During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

During an ob.gyn. rotation, a medical student quickly learns the risks related to endometriosis; that is, pelvic pain, abnormal uterine bleeding, and infertility. With more experience, the young practitioner realizes the concern of unopposed estrogen therapy in patients with a history of endometriosis (i.e., cancer).

Now, in this excellent discussion by Dr. Farr Nezhat, for the current edition of the Master Class in Gynecologic Surgery, he describes the risk of endometriosis and ovarian cancer. Not only does Dr. Nezhat present data revealing the increased association between ovarian cancer and endometriosis, but he goes on to describe the usual type of epithelial ovarian cancer that is noted in the patient with endometriosis.

Dr. Nezhat describes women who appear to be predisposed to malignant transformation and provides current recommendations to lower the risk of malignancy in patients with endometriosis. This includes complete surgical resection of endometriosis, routine ultrasound/MRI if endometriosis is not resected, suppressive hormonal therapy, and bilateral salpingectomy. Moreover, Dr. Nezhat looks to the future and the possibility of genetic screening tests.

Dr. Nezhat is board certified in gynecologic oncology and is world renowned for his work with advanced laparoscopic and robotic surgery for the treatment of gynecologic cancers and complex benign conditions. He is the director of minimally invasive gynecologic surgery and robotics at Winthrop University Hospital in Mineola, N.Y., and an adjunct professor of obstetrics, gynecology, and reproductive medicine at State University of New York at Stony Brook.

His main areas of interest and research include early detection and treatment of early and advanced ovarian cancer, as well as cancer arising in endometriosis. Dr. Nezhat has authored and coauthored more than 200 medical and scientific manuscripts and book chapters.

Dr. Miller is a clinical associate professor at the University of Illinois at Chicago, and a past president of the AAGL and the International Society for Gynecologic Endoscopy (ISGE). He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/Society of Reproductive Surgery fellowship in minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. Dr. Miller reported having no financial disclosures relevant to this column.

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].

Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.

Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.

In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.

Terminology

The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.

In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).

With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.

©monkeybusinessimages/Thinkstock

Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.

Diagnosis

There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.

If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.

Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.

HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.

Management

Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.

If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.

There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.

In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).

The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.

Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.

Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].

Clinical question: Does AIMS65 risk stratification score predict inpatient mortality in patients with acute upper gastrointestinal bleed (UGIB)?

Background: Acute UGIB is associated with significant morbidity and mortality, which makes it crucial to identify high-risk patients early. Several prognostic algorithms such as Glasgow-Blatchford (GBS) and pre-endoscopy (pre-RS) and post-endoscopy (post-RS) Rockall scores are available to triage such patients. The goal of this study was to validate AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB compared to these other prognostic scores.

Study Design: Retrospective, cohort study.

Setting: Tertiary-care center in Australia, January 2010 to June 2013.

Synopsis: Using ICD-10 diagnosis codes, investigators identified 424 patients with UGIB requiring endoscopy. All patients were risk-stratified using AIMS65, GBS, pre-RS, and post-RS. The AIMS65 score was found to be superior in predicting inpatient mortality compared to GBS and pre-RS scores and statistically superior to all other scores in predicting need for ICU admission.

In addition to being a single-center, retrospective study, other limitations include the use of ICD-10 codes to identify patients. Further prospective studies are needed to further validate the AIMS65 in acute UGIB.

Bottom line: AIMS65 is a simple and useful tool in predicting inpatient mortality in patients with acute UGIB. However, its applicability in making clinical decisions remains unclear.

Citation: Robertson M, Majumdar A, Boyapati R, et al. Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems [published online ahead of print October 16, 2015]. Gastrointest Endosc. doi:10.1016/j.gie.2015.10.021.

Clinical question: Does AIMS65 risk stratification score predict inpatient mortality in patients with acute upper gastrointestinal bleed (UGIB)?

Background: Acute UGIB is associated with significant morbidity and mortality, which makes it crucial to identify high-risk patients early. Several prognostic algorithms such as Glasgow-Blatchford (GBS) and pre-endoscopy (pre-RS) and post-endoscopy (post-RS) Rockall scores are available to triage such patients. The goal of this study was to validate AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB compared to these other prognostic scores.

Study Design: Retrospective, cohort study.

Setting: Tertiary-care center in Australia, January 2010 to June 2013.

Synopsis: Using ICD-10 diagnosis codes, investigators identified 424 patients with UGIB requiring endoscopy. All patients were risk-stratified using AIMS65, GBS, pre-RS, and post-RS. The AIMS65 score was found to be superior in predicting inpatient mortality compared to GBS and pre-RS scores and statistically superior to all other scores in predicting need for ICU admission.

In addition to being a single-center, retrospective study, other limitations include the use of ICD-10 codes to identify patients. Further prospective studies are needed to further validate the AIMS65 in acute UGIB.

Bottom line: AIMS65 is a simple and useful tool in predicting inpatient mortality in patients with acute UGIB. However, its applicability in making clinical decisions remains unclear.

Citation: Robertson M, Majumdar A, Boyapati R, et al. Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems [published online ahead of print October 16, 2015]. Gastrointest Endosc. doi:10.1016/j.gie.2015.10.021.

Clinical question: Does AIMS65 risk stratification score predict inpatient mortality in patients with acute upper gastrointestinal bleed (UGIB)?

Background: Acute UGIB is associated with significant morbidity and mortality, which makes it crucial to identify high-risk patients early. Several prognostic algorithms such as Glasgow-Blatchford (GBS) and pre-endoscopy (pre-RS) and post-endoscopy (post-RS) Rockall scores are available to triage such patients. The goal of this study was to validate AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB compared to these other prognostic scores.

Study Design: Retrospective, cohort study.

Setting: Tertiary-care center in Australia, January 2010 to June 2013.

