Postmenopausal bleeding (PMB) is the presenting sign in most cases of endometrial carcinoma. Prompt evaluation of PMB can exclude, or diagnose, endometrial carcinoma.¹ Although no general consensus exists for PMB evaluation, it involves endometrial assessment with transvaginal ultrasonography (TVUS) and subsequent endometrial biopsy when a thickened endometrium is found. When biopsy results reveal insufficient or scant tissue, further investigation into the etiology of PMB should include office hysteroscopy with possible directed biopsy. In this article I discuss the prevalence of PMB and steps for evaluation, providing clinical takeaways.

Postmenopausal bleeding: Its risk for cancer

Abnormal uterine bleeding (AUB) in a postmenopausal woman is of particular concern to the gynecologist and the patient because of the increased possibility of endometrial carcinoma in this age group. AUB is present in more than 90% of postmenopausal women with endometrial carcinoma, which leads to diagnosis in the early stages of the disease. Approximately 3% to 7% of postmenopausal women with PMB will have endometrial carcinoma.² Most women with PMB, however, experience bleeding secondary to atrophic changes of the vagina or endometrium and not to endometrial carcinoma. (FIGURE 1, VIDEO 1) In addition, women who take gonadal steroids for hormone replacement therapy (HRT) may experience breakthrough bleeding that leads to initial investigation with TVUS.

Video 1

Vidyard Video

The risk of malignancy in polyps in postmenopausal women over the age of 59 who present with PMB is approximately 12%, and hysteroscopic resection should routinely be performed. For asymptomatic patients, the risk of a malignant lesion is low—approximately 3%—and for these women intervention should be assessed individually for the risks of carcinoma and benefits of hysteroscopic removal.³

Clinical takeaway. The high possibility of endometrial carcinoma in postmenopausal women warrants that any patient who is symptomatic with PMB should be presumed to have endometrial cancer until the diagnostic evaluation process proves she does not.

Evaluation of postmenopausal bleeding

Transvaginal ultrasound

As mentioned, no general consensus exists for the evaluation of PMB; however, initial evaluation by TVUS is recommended. The American College of Obstetricians and Gynecologists (ACOG) concluded that when the endometrium measures ≤4 mm with TVUS, the likelihood that bleeding is secondary to endometrial carcinoma is less than 1% (negative predictive value 99%), and endometrial biopsy is not recommended.³ Endometrial sampling in this clinical scenario likely will result in insufficient tissue for evaluation, and it is reasonable to consider initial management for atrophy. A thickened endometrium on TVUS (>4 mm in a postmenopausal woman with PMB) warrants additional evaluation with endometrial sampling (FIGURE 2).

Clinical takeaway. A thickened endometrium on TVUS ≥4 mm in a postmenopausal woman with PMB warrants additional evaluation with endometrial sampling.

Endometrial biopsy

An endometrial biopsy is performed to determine whether endometrial cancer or precancer is present in women with AUB. ACOG recommends that endometrial biopsy be performed for women older than age 45. It is also appropriate in women younger than 45 years if they have risk factors for developing endometrial cancer, including unopposed estrogen exposure (obesity, ovulatory dysfunction), failed medical management of AUB, or persistence of AUB.⁴

Continue to: Endometrial biopsy has some...

 

 

Endometrial biopsy has some diagnostic shortcomings, however. In 2016 a systematic review and meta-analysis found that, in women with PMB, the specificity of endometrial biopsy was 98% to 100% (accurate diagnosis with a positive result). The sensitivity (ability to make an accurate diagnosis) of endometrial biopsy to identify endometrial pathology (carcinoma, atypical hyperplasia, and polyps) is lower than typically thought. These investigators found an endometrial biopsy failure rate of 11% (range, 1% to 53%) and rate of insufficient samples of 31% (range, 7% to 76%). In women with insufficient or failed samples, endometrial cancer or precancer was found in 7% (range, 0% to 18%).⁵ Therefore, a negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative. The results of endometrial biopsy are only an endpoint to the evaluation of PMB when atypical hyperplasia or endometrial cancer is identified.

Clinical takeaway. A negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative.

 

Hysteroscopy

Hysteroscopy is the gold standard for evaluating the uterine cavity, diagnosing intrauterine pathology, and operative intervention for some causes of AUB. It also is easily performed in the office. This makes the hysteroscope an essential instrument for the gynecologist. Dr. Linda Bradley, a preeminent leader in hysteroscopic surgical education, has coined the phrase, “My hysteroscope is my stethoscope.”⁶ As gynecologists, we should be as adept at using a hysteroscope in the office as the cardiologist is at using a stethoscope.

