Opinion

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two phase 2 trials in stage IV non–small cell lung cancer (NSCLC) patients that appeared recently in JAMA Oncology. One summarizes a trial in stage IV NSCLC with four or fewer sites of metastasis (oligometastatic disease or OM), in which pembrolizumab is added to locally ablative therapy (LAT). The other examines whether LAT potentiates the response to immuno-oncology (I/O) in distant sites that were unexposed to LAT.

©Sergey Nivens/thinkstockphotos

I/O added to LAT in OM-NSCLC

Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues, published findings from a nonrandomized phase 2 trial in OM-NSCLC in which patients could receive LAT by any technique (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449). Patients could have synchronous or metachronous OM-NSCLC, any histology, and any PD-L1 tumor proportion score. Patients with more than four sites of metastatic disease that regressed to OM-NSCLC after prior therapy (i.e., “oligoremnant NSCLC”) were excluded.

They reported on 51 patients who received conventional-dose pembrolizumab for eight cycles after LAT. Patients without toxicity or progression were allowed to receive up to eight additional cycles of pembrolizumab. The median progression-free survival (PFS) was 19.1 months (95% confidence interval, 9.4-28.7 months), significantly longer than the historical comparison group (median PFS, 6.6 months; P = .005). Additionally, the 24-month overall survival (OS) was 77.5%. With respect to safety, no quality of life decrement or new safety signals were seen.
 

What this means in practice

As Dr. Bauml and colleagues suggest, there is strong theoretical rationale for believing that OM-NSCLC represents a special, potentially curable, population of stage IV NSCLC patients. Like the recently published work of Daniel R. Gomez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues (J Clin Oncol. 2019 Jun 20;37[18]:1558-65), who studied LAT in comparison with consolidative/maintenance chemotherapy in a slightly different population of OM-NSCLC patients, the current trial moves clinical research forward.

Practically, this study has limitations that should temper a clinician’s enthusiasm for adopting the strategy of LAT, followed by I/O, as standard practice: small patient numbers, most with only one site of OM-NSCLC; comparison with historical controls; and no meaningful information about patient subsets who benefit from I/O and who do not. As the authors suggest, this study provides a strong rationale for a phase 3 trial with stratification for variables that could influence outcome. It does not inform clinical practice at the present time.
 

LAT added to I/O in stage IV NSCLC

We have limited ability to identify (the majority of) patients with metastatic NSCLC who will not benefit from I/O and no proven interventions to augment benefit in (the majority of) patients with low PD-L1 tumor proportion scores and/or low tumor mutation burden. However, the PEMBRO-RT study was designed to investigate whether LAT with stereotactic body radiation therapy (SBRT) could exploit the hypothesized increase in tumor antigen release and antigen presentation that could lead to better responses to I/O in untreated sites of disease among all patients with stage IV NSCLC.

As reported by Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues, the PEMBRO-RT study randomized 76 patients with stage IV NSCLC to pembro following SBRT to a single metastatic site (the experimental arm of the trial) or pembrolizumab alone. Pembrolizumab was given in a conventional dose and schedule in both arms of the trial and was administered within 7 days after SBRT on the experimental arm (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478).

The primary outcome was the overall response rate (ORR) at 12 weeks. Among patients on the experimental versus control arms, the ORR was 36% and 18%, respectively (P = .07). This did not meet the prespecified endpoint of improving ORR from 20% to 50% at 12 weeks. Additionally, although improved on the pembro plus SBRT arm of the trial, the median PFS and OS did not meet statistical criteria for improvement over the control arm, except among the 47 patients in the PD-L1 negative subset.

What this means in practice

There are a lot of potentially relevant variables in this small, randomized phase 2 study. As the authors discuss, if there is a dose and schedule of RT that facilitates antigen release and presentation and or an ideal latent period after radiotherapy that promotes an “abscopal effect” from I/O, it is unclear whether the ideal schema was used in the PEMBRO-RT trial.

At present, if a patient with stage IV NSCLC requires LAT for clinical reasons during I/O treatment, the patient can receive it safely, but without the expectation that the LAT will augment overall benefit from I/O. Additional preclinical work will need to help guide us about a rational way to design the next trial to test the concept of supra-additive benefit from these modalities. Not only is this combination “not ready for prime time” in clinical care, but it’s not ready for the large numbers of patients in a phase 3 clinical trial.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

Mr. M wanted a second opinion. He was almost 80 years old and had been healthy his entire life. But recent abdominal discomfort prompted a CT scan, which prompted a biopsy. It appeared the tumor had started in his pancreas and then spread to the lymph nodes and the wall of his abdomen.

He asked his doctor to “give it to him straight,” and she did. She told him that it was incurable, but that chemotherapy might slow it down. He asked how long he had, and she said less than a year.

He wanted a straight answer, but that wasn’t the answer he wanted. Who would? So he did some reading and decided to come to a large academic hospital an hour away for a second opinion.

I interviewed him and then scrolled through his CT scans outside the room. There were a few things we could do, the attending and I discussed. We would send his tumor for genetic testing to see if there were any cancer mutations that could be targeted with drugs more specific than standard chemotherapy. We would also refer him to our cancer genetics clinic to get his blood tested for inherited mutations.

But mostly, all of that would likely turn up negative. Mostly, we agreed with his local oncologist.

We went back in the room. Explaining the genetic testing took the length of the visit because this is not a straightforward concept. We explained the difference between tumor mutations and inherited mutations. We wrote down a list of genetic variations we could discover. We discussed treatment options that could go along with each.

Do you have any questions?

He broke down. He reached for the tissue box sitting on the exam room table. “I feel so much better,” he said. “This is why I came here.” He felt safe, reassured, and hopeful.

I was happy to be helpful, but later, as I wrote my clinic note about him, I felt uneasy about the visit.

Everything we said was true. But somehow, it still felt as though we left him with an overly optimistic view of his illness. Did our emphasis on what could be done overshadow that it was unlikely to change the big picture? Did our in-depth discussion of slim possibilities mask that his prognosis was, in fact, still grim?

Working at a large academic medical center, I see many patients who come for a second opinion. I’m incredibly fortunate to learn at a place that is not just up to date in the most cutting-edge treatments but often leading in innovation.

And so we offer patients these options. They sound novel and exciting. They fill patients with hope because they fill the field with hope. I, too, get enraptured with the possibilities – circulating tumor DNA and clinical trials and targeted therapies.

At big cancer meetings every year, oncologists come together and speak about cancer therapies with enthusiasm and hope. Advances have exploded; it’s an exciting time to be learning and practicing.

And yet, the reality for many patients is very different. We are still discussing hospice after one line of chemotherapy has failed. We are still gently holding hands and saying that we have no more options to treat their aggressive cancers.

How can both of these worlds coexist? How can both be true?

A few years ago, a friend was diagnosed with a devastating neurologic condition. I went to a clinical trials website and typed in her disease. Immediately, hundreds of options popped up. I felt hopeful. The field is moving forward, I thought. There are options.

But in the exam room, there were none. When I asked about what I had read, the neurologist explained how many of these possibilities were being investigated. But in the end, my friend really had no good options.

After my visit with Mr. M, I thought about how commonly this story plays out in my field of hematology and oncology. Yes, there are instances in which we find a mutation that drastically changes management. It’s wonderful to witness: patients handed an ominous diagnosis and then living their normal lives, in remission or with stable disease, years later.

We all hope for that. But we rarely get it. The challenge comes when we spend 95% of a visit talking about something with a 1% chance of working. The numbers don’t add up – it’s an equation that easily results in false understanding. Cancer can be glossed with a veneer of innovative options, obscuring the reality that none are likely to work.

Weaving both truths into the conversation is a difficult skill, but one I decided to be more cognizant of after my encounter with Mr. M.

At our next visit, we were still waiting on the test results. But I decided to speak with him candidly. It’s important to have a plan B, I said, and asked what would be important to him if his time were limited. He nodded, thinking about this. “I’ve just been holding out hope for the mutation,” he admitted.

The next week his genetic testing came back negative, and he decided to get palliative chemotherapy closer to home. He had no reason to come to a large academic hospital anymore. With nothing special to offer him, I never saw him again.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.

Mr. M wanted a second opinion. He was almost 80 years old and had been healthy his entire life. But recent abdominal discomfort prompted a CT scan, which prompted a biopsy. It appeared the tumor had started in his pancreas and then spread to the lymph nodes and the wall of his abdomen.

He asked his doctor to “give it to him straight,” and she did. She told him that it was incurable, but that chemotherapy might slow it down. He asked how long he had, and she said less than a year.

He wanted a straight answer, but that wasn’t the answer he wanted. Who would? So he did some reading and decided to come to a large academic hospital an hour away for a second opinion.

I interviewed him and then scrolled through his CT scans outside the room. There were a few things we could do, the attending and I discussed. We would send his tumor for genetic testing to see if there were any cancer mutations that could be targeted with drugs more specific than standard chemotherapy. We would also refer him to our cancer genetics clinic to get his blood tested for inherited mutations.

But mostly, all of that would likely turn up negative. Mostly, we agreed with his local oncologist.

We went back in the room. Explaining the genetic testing took the length of the visit because this is not a straightforward concept. We explained the difference between tumor mutations and inherited mutations. We wrote down a list of genetic variations we could discover. We discussed treatment options that could go along with each.

Do you have any questions?

He broke down. He reached for the tissue box sitting on the exam room table. “I feel so much better,” he said. “This is why I came here.” He felt safe, reassured, and hopeful.

I was happy to be helpful, but later, as I wrote my clinic note about him, I felt uneasy about the visit.

Everything we said was true. But somehow, it still felt as though we left him with an overly optimistic view of his illness. Did our emphasis on what could be done overshadow that it was unlikely to change the big picture? Did our in-depth discussion of slim possibilities mask that his prognosis was, in fact, still grim?

Working at a large academic medical center, I see many patients who come for a second opinion. I’m incredibly fortunate to learn at a place that is not just up to date in the most cutting-edge treatments but often leading in innovation.

And so we offer patients these options. They sound novel and exciting. They fill patients with hope because they fill the field with hope. I, too, get enraptured with the possibilities – circulating tumor DNA and clinical trials and targeted therapies.

At big cancer meetings every year, oncologists come together and speak about cancer therapies with enthusiasm and hope. Advances have exploded; it’s an exciting time to be learning and practicing.

And yet, the reality for many patients is very different. We are still discussing hospice after one line of chemotherapy has failed. We are still gently holding hands and saying that we have no more options to treat their aggressive cancers.

How can both of these worlds coexist? How can both be true?

A few years ago, a friend was diagnosed with a devastating neurologic condition. I went to a clinical trials website and typed in her disease. Immediately, hundreds of options popped up. I felt hopeful. The field is moving forward, I thought. There are options.

But in the exam room, there were none. When I asked about what I had read, the neurologist explained how many of these possibilities were being investigated. But in the end, my friend really had no good options.

After my visit with Mr. M, I thought about how commonly this story plays out in my field of hematology and oncology. Yes, there are instances in which we find a mutation that drastically changes management. It’s wonderful to witness: patients handed an ominous diagnosis and then living their normal lives, in remission or with stable disease, years later.

We all hope for that. But we rarely get it. The challenge comes when we spend 95% of a visit talking about something with a 1% chance of working. The numbers don’t add up – it’s an equation that easily results in false understanding. Cancer can be glossed with a veneer of innovative options, obscuring the reality that none are likely to work.

Weaving both truths into the conversation is a difficult skill, but one I decided to be more cognizant of after my encounter with Mr. M.

At our next visit, we were still waiting on the test results. But I decided to speak with him candidly. It’s important to have a plan B, I said, and asked what would be important to him if his time were limited. He nodded, thinking about this. “I’ve just been holding out hope for the mutation,” he admitted.

The next week his genetic testing came back negative, and he decided to get palliative chemotherapy closer to home. He had no reason to come to a large academic hospital anymore. With nothing special to offer him, I never saw him again.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.

Mr. M wanted a second opinion. He was almost 80 years old and had been healthy his entire life. But recent abdominal discomfort prompted a CT scan, which prompted a biopsy. It appeared the tumor had started in his pancreas and then spread to the lymph nodes and the wall of his abdomen.

He asked his doctor to “give it to him straight,” and she did. She told him that it was incurable, but that chemotherapy might slow it down. He asked how long he had, and she said less than a year.

