Allogeneic stem-cell transplantation is not always the best option when pediatric acute lymphoblastic leukemia fails to respond adequately to induction therapy, according to a report in the April 12 issue of the New England Journal of Medicine.

Children who have the precursor B-cell subtype and no other adverse features do better when treated with chemotherapy, investigators report. Those with T-cell leukemia appear to have better outcomes with allogeneic stem-cell transplantation, a common treatment of choice after induction failure.

Eighty percent of children with pediatric acute lymphoblastic leukemia (ALL) can be cured with standard treatments. The small proportion of children in the very-high-risk group that does not respond to induction therapy is much more heterogeneous than clinicians may realize, according to Dr. Martin Schrappe of Schleswig-Holstein University Medical Center, Christian-Albrechts University, Kiel (Germany) and his associates.

The authors pooled the findings of multiple clinical trials performed by 14 cooperative study groups in North America, Europe, and Asia between 1985 and 2000. Based on this observational analysis, ALL with induction failure was found to be a highly varied entity, with different clinical and biologic traits and a wide range of prognoses.

The study assessed outcomes in 44,017 children and adolescents (aged 0-18 years) with newly diagnosed ALL who were enrolled in clinical trials during that interval and were followed for a median of 8.3 years (range, 1.5-22.1 years). A total of 1,041 (2.4%) failed induction therapy, showing persistent leukemic blasts in the bone marrow or at extramedullary sites.

Overall 10-year survival was 32% but varied greatly across the cohort, from 4% to 73%, depending on biological and clinical factors.

Patients with induction failure were much more likely than ALL patients as a whole to have conventional adverse prognostic factors such as a high leukocyte count, older age at disease onset, the BCR-ABL1 gene, and T-cell phenotypes – and these factors conferred an even worse prognosis in this already high-risk population.

"Indeed, the clinical and biologic characteristics of the patients in our study and the course of the disease were similar to those in patients with relapse during receipt of therapy, another group of patients with a highly unfavorable prognosis," the researchers said.

Among patients who eventually achieved a late remission, 10-year survival was significantly higher (48%) than among those who never achieved a remission (14%).

A total of 198 patients underwent hematopoietic stem-cell transplantation and 427 received chemotherapy only. The 10-year survival was 43% with transplantation and 41% without it.

Surprisingly, allogeneic transplantation was shown to be of no benefit in patients younger than 6 years who had precursor B-cell ALL with induction failure and no high-risk features, compared with chemotherapy alone. This finding has "considerable clinical implications, since transplantation is generally considered to be the standard of care for such patients," Dr. Schrappe and his colleagues said (N. Engl. J. Med. 2012;366:1371-81).

In patients aged 6 years and older who had precursor B-cell ALL, a transplant from a matched, related donor appeared to improve outcome, while other types of allogeneic transplants actually worsened outcomes. This was due in part to a high number of transplantation-related deaths in the latter group.

In contrast, allogeneic transplantation appeared to improve outcomes in the subgroup of patients who had T-cell ALL and failed induction therapy.

Patients with high hyperdiploidy (more than 50 chromosomes) showed an excellent outcome, with a 10-year survival rate of 71%. This favorable outcome "may be due to the increased sensitivity of the blast cells to methotrexate and mercaptopurine, drugs that are generally not used during remission induction but are used at high doses after remission," the investigators said.

Patients who carried the genetic aberration ETV6-RUNX1 also had a high 10-year survival of 73%, which is more than double the survival rate in the cohort as a whole.

Survival was lower among patients who had M3 marrow after induction therapy, compared with those who had M1 marrow and extramedullary disease or M2 marrow. Subgroups with the worst outcomes included patients aged 6 years or older who had M3 marrow (10-year survival, 22%) and those of any age who had T-cell ALL and M3 marrow (10-year survival, 19%).

Among infants who had precursor B-cell ALL and did not have a rearrangement of the MLL gene or fusion of the BCR-ABL1 gene, outcomes were similar to those in children aged 1-5 years (10-year survivals of 65% and 63%, respectively). In contrast, infants who had a rearrangement of the MLL gene fared very poorly (10-year survival, 4%) compared with older children who had the same genetic abnormality (10-year survival, 26%).

Numerous hospitals, charities, and government agencies supported this study. Dr. Schrappe reported ties to Medoc and EUSA Pharm; his associates reported ties to numerous industry sources.

Allogeneic stem-cell transplantation is not always the best option when pediatric acute lymphoblastic leukemia fails to respond adequately to induction therapy, according to a report in the April 12 issue of the New England Journal of Medicine.

Children who have the precursor B-cell subtype and no other adverse features do better when treated with chemotherapy, investigators report. Those with T-cell leukemia appear to have better outcomes with allogeneic stem-cell transplantation, a common treatment of choice after induction failure.

Eighty percent of children with pediatric acute lymphoblastic leukemia (ALL) can be cured with standard treatments. The small proportion of children in the very-high-risk group that does not respond to induction therapy is much more heterogeneous than clinicians may realize, according to Dr. Martin Schrappe of Schleswig-Holstein University Medical Center, Christian-Albrechts University, Kiel (Germany) and his associates.

The authors pooled the findings of multiple clinical trials performed by 14 cooperative study groups in North America, Europe, and Asia between 1985 and 2000. Based on this observational analysis, ALL with induction failure was found to be a highly varied entity, with different clinical and biologic traits and a wide range of prognoses.

The study assessed outcomes in 44,017 children and adolescents (aged 0-18 years) with newly diagnosed ALL who were enrolled in clinical trials during that interval and were followed for a median of 8.3 years (range, 1.5-22.1 years). A total of 1,041 (2.4%) failed induction therapy, showing persistent leukemic blasts in the bone marrow or at extramedullary sites.

Overall 10-year survival was 32% but varied greatly across the cohort, from 4% to 73%, depending on biological and clinical factors.

Patients with induction failure were much more likely than ALL patients as a whole to have conventional adverse prognostic factors such as a high leukocyte count, older age at disease onset, the BCR-ABL1 gene, and T-cell phenotypes – and these factors conferred an even worse prognosis in this already high-risk population.

"Indeed, the clinical and biologic characteristics of the patients in our study and the course of the disease were similar to those in patients with relapse during receipt of therapy, another group of patients with a highly unfavorable prognosis," the researchers said.

Among patients who eventually achieved a late remission, 10-year survival was significantly higher (48%) than among those who never achieved a remission (14%).

A total of 198 patients underwent hematopoietic stem-cell transplantation and 427 received chemotherapy only. The 10-year survival was 43% with transplantation and 41% without it.

Surprisingly, allogeneic transplantation was shown to be of no benefit in patients younger than 6 years who had precursor B-cell ALL with induction failure and no high-risk features, compared with chemotherapy alone. This finding has "considerable clinical implications, since transplantation is generally considered to be the standard of care for such patients," Dr. Schrappe and his colleagues said (N. Engl. J. Med. 2012;366:1371-81).

In patients aged 6 years and older who had precursor B-cell ALL, a transplant from a matched, related donor appeared to improve outcome, while other types of allogeneic transplants actually worsened outcomes. This was due in part to a high number of transplantation-related deaths in the latter group.

In contrast, allogeneic transplantation appeared to improve outcomes in the subgroup of patients who had T-cell ALL and failed induction therapy.

Patients with high hyperdiploidy (more than 50 chromosomes) showed an excellent outcome, with a 10-year survival rate of 71%. This favorable outcome "may be due to the increased sensitivity of the blast cells to methotrexate and mercaptopurine, drugs that are generally not used during remission induction but are used at high doses after remission," the investigators said.

Patients who carried the genetic aberration ETV6-RUNX1 also had a high 10-year survival of 73%, which is more than double the survival rate in the cohort as a whole.

Survival was lower among patients who had M3 marrow after induction therapy, compared with those who had M1 marrow and extramedullary disease or M2 marrow. Subgroups with the worst outcomes included patients aged 6 years or older who had M3 marrow (10-year survival, 22%) and those of any age who had T-cell ALL and M3 marrow (10-year survival, 19%).

Among infants who had precursor B-cell ALL and did not have a rearrangement of the MLL gene or fusion of the BCR-ABL1 gene, outcomes were similar to those in children aged 1-5 years (10-year survivals of 65% and 63%, respectively). In contrast, infants who had a rearrangement of the MLL gene fared very poorly (10-year survival, 4%) compared with older children who had the same genetic abnormality (10-year survival, 26%).

Numerous hospitals, charities, and government agencies supported this study. Dr. Schrappe reported ties to Medoc and EUSA Pharm; his associates reported ties to numerous industry sources.