It has been known for some time that hysteroscopy improves our diagnostic capabilities over blinded procedures such as endometrial biopsy and dilation and curettage (D&C). As far back as 1989, Dr. Frank Loffer reported the increased sensitivity (ability to make an accurate diagnosis) of hysteroscopy with directed biopsy over blinded D&C (98% vs 65%) in the evaluation of AUB.⁷ Evaluation of the endometrium with D&C is no longer recommended; yet today, few gynecologists perform hysteroscopic-directed biopsy for AUB evaluation instead of blinded tissue sampling despite the clinical superiority and in-office capabilities (FIGURE 3).

Continue to: Hysteroscopy and endometrial carcinoma...

 

 

Hysteroscopy and endometrial carcinoma

The most common type of gynecologic cancer in the United States is endometrial adenocarcinoma (type 1 endometrial cancer). There is some concern about the effect of hysteroscopy on endometrial cancer prognosis and the spread of cells to the peritoneum at the time of hysteroscopy. A large meta-analysis found that hysteroscopy performed in the presence of type 1 endometrial cancer statistically significantly increased the likelihood of positive intraperitoneal cytology; however, it did not alter the clinical outcome. It was recommended that hysteroscopy not be avoided for this reason and is helpful in the diagnosis of endometrial cancer, especially in the early stages of disease.⁸

For endometrial cancer type 2 (serous carcinoma, clear cell carcinoma, and carcinosarcoma), Chen and colleagues reported a statistically significant increase in positive peritoneal cytology for cancers evaluated by hysteroscopy versus D&C. The disease-specific survival for the hysteroscopy group was 60 months, compared with 71 months for the D&C group. While this finding was not statistically significant, it was clinically relevant, and the effect of hysteroscopy on prognosis with type 2 endometrial cancer is unclear.⁹

Three clinical scenarios

---

A common occurrence in the evaluation of postmenopausal bleeding (PMB) is an initial TVUS finding of an enlarged endometrium and an endometrial biopsy that is negative or reveals scant or insufficient tissue. Unfortunately, the diagnostic evaluation process often stops here, and a diagnosis for the PMB is never actually identified. Here are several clinical scenarios that highlight the need for hysteroscopy in the initial evaluation of PMB, especially when there is a discordance between transvaginal ultrasonography (TVUS) and endometrial biopsy findings.

Patient 1: Discordant TVUS and biopsy, with benign findings

The patient is a 52-year-old woman who presented to her gynecologist reporting abnormal uterine bleeding (AUB). She has a history of breast cancer, and she completed tamoxifen treatment. Pelvic ultrasonography was performed; an enlarged endometrial stripe of 1.3 cm was found (FIGURE 4A). Endometrial biopsy was performed, showing adequate tissue but with a negative result. The patient is told that she is likely perimenopausal, which is the reason for her bleeding.

At the time of referral, the patient is evaluated with in-office hysteroscopy. Diagnosis of a 5 cm x 7 cm benign endometrial polyp is made. An uneventful hysteroscopic polypectomy is performed (VIDEO 2).

Video 2

Vidyard Video

This scenario illustrates the shortcoming of initial evaluation by not performing a hysteroscopy, especially in a woman with a thickened endometrium with previous tamoxifen therapy. Subsequent visits failed to correlate bleeding etiology with discordant TVUS and endometrial biopsy results with hysteroscopy, and no hysteroscopy was performed in the operating room at the time of D&C.

Patient 2: Discordant TVUS and biopsy, with premalignant findings

The patient is a 62-year-old woman who had incidental findings of a thickened endometrium on computed tomography scan of the pelvis. TVUS confirmed a thickened endometrium measuring 17 mm, and an endometrial biopsy showed scant tissue.

At the time of referral, a diagnostic hysteroscopy was performed in the office. Endometrial atrophy, a large benign appearing polyp, and focal abnormal appearing tissue were seen (FIGURE 5). A decision for polypectomy and directed biopsy was made. Histology findings confirmed benign polyp and atypical hyperplasia (VIDEO 3).

Video 3

Vidyard Video

This scenario illustrates that while the patient was asymptomatic, there was discordance between the TVUS and endometrial biopsy. Hysteroscopy identified a benign endometrial polyp, which is common in asymptomatic postmenopausal patients with a thickened endometrium and endometrial biopsy showing scant tissue. However, addition of the diagnostic hysteroscopy identified focal precancerous tissue, removed under directed biopsy.

Patient 3: Discordant TVUS and biopsy, with malignant findings

The patient is a 68-year-old woman with PMB. TVUS showed a thickened endometrium measuring 14 mm. An endometrial biopsy was negative, showing scant tissue. No additional diagnostic evaluation or management was offered.