Synopsis: Using ICD-10 diagnosis codes, investigators identified 424 patients with UGIB requiring endoscopy. All patients were risk-stratified using AIMS65, GBS, pre-RS, and post-RS. The AIMS65 score was found to be superior in predicting inpatient mortality compared to GBS and pre-RS scores and statistically superior to all other scores in predicting need for ICU admission.

In addition to being a single-center, retrospective study, other limitations include the use of ICD-10 codes to identify patients. Further prospective studies are needed to further validate the AIMS65 in acute UGIB.

Bottom line: AIMS65 is a simple and useful tool in predicting inpatient mortality in patients with acute UGIB. However, its applicability in making clinical decisions remains unclear.

Citation: Robertson M, Majumdar A, Boyapati R, et al. Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems [published online ahead of print October 16, 2015]. Gastrointest Endosc. doi:10.1016/j.gie.2015.10.021.

Thrombus

Image by Andre E.X. Brown

Results of a case-control study indicate that estrogen-only hormone therapy carries a lower risk of venous thromboembolism (VTE) than combined estrogen-progestogen therapy.

The study also suggests the type of progestogen a patient receives does not significantly impact the risk of VTE, but the route of administration for estrogen does.

Annica Bergendal, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and her colleagues reported these findings in Menopause.

The study was conducted in Sweden between 2003 and 2009. It included 838 women with VTE and 891 age-matched control subjects.

Analyses suggested the risk of VTE was almost 2-fold higher in women currently on hormone therapy than in those not taking hormones. The odds ratio (OR)—which was adjusted for smoking, body mass index, and immobilization—was 1.72 (95% CI 1.34-2.20).

Women who took combined estrogen-progestogen therapy had nearly 3 times the VTE risk of those who took no hormones (OR 2.85, 95% CI 2.08-3.90), but the risk was much lower for women who took estrogen alone (OR 1.31, 95% CI 0.78-2.21).

The risk of VTE with combined estrogen-progestogen treatment was about double that of estrogen alone (OR 2.18, 95% CI 1.21-3.92).

Researchers have wondered whether the type of progestogen used makes a difference in the risk of VTE, but this study didn’t show any significant difference in risk between 2 commonly used progestogens.

When oral estrogen was combined with progestogen, the risk of VTE was somewhat, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among users of norethisterone acetate (OR 2.29, 95% CI 1.50-3.40).

On the other hand, the way estrogen was delivered appeared to impact the risk of VTE, with oral estrogen conferring the highest risk.

When the researchers used transdermal estrogen—given alone—as reference, they observed an increased risk of VTE associated with oral estrogen alone (OR 1.84, 95% CI 0.62-5.52).

And when the researchers used locally (vaginally) administered estrogen alone as reference, they saw an increased risk of VTE associated with oral estrogen alone (OR 2.64, 95% CI 1.30-5.38).

Among women using combined estrogen-progestogen treatment, with transdermal estrogen as a reference, there was an increase in VTE risk associated with oral estrogen (OR 2.21, 95% CI 0.88-5.60).

“This study adds to our knowledge that transdermal estrogen therapies are safer than oral, and that different estrogen or progestogen combinations may have different risks,” said JoAnn V. Pinkerton, MD, executive director of the North American Menopause Society, who was not involved in this study.

“The lack of blood clots with transdermal estrogen and with vaginal estrogen is very reassuring for women who need to continue taking hormones as they age, when risk of blood clots increases.”

Thrombus

Image by Andre E.X. Brown

Results of a case-control study indicate that estrogen-only hormone therapy carries a lower risk of venous thromboembolism (VTE) than combined estrogen-progestogen therapy.

The study also suggests the type of progestogen a patient receives does not significantly impact the risk of VTE, but the route of administration for estrogen does.

Annica Bergendal, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and her colleagues reported these findings in Menopause.

The study was conducted in Sweden between 2003 and 2009. It included 838 women with VTE and 891 age-matched control subjects.

Analyses suggested the risk of VTE was almost 2-fold higher in women currently on hormone therapy than in those not taking hormones. The odds ratio (OR)—which was adjusted for smoking, body mass index, and immobilization—was 1.72 (95% CI 1.34-2.20).

Women who took combined estrogen-progestogen therapy had nearly 3 times the VTE risk of those who took no hormones (OR 2.85, 95% CI 2.08-3.90), but the risk was much lower for women who took estrogen alone (OR 1.31, 95% CI 0.78-2.21).

The risk of VTE with combined estrogen-progestogen treatment was about double that of estrogen alone (OR 2.18, 95% CI 1.21-3.92).

Researchers have wondered whether the type of progestogen used makes a difference in the risk of VTE, but this study didn’t show any significant difference in risk between 2 commonly used progestogens.

When oral estrogen was combined with progestogen, the risk of VTE was somewhat, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among users of norethisterone acetate (OR 2.29, 95% CI 1.50-3.40).

On the other hand, the way estrogen was delivered appeared to impact the risk of VTE, with oral estrogen conferring the highest risk.

When the researchers used transdermal estrogen—given alone—as reference, they observed an increased risk of VTE associated with oral estrogen alone (OR 1.84, 95% CI 0.62-5.52).

And when the researchers used locally (vaginally) administered estrogen alone as reference, they saw an increased risk of VTE associated with oral estrogen alone (OR 2.64, 95% CI 1.30-5.38).

Among women using combined estrogen-progestogen treatment, with transdermal estrogen as a reference, there was an increase in VTE risk associated with oral estrogen (OR 2.21, 95% CI 0.88-5.60).

“This study adds to our knowledge that transdermal estrogen therapies are safer than oral, and that different estrogen or progestogen combinations may have different risks,” said JoAnn V. Pinkerton, MD, executive director of the North American Menopause Society, who was not involved in this study.

