate analysis, however, only male fetal sex, cesarean delivery, and hospitalization remained statistically significant. The authors did not have the data to analyze the risk for recurrence in these patients.
Comment: PUPPP or PEP does not occur only in primigravid women; it does not always occur in the third trimester of pregnancy and does not appear to be related to maternal weight gain. This condition appears to be more frequent in pregnancies with male fetuses and may yet prove to be related to multiple-gestation pregnancy. Patients with this disorder also have more-frequent cesarean delivery and more-frequent hospitalization. We wonder whether our standing belief that this disorder does not recur may soon be disproved.
— Jeffrey P. Callen, MD
Published in Journal Watch Dermatology February 8, 2008
Citation(s):
Regnier S et al. A case-control study of polymorphic eruption of pregnancy. J Am Acad Dermatol 2008 Jan; 58:63.
An eruption occurring in the third trimester of pregnancy, primarily in primigravid women, was first described in 1979 and given the designation pruritic urticarial papules and plaques of pregnancy (PUPPP). Later investigation linked the syndrome to twin pregnancies and excessive weight gain. Several subsequent studies found greater frequency when the fetus was male, but one other study found greater frequency with female fetal sex. Researchers have suggested that all eruptions of pregnancy be categorized together as polymorphic eruption of pregnancy (PEP).
These authors performed a retrospective, case-control study of 200 pregnancies: 40 women with PEP and 4 matched healthy controls each. The researchers noted a number of factors that were statistically associated with PEP in univariate analysis, including primigravidas, multiple-gestation pregnancy, maternal weight gain, male fetal sex, cesarean delivery, and hospitalization. In multivariate analysis, however, only male fetal sex, cesarean delivery, and hospitalization remained statistically significant. The authors did not have the data to analyze the risk for recurrence in these patients.
Comment: PUPPP or PEP does not occur only in primigravid women; it does not always occur in the third trimester of pregnancy and does not appear to be related to maternal weight gain. This condition appears to be more frequent in pregnancies with male fetuses and may yet prove to be related to multiple-gestation pregnancy. Patients with this disorder also have more-frequent cesarean delivery and more-frequent hospitalization. We wonder whether our standing belief that this disorder does not recur may soon be disproved.
— Jeffrey P. Callen, MD
Published in Journal Watch Dermatology February 8, 2008
Citation(s):
Regnier S et al. A case-control study of polymorphic eruption of pregnancy. J Am Acad Dermatol 2008 Jan; 58:63.
Friday, February 15, 2008
Glucose-Control Arm of ACCORD Trial Halted Early
Increased mortality associated with aggressive glucose reduction raises safety concerns.
The National Heart, Lung, and Blood Institute has announced the early termination of one treatment arm of the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial because of an increased risk for death among patients assigned to intensive glucose-lowering therapy (press release, February 6, 2008). The 5128 participants (at 77 North American sites) randomized to treatment aimed at reducing HbA1c levels to <6.0% will now be treated to a target HbA1c level of 7.0% to 7.9%, the same as participants in the control group. Two concurrent trials of management strategies for cholesterol and hypertension will continue as planned.
The Data and Safety Monitoring Board of ACCORD recommended stopping intensive glucose-lowering therapy after it found that 257 patients in that group had died, compared with 203 in the standard therapy group: a difference of 3 per 1000 participants per year during a mean of about 4 years of treatment. Preliminary analyses have found no association of the mortality increase with any specific drug or drug combination. All participants in the ACCORD study have type 2 diabetes and either coronary heart disease or at least two risk factors for adverse cardiovascular events.
Comment: The ACCORD trial was inspired by previous research that found a link between tightly controlled blood sugar and reduced risk for many complications of type 2 diabetes. Why an increased risk for death was associated with tight glucose control in this trial remains unclear. These results raise questions about intensity of and appropriate targets for glucose-lowering treatment in patients with type 2 diabetes, but they do not alter current guidelines or treatment strategies for most diabetic patients.