He wanted a straight answer, but that wasn’t the answer he wanted. Who would? So he did some reading and decided to come to a large academic hospital an hour away for a second opinion.

I interviewed him and then scrolled through his CT scans outside the room. There were a few things we could do, the attending and I discussed. We would send his tumor for genetic testing to see if there were any cancer mutations that could be targeted with drugs more specific than standard chemotherapy. We would also refer him to our cancer genetics clinic to get his blood tested for inherited mutations.

But mostly, all of that would likely turn up negative. Mostly, we agreed with his local oncologist.

We went back in the room. Explaining the genetic testing took the length of the visit because this is not a straightforward concept. We explained the difference between tumor mutations and inherited mutations. We wrote down a list of genetic variations we could discover. We discussed treatment options that could go along with each.

Do you have any questions?

He broke down. He reached for the tissue box sitting on the exam room table. “I feel so much better,” he said. “This is why I came here.” He felt safe, reassured, and hopeful.

I was happy to be helpful, but later, as I wrote my clinic note about him, I felt uneasy about the visit.

Everything we said was true. But somehow, it still felt as though we left him with an overly optimistic view of his illness. Did our emphasis on what could be done overshadow that it was unlikely to change the big picture? Did our in-depth discussion of slim possibilities mask that his prognosis was, in fact, still grim?

Working at a large academic medical center, I see many patients who come for a second opinion. I’m incredibly fortunate to learn at a place that is not just up to date in the most cutting-edge treatments but often leading in innovation.

And so we offer patients these options. They sound novel and exciting. They fill patients with hope because they fill the field with hope. I, too, get enraptured with the possibilities – circulating tumor DNA and clinical trials and targeted therapies.

At big cancer meetings every year, oncologists come together and speak about cancer therapies with enthusiasm and hope. Advances have exploded; it’s an exciting time to be learning and practicing.

And yet, the reality for many patients is very different. We are still discussing hospice after one line of chemotherapy has failed. We are still gently holding hands and saying that we have no more options to treat their aggressive cancers.

How can both of these worlds coexist? How can both be true?

A few years ago, a friend was diagnosed with a devastating neurologic condition. I went to a clinical trials website and typed in her disease. Immediately, hundreds of options popped up. I felt hopeful. The field is moving forward, I thought. There are options.

But in the exam room, there were none. When I asked about what I had read, the neurologist explained how many of these possibilities were being investigated. But in the end, my friend really had no good options.

After my visit with Mr. M, I thought about how commonly this story plays out in my field of hematology and oncology. Yes, there are instances in which we find a mutation that drastically changes management. It’s wonderful to witness: patients handed an ominous diagnosis and then living their normal lives, in remission or with stable disease, years later.

We all hope for that. But we rarely get it. The challenge comes when we spend 95% of a visit talking about something with a 1% chance of working. The numbers don’t add up – it’s an equation that easily results in false understanding. Cancer can be glossed with a veneer of innovative options, obscuring the reality that none are likely to work.

Weaving both truths into the conversation is a difficult skill, but one I decided to be more cognizant of after my encounter with Mr. M.

At our next visit, we were still waiting on the test results. But I decided to speak with him candidly. It’s important to have a plan B, I said, and asked what would be important to him if his time were limited. He nodded, thinking about this. “I’ve just been holding out hope for the mutation,” he admitted.

The next week his genetic testing came back negative, and he decided to get palliative chemotherapy closer to home. He had no reason to come to a large academic hospital anymore. With nothing special to offer him, I never saw him again.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz and listen to her each week on the Blood & Cancer podcast.

In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

In Walter Mitty moments, many of us daydream of glory: We’ll make that big discovery, score that disruptive app, homer in the bottom of the ninth to win the series. Then we wake up.

Those of us in the helping professions have fantasies, too, though fewer as times goes by. It gets harder even to daydream that we’ll make a rare diagnosis everyone missed or cure the condition no one could. But the temptation to dream, day or night, never quite goes away. ...

Curtis is 45. He’s had eczema forever. It covers half his body. Topical steroids and courses of prednisone have failed him for decades. Maybe he’ll respond to dupilumab. Maybe his insurer will let him try.

The insurer rejects my Prior Authorization request; guidelines won’t authorize dupilumab unless the patient has failed on pimecrolimus.

Pimecrolimus?!!!

I figure – what the heck – I’ll dash off a stem-winder of a letter to the insurer’s medical director.

Esteemed Director,

Like every doctor, I spend my days filling out Prior Authorization forms. These are tedious but at least make some sense on their own terms. But your rejection of dupilumab is so silly that I must object.

My patient is 6-feet tall. Half his body has been covered with eczema for a long time. No expert could possibly have told you that someone who failed oral and topical steroids would respond to pimecrolimus. Besides, how many gallons of pimecrolimus would it take to smear all over a man this size in a useless effort to show it doesn’t work?

Cordially,

Two days later they approved dupilumab. Triumph! Excited, I call Curtis to tell him the news.

Curtis does not respond.

My staff calls three times. He doesn’t call back.

I write Curtis a letter. Nothing.

Maybe the Prior Authorization form chased away his eczema.

Not long after Curtis, Warren comes by. In his mid-50s, Warren is miserable. “I had a responsible job,” he says. “Now I feel as though my brain is disintegrating. For the last month, I’ve had worms crawling out of my pores. ...”

I don’t know about you, dear colleagues, but nothing stirs within me a deeper sense of futility than a patient with parasitical delusions.

“Here,” says Warren, on cue, “I brought some worms in,” handing me the requisite rumpled tissue filled with squiggles of mucus.

“Look, Warren,” I say, “you’re not going to like hearing this, but there are no worms coming out of you.”

“There aren’t?”

“You think you have them, but you need help realizing you don’t. You should see a psychiatrist.”

“Really?” says Warren. “If you think it would help, that would be wonderful. Could you help me find one?”

In all my years, no patient with parasitic delusions has ever responded positively to my suggesting a psychiatric referral. Maybe I can actually help this man!

A shrink I know refers me to a colleague at TweedleDum Medical Empire, who is most cordial. “Yes,” he says, “we work closely with dermatology and handle such patients all the time. Recent symptom onset does suggest an organic cause. Have him call my appointment coordinator.”

Which I do, with great excitement. Warren is enthused too. His emails express optimism and deep gratitude, catnip to a rescue fantasist.

What follows is – not much. Warren calls me. His insurer has balked, because his primary care is at TweedleDee Medical Empire. Courtney at TweedleDum should straighten it out, but she is away. For a very long time. And so forth.

Days go by. Weeks. Emails fly back and forth. Warren wavers between hope and despair. He is waiting for Courtney. I am waiting for Godot.

I put my staff on it. Three hours later they find Courtney. In person. It’s all set!

I let Warren know. And then ...

Nothing.

Warren stops answering my emails. I write the cordial psychiatrist at TweedleDum.

No response.

My batting average with delusional parasitosis remains an immaculate 0.000.

Rescuing people is tricky. You need to know a bit. You need to persevere. You need contacts. You need luck.

And the patient needs to want to be rescued.

Not for nothing do they call them Rescue Fantasies.

Now I can go back to work on that disruptive app. Just wait, my friends – it’s going to disrupt the world and change everything!
 

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. He had no disclosures relevant to this column. Write to him at dermnews@mdedge.com.

It is with great sadness that we note the passing (June 2, 2019; age 91) of Dr. Henry Lynch. Dr. Lynch almost singlehandedly brought attention to the genetic syndrome that bears his name. In 1913 Aldred Warthin (pathology chair at the University of Michigan) first described family “G”, the family of his seamstress who had told him that her family all dies of cancer. She herself succumbed to endometrial cancer. A plaque commemorating Dr. Warthin hangs down the hallway from my office at Michigan. His report fell into obscurity until the 1960s when Dr. Lynch arranged a reunion of family G in Ann Arbor, leading to a detailed update of the family in 1971. He recognized the autosomal dominance of the pedigree pattern.

In 1973, C. Richard Boland, MD, AGAF (past AGA President), wrote a medical school thesis entitled “A Familial Cancer Syndrome” and subsequently published two papers in which he first used the term “Lynch syndrome (I and II). Dr. Boland (whose family also carried a Lynch syndrome variant) spent his career adding to our molecular and clinical knowledge about nonpolyposis colon cancer syndromes. In the 1990s Vogelstein and others first described the molecular pathways that lead to colon cancer – and the rest is history.

I was a young faculty gastroenterologist at the Minneapolis VA Medical Center when one day my phone rang; it was Henry Lynch. He wanted to alert me that one of his patients was coming to me for surveillance colonoscopy. He explained the importance of what I was to do and how I should follow this man. I was overwhelmed by his attention to his patient (one of thousands) and his kindness to me. I had the privilege of traveling with him as visiting professors on a trip to South America. He was one of the kindest, most intelligent, and gracious persons I had ever met. I never forgot that experience.

We owe a lot to scientists, clinicians, and thought leaders like Henry Lynch who provide us the scientific basis of the care we give our patients.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

It is with great sadness that we note the passing (June 2, 2019; age 91) of Dr. Henry Lynch. Dr. Lynch almost singlehandedly brought attention to the genetic syndrome that bears his name. In 1913 Aldred Warthin (pathology chair at the University of Michigan) first described family “G”, the family of his seamstress who had told him that her family all dies of cancer. She herself succumbed to endometrial cancer. A plaque commemorating Dr. Warthin hangs down the hallway from my office at Michigan. His report fell into obscurity until the 1960s when Dr. Lynch arranged a reunion of family G in Ann Arbor, leading to a detailed update of the family in 1971. He recognized the autosomal dominance of the pedigree pattern.

In 1973, C. Richard Boland, MD, AGAF (past AGA President), wrote a medical school thesis entitled “A Familial Cancer Syndrome” and subsequently published two papers in which he first used the term “Lynch syndrome (I and II). Dr. Boland (whose family also carried a Lynch syndrome variant) spent his career adding to our molecular and clinical knowledge about nonpolyposis colon cancer syndromes. In the 1990s Vogelstein and others first described the molecular pathways that lead to colon cancer – and the rest is history.

I was a young faculty gastroenterologist at the Minneapolis VA Medical Center when one day my phone rang; it was Henry Lynch. He wanted to alert me that one of his patients was coming to me for surveillance colonoscopy. He explained the importance of what I was to do and how I should follow this man. I was overwhelmed by his attention to his patient (one of thousands) and his kindness to me. I had the privilege of traveling with him as visiting professors on a trip to South America. He was one of the kindest, most intelligent, and gracious persons I had ever met. I never forgot that experience.

We owe a lot to scientists, clinicians, and thought leaders like Henry Lynch who provide us the scientific basis of the care we give our patients.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

It is with great sadness that we note the passing (June 2, 2019; age 91) of Dr. Henry Lynch. Dr. Lynch almost singlehandedly brought attention to the genetic syndrome that bears his name. In 1913 Aldred Warthin (pathology chair at the University of Michigan) first described family “G”, the family of his seamstress who had told him that her family all dies of cancer. She herself succumbed to endometrial cancer. A plaque commemorating Dr. Warthin hangs down the hallway from my office at Michigan. His report fell into obscurity until the 1960s when Dr. Lynch arranged a reunion of family G in Ann Arbor, leading to a detailed update of the family in 1971. He recognized the autosomal dominance of the pedigree pattern.

In 1973, C. Richard Boland, MD, AGAF (past AGA President), wrote a medical school thesis entitled “A Familial Cancer Syndrome” and subsequently published two papers in which he first used the term “Lynch syndrome (I and II). Dr. Boland (whose family also carried a Lynch syndrome variant) spent his career adding to our molecular and clinical knowledge about nonpolyposis colon cancer syndromes. In the 1990s Vogelstein and others first described the molecular pathways that lead to colon cancer – and the rest is history.

I was a young faculty gastroenterologist at the Minneapolis VA Medical Center when one day my phone rang; it was Henry Lynch. He wanted to alert me that one of his patients was coming to me for surveillance colonoscopy. He explained the importance of what I was to do and how I should follow this man. I was overwhelmed by his attention to his patient (one of thousands) and his kindness to me. I had the privilege of traveling with him as visiting professors on a trip to South America. He was one of the kindest, most intelligent, and gracious persons I had ever met. I never forgot that experience.