Video 4A

Vidyard Video

At the time of referral, the patient was evaluated with in-office diagnostic hysteroscopy, and the patient was found to have endometrial atrophy, benign appearing polyps, and focal abnormal tissue (FIGURE 6). A decision for polypectomy and directed biopsy was made. Histology confirmed benign polyps and grade 1 adenocarcinoma (VIDEOS 4A, 4B, 4C).

Video 4B

Vidyard Video

This scenario illustrates the possibility of having multiple endometrial pathologies present at the time of discordant TVUS and endometrial biopsy. Hysteroscopy plays a critical role in additional evaluation and diagnosis of endometrial carcinoma with directed biopsy, especially in a symptomatic woman with PMB.

Video 4C

Vidyard Video

 

 

Conclusion

Evaluation of PMB begins with a screening TVUS. Findings of an endometrium of ≤4 mm indicate a very low likelihood of the presence of endometrial cancer, and treatment for atrophy or changes to hormone replacement therapy regimen is reasonable first-line management; endometrial biopsy is not recommended. For patients with persistent PMB or thickened endometrium ≥4 mm on TVUS, biopsy sampling of the endometrium should be performed. If the endometrial biopsy does not explain the etiology of the PMB with atypical hyperplasia or endometrial cancer, then hysteroscopy should be performed to evaluate for focal endometrial disease and possible directed biopsy.

Postmenopausal bleeding (PMB) is the presenting sign in most cases of endometrial carcinoma. Prompt evaluation of PMB can exclude, or diagnose, endometrial carcinoma.¹ Although no general consensus exists for PMB evaluation, it involves endometrial assessment with transvaginal ultrasonography (TVUS) and subsequent endometrial biopsy when a thickened endometrium is found. When biopsy results reveal insufficient or scant tissue, further investigation into the etiology of PMB should include office hysteroscopy with possible directed biopsy. In this article I discuss the prevalence of PMB and steps for evaluation, providing clinical takeaways.

Postmenopausal bleeding: Its risk for cancer

Abnormal uterine bleeding (AUB) in a postmenopausal woman is of particular concern to the gynecologist and the patient because of the increased possibility of endometrial carcinoma in this age group. AUB is present in more than 90% of postmenopausal women with endometrial carcinoma, which leads to diagnosis in the early stages of the disease. Approximately 3% to 7% of postmenopausal women with PMB will have endometrial carcinoma.² Most women with PMB, however, experience bleeding secondary to atrophic changes of the vagina or endometrium and not to endometrial carcinoma. (FIGURE 1, VIDEO 1) In addition, women who take gonadal steroids for hormone replacement therapy (HRT) may experience breakthrough bleeding that leads to initial investigation with TVUS.

Video 1

Vidyard Video

The risk of malignancy in polyps in postmenopausal women over the age of 59 who present with PMB is approximately 12%, and hysteroscopic resection should routinely be performed. For asymptomatic patients, the risk of a malignant lesion is low—approximately 3%—and for these women intervention should be assessed individually for the risks of carcinoma and benefits of hysteroscopic removal.³

Clinical takeaway. The high possibility of endometrial carcinoma in postmenopausal women warrants that any patient who is symptomatic with PMB should be presumed to have endometrial cancer until the diagnostic evaluation process proves she does not.

Evaluation of postmenopausal bleeding

Transvaginal ultrasound

As mentioned, no general consensus exists for the evaluation of PMB; however, initial evaluation by TVUS is recommended. The American College of Obstetricians and Gynecologists (ACOG) concluded that when the endometrium measures ≤4 mm with TVUS, the likelihood that bleeding is secondary to endometrial carcinoma is less than 1% (negative predictive value 99%), and endometrial biopsy is not recommended.³ Endometrial sampling in this clinical scenario likely will result in insufficient tissue for evaluation, and it is reasonable to consider initial management for atrophy. A thickened endometrium on TVUS (>4 mm in a postmenopausal woman with PMB) warrants additional evaluation with endometrial sampling (FIGURE 2).

Clinical takeaway. A thickened endometrium on TVUS ≥4 mm in a postmenopausal woman with PMB warrants additional evaluation with endometrial sampling.

Endometrial biopsy

An endometrial biopsy is performed to determine whether endometrial cancer or precancer is present in women with AUB. ACOG recommends that endometrial biopsy be performed for women older than age 45. It is also appropriate in women younger than 45 years if they have risk factors for developing endometrial cancer, including unopposed estrogen exposure (obesity, ovulatory dysfunction), failed medical management of AUB, or persistence of AUB.⁴

Continue to: Endometrial biopsy has some...