“The lack of blood clots with transdermal estrogen and with vaginal estrogen is very reassuring for women who need to continue taking hormones as they age, when risk of blood clots increases.”

Thrombus

Image by Andre E.X. Brown

Results of a case-control study indicate that estrogen-only hormone therapy carries a lower risk of venous thromboembolism (VTE) than combined estrogen-progestogen therapy.

The study also suggests the type of progestogen a patient receives does not significantly impact the risk of VTE, but the route of administration for estrogen does.

Annica Bergendal, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and her colleagues reported these findings in Menopause.

The study was conducted in Sweden between 2003 and 2009. It included 838 women with VTE and 891 age-matched control subjects.

Analyses suggested the risk of VTE was almost 2-fold higher in women currently on hormone therapy than in those not taking hormones. The odds ratio (OR)—which was adjusted for smoking, body mass index, and immobilization—was 1.72 (95% CI 1.34-2.20).

Women who took combined estrogen-progestogen therapy had nearly 3 times the VTE risk of those who took no hormones (OR 2.85, 95% CI 2.08-3.90), but the risk was much lower for women who took estrogen alone (OR 1.31, 95% CI 0.78-2.21).

The risk of VTE with combined estrogen-progestogen treatment was about double that of estrogen alone (OR 2.18, 95% CI 1.21-3.92).

Researchers have wondered whether the type of progestogen used makes a difference in the risk of VTE, but this study didn’t show any significant difference in risk between 2 commonly used progestogens.

When oral estrogen was combined with progestogen, the risk of VTE was somewhat, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among users of norethisterone acetate (OR 2.29, 95% CI 1.50-3.40).

On the other hand, the way estrogen was delivered appeared to impact the risk of VTE, with oral estrogen conferring the highest risk.

When the researchers used transdermal estrogen—given alone—as reference, they observed an increased risk of VTE associated with oral estrogen alone (OR 1.84, 95% CI 0.62-5.52).

And when the researchers used locally (vaginally) administered estrogen alone as reference, they saw an increased risk of VTE associated with oral estrogen alone (OR 2.64, 95% CI 1.30-5.38).

Among women using combined estrogen-progestogen treatment, with transdermal estrogen as a reference, there was an increase in VTE risk associated with oral estrogen (OR 2.21, 95% CI 0.88-5.60).

“This study adds to our knowledge that transdermal estrogen therapies are safer than oral, and that different estrogen or progestogen combinations may have different risks,” said JoAnn V. Pinkerton, MD, executive director of the North American Menopause Society, who was not involved in this study.

“The lack of blood clots with transdermal estrogen and with vaginal estrogen is very reassuring for women who need to continue taking hormones as they age, when risk of blood clots increases.”

Acute promyelocytic leukemia

Image courtesy of The Armed

Forces Institute of Pathology

A class of circular RNAs may play a key role in the development and progression of certain leukemias and other cancers, according to research published in Cell.

Investigators found that cancer-associated chromosomal translocations give rise to fusion circular RNAs (f-circRNAs).

And these f-circRNAs aid cellular transformation, promote cell viability, confer treatment resistance, and exhibit tumor-promoting properties in vivo.

“Cancer is essentially a disease of mutated or broken genes, so that motivated us to examine whether circular RNAs, like proteins, can be affected by these chromosomal breaks,” said study author Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“Our work paves the way to discovering many more of these unusual RNAs and how they contribute to cancer, which could reveal new mechanisms and druggable pathways involved in tumor progression.”

Curious about the possibility of circular RNAs contributing to cancer, Dr Pandolfi and his colleagues set out to see if they could detect relevant changes in tumors known to harbor distinct fusion proteins.

The team examined acute promyelocytic leukemia, which often carries a translocation between the PML and RARα genes, and acute myeloid leukemia, which can harbor a translocation between the MLL and AF9 genes.

The investigators found f-circRNAs corresponding to different exons associated with the PML-RARα gene fusion and the MLL-AF9 gene fusion. Normally, multiple circular RNAs can be generated from a single gene, so the team was not surprised to find different f-circRNAs emerging from the same fusion gene.

Dr Pandolfi and his colleagues also uncovered f-circRNAs in solid tumors—in Ewing sarcoma and lung cancer.

The team identified the f-circRNAs using 2 distinct methods—PCR-based amplification and sequencing-based approaches. They said this suggests f-circRNAs are bona fide biological entities, rather than experimental artifacts.

“Our ability to readily detect these fusion-circular RNAs—and their normal, non-fused counterparts—will be enhanced by advances in sequencing technology and analytic methods,” said study author Jlenia Guarnerio, PhD, also of Beth Israel Deaconess Medical Center.

“Indeed, as we look ahead to cataloguing them comprehensively across all cancers and to deeply understanding their mechanisms of action, we will need to propel these new methodologies even further.”

To determine whether f-circRNAs play a functional role in cancer, the investigators introduced the RNAs into cells. This caused the cells to increase their proliferation and tendency to overgrow—features shared by tumor cells.

On the other hand, when the team blocked f-circRNA activity, the cells’ normal behaviors were restored.

Dr Pandolfi and his colleagues also conducted experiments using a mouse model of leukemia. They focused on a specific f-circRNA associated with the MLL-AF9 fusion gene, called f-circM9.

Although f-circM9 could not trigger leukemia on its own, it appeared to work with other cancer-promoting signals—such as the MLL-AF9 fusion protein—to cause leukemia.

Additional experiments suggested that f-circM9 may also help tumor cells persist despite treatment with anticancer drugs.

“These results are particularly exciting because they suggest that drugs directed at fusion-circular RNAs could be a powerful strategy to pursue for future therapeutic development in cancer,” Dr Pandolfi said.