— Joel M. Gore, MD
Published in Journal Watch Cardiology February 13, 2008
The National Heart, Lung, and Blood Institute has announced the early termination of one treatment arm of the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial because of an increased risk for death among patients assigned to intensive glucose-lowering therapy (press release, February 6, 2008). The 5128 participants (at 77 North American sites) randomized to treatment aimed at reducing HbA1c levels to <6.0% will now be treated to a target HbA1c level of 7.0% to 7.9%, the same as participants in the control group. Two concurrent trials of management strategies for cholesterol and hypertension will continue as planned.
The Data and Safety Monitoring Board of ACCORD recommended stopping intensive glucose-lowering therapy after it found that 257 patients in that group had died, compared with 203 in the standard therapy group: a difference of 3 per 1000 participants per year during a mean of about 4 years of treatment. Preliminary analyses have found no association of the mortality increase with any specific drug or drug combination. All participants in the ACCORD study have type 2 diabetes and either coronary heart disease or at least two risk factors for adverse cardiovascular events.
Comment: The ACCORD trial was inspired by previous research that found a link between tightly controlled blood sugar and reduced risk for many complications of type 2 diabetes. Why an increased risk for death was associated with tight glucose control in this trial remains unclear. These results raise questions about intensity of and appropriate targets for glucose-lowering treatment in patients with type 2 diabetes, but they do not alter current guidelines or treatment strategies for most diabetic patients.
— Joel M. Gore, MD
Published in Journal Watch Cardiology February 13, 2008
Wednesday, February 13, 2008
Best Strategies for Urinary and Fecal incontinence
Complete Review Annals of Internal Medicine
The best approaches to treating and preventing adult incontinence are the subject of two articles released early by Annals of Internal Medicine.
One article, an examination of published evidence concerning nonsurgical treatment of urinary incontinence in women, reaches the following conclusions:
Pelvic floor muscle training would resolve 490 cases of stress incontinence per 1000 cases treated.
Oral hormonal therapy increased rates of incontinence, and estrogens administered transdermally or vaginally produced inconsistent improvements.
Oxybutynin and tolterodine increased continence rates, but duloxetine was not better than placebo.
Adrenergic drugs (clenbuterol, norepinephrine, and phenylpropanolamine) were not effective.
The other article, a "state-of-the-science" statement on adult incontinence from an NIH-sponsored conference, concludes:
"Routine episiotomy is the most easily preventable risk factor for fecal incontinence."
Pelvic floor muscle training may "prevent or reduce urinary incontinence in older women and in men undergoing prostate surgery," while lifestyle changes, such as weight loss and exercise, may prevent both urinary and fecal incontinence
The best approaches to treating and preventing adult incontinence are the subject of two articles released early by Annals of Internal Medicine.
One article, an examination of published evidence concerning nonsurgical treatment of urinary incontinence in women, reaches the following conclusions:
Pelvic floor muscle training would resolve 490 cases of stress incontinence per 1000 cases treated.
Oral hormonal therapy increased rates of incontinence, and estrogens administered transdermally or vaginally produced inconsistent improvements.
Oxybutynin and tolterodine increased continence rates, but duloxetine was not better than placebo.
Adrenergic drugs (clenbuterol, norepinephrine, and phenylpropanolamine) were not effective.
The other article, a "state-of-the-science" statement on adult incontinence from an NIH-sponsored conference, concludes:
"Routine episiotomy is the most easily preventable risk factor for fecal incontinence."
Pelvic floor muscle training may "prevent or reduce urinary incontinence in older women and in men undergoing prostate surgery," while lifestyle changes, such as weight loss and exercise, may prevent both urinary and fecal incontinence
Tuesday, January 15, 2008
USPSTF Recommends Against Screening for Asymptomatic Carotid Artery Stenosis
USPSTF Recommends Against Screening for Asymptomatic Carotid Artery Stenosis
At first glance, the recommendation seems surprising — but upon further examination, it makes sense.