 

 

Endometrial biopsy has some diagnostic shortcomings, however. In 2016 a systematic review and meta-analysis found that, in women with PMB, the specificity of endometrial biopsy was 98% to 100% (accurate diagnosis with a positive result). The sensitivity (ability to make an accurate diagnosis) of endometrial biopsy to identify endometrial pathology (carcinoma, atypical hyperplasia, and polyps) is lower than typically thought. These investigators found an endometrial biopsy failure rate of 11% (range, 1% to 53%) and rate of insufficient samples of 31% (range, 7% to 76%). In women with insufficient or failed samples, endometrial cancer or precancer was found in 7% (range, 0% to 18%).⁵ Therefore, a negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative. The results of endometrial biopsy are only an endpoint to the evaluation of PMB when atypical hyperplasia or endometrial cancer is identified.

Clinical takeaway. A negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative.

 

Hysteroscopy

Hysteroscopy is the gold standard for evaluating the uterine cavity, diagnosing intrauterine pathology, and operative intervention for some causes of AUB. It also is easily performed in the office. This makes the hysteroscope an essential instrument for the gynecologist. Dr. Linda Bradley, a preeminent leader in hysteroscopic surgical education, has coined the phrase, “My hysteroscope is my stethoscope.”⁶ As gynecologists, we should be as adept at using a hysteroscope in the office as the cardiologist is at using a stethoscope.

It has been known for some time that hysteroscopy improves our diagnostic capabilities over blinded procedures such as endometrial biopsy and dilation and curettage (D&C). As far back as 1989, Dr. Frank Loffer reported the increased sensitivity (ability to make an accurate diagnosis) of hysteroscopy with directed biopsy over blinded D&C (98% vs 65%) in the evaluation of AUB.⁷ Evaluation of the endometrium with D&C is no longer recommended; yet today, few gynecologists perform hysteroscopic-directed biopsy for AUB evaluation instead of blinded tissue sampling despite the clinical superiority and in-office capabilities (FIGURE 3).

Continue to: Hysteroscopy and endometrial carcinoma...

 

 

Hysteroscopy and endometrial carcinoma

The most common type of gynecologic cancer in the United States is endometrial adenocarcinoma (type 1 endometrial cancer). There is some concern about the effect of hysteroscopy on endometrial cancer prognosis and the spread of cells to the peritoneum at the time of hysteroscopy. A large meta-analysis found that hysteroscopy performed in the presence of type 1 endometrial cancer statistically significantly increased the likelihood of positive intraperitoneal cytology; however, it did not alter the clinical outcome. It was recommended that hysteroscopy not be avoided for this reason and is helpful in the diagnosis of endometrial cancer, especially in the early stages of disease.⁸

For endometrial cancer type 2 (serous carcinoma, clear cell carcinoma, and carcinosarcoma), Chen and colleagues reported a statistically significant increase in positive peritoneal cytology for cancers evaluated by hysteroscopy versus D&C. The disease-specific survival for the hysteroscopy group was 60 months, compared with 71 months for the D&C group. While this finding was not statistically significant, it was clinically relevant, and the effect of hysteroscopy on prognosis with type 2 endometrial cancer is unclear.⁹

Three clinical scenarios

---

A common occurrence in the evaluation of postmenopausal bleeding (PMB) is an initial TVUS finding of an enlarged endometrium and an endometrial biopsy that is negative or reveals scant or insufficient tissue. Unfortunately, the diagnostic evaluation process often stops here, and a diagnosis for the PMB is never actually identified. Here are several clinical scenarios that highlight the need for hysteroscopy in the initial evaluation of PMB, especially when there is a discordance between transvaginal ultrasonography (TVUS) and endometrial biopsy findings.

Patient 1: Discordant TVUS and biopsy, with benign findings

The patient is a 52-year-old woman who presented to her gynecologist reporting abnormal uterine bleeding (AUB). She has a history of breast cancer, and she completed tamoxifen treatment. Pelvic ultrasonography was performed; an enlarged endometrial stripe of 1.3 cm was found (FIGURE 4A). Endometrial biopsy was performed, showing adequate tissue but with a negative result. The patient is told that she is likely perimenopausal, which is the reason for her bleeding.

At the time of referral, the patient is evaluated with in-office hysteroscopy. Diagnosis of a 5 cm x 7 cm benign endometrial polyp is made. An uneventful hysteroscopic polypectomy is performed (VIDEO 2).

Video 2

Vidyard Video

This scenario illustrates the shortcoming of initial evaluation by not performing a hysteroscopy, especially in a woman with a thickened endometrium with previous tamoxifen therapy. Subsequent visits failed to correlate bleeding etiology with discordant TVUS and endometrial biopsy results with hysteroscopy, and no hysteroscopy was performed in the operating room at the time of D&C.

Patient 2: Discordant TVUS and biopsy, with premalignant findings

The patient is a 62-year-old woman who had incidental findings of a thickened endometrium on computed tomography scan of the pelvis. TVUS confirmed a thickened endometrium measuring 17 mm, and an endometrial biopsy showed scant tissue.