Allogeneic stem-cell transplantation is not always the best option when pediatric acute lymphoblastic leukemia fails to respond adequately to induction therapy, according to a report in the April 12 issue of the New England Journal of Medicine.

Children who have the precursor B-cell subtype and no other adverse features do better when treated with chemotherapy, investigators report. Those with T-cell leukemia appear to have better outcomes with allogeneic stem-cell transplantation, a common treatment of choice after induction failure.

Eighty percent of children with pediatric acute lymphoblastic leukemia (ALL) can be cured with standard treatments. The small proportion of children in the very-high-risk group that does not respond to induction therapy is much more heterogeneous than clinicians may realize, according to Dr. Martin Schrappe of Schleswig-Holstein University Medical Center, Christian-Albrechts University, Kiel (Germany) and his associates.

The authors pooled the findings of multiple clinical trials performed by 14 cooperative study groups in North America, Europe, and Asia between 1985 and 2000. Based on this observational analysis, ALL with induction failure was found to be a highly varied entity, with different clinical and biologic traits and a wide range of prognoses.

The study assessed outcomes in 44,017 children and adolescents (aged 0-18 years) with newly diagnosed ALL who were enrolled in clinical trials during that interval and were followed for a median of 8.3 years (range, 1.5-22.1 years). A total of 1,041 (2.4%) failed induction therapy, showing persistent leukemic blasts in the bone marrow or at extramedullary sites.

Overall 10-year survival was 32% but varied greatly across the cohort, from 4% to 73%, depending on biological and clinical factors.

Patients with induction failure were much more likely than ALL patients as a whole to have conventional adverse prognostic factors such as a high leukocyte count, older age at disease onset, the BCR-ABL1 gene, and T-cell phenotypes – and these factors conferred an even worse prognosis in this already high-risk population.

"Indeed, the clinical and biologic characteristics of the patients in our study and the course of the disease were similar to those in patients with relapse during receipt of therapy, another group of patients with a highly unfavorable prognosis," the researchers said.

Among patients who eventually achieved a late remission, 10-year survival was significantly higher (48%) than among those who never achieved a remission (14%).

A total of 198 patients underwent hematopoietic stem-cell transplantation and 427 received chemotherapy only. The 10-year survival was 43% with transplantation and 41% without it.

Surprisingly, allogeneic transplantation was shown to be of no benefit in patients younger than 6 years who had precursor B-cell ALL with induction failure and no high-risk features, compared with chemotherapy alone. This finding has "considerable clinical implications, since transplantation is generally considered to be the standard of care for such patients," Dr. Schrappe and his colleagues said (N. Engl. J. Med. 2012;366:1371-81).

In patients aged 6 years and older who had precursor B-cell ALL, a transplant from a matched, related donor appeared to improve outcome, while other types of allogeneic transplants actually worsened outcomes. This was due in part to a high number of transplantation-related deaths in the latter group.

In contrast, allogeneic transplantation appeared to improve outcomes in the subgroup of patients who had T-cell ALL and failed induction therapy.

Patients with high hyperdiploidy (more than 50 chromosomes) showed an excellent outcome, with a 10-year survival rate of 71%. This favorable outcome "may be due to the increased sensitivity of the blast cells to methotrexate and mercaptopurine, drugs that are generally not used during remission induction but are used at high doses after remission," the investigators said.

Patients who carried the genetic aberration ETV6-RUNX1 also had a high 10-year survival of 73%, which is more than double the survival rate in the cohort as a whole.

Survival was lower among patients who had M3 marrow after induction therapy, compared with those who had M1 marrow and extramedullary disease or M2 marrow. Subgroups with the worst outcomes included patients aged 6 years or older who had M3 marrow (10-year survival, 22%) and those of any age who had T-cell ALL and M3 marrow (10-year survival, 19%).

Among infants who had precursor B-cell ALL and did not have a rearrangement of the MLL gene or fusion of the BCR-ABL1 gene, outcomes were similar to those in children aged 1-5 years (10-year survivals of 65% and 63%, respectively). In contrast, infants who had a rearrangement of the MLL gene fared very poorly (10-year survival, 4%) compared with older children who had the same genetic abnormality (10-year survival, 26%).

Numerous hospitals, charities, and government agencies supported this study. Dr. Schrappe reported ties to Medoc and EUSA Pharm; his associates reported ties to numerous industry sources.

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Whenever Hannah Valantine, MD, needs reassurance that female leadership interventions at Stanford University’s School of Medicine are working, she looks at the numbers.

We make this false assumption that your career is going to look the same throughout your life. That’s just not realistic.

—Janet Nagamine, RN, MD, SFHM, hospitalist, Kaiser Permanente Medical Center, Santa Clara, Calif., SHM board member

In the span of five to six years, the medical school has increased the percentage of women at each faculty rank so that it now surpasses national averages as calculated by the Association of American Medical Colleges. Indeed, the percentage of women at the full professor rank jumped to 22% from 14.5%.

“We really are making progress,” says Dr. Valantine, full professor of medicine and the medical school’s senior associate dean for diversity and leadership.

With structural elements, such as tenure clock extension, extended maternity and family leave, onsite childcare, early-stage research funding support, and mentoring in place, Dr. Valantine is turning her attention to the next round of interventions, which focus more on the psychological and social factors that impair women’s advancement. She will use a National Institutes of Health grant to develop interventions for the phenomenon of stereotype threat, which is the fear that one's behavior will confirm an existing stereotype about one’s social group. This fear may lead to an impairment of performance.

Over the next six months, Dr. Valantine and her team will also conduct several pilot programs involving map career customization, a model that encourages people to chart their careers over the next five to 10 to 20 years, taking into consideration their life outside of work. The intent is to help individuals identify their priorities and goals and how they change over time, and also help supervisors better match the ebbs and flows of a person’s life to the workplace and identify and develop aspiring leaders.

Stanford’s medical school is organized around teams of doctors that care for groups of patients. Each team must achieve excellence in four academic missions: clinical care, education, research, and administration. The map career customization pilot programs are aimed at helping doctors within the team plan their career paths around these four missions, then put the individual plans together in a team context in order to meet the team’s goals, says Dr. Valantine.

“This way, the work and the four missions are entirely covered,” she says. “We create a vibrant academic environment where we create new things and have time to think and integrate our life and work. … It’s a little countercultural, but I think people are crying out for that, and I think it stands a great chance of making the culture change.”

Stanford’s burgeoning efforts in map career customization have intrigued SHM board member Janet Nagamine, RN, MD, SFHM, a hospitalist at Kaiser Permanente Medical Center in Santa Clara, Calif., and Stanford alum. She hopes to collaborate with Dr. Valantine and incorporate into hospital medicine the interventions that Stanford is doing while conducting studies and developing workforce planning initiatives specific to hospitalists. The goal is to create a hospital medicine model that replicates Stanford’s success in cultivating female physician leaders.

“We make this false assumption that your career is going to look the same throughout your life,” Dr. Nagamine says. “That’s just not realistic.”

Lisa Ryan is a freelance writer in New Jersey.

Whenever Hannah Valantine, MD, needs reassurance that female leadership interventions at Stanford University’s School of Medicine are working, she looks at the numbers.

We make this false assumption that your career is going to look the same throughout your life. That’s just not realistic.

—Janet Nagamine, RN, MD, SFHM, hospitalist, Kaiser Permanente Medical Center, Santa Clara, Calif., SHM board member

In the span of five to six years, the medical school has increased the percentage of women at each faculty rank so that it now surpasses national averages as calculated by the Association of American Medical Colleges. Indeed, the percentage of women at the full professor rank jumped to 22% from 14.5%.

“We really are making progress,” says Dr. Valantine, full professor of medicine and the medical school’s senior associate dean for diversity and leadership.

With structural elements, such as tenure clock extension, extended maternity and family leave, onsite childcare, early-stage research funding support, and mentoring in place, Dr. Valantine is turning her attention to the next round of interventions, which focus more on the psychological and social factors that impair women’s advancement. She will use a National Institutes of Health grant to develop interventions for the phenomenon of stereotype threat, which is the fear that one's behavior will confirm an existing stereotype about one’s social group. This fear may lead to an impairment of performance.

Over the next six months, Dr. Valantine and her team will also conduct several pilot programs involving map career customization, a model that encourages people to chart their careers over the next five to 10 to 20 years, taking into consideration their life outside of work. The intent is to help individuals identify their priorities and goals and how they change over time, and also help supervisors better match the ebbs and flows of a person’s life to the workplace and identify and develop aspiring leaders.