The U.S. Preventive Services Task Force (USPSTF) has been releasing new and updated guidelines periodically. Along with the release of this recommendation statement, the USPSTF has revised the way it grades its recommendations to make them more clinically useful.
Recommendations concern preventive care for patients without recognized signs or symptoms of a given condition. The USPSTF now grades the recommendations as follows (descriptions of levels of certainty can be found at the guidelines home page):
A — The service is recommended. High certainty that benefit is substantial.
B — The service is recommended. High certainty that benefit is moderate, or moderate certainty that benefit is moderate to substantial.
C — The USPSTF recommends against providing the service routinely. Moderate certainty that the benefit is small. Considerations may support providing the service to individual patients.
D — The USPSTF recommends against the service. Moderate to high certainty of no benefit or that the harms outweigh the benefits.
I — Evidence is insufficient to assess the balance of benefits and harms.
The USPSTF also now provides suggestions for practice: For Grade A or B recommendations, offer the service; Grade C, offer the service only based on individual considerations; Grade D, discourage the service; Grade I, if the service is offered (e.g., based on clinical considerations), patients should understand the uncertainty about the benefits and harms.
In a new guideline, the USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general population. The recommendation is graded "D." The suggestion is that such screening be discouraged.
Although no randomized trials of screening have been performed, some evidence supports the USPSTF recommendation:
Carotid ultrasonography is sensitive for severe carotid stenosis (94% for stenosis 60%) but results in many false-positives.
Angiography provides accurate confirmation but is associated with serious adverse events (e.g., stroke); noninvasive testing (e.g., magnetic resonance imaging) is associated with false-positives (leading to unnecessary surgery and surgery-related stroke and death).
Carotid endarterectomy at excellent centers is associated with, at best, a 3% 30-day rate of stroke or death.
Select patients who undergo carotid endarterectomy performed by selected surgeons experience a 5% decrease in stroke or perioperative death within 5 years, according to results from two good-quality randomized trials; these benefits would be lower in the general population.
Comment: Even though the USPSTF requires the highest levels of evidence to recommend any preventive service, I was surprised by its "not recommended" stance on this one, because randomized trials of endarterectomy in asymptomatic people have suggested modest benefits (primarily in men). But it makes sense. The task force did not cite insufficient evidence as the basis for its recommendation; instead, it used randomized trial evidence, data on screening test accuracy, and projected harms from invasive procedures. We would need to screen more than 4000 people to prevent one stroke (during 5 years); in the process, for each person helped, almost as many people would be harmed by angiography consequences, perioperative stroke, or death. Despite this problematic benefit-to-harm ratio, many patients are undergoing screening carotid ultrasonography that is offered directly by private companies. However, prevention of atherosclerosis or better screening tests and treatments (and not carotid ultrasonography) will be the way to prevent stroke and death from carotid stenoses.
— Richard Saitz, MD, MPH, FACP, FASAM
Published in Journal Watch General Medicine January 15, 2008
Citation(s):
Wolff T et al. Screening for carotid artery stenosis: An update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2007 Dec 18; 147:860.
Original article (Subscription may be required)
Medline abstract (Free)
U.S. Preventive Services Task Force. Screening for carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2007 Dec 18; 147:854.
Original article (Subscription may be required)
Medline abstract (Free)
At first glance, the recommendation seems surprising — but upon further examination, it makes sense.
The U.S. Preventive Services Task Force (USPSTF) has been releasing new and updated guidelines periodically. Along with the release of this recommendation statement, the USPSTF has revised the way it grades its recommendations to make them more clinically useful.
Recommendations concern preventive care for patients without recognized signs or symptoms of a given condition. The USPSTF now grades the recommendations as follows (descriptions of levels of certainty can be found at the guidelines home page):
A — The service is recommended. High certainty that benefit is substantial.
B — The service is recommended. High certainty that benefit is moderate, or moderate certainty that benefit is moderate to substantial.