At the time of referral, a diagnostic hysteroscopy was performed in the office. Endometrial atrophy, a large benign appearing polyp, and focal abnormal appearing tissue were seen (FIGURE 5). A decision for polypectomy and directed biopsy was made. Histology findings confirmed benign polyp and atypical hyperplasia (VIDEO 3).

Video 3

Vidyard Video

This scenario illustrates that while the patient was asymptomatic, there was discordance between the TVUS and endometrial biopsy. Hysteroscopy identified a benign endometrial polyp, which is common in asymptomatic postmenopausal patients with a thickened endometrium and endometrial biopsy showing scant tissue. However, addition of the diagnostic hysteroscopy identified focal precancerous tissue, removed under directed biopsy.

Patient 3: Discordant TVUS and biopsy, with malignant findings

The patient is a 68-year-old woman with PMB. TVUS showed a thickened endometrium measuring 14 mm. An endometrial biopsy was negative, showing scant tissue. No additional diagnostic evaluation or management was offered.

Video 4A

Vidyard Video

At the time of referral, the patient was evaluated with in-office diagnostic hysteroscopy, and the patient was found to have endometrial atrophy, benign appearing polyps, and focal abnormal tissue (FIGURE 6). A decision for polypectomy and directed biopsy was made. Histology confirmed benign polyps and grade 1 adenocarcinoma (VIDEOS 4A, 4B, 4C).

Video 4B

Vidyard Video

This scenario illustrates the possibility of having multiple endometrial pathologies present at the time of discordant TVUS and endometrial biopsy. Hysteroscopy plays a critical role in additional evaluation and diagnosis of endometrial carcinoma with directed biopsy, especially in a symptomatic woman with PMB.

Video 4C

Vidyard Video

 

 

Conclusion

Evaluation of PMB begins with a screening TVUS. Findings of an endometrium of ≤4 mm indicate a very low likelihood of the presence of endometrial cancer, and treatment for atrophy or changes to hormone replacement therapy regimen is reasonable first-line management; endometrial biopsy is not recommended. For patients with persistent PMB or thickened endometrium ≥4 mm on TVUS, biopsy sampling of the endometrium should be performed. If the endometrial biopsy does not explain the etiology of the PMB with atypical hyperplasia or endometrial cancer, then hysteroscopy should be performed to evaluate for focal endometrial disease and possible directed biopsy.

Postmenopausal bleeding (PMB) is the presenting sign in most cases of endometrial carcinoma. Prompt evaluation of PMB can exclude, or diagnose, endometrial carcinoma.¹ Although no general consensus exists for PMB evaluation, it involves endometrial assessment with transvaginal ultrasonography (TVUS) and subsequent endometrial biopsy when a thickened endometrium is found. When biopsy results reveal insufficient or scant tissue, further investigation into the etiology of PMB should include office hysteroscopy with possible directed biopsy. In this article I discuss the prevalence of PMB and steps for evaluation, providing clinical takeaways.

Postmenopausal bleeding: Its risk for cancer

Abnormal uterine bleeding (AUB) in a postmenopausal woman is of particular concern to the gynecologist and the patient because of the increased possibility of endometrial carcinoma in this age group. AUB is present in more than 90% of postmenopausal women with endometrial carcinoma, which leads to diagnosis in the early stages of the disease. Approximately 3% to 7% of postmenopausal women with PMB will have endometrial carcinoma.² Most women with PMB, however, experience bleeding secondary to atrophic changes of the vagina or endometrium and not to endometrial carcinoma. (FIGURE 1, VIDEO 1) In addition, women who take gonadal steroids for hormone replacement therapy (HRT) may experience breakthrough bleeding that leads to initial investigation with TVUS.

Video 1

Vidyard Video

The risk of malignancy in polyps in postmenopausal women over the age of 59 who present with PMB is approximately 12%, and hysteroscopic resection should routinely be performed. For asymptomatic patients, the risk of a malignant lesion is low—approximately 3%—and for these women intervention should be assessed individually for the risks of carcinoma and benefits of hysteroscopic removal.³

Clinical takeaway. The high possibility of endometrial carcinoma in postmenopausal women warrants that any patient who is symptomatic with PMB should be presumed to have endometrial cancer until the diagnostic evaluation process proves she does not.

Evaluation of postmenopausal bleeding

Transvaginal ultrasound

As mentioned, no general consensus exists for the evaluation of PMB; however, initial evaluation by TVUS is recommended. The American College of Obstetricians and Gynecologists (ACOG) concluded that when the endometrium measures ≤4 mm with TVUS, the likelihood that bleeding is secondary to endometrial carcinoma is less than 1% (negative predictive value 99%), and endometrial biopsy is not recommended.³ Endometrial sampling in this clinical scenario likely will result in insufficient tissue for evaluation, and it is reasonable to consider initial management for atrophy. A thickened endometrium on TVUS (>4 mm in a postmenopausal woman with PMB) warrants additional evaluation with endometrial sampling (FIGURE 2).

