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SLN mapping is most cost-effective in low-risk endometrial carcinoma
Researchers conducting a cost-utility analysis of sentinel lymph node (SLN) mapping and lymph node dissection (LND), both selective and routine, for low-risk endometrial carcinoma (clinical stage 1 disease with grade 1-2 endometrioid histology on preoperative endometrial biopsy), found that the SLN mapping had the lowest costs and the highest quality-adjusted survival of the three strategies.
Between the two strategies of LND, selective LND based on intraoperative frozen section was more cost-effective than routine LND.
The researchers created a model using data from past studies and clinical estimates. “Our biggest assumption was that sentinel lymph node mapping is associated with a decreased risk of lymphedema compared with lymph node dissection ... [from] several studies showing that having less than five lymph nodes excised was associated with a much smaller risk of developing lymphedema,” wrote Rudy S. Suidan, MD, of the MD Anderson Cancer Center, Houston, and his coauthors. Lymphedema was the main factor affecting quality of life in the analysis.
The analysis included estimates of rates of lymphadenectomy, bilateral mapping, and unilateral mapping, 3-year disease-specific survival, and overall survival, all of which were compared with third-party reimbursement costs at 2016 Medicare rates.
SLN mapping cost $16,401 per patient, while selective LND cost $17,036 per patient and routine LND cost $18,041 per patient. These strategies had quality-adjusted life years of 2.87, 2.81, and 2.79, respectively.
The superior cost-effectiveness of SLN mapping held, even when the researchers altered several of the variables in the model, including assuming open surgery instead of minimally invasive, and altering the assumed risk of lymphedema.
In addition to the possible limitation of making assumptions about SLN mapping and lymphedema, the researchers also pointed to the 3-year survival rates as shorter-term than preferable, driven by the available literature. The quality-adjusted life years did not differ much between the strategies because “most patients with low-risk cancer tend to have good clinical outcomes,” they wrote.
“This adds to the body of literature evaluating the clinical benefits of this strategy and may help health care providers in the decision-making process as they consider which approach to use,” the researchers wrote.
Dr. Suidan is supported by an NIH grant. Three coauthors reported other grants and fellowships. Five coauthors reported research support from AstraZeneca, Bayer, Clovis Oncology, and several other companies.
SOURCE: Suidan RS et al. Obstet Gynecol. 2018 Jun 11;132:52-8.
Researchers conducting a cost-utility analysis of sentinel lymph node (SLN) mapping and lymph node dissection (LND), both selective and routine, for low-risk endometrial carcinoma (clinical stage 1 disease with grade 1-2 endometrioid histology on preoperative endometrial biopsy), found that the SLN mapping had the lowest costs and the highest quality-adjusted survival of the three strategies.
Between the two strategies of LND, selective LND based on intraoperative frozen section was more cost-effective than routine LND.
The researchers created a model using data from past studies and clinical estimates. “Our biggest assumption was that sentinel lymph node mapping is associated with a decreased risk of lymphedema compared with lymph node dissection ... [from] several studies showing that having less than five lymph nodes excised was associated with a much smaller risk of developing lymphedema,” wrote Rudy S. Suidan, MD, of the MD Anderson Cancer Center, Houston, and his coauthors. Lymphedema was the main factor affecting quality of life in the analysis.
The analysis included estimates of rates of lymphadenectomy, bilateral mapping, and unilateral mapping, 3-year disease-specific survival, and overall survival, all of which were compared with third-party reimbursement costs at 2016 Medicare rates.
SLN mapping cost $16,401 per patient, while selective LND cost $17,036 per patient and routine LND cost $18,041 per patient. These strategies had quality-adjusted life years of 2.87, 2.81, and 2.79, respectively.
The superior cost-effectiveness of SLN mapping held, even when the researchers altered several of the variables in the model, including assuming open surgery instead of minimally invasive, and altering the assumed risk of lymphedema.
In addition to the possible limitation of making assumptions about SLN mapping and lymphedema, the researchers also pointed to the 3-year survival rates as shorter-term than preferable, driven by the available literature. The quality-adjusted life years did not differ much between the strategies because “most patients with low-risk cancer tend to have good clinical outcomes,” they wrote.
“This adds to the body of literature evaluating the clinical benefits of this strategy and may help health care providers in the decision-making process as they consider which approach to use,” the researchers wrote.
Dr. Suidan is supported by an NIH grant. Three coauthors reported other grants and fellowships. Five coauthors reported research support from AstraZeneca, Bayer, Clovis Oncology, and several other companies.
SOURCE: Suidan RS et al. Obstet Gynecol. 2018 Jun 11;132:52-8.
Researchers conducting a cost-utility analysis of sentinel lymph node (SLN) mapping and lymph node dissection (LND), both selective and routine, for low-risk endometrial carcinoma (clinical stage 1 disease with grade 1-2 endometrioid histology on preoperative endometrial biopsy), found that the SLN mapping had the lowest costs and the highest quality-adjusted survival of the three strategies.
Between the two strategies of LND, selective LND based on intraoperative frozen section was more cost-effective than routine LND.
The researchers created a model using data from past studies and clinical estimates. “Our biggest assumption was that sentinel lymph node mapping is associated with a decreased risk of lymphedema compared with lymph node dissection ... [from] several studies showing that having less than five lymph nodes excised was associated with a much smaller risk of developing lymphedema,” wrote Rudy S. Suidan, MD, of the MD Anderson Cancer Center, Houston, and his coauthors. Lymphedema was the main factor affecting quality of life in the analysis.
The analysis included estimates of rates of lymphadenectomy, bilateral mapping, and unilateral mapping, 3-year disease-specific survival, and overall survival, all of which were compared with third-party reimbursement costs at 2016 Medicare rates.
SLN mapping cost $16,401 per patient, while selective LND cost $17,036 per patient and routine LND cost $18,041 per patient. These strategies had quality-adjusted life years of 2.87, 2.81, and 2.79, respectively.
The superior cost-effectiveness of SLN mapping held, even when the researchers altered several of the variables in the model, including assuming open surgery instead of minimally invasive, and altering the assumed risk of lymphedema.
In addition to the possible limitation of making assumptions about SLN mapping and lymphedema, the researchers also pointed to the 3-year survival rates as shorter-term than preferable, driven by the available literature. The quality-adjusted life years did not differ much between the strategies because “most patients with low-risk cancer tend to have good clinical outcomes,” they wrote.
“This adds to the body of literature evaluating the clinical benefits of this strategy and may help health care providers in the decision-making process as they consider which approach to use,” the researchers wrote.
Dr. Suidan is supported by an NIH grant. Three coauthors reported other grants and fellowships. Five coauthors reported research support from AstraZeneca, Bayer, Clovis Oncology, and several other companies.
SOURCE: Suidan RS et al. Obstet Gynecol. 2018 Jun 11;132:52-8.
FROM OBSTETRICS & GYNECOLOGY
A new way to classify endometrial cancer
We classify endometrial cancer so that we can communicate and define each patient’s disease status, the potential for harm, and the likelihood that adjuvant therapies might provide help. Traditional forms of classification have clearly fallen short in achieving this aim, as we all know of patients with apparent low-risk disease (such as stage IA grade 1 endometrioid carcinoma) who have had recurrences and died from their disease, and we know that many patients have been subjected to overtreatment for their cancer and have acquired lifelong toxicities of therapy. This column will explore the newer, more sophisticated molecular-based classifications that are being validated for endometrial cancer, and the ways in which this promises to personalize the treatment of endometrial cancer.
Breast cancer and melanoma are examples of the inclusion of molecular data such as hormone receptor status, HER2/neu status, or BRAF positivity resulting in advancements in personalizing therapeutics. We are now moving toward this for endometrial cancer.
What is the Cancer Genome Atlas?
In 2006 the National Institutes of Health announced an initiative to coordinate work between the National Cancer Institute and the National Human Genome Research Institute taking information about the human genome and analyzing it for key genomic alterations found in 33 common cancers. These data were combined with clinical information (such as survival) to classify the behaviors of those cancers with respect to their individual genomic alternations, in order to look for patterns in mutations and behaviors. The goal of this analysis was to shift the paradigm of cancer classification from being centered around primary organ site toward tumors’ shared genomic patterns.
In 2013 the Cancer Genome Atlas published their results of complete gene sequencing in endometrial cancer.3 The authors identified four discrete subgroups of endometrial cancer with distinct molecular mutational profiles and distinct clinical outcomes: polymerase epsilon (POLE, pronounced “pole-ee”) ultramutated, microsatellite instability (MSI) high, copy number high, and copy number low.
POLE ultramutated
An important subgroup identified in the Cancer Genome Atlas was a group of patients with a POLE ultramutated state. POLE encodes for a subunit of DNA polymerase, the enzyme responsible for replicating the leading DNA strand. Nonfunctioning POLE results in proofreading errors and a subsequent ultramutated cellular state with a predominance of single nucleotide variants. POLE proofreading domain mutations in endometrial cancer and colon cancer are associated with excellent prognosis, likely secondary to the immune response that is elicited by this ultramutated state from creation of “antigenic neoepitopes” that stimulate T-cell response. Effectively, the very mutated cell is seen as “more foreign” to the body’s immune system.
Approximately 10% of patients with endometrial cancer have a POLE ultramutated state, and, as stated above, prognosis is excellent, even if coexisting with a histologic cell type (such as serous) that is normally associated with adverse outcomes. These women tend to be younger, with a lower body mass index, higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and low stage.
MSI high
MSI (microsatellite instability) is a result of epigenetic/hypermethylations or loss of expression in mismatch repair genes (such as MLH1, MSH2, MSH6, PMS2). These genes code for proteins critical in the repair of mismatches in short repeated sequences of DNA. Loss of their function results in an accumulation of errors in these sequences: MSI. It is a feature of the Lynch syndrome inherited state, but is also found sporadically in endometrial tumors. These tumors accumulate a number of mutations during cell replication that, as in POLE hypermutated tumors, are associated with eliciting an immune response.
These tumors tend to be associated with a higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and an advanced stage. Patients with tumors that have been described as MSI high are candidates for “immune therapy” with the PDL1 inhibitor pembrolizumab because of their proinflammatory state and observed favorable responses in clinical trials.4
Copy number high/low
Copy number (CN) high and low refers to the results of microarrays in which hierarchical clustering was applied to identify reoccurring amplification or deletion regions. The CN-high group was associated with the poorest outcomes (recurrence and survival). There is significant overlap with mutations in TP53. Most serous carcinomas were CN high; however, 25% of patients with high-grade endometrioid cell type shared the CN-high classification. These tumors shared great molecular similarity to high-grade serous ovarian cancers and basal-like breast cancer.
Those patients who did not possess mutations that classified them as POLE hypermutated, MSI high, or CN high were classified as CN low. This group included predominantly grades 1 and 2 endometrioid adenocarcinomas of an early stage and had a favorable prognostic profile, though less favorable than those with a POLE ultramutated state, which appears to be somewhat protective.
Molecular/metabolic interactions
While molecular data are clearly important in driving a cancer cell’s behavior, other clinical and metabolic factors influence cancer behavior. For example, body mass index, adiposity, glucose, and lipid metabolism have been shown to be important drivers of cellular behavior and responsiveness to targeted therapies.5,6 Additionally age, race, and other metabolic states contribute to oncologic behavior. Future classifications of endometrial cancer are unlikely to use molecular profiles in isolation but will need to incorporate these additional patient-specific data to better predict and prognosticate outcomes.
Clinical applications
If researchers can better define and describe a patient’s endometrial cancer from the time of their biopsy, important clinical decisions might be able to be tackled. For example, in a premenopausal patient with an endometrial cancer who is considering fertility-sparing treatments, preoperative knowledge of a POLE ultramutated state (and therefore an anticipated good prognosis) might favor fertility preservation or avoid comprehensive staging which may be of limited value. Similarly, if an MSI-high profile is identified leading to a Lynch syndrome diagnosis, she may be more inclined to undergo a hysterectomy with bilateral salpingo-oophorectomy and staging as she is at known increased risk for a more advanced endometrial cancer, as well as the potential for ovarian cancer.