“[However,] our knowledge of circular RNAs is really in its infancy. We know that, normally, they can bind proteins as well as DNA and microRNAs, but much more needs to be done to understand how fusion-circular RNAs work. We have only scratched the surface of these RNAs and their roles in cancer and other diseases.”

Acute promyelocytic leukemia

Image courtesy of The Armed

Forces Institute of Pathology

A class of circular RNAs may play a key role in the development and progression of certain leukemias and other cancers, according to research published in Cell.

Investigators found that cancer-associated chromosomal translocations give rise to fusion circular RNAs (f-circRNAs).

And these f-circRNAs aid cellular transformation, promote cell viability, confer treatment resistance, and exhibit tumor-promoting properties in vivo.

“Cancer is essentially a disease of mutated or broken genes, so that motivated us to examine whether circular RNAs, like proteins, can be affected by these chromosomal breaks,” said study author Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“Our work paves the way to discovering many more of these unusual RNAs and how they contribute to cancer, which could reveal new mechanisms and druggable pathways involved in tumor progression.”

Curious about the possibility of circular RNAs contributing to cancer, Dr Pandolfi and his colleagues set out to see if they could detect relevant changes in tumors known to harbor distinct fusion proteins.

The team examined acute promyelocytic leukemia, which often carries a translocation between the PML and RARα genes, and acute myeloid leukemia, which can harbor a translocation between the MLL and AF9 genes.

The investigators found f-circRNAs corresponding to different exons associated with the PML-RARα gene fusion and the MLL-AF9 gene fusion. Normally, multiple circular RNAs can be generated from a single gene, so the team was not surprised to find different f-circRNAs emerging from the same fusion gene.

Dr Pandolfi and his colleagues also uncovered f-circRNAs in solid tumors—in Ewing sarcoma and lung cancer.

The team identified the f-circRNAs using 2 distinct methods—PCR-based amplification and sequencing-based approaches. They said this suggests f-circRNAs are bona fide biological entities, rather than experimental artifacts.

“Our ability to readily detect these fusion-circular RNAs—and their normal, non-fused counterparts—will be enhanced by advances in sequencing technology and analytic methods,” said study author Jlenia Guarnerio, PhD, also of Beth Israel Deaconess Medical Center.

“Indeed, as we look ahead to cataloguing them comprehensively across all cancers and to deeply understanding their mechanisms of action, we will need to propel these new methodologies even further.”

To determine whether f-circRNAs play a functional role in cancer, the investigators introduced the RNAs into cells. This caused the cells to increase their proliferation and tendency to overgrow—features shared by tumor cells.

On the other hand, when the team blocked f-circRNA activity, the cells’ normal behaviors were restored.

Dr Pandolfi and his colleagues also conducted experiments using a mouse model of leukemia. They focused on a specific f-circRNA associated with the MLL-AF9 fusion gene, called f-circM9.

Although f-circM9 could not trigger leukemia on its own, it appeared to work with other cancer-promoting signals—such as the MLL-AF9 fusion protein—to cause leukemia.

Additional experiments suggested that f-circM9 may also help tumor cells persist despite treatment with anticancer drugs.

“These results are particularly exciting because they suggest that drugs directed at fusion-circular RNAs could be a powerful strategy to pursue for future therapeutic development in cancer,” Dr Pandolfi said.

“[However,] our knowledge of circular RNAs is really in its infancy. We know that, normally, they can bind proteins as well as DNA and microRNAs, but much more needs to be done to understand how fusion-circular RNAs work. We have only scratched the surface of these RNAs and their roles in cancer and other diseases.”

Acute promyelocytic leukemia

Image courtesy of The Armed

Forces Institute of Pathology

A class of circular RNAs may play a key role in the development and progression of certain leukemias and other cancers, according to research published in Cell.

Investigators found that cancer-associated chromosomal translocations give rise to fusion circular RNAs (f-circRNAs).

And these f-circRNAs aid cellular transformation, promote cell viability, confer treatment resistance, and exhibit tumor-promoting properties in vivo.

“Cancer is essentially a disease of mutated or broken genes, so that motivated us to examine whether circular RNAs, like proteins, can be affected by these chromosomal breaks,” said study author Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts.

“Our work paves the way to discovering many more of these unusual RNAs and how they contribute to cancer, which could reveal new mechanisms and druggable pathways involved in tumor progression.”

Curious about the possibility of circular RNAs contributing to cancer, Dr Pandolfi and his colleagues set out to see if they could detect relevant changes in tumors known to harbor distinct fusion proteins.

The team examined acute promyelocytic leukemia, which often carries a translocation between the PML and RARα genes, and acute myeloid leukemia, which can harbor a translocation between the MLL and AF9 genes.

The investigators found f-circRNAs corresponding to different exons associated with the PML-RARα gene fusion and the MLL-AF9 gene fusion. Normally, multiple circular RNAs can be generated from a single gene, so the team was not surprised to find different f-circRNAs emerging from the same fusion gene.

Dr Pandolfi and his colleagues also uncovered f-circRNAs in solid tumors—in Ewing sarcoma and lung cancer.

The team identified the f-circRNAs using 2 distinct methods—PCR-based amplification and sequencing-based approaches. They said this suggests f-circRNAs are bona fide biological entities, rather than experimental artifacts.

“Our ability to readily detect these fusion-circular RNAs—and their normal, non-fused counterparts—will be enhanced by advances in sequencing technology and analytic methods,” said study author Jlenia Guarnerio, PhD, also of Beth Israel Deaconess Medical Center.

“Indeed, as we look ahead to cataloguing them comprehensively across all cancers and to deeply understanding their mechanisms of action, we will need to propel these new methodologies even further.”