We owe a lot to scientists, clinicians, and thought leaders like Henry Lynch who provide us the scientific basis of the care we give our patients.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

In 2016, two researchers published a meta-analysis on gray matter abnormalities in youth who had conduct problems.

The study by Jack C. Rogers, PhD, and Stephane A. De Brito, PhD, found 13 well-done studies that included 394 youth with conduct problems and 390 typically developing youth. Compared with the typically developing youth, the conduct-disordered youth had decreased gray matter volume (JAMA Psychiatry. 2016 Jan;73[1]:64-72).

As I knew one of the researchers in one of the studies that made the cut, I called him up and asked whether their research had controlled for fetal alcohol exposure. They had not. I found this very curious because my experience is that youth who have been labeled with conduct disorder often have histories of prenatal fetal alcohol exposure. In addition, my understanding is that youth who have been exposed to prenatal alcohol often have symptoms of conduct disorder. Furthermore, research has shown that such youth have smaller brains (Dev Med Child Neurol. 2001 Mar;43[3]:148-54). I wondered whether the youth studied in that trial had been exposed to alcohol prenatally.

More recently, this problem has resurfaced. An article by Antonia N. Kaczkurkin, PhD, and associates about a large sample of youth was nicely done. But again, the variable of fetal alcohol exposure was not considered. The study was an elegant one that provides a strong rationale for consideration of a “psychopathology factor” in human life (Am J Psychiatry. 2019 Jun 24. doi: 10.1176/appi.ajp.2019.1807035). It shored up that argument by doing neuroimaging studies on a reasonably large sample of youth and showed that reduced cortical thickness (gray matter volume) was associated with overall psychopathology. With the exception of failing to consider the variable of fetal alcohol exposure, the study is a valuable addition to our understanding of what might be going on with psychiatric disorders.

Unfortunately – while hating to sound like a broken record – I noticed that there was no consideration of fetal alcohol exposure as a cause for the findings of the study. It does not seem like a large leap to hypothesize some of these brain imaging studies that find smaller brain components associated with psychopathology and conduct disorder to be a dynamic of fetal alcohol exposure.

It seems to me that we made a huge mistake in public health in asking women only whether they were drinking while they were pregnant because it was the wrong question. The right question is – “When did you realize you were pregnant, and were you doing any social drinking before you knew you were pregnant?”

Without understanding the etiology of the smaller brains in patients with conduct disorder or psychopathology, we are missing a golden opportunity to prevent such problems. The former editor of the American Journal of Psychiatry – Robert A. Freedman, MD – suggests that by giving phosphatidyl choline to pregnant women, such problems could be prevented.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. In 2019, he was awarded the Adolph Meyer Award by the American Psychiatric Association for lifetime achievement in psychiatric research.

In 2016, two researchers published a meta-analysis on gray matter abnormalities in youth who had conduct problems.

The study by Jack C. Rogers, PhD, and Stephane A. De Brito, PhD, found 13 well-done studies that included 394 youth with conduct problems and 390 typically developing youth. Compared with the typically developing youth, the conduct-disordered youth had decreased gray matter volume (JAMA Psychiatry. 2016 Jan;73[1]:64-72).

As I knew one of the researchers in one of the studies that made the cut, I called him up and asked whether their research had controlled for fetal alcohol exposure. They had not. I found this very curious because my experience is that youth who have been labeled with conduct disorder often have histories of prenatal fetal alcohol exposure. In addition, my understanding is that youth who have been exposed to prenatal alcohol often have symptoms of conduct disorder. Furthermore, research has shown that such youth have smaller brains (Dev Med Child Neurol. 2001 Mar;43[3]:148-54). I wondered whether the youth studied in that trial had been exposed to alcohol prenatally.

More recently, this problem has resurfaced. An article by Antonia N. Kaczkurkin, PhD, and associates about a large sample of youth was nicely done. But again, the variable of fetal alcohol exposure was not considered. The study was an elegant one that provides a strong rationale for consideration of a “psychopathology factor” in human life (Am J Psychiatry. 2019 Jun 24. doi: 10.1176/appi.ajp.2019.1807035). It shored up that argument by doing neuroimaging studies on a reasonably large sample of youth and showed that reduced cortical thickness (gray matter volume) was associated with overall psychopathology. With the exception of failing to consider the variable of fetal alcohol exposure, the study is a valuable addition to our understanding of what might be going on with psychiatric disorders.

Unfortunately – while hating to sound like a broken record – I noticed that there was no consideration of fetal alcohol exposure as a cause for the findings of the study. It does not seem like a large leap to hypothesize some of these brain imaging studies that find smaller brain components associated with psychopathology and conduct disorder to be a dynamic of fetal alcohol exposure.

It seems to me that we made a huge mistake in public health in asking women only whether they were drinking while they were pregnant because it was the wrong question. The right question is – “When did you realize you were pregnant, and were you doing any social drinking before you knew you were pregnant?”

Without understanding the etiology of the smaller brains in patients with conduct disorder or psychopathology, we are missing a golden opportunity to prevent such problems. The former editor of the American Journal of Psychiatry – Robert A. Freedman, MD – suggests that by giving phosphatidyl choline to pregnant women, such problems could be prevented.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. In 2019, he was awarded the Adolph Meyer Award by the American Psychiatric Association for lifetime achievement in psychiatric research.

In 2016, two researchers published a meta-analysis on gray matter abnormalities in youth who had conduct problems.

The study by Jack C. Rogers, PhD, and Stephane A. De Brito, PhD, found 13 well-done studies that included 394 youth with conduct problems and 390 typically developing youth. Compared with the typically developing youth, the conduct-disordered youth had decreased gray matter volume (JAMA Psychiatry. 2016 Jan;73[1]:64-72).

As I knew one of the researchers in one of the studies that made the cut, I called him up and asked whether their research had controlled for fetal alcohol exposure. They had not. I found this very curious because my experience is that youth who have been labeled with conduct disorder often have histories of prenatal fetal alcohol exposure. In addition, my understanding is that youth who have been exposed to prenatal alcohol often have symptoms of conduct disorder. Furthermore, research has shown that such youth have smaller brains (Dev Med Child Neurol. 2001 Mar;43[3]:148-54). I wondered whether the youth studied in that trial had been exposed to alcohol prenatally.

More recently, this problem has resurfaced. An article by Antonia N. Kaczkurkin, PhD, and associates about a large sample of youth was nicely done. But again, the variable of fetal alcohol exposure was not considered. The study was an elegant one that provides a strong rationale for consideration of a “psychopathology factor” in human life (Am J Psychiatry. 2019 Jun 24. doi: 10.1176/appi.ajp.2019.1807035). It shored up that argument by doing neuroimaging studies on a reasonably large sample of youth and showed that reduced cortical thickness (gray matter volume) was associated with overall psychopathology. With the exception of failing to consider the variable of fetal alcohol exposure, the study is a valuable addition to our understanding of what might be going on with psychiatric disorders.

Unfortunately – while hating to sound like a broken record – I noticed that there was no consideration of fetal alcohol exposure as a cause for the findings of the study. It does not seem like a large leap to hypothesize some of these brain imaging studies that find smaller brain components associated with psychopathology and conduct disorder to be a dynamic of fetal alcohol exposure.

It seems to me that we made a huge mistake in public health in asking women only whether they were drinking while they were pregnant because it was the wrong question. The right question is – “When did you realize you were pregnant, and were you doing any social drinking before you knew you were pregnant?”

Without understanding the etiology of the smaller brains in patients with conduct disorder or psychopathology, we are missing a golden opportunity to prevent such problems. The former editor of the American Journal of Psychiatry – Robert A. Freedman, MD – suggests that by giving phosphatidyl choline to pregnant women, such problems could be prevented.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago. In 2019, he was awarded the Adolph Meyer Award by the American Psychiatric Association for lifetime achievement in psychiatric research.

The Florida Society of Rheumatology is an excellent state conference that is very well attended because of the comprehensive clinical topics covered by esteemed faculty. Every year, there is a balance of patient care lectures and updates in advocacy, billing, and coding. Clinicians need a combination of both arenas to be successful with the day-to-day practice of rheumatology and to render evidenced-based patient care. This year, the FSR certainly delivered on this mission as reflected by articles on these presentations published at MDedge Rheumatology. An added focus this year was how to leverage technology in a rheumatology practice to capture patient-reported outcomes (PROs) to better understand issues affecting our patient population and improve therapy plans where indicated.

In his lecture on digital PROs, Jeffrey Curtis, MD, explained the difference between active capture of data through tools such as the Routine Assessment of Patient Index Data 3 (RAPID3) or Health Assessment Questionnaire (HAQ) and passive capture through wearable devices such as a Fitbit or Apple watch. A key point for the audience was that this information improves clinical care and improves medical decision making, and thus all rheumatologists should consider using these tools in practice. Dr. Curtis, William J. Koopman Endowed Professor in Rheumatology and Immunology and director of the UAB Arthritis Clinical Intervention Program at the University of Alabama at Birmingham, is well aware of the practical concerns that face clinicians, namely that this is time consuming. He suggests to keep it short and find a tool that works for you in your practice to understand how your patients are progressing on a treatment regimen. He was clear that “data for the sake of data is not compelling for patients [or clinicians].” The ideal is not to paralyze your practice and drown in patient questionnaires but rather to empower patients to report using standardized tools so we can effect change that will help us to treat rheumatic diseases.

An important point mentioned during this lecture was to keep in mind that, if a patient appears to be a “nonresponder” on RAPID3, for example, it is important to understand whether the patient has a confounding comorbidity, such as fibromyalgia, that may account for the limited improvement.

Michelle Petri, MD, gave two excellent talks at FSR this year. Her lectures are packed with excellent pearls about treating patients with systemic lupus erythematosus. Interestingly, she said to never underestimate the prognostic factor of a low C3. This can indicate a worse clinical course is ahead. In addition, she reminds us as clinicians to protect the kidneys of our lupus patients who have renal disease by avoiding common toxins such as NSAIDs and CT contrast. Of course, she reminds us to use the lowest dose of steroids possible during flares, as prednisone is directly or indirectly responsible for 80% of organ damage over 15 years. She reminds us that lupus patients do not die of lupus. They have a 2.66-fold higher risk of cardiovascular events than the general public. In addition to maintaining lupus patients on hydroxychloroquine, Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore, noted that vitamin D can have cardiovascular and hematologic benefits along with reducing thrombosis in some clinical studies. Low vitamin D was significantly associated with deep venous thrombosis.

In his lecture, Leonard Calabrese, DO, made a compelling argument for the rheumatologists in the audience to call the local oncologists with whom they work. We need to discuss and collaborate on the care of patients experiencing immune-mediated adverse events from exposure to checkpoint inhibitors used to treat malignancy. There is a limited mechanistic understanding of these adverse events, but as rheumatologists we need to get involved and help these patients. We are the experts in managing these newly emerging autoimmune events. We can help to create the best possible therapeutic interventions to help our oncology colleagues with these challenging cases, Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic, said.

Besides paying our dues to be members of the FSR, it is important for us as rheumatologists to get involved at the state legislature and national level to bring about change for our practices and patients. Currently, the climate can be hostile for reimbursement and for our patients to get the therapies they need. In another presentation, Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee, described recent successes at the national level, and he also discussed how we can have our voices heard at the state and national level to protect our profession and the people who rely on our expertise. The FSR and other state rheumatology organizations, as well as the ACR, need our support to continue to be the collective voice for what is right for clinicians and patients alike.
 

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The Florida Society of Rheumatology is an excellent state conference that is very well attended because of the comprehensive clinical topics covered by esteemed faculty. Every year, there is a balance of patient care lectures and updates in advocacy, billing, and coding. Clinicians need a combination of both arenas to be successful with the day-to-day practice of rheumatology and to render evidenced-based patient care. This year, the FSR certainly delivered on this mission as reflected by articles on these presentations published at MDedge Rheumatology. An added focus this year was how to leverage technology in a rheumatology practice to capture patient-reported outcomes (PROs) to better understand issues affecting our patient population and improve therapy plans where indicated.