Postoperative incorporation of molecular data promises to be particularly helpful in guiding adjuvant therapies and sparing some women from unnecessary treatments. For example, women with high-grade endometrioid tumors who are CN high were historically treated with radiotherapy but might do better treated with systemic adjuvant therapies traditionally reserved for nonendometrioid carcinomas. Costly therapies such as immunotherapy can be directed toward those with MSI-high tumors, and the rare patient with a POLE ultramutated state who has a recurrence or advanced disease. Clinical trials will be able to cluster enrollment of patients with CN-high, serouslike cancers with those with serous cancers, rather than combining them with patients whose cancers predictably behave much differently.
Much work is still needed to validate this molecular profiling in endometrial cancer and define the algorithms associated with treatment decisions; however, it is likely that the way we describe endometrial cancer in the near future will be quite different.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-7.
2. Clarke BA et al. Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol. 2010;63(5):410-5.
3. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
4. Ott PA et al. Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016;34(suppl):Abstract 5581.
5. Roque DR et al. Association between differential gene expression and body mass index among endometrial cancers from the Cancer Genome Atlas Project. Gynecol Oncol. 2016;142(2):317-22.
6. Talhouk A et al. New classification of endometrial cancers: The development and potential applications of genomic-based classification in research and clinical care. Gynecol Oncol Res Pract. 2016 Dec;3:14.
We classify endometrial cancer so that we can communicate and define each patient’s disease status, the potential for harm, and the likelihood that adjuvant therapies might provide help. Traditional forms of classification have clearly fallen short in achieving this aim, as we all know of patients with apparent low-risk disease (such as stage IA grade 1 endometrioid carcinoma) who have had recurrences and died from their disease, and we know that many patients have been subjected to overtreatment for their cancer and have acquired lifelong toxicities of therapy. This column will explore the newer, more sophisticated molecular-based classifications that are being validated for endometrial cancer, and the ways in which this promises to personalize the treatment of endometrial cancer.
Breast cancer and melanoma are examples of the inclusion of molecular data such as hormone receptor status, HER2/neu status, or BRAF positivity resulting in advancements in personalizing therapeutics. We are now moving toward this for endometrial cancer.
What is the Cancer Genome Atlas?
In 2006 the National Institutes of Health announced an initiative to coordinate work between the National Cancer Institute and the National Human Genome Research Institute taking information about the human genome and analyzing it for key genomic alterations found in 33 common cancers. These data were combined with clinical information (such as survival) to classify the behaviors of those cancers with respect to their individual genomic alternations, in order to look for patterns in mutations and behaviors. The goal of this analysis was to shift the paradigm of cancer classification from being centered around primary organ site toward tumors’ shared genomic patterns.
In 2013 the Cancer Genome Atlas published their results of complete gene sequencing in endometrial cancer.3 The authors identified four discrete subgroups of endometrial cancer with distinct molecular mutational profiles and distinct clinical outcomes: polymerase epsilon (POLE, pronounced “pole-ee”) ultramutated, microsatellite instability (MSI) high, copy number high, and copy number low.
POLE ultramutated
An important subgroup identified in the Cancer Genome Atlas was a group of patients with a POLE ultramutated state. POLE encodes for a subunit of DNA polymerase, the enzyme responsible for replicating the leading DNA strand. Nonfunctioning POLE results in proofreading errors and a subsequent ultramutated cellular state with a predominance of single nucleotide variants. POLE proofreading domain mutations in endometrial cancer and colon cancer are associated with excellent prognosis, likely secondary to the immune response that is elicited by this ultramutated state from creation of “antigenic neoepitopes” that stimulate T-cell response. Effectively, the very mutated cell is seen as “more foreign” to the body’s immune system.
Approximately 10% of patients with endometrial cancer have a POLE ultramutated state, and, as stated above, prognosis is excellent, even if coexisting with a histologic cell type (such as serous) that is normally associated with adverse outcomes. These women tend to be younger, with a lower body mass index, higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and low stage.
MSI high
MSI (microsatellite instability) is a result of epigenetic/hypermethylations or loss of expression in mismatch repair genes (such as MLH1, MSH2, MSH6, PMS2). These genes code for proteins critical in the repair of mismatches in short repeated sequences of DNA. Loss of their function results in an accumulation of errors in these sequences: MSI. It is a feature of the Lynch syndrome inherited state, but is also found sporadically in endometrial tumors. These tumors accumulate a number of mutations during cell replication that, as in POLE hypermutated tumors, are associated with eliciting an immune response.
These tumors tend to be associated with a higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and an advanced stage. Patients with tumors that have been described as MSI high are candidates for “immune therapy” with the PDL1 inhibitor pembrolizumab because of their proinflammatory state and observed favorable responses in clinical trials.4
Copy number high/low
Copy number (CN) high and low refers to the results of microarrays in which hierarchical clustering was applied to identify reoccurring amplification or deletion regions. The CN-high group was associated with the poorest outcomes (recurrence and survival). There is significant overlap with mutations in TP53. Most serous carcinomas were CN high; however, 25% of patients with high-grade endometrioid cell type shared the CN-high classification. These tumors shared great molecular similarity to high-grade serous ovarian cancers and basal-like breast cancer.
Those patients who did not possess mutations that classified them as POLE hypermutated, MSI high, or CN high were classified as CN low. This group included predominantly grades 1 and 2 endometrioid adenocarcinomas of an early stage and had a favorable prognostic profile, though less favorable than those with a POLE ultramutated state, which appears to be somewhat protective.
Molecular/metabolic interactions
While molecular data are clearly important in driving a cancer cell’s behavior, other clinical and metabolic factors influence cancer behavior. For example, body mass index, adiposity, glucose, and lipid metabolism have been shown to be important drivers of cellular behavior and responsiveness to targeted therapies.5,6 Additionally age, race, and other metabolic states contribute to oncologic behavior. Future classifications of endometrial cancer are unlikely to use molecular profiles in isolation but will need to incorporate these additional patient-specific data to better predict and prognosticate outcomes.
Clinical applications
If researchers can better define and describe a patient’s endometrial cancer from the time of their biopsy, important clinical decisions might be able to be tackled. For example, in a premenopausal patient with an endometrial cancer who is considering fertility-sparing treatments, preoperative knowledge of a POLE ultramutated state (and therefore an anticipated good prognosis) might favor fertility preservation or avoid comprehensive staging which may be of limited value. Similarly, if an MSI-high profile is identified leading to a Lynch syndrome diagnosis, she may be more inclined to undergo a hysterectomy with bilateral salpingo-oophorectomy and staging as she is at known increased risk for a more advanced endometrial cancer, as well as the potential for ovarian cancer.
Postoperative incorporation of molecular data promises to be particularly helpful in guiding adjuvant therapies and sparing some women from unnecessary treatments. For example, women with high-grade endometrioid tumors who are CN high were historically treated with radiotherapy but might do better treated with systemic adjuvant therapies traditionally reserved for nonendometrioid carcinomas. Costly therapies such as immunotherapy can be directed toward those with MSI-high tumors, and the rare patient with a POLE ultramutated state who has a recurrence or advanced disease. Clinical trials will be able to cluster enrollment of patients with CN-high, serouslike cancers with those with serous cancers, rather than combining them with patients whose cancers predictably behave much differently.
Much work is still needed to validate this molecular profiling in endometrial cancer and define the algorithms associated with treatment decisions; however, it is likely that the way we describe endometrial cancer in the near future will be quite different.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-7.
2. Clarke BA et al. Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol. 2010;63(5):410-5.
3. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
4. Ott PA et al. Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016;34(suppl):Abstract 5581.
5. Roque DR et al. Association between differential gene expression and body mass index among endometrial cancers from the Cancer Genome Atlas Project. Gynecol Oncol. 2016;142(2):317-22.
6. Talhouk A et al. New classification of endometrial cancers: The development and potential applications of genomic-based classification in research and clinical care. Gynecol Oncol Res Pract. 2016 Dec;3:14.
We classify endometrial cancer so that we can communicate and define each patient’s disease status, the potential for harm, and the likelihood that adjuvant therapies might provide help. Traditional forms of classification have clearly fallen short in achieving this aim, as we all know of patients with apparent low-risk disease (such as stage IA grade 1 endometrioid carcinoma) who have had recurrences and died from their disease, and we know that many patients have been subjected to overtreatment for their cancer and have acquired lifelong toxicities of therapy. This column will explore the newer, more sophisticated molecular-based classifications that are being validated for endometrial cancer, and the ways in which this promises to personalize the treatment of endometrial cancer.
Breast cancer and melanoma are examples of the inclusion of molecular data such as hormone receptor status, HER2/neu status, or BRAF positivity resulting in advancements in personalizing therapeutics. We are now moving toward this for endometrial cancer.
What is the Cancer Genome Atlas?
In 2006 the National Institutes of Health announced an initiative to coordinate work between the National Cancer Institute and the National Human Genome Research Institute taking information about the human genome and analyzing it for key genomic alterations found in 33 common cancers. These data were combined with clinical information (such as survival) to classify the behaviors of those cancers with respect to their individual genomic alternations, in order to look for patterns in mutations and behaviors. The goal of this analysis was to shift the paradigm of cancer classification from being centered around primary organ site toward tumors’ shared genomic patterns.
In 2013 the Cancer Genome Atlas published their results of complete gene sequencing in endometrial cancer.3 The authors identified four discrete subgroups of endometrial cancer with distinct molecular mutational profiles and distinct clinical outcomes: polymerase epsilon (POLE, pronounced “pole-ee”) ultramutated, microsatellite instability (MSI) high, copy number high, and copy number low.
POLE ultramutated
An important subgroup identified in the Cancer Genome Atlas was a group of patients with a POLE ultramutated state. POLE encodes for a subunit of DNA polymerase, the enzyme responsible for replicating the leading DNA strand. Nonfunctioning POLE results in proofreading errors and a subsequent ultramutated cellular state with a predominance of single nucleotide variants. POLE proofreading domain mutations in endometrial cancer and colon cancer are associated with excellent prognosis, likely secondary to the immune response that is elicited by this ultramutated state from creation of “antigenic neoepitopes” that stimulate T-cell response. Effectively, the very mutated cell is seen as “more foreign” to the body’s immune system.
Approximately 10% of patients with endometrial cancer have a POLE ultramutated state, and, as stated above, prognosis is excellent, even if coexisting with a histologic cell type (such as serous) that is normally associated with adverse outcomes. These women tend to be younger, with a lower body mass index, higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and low stage.
MSI high
MSI (microsatellite instability) is a result of epigenetic/hypermethylations or loss of expression in mismatch repair genes (such as MLH1, MSH2, MSH6, PMS2). These genes code for proteins critical in the repair of mismatches in short repeated sequences of DNA. Loss of their function results in an accumulation of errors in these sequences: MSI. It is a feature of the Lynch syndrome inherited state, but is also found sporadically in endometrial tumors. These tumors accumulate a number of mutations during cell replication that, as in POLE hypermutated tumors, are associated with eliciting an immune response.
These tumors tend to be associated with a higher-grade endometrioid cell type, the presence of lymphovascular space invasion, and an advanced stage. Patients with tumors that have been described as MSI high are candidates for “immune therapy” with the PDL1 inhibitor pembrolizumab because of their proinflammatory state and observed favorable responses in clinical trials.4
Copy number high/low
Copy number (CN) high and low refers to the results of microarrays in which hierarchical clustering was applied to identify reoccurring amplification or deletion regions. The CN-high group was associated with the poorest outcomes (recurrence and survival). There is significant overlap with mutations in TP53. Most serous carcinomas were CN high; however, 25% of patients with high-grade endometrioid cell type shared the CN-high classification. These tumors shared great molecular similarity to high-grade serous ovarian cancers and basal-like breast cancer.
Those patients who did not possess mutations that classified them as POLE hypermutated, MSI high, or CN high were classified as CN low. This group included predominantly grades 1 and 2 endometrioid adenocarcinomas of an early stage and had a favorable prognostic profile, though less favorable than those with a POLE ultramutated state, which appears to be somewhat protective.
Molecular/metabolic interactions
While molecular data are clearly important in driving a cancer cell’s behavior, other clinical and metabolic factors influence cancer behavior. For example, body mass index, adiposity, glucose, and lipid metabolism have been shown to be important drivers of cellular behavior and responsiveness to targeted therapies.5,6 Additionally age, race, and other metabolic states contribute to oncologic behavior. Future classifications of endometrial cancer are unlikely to use molecular profiles in isolation but will need to incorporate these additional patient-specific data to better predict and prognosticate outcomes.