To determine whether f-circRNAs play a functional role in cancer, the investigators introduced the RNAs into cells. This caused the cells to increase their proliferation and tendency to overgrow—features shared by tumor cells.

On the other hand, when the team blocked f-circRNA activity, the cells’ normal behaviors were restored.

Dr Pandolfi and his colleagues also conducted experiments using a mouse model of leukemia. They focused on a specific f-circRNA associated with the MLL-AF9 fusion gene, called f-circM9.

Although f-circM9 could not trigger leukemia on its own, it appeared to work with other cancer-promoting signals—such as the MLL-AF9 fusion protein—to cause leukemia.

Additional experiments suggested that f-circM9 may also help tumor cells persist despite treatment with anticancer drugs.

“These results are particularly exciting because they suggest that drugs directed at fusion-circular RNAs could be a powerful strategy to pursue for future therapeutic development in cancer,” Dr Pandolfi said.

“[However,] our knowledge of circular RNAs is really in its infancy. We know that, normally, they can bind proteins as well as DNA and microRNAs, but much more needs to be done to understand how fusion-circular RNAs work. We have only scratched the surface of these RNAs and their roles in cancer and other diseases.”

Acute myeloid leukemia

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for the radioimmunoconjugate Iomab-B to be used as a conditioning agent for patients with relapsed or refractory acute myeloid leukemia (AML) who are undergoing hematopoietic stem cell transplant (HSCT).

Iomab-B is a radioimmunoconjugate consisting of BC8, a novel murine monoclonal antibody, and the radioisotope iodine-131.

BC8 targets CD45, a pan-leukocytic antigen widely expressed on white blood cells. This makes BC8 potentially useful in targeting white blood cells in preparation for HSCT.

When labeled with radioactive isotopes, BC8 carries radioactivity directly to the site of cancerous growth and bone marrow, while avoiding the effects of radiation on most healthy tissues, according to Actinium Pharmaceuticals, Inc., the company developing Iomab-B.

Actinium said Iomab-B has been tested as a myeloconditioning/myeloablative agent in more than 250 patients with incurable hematologic malignancies.

The company has released data from a phase 1/2 trial of Iomab-B in patients with relapsed/refractory AML who are older than 50.

The data show that patients who received Iomab-B before HSCT (n=27) had higher rates of survival at 1 and 2 years than patients who underwent HSCT with conventional myeloablative conditioning (n=10) or chemotherapy (n=61).

One-year survival rates were 30% in the Iomab-B arm and 10% each in the conventional conditioning and chemotherapy arms. Two-year survival rates were 19%, 0%, and 0%, respectively.

Now, Actinium is planning a phase 3 trial of Iomab-B in relapsed/refractory AML patients over the age of 55.

About orphan designation

The FDA grants orphan designation to drugs intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

Acute myeloid leukemia

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for the radioimmunoconjugate Iomab-B to be used as a conditioning agent for patients with relapsed or refractory acute myeloid leukemia (AML) who are undergoing hematopoietic stem cell transplant (HSCT).

Iomab-B is a radioimmunoconjugate consisting of BC8, a novel murine monoclonal antibody, and the radioisotope iodine-131.

BC8 targets CD45, a pan-leukocytic antigen widely expressed on white blood cells. This makes BC8 potentially useful in targeting white blood cells in preparation for HSCT.

When labeled with radioactive isotopes, BC8 carries radioactivity directly to the site of cancerous growth and bone marrow, while avoiding the effects of radiation on most healthy tissues, according to Actinium Pharmaceuticals, Inc., the company developing Iomab-B.

Actinium said Iomab-B has been tested as a myeloconditioning/myeloablative agent in more than 250 patients with incurable hematologic malignancies.

The company has released data from a phase 1/2 trial of Iomab-B in patients with relapsed/refractory AML who are older than 50.

The data show that patients who received Iomab-B before HSCT (n=27) had higher rates of survival at 1 and 2 years than patients who underwent HSCT with conventional myeloablative conditioning (n=10) or chemotherapy (n=61).

One-year survival rates were 30% in the Iomab-B arm and 10% each in the conventional conditioning and chemotherapy arms. Two-year survival rates were 19%, 0%, and 0%, respectively.

Now, Actinium is planning a phase 3 trial of Iomab-B in relapsed/refractory AML patients over the age of 55.

About orphan designation

The FDA grants orphan designation to drugs intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

Acute myeloid leukemia

Image by Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan designation for the radioimmunoconjugate Iomab-B to be used as a conditioning agent for patients with relapsed or refractory acute myeloid leukemia (AML) who are undergoing hematopoietic stem cell transplant (HSCT).

Iomab-B is a radioimmunoconjugate consisting of BC8, a novel murine monoclonal antibody, and the radioisotope iodine-131.

BC8 targets CD45, a pan-leukocytic antigen widely expressed on white blood cells. This makes BC8 potentially useful in targeting white blood cells in preparation for HSCT.

When labeled with radioactive isotopes, BC8 carries radioactivity directly to the site of cancerous growth and bone marrow, while avoiding the effects of radiation on most healthy tissues, according to Actinium Pharmaceuticals, Inc., the company developing Iomab-B.

Actinium said Iomab-B has been tested as a myeloconditioning/myeloablative agent in more than 250 patients with incurable hematologic malignancies.

The company has released data from a phase 1/2 trial of Iomab-B in patients with relapsed/refractory AML who are older than 50.

The data show that patients who received Iomab-B before HSCT (n=27) had higher rates of survival at 1 and 2 years than patients who underwent HSCT with conventional myeloablative conditioning (n=10) or chemotherapy (n=61).

One-year survival rates were 30% in the Iomab-B arm and 10% each in the conventional conditioning and chemotherapy arms. Two-year survival rates were 19%, 0%, and 0%, respectively.