In his lecture on digital PROs, Jeffrey Curtis, MD, explained the difference between active capture of data through tools such as the Routine Assessment of Patient Index Data 3 (RAPID3) or Health Assessment Questionnaire (HAQ) and passive capture through wearable devices such as a Fitbit or Apple watch. A key point for the audience was that this information improves clinical care and improves medical decision making, and thus all rheumatologists should consider using these tools in practice. Dr. Curtis, William J. Koopman Endowed Professor in Rheumatology and Immunology and director of the UAB Arthritis Clinical Intervention Program at the University of Alabama at Birmingham, is well aware of the practical concerns that face clinicians, namely that this is time consuming. He suggests to keep it short and find a tool that works for you in your practice to understand how your patients are progressing on a treatment regimen. He was clear that “data for the sake of data is not compelling for patients [or clinicians].” The ideal is not to paralyze your practice and drown in patient questionnaires but rather to empower patients to report using standardized tools so we can effect change that will help us to treat rheumatic diseases.

An important point mentioned during this lecture was to keep in mind that, if a patient appears to be a “nonresponder” on RAPID3, for example, it is important to understand whether the patient has a confounding comorbidity, such as fibromyalgia, that may account for the limited improvement.

Michelle Petri, MD, gave two excellent talks at FSR this year. Her lectures are packed with excellent pearls about treating patients with systemic lupus erythematosus. Interestingly, she said to never underestimate the prognostic factor of a low C3. This can indicate a worse clinical course is ahead. In addition, she reminds us as clinicians to protect the kidneys of our lupus patients who have renal disease by avoiding common toxins such as NSAIDs and CT contrast. Of course, she reminds us to use the lowest dose of steroids possible during flares, as prednisone is directly or indirectly responsible for 80% of organ damage over 15 years. She reminds us that lupus patients do not die of lupus. They have a 2.66-fold higher risk of cardiovascular events than the general public. In addition to maintaining lupus patients on hydroxychloroquine, Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore, noted that vitamin D can have cardiovascular and hematologic benefits along with reducing thrombosis in some clinical studies. Low vitamin D was significantly associated with deep venous thrombosis.

In his lecture, Leonard Calabrese, DO, made a compelling argument for the rheumatologists in the audience to call the local oncologists with whom they work. We need to discuss and collaborate on the care of patients experiencing immune-mediated adverse events from exposure to checkpoint inhibitors used to treat malignancy. There is a limited mechanistic understanding of these adverse events, but as rheumatologists we need to get involved and help these patients. We are the experts in managing these newly emerging autoimmune events. We can help to create the best possible therapeutic interventions to help our oncology colleagues with these challenging cases, Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic, said.

Besides paying our dues to be members of the FSR, it is important for us as rheumatologists to get involved at the state legislature and national level to bring about change for our practices and patients. Currently, the climate can be hostile for reimbursement and for our patients to get the therapies they need. In another presentation, Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee, described recent successes at the national level, and he also discussed how we can have our voices heard at the state and national level to protect our profession and the people who rely on our expertise. The FSR and other state rheumatology organizations, as well as the ACR, need our support to continue to be the collective voice for what is right for clinicians and patients alike.
 

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The Florida Society of Rheumatology is an excellent state conference that is very well attended because of the comprehensive clinical topics covered by esteemed faculty. Every year, there is a balance of patient care lectures and updates in advocacy, billing, and coding. Clinicians need a combination of both arenas to be successful with the day-to-day practice of rheumatology and to render evidenced-based patient care. This year, the FSR certainly delivered on this mission as reflected by articles on these presentations published at MDedge Rheumatology. An added focus this year was how to leverage technology in a rheumatology practice to capture patient-reported outcomes (PROs) to better understand issues affecting our patient population and improve therapy plans where indicated.

In his lecture on digital PROs, Jeffrey Curtis, MD, explained the difference between active capture of data through tools such as the Routine Assessment of Patient Index Data 3 (RAPID3) or Health Assessment Questionnaire (HAQ) and passive capture through wearable devices such as a Fitbit or Apple watch. A key point for the audience was that this information improves clinical care and improves medical decision making, and thus all rheumatologists should consider using these tools in practice. Dr. Curtis, William J. Koopman Endowed Professor in Rheumatology and Immunology and director of the UAB Arthritis Clinical Intervention Program at the University of Alabama at Birmingham, is well aware of the practical concerns that face clinicians, namely that this is time consuming. He suggests to keep it short and find a tool that works for you in your practice to understand how your patients are progressing on a treatment regimen. He was clear that “data for the sake of data is not compelling for patients [or clinicians].” The ideal is not to paralyze your practice and drown in patient questionnaires but rather to empower patients to report using standardized tools so we can effect change that will help us to treat rheumatic diseases.

An important point mentioned during this lecture was to keep in mind that, if a patient appears to be a “nonresponder” on RAPID3, for example, it is important to understand whether the patient has a confounding comorbidity, such as fibromyalgia, that may account for the limited improvement.

Michelle Petri, MD, gave two excellent talks at FSR this year. Her lectures are packed with excellent pearls about treating patients with systemic lupus erythematosus. Interestingly, she said to never underestimate the prognostic factor of a low C3. This can indicate a worse clinical course is ahead. In addition, she reminds us as clinicians to protect the kidneys of our lupus patients who have renal disease by avoiding common toxins such as NSAIDs and CT contrast. Of course, she reminds us to use the lowest dose of steroids possible during flares, as prednisone is directly or indirectly responsible for 80% of organ damage over 15 years. She reminds us that lupus patients do not die of lupus. They have a 2.66-fold higher risk of cardiovascular events than the general public. In addition to maintaining lupus patients on hydroxychloroquine, Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore, noted that vitamin D can have cardiovascular and hematologic benefits along with reducing thrombosis in some clinical studies. Low vitamin D was significantly associated with deep venous thrombosis.

In his lecture, Leonard Calabrese, DO, made a compelling argument for the rheumatologists in the audience to call the local oncologists with whom they work. We need to discuss and collaborate on the care of patients experiencing immune-mediated adverse events from exposure to checkpoint inhibitors used to treat malignancy. There is a limited mechanistic understanding of these adverse events, but as rheumatologists we need to get involved and help these patients. We are the experts in managing these newly emerging autoimmune events. We can help to create the best possible therapeutic interventions to help our oncology colleagues with these challenging cases, Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic, said.

Besides paying our dues to be members of the FSR, it is important for us as rheumatologists to get involved at the state legislature and national level to bring about change for our practices and patients. Currently, the climate can be hostile for reimbursement and for our patients to get the therapies they need. In another presentation, Angus Worthing, MD, chair of the American College of Rheumatology’s Government Affairs Committee, described recent successes at the national level, and he also discussed how we can have our voices heard at the state and national level to protect our profession and the people who rely on our expertise. The FSR and other state rheumatology organizations, as well as the ACR, need our support to continue to be the collective voice for what is right for clinicians and patients alike.
 

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

The recently published PIONEER-HF study attempts to move sacubitril/valsartan (Entresto) therapy to the inpatient environment to improve patient and physician acceptance of this therapy for patients with heart failure (N Engl J Med. 2019 Feb 7;380;539-48).

When given to outpatients in the PARADIGM-HF trial, the combination was superior to enalapril for reducing the risks of death and hospitalization for heart failure (N Engl J Med 2014;371:993-1004.) Specifically, sacubitril/valsartan decreased mortality by 15% and hospitalization by 21% as an outpatient therapy for patients with systolic heart failure. Nevertheless, there has not been widespread adoption of this approach. It is well known that physicians can be slow to adopt new therapies, but one overriding factor may be the cost of the drug compared to enalapril, one of the first drugs shown to be effective in heart failure therapy (Entresto costs more than $4,000 per year; enalapril costs about $120 per year).

The investigators in the PIONEER-HF study compared Entresto to enalapril over a 2-month period in patients hospitalized with systolic heart failure. To accelerate the trial, the investigators used the proportional change in patients’ N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as the primary endpoint rather than the traditional outcome of morbidity and mortality. In the short term, no significant clinical benefits were observed, but there was a significant decrease in NT-proBNP of about 30% (P less than .001).

The investigators suggested that this finding extended the previous benefit observed with Entresto during outpatient initiation and could be used as a rationale for initiating Entresto therapy in the hospital. This earlier application of the therapy could make the drug more widely acceptable.

Considerable investigation in BNP measurement has occurred over the last few years, and although it is clear that BNP is elevated in heart failure patients, there is no evidence to confirm that the decrease in BNP is associated with improved outcome. BNP will fall with decrease in ventricular volume, which may have significant physiologic mechanisms but ventricular volume could decrease with fall in blood pressure that may have occurred in this population since hypotension tended to be more frequent with Entresto than with enalapril. The traditional measure of heart failure benefit with beta-blockers, ACE inhibitors, and aldosterone antagonists in the inpatient and early postdischarge period has depended on clinical outcomes.

Regardless of the physiologic explanation of this fall in BNP, we must pause in our assumptions when a surrogate measure is used to assess clinical benefit as inpatient therapy. The Food and Drug Administration has long given up using surrogate measures as proof of efficacy, and rightly so. Clinical medicine is replete with dubious drug benefits based on surrogate measures. Let’s not forget that only a few years ago suppression of premature ventricular contractions was considered to be a measure of the pharmacologic prevention of sudden death. We have come a long way from that and other clinical missteps to use BNP, an uncertain marker at best of clinical improvement, as a surrogate for the improvement in heart failure.

There is a substantial amount of data supporting the benefit of Entresto in the clinical management of outpatients with heart failure without using the PIONEER-HF trial results as a pretense to initiate therapy when patients are hospitalized. One might suggest that if Novartis is concerned about introducing the drug in the clinical management of heart failure, the company might consider the possibility of decreasing its price.

Dr. Goldstein is professor of medicine at Wayne State University and the division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit.

An estimated 1-1.8 million sport-related concussions (SRC) occur per year in patients younger than 18 years of age. Concussion is defined as “a traumatically induced transient disturbance of brain function.” More than 50% of concussions among high school youth are not related to organized sports and between 2% and 15% of athletes in organized sports will sustain a concussion during a season of play.

©s-c-s/Thinkstock

In its position statement on concussion in sports, the American Medical Society for Sports Medicine recommends that student athletes receive specific evaluations, which will be described in this article. The guidelines include recommendations for imaging, treatment, and decision making regarding when as well as whether to return to play. Here is a brief summary of those recommendations.


Preseason: Preseason evaluation includes a preparticipation physical evaluation and discussion of concussion history as well as risk factors associated with prolonged concussion recovery. Neurocognitive tests are available for baseline evaluation. While these may assist with diagnosis and return-to-play decisions, there can be considerable variation in an individual’s baseline score as well as the possibility of changes in that baseline over time. Because of this potential for variability, these tests are not required or accepted as the standard of care.

Sideline assessment: Familiarity with the athlete is the best way to detect subtle changes in personality or performance. Looking at symptoms is still the most sensitive way to diagnose a concussion. Loss of consciousness, seizure, tonic posturing, lack of motor coordination, confusion, amnesia, difficulty with balance, or any cognitive difficulty should prompt removal from play for possible concussion. Once a potential injury is identified, how the athlete responds to the elements of orientation, memory, concentration, speech pattern, and balance should be evaluated. If an athlete has a probable or definite concussion, the athlete needs to be removed from play and cannot return to same-day play, and a more detailed evaluation needs to be done.

Office assessment: It is not unusual for symptoms and testing to normalize by the time an office visit occurs. If this is the case, the visit should focus on recommendations for safe return to school and sport. A standard office evaluation should include taking a history with details of the mechanism of injury and preexisting conditions – such as depression and prior concussion – that can affect concussion recovery. The history should focus on detecting symptoms that typically cause impairment from concussion: headache, ocular-vestibular issues leading to problems with balance, and cognitive issues with difficulty concentrating and remembering, as well as fatigue and mood issues such as anxiety, irritability, and depression. The physical exam should include assessment of ocular and vestibular function, gait, and balance in addition to a neurological exam.

Imaging: Head CT or MRI are rarely indicated. Intracranial bleeds are rare in the context of SRC but can occur. If there is concern for a bleed, then CT scan is the imaging test of choice. MRI may have value for evaluation for atypical or prolonged recovery.

Recovery time: The large majority (80%-90%) of concussed older adolescents and adults return to preinjury levels of function within 2 weeks; in younger athletes, clinical recovery may take up to 4 weeks. The best predictor of recovery from SRC is the number and severity of symptoms.