Clinical applications
If researchers can better define and describe a patient’s endometrial cancer from the time of their biopsy, important clinical decisions might be able to be tackled. For example, in a premenopausal patient with an endometrial cancer who is considering fertility-sparing treatments, preoperative knowledge of a POLE ultramutated state (and therefore an anticipated good prognosis) might favor fertility preservation or avoid comprehensive staging which may be of limited value. Similarly, if an MSI-high profile is identified leading to a Lynch syndrome diagnosis, she may be more inclined to undergo a hysterectomy with bilateral salpingo-oophorectomy and staging as she is at known increased risk for a more advanced endometrial cancer, as well as the potential for ovarian cancer.
Postoperative incorporation of molecular data promises to be particularly helpful in guiding adjuvant therapies and sparing some women from unnecessary treatments. For example, women with high-grade endometrioid tumors who are CN high were historically treated with radiotherapy but might do better treated with systemic adjuvant therapies traditionally reserved for nonendometrioid carcinomas. Costly therapies such as immunotherapy can be directed toward those with MSI-high tumors, and the rare patient with a POLE ultramutated state who has a recurrence or advanced disease. Clinical trials will be able to cluster enrollment of patients with CN-high, serouslike cancers with those with serous cancers, rather than combining them with patients whose cancers predictably behave much differently.
Much work is still needed to validate this molecular profiling in endometrial cancer and define the algorithms associated with treatment decisions; however, it is likely that the way we describe endometrial cancer in the near future will be quite different.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no disclosures.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-7.
2. Clarke BA et al. Endometrial carcinoma: controversies in histopathological assessment of grade and tumour cell type. J Clin Pathol. 2010;63(5):410-5.
3. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
4. Ott PA et al. Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016;34(suppl):Abstract 5581.
5. Roque DR et al. Association between differential gene expression and body mass index among endometrial cancers from the Cancer Genome Atlas Project. Gynecol Oncol. 2016;142(2):317-22.
6. Talhouk A et al. New classification of endometrial cancers: The development and potential applications of genomic-based classification in research and clinical care. Gynecol Oncol Res Pract. 2016 Dec;3:14.
Trachelectomy rate for early-stage cervical cancer rises to 17% in younger women
based on a recent analysis of the National Cancer Database.
Of 15,150 patients analyzed, the vast majority (97.1%) underwent hysterectomy, but trachelectomy performance increased from 1.5% (95% confidence interval, 0.8%-2.2%; P less than .001) in 2004 to 3.8% (95% CI, 2.7%-4.8%; P less than .001) by 2014. The increase was mostly seen among women younger than 30 years old. In that group, trachelectomy increased from 4.6% (95% CI, 1.0%-8.2%; P less than .001) in 2004 to 17% (95% CI, 10.2%-23.7%; P less than .001) in 2014. Rates among women aged 30-49 years were relatively stable over the same period.
“A possible explanation for this rise in trachelectomy is the trend in delayed childbearing in women in the United States,” wrote Rosa R. Cui, MD, a resident at Columbia University, New York, and her coauthors.
In the analysis, mortality risk and 5-year survival rates were similar between the two procedures. Overall cohort 5-year survival was nearly identical with hysterectomy and trachelectomy at 92.4% and 92.3%, respectively. For stages IA2, IB1, and IB not specified, tumor stage was not associated with differences in 5-year survival for the two procedures. As few patients with stage IB2 tumors received trachelectomy, that data was excluded from the analysis.
Though increasing tumor size made trachelectomy less likely, 30% of patients in the study who underwent trachelectomy had a tumor greater than 2 cm in diameter, and 4% had a tumor greater than 4 cm in diameter. The researchers noted studies published in the past few years suggest abdominal radical trachelectomy may be a safe option for larger tumors, compared with vaginal trachelectomy. In the current analysis, they did not find a statistically significant decrease in survival for trachelectomy patients with tumors greater than 2 cm in diameter, but the sample size was small.
“The trachelectomy procedure has evolved significantly since it was initially described and now encompasses several approaches,” and can be performed more or less conservatively depending on the diagnosis “without compromising outcomes,” wrote Dr. Cui and her coauthors.
The researchers noted that the National Cancer Database does not have data on fertility outcomes, a possible focus of future studies of trachelectomy.
Two coauthors disclosed grants and a fellowship from the National Cancer Institute, and others disclosed consulting for several pharmaceutical companies including Pfizer, Teva, and Eisai.
SOURCE: Cui RR et al. Obstet Gynecol. 2018 Jun;131(6):1085-94.
based on a recent analysis of the National Cancer Database.
Of 15,150 patients analyzed, the vast majority (97.1%) underwent hysterectomy, but trachelectomy performance increased from 1.5% (95% confidence interval, 0.8%-2.2%; P less than .001) in 2004 to 3.8% (95% CI, 2.7%-4.8%; P less than .001) by 2014. The increase was mostly seen among women younger than 30 years old. In that group, trachelectomy increased from 4.6% (95% CI, 1.0%-8.2%; P less than .001) in 2004 to 17% (95% CI, 10.2%-23.7%; P less than .001) in 2014. Rates among women aged 30-49 years were relatively stable over the same period.
“A possible explanation for this rise in trachelectomy is the trend in delayed childbearing in women in the United States,” wrote Rosa R. Cui, MD, a resident at Columbia University, New York, and her coauthors.
In the analysis, mortality risk and 5-year survival rates were similar between the two procedures. Overall cohort 5-year survival was nearly identical with hysterectomy and trachelectomy at 92.4% and 92.3%, respectively. For stages IA2, IB1, and IB not specified, tumor stage was not associated with differences in 5-year survival for the two procedures. As few patients with stage IB2 tumors received trachelectomy, that data was excluded from the analysis.
Though increasing tumor size made trachelectomy less likely, 30% of patients in the study who underwent trachelectomy had a tumor greater than 2 cm in diameter, and 4% had a tumor greater than 4 cm in diameter. The researchers noted studies published in the past few years suggest abdominal radical trachelectomy may be a safe option for larger tumors, compared with vaginal trachelectomy. In the current analysis, they did not find a statistically significant decrease in survival for trachelectomy patients with tumors greater than 2 cm in diameter, but the sample size was small.
“The trachelectomy procedure has evolved significantly since it was initially described and now encompasses several approaches,” and can be performed more or less conservatively depending on the diagnosis “without compromising outcomes,” wrote Dr. Cui and her coauthors.
The researchers noted that the National Cancer Database does not have data on fertility outcomes, a possible focus of future studies of trachelectomy.
Two coauthors disclosed grants and a fellowship from the National Cancer Institute, and others disclosed consulting for several pharmaceutical companies including Pfizer, Teva, and Eisai.
SOURCE: Cui RR et al. Obstet Gynecol. 2018 Jun;131(6):1085-94.
based on a recent analysis of the National Cancer Database.
Of 15,150 patients analyzed, the vast majority (97.1%) underwent hysterectomy, but trachelectomy performance increased from 1.5% (95% confidence interval, 0.8%-2.2%; P less than .001) in 2004 to 3.8% (95% CI, 2.7%-4.8%; P less than .001) by 2014. The increase was mostly seen among women younger than 30 years old. In that group, trachelectomy increased from 4.6% (95% CI, 1.0%-8.2%; P less than .001) in 2004 to 17% (95% CI, 10.2%-23.7%; P less than .001) in 2014. Rates among women aged 30-49 years were relatively stable over the same period.
“A possible explanation for this rise in trachelectomy is the trend in delayed childbearing in women in the United States,” wrote Rosa R. Cui, MD, a resident at Columbia University, New York, and her coauthors.
In the analysis, mortality risk and 5-year survival rates were similar between the two procedures. Overall cohort 5-year survival was nearly identical with hysterectomy and trachelectomy at 92.4% and 92.3%, respectively. For stages IA2, IB1, and IB not specified, tumor stage was not associated with differences in 5-year survival for the two procedures. As few patients with stage IB2 tumors received trachelectomy, that data was excluded from the analysis.
Though increasing tumor size made trachelectomy less likely, 30% of patients in the study who underwent trachelectomy had a tumor greater than 2 cm in diameter, and 4% had a tumor greater than 4 cm in diameter. The researchers noted studies published in the past few years suggest abdominal radical trachelectomy may be a safe option for larger tumors, compared with vaginal trachelectomy. In the current analysis, they did not find a statistically significant decrease in survival for trachelectomy patients with tumors greater than 2 cm in diameter, but the sample size was small.
“The trachelectomy procedure has evolved significantly since it was initially described and now encompasses several approaches,” and can be performed more or less conservatively depending on the diagnosis “without compromising outcomes,” wrote Dr. Cui and her coauthors.
The researchers noted that the National Cancer Database does not have data on fertility outcomes, a possible focus of future studies of trachelectomy.
Two coauthors disclosed grants and a fellowship from the National Cancer Institute, and others disclosed consulting for several pharmaceutical companies including Pfizer, Teva, and Eisai.
SOURCE: Cui RR et al. Obstet Gynecol. 2018 Jun;131(6):1085-94.
FROM OBSTETRICS & GYNECOLOGY
The diagnosis and treatment of ureteral injury
A gynecologic surgeon learns very early in his/her career to respect the ureter. Whether from the procedure being performed (endometriosis surgery, hysterectomy, myomectomy for ligamentous fibroids, salpingo-oophorectomy, excision of ovarian remnants, adhesiolysis), blood loss that obscures visualization and must be controlled, or use of energy for cutting, desiccation, and coagulation leading to potential lateral tissue damage, ureteral injury is a well-known complication. Even normal anatomic variations may put some women at greater risk; according to Hurd et al. (Am J Obstet Gynecol. 2001;184:336-9). In a small subset of women, the distance between the cervix and the ureter may be less than 0.5 cm.
As a practicing minimally invasive gynecologic surgeon for the past 30 years, and an early adapter to laparoscopic hysterectomy, I remember quite well the recommendation to always dissect out ureters at time of the procedure. At present, most will agree that selective dissection is safe and thus, more desirable, as bleeding, damage secondary to desiccation, and ureter devascularization with subsequent necrosis are all increased with ureterolysis.
I agree with Dr. Kenton and Dr. Mueller that ureteral stenting has not been shown to significantly decrease ureteral injury rates. Often times, with loss of peristalsis secondary to stent placement, locating the ureter may be even more difficult. Recent advances using lighted stents or indocyanine green, which fluoresces in response to near-infrared laser and can be injected into the ureter via the ureteral catheter tip, are still in the feasibility phase of evaluation and can be costly.
As most urogenital fistulae are secondary to unrecognized injuries at time of surgery, and due to the fact that intraoperative recognition of the injury allows for primary repair, thus, decreasing the rate of secondary surgery and the associated increased morbidity, I recommend cystoscopy to check for ureteral jets (ureteral efflux) be performed when there is concern regarding ureter compromise.
Currently, I utilize a 70° cystoscope to visualize the ureters. While in the past, I have used intravenous indigo carmine, methylene blue, or fluorescein sodium, I currently use Pyridium (phenazopyridine) 200 mg taken by mouth 1 hour prior to the procedure.
Unfortunately, ureteral jetting still may be noted despite partial ligation, laceration, or desiccation of the ureter.
If ureteral injury is not recognized at time of surgery, it can lead to various postoperative symptoms. If there is a ureteral defect, the patient may note profuse wound leakage, increased abdominal fluid, or a urinoma, ileus, fever, peritonitis, or hematuria. With ureteral obstruction, flank or abdominal pain or anuria can be noted; while, with fistula formation, the patient will likely present with urinary incontinence or watery vaginal discharge.
Dr. Miller is a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL.
A gynecologic surgeon learns very early in his/her career to respect the ureter. Whether from the procedure being performed (endometriosis surgery, hysterectomy, myomectomy for ligamentous fibroids, salpingo-oophorectomy, excision of ovarian remnants, adhesiolysis), blood loss that obscures visualization and must be controlled, or use of energy for cutting, desiccation, and coagulation leading to potential lateral tissue damage, ureteral injury is a well-known complication. Even normal anatomic variations may put some women at greater risk; according to Hurd et al. (Am J Obstet Gynecol. 2001;184:336-9). In a small subset of women, the distance between the cervix and the ureter may be less than 0.5 cm.