C — The USPSTF recommends against providing the service routinely. Moderate certainty that the benefit is small. Considerations may support providing the service to individual patients.
D — The USPSTF recommends against the service. Moderate to high certainty of no benefit or that the harms outweigh the benefits.
I — Evidence is insufficient to assess the balance of benefits and harms.
The USPSTF also now provides suggestions for practice: For Grade A or B recommendations, offer the service; Grade C, offer the service only based on individual considerations; Grade D, discourage the service; Grade I, if the service is offered (e.g., based on clinical considerations), patients should understand the uncertainty about the benefits and harms.
In a new guideline, the USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general population. The recommendation is graded "D." The suggestion is that such screening be discouraged.
Although no randomized trials of screening have been performed, some evidence supports the USPSTF recommendation:
Carotid ultrasonography is sensitive for severe carotid stenosis (94% for stenosis 60%) but results in many false-positives.
Angiography provides accurate confirmation but is associated with serious adverse events (e.g., stroke); noninvasive testing (e.g., magnetic resonance imaging) is associated with false-positives (leading to unnecessary surgery and surgery-related stroke and death).
Carotid endarterectomy at excellent centers is associated with, at best, a 3% 30-day rate of stroke or death.
Select patients who undergo carotid endarterectomy performed by selected surgeons experience a 5% decrease in stroke or perioperative death within 5 years, according to results from two good-quality randomized trials; these benefits would be lower in the general population.
Comment: Even though the USPSTF requires the highest levels of evidence to recommend any preventive service, I was surprised by its "not recommended" stance on this one, because randomized trials of endarterectomy in asymptomatic people have suggested modest benefits (primarily in men). But it makes sense. The task force did not cite insufficient evidence as the basis for its recommendation; instead, it used randomized trial evidence, data on screening test accuracy, and projected harms from invasive procedures. We would need to screen more than 4000 people to prevent one stroke (during 5 years); in the process, for each person helped, almost as many people would be harmed by angiography consequences, perioperative stroke, or death. Despite this problematic benefit-to-harm ratio, many patients are undergoing screening carotid ultrasonography that is offered directly by private companies. However, prevention of atherosclerosis or better screening tests and treatments (and not carotid ultrasonography) will be the way to prevent stroke and death from carotid stenoses.
— Richard Saitz, MD, MPH, FACP, FASAM
Published in Journal Watch General Medicine January 15, 2008
Citation(s):
Wolff T et al. Screening for carotid artery stenosis: An update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2007 Dec 18; 147:860.
Original article (Subscription may be required)
Medline abstract (Free)
U.S. Preventive Services Task Force. Screening for carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2007 Dec 18; 147:854.
Original article (Subscription may be required)
Medline abstract (Free)
Monday, January 14, 2008
CDC Immunization Schedule Site
CDC Issues 2008 Childhood Vaccination Schedules
Vaccine Schedules CDC site
The 2008 recommended immunization schedules for children 18 years and younger have been published in MMWR.
Among the changes from 2007:
The live attenuated influenza vaccine (FluMist) is now recommended for children as young as age 2.
The meningococcal conjugate vaccine (MCV4) is recommended for high-risk children aged 2 to 10 years and all children 13 to 18 who haven't been previously immunized. (Routine MCV4 vaccination continues to be recommended for normal-risk children aged 11 to 12, as well as children through age 18 at increased risk for meningococcal disease.)
A new catch-up schedule advises that children aged 7 to 18 who received their first dose of the tetanus and diphtheria toxoids/tetanus and diphtheria toxoids and acelluar pertussis vaccine (Td/Tdap) before age 1 should be given four doses, with 4 or more weeks between the second and third doses.
Vaccine Schedules CDC site
The 2008 recommended immunization schedules for children 18 years and younger have been published in MMWR.
Among the changes from 2007:
The live attenuated influenza vaccine (FluMist) is now recommended for children as young as age 2.