Stanford’s medical school is organized around teams of doctors that care for groups of patients. Each team must achieve excellence in four academic missions: clinical care, education, research, and administration. The map career customization pilot programs are aimed at helping doctors within the team plan their career paths around these four missions, then put the individual plans together in a team context in order to meet the team’s goals, says Dr. Valantine.

“This way, the work and the four missions are entirely covered,” she says. “We create a vibrant academic environment where we create new things and have time to think and integrate our life and work. … It’s a little countercultural, but I think people are crying out for that, and I think it stands a great chance of making the culture change.”

Stanford’s burgeoning efforts in map career customization have intrigued SHM board member Janet Nagamine, RN, MD, SFHM, a hospitalist at Kaiser Permanente Medical Center in Santa Clara, Calif., and Stanford alum. She hopes to collaborate with Dr. Valantine and incorporate into hospital medicine the interventions that Stanford is doing while conducting studies and developing workforce planning initiatives specific to hospitalists. The goal is to create a hospital medicine model that replicates Stanford’s success in cultivating female physician leaders.

“We make this false assumption that your career is going to look the same throughout your life,” Dr. Nagamine says. “That’s just not realistic.”

Lisa Ryan is a freelance writer in New Jersey.

Whenever Hannah Valantine, MD, needs reassurance that female leadership interventions at Stanford University’s School of Medicine are working, she looks at the numbers.

We make this false assumption that your career is going to look the same throughout your life. That’s just not realistic.

—Janet Nagamine, RN, MD, SFHM, hospitalist, Kaiser Permanente Medical Center, Santa Clara, Calif., SHM board member

In the span of five to six years, the medical school has increased the percentage of women at each faculty rank so that it now surpasses national averages as calculated by the Association of American Medical Colleges. Indeed, the percentage of women at the full professor rank jumped to 22% from 14.5%.

“We really are making progress,” says Dr. Valantine, full professor of medicine and the medical school’s senior associate dean for diversity and leadership.

With structural elements, such as tenure clock extension, extended maternity and family leave, onsite childcare, early-stage research funding support, and mentoring in place, Dr. Valantine is turning her attention to the next round of interventions, which focus more on the psychological and social factors that impair women’s advancement. She will use a National Institutes of Health grant to develop interventions for the phenomenon of stereotype threat, which is the fear that one's behavior will confirm an existing stereotype about one’s social group. This fear may lead to an impairment of performance.

Over the next six months, Dr. Valantine and her team will also conduct several pilot programs involving map career customization, a model that encourages people to chart their careers over the next five to 10 to 20 years, taking into consideration their life outside of work. The intent is to help individuals identify their priorities and goals and how they change over time, and also help supervisors better match the ebbs and flows of a person’s life to the workplace and identify and develop aspiring leaders.

Stanford’s medical school is organized around teams of doctors that care for groups of patients. Each team must achieve excellence in four academic missions: clinical care, education, research, and administration. The map career customization pilot programs are aimed at helping doctors within the team plan their career paths around these four missions, then put the individual plans together in a team context in order to meet the team’s goals, says Dr. Valantine.

“This way, the work and the four missions are entirely covered,” she says. “We create a vibrant academic environment where we create new things and have time to think and integrate our life and work. … It’s a little countercultural, but I think people are crying out for that, and I think it stands a great chance of making the culture change.”

Stanford’s burgeoning efforts in map career customization have intrigued SHM board member Janet Nagamine, RN, MD, SFHM, a hospitalist at Kaiser Permanente Medical Center in Santa Clara, Calif., and Stanford alum. She hopes to collaborate with Dr. Valantine and incorporate into hospital medicine the interventions that Stanford is doing while conducting studies and developing workforce planning initiatives specific to hospitalists. The goal is to create a hospital medicine model that replicates Stanford’s success in cultivating female physician leaders.

“We make this false assumption that your career is going to look the same throughout your life,” Dr. Nagamine says. “That’s just not realistic.”

Lisa Ryan is a freelance writer in New Jersey.

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A new report that suggests cognitive function tends to decline substantially when older patients are admitted to the hospital could be an opportunity for hospitalists to be proactive in developing interventional therapies to combat the deterioration.

"Cognitive Decline after Hospitalization in a Community Population of Older Persons," published last month in Neurology, found that patients' global cognitive score declined a mean of 0.031 units per year before the first hospitalization, compared with 0.075 units per year thereafter, a more-than-twofold increase. Similar declines were seen in episodic memory (a 3.3-fold increase post-hospitalization) and executive function (a 1.7-fold increase post-hospitalization), according to the survey. More severe illness, longer hospital stay, and older age were associated with even faster cognitive decline after hospitalization.

David Likosky, MD, SFHM, a hospitalist and medical director of The Evergreen Neuroscience Institute in Kirkland, Wash., and a faculty member at HM12 last week in San Diego, says that more research could identify why cognitive functions decrease, as well as assist in developing techniques and therapies that could address the issue.

"A great next step would be to assess short-term cognitive changes post-hospitalization and [watch] how those evolve in the months that follow," Dr. Likosky tells The Hospitalist. "This has implications for discharge planning, and potentially for readmission risk. The step after that will be to determine what strategies might help prevent the cognitive decline seen in the study."

Such a process, he says, has a multiple advantages: First, it can help patients and their families prepare for possible scenarios; second, it provides opportunities for hospitalists to proactively address the issue of cognitive decline.

"If we as hospitalists can intervene to change this rate of decline," says Dr. Likosky, "we can make a great difference in patients' lives."

A new report that suggests cognitive function tends to decline substantially when older patients are admitted to the hospital could be an opportunity for hospitalists to be proactive in developing interventional therapies to combat the deterioration.

"Cognitive Decline after Hospitalization in a Community Population of Older Persons," published last month in Neurology, found that patients' global cognitive score declined a mean of 0.031 units per year before the first hospitalization, compared with 0.075 units per year thereafter, a more-than-twofold increase. Similar declines were seen in episodic memory (a 3.3-fold increase post-hospitalization) and executive function (a 1.7-fold increase post-hospitalization), according to the survey. More severe illness, longer hospital stay, and older age were associated with even faster cognitive decline after hospitalization.

David Likosky, MD, SFHM, a hospitalist and medical director of The Evergreen Neuroscience Institute in Kirkland, Wash., and a faculty member at HM12 last week in San Diego, says that more research could identify why cognitive functions decrease, as well as assist in developing techniques and therapies that could address the issue.

"A great next step would be to assess short-term cognitive changes post-hospitalization and [watch] how those evolve in the months that follow," Dr. Likosky tells The Hospitalist. "This has implications for discharge planning, and potentially for readmission risk. The step after that will be to determine what strategies might help prevent the cognitive decline seen in the study."

Such a process, he says, has a multiple advantages: First, it can help patients and their families prepare for possible scenarios; second, it provides opportunities for hospitalists to proactively address the issue of cognitive decline.

"If we as hospitalists can intervene to change this rate of decline," says Dr. Likosky, "we can make a great difference in patients' lives."

A new report that suggests cognitive function tends to decline substantially when older patients are admitted to the hospital could be an opportunity for hospitalists to be proactive in developing interventional therapies to combat the deterioration.

"Cognitive Decline after Hospitalization in a Community Population of Older Persons," published last month in Neurology, found that patients' global cognitive score declined a mean of 0.031 units per year before the first hospitalization, compared with 0.075 units per year thereafter, a more-than-twofold increase. Similar declines were seen in episodic memory (a 3.3-fold increase post-hospitalization) and executive function (a 1.7-fold increase post-hospitalization), according to the survey. More severe illness, longer hospital stay, and older age were associated with even faster cognitive decline after hospitalization.

David Likosky, MD, SFHM, a hospitalist and medical director of The Evergreen Neuroscience Institute in Kirkland, Wash., and a faculty member at HM12 last week in San Diego, says that more research could identify why cognitive functions decrease, as well as assist in developing techniques and therapies that could address the issue.

"A great next step would be to assess short-term cognitive changes post-hospitalization and [watch] how those evolve in the months that follow," Dr. Likosky tells The Hospitalist. "This has implications for discharge planning, and potentially for readmission risk. The step after that will be to determine what strategies might help prevent the cognitive decline seen in the study."

Such a process, he says, has a multiple advantages: First, it can help patients and their families prepare for possible scenarios; second, it provides opportunities for hospitalists to proactively address the issue of cognitive decline.

"If we as hospitalists can intervene to change this rate of decline," says Dr. Likosky, "we can make a great difference in patients' lives."

Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?

Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.

Study design: Prospective cohort.

Setting: Parkland Memorial Hospital, Dallas.

Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.

Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.

Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.

Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?

Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.

Study design: Prospective cohort.