Treatment: For decades, cognitive and physical rest has been the standard of treatment. However, this is no longer the “gold standard” as it has been shown that strict rest (“cocoon therapy”) after SRC slows recovery and leads to an increased chance of prolonged symptoms. Current consensus guidelines support 24-48 hours of symptom-limited rest, both cognitive and physical, followed by a gradual increase in activity, staying below symptom-exacerbation thresholds. Activity, along with good sleep hygiene, appears to be helpful in facilitating recovery from SRC. In athletes with persistent post concussive symptoms that continue beyond the expected recovery time frame, activities of daily living, school, and exercise that do not significantly exacerbate symptoms are recommended.

Return to learning/play: A concussion can cause temporary deficits in attention, cognitive processing, short-term memory, and executive functioning. School personnel should be informed of the injury and assist in employing an individualized return to learn plan, including academic accommodations. Ultimately, return to sports activities should follow a successful return to the classroom. Return to play involves a stepwise increase in physical demands/activity without symptoms before a student is allowed to participate in full contact play.

Concussion-related risks: Continuing to participate in sports before resolution of concussion can worsen and prolong symptoms of SRC. Returning too early after concussion, before full recovery, increases the risk of recurrent SRC. During the initial post-injury period, returning to sports too early increases the risk for a rare but devastating possibility of second impact syndrome that can be a life-threatening repeat head injury. Studies of long-term mental health diagnoses are conflicting and inconsistent. Chronic traumatic encephalopathy has been described in athletes with a long history of concussions and repetitive sub-symptom head impacts. The degree of exposure needed appears to be variable and dependent on the individual.

Disqualification from play: Because each athlete is individually assessed after SRC, there are no evidence-based studies indicating how many concussions are “safe” for an athlete to have in a lifetime. The decision to stop playing sports is both serious and difficult for most athletes and requires shared decision making between clinician, the athlete, and the athlete’s parents. Factors to consider when determining if disqualification from play is warranted include:

• The total number of concussions experienced by a patient.
• Whether a patient has sustained subsequent concussions with progressively less forceful blows to the head.
• If a patient has sustained multiple concussions,whether the time to complete a full recovery after each concussion event increased.

The bottom line: “Cocoon therapy” is no longer recommended. Consensus guidelines endorse 24-48 hours of symptom-limited cognitive and physical rest followed by a gradual increase in activity, including noncontact physical activity that does not provoke symptoms.

Dr. Belogorodsky is a second-year resident and Dr. Fidler is an associate director in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

Reference

Harmon KG et al. American Medical Society for Sports Medicine position statement on concussion in sport. Br J Sports Med. 2019;53:213-25.

An estimated 1-1.8 million sport-related concussions (SRC) occur per year in patients younger than 18 years of age. Concussion is defined as “a traumatically induced transient disturbance of brain function.” More than 50% of concussions among high school youth are not related to organized sports and between 2% and 15% of athletes in organized sports will sustain a concussion during a season of play.

©s-c-s/Thinkstock

In its position statement on concussion in sports, the American Medical Society for Sports Medicine recommends that student athletes receive specific evaluations, which will be described in this article. The guidelines include recommendations for imaging, treatment, and decision making regarding when as well as whether to return to play. Here is a brief summary of those recommendations.


Preseason: Preseason evaluation includes a preparticipation physical evaluation and discussion of concussion history as well as risk factors associated with prolonged concussion recovery. Neurocognitive tests are available for baseline evaluation. While these may assist with diagnosis and return-to-play decisions, there can be considerable variation in an individual’s baseline score as well as the possibility of changes in that baseline over time. Because of this potential for variability, these tests are not required or accepted as the standard of care.

Sideline assessment: Familiarity with the athlete is the best way to detect subtle changes in personality or performance. Looking at symptoms is still the most sensitive way to diagnose a concussion. Loss of consciousness, seizure, tonic posturing, lack of motor coordination, confusion, amnesia, difficulty with balance, or any cognitive difficulty should prompt removal from play for possible concussion. Once a potential injury is identified, how the athlete responds to the elements of orientation, memory, concentration, speech pattern, and balance should be evaluated. If an athlete has a probable or definite concussion, the athlete needs to be removed from play and cannot return to same-day play, and a more detailed evaluation needs to be done.

Office assessment: It is not unusual for symptoms and testing to normalize by the time an office visit occurs. If this is the case, the visit should focus on recommendations for safe return to school and sport. A standard office evaluation should include taking a history with details of the mechanism of injury and preexisting conditions – such as depression and prior concussion – that can affect concussion recovery. The history should focus on detecting symptoms that typically cause impairment from concussion: headache, ocular-vestibular issues leading to problems with balance, and cognitive issues with difficulty concentrating and remembering, as well as fatigue and mood issues such as anxiety, irritability, and depression. The physical exam should include assessment of ocular and vestibular function, gait, and balance in addition to a neurological exam.

Imaging: Head CT or MRI are rarely indicated. Intracranial bleeds are rare in the context of SRC but can occur. If there is concern for a bleed, then CT scan is the imaging test of choice. MRI may have value for evaluation for atypical or prolonged recovery.

Recovery time: The large majority (80%-90%) of concussed older adolescents and adults return to preinjury levels of function within 2 weeks; in younger athletes, clinical recovery may take up to 4 weeks. The best predictor of recovery from SRC is the number and severity of symptoms.

Treatment: For decades, cognitive and physical rest has been the standard of treatment. However, this is no longer the “gold standard” as it has been shown that strict rest (“cocoon therapy”) after SRC slows recovery and leads to an increased chance of prolonged symptoms. Current consensus guidelines support 24-48 hours of symptom-limited rest, both cognitive and physical, followed by a gradual increase in activity, staying below symptom-exacerbation thresholds. Activity, along with good sleep hygiene, appears to be helpful in facilitating recovery from SRC. In athletes with persistent post concussive symptoms that continue beyond the expected recovery time frame, activities of daily living, school, and exercise that do not significantly exacerbate symptoms are recommended.

Return to learning/play: A concussion can cause temporary deficits in attention, cognitive processing, short-term memory, and executive functioning. School personnel should be informed of the injury and assist in employing an individualized return to learn plan, including academic accommodations. Ultimately, return to sports activities should follow a successful return to the classroom. Return to play involves a stepwise increase in physical demands/activity without symptoms before a student is allowed to participate in full contact play.

Concussion-related risks: Continuing to participate in sports before resolution of concussion can worsen and prolong symptoms of SRC. Returning too early after concussion, before full recovery, increases the risk of recurrent SRC. During the initial post-injury period, returning to sports too early increases the risk for a rare but devastating possibility of second impact syndrome that can be a life-threatening repeat head injury. Studies of long-term mental health diagnoses are conflicting and inconsistent. Chronic traumatic encephalopathy has been described in athletes with a long history of concussions and repetitive sub-symptom head impacts. The degree of exposure needed appears to be variable and dependent on the individual.

Disqualification from play: Because each athlete is individually assessed after SRC, there are no evidence-based studies indicating how many concussions are “safe” for an athlete to have in a lifetime. The decision to stop playing sports is both serious and difficult for most athletes and requires shared decision making between clinician, the athlete, and the athlete’s parents. Factors to consider when determining if disqualification from play is warranted include:

• The total number of concussions experienced by a patient.
• Whether a patient has sustained subsequent concussions with progressively less forceful blows to the head.
• If a patient has sustained multiple concussions,whether the time to complete a full recovery after each concussion event increased.

The bottom line: “Cocoon therapy” is no longer recommended. Consensus guidelines endorse 24-48 hours of symptom-limited cognitive and physical rest followed by a gradual increase in activity, including noncontact physical activity that does not provoke symptoms.

Dr. Belogorodsky is a second-year resident and Dr. Fidler is an associate director in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

Reference

Harmon KG et al. American Medical Society for Sports Medicine position statement on concussion in sport. Br J Sports Med. 2019;53:213-25.

An estimated 1-1.8 million sport-related concussions (SRC) occur per year in patients younger than 18 years of age. Concussion is defined as “a traumatically induced transient disturbance of brain function.” More than 50% of concussions among high school youth are not related to organized sports and between 2% and 15% of athletes in organized sports will sustain a concussion during a season of play.

©s-c-s/Thinkstock

In its position statement on concussion in sports, the American Medical Society for Sports Medicine recommends that student athletes receive specific evaluations, which will be described in this article. The guidelines include recommendations for imaging, treatment, and decision making regarding when as well as whether to return to play. Here is a brief summary of those recommendations.


Preseason: Preseason evaluation includes a preparticipation physical evaluation and discussion of concussion history as well as risk factors associated with prolonged concussion recovery. Neurocognitive tests are available for baseline evaluation. While these may assist with diagnosis and return-to-play decisions, there can be considerable variation in an individual’s baseline score as well as the possibility of changes in that baseline over time. Because of this potential for variability, these tests are not required or accepted as the standard of care.

Sideline assessment: Familiarity with the athlete is the best way to detect subtle changes in personality or performance. Looking at symptoms is still the most sensitive way to diagnose a concussion. Loss of consciousness, seizure, tonic posturing, lack of motor coordination, confusion, amnesia, difficulty with balance, or any cognitive difficulty should prompt removal from play for possible concussion. Once a potential injury is identified, how the athlete responds to the elements of orientation, memory, concentration, speech pattern, and balance should be evaluated. If an athlete has a probable or definite concussion, the athlete needs to be removed from play and cannot return to same-day play, and a more detailed evaluation needs to be done.

Office assessment: It is not unusual for symptoms and testing to normalize by the time an office visit occurs. If this is the case, the visit should focus on recommendations for safe return to school and sport. A standard office evaluation should include taking a history with details of the mechanism of injury and preexisting conditions – such as depression and prior concussion – that can affect concussion recovery. The history should focus on detecting symptoms that typically cause impairment from concussion: headache, ocular-vestibular issues leading to problems with balance, and cognitive issues with difficulty concentrating and remembering, as well as fatigue and mood issues such as anxiety, irritability, and depression. The physical exam should include assessment of ocular and vestibular function, gait, and balance in addition to a neurological exam.

Imaging: Head CT or MRI are rarely indicated. Intracranial bleeds are rare in the context of SRC but can occur. If there is concern for a bleed, then CT scan is the imaging test of choice. MRI may have value for evaluation for atypical or prolonged recovery.

Recovery time: The large majority (80%-90%) of concussed older adolescents and adults return to preinjury levels of function within 2 weeks; in younger athletes, clinical recovery may take up to 4 weeks. The best predictor of recovery from SRC is the number and severity of symptoms.

Treatment: For decades, cognitive and physical rest has been the standard of treatment. However, this is no longer the “gold standard” as it has been shown that strict rest (“cocoon therapy”) after SRC slows recovery and leads to an increased chance of prolonged symptoms. Current consensus guidelines support 24-48 hours of symptom-limited rest, both cognitive and physical, followed by a gradual increase in activity, staying below symptom-exacerbation thresholds. Activity, along with good sleep hygiene, appears to be helpful in facilitating recovery from SRC. In athletes with persistent post concussive symptoms that continue beyond the expected recovery time frame, activities of daily living, school, and exercise that do not significantly exacerbate symptoms are recommended.

Return to learning/play: A concussion can cause temporary deficits in attention, cognitive processing, short-term memory, and executive functioning. School personnel should be informed of the injury and assist in employing an individualized return to learn plan, including academic accommodations. Ultimately, return to sports activities should follow a successful return to the classroom. Return to play involves a stepwise increase in physical demands/activity without symptoms before a student is allowed to participate in full contact play.

Concussion-related risks: Continuing to participate in sports before resolution of concussion can worsen and prolong symptoms of SRC. Returning too early after concussion, before full recovery, increases the risk of recurrent SRC. During the initial post-injury period, returning to sports too early increases the risk for a rare but devastating possibility of second impact syndrome that can be a life-threatening repeat head injury. Studies of long-term mental health diagnoses are conflicting and inconsistent. Chronic traumatic encephalopathy has been described in athletes with a long history of concussions and repetitive sub-symptom head impacts. The degree of exposure needed appears to be variable and dependent on the individual.