The meningococcal conjugate vaccine (MCV4) is recommended for high-risk children aged 2 to 10 years and all children 13 to 18 who haven't been previously immunized. (Routine MCV4 vaccination continues to be recommended for normal-risk children aged 11 to 12, as well as children through age 18 at increased risk for meningococcal disease.)
A new catch-up schedule advises that children aged 7 to 18 who received their first dose of the tetanus and diphtheria toxoids/tetanus and diphtheria toxoids and acelluar pertussis vaccine (Td/Tdap) before age 1 should be given four doses, with 4 or more weeks between the second and third doses.
Friday, December 21, 2007
Cervical Cancer Guidelines
Cervical Cancer: New Guidelines for Screening and Prevention
Consensus guidelines for screening and management of abnormal cervical findings have been updated.
In October 2007, evidenced-based guidelines1,2 for the screening and management of cervical cancer were published to replace the 2001 guidelines. The updated guidelines were developed at a 2006 consensus conference of experts representing 29 organizations, including the National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists. Table 1 shows the relevant clinical terms and their abbreviations.
View this table:
[in a new window]
Table 1. 2006 Consensus Guidelines: Clinical Terms
GUIDELINE OVERVIEW
A significant body of evidence (most notably the results of the National Cancer Institute’s ASC-US/LGSIL triage study) has accrued since 2001 and is central to the new consensus guidelines. The authors make it clear that guidelines cannot apply to all situations and therefore should not serve as a substitute for the clinical judgment that must be used in the management of individual patients. Algorithms for the new recommendations are available from the American Society for Colposcopy and Cervical Pathology.3,4
The 2006 guidelines show significant evolution in the management of abnormal cervical cancer screening results, especially in adolescents and in patients with HGSIL. Minor changes also have been incorporated into management of atypical glandular cells and cervical abnormalities in pregnant patients. The management of LGSIL in most patient categories remains essentially unchanged. Noteworthy revisions have been made in the recommended management of CIN 1. Minor modifications have been made to the CIN 2,3 treatment guidelines, and conservative management recommendations in adolescents have been expanded.
The option of offering HPV testing to women 30 and older, first included in a 2004 interim guideline, has been formally adopted. In women who test negative on Pap smear and positive for HPV, both tests should be repeated in 12 months. When cytology and HPV testing are both negative, routine screening need not be performed for 3 years. HPV testing is recommended for routine screening only in women 30 and older.
UPDATED RECOMMENDATIONS: ABNORMAL CERVICAL CANCER SCREENING TESTS
Adolescent women with AS-CUS or LGSIL:2 Adolescents (women 20 and younger) have a much higher prevalence of HPV than do older women; they also have a higher prevalence of low-grade cervical cytologic abnormalities. Adolescents spontaneously clear most infections, and the associated minor cytologic abnormalities are of little long-term significance. The guidelines do not distinguish between ASC-US and LGSIL in adolescents, as the outcomes of both are similar in this age group.
Reflex HPV testing is not recommended for adolescents with ASC-US. In general, HPV testing is unacceptable in adolescents with ASC-US or LGSIL and, if inadvertently performed, should not influence management. Instead, adolescents with a result of ASC-US or LGSIL should undergo repeat cytologic testing 1 year later. If, at 1-year repeat testing:
Cytology is less than HGSIL, then cytology should be performed again 1 year later. If the second cytologic testing (24 months after the initial finding of ASC-US or LGSIL) reveals ASC-US or greater, then colposcopy should be performed.
Cytology is HGSIL or greater, colposcopy should be performed.
Women with ASC-H: Adolescents as well as adult women with ASC-H should undergo colposcopy.
Immunosuppressed women: ASC-US in immunosuppressed women, such as those with HIV infection, should be managed the same as in women in the general population (i.e., colposcopy is not necessarily required).
Pregnant women with LGSIL: Colposcopy is preferred for nonadolescents, but the procedure may be deferred until 6 weeks postpartum. If colposcopy shows no evidence of CIN 2,3, then postpartum follow-up is recommended.