Setting: Parkland Memorial Hospital, Dallas.

Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.

Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.

Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.

Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?

Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.

Study design: Prospective cohort.

Setting: Parkland Memorial Hospital, Dallas.

Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.

Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.

Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.

Pudendal neuralgia is an important but often unrecognized and undiagnosed cause of pelvic floor pain.

Its incidence is unknown, and there is relatively little data and scientific evidence in the literature on its diagnosis and treatment. However, I believe that a significant number of women who have burning pain in the vulva, clitoris, vagina, perineum, or rectum – including women who are diagnosed with interstitial cystitis, pelvic floor muscle spasms, vulvodynia, or other conditions – may in fact have pudendal neuralgia.

Indeed, pudendal neuralgia is largely a diagnosis of exclusion, and such conditions often must be ruled out. But the neuropathic condition should be suspected in women who have burning pain in any area along the distribution of the pudendal nerve. Awareness of the nerve’s anatomy and distribution, and of the hallmark characteristics and symptoms of pudendal neuralgia, is important, because earlier identification and treatment appears to provide better outcomes.

Pudendal neuralgia is but one type of pelvic neuralgia; neuropathic pain in the pelvic region also can stem from injury to the obturator, ilioinguinal, iliohypogastric, or genitofemoral nerves, for instance. Most of the patients in our practice, however, have pudendal neuralgia caused by mechanical compression – what is referred to as pudendal nerve entrapment – rather than disease of the nerve.

The condition is sometimes referred to as cyclist syndrome because, historically, the first documented group of patients with symptoms of pudendal neuralgia was competitive cyclists. There is a misconception, however, that the condition only occurs in cyclists. In fact, pudendal neuralgia and pudendal nerve entrapment specifically may be caused by various forms of pelvic trauma, from vaginal delivery (with or without instrumentation) and heavy lifting or falls on the back or pelvis, to previous gynecologic surgery, such as hysterectomy, cystocele repair, and mesh procedures for prolapse and incontinence.

Pudendal neuralgia is multifactorial, involving not only compression of the nerve, for instance, but also muscle spasm and peripheral and central sensitization of pain. Treatment involves a progression of conservative therapies followed by decompression surgery when these conservative treatments fail. We have made several modifications to the transgluteal approach as it was originally described, and believe this approach affords the best outcomes.

Anatomy and Symptoms

Images courtesy Dr. Michael Hibner

The pudendal nerve originates in the S2-S4 sacral foramina, and divides into three branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve. The nerve thus innervates the clitoris, vulva, labia, vagina, perineum, and rectum. Pain can be present along the entire nerve, or localized to the sites of nerve innervation. Symptoms can be unilateral or bilateral, although with bilateral pain there usually is a more affected side.

In most cases, patients will describe neuropathic pain – a burning, tingling, or numbing pain – that is worse with sitting, and less severe or absent when standing or lying down.

Initially, pain may be present only with sitting, but with time pain becomes more constant and severely aggravated by sitting. Many of my patients cannot tolerate sitting at all. Interestingly, patients usually report less pain when sitting on a toilet seat, a phenomenon that we believe is associated with pressure being applied to the ischial tuberosities rather than to the pelvic floor muscles. Pain usually gets progressively worse through the day.

Patients often will report the sensation of having a foreign body, frequently described as a golf ball or tennis ball, in the vagina, perineum, or rectum.

Pain with urination and/or bowel movements, and problems with frequency and urgency, also are often reported, as is pain with intercourse. Dyspareunia may be associated with penetration, sexual arousal, or orgasm, or any combination. Some patients report feeling persistent sexual arousal.

Occasionally, patients report having pain in regions outside the areas of innervation for the pudendal nerve, such as the lower back or posterior thigh. The presence of sciatica, or pain that radiates down the leg, for instance, should not rule out consideration of pudendal neuralgia.

Just as worsening pain with sitting is a defining characteristic, almost all patients also have an acute onset of discomfort or pain; their pain can be traced to some type of traumatic event.

One of my recent patients, for instance, was in a gym class doing a lunge with barbells on her shoulders when her legs gave out and she experienced the start of continuous pain in her vulvar area. Many of our patients trace the onset of their symptoms to immediately after gynecologic surgery, particularly vaginal procedures for prolapse or incontinence. (The pain in these cases is frequently attributed to normal postoperative pain.) Some patients report a more gradual onset of symptoms after surgery.

The pudendal nerve can be compressed in various locations along its course. The nerve runs between the sacrospinous and sacrotuberous ligaments, for instance, and entrapment between these two ligaments is probably the most common cause of pudendal neuralgia. This is where the nerve is compressed by the suturing of mesh placed during prolapse/incontinence surgery.

Another area of compression is Alcock’s canal; entrapment here is characteristic of pudendal neuralgia following vaginal childbirth. Compression also can occur where the clitoral nerve continues underneath the pubic ramus to the clitoris; this is typically where the nerve is compressed by a bicycle seat.

Diagnosis

The most important element of the diagnosis of pudendal neuralgia is the history, particularly regarding the onset of pain, the location of pain, and the nature of symptoms.

History and physical examination both are important for ruling out other reasons for pain, including vulvodynia, pelvic floor tension muscle spasm, and interstitial cystitis. A pelvic exam often will reveal significant tenderness in the pelvic floor muscles, especially in the area of the sacrospinous ligaments. Patients with pudendal neuralgia often have a trigger point – a place of maximal tenderness and pain – at the ischial spine. Palpation of this area to produce what’s known as a Tinel’s sign (with pain and symptoms) thus should be part of the exam.

Also key to diagnosis are computed tomography–guided blocks of the pudendal nerve. In our practice, we consider any degree of pain relief, for any duration of time after the block, as supportive of a diagnosis of pudendal neuralgia. Patients who do not experience immediate relief from a block are thought not to have the condition. These image-guided blocks must be performed by experienced interventional radiologists with a local anesthetic.

To date, there are no imaging studies that are reliable for diagnosis. Ongoing advances in magnetic resonance imaging (MRI) and magnetic resonance neurography (MRN) may make these modalities valuable in the future, but currently these techniques yield too many false negative results. Pudendal nerve motor terminal latency, which measures the conduction velocity of electrical impulses, is not useful given a high rate of intra- and interobserver variability and variations among patients who have had previous vaginal deliveries or pelvic surgery. Sensory threshold testing also has questionable reliability.

Initial Treatments

The initial approach to pudendal neuralgia should be conservative. Surgical decompression is the treatment of choice in patients with likely nerve entrapment, but determining the likelihood and extent of entrapment is a process. First, time must be spent in trying to identify and address the factors causing pain, and in trying to break the vicious cycle that occurs when neuropathic pain causes spasm of the pelvic floor muscles, which in turn leads to increased compression of the nerve and subsequent increases in pain levels.

While there are no official treatment algorithms, we have found – based on available data and our experience in treating more than 500 patients with pudendal neuralgia – that particular therapies can lead to marked improvements for many patients.

For some patients, especially those in whom bicycling or specific exercises initially caused the pain, avoidance of activities that worsen the pain, and other lifestyle modifications, can be helpful. Medical therapy with analgesics/pain management (such as oral pregabalin) and muscle relaxants also may be helpful for some patients. We have tried all kinds of muscle relaxants and have found that a vaginal suppository combining diazepam and baclofen is superior.

The most important treatment modality, however, is pelvic floor physical therapy. Such therapy is key because many patients have significant muscle spasm and subsequent muscle shortening. Therapists who are specially trained to work with pelvic floor muscle dysfunction can address these and other problems largely through various hands-on techniques, exercises, stretching, and education. Therapists can be identified on the International Pelvic Pain Society’s website, www.pelvicpain.org.

Botulinum toxin A (Botox) injections also are often a key part of therapy for patients with significant muscle spasm. In our practice, we administer approximately 200 units in 20 injections using a pudendal nerve block needle, under anesthesia. Not only does the treatment aid in muscle relaxation (thus increasing the patient’s tolerance to physical therapy), it also helps to differentiate between pain caused solely by muscle spasm, and pain caused by nerve injury and muscle spasm.

While patients who do not have neuralgia whose pain is caused solely or almost solely by muscle spasm will benefit significantly more from Botox injections, some patients with pudendal neuralgia will benefit from occasional, repeated Botox treatment in lieu of surgical decompression therapy. Many of our patients have been receiving Botox injections every 3-4 months, for instance.

Similarly, many other patients get significant pain relief from CT-guided injections of the nerve. While an initial CT-guided injection of anesthetic and steroid serves both diagnostic and therapeutic roles, a second and third injection can be performed to deliver more steroid and anesthetic into the pudendal nerve canal (Alcock’s canal) in a patient who responded to the first injection but whose pain has returned. Again, these injections must be performed by an experienced interventional radiologist in a CT scanner.