Disqualification from play: Because each athlete is individually assessed after SRC, there are no evidence-based studies indicating how many concussions are “safe” for an athlete to have in a lifetime. The decision to stop playing sports is both serious and difficult for most athletes and requires shared decision making between clinician, the athlete, and the athlete’s parents. Factors to consider when determining if disqualification from play is warranted include:

• The total number of concussions experienced by a patient.
• Whether a patient has sustained subsequent concussions with progressively less forceful blows to the head.
• If a patient has sustained multiple concussions,whether the time to complete a full recovery after each concussion event increased.

The bottom line: “Cocoon therapy” is no longer recommended. Consensus guidelines endorse 24-48 hours of symptom-limited cognitive and physical rest followed by a gradual increase in activity, including noncontact physical activity that does not provoke symptoms.

Dr. Belogorodsky is a second-year resident and Dr. Fidler is an associate director in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

Reference

Harmon KG et al. American Medical Society for Sports Medicine position statement on concussion in sport. Br J Sports Med. 2019;53:213-25.

Ovarian remnant syndrome (ORS) is an uncommon problem, but one that seems to be increasing in incidence and one that is important to diagnose and treat properly, as well as prevent. Retrospective cohort studies published in the past 15 years or so have improved our understanding of its presentation and the outcomes of surgical management – and recent literature has demonstrated that a minimally invasive surgical approach with either conventional laparoscopy or robot-assisted laparoscopy yields improved outcomes in a skilled surgeon’s hands.

Diagnosis is based on clinical history and should be further supported with imaging and laboratory evaluation. A definitive diagnosis of the disease comes through surgical intervention and pathological findings.

Patients with ovarian remnants tend to have a history of extensive adhesive disease and/or severe endometriosis including ovarian endometrioma. Surgery therefore is technically challenging, usually requiring complete ureterolysis, careful adhesiolysis (often enterolysis), and excision of much of the pelvic sidewall peritoneum with extirpation of the remnant and endometriosis. High ligation of the ovarian vasculature also often is required.

This complexity and the consequent risk of intraoperative injury to the bowel, bladder, and ureters requires careful preoperative preparation. When an ovarian remnant is suspected, it may be important to have other surgeons – such as gynecologic oncologists, urologists, colorectal surgeons, or general surgeons – either present or on standby during the surgical intervention. In expert hands, surgical intervention has been shown to resolve or improve pain in the majority of patients, with no recurrence of the syndrome.
 

Diagnosis of ORS

Vidyard Video

Courtesy Dr. Charles E. Miller and Dr. Kirsten J. Sasaki

Patients with ORS have had previous oophorectomies with incomplete removal of ovarian tissue. Pelvic pain, either cyclical or most commonly chronic, is a common symptom. Other symptoms can include dyspareunia, dysuria and other urinary symptoms, and bowel symptoms. Ovarian remnants may have an expanding cystic structure – oftentimes secondary to endometriosis – that causes mass-like effects leading to pain and inflammation and to symptoms such as low back pain, constipation, and even urinary retention.

It also is important to discuss the patient’s history of menopausal symptoms, because the absence of these symptoms after oophorectomy may be a sign that ovarian tissue has been left behind. Menopausal symptoms do not exclude the diagnosis, however. Endometriosis, extensive surgical history, and other diseases that lead to significant adhesion formation – and a higher risk of incomplete removal of ovarian tissue, theoretically – also should be explored during history-taking.

Laboratory assessment of serum follicle-stimulating hormone (FSH) and estradiol can be helpful. Values that are indicative of ovarian function – FSH less than 30 mIU/mL and estradiol greater than 35 pg/mL – point towards ORS, but the absence of such premenopausal values should not rule out the possibility of an ovarian remnant.

The literature shows that FSH and estradiol levels are variable in women with ORS. A retrospective review published in 2005 by Paul M. Magtibay, MD, and colleagues at the Mayo Clinic, Scottsdale, Ariz., and Rochester, Minn., involved 186 patients treated surgically from 1985 to 2003 with a mean follow-up, via questionnaire, of 1.2 years. This is the largest series published thus far of patients with pathologically confirmed ORS. It reported premenopausal levels of FSH and estradiol in 69% and 63% of patients, respectively, who had preoperative hormonal evaluations.¹

In another retrospective cohort study published in 2011 of 30 women – also with pathologically confirmed ovarian remnants – Deborah Arden, MD, and Ted Lee, MD, of the University of Pittsburgh Medical Center reported premenopausal levels of FSH and estradiol in 59% and 71%, respectively, of women whose concentrations were measured.²

ORS often involves a pelvic mass, and preoperative imaging is important in this regard. In Dr. Magtibay’s series, a pelvic mass was identified in 93%, 92%, and 78% of those who were imaged presurgically with ultrasonography, computed tomography, and magnetic resonance imaging, respectively.¹ As with laboratory testing, however, a negative result does not rule out the presence of an ovarian remnant.

Some authors have advocated the use of clomiphene citrate stimulation before preoperative imaging – or before repeat imaging – to identify remnant ovarian tissue. Typically, clomiphene citrate 100 mg is administered for 10 days prior to imaging to potentially induce ovulation in patients with suspected ORS. Alternatively, at the Advanced Gynecologic Surgery Institute in Naperville and Park Ridge, Ill., ovarian stimulation is performed using FSH 300 IUs for 5 days. A finding of cystic structures consistent with ovarian follicles will help narrow the diagnosis.

Use of gonadotropins is superior in that an intact pituitary-ovarian axis is not required. Moreover, monitoring can be in real time; increasing estradiol levels and increasing mass size on ultrasound can be monitored as gonadotropin treatment is rendered. Again, however, negative findings should not necessarily rule out ORS. Unfortunately, there have been no clinical studies looking at the use of controlled ovarian stimulation as a definitive test.

The differential diagnosis includes supernumerary ovary (a rare gynecologic congenital anomaly) and residual ovary syndrome (a condition in which an ovary is intentionally or unintentionally left in place during a hysterectomy, as well as often an intended bilateral oophorectomy, and later causes pain). The latter occurs when surgical anatomy is poor and the surgery is consequently very difficult.
 

Surgical principles and approach

Previously, laparotomy was believed to be the best approach for minimizing intraoperative complications and achieving the extensive dissections necessary for effective treatment of ORS. In recent years, conventional laparoscopy and robot-assisted laparoscopy have been shown in retrospective reviews such as that by Arden et al.² and a 2007 review by Rosanne M. Kho, MD,³ to be just as safe and effective provided that the same surgical principles – extensive retroperitoneal dissections and ureterolysis – are applied.

Good outcomes can be achieved with less blood loss, shorter operating room time, and less time in the hospital. The better visualization with greater magnification afforded by a minimally invasive approach offers a distinct advantage for such complex dissections.

A remnant of ovarian tissue can be located anywhere along the pelvic sidewall, which makes the surgical protocol largely individualized and based on the suspected location of the remnant.

Still, there are certain standard components of any surgical approach to ORS: The retroperitoneum should be entered at the level of the pelvic brim and the ureter must be clearly identified; usually, a partial or complete ureterolysis is necessary. Then, a window into the broad ligament inferior to the infundibulopelvic (IP) ligament is created, or the peritoneum of the broad ligament is removed, in order to completely isolate both the IP ligament and the ureter.

Once the ovarian remnant is isolated, a wide excision at least 2 cm from all ovarian tissue is performed. This wide surgical clearance is critical to prevent recurrence.

These standard components form the crux of the most basic and straightforward surgery for ORS. In some cases, more extensive dissections such as a cystectomy or even a bowel resection might be necessary. Ligation of the IP ligament as high because its connection to the aortic bifurcation also may be necessary – depending, again, on the location of the ovarian remnant.

The risk of intraoperative injury to the bowel, bladder, and ureters is not insignificant, but with careful planning and the involvement of other surgeons in the most complex cases, these risks can be minimized.

For patients who have a significant surgical history and do not want more surgery, pharmacologic therapy, such as leuprolide (Lupron) or danazol, is an option for ORS. It’s important to note, however, that no studies have been done to demonstrate that medical therapy is a curative option. In addition, one must consider the small risk that remnants may harbor or develop malignancy.

Malignancy has been reported in ovarian remnant tissue. While the risk is believed to be very small, 2 of the 20 patients in Dr. Kho’s cohort had malignancy in remnant tissue,³ and it is generally recommended that surgeons send frozen sections of suspected ovarian tissue to pathology. Frozen-section diagnosis of ovarian tissue is about 95% accurate.
 

Preventing ovarian remnants

Oophorectomy is a common procedure performed by gynecologic surgeons. While routine, it is imperative that it be performed correctly to prevent ovarian remnants from occurring. When performing a laparoscopic or robot-assisted laparoscopic oophorectomy, it is important to optimize visualization of the ovary and the IP ligament, and to account for the significant magnification provided by laparoscopic cameras.

Surgeons must make sure all adhesions are completely cleared in order to optimally transect the IP ligament. Furthermore, wide excision around ovarian tissue is critical. Accessory ovarian tissue has been found up to 1.4 cm away from the ovary itself, which is why we recommend that surgeons excise at least 2-3 cm away from the IP in order to safely ensure complete removal of ovarian tissue.
 

Dr. Kooperman completed the American Association of Gynecologic Laparoscopists (AAGL) Fellowship Program in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill., and will be starting practice at the Highland Park (Ill.) North Shore Hospital System in August 2019. He reported no relevant disclosures.
 

References

1. Am J Obstet Gynecol. 2005;193(6):2062-6.

2. J Minim Invasive Gynecol. 2011;18(2):194-9.

3. Fertil Steril. 2007;87(5):1005-9.

Ovarian remnant syndrome (ORS) is an uncommon problem, but one that seems to be increasing in incidence and one that is important to diagnose and treat properly, as well as prevent. Retrospective cohort studies published in the past 15 years or so have improved our understanding of its presentation and the outcomes of surgical management – and recent literature has demonstrated that a minimally invasive surgical approach with either conventional laparoscopy or robot-assisted laparoscopy yields improved outcomes in a skilled surgeon’s hands.

Diagnosis is based on clinical history and should be further supported with imaging and laboratory evaluation. A definitive diagnosis of the disease comes through surgical intervention and pathological findings.

Patients with ovarian remnants tend to have a history of extensive adhesive disease and/or severe endometriosis including ovarian endometrioma. Surgery therefore is technically challenging, usually requiring complete ureterolysis, careful adhesiolysis (often enterolysis), and excision of much of the pelvic sidewall peritoneum with extirpation of the remnant and endometriosis. High ligation of the ovarian vasculature also often is required.

This complexity and the consequent risk of intraoperative injury to the bowel, bladder, and ureters requires careful preoperative preparation. When an ovarian remnant is suspected, it may be important to have other surgeons – such as gynecologic oncologists, urologists, colorectal surgeons, or general surgeons – either present or on standby during the surgical intervention. In expert hands, surgical intervention has been shown to resolve or improve pain in the majority of patients, with no recurrence of the syndrome.
 

Diagnosis of ORS

Vidyard Video

Courtesy Dr. Charles E. Miller and Dr. Kirsten J. Sasaki

Patients with ORS have had previous oophorectomies with incomplete removal of ovarian tissue. Pelvic pain, either cyclical or most commonly chronic, is a common symptom. Other symptoms can include dyspareunia, dysuria and other urinary symptoms, and bowel symptoms. Ovarian remnants may have an expanding cystic structure – oftentimes secondary to endometriosis – that causes mass-like effects leading to pain and inflammation and to symptoms such as low back pain, constipation, and even urinary retention.

It also is important to discuss the patient’s history of menopausal symptoms, because the absence of these symptoms after oophorectomy may be a sign that ovarian tissue has been left behind. Menopausal symptoms do not exclude the diagnosis, however. Endometriosis, extensive surgical history, and other diseases that lead to significant adhesion formation – and a higher risk of incomplete removal of ovarian tissue, theoretically – also should be explored during history-taking.

Laboratory assessment of serum follicle-stimulating hormone (FSH) and estradiol can be helpful. Values that are indicative of ovarian function – FSH less than 30 mIU/mL and estradiol greater than 35 pg/mL – point towards ORS, but the absence of such premenopausal values should not rule out the possibility of an ovarian remnant.