As a practicing minimally invasive gynecologic surgeon for the past 30 years, and an early adapter to laparoscopic hysterectomy, I remember quite well the recommendation to always dissect out ureters at time of the procedure. At present, most will agree that selective dissection is safe and thus, more desirable, as bleeding, damage secondary to desiccation, and ureter devascularization with subsequent necrosis are all increased with ureterolysis.
I agree with Dr. Kenton and Dr. Mueller that ureteral stenting has not been shown to significantly decrease ureteral injury rates. Often times, with loss of peristalsis secondary to stent placement, locating the ureter may be even more difficult. Recent advances using lighted stents or indocyanine green, which fluoresces in response to near-infrared laser and can be injected into the ureter via the ureteral catheter tip, are still in the feasibility phase of evaluation and can be costly.
As most urogenital fistulae are secondary to unrecognized injuries at time of surgery, and due to the fact that intraoperative recognition of the injury allows for primary repair, thus, decreasing the rate of secondary surgery and the associated increased morbidity, I recommend cystoscopy to check for ureteral jets (ureteral efflux) be performed when there is concern regarding ureter compromise.
Currently, I utilize a 70° cystoscope to visualize the ureters. While in the past, I have used intravenous indigo carmine, methylene blue, or fluorescein sodium, I currently use Pyridium (phenazopyridine) 200 mg taken by mouth 1 hour prior to the procedure.
Unfortunately, ureteral jetting still may be noted despite partial ligation, laceration, or desiccation of the ureter.
If ureteral injury is not recognized at time of surgery, it can lead to various postoperative symptoms. If there is a ureteral defect, the patient may note profuse wound leakage, increased abdominal fluid, or a urinoma, ileus, fever, peritonitis, or hematuria. With ureteral obstruction, flank or abdominal pain or anuria can be noted; while, with fistula formation, the patient will likely present with urinary incontinence or watery vaginal discharge.
Dr. Miller is a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL.
A gynecologic surgeon learns very early in his/her career to respect the ureter. Whether from the procedure being performed (endometriosis surgery, hysterectomy, myomectomy for ligamentous fibroids, salpingo-oophorectomy, excision of ovarian remnants, adhesiolysis), blood loss that obscures visualization and must be controlled, or use of energy for cutting, desiccation, and coagulation leading to potential lateral tissue damage, ureteral injury is a well-known complication. Even normal anatomic variations may put some women at greater risk; according to Hurd et al. (Am J Obstet Gynecol. 2001;184:336-9). In a small subset of women, the distance between the cervix and the ureter may be less than 0.5 cm.
As a practicing minimally invasive gynecologic surgeon for the past 30 years, and an early adapter to laparoscopic hysterectomy, I remember quite well the recommendation to always dissect out ureters at time of the procedure. At present, most will agree that selective dissection is safe and thus, more desirable, as bleeding, damage secondary to desiccation, and ureter devascularization with subsequent necrosis are all increased with ureterolysis.
I agree with Dr. Kenton and Dr. Mueller that ureteral stenting has not been shown to significantly decrease ureteral injury rates. Often times, with loss of peristalsis secondary to stent placement, locating the ureter may be even more difficult. Recent advances using lighted stents or indocyanine green, which fluoresces in response to near-infrared laser and can be injected into the ureter via the ureteral catheter tip, are still in the feasibility phase of evaluation and can be costly.
As most urogenital fistulae are secondary to unrecognized injuries at time of surgery, and due to the fact that intraoperative recognition of the injury allows for primary repair, thus, decreasing the rate of secondary surgery and the associated increased morbidity, I recommend cystoscopy to check for ureteral jets (ureteral efflux) be performed when there is concern regarding ureter compromise.
Currently, I utilize a 70° cystoscope to visualize the ureters. While in the past, I have used intravenous indigo carmine, methylene blue, or fluorescein sodium, I currently use Pyridium (phenazopyridine) 200 mg taken by mouth 1 hour prior to the procedure.
Unfortunately, ureteral jetting still may be noted despite partial ligation, laceration, or desiccation of the ureter.
If ureteral injury is not recognized at time of surgery, it can lead to various postoperative symptoms. If there is a ureteral defect, the patient may note profuse wound leakage, increased abdominal fluid, or a urinoma, ileus, fever, peritonitis, or hematuria. With ureteral obstruction, flank or abdominal pain or anuria can be noted; while, with fistula formation, the patient will likely present with urinary incontinence or watery vaginal discharge.
Dr. Miller is a minimally invasive gynecologic surgeon in Naperville, Ill., and a past president of the AAGL.
In abdominal myomectomy, cell salvage may reduce transfusions
ORLANDO – Cell salvage may help reduce the need for allogeneic blood transfusion in patients undergoing abdominal myomectomy, according to findings from a retrospective cohort study.
Of 138 women who underwent abdominal myomectomy, 52 had no cell salvage and 86 had cell salvage ordered. Of those who had cell salvage ordered, 60 had salvage fully set up and 26 had salvage on standby; 46 of the 60 with full set-up had autologous blood returned, and of those, 14 required subsequent allogeneic transfusion of more than 20 U of blood, Julian A. Gingold, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Notable differences between those who did and those who did not have cell salvage ordered included the number of patients with fibroids weighing more than 250 g (52% vs. 13%) and with five or more total fibroids (83% vs. 56%), he said.
“And interestingly, reproductive surgeons were less likely (than general surgeons) to order cell salvage,” he said.
Surgery was performed by a reproductive surgeon in 25% of cases in the cell salvage group vs. in 67% of cases in the non–cell salvage group.
The finding of comparable allogeneic transfusion requirement between the two groups despite differences in blood loss and “arguably less complex surgeries [in those] without cell salvage” was striking, Dr. Gingold said.
“If you take these 86 patients who had cell salvage intraoperatively, 14 of them ultimately required donor blood, and that amounted to 23 units, giving kind of a lower limit for the potential benefit of cell salvage in this patient cohort,” he said.
Abdominal myomectomy often has a high rate of blood loss, with about a 10%-20% rate of transfusion. While the technique of cell salvage is widely used in other fields, it hasn’t been fully investigated in the context of gynecologic surgery, he said, explaining the rationale for the study.
Subjects included were women aged 18-60 years who underwent abdominal myomectomy for benign indications at the Cleveland Clinic during 2011-2016. Those with current malignancy or with surgery performed by a gynecologic oncologist were excluded.
The non–cell salvage and cell salvage groups were comparable with respect to age, body mass index, ethnicity, and preoperative and postoperative hemoglobin.
Dr. Gingold noted that “prospective study with randomization will be required to better define the role of cell salvage in abdominal myomectomies.”
During a question and answer session following his presentation, Charles Ascher-Walsh, MD, of Mount Sinai Health System, N.Y. noted that the transfusion rates and blood loss were high in the study, and that solid data support the use of tourniquets for patients undergoing abdominal myomectomy, with studies showing only a 1%-2% transfusion rate with continuous tourniquet use. Dr. Gingold said the use of tourniquets in the study was low and was dictated by surgeon preference. He agreed that tourniquet use is “certainly an option that should be adjunctive,” and that it would be useful to look at the outcomes in the cases with and without tourniquet use.
Dr. Gingold reported having no disclosures.
SOURCE: Gingold J et al. SGS 2018 Oral Poster 18.
ORLANDO – Cell salvage may help reduce the need for allogeneic blood transfusion in patients undergoing abdominal myomectomy, according to findings from a retrospective cohort study.
Of 138 women who underwent abdominal myomectomy, 52 had no cell salvage and 86 had cell salvage ordered. Of those who had cell salvage ordered, 60 had salvage fully set up and 26 had salvage on standby; 46 of the 60 with full set-up had autologous blood returned, and of those, 14 required subsequent allogeneic transfusion of more than 20 U of blood, Julian A. Gingold, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Notable differences between those who did and those who did not have cell salvage ordered included the number of patients with fibroids weighing more than 250 g (52% vs. 13%) and with five or more total fibroids (83% vs. 56%), he said.
“And interestingly, reproductive surgeons were less likely (than general surgeons) to order cell salvage,” he said.
Surgery was performed by a reproductive surgeon in 25% of cases in the cell salvage group vs. in 67% of cases in the non–cell salvage group.
The finding of comparable allogeneic transfusion requirement between the two groups despite differences in blood loss and “arguably less complex surgeries [in those] without cell salvage” was striking, Dr. Gingold said.
“If you take these 86 patients who had cell salvage intraoperatively, 14 of them ultimately required donor blood, and that amounted to 23 units, giving kind of a lower limit for the potential benefit of cell salvage in this patient cohort,” he said.
Abdominal myomectomy often has a high rate of blood loss, with about a 10%-20% rate of transfusion. While the technique of cell salvage is widely used in other fields, it hasn’t been fully investigated in the context of gynecologic surgery, he said, explaining the rationale for the study.
Subjects included were women aged 18-60 years who underwent abdominal myomectomy for benign indications at the Cleveland Clinic during 2011-2016. Those with current malignancy or with surgery performed by a gynecologic oncologist were excluded.
The non–cell salvage and cell salvage groups were comparable with respect to age, body mass index, ethnicity, and preoperative and postoperative hemoglobin.
Dr. Gingold noted that “prospective study with randomization will be required to better define the role of cell salvage in abdominal myomectomies.”
During a question and answer session following his presentation, Charles Ascher-Walsh, MD, of Mount Sinai Health System, N.Y. noted that the transfusion rates and blood loss were high in the study, and that solid data support the use of tourniquets for patients undergoing abdominal myomectomy, with studies showing only a 1%-2% transfusion rate with continuous tourniquet use. Dr. Gingold said the use of tourniquets in the study was low and was dictated by surgeon preference. He agreed that tourniquet use is “certainly an option that should be adjunctive,” and that it would be useful to look at the outcomes in the cases with and without tourniquet use.
Dr. Gingold reported having no disclosures.
SOURCE: Gingold J et al. SGS 2018 Oral Poster 18.
ORLANDO – Cell salvage may help reduce the need for allogeneic blood transfusion in patients undergoing abdominal myomectomy, according to findings from a retrospective cohort study.
Of 138 women who underwent abdominal myomectomy, 52 had no cell salvage and 86 had cell salvage ordered. Of those who had cell salvage ordered, 60 had salvage fully set up and 26 had salvage on standby; 46 of the 60 with full set-up had autologous blood returned, and of those, 14 required subsequent allogeneic transfusion of more than 20 U of blood, Julian A. Gingold, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
Notable differences between those who did and those who did not have cell salvage ordered included the number of patients with fibroids weighing more than 250 g (52% vs. 13%) and with five or more total fibroids (83% vs. 56%), he said.
“And interestingly, reproductive surgeons were less likely (than general surgeons) to order cell salvage,” he said.
Surgery was performed by a reproductive surgeon in 25% of cases in the cell salvage group vs. in 67% of cases in the non–cell salvage group.
The finding of comparable allogeneic transfusion requirement between the two groups despite differences in blood loss and “arguably less complex surgeries [in those] without cell salvage” was striking, Dr. Gingold said.
“If you take these 86 patients who had cell salvage intraoperatively, 14 of them ultimately required donor blood, and that amounted to 23 units, giving kind of a lower limit for the potential benefit of cell salvage in this patient cohort,” he said.
Abdominal myomectomy often has a high rate of blood loss, with about a 10%-20% rate of transfusion. While the technique of cell salvage is widely used in other fields, it hasn’t been fully investigated in the context of gynecologic surgery, he said, explaining the rationale for the study.
Subjects included were women aged 18-60 years who underwent abdominal myomectomy for benign indications at the Cleveland Clinic during 2011-2016. Those with current malignancy or with surgery performed by a gynecologic oncologist were excluded.
The non–cell salvage and cell salvage groups were comparable with respect to age, body mass index, ethnicity, and preoperative and postoperative hemoglobin.
Dr. Gingold noted that “prospective study with randomization will be required to better define the role of cell salvage in abdominal myomectomies.”
During a question and answer session following his presentation, Charles Ascher-Walsh, MD, of Mount Sinai Health System, N.Y. noted that the transfusion rates and blood loss were high in the study, and that solid data support the use of tourniquets for patients undergoing abdominal myomectomy, with studies showing only a 1%-2% transfusion rate with continuous tourniquet use. Dr. Gingold said the use of tourniquets in the study was low and was dictated by surgeon preference. He agreed that tourniquet use is “certainly an option that should be adjunctive,” and that it would be useful to look at the outcomes in the cases with and without tourniquet use.