Postmenopausal women with LGSIL: Postmenopausal women with LGSIL can be managed less aggressively than premenopausal women because the prevalence of HPV positivity in women with LGSIL declines with age. Options include evaluation with reflex HPV testing, repeat cytologic testing at 6 and 12 months, and colposcopy.
Women with HGSIL: New emphasis is placed on the see-and-treat approach in nonadolescent women. Management options include immediate loop electrosurgical excision or colposcopy with endocervical assessment. Loop electrosurgical excision is unacceptable in adolescent women with HGSIL, for whom colposcopy is recommended.
Women with AGC: For all subcategories of AGC and AIS except atypical endometrial cells, the recommendations call for colposcopy with endocervical sampling, HPV testing, and (in women older than 35 or at risk for endometrial hyperplasia) endometrial sampling. In patients with atypical endometrial cells, endometrial and endocervical sampling are appropriate initial steps. If these samples show no endometrial pathology, then colposcopy is recommended.
UPDATED RECOMMENDATIONS: CIN AND AIS
Women with histologic diagnosis of CIN 1:1 Major changes to the recommendations for CIN 1 treatment are focused on the patient’s prior abnormal cytologic findings and not on the adequacy of the colposcopy. Management does not depend on whether the colposcopy was satisfactory, and treatment is not an acceptable option in women with CIN 1 preceded by cytologic evidence of ASC-US, ASC-H, or LGSIL. Rather, follow-up with cytology every 6 to 12 months or HPV testing at 12 months is recommended. If follow-up HPV is positive or follow-up cytology is greater than or equal to ASC-US, then colposcopy is recommended.
In women with CIN 1 preceded by HGSIL or AGC-NOS (not otherwise specified) three options are acceptable: (1) diagnostic excisional procedure (except in adolescents and pregnant women); (2) observation with colposcopy and cytology at 6-month intervals for 1 year if the colposcopy is satisfactory and endocervical sampling is negative; or (3) review of all findings with revised interpretation if necessary.
Adolescents with CIN 1, 2, or 3: Management of adolescents with CIN 1 is not dependent on prior abnormal cytology, and repeat cytology is recommended every 12 months. In adolescents with CIN 2,3, either observation or treatment is acceptable if the colposcopy is satisfactory. If CIN 2 is specified, then observation is preferred. If CIN 3 is specified or if colposcopy is unsatisfactory, treatment is recommended. If CIN 3 is specified and colposcopy is adequate, then repeat colposcopy and cytology at 6-month intervals is acceptable.
Women with CIN 2,3: Either excision or ablation is acceptable in cases with satisfactory colposcopy. When colposcopy is unsatisfactory, a diagnostic excisional procedure is the recommended treatment. In women with recurrent CIN 2,3, a repeat diagnostic excisional procedure is recommended over transitional zone ablation (T zone; junction of squamous and columnar epithelium). For older women with recurrent CIN 2,3 who have concluded childbearing, either repeat diagnostic excision or hysterectomy is an acceptable option.
Adenocarcinoma in situ: Hysterectomy is the preferred treatment, with conservative management acceptable only if preservation of fertility is desired. In such cases (and when margins are involved or the endocervical sampling is positive), reexcision is recommended.
CONCLUSION
Progress in our understanding of the natural history of cervical intraepithelial lesions and HPV infection has led to significant changes in recommendations for evaluation and treatment of abnormal Pap smears, cervical intraepithelial neoplasias, and adenocarcinoma in situ. These advances, in concert with HPV vaccination, show clear promise in preventing cervical cancer.
— Ann J. Davis, MD
Published in Journal Watch Women's Health November 29, 2007
Citation(s):
1. Wright TC Jr et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007 Oct; 197:340.
Medline abstract (Free)
2. Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346.
Medline abstract (Free)
3. American Society for Colposcopy and Cervical Pathology. Management of women with atypical squamous cells of undetermined significance (ASC-US). 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf)
4. American Society for Colposcopy and Cervical Pathology. Management of women with a histological diagnosis of cervical intraepithelial neoplasia grade 1 (CIN 1) preceded by ASC-US, ASC-H or LSIL cytology. 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_hist_07.pdf)
Consensus guidelines for screening and management of abnormal cervical findings have been updated.