Injections are offered 6 weeks apart, but some patients have significant pain relief for 4-5 months, or even longer, after CT-guided nerve blocks. Patients who have long-term pain relief from CT-guided blocks will not be offered decompression surgery. One of our patients, for instance, is receiving nerve blocks every 8 months as part of her treatment.

Surgical Decompression

If patients do not have sufficient pain relief from conservative therapies (relief that enables them to return to normal daily function), surgical decompression of the nerve is indicated. An estimated 30%-40% of all patients with pudendal neuralgia will benefit from surgery.

Four different procedures have been described for decompressing an entrapped pudendal nerve: transgluteal, transischiorectal, transperineal, and endoscopic.

The transgluteal approach appears to be the most effective technique, allowing the best visualization of the pudendal nerve and the greatest extent of decompression along the length of the nerve. The main concern with this approach since it was originally described by Professor Roger Robert in Nantes, France, has been the required transection of the sacrotuberous ligament and the possible impact on stability of the sacroiliac joint. In our practice, however, we have made several modifications to the approach that minimize these concerns and, we believe, are improving recovery and outcomes.

The patient is placed in a prone jackknife position, and the electrodes of a NIMS monitor (Nerve Integrity Monitoring System; Medtronic, Minneapolis, Minn.) are placed in the anal sphincter.

Images courtesy Dr. Michael Hibner

An incision of approximately 7-10 cm in length is made across the gluteal region overlying the sacrotuberous ligament. The gluteus muscles are spread, with muscle fibers separated longitudinally, and once the ligament is reached, it is transected at its narrowest point.

The pudendal nerve then can be identified immediately below the ligament with use of a surgical microscope and the NIMS. When the surface of the nerve is touched, we are alerted by the NIMS monitor (part of the nerve runs to the anal center). In some patients, the pudendal nerve may actually be attached to the anterior surface of the sacrotuberous ligament.

The nerve is then decompressed along its entire length, from the piriformis muscle and as close as possible to the spinal cord, to the distal Alcock’s canal. Neurolysis is performed along each of the nerve’s branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve – until the nerve is completely free. In our practice, we most often find the nerve entrapped between the sacrospinous and sacrotuberous ligaments, which form a sort of "V" in the pelvis.

Because the sacrospinous ligament does not serve any anatomic purpose, I transect the ligament so that I can transpose the pudendal nerve anteriorly to give it more room.

Images courtesy Dr. Michael Hibner

Repair of the sacrotuberous ligament was not traditionally performed as part of the transgluteal approach, but we believe that repair is important for stability of the sacroiliac joint. Until recently, we used a graft of cadaver tendon to repair the ligament. Now, however, we transect the ligament with a z-shaped cut; this method allows us to repair the ligament without using any cadaver tissue.

In other modifications to the traditional approach, we wrap a piece of NeuraGen Nerve Guide (Integra LifeSciences, Plainsboro, N.J.), a nerve-protecting sheath made of collagen, around the nerve to prevent the formation or reformation of scar tissue. To promote nerve healing, we then cover the nerve with platelet-rich plasma that has been prepared from the patient’s own blood. The plasma contains growth factors that stimulate the production of myelin-producing cells.

Before closure, we also place a pain pump catheter along the course of the nerve. We believe that infusion of bupivacaine for 10-20 days postoperatively decreases the risk of central sensitization to pain and allows patients to be more mobile after surgery, which we encourage. It also may reduce the risk of scar formation. When neuropathic central pain is believed to be a significant problem, as it often is in patients whose nerves have been injured by surgical mesh, we also administer ketamine. An infusion of this old anesthetic can erase or reverse the troubling phenomena of central sensitization to pain.

Images courtesy Dr. Michael Hibner

Nerve entrapment involving mesh requires lengthy surgery. While other surgeons may trim the mesh, I firmly believe in removing all the mesh because we cannot determine which part of the mesh is causing pain.

Outcomes data from France show that approximately 30%-40% of patients are pain free after surgical decompression, with another 30% reporting improvement in pain and 30% reporting no change in their pain levels (Eur. Urol. 2005;47:403-8).

At our institution, using national scientific standards for the reporting of pain and extent of pain improvement, we have found that 70% of patients who undergo transgluteal surgical decompression have at least a 20% improvement in pain. Within this broad category are a significant number of patients who are pain free, and many who report improvements of 50% or more.

Interestingly, we have found that outcomes are similar among our much smaller number of "re-do" surgical patients. Thus far we have performed approximately 20 such transgluteal procedures – 17 on patients who had re-scarring of the nerve after surgery performed at other institutions, and 3 who had surgery many years ago in our practice, before we were able to optimally visualize the entire nerve and before we made modifications to improve the procedure. Just as with our first-time surgeries, approximately 70% of patients who underwent a second procedure had at least a 20% improvement in pain.

In all cases, the pudendal nerve recovers slowly, especially when it has been entrapped and injured for a long time, and improvements in pain often do not occur until about 4 months after surgery. Improvement typically continues for some time, up to 18 months after surgery. Patients may still have pain related to muscle spasms after surgery, so continued physical therapy and/or more Botox injections are often beneficial. Patients must also, of course, continue to avoid any offending factors or activities.

Dr. Hibner is a former fellow in advanced gynecologic surgery at Mayo Clinic, Scottsdale, Ariz., and is now professor of obstetrics and gynecology, Creighton University, Omaha, Neb., and associate clinical professor of obstetrics and gynecology, University of Arizona, Tucson. He also is director of the Arizona Center for Chronic Pelvic Pain, St. Joseph’s Hospital and Medical Center, Phoenix. To review his surgical procedure, visit SurgeryU at www.aagl.org/mastercourse. Dr. Hibner reported that he has no relevant financial disclosures.

Pudendal neuralgia is an important but often unrecognized and undiagnosed cause of pelvic floor pain.

Its incidence is unknown, and there is relatively little data and scientific evidence in the literature on its diagnosis and treatment. However, I believe that a significant number of women who have burning pain in the vulva, clitoris, vagina, perineum, or rectum – including women who are diagnosed with interstitial cystitis, pelvic floor muscle spasms, vulvodynia, or other conditions – may in fact have pudendal neuralgia.

Indeed, pudendal neuralgia is largely a diagnosis of exclusion, and such conditions often must be ruled out. But the neuropathic condition should be suspected in women who have burning pain in any area along the distribution of the pudendal nerve. Awareness of the nerve’s anatomy and distribution, and of the hallmark characteristics and symptoms of pudendal neuralgia, is important, because earlier identification and treatment appears to provide better outcomes.

Pudendal neuralgia is but one type of pelvic neuralgia; neuropathic pain in the pelvic region also can stem from injury to the obturator, ilioinguinal, iliohypogastric, or genitofemoral nerves, for instance. Most of the patients in our practice, however, have pudendal neuralgia caused by mechanical compression – what is referred to as pudendal nerve entrapment – rather than disease of the nerve.

The condition is sometimes referred to as cyclist syndrome because, historically, the first documented group of patients with symptoms of pudendal neuralgia was competitive cyclists. There is a misconception, however, that the condition only occurs in cyclists. In fact, pudendal neuralgia and pudendal nerve entrapment specifically may be caused by various forms of pelvic trauma, from vaginal delivery (with or without instrumentation) and heavy lifting or falls on the back or pelvis, to previous gynecologic surgery, such as hysterectomy, cystocele repair, and mesh procedures for prolapse and incontinence.

Pudendal neuralgia is multifactorial, involving not only compression of the nerve, for instance, but also muscle spasm and peripheral and central sensitization of pain. Treatment involves a progression of conservative therapies followed by decompression surgery when these conservative treatments fail. We have made several modifications to the transgluteal approach as it was originally described, and believe this approach affords the best outcomes.

Anatomy and Symptoms

Images courtesy Dr. Michael Hibner

The pudendal nerve originates in the S2-S4 sacral foramina, and divides into three branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve. The nerve thus innervates the clitoris, vulva, labia, vagina, perineum, and rectum. Pain can be present along the entire nerve, or localized to the sites of nerve innervation. Symptoms can be unilateral or bilateral, although with bilateral pain there usually is a more affected side.

In most cases, patients will describe neuropathic pain – a burning, tingling, or numbing pain – that is worse with sitting, and less severe or absent when standing or lying down.