Dr. Gingold reported having no disclosures.
SOURCE: Gingold J et al. SGS 2018 Oral Poster 18.
REPORTING FROM SGS 2018
Key clinical point: Cell salvage may help reduce the need for allogeneic blood transfusion in patients undergoing abdominal myomectomy.
Major finding: Transfusion rates were similar (23% and 17%) despite greater blood loss in the cell salvage group.
Study details: A retrospective review of 138 patients’ charts.
Disclosures: Dr. Gingold reported having no disclosures.
Source: Gingold J et al. SGS 2018 Oral poster 18.
Oophorectomy for premenopausal breast cancer
One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.1
Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.
In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.4 It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.
BRCA populations
For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.5
Technique
When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.
The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.
The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.6 Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.
Consequences of ovarian ablation
It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.7,8
It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.
Hormone replacement therapy postoperatively
Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.
Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.
2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.
3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.
4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.
5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.
6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.
7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.
8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.
One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.1
Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.
In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.4 It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.
BRCA populations
For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.5
Technique
When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.
The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.
The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.6 Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.
Consequences of ovarian ablation
It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.7,8
It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.
Hormone replacement therapy postoperatively
Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.
Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.
2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.
3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.
4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.
5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.
6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.
7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.
8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.
One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.1
Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.
In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.4 It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.
BRCA populations
For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.5
Technique
When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.
The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.
The decision about whether or not to perform hysterectomy at the time of salpingo-oophorectomy is complex. In patients without hereditary cancer syndromes, such as BRCA or Lynch syndrome, hysterectomy likely offers no benefit to the patient who is undergoing a procedure for the purpose of ovarian ablation. An argument has been made that hysterectomy can eliminate the increased endometrial cancer risk associated with tamoxifen. However, given the previously discussed data, after oophorectomy, aromatase inhibitors are the preferred treatment option, and tamoxifen can be avoided. If a patient has unrelated underlying uterine pathology a hysterectomy might be indicated. Women with BRCA germline mutations, particularly women with BRCA-1 mutations, may be at increased risk for uterine serous carcinoma, and in these patients, hysterectomy at the time of oophorectomy can be discussed and offered, though as yet, it is not a guideline recommendation for all patients.6 Patients who ask to “just take everything out while you are there” without a clear indication for hysterectomy should be counseled that hysterectomy is associated with increased risk, recovery, and cost, compared with bilateral salpingo-oophorectomy. Among patients with elevated surgical risk (such as morbid obesity, known adhesive disease, increased venous thromboembolism risk, diabetes, and so on) it may not always be appropriate to extend the complexity of the procedure given the limited benefit.
Consequences of ovarian ablation
It should be noted that ovarian ablation in the TEXT and SOFT trials was not associated with an increase in overall survival for women with premenopausal breast cancer. Alternatively, large, observational studies such as the Nurses’ Health Study have shown that premenopausal oophorectomy without hormone replacement therapy is associated with increased all-cause mortality. This is primarily driven by the increased cardiopulmonary risk (heart attack and stroke), deaths after osteoporotic hip fractures, and the increased risk for lung and colon cancer.7,8
It is normal for young patients to have heightened concerns regarding their risk of recurrence from their cancer, and less concerned by threats to their health in decades to come. However, it is important to discuss this data with the patient and allow for her to make an informed decision about her immediate versus future risks. If she determines that she is not interested in permanent ovarian ablation with oophorectomy because of either surgical risks, concerns regarding permanent infertility, or increased all-cause mortality, she still has an option for medical ovarian ablation with GnRH analogues in the treatment of her breast cancer.
Hormone replacement therapy postoperatively
Women who undergo oophorectomy for the treatment of breast cancer should not be offered hormone replacement therapy. This is true even for “triple-negative” or hormone receptor–negative breast cancers as there is still some observed benefit of ovarian ablation, and risk from exogenous hormone administration in these women. Alternatively, postoperative hormone replacement therapy remains safe until the age of natural menopause among premenopausal patients with BRCA germline mutations without a preceding breast cancer diagnosis.
Surgical ovarian ablation with bilateral salpingo-oophorectomy is a valuable strategy in the adjuvant therapy of premenopausal breast cancer, particularly among BRCA mutation carriers and women with hormone receptor–positive disease, or among women who find adherence to medical ablation difficult. Patients should be carefully counseled that this may introduce increased long-term cardiovascular risks for them.
Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1996 Nov 2;348:1189-96.
2. Pagani O et al. N Engl J Med. 2014 Jul 10;371(12):107-18.
3. Francis PA et al. N Engl J Med. 2015 Jan 29;372(5):436-46.
4. Ferrandina G et al. Clin Drug Investig. 2017 Nov;37(11):1093-102.
5. Finch AP et al. J Clin Oncol. 2014 May 20;32(15):1547-53.
6. Shu CA et al. JAMA Oncol. 2016 Nov 1;2(11):1434-40.
7. Parker WH et al. Obstet Gynecol. 2013 Apr;121(4):709-16.
8. Rivera CM et al. Menopause. 2009 Jan-Feb;16:15-23.
Complete MUS mesh removal not linked to incontinence
SAN FRANCISCO – Stress urinary incontinence (SUI) following removal of a mid-urethral sling (MUS) mesh is not necessarily associated with increased risk of postsurgical urinary incontinence, according to a retrospective study at a high-volume, tertiary medical center.
Follow-up procedures occurred more often in women with preoperative urodynamic SUI and less often in women who were stress continent.
Among women who were stress continent, obesity and postmenopausal status were linked to postsurgical SUI. There was no association between postsurgical SUI and the extent of mesh excision or prior revisions.
The study grew out of observations that SUI occurred less often than expected.
“There’s an increasing recognition of complications related to synthetic MUS,” said Janine Oliver, MD, who presented the study at the annual meeting of the American Urological Association. “As mesh removal procedures were being performed, we assumed that the majority of patients, if not all, would be incontinent afterward, since we were removing the sling that was put in to fix stress incontinence in most cases.”
In a patient who would benefit from a complete mesh removal, “the fear that it may lead to a higher risk of urinary incontinence is not a good justification to not do it,” Dr. Oliver said. She did note, however, that the procedures were done by specialists, so findings may not be applicable to general practitioners.
The study was performed while Dr. Oliver was a fellow at the University of California, Los Angeles. She is now with the division of urology at the University of Colorado, Anschutz, in Aurora.
Dr. Oliver and her colleagues analyzed data from 233 patients who underwent MUS excision at UCLA for MUS-related complications during 2013-2015, and who had at least 3 months of follow-up. The average patient age was 55.4 years; an average of 5.4 years passed between the placement and excision of MUS. The mean body mass index was 28.9, and mean follow-up was 23.5 months.
A total of 84% of patients underwent a total excision; 45% of MUS were retropubic, 35% were transobturator, 10% were single incision, and 10% were multiple incision.
Nearly half (49%) of patients required a second procedure for SUI, such as bulking agent injection, bladder neck suspension, or repeat sling procedure.
In the entire cohort, multivariate analyses found significant associations between heightened risk of postoperative SUI and increasing time to MUS excision (odds ratio, 1.16; 95% confidence interval, 1.03-1.30), total MUS excision (OR, 4.14; 95% CI, 1.38-12.37), and preoperative urodynamic SUI (OR, 4.66; 95% CI, 2.13-10.19).
Of 51 patients who had preoperative urodynamic SUI, 39 (76%) ultimately underwent another surgery. Although increased time to MUS excision and total mesh removal were associated with urinary incontinence in this group in univariate analyses, they were no longer significant following a multivariate analysis.
Of 140 patients with a negative preoperative urodynamic testing for SUI, 59 (42%) went on to have another SUI procedure. After multivariate analysis, the only risk factors for urinary incontinence were obesity (OR, 4.74; 95% CI, 1.73-13.02) and postmenopausal status (OR, 3.78; 95% CI, 1.16-12.33).
“I think there’s a lot of fear, even among urologists and specialists who see these problems, that complete mesh removal is associated with a higher risk of complications and a higher risk of incontinence,” said Dr. Oliver. “These data would suggest that, in certain subgroups, that’s not true. The risks factors that we identified in a multivariate analysis were being obese and being postmenopausal, but not complete mesh removal.”
The study received no external funding. Dr. Oliver reported having no financial conflicts of interest.
SOURCE: Oliver J et al. AUA Annual Meeting. Abstract PD05-10.
SAN FRANCISCO – Stress urinary incontinence (SUI) following removal of a mid-urethral sling (MUS) mesh is not necessarily associated with increased risk of postsurgical urinary incontinence, according to a retrospective study at a high-volume, tertiary medical center.
Follow-up procedures occurred more often in women with preoperative urodynamic SUI and less often in women who were stress continent.
Among women who were stress continent, obesity and postmenopausal status were linked to postsurgical SUI. There was no association between postsurgical SUI and the extent of mesh excision or prior revisions.
The study grew out of observations that SUI occurred less often than expected.
“There’s an increasing recognition of complications related to synthetic MUS,” said Janine Oliver, MD, who presented the study at the annual meeting of the American Urological Association. “As mesh removal procedures were being performed, we assumed that the majority of patients, if not all, would be incontinent afterward, since we were removing the sling that was put in to fix stress incontinence in most cases.”
In a patient who would benefit from a complete mesh removal, “the fear that it may lead to a higher risk of urinary incontinence is not a good justification to not do it,” Dr. Oliver said. She did note, however, that the procedures were done by specialists, so findings may not be applicable to general practitioners.
The study was performed while Dr. Oliver was a fellow at the University of California, Los Angeles. She is now with the division of urology at the University of Colorado, Anschutz, in Aurora.
Dr. Oliver and her colleagues analyzed data from 233 patients who underwent MUS excision at UCLA for MUS-related complications during 2013-2015, and who had at least 3 months of follow-up. The average patient age was 55.4 years; an average of 5.4 years passed between the placement and excision of MUS. The mean body mass index was 28.9, and mean follow-up was 23.5 months.
A total of 84% of patients underwent a total excision; 45% of MUS were retropubic, 35% were transobturator, 10% were single incision, and 10% were multiple incision.
Nearly half (49%) of patients required a second procedure for SUI, such as bulking agent injection, bladder neck suspension, or repeat sling procedure.
In the entire cohort, multivariate analyses found significant associations between heightened risk of postoperative SUI and increasing time to MUS excision (odds ratio, 1.16; 95% confidence interval, 1.03-1.30), total MUS excision (OR, 4.14; 95% CI, 1.38-12.37), and preoperative urodynamic SUI (OR, 4.66; 95% CI, 2.13-10.19).
Of 51 patients who had preoperative urodynamic SUI, 39 (76%) ultimately underwent another surgery. Although increased time to MUS excision and total mesh removal were associated with urinary incontinence in this group in univariate analyses, they were no longer significant following a multivariate analysis.
Of 140 patients with a negative preoperative urodynamic testing for SUI, 59 (42%) went on to have another SUI procedure. After multivariate analysis, the only risk factors for urinary incontinence were obesity (OR, 4.74; 95% CI, 1.73-13.02) and postmenopausal status (OR, 3.78; 95% CI, 1.16-12.33).
“I think there’s a lot of fear, even among urologists and specialists who see these problems, that complete mesh removal is associated with a higher risk of complications and a higher risk of incontinence,” said Dr. Oliver. “These data would suggest that, in certain subgroups, that’s not true. The risks factors that we identified in a multivariate analysis were being obese and being postmenopausal, but not complete mesh removal.”
The study received no external funding. Dr. Oliver reported having no financial conflicts of interest.
SOURCE: Oliver J et al. AUA Annual Meeting. Abstract PD05-10.
SAN FRANCISCO – Stress urinary incontinence (SUI) following removal of a mid-urethral sling (MUS) mesh is not necessarily associated with increased risk of postsurgical urinary incontinence, according to a retrospective study at a high-volume, tertiary medical center.
Follow-up procedures occurred more often in women with preoperative urodynamic SUI and less often in women who were stress continent.
Among women who were stress continent, obesity and postmenopausal status were linked to postsurgical SUI. There was no association between postsurgical SUI and the extent of mesh excision or prior revisions.
The study grew out of observations that SUI occurred less often than expected.