In October 2007, evidenced-based guidelines1,2 for the screening and management of cervical cancer were published to replace the 2001 guidelines. The updated guidelines were developed at a 2006 consensus conference of experts representing 29 organizations, including the National Institutes of Health, the American Cancer Society, and the American College of Obstetricians and Gynecologists. Table 1 shows the relevant clinical terms and their abbreviations.
View this table:
[in a new window]
Table 1. 2006 Consensus Guidelines: Clinical Terms
GUIDELINE OVERVIEW
A significant body of evidence (most notably the results of the National Cancer Institute’s ASC-US/LGSIL triage study) has accrued since 2001 and is central to the new consensus guidelines. The authors make it clear that guidelines cannot apply to all situations and therefore should not serve as a substitute for the clinical judgment that must be used in the management of individual patients. Algorithms for the new recommendations are available from the American Society for Colposcopy and Cervical Pathology.3,4
The 2006 guidelines show significant evolution in the management of abnormal cervical cancer screening results, especially in adolescents and in patients with HGSIL. Minor changes also have been incorporated into management of atypical glandular cells and cervical abnormalities in pregnant patients. The management of LGSIL in most patient categories remains essentially unchanged. Noteworthy revisions have been made in the recommended management of CIN 1. Minor modifications have been made to the CIN 2,3 treatment guidelines, and conservative management recommendations in adolescents have been expanded.
The option of offering HPV testing to women 30 and older, first included in a 2004 interim guideline, has been formally adopted. In women who test negative on Pap smear and positive for HPV, both tests should be repeated in 12 months. When cytology and HPV testing are both negative, routine screening need not be performed for 3 years. HPV testing is recommended for routine screening only in women 30 and older.
UPDATED RECOMMENDATIONS: ABNORMAL CERVICAL CANCER SCREENING TESTS
Adolescent women with AS-CUS or LGSIL:2 Adolescents (women 20 and younger) have a much higher prevalence of HPV than do older women; they also have a higher prevalence of low-grade cervical cytologic abnormalities. Adolescents spontaneously clear most infections, and the associated minor cytologic abnormalities are of little long-term significance. The guidelines do not distinguish between ASC-US and LGSIL in adolescents, as the outcomes of both are similar in this age group.
Reflex HPV testing is not recommended for adolescents with ASC-US. In general, HPV testing is unacceptable in adolescents with ASC-US or LGSIL and, if inadvertently performed, should not influence management. Instead, adolescents with a result of ASC-US or LGSIL should undergo repeat cytologic testing 1 year later. If, at 1-year repeat testing:
Cytology is less than HGSIL, then cytology should be performed again 1 year later. If the second cytologic testing (24 months after the initial finding of ASC-US or LGSIL) reveals ASC-US or greater, then colposcopy should be performed.
Cytology is HGSIL or greater, colposcopy should be performed.
Women with ASC-H: Adolescents as well as adult women with ASC-H should undergo colposcopy.
Immunosuppressed women: ASC-US in immunosuppressed women, such as those with HIV infection, should be managed the same as in women in the general population (i.e., colposcopy is not necessarily required).
Pregnant women with LGSIL: Colposcopy is preferred for nonadolescents, but the procedure may be deferred until 6 weeks postpartum. If colposcopy shows no evidence of CIN 2,3, then postpartum follow-up is recommended.
Postmenopausal women with LGSIL: Postmenopausal women with LGSIL can be managed less aggressively than premenopausal women because the prevalence of HPV positivity in women with LGSIL declines with age. Options include evaluation with reflex HPV testing, repeat cytologic testing at 6 and 12 months, and colposcopy.