Now, Actinium is planning a phase 3 trial of Iomab-B in relapsed/refractory AML patients over the age of 55.

About orphan designation

The FDA grants orphan designation to drugs intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.

The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.

Red blood cells

Top-line results from a phase 3 trial suggest the oral, iron-based drug ferric citrate is more effective than placebo for treating iron deficiency anemia in adults with stage 3-5, non-dialysis-dependent chronic kidney disease.

Fifty-two percent of patients who received ferric citrate achieved at least a 1 g/dL increase in hemoglobin over a 16-week period, compared to 19% of patients who received placebo.

Researchers said the safety profile of ferric citrate in this trial was consistent with that in previous studies.

Keryx Biopharmaceuticals, Inc., the company developing ferric citrate, recently announced these results.

Patients and treatment

In this phase 3 study, researchers compared treatment with ferric citrate to placebo in 234 patients who previously had not adequately responded to or tolerated current oral iron therapies. The patients were not allowed to receive any iron (intravenous or oral) or erythropoiesis-stimulating agents during this study.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=115). Two patients in the placebo arm discontinued the study and were not included in the efficacy analysis. One discontinued after randomization prior to receiving placebo, and the other discontinued after taking a dose of placebo but before having laboratory values drawn.

The study had a 16-week, randomized, double-blind, placebo-controlled efficacy period, followed by an 8-week, open-label safety extension period. During the extension period, all patients remaining in the study, including the placebo arm, received ferric citrate.

During the efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day, with food, and could be titrated every 4 weeks by an additional 3 tablets, for up to 12 tablets per day. The mean dose of ferric citrate was 5 tablets per day.

Baseline laboratory values were similar between the treatment arms. The mean hemoglobin was 10.4 g/dL in both arms.

The mean transferrin saturation was 20.2% in the ferric citrate arm and 19.6% in the placebo arm. The mean ferritin was 85.9 ng/mL and 81.7 ng/mL, respectively. And the mean serum phosphate was 4.2 mg/dL and 4.1 mg/dL, respectively.

Efficacy results

The study achieved its primary endpoint, with 52.1% (61/117) of patients who received ferric citrate achieving a 1g/dL or greater rise in hemoglobin at any time point during the 16-week efficacy period, compared to 19.1% (22/115) of patients in the placebo arm (P<0.001).

The researchers also observed significant differences in all pre-specified secondary efficacy endpoints.

The mean change in hemoglobin was 0.75 g/dL in the ferric citrate arm and -0.08 g/dL in the placebo arm (P<0.001). The mean change in transferrin saturation was 17.8% and -0.6%, respectively (P<0.001).

The mean change in ferritin was 162.5 ng/mL and -7.7 ng/mL, respectively (P<0.001). And the mean change in serum phosphate was -0.43 mg/dL and -0.22 mg/dL, respectively (P=0.02).

The proportion of patients with a durable response during the efficacy period was 48.7% in the ferric citrate arm and 14.8% in the placebo arm (P<0.001).

A durable response was defined as a mean change in hemoglobin from baseline of at least 0.75 g/dL over any 4-week time period during the efficacy period, provided that an increase of at least 1.0 g/dL had occurred during that 4-week period.

Safety results

During the efficacy period, the majority of adverse events (AEs) were mild to moderate. The most common AEs—in the ferric citrate and placebo arms, respectively—were diarrhea (20.5% vs 16.4%), constipation (18.8% vs 12.9%), discolored feces (14.5% vs 0%), and nausea (11.1% vs 2.6%).

Hypophosphatemia was reported in 4 patients—1 in the ferric citrate arm and 3 in the placebo arm.

Twenty-six percent (31/117) of ferric citrate-treated patients and 30% (35/116) of patients receiving placebo discontinued treatment during the efficacy period. Twelve patients treated with ferric citrate discontinued due to an AE, as did 10 patients who received placebo.

During the efficacy period, the rate of serious AEs was balanced between the ferric citrate and placebo arms, at 12% and 10%, respectively. None of the serious AEs were deemed drug-related.

Over the course of the study, there were 2 deaths reported. Both occurred in patients receiving ferric citrate, but neither were considered drug-related.

Red blood cells

Top-line results from a phase 3 trial suggest the oral, iron-based drug ferric citrate is more effective than placebo for treating iron deficiency anemia in adults with stage 3-5, non-dialysis-dependent chronic kidney disease.

Fifty-two percent of patients who received ferric citrate achieved at least a 1 g/dL increase in hemoglobin over a 16-week period, compared to 19% of patients who received placebo.

Researchers said the safety profile of ferric citrate in this trial was consistent with that in previous studies.

Keryx Biopharmaceuticals, Inc., the company developing ferric citrate, recently announced these results.

Patients and treatment

In this phase 3 study, researchers compared treatment with ferric citrate to placebo in 234 patients who previously had not adequately responded to or tolerated current oral iron therapies. The patients were not allowed to receive any iron (intravenous or oral) or erythropoiesis-stimulating agents during this study.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=115). Two patients in the placebo arm discontinued the study and were not included in the efficacy analysis. One discontinued after randomization prior to receiving placebo, and the other discontinued after taking a dose of placebo but before having laboratory values drawn.

The study had a 16-week, randomized, double-blind, placebo-controlled efficacy period, followed by an 8-week, open-label safety extension period. During the extension period, all patients remaining in the study, including the placebo arm, received ferric citrate.

During the efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day, with food, and could be titrated every 4 weeks by an additional 3 tablets, for up to 12 tablets per day. The mean dose of ferric citrate was 5 tablets per day.

Baseline laboratory values were similar between the treatment arms. The mean hemoglobin was 10.4 g/dL in both arms.