Clinical takeaway. A thickened endometrium on TVUS ≥4 mm in a postmenopausal woman with PMB warrants additional evaluation with endometrial sampling.

Endometrial biopsy

An endometrial biopsy is performed to determine whether endometrial cancer or precancer is present in women with AUB. ACOG recommends that endometrial biopsy be performed for women older than age 45. It is also appropriate in women younger than 45 years if they have risk factors for developing endometrial cancer, including unopposed estrogen exposure (obesity, ovulatory dysfunction), failed medical management of AUB, or persistence of AUB.⁴

Continue to: Endometrial biopsy has some...

 

 

Endometrial biopsy has some diagnostic shortcomings, however. In 2016 a systematic review and meta-analysis found that, in women with PMB, the specificity of endometrial biopsy was 98% to 100% (accurate diagnosis with a positive result). The sensitivity (ability to make an accurate diagnosis) of endometrial biopsy to identify endometrial pathology (carcinoma, atypical hyperplasia, and polyps) is lower than typically thought. These investigators found an endometrial biopsy failure rate of 11% (range, 1% to 53%) and rate of insufficient samples of 31% (range, 7% to 76%). In women with insufficient or failed samples, endometrial cancer or precancer was found in 7% (range, 0% to 18%).⁵ Therefore, a negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative. The results of endometrial biopsy are only an endpoint to the evaluation of PMB when atypical hyperplasia or endometrial cancer is identified.

Clinical takeaway. A negative tissue biopsy result in women with PMB is not considered to be an endpoint, and further evaluation with hysteroscopy to evaluate for focal disease is imperative.

 

Hysteroscopy

Hysteroscopy is the gold standard for evaluating the uterine cavity, diagnosing intrauterine pathology, and operative intervention for some causes of AUB. It also is easily performed in the office. This makes the hysteroscope an essential instrument for the gynecologist. Dr. Linda Bradley, a preeminent leader in hysteroscopic surgical education, has coined the phrase, “My hysteroscope is my stethoscope.”⁶ As gynecologists, we should be as adept at using a hysteroscope in the office as the cardiologist is at using a stethoscope.

It has been known for some time that hysteroscopy improves our diagnostic capabilities over blinded procedures such as endometrial biopsy and dilation and curettage (D&C). As far back as 1989, Dr. Frank Loffer reported the increased sensitivity (ability to make an accurate diagnosis) of hysteroscopy with directed biopsy over blinded D&C (98% vs 65%) in the evaluation of AUB.⁷ Evaluation of the endometrium with D&C is no longer recommended; yet today, few gynecologists perform hysteroscopic-directed biopsy for AUB evaluation instead of blinded tissue sampling despite the clinical superiority and in-office capabilities (FIGURE 3).

Continue to: Hysteroscopy and endometrial carcinoma...

 

 

Hysteroscopy and endometrial carcinoma

The most common type of gynecologic cancer in the United States is endometrial adenocarcinoma (type 1 endometrial cancer). There is some concern about the effect of hysteroscopy on endometrial cancer prognosis and the spread of cells to the peritoneum at the time of hysteroscopy. A large meta-analysis found that hysteroscopy performed in the presence of type 1 endometrial cancer statistically significantly increased the likelihood of positive intraperitoneal cytology; however, it did not alter the clinical outcome. It was recommended that hysteroscopy not be avoided for this reason and is helpful in the diagnosis of endometrial cancer, especially in the early stages of disease.⁸

For endometrial cancer type 2 (serous carcinoma, clear cell carcinoma, and carcinosarcoma), Chen and colleagues reported a statistically significant increase in positive peritoneal cytology for cancers evaluated by hysteroscopy versus D&C. The disease-specific survival for the hysteroscopy group was 60 months, compared with 71 months for the D&C group. While this finding was not statistically significant, it was clinically relevant, and the effect of hysteroscopy on prognosis with type 2 endometrial cancer is unclear.⁹

Three clinical scenarios

---

A common occurrence in the evaluation of postmenopausal bleeding (PMB) is an initial TVUS finding of an enlarged endometrium and an endometrial biopsy that is negative or reveals scant or insufficient tissue. Unfortunately, the diagnostic evaluation process often stops here, and a diagnosis for the PMB is never actually identified. Here are several clinical scenarios that highlight the need for hysteroscopy in the initial evaluation of PMB, especially when there is a discordance between transvaginal ultrasonography (TVUS) and endometrial biopsy findings.