“There’s an increasing recognition of complications related to synthetic MUS,” said Janine Oliver, MD, who presented the study at the annual meeting of the American Urological Association. “As mesh removal procedures were being performed, we assumed that the majority of patients, if not all, would be incontinent afterward, since we were removing the sling that was put in to fix stress incontinence in most cases.”
In a patient who would benefit from a complete mesh removal, “the fear that it may lead to a higher risk of urinary incontinence is not a good justification to not do it,” Dr. Oliver said. She did note, however, that the procedures were done by specialists, so findings may not be applicable to general practitioners.
The study was performed while Dr. Oliver was a fellow at the University of California, Los Angeles. She is now with the division of urology at the University of Colorado, Anschutz, in Aurora.
Dr. Oliver and her colleagues analyzed data from 233 patients who underwent MUS excision at UCLA for MUS-related complications during 2013-2015, and who had at least 3 months of follow-up. The average patient age was 55.4 years; an average of 5.4 years passed between the placement and excision of MUS. The mean body mass index was 28.9, and mean follow-up was 23.5 months.
A total of 84% of patients underwent a total excision; 45% of MUS were retropubic, 35% were transobturator, 10% were single incision, and 10% were multiple incision.
Nearly half (49%) of patients required a second procedure for SUI, such as bulking agent injection, bladder neck suspension, or repeat sling procedure.
In the entire cohort, multivariate analyses found significant associations between heightened risk of postoperative SUI and increasing time to MUS excision (odds ratio, 1.16; 95% confidence interval, 1.03-1.30), total MUS excision (OR, 4.14; 95% CI, 1.38-12.37), and preoperative urodynamic SUI (OR, 4.66; 95% CI, 2.13-10.19).
Of 51 patients who had preoperative urodynamic SUI, 39 (76%) ultimately underwent another surgery. Although increased time to MUS excision and total mesh removal were associated with urinary incontinence in this group in univariate analyses, they were no longer significant following a multivariate analysis.
Of 140 patients with a negative preoperative urodynamic testing for SUI, 59 (42%) went on to have another SUI procedure. After multivariate analysis, the only risk factors for urinary incontinence were obesity (OR, 4.74; 95% CI, 1.73-13.02) and postmenopausal status (OR, 3.78; 95% CI, 1.16-12.33).
“I think there’s a lot of fear, even among urologists and specialists who see these problems, that complete mesh removal is associated with a higher risk of complications and a higher risk of incontinence,” said Dr. Oliver. “These data would suggest that, in certain subgroups, that’s not true. The risks factors that we identified in a multivariate analysis were being obese and being postmenopausal, but not complete mesh removal.”
The study received no external funding. Dr. Oliver reported having no financial conflicts of interest.
SOURCE: Oliver J et al. AUA Annual Meeting. Abstract PD05-10.
REPORTING FROM THE AUA ANNUAL MEETING
Key clinical point: There was no association between postsurgical incontinence risk and complete mesh removal.
Major finding: In patients without presurgical urodynamic incontinence, only obesity (OR, 4.74) and postmenopausal status (OR, 3.78) were linked to incontinence risk.
Study details: A retrospective analysis of 233 patients.
Disclosures: The study received no external funding. Dr. Oliver reported having no financial conflicts of interest.
Source: Oliver J et al. AUA Annual Meeting. Abstract PD05-10.
Leg lymphedema after gynecologic lymphadenectomy exceeds expectations
NEW ORLEANS – Leg lymphedema occurred in 19%-40% of women with a gynecologic cancer who underwent surgery with lymphadenectomy in a prospective study of 821 U.S. patients.
The incidence of lymphedema of the lower extremity (LLE) during 2 years of follow-up was 18% among 672 endometrial cancer patients, 25% among 124 cervical cancer patients, and 40% among 24 vulvar cancer patients, Jay W. Carlson, DO, said at the annual meeting of the Society of Gynecologic Oncology.
Although the study followed patients for 2 years after surgery, 84% of the LLE events occurred within the first 6 months after surgery, and 95% within the first 12 months. The robust incidence rates documented in this study contrasted with a general perception that LLE is relatively uncommon, leading Dr. Carlson to note that the new data show “the incidence of LLE is under recognized.” The findings also bucked conventional wisdom by showing no link between the incidence of LLE and number of lymph nodes dissected or with use of radiation treatment, said Dr. Carlson, a gynecologic oncologist at Mercy Clinic Women’s Oncology in Springfield, Mo.
To better define the incidence of LLE after lymphadenectomy for gynecologic cancers, the Gynecologic Oncology Group organized the Lymphedema and Gynecologic Cancer (LEG) study, run at more than 70 U.S. centers during June 2012–November 2014. The study enrolled patients scheduled for surgery to treat endometrial, cervical, or vulvar cancer, and applied systematic leg measurement to patients just before and at several prespecified times following surgery through 2 years of follow-up.
The study began with a total of 1,054 patients, but the final analysis that Dr. Carlson presented excluded patients who did not actually undergo lymphadenectomy during their surgery, did not have leg volume data available both before and after their surgery, or had a comorbidity or change in body mass that could have caused the change in leg size. The researchers also required patients identified with LLE to have completed the Gynecologic Cancer Lymphedema Questionnaire (Gynecol Oncol. 2010 May;117[2]:317-23) and tallied a score of at least 4, and to have at least a 10% increase in leg volume at the time of diagnosis, compared with the presurgical volume.
The exclusions yielded a total of 672 patients with endometrial cancer, including 127 who developed LLE (19%); 124 patients with cervical cancer, including 31 who developed LLE (25%); and 25 patients with vulvar cancer, including 10 who developed LLE (40%), Dr. Carlson reported.
Analysis of the patients who developed LLE showed no significant association with type of surgery (open, robotic, or laparoscopic), and no significant associations with several patient-specific factors including age, race, cancer stage, surgical blood loss, or serum albumin, he said.
mzoler@MDedge.com
On Twitter @mitchelzoler
SOURCE: Carlson J et al. SGO 2018, Abstract 11.
NEW ORLEANS – Leg lymphedema occurred in 19%-40% of women with a gynecologic cancer who underwent surgery with lymphadenectomy in a prospective study of 821 U.S. patients.
The incidence of lymphedema of the lower extremity (LLE) during 2 years of follow-up was 18% among 672 endometrial cancer patients, 25% among 124 cervical cancer patients, and 40% among 24 vulvar cancer patients, Jay W. Carlson, DO, said at the annual meeting of the Society of Gynecologic Oncology.
Although the study followed patients for 2 years after surgery, 84% of the LLE events occurred within the first 6 months after surgery, and 95% within the first 12 months. The robust incidence rates documented in this study contrasted with a general perception that LLE is relatively uncommon, leading Dr. Carlson to note that the new data show “the incidence of LLE is under recognized.” The findings also bucked conventional wisdom by showing no link between the incidence of LLE and number of lymph nodes dissected or with use of radiation treatment, said Dr. Carlson, a gynecologic oncologist at Mercy Clinic Women’s Oncology in Springfield, Mo.
To better define the incidence of LLE after lymphadenectomy for gynecologic cancers, the Gynecologic Oncology Group organized the Lymphedema and Gynecologic Cancer (LEG) study, run at more than 70 U.S. centers during June 2012–November 2014. The study enrolled patients scheduled for surgery to treat endometrial, cervical, or vulvar cancer, and applied systematic leg measurement to patients just before and at several prespecified times following surgery through 2 years of follow-up.
The study began with a total of 1,054 patients, but the final analysis that Dr. Carlson presented excluded patients who did not actually undergo lymphadenectomy during their surgery, did not have leg volume data available both before and after their surgery, or had a comorbidity or change in body mass that could have caused the change in leg size. The researchers also required patients identified with LLE to have completed the Gynecologic Cancer Lymphedema Questionnaire (Gynecol Oncol. 2010 May;117[2]:317-23) and tallied a score of at least 4, and to have at least a 10% increase in leg volume at the time of diagnosis, compared with the presurgical volume.
The exclusions yielded a total of 672 patients with endometrial cancer, including 127 who developed LLE (19%); 124 patients with cervical cancer, including 31 who developed LLE (25%); and 25 patients with vulvar cancer, including 10 who developed LLE (40%), Dr. Carlson reported.
Analysis of the patients who developed LLE showed no significant association with type of surgery (open, robotic, or laparoscopic), and no significant associations with several patient-specific factors including age, race, cancer stage, surgical blood loss, or serum albumin, he said.
mzoler@MDedge.com
On Twitter @mitchelzoler
SOURCE: Carlson J et al. SGO 2018, Abstract 11.
NEW ORLEANS – Leg lymphedema occurred in 19%-40% of women with a gynecologic cancer who underwent surgery with lymphadenectomy in a prospective study of 821 U.S. patients.
The incidence of lymphedema of the lower extremity (LLE) during 2 years of follow-up was 18% among 672 endometrial cancer patients, 25% among 124 cervical cancer patients, and 40% among 24 vulvar cancer patients, Jay W. Carlson, DO, said at the annual meeting of the Society of Gynecologic Oncology.
Although the study followed patients for 2 years after surgery, 84% of the LLE events occurred within the first 6 months after surgery, and 95% within the first 12 months. The robust incidence rates documented in this study contrasted with a general perception that LLE is relatively uncommon, leading Dr. Carlson to note that the new data show “the incidence of LLE is under recognized.” The findings also bucked conventional wisdom by showing no link between the incidence of LLE and number of lymph nodes dissected or with use of radiation treatment, said Dr. Carlson, a gynecologic oncologist at Mercy Clinic Women’s Oncology in Springfield, Mo.
To better define the incidence of LLE after lymphadenectomy for gynecologic cancers, the Gynecologic Oncology Group organized the Lymphedema and Gynecologic Cancer (LEG) study, run at more than 70 U.S. centers during June 2012–November 2014. The study enrolled patients scheduled for surgery to treat endometrial, cervical, or vulvar cancer, and applied systematic leg measurement to patients just before and at several prespecified times following surgery through 2 years of follow-up.
The study began with a total of 1,054 patients, but the final analysis that Dr. Carlson presented excluded patients who did not actually undergo lymphadenectomy during their surgery, did not have leg volume data available both before and after their surgery, or had a comorbidity or change in body mass that could have caused the change in leg size. The researchers also required patients identified with LLE to have completed the Gynecologic Cancer Lymphedema Questionnaire (Gynecol Oncol. 2010 May;117[2]:317-23) and tallied a score of at least 4, and to have at least a 10% increase in leg volume at the time of diagnosis, compared with the presurgical volume.
The exclusions yielded a total of 672 patients with endometrial cancer, including 127 who developed LLE (19%); 124 patients with cervical cancer, including 31 who developed LLE (25%); and 25 patients with vulvar cancer, including 10 who developed LLE (40%), Dr. Carlson reported.
Analysis of the patients who developed LLE showed no significant association with type of surgery (open, robotic, or laparoscopic), and no significant associations with several patient-specific factors including age, race, cancer stage, surgical blood loss, or serum albumin, he said.
mzoler@MDedge.com
On Twitter @mitchelzoler
SOURCE: Carlson J et al. SGO 2018, Abstract 11.
REPORTING FROM SGO 2018
Key clinical point: Leg lymphedema is common following lymphadenectomy for a gynecologic cancer.
Major finding: Leg lymphedema incidence was 19%-40% during 2-year follow-up after lymphadenectomy during gynecologic cancer surgery.
Study details: LEG, a multicenter, U.S. prospective study with 821 gynecologic cancer patients in the final analysis.
Disclosures: LEG had no commercial funding. Dr. Carlson had no disclosures.
Source: Carlson J et al. SGO 2018, Abstract 11.
Endometriosis pain stemming from pelvic spasms improved with botulinum toxin
LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.
At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.
All 28 women currently enrolled in the trial (median age, 29 years) were evaluated by a gynecologist to confirm pelvic muscle spasm as their primary source of pain. Each also underwent a neuromuscular examination to identify pain points beyond the pelvis.
All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.
Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.
“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”
In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.
A month after the open-label injection, spasm was reduced or absent in all subjects (P = .0005), with 11 of 13 rating pain as absent or mild (P = .0001), Dr. Karp and her colleagues reported. Between 5 and 11 months post injection, five women requested a repeat of the treatment.
Besides the data on pain and disability collected as part of the trial, Dr. Karp and her colleagues are also looking at biomarkers for pain and inflammation, and changes in medication and hormone use. They are preparing a separate literature review on injection techniques and dosages of toxin to the pelvic floor muscles.