The mean transferrin saturation was 20.2% in the ferric citrate arm and 19.6% in the placebo arm. The mean ferritin was 85.9 ng/mL and 81.7 ng/mL, respectively. And the mean serum phosphate was 4.2 mg/dL and 4.1 mg/dL, respectively.

Efficacy results

The study achieved its primary endpoint, with 52.1% (61/117) of patients who received ferric citrate achieving a 1g/dL or greater rise in hemoglobin at any time point during the 16-week efficacy period, compared to 19.1% (22/115) of patients in the placebo arm (P<0.001).

The researchers also observed significant differences in all pre-specified secondary efficacy endpoints.

The mean change in hemoglobin was 0.75 g/dL in the ferric citrate arm and -0.08 g/dL in the placebo arm (P<0.001). The mean change in transferrin saturation was 17.8% and -0.6%, respectively (P<0.001).

The mean change in ferritin was 162.5 ng/mL and -7.7 ng/mL, respectively (P<0.001). And the mean change in serum phosphate was -0.43 mg/dL and -0.22 mg/dL, respectively (P=0.02).

The proportion of patients with a durable response during the efficacy period was 48.7% in the ferric citrate arm and 14.8% in the placebo arm (P<0.001).

A durable response was defined as a mean change in hemoglobin from baseline of at least 0.75 g/dL over any 4-week time period during the efficacy period, provided that an increase of at least 1.0 g/dL had occurred during that 4-week period.

Safety results

During the efficacy period, the majority of adverse events (AEs) were mild to moderate. The most common AEs—in the ferric citrate and placebo arms, respectively—were diarrhea (20.5% vs 16.4%), constipation (18.8% vs 12.9%), discolored feces (14.5% vs 0%), and nausea (11.1% vs 2.6%).

Hypophosphatemia was reported in 4 patients—1 in the ferric citrate arm and 3 in the placebo arm.

Twenty-six percent (31/117) of ferric citrate-treated patients and 30% (35/116) of patients receiving placebo discontinued treatment during the efficacy period. Twelve patients treated with ferric citrate discontinued due to an AE, as did 10 patients who received placebo.

During the efficacy period, the rate of serious AEs was balanced between the ferric citrate and placebo arms, at 12% and 10%, respectively. None of the serious AEs were deemed drug-related.

Over the course of the study, there were 2 deaths reported. Both occurred in patients receiving ferric citrate, but neither were considered drug-related.

Red blood cells

Top-line results from a phase 3 trial suggest the oral, iron-based drug ferric citrate is more effective than placebo for treating iron deficiency anemia in adults with stage 3-5, non-dialysis-dependent chronic kidney disease.

Fifty-two percent of patients who received ferric citrate achieved at least a 1 g/dL increase in hemoglobin over a 16-week period, compared to 19% of patients who received placebo.

Researchers said the safety profile of ferric citrate in this trial was consistent with that in previous studies.

Keryx Biopharmaceuticals, Inc., the company developing ferric citrate, recently announced these results.

Patients and treatment

In this phase 3 study, researchers compared treatment with ferric citrate to placebo in 234 patients who previously had not adequately responded to or tolerated current oral iron therapies. The patients were not allowed to receive any iron (intravenous or oral) or erythropoiesis-stimulating agents during this study.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=115). Two patients in the placebo arm discontinued the study and were not included in the efficacy analysis. One discontinued after randomization prior to receiving placebo, and the other discontinued after taking a dose of placebo but before having laboratory values drawn.

The study had a 16-week, randomized, double-blind, placebo-controlled efficacy period, followed by an 8-week, open-label safety extension period. During the extension period, all patients remaining in the study, including the placebo arm, received ferric citrate.

During the efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day, with food, and could be titrated every 4 weeks by an additional 3 tablets, for up to 12 tablets per day. The mean dose of ferric citrate was 5 tablets per day.

Baseline laboratory values were similar between the treatment arms. The mean hemoglobin was 10.4 g/dL in both arms.

The mean transferrin saturation was 20.2% in the ferric citrate arm and 19.6% in the placebo arm. The mean ferritin was 85.9 ng/mL and 81.7 ng/mL, respectively. And the mean serum phosphate was 4.2 mg/dL and 4.1 mg/dL, respectively.

Efficacy results

The study achieved its primary endpoint, with 52.1% (61/117) of patients who received ferric citrate achieving a 1g/dL or greater rise in hemoglobin at any time point during the 16-week efficacy period, compared to 19.1% (22/115) of patients in the placebo arm (P<0.001).

The researchers also observed significant differences in all pre-specified secondary efficacy endpoints.

The mean change in hemoglobin was 0.75 g/dL in the ferric citrate arm and -0.08 g/dL in the placebo arm (P<0.001). The mean change in transferrin saturation was 17.8% and -0.6%, respectively (P<0.001).

The mean change in ferritin was 162.5 ng/mL and -7.7 ng/mL, respectively (P<0.001). And the mean change in serum phosphate was -0.43 mg/dL and -0.22 mg/dL, respectively (P=0.02).

The proportion of patients with a durable response during the efficacy period was 48.7% in the ferric citrate arm and 14.8% in the placebo arm (P<0.001).

A durable response was defined as a mean change in hemoglobin from baseline of at least 0.75 g/dL over any 4-week time period during the efficacy period, provided that an increase of at least 1.0 g/dL had occurred during that 4-week period.

Safety results

During the efficacy period, the majority of adverse events (AEs) were mild to moderate. The most common AEs—in the ferric citrate and placebo arms, respectively—were diarrhea (20.5% vs 16.4%), constipation (18.8% vs 12.9%), discolored feces (14.5% vs 0%), and nausea (11.1% vs 2.6%).

Hypophosphatemia was reported in 4 patients—1 in the ferric citrate arm and 3 in the placebo arm.