Initially, pain may be present only with sitting, but with time pain becomes more constant and severely aggravated by sitting. Many of my patients cannot tolerate sitting at all. Interestingly, patients usually report less pain when sitting on a toilet seat, a phenomenon that we believe is associated with pressure being applied to the ischial tuberosities rather than to the pelvic floor muscles. Pain usually gets progressively worse through the day.

Patients often will report the sensation of having a foreign body, frequently described as a golf ball or tennis ball, in the vagina, perineum, or rectum.

Pain with urination and/or bowel movements, and problems with frequency and urgency, also are often reported, as is pain with intercourse. Dyspareunia may be associated with penetration, sexual arousal, or orgasm, or any combination. Some patients report feeling persistent sexual arousal.

Occasionally, patients report having pain in regions outside the areas of innervation for the pudendal nerve, such as the lower back or posterior thigh. The presence of sciatica, or pain that radiates down the leg, for instance, should not rule out consideration of pudendal neuralgia.

Just as worsening pain with sitting is a defining characteristic, almost all patients also have an acute onset of discomfort or pain; their pain can be traced to some type of traumatic event.

One of my recent patients, for instance, was in a gym class doing a lunge with barbells on her shoulders when her legs gave out and she experienced the start of continuous pain in her vulvar area. Many of our patients trace the onset of their symptoms to immediately after gynecologic surgery, particularly vaginal procedures for prolapse or incontinence. (The pain in these cases is frequently attributed to normal postoperative pain.) Some patients report a more gradual onset of symptoms after surgery.

The pudendal nerve can be compressed in various locations along its course. The nerve runs between the sacrospinous and sacrotuberous ligaments, for instance, and entrapment between these two ligaments is probably the most common cause of pudendal neuralgia. This is where the nerve is compressed by the suturing of mesh placed during prolapse/incontinence surgery.

Another area of compression is Alcock’s canal; entrapment here is characteristic of pudendal neuralgia following vaginal childbirth. Compression also can occur where the clitoral nerve continues underneath the pubic ramus to the clitoris; this is typically where the nerve is compressed by a bicycle seat.

Diagnosis

The most important element of the diagnosis of pudendal neuralgia is the history, particularly regarding the onset of pain, the location of pain, and the nature of symptoms.

History and physical examination both are important for ruling out other reasons for pain, including vulvodynia, pelvic floor tension muscle spasm, and interstitial cystitis. A pelvic exam often will reveal significant tenderness in the pelvic floor muscles, especially in the area of the sacrospinous ligaments. Patients with pudendal neuralgia often have a trigger point – a place of maximal tenderness and pain – at the ischial spine. Palpation of this area to produce what’s known as a Tinel’s sign (with pain and symptoms) thus should be part of the exam.

Also key to diagnosis are computed tomography–guided blocks of the pudendal nerve. In our practice, we consider any degree of pain relief, for any duration of time after the block, as supportive of a diagnosis of pudendal neuralgia. Patients who do not experience immediate relief from a block are thought not to have the condition. These image-guided blocks must be performed by experienced interventional radiologists with a local anesthetic.

To date, there are no imaging studies that are reliable for diagnosis. Ongoing advances in magnetic resonance imaging (MRI) and magnetic resonance neurography (MRN) may make these modalities valuable in the future, but currently these techniques yield too many false negative results. Pudendal nerve motor terminal latency, which measures the conduction velocity of electrical impulses, is not useful given a high rate of intra- and interobserver variability and variations among patients who have had previous vaginal deliveries or pelvic surgery. Sensory threshold testing also has questionable reliability.

Initial Treatments

The initial approach to pudendal neuralgia should be conservative. Surgical decompression is the treatment of choice in patients with likely nerve entrapment, but determining the likelihood and extent of entrapment is a process. First, time must be spent in trying to identify and address the factors causing pain, and in trying to break the vicious cycle that occurs when neuropathic pain causes spasm of the pelvic floor muscles, which in turn leads to increased compression of the nerve and subsequent increases in pain levels.

While there are no official treatment algorithms, we have found – based on available data and our experience in treating more than 500 patients with pudendal neuralgia – that particular therapies can lead to marked improvements for many patients.

For some patients, especially those in whom bicycling or specific exercises initially caused the pain, avoidance of activities that worsen the pain, and other lifestyle modifications, can be helpful. Medical therapy with analgesics/pain management (such as oral pregabalin) and muscle relaxants also may be helpful for some patients. We have tried all kinds of muscle relaxants and have found that a vaginal suppository combining diazepam and baclofen is superior.

The most important treatment modality, however, is pelvic floor physical therapy. Such therapy is key because many patients have significant muscle spasm and subsequent muscle shortening. Therapists who are specially trained to work with pelvic floor muscle dysfunction can address these and other problems largely through various hands-on techniques, exercises, stretching, and education. Therapists can be identified on the International Pelvic Pain Society’s website, www.pelvicpain.org.

Botulinum toxin A (Botox) injections also are often a key part of therapy for patients with significant muscle spasm. In our practice, we administer approximately 200 units in 20 injections using a pudendal nerve block needle, under anesthesia. Not only does the treatment aid in muscle relaxation (thus increasing the patient’s tolerance to physical therapy), it also helps to differentiate between pain caused solely by muscle spasm, and pain caused by nerve injury and muscle spasm.

While patients who do not have neuralgia whose pain is caused solely or almost solely by muscle spasm will benefit significantly more from Botox injections, some patients with pudendal neuralgia will benefit from occasional, repeated Botox treatment in lieu of surgical decompression therapy. Many of our patients have been receiving Botox injections every 3-4 months, for instance.

Similarly, many other patients get significant pain relief from CT-guided injections of the nerve. While an initial CT-guided injection of anesthetic and steroid serves both diagnostic and therapeutic roles, a second and third injection can be performed to deliver more steroid and anesthetic into the pudendal nerve canal (Alcock’s canal) in a patient who responded to the first injection but whose pain has returned. Again, these injections must be performed by an experienced interventional radiologist in a CT scanner.

Injections are offered 6 weeks apart, but some patients have significant pain relief for 4-5 months, or even longer, after CT-guided nerve blocks. Patients who have long-term pain relief from CT-guided blocks will not be offered decompression surgery. One of our patients, for instance, is receiving nerve blocks every 8 months as part of her treatment.

Surgical Decompression

If patients do not have sufficient pain relief from conservative therapies (relief that enables them to return to normal daily function), surgical decompression of the nerve is indicated. An estimated 30%-40% of all patients with pudendal neuralgia will benefit from surgery.

Four different procedures have been described for decompressing an entrapped pudendal nerve: transgluteal, transischiorectal, transperineal, and endoscopic.

The transgluteal approach appears to be the most effective technique, allowing the best visualization of the pudendal nerve and the greatest extent of decompression along the length of the nerve. The main concern with this approach since it was originally described by Professor Roger Robert in Nantes, France, has been the required transection of the sacrotuberous ligament and the possible impact on stability of the sacroiliac joint. In our practice, however, we have made several modifications to the approach that minimize these concerns and, we believe, are improving recovery and outcomes.

The patient is placed in a prone jackknife position, and the electrodes of a NIMS monitor (Nerve Integrity Monitoring System; Medtronic, Minneapolis, Minn.) are placed in the anal sphincter.

Images courtesy Dr. Michael Hibner

An incision of approximately 7-10 cm in length is made across the gluteal region overlying the sacrotuberous ligament. The gluteus muscles are spread, with muscle fibers separated longitudinally, and once the ligament is reached, it is transected at its narrowest point.

The pudendal nerve then can be identified immediately below the ligament with use of a surgical microscope and the NIMS. When the surface of the nerve is touched, we are alerted by the NIMS monitor (part of the nerve runs to the anal center). In some patients, the pudendal nerve may actually be attached to the anterior surface of the sacrotuberous ligament.

The nerve is then decompressed along its entire length, from the piriformis muscle and as close as possible to the spinal cord, to the distal Alcock’s canal. Neurolysis is performed along each of the nerve’s branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve – until the nerve is completely free. In our practice, we most often find the nerve entrapped between the sacrospinous and sacrotuberous ligaments, which form a sort of "V" in the pelvis.

Because the sacrospinous ligament does not serve any anatomic purpose, I transect the ligament so that I can transpose the pudendal nerve anteriorly to give it more room.

Images courtesy Dr. Michael Hibner

Repair of the sacrotuberous ligament was not traditionally performed as part of the transgluteal approach, but we believe that repair is important for stability of the sacroiliac joint. Until recently, we used a graft of cadaver tendon to repair the ligament. Now, however, we transect the ligament with a z-shaped cut; this method allows us to repair the ligament without using any cadaver tissue.