“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.
The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”
Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.
SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.
LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.
At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.
All 28 women currently enrolled in the trial (median age, 29 years) were evaluated by a gynecologist to confirm pelvic muscle spasm as their primary source of pain. Each also underwent a neuromuscular examination to identify pain points beyond the pelvis.
All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.
Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.
“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”
In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.
A month after the open-label injection, spasm was reduced or absent in all subjects (P = .0005), with 11 of 13 rating pain as absent or mild (P = .0001), Dr. Karp and her colleagues reported. Between 5 and 11 months post injection, five women requested a repeat of the treatment.
Besides the data on pain and disability collected as part of the trial, Dr. Karp and her colleagues are also looking at biomarkers for pain and inflammation, and changes in medication and hormone use. They are preparing a separate literature review on injection techniques and dosages of toxin to the pelvic floor muscles.
“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.
The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”
Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.
SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.
LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.
At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.
All 28 women currently enrolled in the trial (median age, 29 years) were evaluated by a gynecologist to confirm pelvic muscle spasm as their primary source of pain. Each also underwent a neuromuscular examination to identify pain points beyond the pelvis.
All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.
Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.
“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”
In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.
A month after the open-label injection, spasm was reduced or absent in all subjects (P = .0005), with 11 of 13 rating pain as absent or mild (P = .0001), Dr. Karp and her colleagues reported. Between 5 and 11 months post injection, five women requested a repeat of the treatment.
Besides the data on pain and disability collected as part of the trial, Dr. Karp and her colleagues are also looking at biomarkers for pain and inflammation, and changes in medication and hormone use. They are preparing a separate literature review on injection techniques and dosages of toxin to the pelvic floor muscles.
“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.
The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”
Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.
SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.
REPORTING FROM AAN 2018
Key clinical point:
Major finding: A month after the open-label injection, spasm was reduced or absent in all subjects (P = .0005), with 11 of 13 rating pain as absent or mild (P = .0001).
Study details: An open-label extension in 13 of 28 patients enrolled in a randomized trial.
Disclosures: Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.
Source: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.
ERAS reduced opioid use, improved same-day discharge after gyn surgery
ORLANDO – The implementation of enhanced recovery after surgery (ERAS) pathways increased same-day discharge rates, but also was associated with a slight increase in readmissions within 30 days, according to a retrospective review of urogynecology cases at a single institution.
ERAS implementation also decreased total opioid use and pain scores, increased preemptive antiemetic use, and reduced rescue antiemetic needs in the postanesthesia care unit, Charelle M. Carter-Brooks, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
In a separate study at an urban safety-net hospital, ERAS implementation was feasible and rapidly accomplished, and resulted in a number of improved outcomes among gynecologic surgery patients, including reduced intraoperative opioid and intravenous fluid use, reduced postoperative intravenous opioid use, and shorter Foley catheter duration – all without an increase in total adverse events.
In the first study, same-day discharge rates were 91.7% in 137 women who underwent urogynecologic surgery after ERAS implementation vs. 25.9% in 121 patients who underwent surgery before ERAS implementation, and average length of admission decreased by 17.4 hours (27.7 vs. 10.3 hours), Dr. Carter-Brooks of Magee-Womens Hospital, University of Pittsburgh Medical Center, reported in an oral paper presentation.
Operative time and postsurgical recovery room times were similar before and after ERAS implementation, but earlier discharge in the ERAS group was associated with about a 5% increase in readmission rates within 30 days (readmission rates of 1.5% and 6.7% before and after implementation), she noted.
Other outcomes, including postoperative complications, urinary tract infections, emergency room visits, unanticipated office visits, and returns to the operating room were similar in the two groups, she said.
After adjusting for age, body mass index, comorbidities, and operative time, length of stay decreased by 13.6 hours after ERAS implementation; after adjusting for age and operative time, same-day discharge was 32 times more likely after ERAS implementation; and after adjusting for age, operative time, and prolapse surgery type, readmission was 5.7 times more likely after ERAS implementation, she said.
In a survey of 77 post-ERAS implementation patients conducted during postoperative nursing calls, 86.7%, 89.6%, and 93.5% reported very good or excellent pain control, surgery preparedness, and overall surgical experience, respectively, and 90% said they did not recall experiencing postoperative nausea during recovery, she added.
In a poster presented at the meeting, Dr. Carter-Brooks further noted that there was a 69% reduction in overall opioid use in the patients who underwent surgery after ERAS implementation, as well as a doubling in the median number of preemptive antiemetic doses (4 vs. 2) and a significant reduction in the percentage of patients receiving a rescue antiemetic after implementation (21.6% vs. 13.6%).
Patients included in the study were women with a mean age of 65.5 years and mean body mass index of 28.2 kg/m2. The most common preoperative diagnosis (in 93.8% of patients) was prolapse. Apical suspension procedures performed were transvaginal in 58 cases, laparoscopic or robotic in 112, and obliterative in 61. Most patients had a hysterectomy, including 83 laparoscopic or robotic, 64 transvaginal, and 1 combined procedure. Demographic and surgical procedures did not differ significantly in the pre- and post-ERAS groups, Dr. Carter-Brooks noted.
Surgeries were performed by seven different surgeons either before ERAS implementation (Jan. 1 to June 30, 2016) or after implementation (Feb. 2 to July 31, 2017).
ERAS – a multidisciplinary approach to patient perioperative care – involves implementation of evidence-based interventions to improve early discharge and length of stay in patients undergoing major elective surgery.
ERAS pathways, which are commonly used in colorectal surgery, were developed to hasten postoperative recovery and are now being increasingly adopted for gynecologic procedures, but data focusing on outcomes with ERAS in the prolapse repair setting are limited, Dr. Carter-Brooks noted.
The ERAS pathway in her study involved a preoperative optimization phase that included counseling about tobacco and alcohol cessation, education about ERAS pathway expectations, and recommendations regarding diet and exercise 1-2 weeks prior to surgery. On the day of surgery, the pathway involved a multimodal pain regimen and postoperative nausea and vomiting prevention.
In response to discussion questions about which interventions contributed most to improvements in same-day discharge rates and patient satisfaction, which interventions were most difficult to implement, and whether additional interventions could prevent readmissions, Dr. Carter-Brooks said that, in her experience the multimodal focus on pain and nausea/vomiting prevention has been particularly helpful, as has the emphasis on educating patients about the interventions and expectations.
“For the preoperative appointment we really spend about 15-30 minutes on education and expectations and prepare the patient to go home. We also encourage them to be advocates and stakeholders in their own recovery, and ... we think that has significantly improved our patients wanting to go home the day of surgery,” she said.
The most difficult aspect of implementation was changing the culture in the hospital, she added.
Support of leadership team members who advocated for change was key to achieving that. Regular audits to review outcomes and make changes as needed to achieve the intended benefit were also important, she noted.
As for readmissions, the numbers overall were small, and their relation to ERAS is questionable and something that is still being tracked and assessed, she said.
In the second study, early outcomes after ERAS implementation were encouraging. Compared with 96 patients who underwent gynecologic surgery between June 1 and Aug. 31, 2015 (before ERAS implementation), 65 who underwent surgery afterward (between February and April 2017) had decreased intraoperative opioid use in open surgery (95 mg vs. 115 mg) and in minimally invasive surgery (75 mg vs. 95 mg), as well as decreased intravenous opioid use postoperatively for open surgery (44% vs. 71%), Mary Louise Fowler, a 4th-year medical student at Boston University, reported at the conference.
The ERAS patients also had shorter Foley catheter duration for minimally invasive surgery (16 vs. 2.3 hours), and they had a trend toward decreased intraoperative fluids for minimally invasive surgery (3.3 vs. 4.2 mL/kg per hour), Ms. Fowler said.
“We also found that there was no significant difference in the length of stay and postdischarge 3-day adverse outcomes,” she said.
The multidisciplinary consensus-based ERAS pathway developed at her institution was implemented beginning Feb. 1, 2017, in response to the national call to reduce opioid use, she explained, noting that a predetermined 4-month time line facilitated implementation by the target date.
Eligible patients included those undergoing benign or oncologic gynecologic surgery with a planned overnight stay.
“Preliminary positive outcomes have been found [with ERAS] at our urban safety-net hospital, specifically in looking at decreased opioid use without a resultant total adverse event increase. It is important for us to continue to monitor ERAS in terms of long-term care to ensure adherence, safety, and effectiveness,” she said, adding that tracking of outcomes will continue, and a future goal is to assess impacts on cost.
Dr. Carter-Brooks’s study was supported by a National Institutes of Health grant. She and Ms. Fowler each reported having no disclosures.
SOURCES: Carter-Brooks C et al.; Fowler M et al. SGS 2018, Oral presentation 2; Oral posters 1 and 16.
The ERAS pathway described by Dr. Carter-Brooks embraces the core tenets of enhanced recovery, including standardized patient education, multimodal analgesia, and predefined postoperative metrics, according to invited discussant Mark Walters, MD.
In fact, systematic culture change requires the involvement of surgeons, nurses, anesthesiologists, and administrative staff, Dr. Walters added.
“Additionally, such significant behavioral changes inevitably result in unintended consequences that must be carefully documented to learn how to mitigate harm in future patients,” he said.
Dr. Walters is professor and vice chair of gynecology in the Center of Urogynecology and Reconstructive Pelvic Surgery, department of obstetrics and gynecology at the Cleveland Clinic. He is a consultant and teacher for Coloplast.
The ERAS pathway described by Dr. Carter-Brooks embraces the core tenets of enhanced recovery, including standardized patient education, multimodal analgesia, and predefined postoperative metrics, according to invited discussant Mark Walters, MD.
In fact, systematic culture change requires the involvement of surgeons, nurses, anesthesiologists, and administrative staff, Dr. Walters added.
“Additionally, such significant behavioral changes inevitably result in unintended consequences that must be carefully documented to learn how to mitigate harm in future patients,” he said.
Dr. Walters is professor and vice chair of gynecology in the Center of Urogynecology and Reconstructive Pelvic Surgery, department of obstetrics and gynecology at the Cleveland Clinic. He is a consultant and teacher for Coloplast.
The ERAS pathway described by Dr. Carter-Brooks embraces the core tenets of enhanced recovery, including standardized patient education, multimodal analgesia, and predefined postoperative metrics, according to invited discussant Mark Walters, MD.
In fact, systematic culture change requires the involvement of surgeons, nurses, anesthesiologists, and administrative staff, Dr. Walters added.
“Additionally, such significant behavioral changes inevitably result in unintended consequences that must be carefully documented to learn how to mitigate harm in future patients,” he said.
Dr. Walters is professor and vice chair of gynecology in the Center of Urogynecology and Reconstructive Pelvic Surgery, department of obstetrics and gynecology at the Cleveland Clinic. He is a consultant and teacher for Coloplast.
ORLANDO – The implementation of enhanced recovery after surgery (ERAS) pathways increased same-day discharge rates, but also was associated with a slight increase in readmissions within 30 days, according to a retrospective review of urogynecology cases at a single institution.
ERAS implementation also decreased total opioid use and pain scores, increased preemptive antiemetic use, and reduced rescue antiemetic needs in the postanesthesia care unit, Charelle M. Carter-Brooks, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
In a separate study at an urban safety-net hospital, ERAS implementation was feasible and rapidly accomplished, and resulted in a number of improved outcomes among gynecologic surgery patients, including reduced intraoperative opioid and intravenous fluid use, reduced postoperative intravenous opioid use, and shorter Foley catheter duration – all without an increase in total adverse events.
In the first study, same-day discharge rates were 91.7% in 137 women who underwent urogynecologic surgery after ERAS implementation vs. 25.9% in 121 patients who underwent surgery before ERAS implementation, and average length of admission decreased by 17.4 hours (27.7 vs. 10.3 hours), Dr. Carter-Brooks of Magee-Womens Hospital, University of Pittsburgh Medical Center, reported in an oral paper presentation.
Operative time and postsurgical recovery room times were similar before and after ERAS implementation, but earlier discharge in the ERAS group was associated with about a 5% increase in readmission rates within 30 days (readmission rates of 1.5% and 6.7% before and after implementation), she noted.
Other outcomes, including postoperative complications, urinary tract infections, emergency room visits, unanticipated office visits, and returns to the operating room were similar in the two groups, she said.