Patient 1: Discordant TVUS and biopsy, with benign findings

The patient is a 52-year-old woman who presented to her gynecologist reporting abnormal uterine bleeding (AUB). She has a history of breast cancer, and she completed tamoxifen treatment. Pelvic ultrasonography was performed; an enlarged endometrial stripe of 1.3 cm was found (FIGURE 4A). Endometrial biopsy was performed, showing adequate tissue but with a negative result. The patient is told that she is likely perimenopausal, which is the reason for her bleeding.

At the time of referral, the patient is evaluated with in-office hysteroscopy. Diagnosis of a 5 cm x 7 cm benign endometrial polyp is made. An uneventful hysteroscopic polypectomy is performed (VIDEO 2).

Video 2

Vidyard Video

This scenario illustrates the shortcoming of initial evaluation by not performing a hysteroscopy, especially in a woman with a thickened endometrium with previous tamoxifen therapy. Subsequent visits failed to correlate bleeding etiology with discordant TVUS and endometrial biopsy results with hysteroscopy, and no hysteroscopy was performed in the operating room at the time of D&C.

Patient 2: Discordant TVUS and biopsy, with premalignant findings

The patient is a 62-year-old woman who had incidental findings of a thickened endometrium on computed tomography scan of the pelvis. TVUS confirmed a thickened endometrium measuring 17 mm, and an endometrial biopsy showed scant tissue.

At the time of referral, a diagnostic hysteroscopy was performed in the office. Endometrial atrophy, a large benign appearing polyp, and focal abnormal appearing tissue were seen (FIGURE 5). A decision for polypectomy and directed biopsy was made. Histology findings confirmed benign polyp and atypical hyperplasia (VIDEO 3).

Video 3

Vidyard Video

This scenario illustrates that while the patient was asymptomatic, there was discordance between the TVUS and endometrial biopsy. Hysteroscopy identified a benign endometrial polyp, which is common in asymptomatic postmenopausal patients with a thickened endometrium and endometrial biopsy showing scant tissue. However, addition of the diagnostic hysteroscopy identified focal precancerous tissue, removed under directed biopsy.

Patient 3: Discordant TVUS and biopsy, with malignant findings

The patient is a 68-year-old woman with PMB. TVUS showed a thickened endometrium measuring 14 mm. An endometrial biopsy was negative, showing scant tissue. No additional diagnostic evaluation or management was offered.

Video 4A

Vidyard Video

At the time of referral, the patient was evaluated with in-office diagnostic hysteroscopy, and the patient was found to have endometrial atrophy, benign appearing polyps, and focal abnormal tissue (FIGURE 6). A decision for polypectomy and directed biopsy was made. Histology confirmed benign polyps and grade 1 adenocarcinoma (VIDEOS 4A, 4B, 4C).

Video 4B

Vidyard Video

This scenario illustrates the possibility of having multiple endometrial pathologies present at the time of discordant TVUS and endometrial biopsy. Hysteroscopy plays a critical role in additional evaluation and diagnosis of endometrial carcinoma with directed biopsy, especially in a symptomatic woman with PMB.

Video 4C

Vidyard Video

 

 

Conclusion

Evaluation of PMB begins with a screening TVUS. Findings of an endometrium of ≤4 mm indicate a very low likelihood of the presence of endometrial cancer, and treatment for atrophy or changes to hormone replacement therapy regimen is reasonable first-line management; endometrial biopsy is not recommended. For patients with persistent PMB or thickened endometrium ≥4 mm on TVUS, biopsy sampling of the endometrium should be performed. If the endometrial biopsy does not explain the etiology of the PMB with atypical hyperplasia or endometrial cancer, then hysteroscopy should be performed to evaluate for focal endometrial disease and possible directed biopsy.

The state with the best hospital now has the best health care to go along with it, and the last frontier is also last in the nation in health care.

In the 2019 edition of its annual ranking of state health care systems, personal finance website WalletHub named Minnesota the best less than a week after U.S. News & World Report called the Mayo Clinic the top hospital in the country.

The WalletHub ranking, which included Washington, D.C., also put Alaska’s health care system at No. 51. Just one step above in the 50th spot was North Carolina, with Mississippi (49), South Carolina (48), and Arkansas (47) occupying the rest of the bottom five. Louisiana, which jumped from 51st in 2018 to 44th this year, was the only state to move out of the bottom five, WalletHub reported.

Joining Minnesota in the top five were Massachusetts (2), Rhode Island (3), D.C. (4), and Vermont (5), which was the home of last year’s best health care. North Dakota, which moved up 12 spots this year all the way to 9th, had the second-largest climb of any state: Montana catapulted 15 spots this year to finish 17th overall, WalletHub said.