The literature shows that FSH and estradiol levels are variable in women with ORS. A retrospective review published in 2005 by Paul M. Magtibay, MD, and colleagues at the Mayo Clinic, Scottsdale, Ariz., and Rochester, Minn., involved 186 patients treated surgically from 1985 to 2003 with a mean follow-up, via questionnaire, of 1.2 years. This is the largest series published thus far of patients with pathologically confirmed ORS. It reported premenopausal levels of FSH and estradiol in 69% and 63% of patients, respectively, who had preoperative hormonal evaluations.¹

In another retrospective cohort study published in 2011 of 30 women – also with pathologically confirmed ovarian remnants – Deborah Arden, MD, and Ted Lee, MD, of the University of Pittsburgh Medical Center reported premenopausal levels of FSH and estradiol in 59% and 71%, respectively, of women whose concentrations were measured.²

ORS often involves a pelvic mass, and preoperative imaging is important in this regard. In Dr. Magtibay’s series, a pelvic mass was identified in 93%, 92%, and 78% of those who were imaged presurgically with ultrasonography, computed tomography, and magnetic resonance imaging, respectively.¹ As with laboratory testing, however, a negative result does not rule out the presence of an ovarian remnant.

Some authors have advocated the use of clomiphene citrate stimulation before preoperative imaging – or before repeat imaging – to identify remnant ovarian tissue. Typically, clomiphene citrate 100 mg is administered for 10 days prior to imaging to potentially induce ovulation in patients with suspected ORS. Alternatively, at the Advanced Gynecologic Surgery Institute in Naperville and Park Ridge, Ill., ovarian stimulation is performed using FSH 300 IUs for 5 days. A finding of cystic structures consistent with ovarian follicles will help narrow the diagnosis.

Use of gonadotropins is superior in that an intact pituitary-ovarian axis is not required. Moreover, monitoring can be in real time; increasing estradiol levels and increasing mass size on ultrasound can be monitored as gonadotropin treatment is rendered. Again, however, negative findings should not necessarily rule out ORS. Unfortunately, there have been no clinical studies looking at the use of controlled ovarian stimulation as a definitive test.

The differential diagnosis includes supernumerary ovary (a rare gynecologic congenital anomaly) and residual ovary syndrome (a condition in which an ovary is intentionally or unintentionally left in place during a hysterectomy, as well as often an intended bilateral oophorectomy, and later causes pain). The latter occurs when surgical anatomy is poor and the surgery is consequently very difficult.
 

Surgical principles and approach

Previously, laparotomy was believed to be the best approach for minimizing intraoperative complications and achieving the extensive dissections necessary for effective treatment of ORS. In recent years, conventional laparoscopy and robot-assisted laparoscopy have been shown in retrospective reviews such as that by Arden et al.² and a 2007 review by Rosanne M. Kho, MD,³ to be just as safe and effective provided that the same surgical principles – extensive retroperitoneal dissections and ureterolysis – are applied.

Good outcomes can be achieved with less blood loss, shorter operating room time, and less time in the hospital. The better visualization with greater magnification afforded by a minimally invasive approach offers a distinct advantage for such complex dissections.

A remnant of ovarian tissue can be located anywhere along the pelvic sidewall, which makes the surgical protocol largely individualized and based on the suspected location of the remnant.

Still, there are certain standard components of any surgical approach to ORS: The retroperitoneum should be entered at the level of the pelvic brim and the ureter must be clearly identified; usually, a partial or complete ureterolysis is necessary. Then, a window into the broad ligament inferior to the infundibulopelvic (IP) ligament is created, or the peritoneum of the broad ligament is removed, in order to completely isolate both the IP ligament and the ureter.

Once the ovarian remnant is isolated, a wide excision at least 2 cm from all ovarian tissue is performed. This wide surgical clearance is critical to prevent recurrence.

These standard components form the crux of the most basic and straightforward surgery for ORS. In some cases, more extensive dissections such as a cystectomy or even a bowel resection might be necessary. Ligation of the IP ligament as high because its connection to the aortic bifurcation also may be necessary – depending, again, on the location of the ovarian remnant.

The risk of intraoperative injury to the bowel, bladder, and ureters is not insignificant, but with careful planning and the involvement of other surgeons in the most complex cases, these risks can be minimized.

For patients who have a significant surgical history and do not want more surgery, pharmacologic therapy, such as leuprolide (Lupron) or danazol, is an option for ORS. It’s important to note, however, that no studies have been done to demonstrate that medical therapy is a curative option. In addition, one must consider the small risk that remnants may harbor or develop malignancy.

Malignancy has been reported in ovarian remnant tissue. While the risk is believed to be very small, 2 of the 20 patients in Dr. Kho’s cohort had malignancy in remnant tissue,³ and it is generally recommended that surgeons send frozen sections of suspected ovarian tissue to pathology. Frozen-section diagnosis of ovarian tissue is about 95% accurate.
 

Preventing ovarian remnants

Oophorectomy is a common procedure performed by gynecologic surgeons. While routine, it is imperative that it be performed correctly to prevent ovarian remnants from occurring. When performing a laparoscopic or robot-assisted laparoscopic oophorectomy, it is important to optimize visualization of the ovary and the IP ligament, and to account for the significant magnification provided by laparoscopic cameras.

Surgeons must make sure all adhesions are completely cleared in order to optimally transect the IP ligament. Furthermore, wide excision around ovarian tissue is critical. Accessory ovarian tissue has been found up to 1.4 cm away from the ovary itself, which is why we recommend that surgeons excise at least 2-3 cm away from the IP in order to safely ensure complete removal of ovarian tissue.
 

Dr. Kooperman completed the American Association of Gynecologic Laparoscopists (AAGL) Fellowship Program in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill., and will be starting practice at the Highland Park (Ill.) North Shore Hospital System in August 2019. He reported no relevant disclosures.
 

References

1. Am J Obstet Gynecol. 2005;193(6):2062-6.

2. J Minim Invasive Gynecol. 2011;18(2):194-9.

3. Fertil Steril. 2007;87(5):1005-9.

Ovarian remnant syndrome (ORS) is an uncommon problem, but one that seems to be increasing in incidence and one that is important to diagnose and treat properly, as well as prevent. Retrospective cohort studies published in the past 15 years or so have improved our understanding of its presentation and the outcomes of surgical management – and recent literature has demonstrated that a minimally invasive surgical approach with either conventional laparoscopy or robot-assisted laparoscopy yields improved outcomes in a skilled surgeon’s hands.

Diagnosis is based on clinical history and should be further supported with imaging and laboratory evaluation. A definitive diagnosis of the disease comes through surgical intervention and pathological findings.

Patients with ovarian remnants tend to have a history of extensive adhesive disease and/or severe endometriosis including ovarian endometrioma. Surgery therefore is technically challenging, usually requiring complete ureterolysis, careful adhesiolysis (often enterolysis), and excision of much of the pelvic sidewall peritoneum with extirpation of the remnant and endometriosis. High ligation of the ovarian vasculature also often is required.

This complexity and the consequent risk of intraoperative injury to the bowel, bladder, and ureters requires careful preoperative preparation. When an ovarian remnant is suspected, it may be important to have other surgeons – such as gynecologic oncologists, urologists, colorectal surgeons, or general surgeons – either present or on standby during the surgical intervention. In expert hands, surgical intervention has been shown to resolve or improve pain in the majority of patients, with no recurrence of the syndrome.
 

Diagnosis of ORS

Vidyard Video

Courtesy Dr. Charles E. Miller and Dr. Kirsten J. Sasaki

Patients with ORS have had previous oophorectomies with incomplete removal of ovarian tissue. Pelvic pain, either cyclical or most commonly chronic, is a common symptom. Other symptoms can include dyspareunia, dysuria and other urinary symptoms, and bowel symptoms. Ovarian remnants may have an expanding cystic structure – oftentimes secondary to endometriosis – that causes mass-like effects leading to pain and inflammation and to symptoms such as low back pain, constipation, and even urinary retention.

It also is important to discuss the patient’s history of menopausal symptoms, because the absence of these symptoms after oophorectomy may be a sign that ovarian tissue has been left behind. Menopausal symptoms do not exclude the diagnosis, however. Endometriosis, extensive surgical history, and other diseases that lead to significant adhesion formation – and a higher risk of incomplete removal of ovarian tissue, theoretically – also should be explored during history-taking.

Laboratory assessment of serum follicle-stimulating hormone (FSH) and estradiol can be helpful. Values that are indicative of ovarian function – FSH less than 30 mIU/mL and estradiol greater than 35 pg/mL – point towards ORS, but the absence of such premenopausal values should not rule out the possibility of an ovarian remnant.

The literature shows that FSH and estradiol levels are variable in women with ORS. A retrospective review published in 2005 by Paul M. Magtibay, MD, and colleagues at the Mayo Clinic, Scottsdale, Ariz., and Rochester, Minn., involved 186 patients treated surgically from 1985 to 2003 with a mean follow-up, via questionnaire, of 1.2 years. This is the largest series published thus far of patients with pathologically confirmed ORS. It reported premenopausal levels of FSH and estradiol in 69% and 63% of patients, respectively, who had preoperative hormonal evaluations.¹

In another retrospective cohort study published in 2011 of 30 women – also with pathologically confirmed ovarian remnants – Deborah Arden, MD, and Ted Lee, MD, of the University of Pittsburgh Medical Center reported premenopausal levels of FSH and estradiol in 59% and 71%, respectively, of women whose concentrations were measured.²

ORS often involves a pelvic mass, and preoperative imaging is important in this regard. In Dr. Magtibay’s series, a pelvic mass was identified in 93%, 92%, and 78% of those who were imaged presurgically with ultrasonography, computed tomography, and magnetic resonance imaging, respectively.¹ As with laboratory testing, however, a negative result does not rule out the presence of an ovarian remnant.

Some authors have advocated the use of clomiphene citrate stimulation before preoperative imaging – or before repeat imaging – to identify remnant ovarian tissue. Typically, clomiphene citrate 100 mg is administered for 10 days prior to imaging to potentially induce ovulation in patients with suspected ORS. Alternatively, at the Advanced Gynecologic Surgery Institute in Naperville and Park Ridge, Ill., ovarian stimulation is performed using FSH 300 IUs for 5 days. A finding of cystic structures consistent with ovarian follicles will help narrow the diagnosis.

Use of gonadotropins is superior in that an intact pituitary-ovarian axis is not required. Moreover, monitoring can be in real time; increasing estradiol levels and increasing mass size on ultrasound can be monitored as gonadotropin treatment is rendered. Again, however, negative findings should not necessarily rule out ORS. Unfortunately, there have been no clinical studies looking at the use of controlled ovarian stimulation as a definitive test.

The differential diagnosis includes supernumerary ovary (a rare gynecologic congenital anomaly) and residual ovary syndrome (a condition in which an ovary is intentionally or unintentionally left in place during a hysterectomy, as well as often an intended bilateral oophorectomy, and later causes pain). The latter occurs when surgical anatomy is poor and the surgery is consequently very difficult.
 

Surgical principles and approach

Previously, laparotomy was believed to be the best approach for minimizing intraoperative complications and achieving the extensive dissections necessary for effective treatment of ORS. In recent years, conventional laparoscopy and robot-assisted laparoscopy have been shown in retrospective reviews such as that by Arden et al.² and a 2007 review by Rosanne M. Kho, MD,³ to be just as safe and effective provided that the same surgical principles – extensive retroperitoneal dissections and ureterolysis – are applied.

Good outcomes can be achieved with less blood loss, shorter operating room time, and less time in the hospital. The better visualization with greater magnification afforded by a minimally invasive approach offers a distinct advantage for such complex dissections.

A remnant of ovarian tissue can be located anywhere along the pelvic sidewall, which makes the surgical protocol largely individualized and based on the suspected location of the remnant.

Still, there are certain standard components of any surgical approach to ORS: The retroperitoneum should be entered at the level of the pelvic brim and the ureter must be clearly identified; usually, a partial or complete ureterolysis is necessary. Then, a window into the broad ligament inferior to the infundibulopelvic (IP) ligament is created, or the peritoneum of the broad ligament is removed, in order to completely isolate both the IP ligament and the ureter.

Once the ovarian remnant is isolated, a wide excision at least 2 cm from all ovarian tissue is performed. This wide surgical clearance is critical to prevent recurrence.

These standard components form the crux of the most basic and straightforward surgery for ORS. In some cases, more extensive dissections such as a cystectomy or even a bowel resection might be necessary. Ligation of the IP ligament as high because its connection to the aortic bifurcation also may be necessary – depending, again, on the location of the ovarian remnant.