In other modifications to the traditional approach, we wrap a piece of NeuraGen Nerve Guide (Integra LifeSciences, Plainsboro, N.J.), a nerve-protecting sheath made of collagen, around the nerve to prevent the formation or reformation of scar tissue. To promote nerve healing, we then cover the nerve with platelet-rich plasma that has been prepared from the patient’s own blood. The plasma contains growth factors that stimulate the production of myelin-producing cells.

Before closure, we also place a pain pump catheter along the course of the nerve. We believe that infusion of bupivacaine for 10-20 days postoperatively decreases the risk of central sensitization to pain and allows patients to be more mobile after surgery, which we encourage. It also may reduce the risk of scar formation. When neuropathic central pain is believed to be a significant problem, as it often is in patients whose nerves have been injured by surgical mesh, we also administer ketamine. An infusion of this old anesthetic can erase or reverse the troubling phenomena of central sensitization to pain.

Images courtesy Dr. Michael Hibner

Nerve entrapment involving mesh requires lengthy surgery. While other surgeons may trim the mesh, I firmly believe in removing all the mesh because we cannot determine which part of the mesh is causing pain.

Outcomes data from France show that approximately 30%-40% of patients are pain free after surgical decompression, with another 30% reporting improvement in pain and 30% reporting no change in their pain levels (Eur. Urol. 2005;47:403-8).

At our institution, using national scientific standards for the reporting of pain and extent of pain improvement, we have found that 70% of patients who undergo transgluteal surgical decompression have at least a 20% improvement in pain. Within this broad category are a significant number of patients who are pain free, and many who report improvements of 50% or more.

Interestingly, we have found that outcomes are similar among our much smaller number of "re-do" surgical patients. Thus far we have performed approximately 20 such transgluteal procedures – 17 on patients who had re-scarring of the nerve after surgery performed at other institutions, and 3 who had surgery many years ago in our practice, before we were able to optimally visualize the entire nerve and before we made modifications to improve the procedure. Just as with our first-time surgeries, approximately 70% of patients who underwent a second procedure had at least a 20% improvement in pain.

In all cases, the pudendal nerve recovers slowly, especially when it has been entrapped and injured for a long time, and improvements in pain often do not occur until about 4 months after surgery. Improvement typically continues for some time, up to 18 months after surgery. Patients may still have pain related to muscle spasms after surgery, so continued physical therapy and/or more Botox injections are often beneficial. Patients must also, of course, continue to avoid any offending factors or activities.

Dr. Hibner is a former fellow in advanced gynecologic surgery at Mayo Clinic, Scottsdale, Ariz., and is now professor of obstetrics and gynecology, Creighton University, Omaha, Neb., and associate clinical professor of obstetrics and gynecology, University of Arizona, Tucson. He also is director of the Arizona Center for Chronic Pelvic Pain, St. Joseph’s Hospital and Medical Center, Phoenix. To review his surgical procedure, visit SurgeryU at www.aagl.org/mastercourse. Dr. Hibner reported that he has no relevant financial disclosures.

Pudendal neuralgia is an important but often unrecognized and undiagnosed cause of pelvic floor pain.

Its incidence is unknown, and there is relatively little data and scientific evidence in the literature on its diagnosis and treatment. However, I believe that a significant number of women who have burning pain in the vulva, clitoris, vagina, perineum, or rectum – including women who are diagnosed with interstitial cystitis, pelvic floor muscle spasms, vulvodynia, or other conditions – may in fact have pudendal neuralgia.

Indeed, pudendal neuralgia is largely a diagnosis of exclusion, and such conditions often must be ruled out. But the neuropathic condition should be suspected in women who have burning pain in any area along the distribution of the pudendal nerve. Awareness of the nerve’s anatomy and distribution, and of the hallmark characteristics and symptoms of pudendal neuralgia, is important, because earlier identification and treatment appears to provide better outcomes.

Pudendal neuralgia is but one type of pelvic neuralgia; neuropathic pain in the pelvic region also can stem from injury to the obturator, ilioinguinal, iliohypogastric, or genitofemoral nerves, for instance. Most of the patients in our practice, however, have pudendal neuralgia caused by mechanical compression – what is referred to as pudendal nerve entrapment – rather than disease of the nerve.

The condition is sometimes referred to as cyclist syndrome because, historically, the first documented group of patients with symptoms of pudendal neuralgia was competitive cyclists. There is a misconception, however, that the condition only occurs in cyclists. In fact, pudendal neuralgia and pudendal nerve entrapment specifically may be caused by various forms of pelvic trauma, from vaginal delivery (with or without instrumentation) and heavy lifting or falls on the back or pelvis, to previous gynecologic surgery, such as hysterectomy, cystocele repair, and mesh procedures for prolapse and incontinence.

Pudendal neuralgia is multifactorial, involving not only compression of the nerve, for instance, but also muscle spasm and peripheral and central sensitization of pain. Treatment involves a progression of conservative therapies followed by decompression surgery when these conservative treatments fail. We have made several modifications to the transgluteal approach as it was originally described, and believe this approach affords the best outcomes.

Anatomy and Symptoms

Images courtesy Dr. Michael Hibner

The pudendal nerve originates in the S2-S4 sacral foramina, and divides into three branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve. The nerve thus innervates the clitoris, vulva, labia, vagina, perineum, and rectum. Pain can be present along the entire nerve, or localized to the sites of nerve innervation. Symptoms can be unilateral or bilateral, although with bilateral pain there usually is a more affected side.

In most cases, patients will describe neuropathic pain – a burning, tingling, or numbing pain – that is worse with sitting, and less severe or absent when standing or lying down.

Initially, pain may be present only with sitting, but with time pain becomes more constant and severely aggravated by sitting. Many of my patients cannot tolerate sitting at all. Interestingly, patients usually report less pain when sitting on a toilet seat, a phenomenon that we believe is associated with pressure being applied to the ischial tuberosities rather than to the pelvic floor muscles. Pain usually gets progressively worse through the day.

Patients often will report the sensation of having a foreign body, frequently described as a golf ball or tennis ball, in the vagina, perineum, or rectum.

Pain with urination and/or bowel movements, and problems with frequency and urgency, also are often reported, as is pain with intercourse. Dyspareunia may be associated with penetration, sexual arousal, or orgasm, or any combination. Some patients report feeling persistent sexual arousal.

Occasionally, patients report having pain in regions outside the areas of innervation for the pudendal nerve, such as the lower back or posterior thigh. The presence of sciatica, or pain that radiates down the leg, for instance, should not rule out consideration of pudendal neuralgia.

Just as worsening pain with sitting is a defining characteristic, almost all patients also have an acute onset of discomfort or pain; their pain can be traced to some type of traumatic event.

One of my recent patients, for instance, was in a gym class doing a lunge with barbells on her shoulders when her legs gave out and she experienced the start of continuous pain in her vulvar area. Many of our patients trace the onset of their symptoms to immediately after gynecologic surgery, particularly vaginal procedures for prolapse or incontinence. (The pain in these cases is frequently attributed to normal postoperative pain.) Some patients report a more gradual onset of symptoms after surgery.

The pudendal nerve can be compressed in various locations along its course. The nerve runs between the sacrospinous and sacrotuberous ligaments, for instance, and entrapment between these two ligaments is probably the most common cause of pudendal neuralgia. This is where the nerve is compressed by the suturing of mesh placed during prolapse/incontinence surgery.

Another area of compression is Alcock’s canal; entrapment here is characteristic of pudendal neuralgia following vaginal childbirth. Compression also can occur where the clitoral nerve continues underneath the pubic ramus to the clitoris; this is typically where the nerve is compressed by a bicycle seat.

Diagnosis

The most important element of the diagnosis of pudendal neuralgia is the history, particularly regarding the onset of pain, the location of pain, and the nature of symptoms.

History and physical examination both are important for ruling out other reasons for pain, including vulvodynia, pelvic floor tension muscle spasm, and interstitial cystitis. A pelvic exam often will reveal significant tenderness in the pelvic floor muscles, especially in the area of the sacrospinous ligaments. Patients with pudendal neuralgia often have a trigger point – a place of maximal tenderness and pain – at the ischial spine. Palpation of this area to produce what’s known as a Tinel’s sign (with pain and symptoms) thus should be part of the exam.

Also key to diagnosis are computed tomography–guided blocks of the pudendal nerve. In our practice, we consider any degree of pain relief, for any duration of time after the block, as supportive of a diagnosis of pudendal neuralgia. Patients who do not experience immediate relief from a block are thought not to have the condition. These image-guided blocks must be performed by experienced interventional radiologists with a local anesthetic.