After adjusting for age, body mass index, comorbidities, and operative time, length of stay decreased by 13.6 hours after ERAS implementation; after adjusting for age and operative time, same-day discharge was 32 times more likely after ERAS implementation; and after adjusting for age, operative time, and prolapse surgery type, readmission was 5.7 times more likely after ERAS implementation, she said.
In a survey of 77 post-ERAS implementation patients conducted during postoperative nursing calls, 86.7%, 89.6%, and 93.5% reported very good or excellent pain control, surgery preparedness, and overall surgical experience, respectively, and 90% said they did not recall experiencing postoperative nausea during recovery, she added.
In a poster presented at the meeting, Dr. Carter-Brooks further noted that there was a 69% reduction in overall opioid use in the patients who underwent surgery after ERAS implementation, as well as a doubling in the median number of preemptive antiemetic doses (4 vs. 2) and a significant reduction in the percentage of patients receiving a rescue antiemetic after implementation (21.6% vs. 13.6%).
Patients included in the study were women with a mean age of 65.5 years and mean body mass index of 28.2 kg/m2. The most common preoperative diagnosis (in 93.8% of patients) was prolapse. Apical suspension procedures performed were transvaginal in 58 cases, laparoscopic or robotic in 112, and obliterative in 61. Most patients had a hysterectomy, including 83 laparoscopic or robotic, 64 transvaginal, and 1 combined procedure. Demographic and surgical procedures did not differ significantly in the pre- and post-ERAS groups, Dr. Carter-Brooks noted.
Surgeries were performed by seven different surgeons either before ERAS implementation (Jan. 1 to June 30, 2016) or after implementation (Feb. 2 to July 31, 2017).
ERAS – a multidisciplinary approach to patient perioperative care – involves implementation of evidence-based interventions to improve early discharge and length of stay in patients undergoing major elective surgery.
ERAS pathways, which are commonly used in colorectal surgery, were developed to hasten postoperative recovery and are now being increasingly adopted for gynecologic procedures, but data focusing on outcomes with ERAS in the prolapse repair setting are limited, Dr. Carter-Brooks noted.
The ERAS pathway in her study involved a preoperative optimization phase that included counseling about tobacco and alcohol cessation, education about ERAS pathway expectations, and recommendations regarding diet and exercise 1-2 weeks prior to surgery. On the day of surgery, the pathway involved a multimodal pain regimen and postoperative nausea and vomiting prevention.
In response to discussion questions about which interventions contributed most to improvements in same-day discharge rates and patient satisfaction, which interventions were most difficult to implement, and whether additional interventions could prevent readmissions, Dr. Carter-Brooks said that, in her experience the multimodal focus on pain and nausea/vomiting prevention has been particularly helpful, as has the emphasis on educating patients about the interventions and expectations.
“For the preoperative appointment we really spend about 15-30 minutes on education and expectations and prepare the patient to go home. We also encourage them to be advocates and stakeholders in their own recovery, and ... we think that has significantly improved our patients wanting to go home the day of surgery,” she said.
The most difficult aspect of implementation was changing the culture in the hospital, she added.
Support of leadership team members who advocated for change was key to achieving that. Regular audits to review outcomes and make changes as needed to achieve the intended benefit were also important, she noted.
As for readmissions, the numbers overall were small, and their relation to ERAS is questionable and something that is still being tracked and assessed, she said.
In the second study, early outcomes after ERAS implementation were encouraging. Compared with 96 patients who underwent gynecologic surgery between June 1 and Aug. 31, 2015 (before ERAS implementation), 65 who underwent surgery afterward (between February and April 2017) had decreased intraoperative opioid use in open surgery (95 mg vs. 115 mg) and in minimally invasive surgery (75 mg vs. 95 mg), as well as decreased intravenous opioid use postoperatively for open surgery (44% vs. 71%), Mary Louise Fowler, a 4th-year medical student at Boston University, reported at the conference.
The ERAS patients also had shorter Foley catheter duration for minimally invasive surgery (16 vs. 2.3 hours), and they had a trend toward decreased intraoperative fluids for minimally invasive surgery (3.3 vs. 4.2 mL/kg per hour), Ms. Fowler said.
“We also found that there was no significant difference in the length of stay and postdischarge 3-day adverse outcomes,” she said.
The multidisciplinary consensus-based ERAS pathway developed at her institution was implemented beginning Feb. 1, 2017, in response to the national call to reduce opioid use, she explained, noting that a predetermined 4-month time line facilitated implementation by the target date.
Eligible patients included those undergoing benign or oncologic gynecologic surgery with a planned overnight stay.
“Preliminary positive outcomes have been found [with ERAS] at our urban safety-net hospital, specifically in looking at decreased opioid use without a resultant total adverse event increase. It is important for us to continue to monitor ERAS in terms of long-term care to ensure adherence, safety, and effectiveness,” she said, adding that tracking of outcomes will continue, and a future goal is to assess impacts on cost.
Dr. Carter-Brooks’s study was supported by a National Institutes of Health grant. She and Ms. Fowler each reported having no disclosures.
SOURCES: Carter-Brooks C et al.; Fowler M et al. SGS 2018, Oral presentation 2; Oral posters 1 and 16.
ORLANDO – The implementation of enhanced recovery after surgery (ERAS) pathways increased same-day discharge rates, but also was associated with a slight increase in readmissions within 30 days, according to a retrospective review of urogynecology cases at a single institution.
ERAS implementation also decreased total opioid use and pain scores, increased preemptive antiemetic use, and reduced rescue antiemetic needs in the postanesthesia care unit, Charelle M. Carter-Brooks, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.
In a separate study at an urban safety-net hospital, ERAS implementation was feasible and rapidly accomplished, and resulted in a number of improved outcomes among gynecologic surgery patients, including reduced intraoperative opioid and intravenous fluid use, reduced postoperative intravenous opioid use, and shorter Foley catheter duration – all without an increase in total adverse events.
In the first study, same-day discharge rates were 91.7% in 137 women who underwent urogynecologic surgery after ERAS implementation vs. 25.9% in 121 patients who underwent surgery before ERAS implementation, and average length of admission decreased by 17.4 hours (27.7 vs. 10.3 hours), Dr. Carter-Brooks of Magee-Womens Hospital, University of Pittsburgh Medical Center, reported in an oral paper presentation.
Operative time and postsurgical recovery room times were similar before and after ERAS implementation, but earlier discharge in the ERAS group was associated with about a 5% increase in readmission rates within 30 days (readmission rates of 1.5% and 6.7% before and after implementation), she noted.
Other outcomes, including postoperative complications, urinary tract infections, emergency room visits, unanticipated office visits, and returns to the operating room were similar in the two groups, she said.
After adjusting for age, body mass index, comorbidities, and operative time, length of stay decreased by 13.6 hours after ERAS implementation; after adjusting for age and operative time, same-day discharge was 32 times more likely after ERAS implementation; and after adjusting for age, operative time, and prolapse surgery type, readmission was 5.7 times more likely after ERAS implementation, she said.
In a survey of 77 post-ERAS implementation patients conducted during postoperative nursing calls, 86.7%, 89.6%, and 93.5% reported very good or excellent pain control, surgery preparedness, and overall surgical experience, respectively, and 90% said they did not recall experiencing postoperative nausea during recovery, she added.
In a poster presented at the meeting, Dr. Carter-Brooks further noted that there was a 69% reduction in overall opioid use in the patients who underwent surgery after ERAS implementation, as well as a doubling in the median number of preemptive antiemetic doses (4 vs. 2) and a significant reduction in the percentage of patients receiving a rescue antiemetic after implementation (21.6% vs. 13.6%).
Patients included in the study were women with a mean age of 65.5 years and mean body mass index of 28.2 kg/m2. The most common preoperative diagnosis (in 93.8% of patients) was prolapse. Apical suspension procedures performed were transvaginal in 58 cases, laparoscopic or robotic in 112, and obliterative in 61. Most patients had a hysterectomy, including 83 laparoscopic or robotic, 64 transvaginal, and 1 combined procedure. Demographic and surgical procedures did not differ significantly in the pre- and post-ERAS groups, Dr. Carter-Brooks noted.
Surgeries were performed by seven different surgeons either before ERAS implementation (Jan. 1 to June 30, 2016) or after implementation (Feb. 2 to July 31, 2017).
ERAS – a multidisciplinary approach to patient perioperative care – involves implementation of evidence-based interventions to improve early discharge and length of stay in patients undergoing major elective surgery.
ERAS pathways, which are commonly used in colorectal surgery, were developed to hasten postoperative recovery and are now being increasingly adopted for gynecologic procedures, but data focusing on outcomes with ERAS in the prolapse repair setting are limited, Dr. Carter-Brooks noted.
The ERAS pathway in her study involved a preoperative optimization phase that included counseling about tobacco and alcohol cessation, education about ERAS pathway expectations, and recommendations regarding diet and exercise 1-2 weeks prior to surgery. On the day of surgery, the pathway involved a multimodal pain regimen and postoperative nausea and vomiting prevention.
In response to discussion questions about which interventions contributed most to improvements in same-day discharge rates and patient satisfaction, which interventions were most difficult to implement, and whether additional interventions could prevent readmissions, Dr. Carter-Brooks said that, in her experience the multimodal focus on pain and nausea/vomiting prevention has been particularly helpful, as has the emphasis on educating patients about the interventions and expectations.
“For the preoperative appointment we really spend about 15-30 minutes on education and expectations and prepare the patient to go home. We also encourage them to be advocates and stakeholders in their own recovery, and ... we think that has significantly improved our patients wanting to go home the day of surgery,” she said.
The most difficult aspect of implementation was changing the culture in the hospital, she added.
Support of leadership team members who advocated for change was key to achieving that. Regular audits to review outcomes and make changes as needed to achieve the intended benefit were also important, she noted.
As for readmissions, the numbers overall were small, and their relation to ERAS is questionable and something that is still being tracked and assessed, she said.
In the second study, early outcomes after ERAS implementation were encouraging. Compared with 96 patients who underwent gynecologic surgery between June 1 and Aug. 31, 2015 (before ERAS implementation), 65 who underwent surgery afterward (between February and April 2017) had decreased intraoperative opioid use in open surgery (95 mg vs. 115 mg) and in minimally invasive surgery (75 mg vs. 95 mg), as well as decreased intravenous opioid use postoperatively for open surgery (44% vs. 71%), Mary Louise Fowler, a 4th-year medical student at Boston University, reported at the conference.
The ERAS patients also had shorter Foley catheter duration for minimally invasive surgery (16 vs. 2.3 hours), and they had a trend toward decreased intraoperative fluids for minimally invasive surgery (3.3 vs. 4.2 mL/kg per hour), Ms. Fowler said.
“We also found that there was no significant difference in the length of stay and postdischarge 3-day adverse outcomes,” she said.
The multidisciplinary consensus-based ERAS pathway developed at her institution was implemented beginning Feb. 1, 2017, in response to the national call to reduce opioid use, she explained, noting that a predetermined 4-month time line facilitated implementation by the target date.
Eligible patients included those undergoing benign or oncologic gynecologic surgery with a planned overnight stay.
“Preliminary positive outcomes have been found [with ERAS] at our urban safety-net hospital, specifically in looking at decreased opioid use without a resultant total adverse event increase. It is important for us to continue to monitor ERAS in terms of long-term care to ensure adherence, safety, and effectiveness,” she said, adding that tracking of outcomes will continue, and a future goal is to assess impacts on cost.
Dr. Carter-Brooks’s study was supported by a National Institutes of Health grant. She and Ms. Fowler each reported having no disclosures.
SOURCES: Carter-Brooks C et al.; Fowler M et al. SGS 2018, Oral presentation 2; Oral posters 1 and 16.
REPORTING FROM SGS 2018
Key clinical point: ERAS pathways improve same-day discharge rates and reduce opioid use in gynecologic surgery.
Major finding: Same-day discharge rates before and after ERAS were 25.9% and 91.7%, respectively.
Study details: A retrospective review of 258 patients; a study of 161 patients.
Disclosures: Dr. Carter-Brooks’s study was supported by a National Institutes of Health grant. She and Ms. Fowler each reported having no disclosures.
Sources: Carter-Brooks C et al.; Fowler M et al. SGS 2018, Oral presentation 2; Oral posters 1 and 16.