The risk of intraoperative injury to the bowel, bladder, and ureters is not insignificant, but with careful planning and the involvement of other surgeons in the most complex cases, these risks can be minimized.

For patients who have a significant surgical history and do not want more surgery, pharmacologic therapy, such as leuprolide (Lupron) or danazol, is an option for ORS. It’s important to note, however, that no studies have been done to demonstrate that medical therapy is a curative option. In addition, one must consider the small risk that remnants may harbor or develop malignancy.

Malignancy has been reported in ovarian remnant tissue. While the risk is believed to be very small, 2 of the 20 patients in Dr. Kho’s cohort had malignancy in remnant tissue,³ and it is generally recommended that surgeons send frozen sections of suspected ovarian tissue to pathology. Frozen-section diagnosis of ovarian tissue is about 95% accurate.
 

Preventing ovarian remnants

Oophorectomy is a common procedure performed by gynecologic surgeons. While routine, it is imperative that it be performed correctly to prevent ovarian remnants from occurring. When performing a laparoscopic or robot-assisted laparoscopic oophorectomy, it is important to optimize visualization of the ovary and the IP ligament, and to account for the significant magnification provided by laparoscopic cameras.

Surgeons must make sure all adhesions are completely cleared in order to optimally transect the IP ligament. Furthermore, wide excision around ovarian tissue is critical. Accessory ovarian tissue has been found up to 1.4 cm away from the ovary itself, which is why we recommend that surgeons excise at least 2-3 cm away from the IP in order to safely ensure complete removal of ovarian tissue.
 

Dr. Kooperman completed the American Association of Gynecologic Laparoscopists (AAGL) Fellowship Program in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill., and will be starting practice at the Highland Park (Ill.) North Shore Hospital System in August 2019. He reported no relevant disclosures.
 

References

1. Am J Obstet Gynecol. 2005;193(6):2062-6.

2. J Minim Invasive Gynecol. 2011;18(2):194-9.

3. Fertil Steril. 2007;87(5):1005-9.

A 45-year old woman was referred by her physician to my clinic for continued pain after total hysterectomy and bilateral salpingo-oophorectomy. The patient initially had undergone a robot-assisted total laparoscopic hysterectomy, bilateral salpingectomy, and excision of stage 1 endometriosis secondary to pelvic pain. Because of continued pain and new onset of persistent ovarian cysts, she once again underwent robotic-assisted laparoscopic surgery, this time to remove both ovaries. Interestingly, severe periadnexal adhesions were noted in the second surgical report. A hemorrhagic cyst and a corpus luteal cyst were noted. Unfortunately, the patient continued to have left lower abdominal pain; thus, the referral to my clinic.

Given the history of pelvic pain, especially in light of severe periadnexal adhesions at the second surgery, I voiced my concern about possible ovarian remnant syndrome. At the patient’s initial visit, an estradiol (E2), progesterone (P4) and follicle-stimulating hormone (FSH) test were ordered. Interestingly, while the E2 and P4 were quite low, the FSH was 10.9 IU/mL. Certainly, this was not consistent with menopause but could point to ovarian remnant syndrome.

A follow-up examination and ultrasound revealed a 15-mm exquisitely tender left adnexal mass, again consistent with ovarian remnant syndrome. My plan now is to proceed with surgery with the presumptive diagnosis of ovarian remnant syndrome.

Ovarian remnant syndrome (ORS), first described by Shemwell and Weed in 1970, is defined as a pelvic mass with residual ovarian tissue postoophorectomy.^1-3 ORS may be associated with endometriosis or ovarian cancer. Remnant ovarian tissue also may stimulate endometriosis and cyclic pelvic pain, similar to symptoms of the remnant itself.⁴

ORS is caused by surgical factors that limit surgical exposure or compromise surgical technique. Pelvic adhesions may be secondary to previous surgery, intraoperative bleeding, previous appendectomy, inflammatory bowel disease, pelvic inflammatory disease, or endometriosis, the latter of which is the most common cause of initial oophorectomy. Moreover, surgical technique may be causal. This includes inability to achieve adequate exposure, inability to restore normal anatomy, and imprecise site of surgical incision.^5-7

For this edition of the Master Class in Gynecologic Surgery, I have enlisted the assistance of Ryan S. Kooperman, DO, who recently completed his 2-year American Association of Gynecologic Laparoscopists (AAGL) Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital in Park Ridge, Ill., where I am currently the program director.

In 2016, Dr. Kooperman was the recipient of the National Outstanding Resident of the Year in Obstetrics and Gynecology (American Osteopathic Foundation/Medical Education Foundation of the American College of Osteopathic Obstetricians and Gynecologists). Dr. Kooperman is a very skilled surgeon and adroit clinician. He will be starting practice at Highland Park (Ill.) North Shore Hospital System in August 2019. It is a pleasure to welcome Dr. Kooperman to this edition of the Master Class in Gynecologic Surgery.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital. He has no disclosures relevant to this Master Class.

References

1. Obstet Gynecol. 1970 Aug;36(2):299-303.

2. Aust N Z J Obstet Gynaecol. 1989 Nov;29(4):433-5.

3. Curr Opin Obstet Gynecol. 2012 Aug;24(4):210-4.

4. Int J Gynaecol Obstet. 1988 Feb;26(1):93-103.

5. Oncol Lett. 2014 Jul;8(1):3-6.

6. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):194-9.

7. Fertil Steril. 2007 May;87(5):1005-9.

A 45-year old woman was referred by her physician to my clinic for continued pain after total hysterectomy and bilateral salpingo-oophorectomy. The patient initially had undergone a robot-assisted total laparoscopic hysterectomy, bilateral salpingectomy, and excision of stage 1 endometriosis secondary to pelvic pain. Because of continued pain and new onset of persistent ovarian cysts, she once again underwent robotic-assisted laparoscopic surgery, this time to remove both ovaries. Interestingly, severe periadnexal adhesions were noted in the second surgical report. A hemorrhagic cyst and a corpus luteal cyst were noted. Unfortunately, the patient continued to have left lower abdominal pain; thus, the referral to my clinic.

Given the history of pelvic pain, especially in light of severe periadnexal adhesions at the second surgery, I voiced my concern about possible ovarian remnant syndrome. At the patient’s initial visit, an estradiol (E2), progesterone (P4) and follicle-stimulating hormone (FSH) test were ordered. Interestingly, while the E2 and P4 were quite low, the FSH was 10.9 IU/mL. Certainly, this was not consistent with menopause but could point to ovarian remnant syndrome.

A follow-up examination and ultrasound revealed a 15-mm exquisitely tender left adnexal mass, again consistent with ovarian remnant syndrome. My plan now is to proceed with surgery with the presumptive diagnosis of ovarian remnant syndrome.

Ovarian remnant syndrome (ORS), first described by Shemwell and Weed in 1970, is defined as a pelvic mass with residual ovarian tissue postoophorectomy.^1-3 ORS may be associated with endometriosis or ovarian cancer. Remnant ovarian tissue also may stimulate endometriosis and cyclic pelvic pain, similar to symptoms of the remnant itself.⁴

ORS is caused by surgical factors that limit surgical exposure or compromise surgical technique. Pelvic adhesions may be secondary to previous surgery, intraoperative bleeding, previous appendectomy, inflammatory bowel disease, pelvic inflammatory disease, or endometriosis, the latter of which is the most common cause of initial oophorectomy. Moreover, surgical technique may be causal. This includes inability to achieve adequate exposure, inability to restore normal anatomy, and imprecise site of surgical incision.^5-7

For this edition of the Master Class in Gynecologic Surgery, I have enlisted the assistance of Ryan S. Kooperman, DO, who recently completed his 2-year American Association of Gynecologic Laparoscopists (AAGL) Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital in Park Ridge, Ill., where I am currently the program director.

In 2016, Dr. Kooperman was the recipient of the National Outstanding Resident of the Year in Obstetrics and Gynecology (American Osteopathic Foundation/Medical Education Foundation of the American College of Osteopathic Obstetricians and Gynecologists). Dr. Kooperman is a very skilled surgeon and adroit clinician. He will be starting practice at Highland Park (Ill.) North Shore Hospital System in August 2019. It is a pleasure to welcome Dr. Kooperman to this edition of the Master Class in Gynecologic Surgery.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital. He has no disclosures relevant to this Master Class.

References

1. Obstet Gynecol. 1970 Aug;36(2):299-303.

2. Aust N Z J Obstet Gynaecol. 1989 Nov;29(4):433-5.

3. Curr Opin Obstet Gynecol. 2012 Aug;24(4):210-4.

4. Int J Gynaecol Obstet. 1988 Feb;26(1):93-103.

5. Oncol Lett. 2014 Jul;8(1):3-6.

6. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):194-9.

7. Fertil Steril. 2007 May;87(5):1005-9.

A 45-year old woman was referred by her physician to my clinic for continued pain after total hysterectomy and bilateral salpingo-oophorectomy. The patient initially had undergone a robot-assisted total laparoscopic hysterectomy, bilateral salpingectomy, and excision of stage 1 endometriosis secondary to pelvic pain. Because of continued pain and new onset of persistent ovarian cysts, she once again underwent robotic-assisted laparoscopic surgery, this time to remove both ovaries. Interestingly, severe periadnexal adhesions were noted in the second surgical report. A hemorrhagic cyst and a corpus luteal cyst were noted. Unfortunately, the patient continued to have left lower abdominal pain; thus, the referral to my clinic.

Given the history of pelvic pain, especially in light of severe periadnexal adhesions at the second surgery, I voiced my concern about possible ovarian remnant syndrome. At the patient’s initial visit, an estradiol (E2), progesterone (P4) and follicle-stimulating hormone (FSH) test were ordered. Interestingly, while the E2 and P4 were quite low, the FSH was 10.9 IU/mL. Certainly, this was not consistent with menopause but could point to ovarian remnant syndrome.

A follow-up examination and ultrasound revealed a 15-mm exquisitely tender left adnexal mass, again consistent with ovarian remnant syndrome. My plan now is to proceed with surgery with the presumptive diagnosis of ovarian remnant syndrome.

Ovarian remnant syndrome (ORS), first described by Shemwell and Weed in 1970, is defined as a pelvic mass with residual ovarian tissue postoophorectomy.^1-3 ORS may be associated with endometriosis or ovarian cancer. Remnant ovarian tissue also may stimulate endometriosis and cyclic pelvic pain, similar to symptoms of the remnant itself.⁴

ORS is caused by surgical factors that limit surgical exposure or compromise surgical technique. Pelvic adhesions may be secondary to previous surgery, intraoperative bleeding, previous appendectomy, inflammatory bowel disease, pelvic inflammatory disease, or endometriosis, the latter of which is the most common cause of initial oophorectomy. Moreover, surgical technique may be causal. This includes inability to achieve adequate exposure, inability to restore normal anatomy, and imprecise site of surgical incision.^5-7

For this edition of the Master Class in Gynecologic Surgery, I have enlisted the assistance of Ryan S. Kooperman, DO, who recently completed his 2-year American Association of Gynecologic Laparoscopists (AAGL) Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital in Park Ridge, Ill., where I am currently the program director.

In 2016, Dr. Kooperman was the recipient of the National Outstanding Resident of the Year in Obstetrics and Gynecology (American Osteopathic Foundation/Medical Education Foundation of the American College of Osteopathic Obstetricians and Gynecologists). Dr. Kooperman is a very skilled surgeon and adroit clinician. He will be starting practice at Highland Park (Ill.) North Shore Hospital System in August 2019. It is a pleasure to welcome Dr. Kooperman to this edition of the Master Class in Gynecologic Surgery.
 

Dr. Miller is a clinical associate professor at the University of Illinois in Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago and the director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital. He has no disclosures relevant to this Master Class.

References

1. Obstet Gynecol. 1970 Aug;36(2):299-303.

2. Aust N Z J Obstet Gynaecol. 1989 Nov;29(4):433-5.

3. Curr Opin Obstet Gynecol. 2012 Aug;24(4):210-4.

4. Int J Gynaecol Obstet. 1988 Feb;26(1):93-103.

5. Oncol Lett. 2014 Jul;8(1):3-6.

6. J Minim Invasive Gynecol. 2011 Mar-Apr;18(2):194-9.

7. Fertil Steril. 2007 May;87(5):1005-9.