Twenty-six percent (31/117) of ferric citrate-treated patients and 30% (35/116) of patients receiving placebo discontinued treatment during the efficacy period. Twelve patients treated with ferric citrate discontinued due to an AE, as did 10 patients who received placebo.

During the efficacy period, the rate of serious AEs was balanced between the ferric citrate and placebo arms, at 12% and 10%, respectively. None of the serious AEs were deemed drug-related.

Over the course of the study, there were 2 deaths reported. Both occurred in patients receiving ferric citrate, but neither were considered drug-related.

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Table of Contents

• Lessons From History: The Ethical Foundation of VA Health Care
• Calcium-Containing Crystal-Associated Arthropathies in the Elderly
• Recurrent Abdominal Pain and Bowel Edema in a Middle-Aged Woman
• Implementing the EQUiPPED Medication Management Program
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 1
• An ECHO-Based Program to Provide Geriatric Specialty Care Consultation and Education
• Possible Simeprevir/Sofosbuvir-Induced Hepatic Decompensation With Acute Kidney Failure

Table of Contents

• Lessons From History: The Ethical Foundation of VA Health Care
• Calcium-Containing Crystal-Associated Arthropathies in the Elderly
• Recurrent Abdominal Pain and Bowel Edema in a Middle-Aged Woman
• Implementing the EQUiPPED Medication Management Program
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 1
• An ECHO-Based Program to Provide Geriatric Specialty Care Consultation and Education
• Possible Simeprevir/Sofosbuvir-Induced Hepatic Decompensation With Acute Kidney Failure

Table of Contents

• Lessons From History: The Ethical Foundation of VA Health Care
• Calcium-Containing Crystal-Associated Arthropathies in the Elderly
• Recurrent Abdominal Pain and Bowel Edema in a Middle-Aged Woman
• Implementing the EQUiPPED Medication Management Program
• Academic Reasonable Accommodations for Post-9/11 Veterans With Psychiatric Diagnoses, Part 1
• An ECHO-Based Program to Provide Geriatric Specialty Care Consultation and Education
• Possible Simeprevir/Sofosbuvir-Induced Hepatic Decompensation With Acute Kidney Failure

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]

Health care providers performing esophageal manometry should keep in mind eight new quality measures listed and validated in a recent study published in the April issue of Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol. 2015 Oct 20. doi: 10.1016/j.cgh.2015.10.006), which researchers believe will significantly improve the performance of esophageal manometry and interpretation of data culled from such procedures.

“Despite its critical importance in the diagnosis and management of esophageal motility disorders, features of a high-quality esophageal manometry [study] have not been formally defined,” said the study authors, led by Dr. Rena Yadlapati of Northwestern University in Chicago. “Standardizing key aspects of esophageal manometry is imperative to ensure the delivery of high-quality care.”

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Dr. Yadlapati and her coinvestigators carried out the study in accordance with guidelines set out by the RAND/UCLA Appropriateness Method (RAM), They began by recruiting a panel of 15 esophageal manometry experts with leadership, geographical diversity, and a wide range of practice settings being the key criteria in their selection.

Investigators then conducted a literature review, selecting the 30 most relevant randomized, controlled trials, retrospective studies, and systematic reviews from the past 10 years. From this review, investigators created a list of 30 possible quality measures, all of which were then sent to each member of the expert panel via email for them to rank on a 9-point interval scale, and modify if necessary.

Those rankings were then used to determine the appropriateness of each proposed quality measure at a face-to-face meeting among the investigators and the 15-member expert panel, at which 17 quality measures were determined to be appropriate. In all, 2 measures dealt with competency, 2 pertained to assessment before procedure, 3 were regarding performance of the procedure itself, and 10 were about interpretation of data obtained from esophageal manometry; the 10 measures concerning interpretation of data were compiled into 1 measure, leaving a total of 8 that were ultimately approved.

The quality measures for competency are as follows:

• “If esophageal manometry is performed, then the technician must be competent to perform esophageal manometry.”

• “If a physician is considered competent to interpret esophageal manometry, then the physician must interpret a minimum number of esophageal manometry studies annually.”

For assessment before procedure, the measures state the following:

• “If a patient is referred for esophageal manometry, then the patient should have undergone an evaluation for structural abnormalities before manometry.”

• “If an esophageal manometry is performed, then informed consent must be obtained and documented.”

Quality measures regarding the procedure itself state the following:

• “If an esophageal manometry study is performed, then a time interval of at least 30 seconds should occur between swallows.”

• “If an esophageal manometry study is performed, then at least 10 wet swallows should be attempted.”

• “If an esophageal manometry study is performed, then at least seven evaluable wet swallows should be included.”

Finally, regarding interpretation of data, the single quality measures states that “If an esophageal manometry study is interpreted, then a complete procedure report should document the following:

• “Reason for referral.”

• “Clinical diagnosis.”

• “Diagnosis according to formally validated classification scheme.”

• “Documentation of formally validated classification scheme used.”

• “Summary of results”

• “Tabulated results including upper esophageal sphincter activity, interpretation of esophagogastric junction relaxation, documentation of pressure inversion point if technically feasible, pressurization pattern and contractile pattern.”

• “Technical limitation (if applicable).”

• “Communication to referring provider.”

“These eight appropriate quality measures are considered absolutely necessary in the performance and interpretation of esophageal manometry,” the authors concluded. “In particular, measures 3-8 are clinically feasible and measurable, and should serve as an initial framework to benchmark quality and reduce variability in esophageal manometry practices.”

This study was funded by the Alumnae of Northwestern University, and a grant to Dr. Yadlapati (T32 DK101363-02). Five coinvestigators disclosed consultancy and speaking relationships with Boston Scientific, Cook Endoscopy, EndoStim, Given Imaging, Covidien, and Sandhill Scientific.

[email protected]