Women with HGSIL: New emphasis is placed on the see-and-treat approach in nonadolescent women. Management options include immediate loop electrosurgical excision or colposcopy with endocervical assessment. Loop electrosurgical excision is unacceptable in adolescent women with HGSIL, for whom colposcopy is recommended.
Women with AGC: For all subcategories of AGC and AIS except atypical endometrial cells, the recommendations call for colposcopy with endocervical sampling, HPV testing, and (in women older than 35 or at risk for endometrial hyperplasia) endometrial sampling. In patients with atypical endometrial cells, endometrial and endocervical sampling are appropriate initial steps. If these samples show no endometrial pathology, then colposcopy is recommended.
UPDATED RECOMMENDATIONS: CIN AND AIS
Women with histologic diagnosis of CIN 1:1 Major changes to the recommendations for CIN 1 treatment are focused on the patient’s prior abnormal cytologic findings and not on the adequacy of the colposcopy. Management does not depend on whether the colposcopy was satisfactory, and treatment is not an acceptable option in women with CIN 1 preceded by cytologic evidence of ASC-US, ASC-H, or LGSIL. Rather, follow-up with cytology every 6 to 12 months or HPV testing at 12 months is recommended. If follow-up HPV is positive or follow-up cytology is greater than or equal to ASC-US, then colposcopy is recommended.
In women with CIN 1 preceded by HGSIL or AGC-NOS (not otherwise specified) three options are acceptable: (1) diagnostic excisional procedure (except in adolescents and pregnant women); (2) observation with colposcopy and cytology at 6-month intervals for 1 year if the colposcopy is satisfactory and endocervical sampling is negative; or (3) review of all findings with revised interpretation if necessary.
Adolescents with CIN 1, 2, or 3: Management of adolescents with CIN 1 is not dependent on prior abnormal cytology, and repeat cytology is recommended every 12 months. In adolescents with CIN 2,3, either observation or treatment is acceptable if the colposcopy is satisfactory. If CIN 2 is specified, then observation is preferred. If CIN 3 is specified or if colposcopy is unsatisfactory, treatment is recommended. If CIN 3 is specified and colposcopy is adequate, then repeat colposcopy and cytology at 6-month intervals is acceptable.
Women with CIN 2,3: Either excision or ablation is acceptable in cases with satisfactory colposcopy. When colposcopy is unsatisfactory, a diagnostic excisional procedure is the recommended treatment. In women with recurrent CIN 2,3, a repeat diagnostic excisional procedure is recommended over transitional zone ablation (T zone; junction of squamous and columnar epithelium). For older women with recurrent CIN 2,3 who have concluded childbearing, either repeat diagnostic excision or hysterectomy is an acceptable option.
Adenocarcinoma in situ: Hysterectomy is the preferred treatment, with conservative management acceptable only if preservation of fertility is desired. In such cases (and when margins are involved or the endocervical sampling is positive), reexcision is recommended.
CONCLUSION
Progress in our understanding of the natural history of cervical intraepithelial lesions and HPV infection has led to significant changes in recommendations for evaluation and treatment of abnormal Pap smears, cervical intraepithelial neoplasias, and adenocarcinoma in situ. These advances, in concert with HPV vaccination, show clear promise in preventing cervical cancer.
— Ann J. Davis, MD
Published in Journal Watch Women's Health November 29, 2007
Citation(s):
1. Wright TC Jr et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007 Oct; 197:340.
Medline abstract (Free)
2. Wright TC Jr et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007 Oct; 197:346.
Medline abstract (Free)
3. American Society for Colposcopy and Cervical Pathology. Management of women with atypical squamous cells of undetermined significance (ASC-US). 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_cyto_07.pdf)
4. American Society for Colposcopy and Cervical Pathology. Management of women with a histological diagnosis of cervical intraepithelial neoplasia grade 1 (CIN 1) preceded by ASC-US, ASC-H or LSIL cytology. 2006, 2007. (http://www.asccp.org/pdfs/consensus/algorithms_hist_07.pdf)
Subscribe to:
Posts (Atom)