To date, there are no imaging studies that are reliable for diagnosis. Ongoing advances in magnetic resonance imaging (MRI) and magnetic resonance neurography (MRN) may make these modalities valuable in the future, but currently these techniques yield too many false negative results. Pudendal nerve motor terminal latency, which measures the conduction velocity of electrical impulses, is not useful given a high rate of intra- and interobserver variability and variations among patients who have had previous vaginal deliveries or pelvic surgery. Sensory threshold testing also has questionable reliability.

Initial Treatments

The initial approach to pudendal neuralgia should be conservative. Surgical decompression is the treatment of choice in patients with likely nerve entrapment, but determining the likelihood and extent of entrapment is a process. First, time must be spent in trying to identify and address the factors causing pain, and in trying to break the vicious cycle that occurs when neuropathic pain causes spasm of the pelvic floor muscles, which in turn leads to increased compression of the nerve and subsequent increases in pain levels.

While there are no official treatment algorithms, we have found – based on available data and our experience in treating more than 500 patients with pudendal neuralgia – that particular therapies can lead to marked improvements for many patients.

For some patients, especially those in whom bicycling or specific exercises initially caused the pain, avoidance of activities that worsen the pain, and other lifestyle modifications, can be helpful. Medical therapy with analgesics/pain management (such as oral pregabalin) and muscle relaxants also may be helpful for some patients. We have tried all kinds of muscle relaxants and have found that a vaginal suppository combining diazepam and baclofen is superior.

The most important treatment modality, however, is pelvic floor physical therapy. Such therapy is key because many patients have significant muscle spasm and subsequent muscle shortening. Therapists who are specially trained to work with pelvic floor muscle dysfunction can address these and other problems largely through various hands-on techniques, exercises, stretching, and education. Therapists can be identified on the International Pelvic Pain Society’s website, www.pelvicpain.org.

Botulinum toxin A (Botox) injections also are often a key part of therapy for patients with significant muscle spasm. In our practice, we administer approximately 200 units in 20 injections using a pudendal nerve block needle, under anesthesia. Not only does the treatment aid in muscle relaxation (thus increasing the patient’s tolerance to physical therapy), it also helps to differentiate between pain caused solely by muscle spasm, and pain caused by nerve injury and muscle spasm.

While patients who do not have neuralgia whose pain is caused solely or almost solely by muscle spasm will benefit significantly more from Botox injections, some patients with pudendal neuralgia will benefit from occasional, repeated Botox treatment in lieu of surgical decompression therapy. Many of our patients have been receiving Botox injections every 3-4 months, for instance.

Similarly, many other patients get significant pain relief from CT-guided injections of the nerve. While an initial CT-guided injection of anesthetic and steroid serves both diagnostic and therapeutic roles, a second and third injection can be performed to deliver more steroid and anesthetic into the pudendal nerve canal (Alcock’s canal) in a patient who responded to the first injection but whose pain has returned. Again, these injections must be performed by an experienced interventional radiologist in a CT scanner.

Injections are offered 6 weeks apart, but some patients have significant pain relief for 4-5 months, or even longer, after CT-guided nerve blocks. Patients who have long-term pain relief from CT-guided blocks will not be offered decompression surgery. One of our patients, for instance, is receiving nerve blocks every 8 months as part of her treatment.

Surgical Decompression

If patients do not have sufficient pain relief from conservative therapies (relief that enables them to return to normal daily function), surgical decompression of the nerve is indicated. An estimated 30%-40% of all patients with pudendal neuralgia will benefit from surgery.

Four different procedures have been described for decompressing an entrapped pudendal nerve: transgluteal, transischiorectal, transperineal, and endoscopic.

The transgluteal approach appears to be the most effective technique, allowing the best visualization of the pudendal nerve and the greatest extent of decompression along the length of the nerve. The main concern with this approach since it was originally described by Professor Roger Robert in Nantes, France, has been the required transection of the sacrotuberous ligament and the possible impact on stability of the sacroiliac joint. In our practice, however, we have made several modifications to the approach that minimize these concerns and, we believe, are improving recovery and outcomes.

The patient is placed in a prone jackknife position, and the electrodes of a NIMS monitor (Nerve Integrity Monitoring System; Medtronic, Minneapolis, Minn.) are placed in the anal sphincter.

Images courtesy Dr. Michael Hibner

An incision of approximately 7-10 cm in length is made across the gluteal region overlying the sacrotuberous ligament. The gluteus muscles are spread, with muscle fibers separated longitudinally, and once the ligament is reached, it is transected at its narrowest point.

The pudendal nerve then can be identified immediately below the ligament with use of a surgical microscope and the NIMS. When the surface of the nerve is touched, we are alerted by the NIMS monitor (part of the nerve runs to the anal center). In some patients, the pudendal nerve may actually be attached to the anterior surface of the sacrotuberous ligament.

The nerve is then decompressed along its entire length, from the piriformis muscle and as close as possible to the spinal cord, to the distal Alcock’s canal. Neurolysis is performed along each of the nerve’s branches – the inferior rectal nerve, the perineal nerve, and the dorsal clitoral nerve – until the nerve is completely free. In our practice, we most often find the nerve entrapped between the sacrospinous and sacrotuberous ligaments, which form a sort of "V" in the pelvis.

Because the sacrospinous ligament does not serve any anatomic purpose, I transect the ligament so that I can transpose the pudendal nerve anteriorly to give it more room.

Images courtesy Dr. Michael Hibner

Repair of the sacrotuberous ligament was not traditionally performed as part of the transgluteal approach, but we believe that repair is important for stability of the sacroiliac joint. Until recently, we used a graft of cadaver tendon to repair the ligament. Now, however, we transect the ligament with a z-shaped cut; this method allows us to repair the ligament without using any cadaver tissue.

In other modifications to the traditional approach, we wrap a piece of NeuraGen Nerve Guide (Integra LifeSciences, Plainsboro, N.J.), a nerve-protecting sheath made of collagen, around the nerve to prevent the formation or reformation of scar tissue. To promote nerve healing, we then cover the nerve with platelet-rich plasma that has been prepared from the patient’s own blood. The plasma contains growth factors that stimulate the production of myelin-producing cells.

Before closure, we also place a pain pump catheter along the course of the nerve. We believe that infusion of bupivacaine for 10-20 days postoperatively decreases the risk of central sensitization to pain and allows patients to be more mobile after surgery, which we encourage. It also may reduce the risk of scar formation. When neuropathic central pain is believed to be a significant problem, as it often is in patients whose nerves have been injured by surgical mesh, we also administer ketamine. An infusion of this old anesthetic can erase or reverse the troubling phenomena of central sensitization to pain.

Images courtesy Dr. Michael Hibner

Nerve entrapment involving mesh requires lengthy surgery. While other surgeons may trim the mesh, I firmly believe in removing all the mesh because we cannot determine which part of the mesh is causing pain.

Outcomes data from France show that approximately 30%-40% of patients are pain free after surgical decompression, with another 30% reporting improvement in pain and 30% reporting no change in their pain levels (Eur. Urol. 2005;47:403-8).

At our institution, using national scientific standards for the reporting of pain and extent of pain improvement, we have found that 70% of patients who undergo transgluteal surgical decompression have at least a 20% improvement in pain. Within this broad category are a significant number of patients who are pain free, and many who report improvements of 50% or more.

Interestingly, we have found that outcomes are similar among our much smaller number of "re-do" surgical patients. Thus far we have performed approximately 20 such transgluteal procedures – 17 on patients who had re-scarring of the nerve after surgery performed at other institutions, and 3 who had surgery many years ago in our practice, before we were able to optimally visualize the entire nerve and before we made modifications to improve the procedure. Just as with our first-time surgeries, approximately 70% of patients who underwent a second procedure had at least a 20% improvement in pain.

In all cases, the pudendal nerve recovers slowly, especially when it has been entrapped and injured for a long time, and improvements in pain often do not occur until about 4 months after surgery. Improvement typically continues for some time, up to 18 months after surgery. Patients may still have pain related to muscle spasms after surgery, so continued physical therapy and/or more Botox injections are often beneficial. Patients must also, of course, continue to avoid any offending factors or activities.

Dr. Hibner is a former fellow in advanced gynecologic surgery at Mayo Clinic, Scottsdale, Ariz., and is now professor of obstetrics and gynecology, Creighton University, Omaha, Neb., and associate clinical professor of obstetrics and gynecology, University of Arizona, Tucson. He also is director of the Arizona Center for Chronic Pelvic Pain, St. Joseph’s Hospital and Medical Center, Phoenix. To review his surgical procedure, visit SurgeryU at www.aagl.org/mastercourse. Dr. Hibner reported that he has no relevant financial disclosures.