For 2019, the company compared the states and D.C. using 43 measures of cost, accessibility, and outcome. The cost dimension’s six metrics included cost of a medical visit and share of adults with no doctor visits because of cost. The accessibility dimension consisted of 23 metrics, including hospital beds per capita, geriatricians per population aged 65 years and older, and Medicaid acceptance rate among physicians. The outcomes dimension included 14 metrics, among them share of patients readmitted to hospitals and share of nonimmunized children.


Minnesota was the only state to finish in the top 10 of all three dimensions. D.C. was ranked first in cost and Maine was the leader in access – as each was last year – and Massachusetts was ranked first in outcomes, the WalletHub data show.

The lowest-ranked states for each category in 2019 were the same as in 2018: Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from 21 sources, including the Bureau of Labor Statistics, the Centers for Medicare & Medicaid Services, and the Kaiser Family Foundation.

[email protected]

The state with the best hospital now has the best health care to go along with it, and the last frontier is also last in the nation in health care.

In the 2019 edition of its annual ranking of state health care systems, personal finance website WalletHub named Minnesota the best less than a week after U.S. News & World Report called the Mayo Clinic the top hospital in the country.

The WalletHub ranking, which included Washington, D.C., also put Alaska’s health care system at No. 51. Just one step above in the 50th spot was North Carolina, with Mississippi (49), South Carolina (48), and Arkansas (47) occupying the rest of the bottom five. Louisiana, which jumped from 51st in 2018 to 44th this year, was the only state to move out of the bottom five, WalletHub reported.

Joining Minnesota in the top five were Massachusetts (2), Rhode Island (3), D.C. (4), and Vermont (5), which was the home of last year’s best health care. North Dakota, which moved up 12 spots this year all the way to 9th, had the second-largest climb of any state: Montana catapulted 15 spots this year to finish 17th overall, WalletHub said.

For 2019, the company compared the states and D.C. using 43 measures of cost, accessibility, and outcome. The cost dimension’s six metrics included cost of a medical visit and share of adults with no doctor visits because of cost. The accessibility dimension consisted of 23 metrics, including hospital beds per capita, geriatricians per population aged 65 years and older, and Medicaid acceptance rate among physicians. The outcomes dimension included 14 metrics, among them share of patients readmitted to hospitals and share of nonimmunized children.


Minnesota was the only state to finish in the top 10 of all three dimensions. D.C. was ranked first in cost and Maine was the leader in access – as each was last year – and Massachusetts was ranked first in outcomes, the WalletHub data show.

The lowest-ranked states for each category in 2019 were the same as in 2018: Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from 21 sources, including the Bureau of Labor Statistics, the Centers for Medicare & Medicaid Services, and the Kaiser Family Foundation.

[email protected]

The state with the best hospital now has the best health care to go along with it, and the last frontier is also last in the nation in health care.

In the 2019 edition of its annual ranking of state health care systems, personal finance website WalletHub named Minnesota the best less than a week after U.S. News & World Report called the Mayo Clinic the top hospital in the country.

The WalletHub ranking, which included Washington, D.C., also put Alaska’s health care system at No. 51. Just one step above in the 50th spot was North Carolina, with Mississippi (49), South Carolina (48), and Arkansas (47) occupying the rest of the bottom five. Louisiana, which jumped from 51st in 2018 to 44th this year, was the only state to move out of the bottom five, WalletHub reported.

Joining Minnesota in the top five were Massachusetts (2), Rhode Island (3), D.C. (4), and Vermont (5), which was the home of last year’s best health care. North Dakota, which moved up 12 spots this year all the way to 9th, had the second-largest climb of any state: Montana catapulted 15 spots this year to finish 17th overall, WalletHub said.

For 2019, the company compared the states and D.C. using 43 measures of cost, accessibility, and outcome. The cost dimension’s six metrics included cost of a medical visit and share of adults with no doctor visits because of cost. The accessibility dimension consisted of 23 metrics, including hospital beds per capita, geriatricians per population aged 65 years and older, and Medicaid acceptance rate among physicians. The outcomes dimension included 14 metrics, among them share of patients readmitted to hospitals and share of nonimmunized children.


Minnesota was the only state to finish in the top 10 of all three dimensions. D.C. was ranked first in cost and Maine was the leader in access – as each was last year – and Massachusetts was ranked first in outcomes, the WalletHub data show.

The lowest-ranked states for each category in 2019 were the same as in 2018: Alaska (cost), Texas (access), and Mississippi (outcomes), according to the WalletHub analysis, which was based on data from 21 sources, including the Bureau of Labor Statistics, the Centers for Medicare & Medicaid Services, and the Kaiser Family Foundation.

[email protected]

More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]